bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic value of chemiluminescence for urinary lipoarabinomannan antigen assay in active tuberculosis: insights from a retrospective study
Authors: Huang Luyi , Niu Yayan , Zhang Li , Yang Rong , Wu Meiying
Published: December 2023

Purpose

This study aimed to assess the efficacy of chemiluminescence-based urinary lipoarabinomannan (LAM) antigen assay as a diagnostic tool for identifying active tuberculosis.

Methods

A retrospective study was conducted on 166 Tuberculosis (TB), 22 Non-Tuberculous Mycobacteria (NTM), 69 Non-TB cases, and 73 healthy controls from Zhangjiagang First Peoples Hospital between July 2022 and November 2022. Clinical and laboratory data were collected, including urine samples for LAM antigen detection, sputum samples and pleural effusion for GeneXpert, TB-DNA, and culture.

Results

TB group exhibited a higher LAM positivity rate (P < 0.001). CD4 count and diabetes as independent factors influencing the diagnostic accuracy of LAM. The LAM assay showed a sensitivity of 50.6% and a specificity of 95.65%. Notably, LAM’s sensitivity was superior to TB-DNA (50.60% vs. 38.16%, P < 0.05). LAM’s PTB detection rate was 51.7%, superior to TB-DNA (P = 0.047). Moreover, in EPTB cases, the LAM detection rate was 42.11%, surpassing Gene Xpert (P = 0.042), as well as exceeding the detection rates of TB-DNA and sputum culture.

Conclusion

LAM antigen detection using chemiluminescence has demonstrated outstanding clinical diagnostic value for active TB, especially in the diagnosis of extrapulmonary TB. The convenience of sample collection in this diagnostic approach allows for widespread application in the clinical diagnosis of active tuberculosis, particularly in cases of EPTB and sputum-negative patients.
Solving polymicrobial puzzles: evolutionary dynamics and future directions
Authors: Srinivasan Abijith , Sajeevan Anusree , Rajaramon Shobana , David Helma , Solomon Adline Princy
Published: December 2023

Polymicrobial infections include various microorganisms, often necessitating different treatment methods than a monomicrobial infection. Scientists have been puzzled by the complex interactions within these communities for generations. The presence of specific microorganisms warrants a chronic infection and impacts crucial factors such as virulence and antibiotic susceptibility. Game theory is valuable for scenarios involving multiple decision-makers, but its relevance to polymicrobial infections is limited. Eco-evolutionary dynamics introduce causation for multiple proteomic interactions like metabolic syntropy and niche segregation. The review culminates both these giants to form evolutionary dynamics (ED). There is a significant amount of literature on inter-bacterial interactions that remain unsynchronised. Such raw data can only be moulded by analysing the ED involved. The review culminates the inter-bacterial interactions in multiple clinically relevant polymicrobial infections like chronic wounds, CAUTI, otitis media and dental carries. The data is further moulded with ED to analyse the niche colonisation of two notoriously competitive bacteria: S.aureus and P.aeruginosa. The review attempts to develop a future trajectory for polymicrobial research by following recent innovative strategies incorporating ED to curb polymicrobial infections.
Prediction of monthly average and extreme atmospheric temperatures in Zhengzhou based on artificial neural network and deep learning models
Authors: Guo Qingchun , He Zhenfang , Wang Zhaosheng
Published: December 2023

Introduction

Atmospheric temperature affects the growth and development of plants and has an important impact on the sustainable development of forest ecological systems. Predicting atmospheric temperature is crucial for forest management planning.

Methods

Artificial neural network (ANN) and deep learning models such as gate recurrent unit (GRU), long short-term memory (LSTM), convolutional neural network (CNN), CNN-GRU, and CNN-LSTM, were utilized to predict the change of monthly average and extreme atmospheric temperatures in Zhengzhou City. Average and extreme atmospheric temperature data from 1951 to 2022 were divided into training data sets (1951–2000) and prediction data sets (2001–2022), and 22 months of data were used as the model input to predict the average and extreme temperatures in the next month.

Results and Discussion

The number of neurons in the hidden layer was 14. Six different learning algorithms, along with 13 various learning functions, were trained and compared. The ANN model and deep learning models were evaluated in terms of correlation coefficient (R), root mean square error (RMSE), and mean absolute error (MAE), and good results were obtained. Bayesian regularization (trainbr) in the ANN model was the best performing algorithm in predicting average, minimum and maximum atmospheric temperatures compared to other algorithms in terms of R (0.9952, 0.9899, and 0.9721), and showed the lowest error values for RMSE (0.9432, 1.4034, and 2.0505), and MAE (0.7204, 1.0787, and 1.6224). The CNN-LSTM model showed the best performance. This CNN-LSTM method had good generalization ability and could be used to forecast average and extreme atmospheric temperature in other areas. Future climate changes were projected using the CNN-LSTM model. The average atmospheric temperature, minimum atmospheric temperature, and maximum atmospheric temperature in 2030 were predicted to be 17.23 °C, −5.06 °C, and 42.44 °C, whereas those in 2040 were predicted to be 17.36 °C, −3.74 °C, and 42.68 °C, respectively. These results suggest that the climate is projected to continue warming in the future.
Progress and challenges of plant-derived nucleic acids as therapeutics in macrophage-mediated RNA therapy
Authors: Liu Yu-Da , Chen Hao-Ran , Zhang Yao , Yan Ge , Yan Hao-Jie , Zhu Qi , Peng Li-Hua
Published: December 2023

Plant-derived nucleic acids, especially small RNAs have been proved by increasing evidence in the pharmacological activities and disease treatment values in macrophage meditated anti-tumor performance, immune regulating functions and antiviral activities. But the uptake, application and delivery strategies of RNAs as biodrugs are different from the small molecules and recombinant protein drugs. This article summarizes the reported evidence for cross-kingdom regulation by plant derived functional mRNAs and miRNAs. Based on that, their involvement and potentials in macrophage-mediated anti-tumor/inflammatory therapies are mainly discussed, as well as the load prospect of plant RNAs in viruses and natural exosome vehicles, and their delivery to mammalian cells through macrophage were also summarized. This review is to provide evidence and views for the plant derived RNAs as next generation of drugs with application potential in nucleic acid-based bio-therapy.
PANDORA v2.0: Benchmarking peptide-MHC II models and software improvements
Authors: Parizi Farzaneh M. , Marzella Dario F. , Ramakrishnan Gayatri , ‘t Hoen Peter A. C. , Karimi-Jafari Mohammad Hossein , Xue Li C.
Published: December 2023

T-cell specificity to differentiate between self and non-self relies on T-cell receptor (TCR) recognition of peptides presented by the Major Histocompatibility Complex (MHC). Investigations into the three-dimensional (3D) structures of peptide:MHC (pMHC) complexes have provided valuable insights of MHC functions. Given the limited availability of experimental pMHC structures and considerable diversity of peptides and MHC alleles, it calls for the development of efficient and reliable computational approaches for modeling pMHC structures. Here we present an update of PANDORA and the systematic evaluation of its performance in modelling 3D structures of pMHC class II complexes (pMHC-II), which play a key role in the cancer immune response. PANDORA is a modelling software that can build low-energy models in a few minutes by restraining peptide residues inside the MHC-II binding groove. We benchmarked PANDORA on 136 experimentally determined pMHC-II structures covering 44 unique αβ chain pairs. Our pipeline achieves a median backbone Ligand-Root Mean Squared Deviation (L-RMSD) of 0.42 Å on the binding core and 0.88 Å on the whole peptide for the benchmark dataset. We incorporated software improvements to make PANDORA a pan-allele framework and improved the user interface and software quality. Its computational efficiency allows enriching the wealth of pMHC binding affinity and mass spectrometry data with 3D models. These models can be used as a starting point for molecular dynamics simulations or structure-boosted deep learning algorithms to identify MHC-binding peptides. PANDORA is available as a Python package through Conda or as a source installation at https://github.com/X-lab-3D/PANDORA.
HER2 positivity predicts BCG unresponsiveness and adaptive immune cell exhaustion in EORTC risk-stratified cohort of bladder cancer
Authors: Nam Wook , Chae Han Kyu , Jung Yeonuk , Kang Homin , Park Myungchan , Choi Ahnryul , Park Jong Yeon , Eom Dae-Woon , Kim Sung Jin
Published: December 2023

Introduction

Predicting the response to Bacillus Calmette–Guérin (BCG) therapy in high-risk patients with non-muscle invasive bladder cancer (NMIBC) is crucial, as failure may necessitate interventions, such as radical cystectomy or salvage therapy. With the recent classification of genetic class 2a (which has HER2 protein abundance as its signature mutation of ERBB2), evaluating its prognostic role and relationship with BCG response could yield important results.

Methods

This retrospective study included 160 patients with NMIBC who underwent transurethral resection of bladder tumors at Gangneung Asan Hospital between 2000 and 2013 and were stratified based on the European Organization for Research and Treatment of Cancer (EORTC) risk criteria. In addition, we analyzed a subset of 67 patients who had received BCG induction therapy to identify factors predictive of BCG treatment response. Univariate and multivariate analyses were used to assess the impact of clinicopathological factors, HER2 positivity, and EORTC risk on recurrence, progression, survival, and BCG response. Each variable’s prognostic significance was determined using the Kaplan–Meier analysis. The tumor microenvironments (TMEs) were evaluated in relation to HER2 and EORTC risk.

Results

Patients with HER2+ had a higher median age, a greater prevalence of high-grade tumors, and more frequent recurrences. The univariate analysis demonstrated that the HER2+, intermediate (vs. low-risk) high (vs. low-risk), and EORTC recurrence risk groups were significantly associated with recurrence. In patients treated with BCG, only the HER2+ status predicted recurrence. In the univariate analysis for progression, age, high EORTC progression risk (vs. low-to-intermediate), HER2+, and programmed death-ligand 1 positive (PD-L1+) were significant factors. In multivariate analyses for progression, age, high EORTC progression risk, and PD-L1+ were significant factors for progression. HER2 expression was associated with the TME, influencing the proportion of PD-L1+ cells, as well as other markers of PD-1, CD8, and Ki67.

Conclusion

The HER2+ status may be related to genetic characteristics that appear more frequently in older age, which suggests a potential for predicting the recurrence and response to BCG treatment. Additionally, analyzing TME trends of aggressive adaptive immune response characterized by HER2 expression provides insight into recurrence and BCG response mechanisms.
Observing Antarctic Bottom Water in the Southern Ocean
Authors: Silvano Alessandro , Purkey Sarah , Gordon Arnold L. , Castagno Pasquale , Stewart Andrew L. , Rintoul Stephen R. , Foppert Annie , Gunn Kathryn L. , Herraiz-Borreguero Laura , Aoki Shigeru , Nakayama Yoshihiro , Naveira Garabato Alberto C. , Spingys Carl , Akhoudas Camille Hayatte , Sallée Jean-Baptiste , de Lavergne Casimir , Abrahamsen E. Povl , Meijers Andrew J. S. , Meredith Michael P. , Zhou Shenjie , Tamura Takeshi , Yamazaki Kaihe , Ohshima Kay I. , Falco Pierpaolo , Budillon Giorgio , Hattermann Tore , Janout Markus A. , Llanillo Pedro , Bowen Melissa M. , Darelius Elin , Østerhus Svein , Nicholls Keith W. , Stevens Craig , Fernandez Denise , Cimoli Laura , Jacobs Stanley S. , Morrison Adele K. , Hogg Andrew McC. , Haumann F. Alexander , Mashayek Ali , Wang Zhaomin , Kerr Rodrigo , Williams Guy D. , Lee Won Sang
Published: December 2023

Dense, cold waters formed on Antarctic continental shelves descend along the Antarctic continental margin, where they mix with other Southern Ocean waters to form Antarctic Bottom Water (AABW). AABW then spreads into the deepest parts of all major ocean basins, isolating heat and carbon from the atmosphere for centuries. Despite AABW’s key role in regulating Earth’s climate on long time scales and in recording Southern Ocean conditions, AABW remains poorly observed. This lack of observational data is mostly due to two factors. First, AABW originates on the Antarctic continental shelf and slope where in situ measurements are limited and ocean observations by satellites are hampered by persistent sea ice cover and long periods of darkness in winter. Second, north of the Antarctic continental slope, AABW is found below approximately 2 km depth, where in situ observations are also scarce and satellites cannot provide direct measurements. Here, we review progress made during the past decades in observing AABW. We describe 1) long-term monitoring obtained by moorings, by ship-based surveys, and beneath ice shelves through bore holes; 2) the recent development of autonomous observing tools in coastal Antarctic and deep ocean systems; and 3) alternative approaches including data assimilation models and satellite-derived proxies. The variety of approaches is beginning to transform our understanding of AABW, including its formation processes, temporal variability, and contribution to the lower limb of the global ocean meridional overturning circulation. In particular, these observations highlight the key role played by winds, sea ice, and the Antarctic Ice Sheet in AABW-related processes. We conclude by discussing future avenues for observing and understanding AABW, impressing the need for a sustained and coordinated observing system.
Seasonal and developmental variation in feeding by the copepod Calanus sinicus in the Yellow Sea
Authors: Kim Garam , Park Wongyu , Noh Jae Hoon , Kang Hyung–Ku
Published: December 2023

We investigated feeding by Calanus sinicus in the Yellow Sea over four seasons in 2019–2022 using the gut pigment method. Studying the feeding of copepods is important for understanding processes within food webs, but little is known about the feeding ecology of C. sinicus, a major consumer of primary production in the Yellow Sea. The seasonal mean ingestion rate of C. sinicus was 16.6–42.1 for copepodite stage I (CI), 24.1–41.8 for CII, and 32.7–58.5 ng chl ind.−1 d−1 for CIII, with different seasonal fluctuations in each stage. The seasonal mean ingestion rate was 45.8–114.4 for CIV, 50.2–189.3 for CV, 96.9–438.9 for females, and 69.8–132.3 ng chl ind.−1 d−1 for males, with higher values in spring and lower values in summer. The combined grazing impacts of C. sinicus from the CI to adult stages were 1.66%, 1.43%, 2.04%, and 0.65% in spring, summer, autumn, and winter, respectively. The ingestion rate of later developmental stages from CIV to adults was positively related to chlorophyll-a concentration rather than water temperature or salinity, according to a redundancy analysis. These results suggest that C. sinicus population in the Yellow Sea actively feeds on phytoplankton in spring and that most of the grazing impact is attributed to females.
Patients’ perspectives on prescription cannabinoid therapies: a cross-sectional, exploratory, anonymous, one-time web-based survey among German patients
Authors: Fischer Jan Moritz , Kandil Farid I. , Katsarova Ekaterina , Zager Laura Sophie , Jeitler Michael , Kugler Felix , Fitzner Franziska , Murthy Vijayendra , Hanslian Etienne , Wendelmuth Christoph , Michalsen Andreas , Karst Matthias , Kessler Christian S.
Published: December 2023

Introduction

Since cannabinoids were partially legalized as prescription medicines in Germany in 2017, they are mostly used when conventional therapies do not suffice. Ambiguities remain regarding use, benefits and risks. This web-based survey explored the perspectives of patients whose experiences are not well enough known to date.

Methods

In an anonymous, exploratory, cross-sectional, one-time web-based observational study, participants receiving cannabinoid therapy on prescription documented aspects of their medical history, diagnoses, attitudes toward cannabinoids, physical symptoms, and emotional states. Participants completed the questionnaires twice here: first regarding the time of the survey and then, retrospectively, for the time before their cannabinoid therapy. Participants were recruited in a stratified manner in three German federal states.

Results

N = 216 participants (48.1% female, aged 51.8 ± 14.0) completed the survey, most of which (72%, n = 155) reported pain as their main reason for cannabinoid therapy. When comparing the current state with the retrospectively assessed state, participants reported greater satisfaction with their overall medical therapy (TSQM II: +47.9 ± 36.5, p < 0.001); improved well-being (WHO-5: +7.8 ± 5.9, p < 0.001) and fewer problems in PROMIS subscales (all p < 0.001). Patients suffering primarily from pain (72%, n = 155) reported a reduction of daily pain (NRS: −3.2 ± 2.0, p < 0.001), while participants suffering mainly from spasticity (8%, n = 17) stated decreased muscle spasticity (MSSS: −1.5 ± 0.6, p < 0.001) and better physical mobility (−0.8 ± 0.8, p < 0.001). Data suggests clinically relevant effects for most scores. Participants’ attitudes toward cannabinoids (on a 5-point scale) improved (+1.1 ± 1.1, p < 0.001). Most patients (n = 146, 69%) did not report major difficulties with the cannabinoid prescription process, while (n = 27; 19%) had their cannabinoid therapy changed due to side effects.

Discussion

Most participants experienced their therapy with cannabinoids as more effective than their previous therapy. There are extensive limitations to this cross-sectional study: the originally intended representativeness of the dataset was not reached, partly due to the SARS-CoV-2 pandemic; the sample has a larger proportion of privately insured and self-paying patients. Results does not suggest that cannabinoid patients belong to a particular clientele. Effect sizes observed for pain reduction, quality of life, social participation, and other outcomes suggest a therapeutic potential, particularly in the treatment of chronic pain.
Evaluation of tracheostomy suctioning procedure among nursing and respiratory therapy students: wearable manikin vs. standard manikin
Authors: Lumowa Kevin , Lui Kin Long , Daher Noha , Baek Caroline , Tan Laren D. , Alismail Abdullah
Published: December 2023

Introduction

This study aims to evaluate cognitive load (CL), emotional levels (EL), and stress levels (SL) of students when using a wearable manikin vs. a standard manikin for tracheostomy suctioning (TS).

Methods

This study was approved by the Institutional Review Board. Subjects were recruited by email. Subjects completed a baseline demographics questionnaire, then they were randomized into two groups: wearable manikin group (WMG) or standard manikin group (SMG). For the WMG, an actor simulated a patient by wearing the device. In phase I, both groups were educated on how to perform TS by video and offered hands-on practice. Then I put through a tracheostomy suctioning clinical simulation and completed a post sim-survey. In phase II, the same survey was repeated after encountering a real patient as part of their clinical rotation.

Results

A total of 30 subjects with a mean age 26.0 ± 5.5 years participated. 20 (66.7%) were respiratory care students and 10 (33.3%) were nursing students. In the WMG, the median stress level dropped significantly post phase II compared to post phase I [2(1,4) vs.3(1,5), p = 0.04]. There were no significant changes in median CL, confidence, and satisfaction levels between post phase II and post phase I (p > 0.05). In the SMG, the satisfaction level increased significantly post phase II compared to post phase I [5(4,5) vs.4(2,5), p = 0.004], but there were no significant changes in CL, SL, and confidence levels between post phase I and phase II. There was no significant difference in mean EL scores over time and these changes did not differ by group. Subjects in the WMG showed a higher mean competency score than those in the SMG (85.5 ± 13.6 vs. 78.5 ± 20.8, p = 0.14, Cohen’s d = 0.4), yet not significant.

Conclusion

Our results showed that the WMG is beneficial in helping bridge the gap of learning TS from the sim setting to the real-world clinical setting. More studies with higher sample size and use of other CL scales that assesses the different types of CL are needed to validate our findings.
Case report: Deep vein thrombosis as the sole clinical feature of Behcet’s syndrome
Authors: Omara Abdelrahman , Alkhuboli Mohamed , Nauman Javaid , Al Nokhatha Shamma , Almarshoodi Mozah
Published: December 2023

Introduction

Behcet’s syndrome is a rare, chronic, systemic condition often categorized within the group of vasculitides. It presents a diagnostic challenge due to its varied clinical manifestations and the absence of a definitive laboratory test. Its etiology remains unclear but may involve genetic, infectious, and environmental factors.

Case presentation

We report the case of a 16-year-old male who presented with deep vein thrombosis, followed by recurrent episodes of breakthrough thrombosis, despite adequate anticoagulant therapy. The patient did not meet the International Study Group (ISG) criteria nor the International Criteria for Behcet’s syndrome (ICBD) due to the absence of characteristic features such as oral aphthous ulcers, genital ulcers, and uveitis. Later in the disease course, after ruling out other causes of breakthrough thrombosis, he tested positive for HLA-B51, an allele associated with Behcet’s syndrome, and exhibited a pathergy reaction.

Discussion

The patient’s clinical course underlines the diagnostic complexity associated with Behcet’s syndrome and highlights the importance of maintaining a broad differential diagnosis in cases of recurrent thrombosis. Although HLA-B51 testing is not routinely recommended, it played a pivotal role in our case, underscoring the value of an integrated diagnostic approach. Furthermore, this case reinforces the potential for atypical presentations of Behcet’s syndrome, necessitating vigilant clinical awareness. After establishing the diagnosis, we successfully treated the patient with immunosuppressive therapy, significantly improving his condition.
Bacteriophage SPO1 protein Gp46 suppresses functions of HU protein in Francisella tularensis
Authors: Spidlova Petra , Sokolova Eliska , Pavlik Pavla
Published: December 2023

The nucleoid-associated protein HU is a common bacterial transcription factor, whose role in pathogenesis and virulence has been described in many bacteria. Our recent studies showed that the HU protein is an indispensable virulence factor in the human pathogenic bacterium Francisella tularensis, a causative agent of tularemia disease, and that this protein can be a key target in tularemia treatment or vaccine development. Here, we show that Francisella HU protein is inhibited by Gp46, a protein of Bacillus subtilis bacteriophage SPO1. We predicted that Gp46 could occupy the F. tularensis HU protein DNA binding site, and subsequently confirmed the ability of Gp46 to abolish the DNA-binding capacity of HU protein. Next, we showed that the growth of Francisella wild-type strain expressing Gp46 in trans corresponded to that of a deletion mutant strain lacking the HU protein. Similarly, the efficiency of intracellular proliferation in mouse macrophages resembled that of the deletion mutant strain, but not that of the wild-type strain. These results, in combination with findings from a recent study on Gp46, enabled us to confirm that Gp46 could be a universal inhibitor of HU proteins among bacterial species.
Different responses of mice and rats hippocampus CA1 pyramidal neurons to in vitro and in vivo-like inputs
Authors: Vitale Paola , Librizzi Fabio , Vaiana Andrea C. , Capuana Elisa , Pezzoli Maurizio , Shi Ying , Romani Armando , Migliore Michele , Migliore Rosanna
Published: December 2023

The fundamental role of any neuron within a network is to transform complex spatiotemporal synaptic input patterns into individual output spikes. These spikes, in turn, act as inputs for other neurons in the network. Neurons must execute this function across a diverse range of physiological conditions, often based on species-specific traits. Therefore, it is crucial to determine the extent to which findings can be extrapolated between species and, ultimately, to humans. In this study, we employed a multidisciplinary approach to pinpoint the factors accounting for the observed electrophysiological differences between mice and rats, the two species most used in experimental and computational research. After analyzing the morphological properties of their hippocampal CA1 pyramidal cells, we conducted a statistical comparison of rat and mouse electrophysiological features in response to somatic current injections. This analysis aimed to uncover the parameters underlying these distinctions. Using a well-established computational workflow, we created ten distinct single-cell computational models of mouse CA1 pyramidal neurons, ready to be used in a full-scale hippocampal circuit. By comparing their responses to a variety of somatic and synaptic inputs with those of rat models, we generated experimentally testable hypotheses regarding species-specific differences in ion channel distribution, kinetics, and the electrophysiological mechanisms underlying their distinct responses to synaptic inputs during the behaviorally relevant Gamma and Sharp-Wave rhythms.
Trigeminal neuralgia associated with dural arteriovenous fistula: a case report and literature reviews
Authors: Zhou Hao , Wei Xingrong , Zeng Defeng , Zhang Shuguang , Hu Xueqian , Wei Zhenqin , Li Yang
Published: December 2023

Trigeminal neuralgia is a paroxysmal, intense electric shock-like, or knife-like, recurrent pain that affects one or more sense areas of the unilateral facial trigeminal nerve. It can be classified into two groups from an etiological standpoint: primary and secondary. The pain episodes brought on by such vascular compression are still categorized as primary trigeminal neuralgia, despite the fact that microvascular compression of the trigeminal nerve root has now been demonstrated to be the primary cause. A rare and complicated condition known as a dural arteriovenous fistula (DAVF) can irritate the Gasserian ganglion or compress the trigeminal nerve’s root entry zone (REZ), leading to secondary trigeminal neuralgia (TN). At present, the treatment of DAVF-induced trigeminal neuralgia is not conclusive. This article reports a case of DAVF-induced trigeminal neuralgia cured by MVD and reviews the relevant literature.
Induction of cerebellar cortical neurogenesis immediately following valproic acid exposure in ferret kits
Authors: Kamiya Shiori , Kobayashi Tetsuya , Sawada Kazuhiko
Published: December 2023

Introduction

Valproic acid (VPA) is an anticonvulsant/antiepileptic drug that regulates neurogenesis. Its effects vary depending on the timing of exposure and the types of neural progenitors involved. Neonatal exposure to VPA causes autism spectrum disorder-like behaviors in some mammalian species, including ferrets. Ferrets experience the cerebellar cortical histogenesis during early postnatal period. However, no studies have evaluated the effect of VPA on cerebellar corticohistogenesis. The present study aimed to determine the effects of VPA exposure on the developing cerebellar cortex in ferret kits with a particular focus on the cortical neurogenesis.

Methods

The experimental kits each received an intraperitoneal injection of VPA, 200 μg/g body weight, on postnatal days 6 and 7. EdU and BrdU were administered on postnatal days 5 and 7, respectively, to label cells proliferating prior to and following exposure to VPA.

Results

We found that 2 h post BrdU injection, BrdU-labeled cells were abundantly distributed in the internal granular layer (IGL), whereas EdU-labeled cells were primarily relegated to the inner pre-migratory zone of the external granular layer (EGL). The density of BrdU-single-labeled cells was significantly lower in the EGL and significantly higher in the IGL of the VPA-exposed group, as compared to the control group. Immunostaining for doublecortin, a marker of immature neurons, was observed in BrdU-single-labeled cells in the IGL of the VPA-exposed group, which was significantly higher than that observed in the control group. EdU-single-labeled cells that had proliferated prior to VPA exposure were also detected in the IGL. While the cell density remained unchanged, significant changes were observed in the proportions of EdU-single-labeled cells immunostained with marker antigens; higher proportion of PCNA immunostaining, but lower proportion of S100 immunostaining in the VPA-exposed group compared to the control group.

Discussion

These findings suggest the presence of progenitors in the IGL of the developing cerebellar cortex in ferret kits. We called them “internal granular progenitors.” The progenitors may proliferate in response to VPA, leading the differentiated lineage more toward neurons than to glial cells. Thus, VPA may facilitate the differentiative division of internal granular progenitors to produce cerebellar granular neurons.
The prognostic value of zonal origin in clinically localized prostate cancer: a systematic review and meta-analysis
Authors: Jin Shijie , Wu Liyi , Liang Zhen , Yan Weigang
Published: December 2023

Introduction

Correlation between zonal origin of clinically localized prostate cancer (PC) and biochemical recurrence (BCR) after treatment is still controversial.

Methods

We performed a meta-analysis of published articles to investigate the prognostic value of zonal origin in clinically localized PC. Literature was searched from Medline, Embase, Scopus, and Web of Science, from inception to Nov 1st, 2022. The risk of BCR was compared between PC originating from transition zone with peripheral zone. Relative risk (RR) was pooled in a random-effects model. Subgroup analysis and meta-regression were conducted to assess the source of heterogeneity.

Results

16 cohorts and 19,365 patients were included. PC originating from transition zone was associated with a lower risk of BCR (RR, 0.79, 95%CI; 0.69-0.92, I2, 76.8%). The association was consistent in studies with median follow-up time ≥60 months (RR, 0.65; 95%CI, 0.48 to 0.88, I2 56.8%), studies with NOS score ≥8 (RR, 0.70; 95%CI, 0.62 to 0.80, I2 32.4%), and studies using multivariate regression model (RR, 0.57; 95%CI, 0.48 to 0.69, I2 23%).

Discussion

This meta-analysis supported that transition zone origin was an independent prognostic factor of a better biochemical result in clinically localized prostate cancer after treatment.

Systematic review registration

10.37766/inplasy2023.11.0100, identifier INPLASY2023110100.
Pediatric renal lithiasis in Spain: research, diagnostic and therapeutic challenges, and perspectives
Authors: Lumbreras Javier , Madariaga Leire , Rodrigo María Dolores
Published: December 2023

Incidence and prevalence of urolithiasis is apparently increasing worldwide, also among children and adolescents. Nevertheless, robust data have only been obtained in a few countries. In Spain, a voluntary Registry for Pediatric Renal Lithiasis has been active since 2015. Irregular participation limits its applicability, as well as its limitation to patients with a stone available for morphocompositional study, to obtain data about incidence and prevalence. On the other hand, findings about typology of stones and clinical and analytical characteristics of these subjects have been communicated in several meetings. Other valuable efforts in this field are the elaboration of guidelines for the collection and processing of urine samples for the study of urolithiasis in pediatric patients with the consensus of the Spanish Society for Pediatric Nephrology (AENP) as well as the Spanish Society for Laboratory Medicine (SEQC), the collaborative network RenalTube for the diagnosis of primary tubulopathies and the registry of patients with Primary Hyperoxaluria (OxalSpain). In many hospitals from the public healthcare system, pediatric nephrologists are the specialists in charge of the management of children with kidney stones, but there is no formal regulation on this competence. Other specialists, such as urologists, pediatric surgeons or pediatric urologists, in many cases do not offer a complete insight into the etiopathogenic mechanisms and the consequent medical treatment. Access to medication according to standards of treatment is warranted, provided a correct diagnosis is achieved, but criteria for the reimbursement of certain therapies, such as RNAi drugs for primary hyperoxaluria, are arguable.
Case Report: Acute abdomen and large mesenteric mass as another face of multisystem inflammatory syndrome in an adolescent child: measure twice, act once!
Authors: Bakir Mustafa , Iqbal Umair , Gazal Ayoolamide N. , Robertson Daniel
Published: December 2023

Introduction

During the Covid-19 era, acute abdomen and mesenteric lymphadenopathy were encountered as frequent mimic of appendicitis. This phenomenon can further complicate the diagnosis of acute abdominal conditions, not solely due to bacterial or viral intestinal infections but also attributable to post-infectious acute inflammatory states resulting in either undertreatment of inflammatory conditions or unnecessary surgery.

Case presentation

In this case study, we present the case of an 11-year-old female who initially presented with fever and right lower quadrant abdominal pain, raising concerns of appendicitis. However, upon further investigation, it was revealed that she harbored a sizable mesenteric mass. Subsequent biopsy results unveiled a significant necrotic mesenteric lymphadenitis. Notably, this patient fulfilled the criteria for Multisystem Inflammatory Syndrome in Children (MIS-C), a condition that manifested following persistent postoperative fever. Remarkably, the patient exhibited a highly favorable response to the treatment administered. This clinical scenario presents an atypical manifestation of MIS-C, as the patient displayed a substantial mesenteric mass alongside symptoms mimicking appendicitis, within the context of an acute abdomen.

Conclusion

Clinicians should consider MIS-C and other post-infectious inflammatory conditions in mind when diagnosing acute abdominal cases. The presented case underscores the importance of recognizing atypical presentations of MIS-C that can mimic appendicitis, sometimes necessitating surgical resection of a large lymph node. We propose diagnostic flow chart to aid in the differentiation of acute bacterial appendicitis from MIS-C.
Cholecystectomy is associated with a higher risk of irritable bowel syndrome in the UK Biobank: a prospective cohort study
Authors: Zhao Jinyu , Tian Liang , Xia Bin , Mi Ningning , He Qiangsheng , Yang Man , Wang Danni , Wu Siqing , Li Zijun , Zhang Shiyong , Zhang Xianzhuo , Yue Ping , Lin Yanyan , Zhao Haitong , Zhang Baoping , Ma Zelong , Jiang Ningzu , Li Matu , Yuan Jinqiu , Nie Peng , Lu Linzhi , Meng Wenbo
Published: December 2023

Background: Recent studies have shown that bile acids are essential in irritable bowel syndrome (IBS) pathology, and cholecystectomy has direct effects on bile acid metabolism. However, whether cholecystectomy increases the risk of IBS remains unclear. We aimed to investigate the association between cholecystectomy and IBS risk in the UK Biobank (UKB).

Methods: This study is a prospective analysis of 413,472 participants who were free of IBS, inflammatory bowel disease, cancer, or common benign digestive tract diseases. We identified incidents of IBS through self-reporting or links to primary healthcare and hospitalization data. We evaluated hazard ratios (HRs) adjusted for sociodemographic characteristics, health behaviours, comorbidities, and medications.

Results: During a median follow-up period of 12.7 years, we observed 15,503 new cases of IBS. Participants with a history of cholecystectomy had a 46% higher risk of IBS than those without (HR = 1.46, 95% CI: 1.32–1.60), and further subtype analysis showed that the risk of IBS with diarrhoea was significantly higher than the risk of IBS without diarrhoea (HR = 1.71, 95% CI: 1.30–2.25 vs. HR = 1.42, 95% CI: 1.28–1.58). The overall covariate-adjusted HRs for IBS were similar between the group with both cholecystectomy and gallstones (HR = 1.45, 95% CI: 1.32–1.58) and the group with cholecystectomy without gallstones (HR = 1.50, 95% CI: 1.36–1.67) when the group without both cholecystectomy and gallstones was used as a reference. The overall covariate-adjusted HR was not significantly different in the group without cholecystectomy with gallstones (HR = 1.18, 95% CI: 0.95–1.47). The positive association of cholecystectomy with IBS risk did not change when stratifying the data based on age, sex, BMI, smoking, alcohol consumption, healthy diet, quality sleep, physical activity, type 2 diabetes, hypertension, hyperlipidaemia, mental illness, NSAID intake, or acid inhibitor intake. Sensitivity analyses, including propensity score matching analysis and lagging the exposure for two or four years, indicated that the effects were robust.

Conclusion: Cholecystectomy was associated with a higher risk of IBS, especially IBS with diarrhoea. Additional prospective randomized controlled and experimental studies are warranted to further validate the association and to explore the relevant biological mechanisms.
Recent progress in the role of endogenous metal ions in doxorubicin-induced cardiotoxicity
Authors: Zhou Ni , Wei Shanshan , Sun Taoli , Xie Suifen , Liu Jian , Li Wenqun , Zhang Bikui
Published: December 2023

Doxorubicin is a widely used anticancer drug in clinical practice for the treatment of various human tumors. However, its administration is associated with cardiotoxicity. Administration of doxorubicin with low side effects for cancer treatment and prevention are, accordingly, urgently required. The human body harbors various endogenous metal ions that exert substantial influences. Consequently, extensive research has been conducted over several decades to investigate the potential of targeting endogenous metal ions to mitigate doxorubicin’s side effects and impede tumor progression. In recent years, there has been a growing body of research indicating the potential efficacy of metal ion-associated therapeutic strategies in inhibiting doxorubicin-induced cardiotoxicity (DIC). These strategies offer a combination of favorable safety profiles and potential clinical utility. Alterations in intracellular levels of metal ions have been found to either facilitate or mitigate the development of DIC. For instance, ferroptosis, a cellular death mechanism, and metal ions such as copper, zinc, and calcium have been identified as significant contributors to DIC. This understanding can contribute to advancements in cancer treatment and provide valuable insights for mitigating the cardiotoxic effects of other therapeutic drugs. Furthermore, potential therapeutic strategies have been investigated to alleviate DIC in clinical settings. The ultimate goal is to improve the efficacy and safety of Dox and offer valuable insights for future research in this field.
Efficacies of S-nitrosoglutathione (GSNO) and GSNO reductase inhibitor in SARS-CoV-2 spike protein induced acute lung disease in mice
Authors: Kim Judong , Qiao Fei , Singh Avtar K. , Won Jeseong , Singh Inderjit
Published: December 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially surfaced in late 2019, often triggers severe pulmonary complications, encompassing various disease mechanisms such as intense lung inflammation, vascular dysfunction, and pulmonary embolism. Currently, however, there’s no drug addressing all these mechanisms simultaneously. This study explored the multi-targeting potential of S-nitrosoglutathione (GSNO) and N6022, an inhibitor of GSNO reductase (GSNOR) on markers of inflammatory, vascular, and thrombotic diseases related to COVID-19-induced acute lung disease. For this, acute lung disease was induced in C57BL/6 mice through intranasal administration of recombinant SARS-CoV-2 spike protein S1 domain (SP-S1). The mice exhibited fever, body weight loss, and increased blood levels and lung expression of proinflammatory cytokines (e.g., TNF-α and IL-6) as well as increased vascular inflammation mediated by ICAM-1 and VCAM-1 and lung infiltration by immune cells (e.g., neutrophils, monocytes, and activated cytotoxic and helper T cells). Further, the mice exhibited increased lung hyperpermeability (lung Evans blue extravasation) leading to lung edema development as well as elevated blood coagulation factors (e.g., fibrinogen, thrombin, activated platelets, and von Willebrand factor) and lung fibrin deposition. Similar to the patients with COVID-19, male mice showed more severe disease than female mice, along with higher GSNOR expression in the lungs. Optimization of GSNO by treatment with exogenous GSNO or inhibition of GSNOR by N6022 (or GSNO knockout) protects against SP-S1-induced lung diseases in both genders. These findings provide evidence for the potential efficacies of GSNO and GSNOR inhibitors in addressing the multi-mechanistic nature of SARS-CoV-2 SP-associated acute-lung disease.
TRPA1 channel mediates methylglyoxal-induced mouse bladder dysfunction
Authors: Oliveira Akila L. , Medeiros Matheus L. , Gomes Erick de Toledo , Mello Glaucia Coelho , Costa Soraia Katia Pereira , Mónica Fabíola Z. , Antunes Edson
Published: December 2023

Introduction: The transient receptor potential ankyrin 1 channel (TRPA1) is expressed in urothelial cells and bladder nerve endings. Hyperglycemia in diabetic individuals induces accumulation of the highly reactive dicarbonyl compound methylglyoxal (MGO), which modulates TRPA1 activity. Long-term oral intake of MGO causes mouse bladder dysfunction. We hypothesized that TRPA1 takes part in the machinery that leads to MGO-induced bladder dysfunction. Therefore, we evaluated TRPA1 expression in the bladder and the effects of 1 h-intravesical infusion of the selective TRPA1 blocker HC-030031 (1 nmol/min) on MGO-induced cystometric alterations.

Methods: Five-week-old female C57BL/6 mice received 0.5% MGO in their drinking water for 12 weeks, whereas control mice received tap water alone.

Results: Compared to the control group, the protein levels and immunostaining for the MGO-derived hydroimidazolone isomer MG-H1 was increased in bladders of the MGO group, as observed in urothelium and detrusor smooth muscle. TRPA1 protein expression was significantly higher in bladder tissues of MGO compared to control group with TRPA1 immunostaining both lamina propria and urothelium, but not the detrusor smooth muscle. Void spot assays in conscious mice revealed an overactive bladder phenotype in MGO-treated mice characterized by increased number of voids and reduced volume per void. Filling cystometry in anaesthetized animals revealed an increased voiding frequency, reduced bladder capacity, and reduced voided volume in MGO compared to vehicle group, which were all reversed by HC-030031 infusion.

Conclusion: TRPA1 activation is implicated in MGO-induced mouse overactive bladder. TRPA1 blockers may be useful to treat diabetic bladder dysfunction in individuals with high MGO levels.
Fat oxidation rates and cardiorespiratory responses during exercise in different subject populations with post-acute sequelae of SARS-CoV-2 infection: a comparison with normative percentile values
Authors: Meloni Andrea , Codella Roberto , Gotti Daniel , Di Gennaro Simone , Luzi Livio , Filipas Luca
Published: December 2023

Introduction: Post-acute sequelae of SARS-CoV-2 infection (PASC) presents a spectrum of symptoms following acute COVID-19, with exercise intolerance being a prevalent manifestation likely linked to disrupted oxygen metabolism and mitochondrial function. This study aims to assess maximal fat oxidation (MFO) and exercise intensity at MFO (FATmax) in distinct PASC subject groups and compare these findings with normative data.

Methods: Eight male subjects with PASC were involved in this study. The participants were divided into two groups: “endurance-trained” subjects (V˙O2max > 55 mL/min/kg) and “recreationally active” subjects (V˙O2max < 55 mL/min/kg). Each subject performed a graded exercise test until maximal oxygen consumption (V˙O2max) to measure fat oxidation. Subsequently, MFO was assessed, and FATmax was calculated as the ratio between V˙O2 at MFO and V˙O2 max.

Results: The MFO and FATmax of “endurance-trained” subjects were 0.85, 0.89, 0.71, and 0.42 and 68%, 69%, 64%, and 53%, respectively. Three out of four subjects showed both MFO and FATmax values placed over the 80th percentile of normative data. The MFO and FATmax of “recreationally active” subjects were 0.34, 0.27, 0.35, and 0.38 and 47%, 39%, 43%, and 41%, respectively. All MFO and FATmax values of those subjects placed below the 20th percentile or between the 20th and 40th percentile.

Discussion: Significant differences in MFO and FATmax values between ‘endurance-trained’ and “recreationally active” subjects suggest that specific endurance training, rather than simply an active lifestyle, may provide protective effects against alterations in mitochondrial function during exercise in subjects with PASC.
An improved Deeplab V3+ network based coconut CT image segmentation method
Authors: Liu Qianfan , Zhang Yu , Chen Jing , Sun Chengxu , Huang Mengxing , Che Mingwei , Li Chun , Lin Shenghuang
Published: December 2023

Due to the unique structure of coconuts, their cultivation heavily relies on manual experience, making it difficult to accurately and timely observe their internal characteristics. This limitation severely hinders the optimization of coconut breeding. To address this issue, we propose a new model based on the improved architecture of Deeplab V3+. We replace the original ASPP(Atrous Spatial Pyramid Pooling) structure with a dense atrous spatial pyramid pooling module and introduce CBAM(Convolutional Block Attention Module). This approach resolves the issue of information loss due to sparse sampling and effectively captures global features. Additionally, we embed a RRM(residual refinement module) after the output level of the decoder to optimize boundary information between organs. Multiple model comparisons and ablation experiments are conducted, demonstrating that the improved segmentation algorithm achieves higher accuracy when dealing with diverse coconut organ CT(Computed Tomography) images. Our work provides a new solution for accurately segmenting internal coconut organs, which facilitates scientific decision-making for coconut researchers at different stages of growth.