bluuebunny/crossref_metadata_2025 huggingface dataset:
From conception to recruitment: Nutritional condition of the dam dictates the likelihood of success in a temperate ungulate
Authors: Lamb Sydney , McMillan Brock R. , van de Kerk Madelon , Frandsen Paul B. , Hersey Kent R. , Larsen Randy T.
Published: March 2023

Maternal effects are the influence of maternal phenotype and the maternally-provided environment on the phenotype (i.e., expression of traits) of offspring. Frequently, maternal effects are manifest both before and after parturition. Pre-parturition effects are primarily direct allocation of energy to the offspring that isin utero. Post-parturition effects can include direct (e.g., nursing and defending offspring) and indirect (e.g., selection of habitat that is relatively safe or has high nutritional value) influences. While both direct and indirect effects are often discussed, there is a paucity of information on the relative importance of each type on offspring due to the difficulty in monitoring mothers prior to parturition and mother-offspring relationships after parturition in free-ranging animals. Our objective was to determine the importance of direct maternal effects on birth weight, growth rates, and survival of mule deer (Odocoileus hemionus) fawns from birth through the first 18 months of life. We determined the effect of nutritional condition of the dam (mother) on birth weight (pre-parturition direct effect). We also examined the post-parturition direct effect of dam nutritional condition on growth rates and survival of fawns. Direct maternal effects were evident both before and after parturition; dams in better nutritional condition produced offspring with greater mass at birth, higher rates of growth, and increased survival. Our findings demonstrate that maternal nutritional condition influences fawn health from gestation through recruitment. These links highlight the importance of considering direct maternal effects when examining population dynamics and reproductive success in long-lived mammals. Management plans for ungulates should include assessment of nutritional condition of adult females to maximize likelihood of effective conservation.
Vitamin B12 attenuates leukocyte inflammatory signature in COVID-19 via methyl-dependent changes in epigenetic markings
Authors: Cassiano Larissa M. G. , Cavalcante-Silva Vanessa , Oliveira Marina S. , Prado Bárbara V. O. , Cardoso Cristianne G. , Salim Anna C. M. , Franco Gloria R. , D’Almeida Vânia , Francisco Saionara C. , Coimbra Roney S.
Published: March 2023

COVID-19 induces chromatin remodeling in host immune cells, and it had previously been shown that vitamin B12 downregulates some inflammatory genes via methyl-dependent epigenetic mechanisms. In this work, whole blood cultures from moderate or severe COVID-19 patients were used to assess the potential of B12 as adjuvant drug. The vitamin normalized the expression of a panel of inflammatory genes still dysregulated in the leukocytes despite glucocorticoid therapy during hospitalization. B12 also increased the flux of the sulfur amino acid pathway, that regulates the bioavailability of methyl. Accordingly, B12-induced downregulation of CCL3 strongly and negatively correlated with the hypermethylation of CpGs in its regulatory regions. Transcriptome analysis revealed that B12 attenuates the effects of COVID-19 on most inflammation-related pathways affected by the disease. As far as we are aware, this is the first study to demonstrate that pharmacological modulation of epigenetic markings in leukocytes favorably regulates central components of COVID-19 physiopathology.
Proteomic characterisation of perhexiline treatment on THP-1 M1 macrophage differentiation
Authors: Dhakal Bimala , Li Celine Man Ying , Ramezanpour Mahnaz , Houtak Ghais , Li Runhao , Bouras George , Collela Alex , Chegeni Nusha , Chataway Tim Kennion , Drew Paul , Sallustio Benedetta C. , Vreugde Sarah , Smith Eric , Maddern Guy , Licari Giovanni , Fenix Kevin
Published: March 2023

Background

Dysregulated inflammation is important in the pathogenesis of many diseases including cancer, allergy, and autoimmunity. Macrophage activation and polarisation are commonly involved in the initiation, maintenance and resolution of inflammation. Perhexiline (PHX), an antianginal drug, has been suggested to modulate macrophage function, but the molecular effects of PHX on macrophages are unknown. In this study we investigated the effect of PHX treatment on macrophage activation and polarization and reveal the underlying proteomic changes induced.

Methods

We used an established protocol to differentiate human THP-1 monocytes into M1 or M2 macrophages involving three distinct, sequential stages (priming, rest, and differentiation). We examined the effect of PHX treatment at each stage on the polarization into either M1 or M2 macrophages using flow cytometry, quantitative polymerase chain reaction (qPCR) and enzyme linked immunosorbent assay (ELISA). Quantitative changes in the proteome were investigated using data independent acquisition mass spectrometry (DIA MS).

Results

PHX treatment promoted M1 macrophage polarization, including increased STAT1 and CCL2 expression and IL-1β secretion. This effect occurred when PHX was added at the differentiation stage of the M1 cultures. Proteomic profiling of PHX treated M1 cultures identified changes in metabolic (fatty acid metabolism, cholesterol homeostasis and oxidative phosphorylation) and immune signalling (Receptor Tyrosine Kinase, Rho GTPase and interferon) pathways.

Conclusion

This is the first study to report on the action of PHX on THP-1 macrophage polarization and the associated changes in the proteome of these cells.
Development of multi-epitope vaccines against the monkeypox virus based on envelope proteins using immunoinformatics approaches
Authors: Tan Caixia , Zhu Fei , Pan Pinhua , Wu Anhua , Li Chunhui
Published: March 2023

Background

Since May 2022, cases of monkeypox, a zoonotic disease caused by the monkeypox virus (MPXV), have been increasingly reported worldwide. There are, however, no proven therapies or vaccines available for monkeypox. In this study, several multi-epitope vaccines were designed against the MPXV using immunoinformatics approaches.

Methods

Three target proteins, A35R and B6R, enveloped virion (EV) form-derived antigens, and H3L, expressed on the mature virion (MV) form, were selected for epitope identification. The shortlisted epitopes were fused with appropriate adjuvants and linkers to vaccine candidates. The biophysical andbiochemical features of vaccine candidates were evaluated. The Molecular docking and molecular dynamics(MD) simulation were run to understand the binding mode and binding stability between the vaccines and Toll-like receptors (TLRs) and major histocompatibility complexes (MHCs). The immunogenicity of the designed vaccines was evaluated via immune simulation.

Results

Five vaccine constructs (MPXV-1-5) were formed. After the evaluation of various immunological and physicochemical parameters, MPXV-2 and MPXV-5 were selected for further analysis. The results of molecular docking showed that the MPXV-2 and MPXV-5 had a stronger affinity to TLRs (TLR2 and TLR4) and MHC (HLA-A*02:01 and HLA-DRB1*02:01) molecules, and the analyses of molecular dynamics (MD) simulation have further confirmed the strong binding stability of MPXV-2 and MPXV-5 with TLRs and MHC molecules. The results of the immune simulation indicated that both MPXV-2 and MPXV-5 could effectively induce robust protective immune responses in the human body.

Conclusion

The MPXV-2 and MPXV-5 have good efficacy against the MPXV in theory, but further studies are required to validate their safety and efficacy.
A multiscale mechanistic model of human dendritic cells for in-silico investigation of immune responses and novel therapeutics discovery
Authors: Aghamiri Sara Sadat , Puniya Bhanwar Lal , Amin Rada , Helikar Tomáš
Published: March 2023

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) with the unique ability to mediate inflammatory responses of the immune system. Given the critical role of DCs in shaping immunity, they present an attractive avenue as a therapeutic target to program the immune system and reverse immune disease disorders. To ensure appropriate immune response, DCs utilize intricate and complex molecular and cellular interactions that converge into a seamless phenotype. Computational models open novel frontiers in research by integrating large-scale interaction to interrogate the influence of complex biological behavior across scales. The ability to model large biological networks will likely pave the way to understanding any complex system in more approachable ways. We developed a logical and predictive model of DC function that integrates the heterogeneity of DCs population, APC function, and cell-cell interaction, spanning molecular to population levels. Our logical model consists of 281 components that connect environmental stimuli with various layers of the cell compartments, including the plasma membrane, cytoplasm, and nucleus to represent the dynamic processes within and outside the DC, such as signaling pathways and cell-cell interactions. We also provided three sample use cases to apply the model in the context of studying cell dynamics and disease environments. First, we characterized the DC response to Sars-CoV-2 and influenza co-infection by in-silico experiments and analyzed the activity level of 107 molecules that play a role in this co-infection. The second example presents simulations to predict the crosstalk between DCs and T cells in a cancer microenvironment. Finally, for the third example, we used the Kyoto Encyclopedia of Genes and Genomes enrichment analysis against the model’s components to identify 45 diseases and 24 molecular pathways that the DC model can address. This study presents a resource to decode the complex dynamics underlying DC-derived APC communication and provides a platform for researchers to perform in-silico experiments on human DC for vaccine design, drug discovery, and immunotherapies.
From a cell model to a fish trial: Immunomodulatory effects of heat-killed Lactiplantibacillus plantarum as a functional ingredient in aquafeeds for salmonids
Authors: Rocha Sérgio Domingos Cardoso , Lei Peng , Morales-Lange Byron , Mydland Liv Torunn , Øverland Margareth
Published: March 2023

Paraprobiotics (dead/inactivated probiotics) are promising candidates in functional feeds to promote growth performance, modulate intestinal microbiota and enhance immune response of fish. During industrial production, fish are exposed to several stressful conditions such as handling, sub-optimal nutrition and diseases that can lead to reduced growth, increased mortalities and large economical losses. Such problems can be mitigated by use of functional feeds, leading to more-sustainable aquaculture and improved animal welfare. Lactiplantibacillus plantarum strain L-137 is a common bacterium found in fermented Southeast Asian dish made from fish and rice. The benefits of its heat-killed form (HK L-137) related to growth performance and immunomodulation have been studied in farmed fish such as Nile Tilapia (Oreochromis niloticus), striped catfish (Pangasianodon hypophthalmus) and bighead catfish (Clarias macrocephalus). To study if such benefits can also be observed in salmonids, we worked both at in vitro level using an intestinal epithelium cell line from rainbow trout (Oncorhynchus mykiss; RTgutGC) stimulated with HK L-137 (Feed LP20™) and at in vivo level with pre-smolt Atlantic salmon (Salmo salar) fed HK L-137 at different inclusion levels (20, 100 and 500 mg of Feed LP20™ kg-1 feed). In RTgutGC, the results showed that the barrier function of the cell monolayer was strengthened along with an increased production of IL-1β and a decreased production of Anxa1, indicating a modulation of the immune response. Interestingly, a similar trend was detected at the in vivo level in distal intestine from fish fed the highest inclusion level of HK L-137. Here, a lower production of Anxa1 was also detected (after a 61-day feeding period) in addition to an increase of total plasma IgM in the same group. Furthermore, the RNA-seq analysis showed that HK L-137 was able to modulate the gene expression of pathways related to molecular function, biological process and cellular component in distal intestine, without compromising fish performance and gut microbiota. Taken together, our study has shown that HK L-137 can modulate physiological response of Atlantic salmon, making fish more robust against stressful conditions during production.
The effects of organic matter and anaerobic oxidation of methane on the microbial sulfate reduction in cold seeps
Authors: Sun Tiantian , Wu Daidai , Wu Nengyou , Yin Ping
Published: March 2023

Cold seep sediments are dominated by intensive microbial sulfate reduction coupled to anaerobic oxidation of methane. However, the contribution proportion between this process and the role of organic matter has remained enigmatic. Here, pore water data combined with PROFILE model, fluxes of sulfate and methane concentration calculated from Fick's first law, and δ34SSO4 and δ18OSO4 of pore water sulfate were studied to reconstruct co-occurring microbial organoclastic sulfate reduction and anaerobic oxidation of methane coupled with sulfate reduction in methane seep sediments collected from South China Sea. The sulfate concentration profiles of C9 and C14 in Qiongdongnan Basin generally show quasilinear depletion with depth. Reaction-transport modeling provided close fits to concentration data. δ18OSO4 and δ34SSO4 increase fastest with sediment depth above 400 cmbsf and slowest below that depth. The values of methane flux are always lower than those of total sulfate reduction of sulfate diffusive flux at GC-10, GC-9, GC-11 and HD319 sites in Taixinan Basin. Besides, positions of sulfate methane transition zone in all study sites are approximately ~400 to 800 centimeters below seafloor. These results showed that microbial sulfate reduction in sediments is mainly controlled by intense anaerobic oxidation of methane, but there is a certain relationship with organic matter metabolism process. This emphasizes that traditional redox order of bacterial respiration is highly simplified, where, in sediments such as these seeps, all of these microbial sulfate reduction processes can occur together with complex couplings between them.
Characteristics of auditory brainstem response in wild yellow grouper Epinephelus awoara
Authors: Zhu Xiangyu , Zhang Xinhai , Chen Mingru , Xu Xiaomei
Published: March 2023

Auditory brainstem response (ABR) technology is used to set up a fish auditory threshold detection system, and the auditory threshold of wild yellow grouper Epinephelus awoara caught in the Taiwan Strait is studied. The ABRs of 10 wild yellow groupers (TL150-200 mm) to 12 different frequencies of sound stimulation from 100 to 2000 Hz are recorded and analyzed. The results show that the auditory threshold of wild yellow grouper fish increases with the increase of frequency in the frequency of 200-2000Hz. The fish is sensitive to low frequency sound signal of 100-300Hz with the most sensitive frequency of 200Hz, and the auditory threshold is 90 dB re 1μPa. The ABR waveform shows three periods: response period, real hearing period and extension period. In the range of 100-2000Hz, the response time decreases with the increase of frequency at the same sound pressure level. At the same frequency, the response time increases with the decrease of sound pressure level. The first amplitude sound pressure of real hearing period is between 50-150nv, and the real hearing period contains the greatest amplitude. When the greatest amplitude is about 50nv and the next sound pressure level is below 50nv, the sound pressure level is the auditory threshold. The extension period is proportional to the response period.
China’s shipping market supervision system under theRCEP: Influence, challenges and countermeasures
Authors: Shi Yuanhong
Published: March 2023

The entry into force of the Regional Comprehensive Economic Partnership (RCEP), the world’s largest free trade agreement, has injected new vitality into multilateralism and free trade, against a background of global economic and political instability. Its core concept is to liberalize and facilitate trade. Regulation of the shipping market warrants attention. Under the RCEP, the international shipping industry is characterized by a digital development trend in shipping supervision, continuous upgrading of shipping management and supervision capabilities, and more open and transparent shipping market supervision. However, in the process of implementing new rules for shipping market supervision, there are still some challenges, such as logistics risks and loopholes in shipping supply chains, insufficient coordination of shipping supervision among RCEP member countries, and an imperfect legal and regulatory system. This paper therefore suggests that under the RCEP, China should strengthen the anti-risk ability of shipping supply chains, promote coordinated supervision among member countries, strengthen environmental protection, and promote the coordination of digital supervision.
Ultrasound-guided transversus abdominis plane block as an effective anesthetic technique for transverse colostomy in a high-risk elderly patient: A case report
Authors: Li Chao , Shi Jingpu , Jia Huiqun
Published: March 2023

Ultrasound-guided transversus abdominis plane (TAP) block is considered to be one of most prevalent and effective adjuvant analgesic methods for various abdominal surgeries. However, whether TAP blocks can be used alone as an effective anesthetic technique in minor abdominal operations has rarely been reported. Here we presented a 66-year-old male who had sustained right somatic dysfunction and mild brain dysfunction caused by cerebral infarctions and poorly treated hypertension. The patient received a confine operation of transverse colostomy to alleviate an intestinal obstruction caused by rectal cancer. A 22G needle was advanced in the plane under ultrasound guidance until it reached the TAP. A total of 10 mL 0.375% ropivacaine with 5 mg dexamethasone and 10 μg dexmedetomidine was injected into the TAP. The operation went stably and smoothly without any complaints. After the operation, the patient returned to the care of the surgical recovery staff with patient-controlled intravenous analgesia (PCIA) containing 0.7 mg/kg oxycodone and 2.5 μg/kg dexmedetomidine. During the perioperative period, the elderly patient did not experience apparent or unbearable pain. All these evidences indicated the ultrasound-guided subcostal and lateral TAP block was a simple and effective procedure for transverse colostomy in a high-risk elderly patient.
The association between retinal microvasculature derived from optical coherence tomography angiography and systemic factors in type 2 diabetics
Authors: Li Yi , Wu Kunfang , Chen Zilin , Xu Guihua , Wang Dingding , Wang Juanjuan , Bulloch Gabriella , Borchert Grace , Fan Huiya
Published: March 2023

Aims

To investigate the correlation between the retinal microvasculature using optical coherence tomography angiography (OCTA) and systemic factors in type 2 diabetes mellitus (T2DM) patients.

Methods

This cross-sectional study obtained OCTA data from patients with T2DM administered at hospital and referred to ophthalmic services. Patient data about demographics, comorbid conditions, and blood biomarkers were extracted from electronic medical records. Data from OCTA scans obtained by CIRRUS HD-OCT Model 5,000 were obtained. Vessel density (VD) and perfusion density (PD) within the superficial capillary plexus, and foveal avascular zone (FAZ) area were automatically segmented. These parameters were tested for their correlations with systemic factors by univariate and multivariable linear regression analyses.

Results

A total of 144 T2DM patients (236 eyes) were available for analysis, with mean age of 53.6 (SD = 10.34) and 56.9% were male. Chronic kidney disease, cardiovascular disease, increased serum creatinine (Scr), red blood cell count (RBC), platelets (PLT), apolipoprotein B (APOB), and decreased urine albumin to creatinine ratio (UACR) were significantly associated with lower VD and PD (all p < 0.013). UACR and triglyceride (TRIG) were significantly correlated with FAZ area (all p < 0.017). In multivariate analyses, PLT, eGFR, and APOB were independent risk factors for retinal rarefaction, and UACR was a significant predictor of FAZ area.

Conclusion

We found several systemic risk factors, such as PLT, renal function and lipid profiles were associated with PD, VD, and FAZ area among Chinese T2DM patients.
Prevalence of food insecurity and its association with depressive and anxiety symptoms in older adults during the COVID-19 pandemic in Mexico: A secondary analysis of ENCOVID-19 survey
Authors: Alán De la Vega Martínez , Oscar Rosas-Carrasco , Pablo Gaitán-Rossi , Mónica Ancira-Moreno , Miriam López-Teros
Published: March 2023

Introduction

COVID-19 infection has caused high rates of morbi-mortality in older adults (OAs). In addition, conditions such as depression, anxiety, unemployment, and poverty frequently contribute to this population being at higher risk of food insecurity (FI) during the COVID-19 pandemic.

Objective

This study aimed to analyze the prevalence of FI and its association with depressive and anxiety symptoms in Mexican OAs during the COVID-19 pandemic.

Methods

This study involved a secondary analysis of the National Survey on the Effects of COVID-19 on the Wellbeing of Mexican Households (ENCOVID-19), a series of cross-sectional telephone surveys conducted between April and October 2020. The OA subsample was 1,065. FI was measured by using the Latin American and Caribbean Food Security Scale (ELCSA), and depression and anxiety symptoms were measured by using the Depression Scale of the Center for Epidemiological Studies (CESD-7) and the Generalized Anxiety Disorder Scale (GAD-2), respectively. Socioeconomic status (SES), occupation, schooling, and pension were also evaluated. ANOVA was used to compare the variables between the different FI groups, and logistic regression was used to analyze the risk between FI and the anxiety and depression variables.

Results

The mean age of the participants was 67.31 ± 6.4 years, and FI was classified as mild, moderate, and severe, with prevalences of 38.6, 15.04, and 8.16%, respectively. Overall, 28.01% of the OAs presented symptoms of anxiety and 39.09% of depression. In the comparison between groups, a higher prevalence of depressive symptoms was observed with a higher degree of FI, with 65.75% in moderate-to-severe, 10.39% in mild, and 9.40% without FI, p ≤ 0.000. Regarding anxiety symptoms, 48% of the OAs showed moderate-to-severe, 30.05% showed mild, and 15.38% were without FI, p ≤ 0.000. Using multiple logistic regression, an OR of 5.50 (95% CI 2.74–11.04) was observed for depressive symptoms when moderate-to-severe FI is present. In the case of the risk of anxiety symptoms, it was significant in all degrees of FI, in mild (OR = 2.43, 95% CI 1.66–3.59) and in moderate-to-severe (OR = 5.32, 95% CI 3.45–8.19).

Conclusion

There is a high prevalence of FI in Mexican OAs during the COVID-19 pandemic. FI increases the risk of other conditions such as depression and anxiety. It is important to design and implement programs aimed at OAs with these conditions to reduce or prevent FI.
Targeting intracellular pathways in idiopathic inflammatory myopathies: A narrative review
Authors: La Rocca Gaetano , Ferro Francesco , Baldini Chiara , Libra Alessandro , Sambataro Domenico , Colaci Michele , Malatino Lorenzo , Palmucci Stefano , Vancheri Carlo , Sambataro Gianluca
Published: March 2023

In recent decades, several pieces of evidence have drawn greater attention to the topic of innate immunity, in particular, interferon (IFN) and Interleukin 6 in the pathogenesis of idiopathic inflammatory myopathies (IIM). Both of these molecules transduce their signal through a receptor coupled with Janus kinases (JAK)/signal transducer and activator of transcription proteins (STAT). In this review, we discuss the role of the JAK/STAT pathway in IIM, evaluate a possible therapeutic role for JAK inhibitors in this group of diseases, focusing on those with the strongest IFN signature (dermatomyositis and antisynthetase syndrome).
Sacral neuromodulation remote programming in patients with refractory lower urinary tract dysfunction: China’s experience during the COVID-19 pandemic
Authors: Meng Lingfeng , Hou Huimin , Zhang Peng , Gu Yinjun , Shi Benkang , Li Yan , Wang Qingwei , Zhang Yifei , Ren Lijuan , Chen Qi , Yuan Zhen , Guo Fan , Li Dianyou , Ma Yunfu , Dong Sheng , Liu Zhijun , Shang Aijia , Li Bo , Xu Wei , Lv Jianwei , Zhang Yaoguang
Published: March 2023

Objectives

Sacral neuromodulation is an effective, minimally invasive treatment for refractory lower urinary tract dysfunction. However, regular postoperative programming is crucial for the maintenance of the curative effects of electronic sacral stimulator devices. The outbreak of coronavirus disease 2019 (COVID-19) limited the ability of practitioners to perform traditional face-to-face programming of these stimulators. Therefore, this study aimed to evaluate the application of remote programming technology for sacral neuromodulation during the COVID-19 pandemic in China.

Materials and methods

We retrospectively collected data including baseline and programming information of all patients with lower urinary tract dysfunction who underwent sacral neuromodulation remote programming in China after the outbreak of COVID-19 (i.e., December 2019). The patients also completed a self-designed telephone questionnaire on the subject.

Results

A total of 51 patients from 16 centers were included. They underwent 180 total remote programming visits, and 118, 2, 25, and 54 voltage, current, pulse width, and frequency adjustments, respectively, were performed. Additionally, remote switching on and off was performed 8 times; impedance test, 54 times; and stimulation contact replacement, 25 times. The demand for remote programming was the highest during the first 6 months of sacral neuromodulation (average, 2.39 times per person). In total, 36 out of the 51 patients completed the questionnaire survey. Of these, all indicated that they chose remote programming to minimize unnecessary travel because they had been affected by COVID-19. The questionnaire also showed that remote programming could reduce the number of patient visits to the hospital, save time, reduce financial costs, and would be easy for patients to master. All surveyed patients indicated that they were satisfied with remote programming and were willing to recommend it to other patients.

Conclusion

Remote programming for sacral neuromodulation is feasible, effective, safe, and highly recommended by patients with refractory lower urinary tract dysfunction. Remote programming technology has great development and application potential in the post-pandemic era.
Objective evaluation of tongue diagnosis ability using a tongue diagnosis e-learning/e-assessment system based on a standardized tongue image database
Authors: Segawa Makoto , Iizuka Norio , Ogihara Hiroyuki , Tanaka Koichiro , Nakae Hajime , Usuku Koichiro , Yamaguchi Kojiro , Wada Kentaro , Uchizono Akihiro , Nakamura Yuji , Nishida Yoshihiro , Ueda Toshiko , Shiota Atsuko , Hasunuma Naoko , Nakahara Kyoko , Hebiguchi Miwa , Hamamoto Yoshihiko
Published: March 2023

Background

In Kampo medicine, tongue examination is used to diagnose the pathological condition “Sho,” but an objective evaluation method for its diagnostic ability has not been established. We constructed a tongue diagnosis electronic learning and evaluation system based on a standardized tongue image database.

Purpose

This study aims to verify the practicality of this assessment system by evaluating the tongue diagnosis ability of Kampo specialists (KSs), medical professionals, and students.

Methods

In the first study, we analyzed the answer data of 15 KSs in an 80-question tongue diagnosis test that assesses eight aspects of tongue findings and evaluated the (i) test score, (ii) test difficulty and discrimination index, (iii) diagnostic consistency, and (iv) diagnostic match rate between KSs. In the second study, we administered a 20-question common Kampo test and analyzed the answer data of 107 medical professionals and 56 students that assessed the tongue color discrimination ability and evaluated the (v) correct answer rate, (vi) test difficulty, and (vii) factors related to the correct answer rate.

Result

In the first study, the average test score was 62.2 ± 10.7 points. Twenty-eight questions were difficult (correct answer rate, <50%), 34 were moderate (50%–85%), and 18 were easy (≥85%). Regarding intrarater reliability, the average diagnostic match rate of five KSs involved in database construction was 0.66 ± 0.08, and as for interrater reliability, the diagnostic match rate between the 15 KSs was 0.52 (95% confidence interval, 0.38–0.65) for Gwet's agreement coefficient 1, and the degree of the match rate was moderate. In the second study, the difficulty level of questions was moderate, with a correct rate of 81.3% for medical professionals and 82.1% for students. The discrimination index was good for medical professionals (0.35) and poor for students (0.06). Among medical professionals, the correct answer group of this question had a significantly higher total score on the Kampo common test than the incorrect answer group (85.3 ± 8.4 points vs. 75.8 ± 11.8 points,p < 0.01).

Conclusion

This system can objectively evaluate tongue diagnosis ability and has high practicality. Utilizing this system can be expected to contribute to improving learners’ tongue diagnosis ability and standardization of tongue diagnosis.
Aflatoxin contamination of maize and groundnut in Burundi: Distribution of contamination, identification of causal agents and potential biocontrol genotypes of Aspergillus flavus
Authors: Nsabiyumva Gedeon , Mutegi Charity K. , Wagacha John M. , Mohamed Asha B. , Njeru Nancy K. , Ndayihanzamaso Privat , Niyuhire Marie Chantal , Atehnkeng Joseph , Njukwe Emmanuel , Callicott Kenneth A. , Cotty Peter J. , Ortega-Beltran Alejandro , Bandyopadhyay Ranajit
Published: March 2023

Aflatoxin contamination of the staples maize and groundnut is a concern for health and economic impacts across sub-Saharan Africa. The current study (i) determined aflatoxin levels in maize and groundnut collected at harvest in Burundi, (ii) characterized populations of Aspergillus section Flavi associated with the two crops, and (iii) assessed aflatoxin-producing potentials among the recovered fungi. A total of 120 groundnut and 380 maize samples were collected at harvest from eight and 16 provinces, respectively. Most of the groundnut (93%) and maize (87%) contained aflatoxin below the European Union threshold, 4 μg/kg. Morphological characterization of the recovered Aspergillus section Flavi fungi revealed that the L-morphotype of A. flavus was the predominant species. Aflatoxin production potentials of the L-morphotype isolates were evaluated in maize fermentations. Some isolates produced over 137,000 μg/kg aflatoxin B1. Thus, despite the relatively low aflatoxin levels at harvest, the association of both crops with highly toxigenic fungi poses significant risk of post-harvest aflatoxin contamination and suggests measures to mitigate aflatoxin contamination in Burundi should be developed. Over 55% of the L-morphotype A. flavus did not produce aflatoxins. These atoxigenic L-morphotype fungi were characterized using molecular markers. Several atoxigenic genotypes were detected across the country and could be used as biocontrol agents. The results from the current study hold promise for developing aflatoxin management strategies centered on biocontrol for use in Burundi to reduce aflatoxin contamination throughout the value chain.
Understanding the mechanisms of halotolerance in members of Pontixanthobacter and Allopontixanthobacter by comparative genome analysis
Authors: Zhou Peng , Bu Yu-Xin , Xu Lin , Xu Xue-Wei , Shen Hong-Bin
Published: March 2023

Halotolerant microorganisms have developed versatile mechanisms for coping with saline stress. With the increasing number of isolated halotolerant strains and their genomes being sequenced, comparative genome analysis would help understand the mechanisms of salt tolerance. Six type strains of Pontixanthobacter and Allopontixanthobacter, two phylogenetically close genera, were isolated from diverse salty environments and showed different NaCl tolerances, from 3 to 10% (w/v). Based on the co-occurrence greater than 0.8 between halotolerance and open reading frame (ORF) among the six strains, possible explanations for halotolerance were discussed regarding osmolyte, membrane permeability, transportation, intracellular signaling, polysaccharide biosynthesis, and SOS response, which provided hypotheses for further investigations. The strategy of analyzing genome-wide co-occurrence between genetic diversity and physiological characteristics sheds light on how microorganisms adapt to the environment.
Soil microbes support Janzen’s mountain passes hypothesis: The role of local-scale climate variability along a tropical montane gradient
Authors: Feng Yifan , Wang Jianbin , Zhang Jian , Qi Xuming , Long Wenxing , Ding Yi , Liu Lan
Published: March 2023

Tropical montane ecosystems are the centers of biodiversity, and Janzen proposed that mountain climate variability plays a key role in sustaining this biodiversity. We test this hypothesis for soil bacteria and fungi along a 265–1,400 m elevational gradient on Hainan Island of tropical China, representing diverse vegetation types from deciduous monsoon forest to cloud forest. We found that bacterial and fungal diversity declined as elevation increased, and the dissimilarity of both groups increased with increasing separation in elevation, although changes in bacteria were larger than in fungi. Seasonal alterations and the range of soil moisture in the growing season were found to be the dominant drivers of fungal richness and Shannon diversity, whereas soil pH was the major driver of bacterial diversity. Dissimilarities of bacterial and fungal communities were best predicted by climate, particularly seasonal changes in soil temperature, with weaker influences of soil physicochemistry and vegetation. The dominant effect of seasonality in soil temperature was further detected in cloud forests, which harbored a higher proportion of unique bacterial species and dissimilarity of bacterial and fungal communities. Our findings suggest that local-climate variability plays a crucial role in structuring the distribution of soil microbial communities along a tropical montane gradient, which generally supports Janzen’s hypothesis. Such a sensitivity to climatic variability suggests that soil microbial communities along tropical montane gradients may shift in response to future climate scenarios.
Aneurysm wall enhancement, hemodynamics, and morphology of intracranial fusiform aneurysms
Authors: Liang Xinyu , Peng Fei , Yao Yunchu , Yang Yuting , Liu Aihua , Chen Duanduan
Published: March 2023

Background and objective

Intracranial fusiform aneurysms (IFAs) are considered to have a complex pathophysiology process and poor natural history. The purpose of this study was to investigate the pathophysiological mechanisms of IFAs based on the characteristics of aneurysm wall enhancement (AWE), hemodynamics, and morphology.

Methods

A total of 21 patients with 21 IFAs (seven fusiform types, seven dolichoectatic types, and seven transitional types) were included in this study. Morphological parameters of IFAs were measured from the vascular model, including the maximum diameter (Dmax), maximum length (Lmax), and centerline curvature and torsion of fusiform aneurysms. The three-dimensional (3D) distribution of AWE in IFAs was obtained based on high-resolution magnetic resonance imaging (HR-MRI). Hemodynamic parameters including time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), gradient oscillatory number (GON), and relative residence time (RRT) were extracted by computational fluid dynamics (CFD) analysis of the vascular model, and the relationship between these parameters and AWE was investigated.

Results

The results showed that Dmax (p = 0.007), Lmax (p = 0.022), enhancement area (p = 0.002), and proportion of enhancement area (p = 0.006) were significantly different among three IFA types, and the transitional type had the largest Dmax, Lmax, and enhancement area. Compared with the non-enhanced regions of IFAs, the enhanced regions had lower TAWSS but higher OSI, GON, and RRT (p < 0.001). Furthermore, Spearman’s correlation analysis showed that AWE was negatively correlated with TAWSS, but positively correlated with OSI, GON, and RRT.

Conclusion

There were significant differences in AWE distributions and morphological features among the three IFA types. Additionally, AWE was positively associated with the aneurysm size, OSI, GON, and RRT, while negatively correlated with TAWSS. However, the underlying pathological mechanism of the three fusiform aneurysm types needs to be further studied.
Sexual Dimorphism in Lesion Size and Sensorimotor Responses Following Spinal Cord Injury
Authors: Osimanjiang Wupu , Allgood JuliAnne E. , Van Sandt Rae L. , Burns Daniel T. , Bushman Jared S.
Published: March 2023

Spinal cord injury (SCI) is a devastating disorder, which impacts the lives of millions of people worldwide with no clinically standardized treatment. Both pro-recovery and anti-recovery factors contribute to the overall outcome after the initial SCI. Sex is emerging as an important variable, which can affect recovery post-SCI. Contusion SCI at T10 was generated in male and female rats. Open-field Basso, Beattie, Bresnahan (BBB) behavioral test, Von Frey test, and CatWalk gate analysis were performed. Histological analysis was performed at the 45-day post-SCI end point. Male/female differences in sensorimotor function recovery, lesion size, and the recruitment of immune cells to the lesion area were measured. A group of males with less severe injuries was included to compare the outcomes for severity. Our results show that both sexes with the same injury level plateaued at a similar final score for locomotor function. Males in the less severe injury group recovered faster and plateaued at a higher BBB score compared to the more severe injury group. Von Frey tests show faster recovery of sensory function in females compared to both male groups. All three groups exhibited reduced mechanical response thresholds after SCI. The lesion area was significantly larger in the male group with severe injury than in females, as well as in males of less severe injury. No significant differences in immune cell recruitment were identified when comparing the three groups. The faster sensorimotor recovery and significantly smaller lesion area in females potentially indicate that neuroprotection against the secondary injury is a likely reason for sex-dependent differences in functional outcomes after SCI.
Occupation-modulated language networks and its lateralization: A resting-state fMRI study of seafarers
Authors: Wu Huijun , Peng Deyuan , Yan Hongjie , Yang Yang , Xu Min , Zeng Weiming , Chang Chunqi , Wang Nizhuan
Published: March 2023

Introduction

Studies have revealed that the language network of Broca’s area and Wernicke’s area is modulated by factors such as disease, gender, aging, and handedness. However, how occupational factors modulate the language network remains unclear.

Methods

In this study, taking professional seafarers as an example, we explored the resting-state functional connectivity (RSFC) of the language network with seeds (the original and flipped Broca’s area and Wernicke’s area).

Results

The results showed seafarers had weakened RSFC of Broca’s area with the left superior/middle frontal gyrus and left precentral gyrus, and enhanced RSFC of Wernicke’s area with the cingulate and precuneus. Further, seafarers had a less right-lateralized RSFC with Broca’s area in the left inferior frontal gyrus, while the controls showed a left-lateralized RSFC pattern in Broca’s area and a right-lateralized one in Wernicke’s area. Moreover, seafarers displayed stronger RSFC with the left seeds of Broca’s area and Wernicke’s area.

Discussion

These findings suggest that years of working experience significantly modulates the RSFC of language networks and their lateralization, providing rich insights into language networks and occupational neuroplasticity.
The signal intensity variation of multiple sclerosis (MS) lesions on magnetic resonance imaging (MRI) as a potential biomarker for patients’ disability: A feasibility study
Authors: Sedaghat Sam , Jang Hyungseok , Athertya Jiyo S. , Groezinger Martin , Corey-Bloom Jody , Du Jiang
Published: March 2023

Introduction

Although many lesion-based MRI biomarkers in multiple sclerosis (MS) patients were investigated, none of the previous studies dealt with the signal intensity variations (SIVs) of MS lesions. In this study, the SIVs of MS lesions on direct myelin imaging and standard clinical sequences as possible MRI biomarkers for disability in MS patients were assessed.

Methods

Twenty seven MS patients were included in this prospective study. IR-UTE, FLAIR, and MPRAGE sequences were employed on a 3T scanner. Regions of interest (ROIs) were manually drawn within the MS lesions, and the cerebrospinal fluid (CSF) and signal intensity ratios (SIR) were calculated from the derived values. Variations coefficients were determined from the standard deviations (Coeff 1) and the absolute differences (Coeff 2) of the SIRs. Disability grade was assessed by the expanded disability status scale (EDSS). Cortical/gray matter, subcortical, infratentorial, and spinal lesions were excluded.

Results

The mean diameter of the lesions was 7.8 ± 1.97 mm, while the mean EDSS score was 4.5 ± 1.73. We found moderate correlations between the EDSS and Coeff 1 and 2 on IR-UTE and MPRAGE images. Accordingly, Pearson’s correlations on IR-UTE were R = 0.51 (p = 0.007) and R = 0.49 (p = 0.01) for Coeff 1 and 2, respectively. For MPRAGE, Pearson’s correlations were R = 0.5 (p = 0.008) and R = 0.48 (p = 0.012) for Coeff 1 and 2, respectively. For FLAIR, only poor correlations could be found.

Conclusion

The SIVs of MS lesions on IR-UTE and MPRAGE images, assessed by Coeff 1 and 2, could be used as novel potential MRI biomarkers for patients’ disability.
Machine learning-based predictive models and drug prediction for schizophrenia in multiple programmed cell death patterns
Authors: Feng Yu , Shen Jing
Published: March 2023

Background

Schizophrenia (SC) is one of the most common mental illnesses. However, the underlying genes that cause it and its effective treatments are unknown. Programmed cell death (PCD) is associated with many immune diseases and plays an important role in schizophrenia, which may be a diagnostic indicator of the disease.

Methods

Two groups as training and validation groups were chosen for schizophrenia datasets from the Gene Expression Omnibus Database (GEO). Furthermore, the PCD-related genes of the 12 patterns were extracted from databases such as KEGG. Limma analysis was performed for differentially expressed genes (DEG) identification and functional enrichment analysis. Machine learning was employed to identify minimum absolute contractions and select operator (LASSO) regression to determine candidate immune-related center genes, construct protein–protein interaction networks (PPI), establish artificial neural networks (ANN), and validate with consensus clustering (CC) analysis, then Receiver operating characteristic curve (ROC curve) was drawn for diagnosis of schizophrenia. Immune cell infiltration was developed to investigate immune cell dysregulation in schizophrenia, and finally, related drugs with candidate genes were collected via the Network analyst online platform.

Results

In schizophrenia, 263 genes were crossed between DEG and PCD-related genes, and machine learning was used to select 42 candidate genes. Ten genes with the most significant differences were selected to establish a diagnostic prediction model by differential expression profiling. It was validated using artificial neural networks (ANN) and consensus clustering (CC), while ROC curves were plotted to assess diagnostic value. According to the findings, the predictive model had a high diagnostic value. Immune infiltration analysis revealed significant differences in Cytotoxic and NK cells in schizophrenia patients. Six candidate gene-related drugs were collected from the Network analyst online platform.

Conclusion

Our study systematically discovered 10 candidate hub genes (DPF2, ATG7, GSK3A, TFDP2, ACVR1, CX3CR1, AP4M1, DEPDC5, NR4A2, and IKBKB). A good diagnostic prediction model was obtained through comprehensive analysis in the training (AUC 0.91, CI 0.95–0.86) and validation group (AUC 0.94, CI 1.00–0.85). Furthermore, drugs that may be useful in the treatment of schizophrenia have been obtained (Valproic Acid, Epigallocatechin gallate).
Ferroptosis in non-alcoholic liver disease: Molecular mechanisms and therapeutic implications
Authors: Cheng Zilu , Chu Huikuan , Zhu Qingjing , Yang Ling
Published: March 2023

Ferroptosis refers to a novel modality of regulated cell death characterized by excessive iron accumulation and overwhelming lipid peroxidation, which takes an important part in multiple pathological processes associated with cell death. Considering the crucial roles of the liver in iron and lipid metabolism and its predisposition to oxidative insults, more and more studies have been conducted to explore the relationship between ferroptosis and various liver disorders, including non-alcoholic fatty liver disease (NAFLD). With increased morbidity and high mortality rates, NAFLD has currently emerged as a global public health issue. However, the etiology of NAFLD is not fully understood. In recent years, an accumulating body of evidence have suggested that ferroptosis plays a pivotal role in the pathogenesis of NAFLD, but the precise mechanisms underlying how ferroptosis affects NAFLD still remain obscure. Here, we summarize the molecular mechanisms of ferroptosis and its complicated regulation systems, delineate the different effects that ferroptosis exerts in different stages of NAFLD, and discuss some potential effective therapies targeting ferroptosis for NAFLD treatment, which putatively points out a novel direction for NAFLD treatment.
High-throughput drug screening identifies fluoxetine as a potential therapeutic agent for neuroendocrine prostate cancer
Authors: Chen Lei , Ji Yiyi , Li Ang , Liu Bo , Shen Kai , Su Ruopeng , Ma Zehua , Zhang Weiwei , Wang Qi , Zhu Yinjie , Xue Wei
Published: March 2023

Introduction

Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer with poor prognosis and resistance to hormone therapy, which has limited therapeutic approaches. Therefore, this study aimed to identify a novel treatment for NEPC and provide evidence of its inhibitory effects.

Methods

We performed a high-throughput drug screening and identified fluoxetine, originally an FDA-approved antidepressant, as candidate therapeutic agent for NEPC. We carried out both in vitro and in vivo experiments to demonstrate the inhibitory effects of fluoxetine on NEPC models and its mechanism in detail.

Results

Our results demonstrated that fluoxetine effectively curbed the neuroendocrine differentiation and inhibited cell viability by targeting the AKT pathway. Preclinical test in NEPC mice model (PBCre4: Ptenf/f; Trp53f/f; Rb1f/f) showed that fluoxetine effectively prolonged the overall survival and reduced the risk of tumor distant metastases.

Discussion

This work repurposed fluoxetine for antitumor application, and supported its clinical development for NEPC therapy, which may provide a promising therapeutic strategy.