bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic analysis of graft liver provides insight into the immune response of rat liver transplantation
Authors: Cao Wanyue , Lu Jing , Li Shanbao , Song Fangbin , Xu Junming
Published: November 2022

Background

As an “immune-privileged organ”, the liver has higher rates of both spontaneous tolerance and operational tolerance after being transplanted compared with other solid organs. Also, a large number of patients still need to take long-term immunosuppression regimens. Liver transplantation (LT) rejection involves varieties of pathophysiological processes and cell types, and a deeper understanding of LT immune response is urgently needed.

Methods

Homogenic and allogeneic rat LT models were established, and recipient tissue was collected on postoperative day 7. The degree of LT rejection was evaluated by liver pathological changes and liver function. Differentially expressed genes (DEGs) were detected by transcriptome sequencing and confirmed by reverse transcription-polymerase chain reaction. The functional properties of DEGs were characterized by the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway analyses. The cells infiltrating the graft and recipient spleen and peripheral blood were evaluated by immunofluorescence and flow cytometry.

Result

A total of 1,465 DEGs were screened, including 1,177 up-regulated genes and 288 down-regulated genes. GO enrichment and KEGG pathway analysis indicated that DEGs were involved in several immunobiological processes, including T cell activation, Th1, Th2 and Th17 cell differentiation, cytokine-cytokine receptor interaction and other immune processes. Reactome results showed that PD-1 signaling was enriched. Further research confirmed that mRNA expression of multiple immune cell markers increased and markers of T cell exhaustion significantly changed. Flow cytometry showed that the proportion of Treg decreased, and that of PD-1+CD4+ T cells and PD-1+CD8+ T cells increased in the allogeneic group.

Conclusion

Using an omic approach, we revealed that the development of LT rejection involved multiple immune cells, activation of various immune pathways, and specific alterations of immune checkpoints, which would benefit risk assessment in the clinic and understanding of pathogenesis regarding LT tolerance. Further clinical validations are warranted for our findings.
Increased stromal PFKFB3-mediated glycolysis in inflammatory bowel disease contributes to intestinal inflammation
Authors: Zhou Zhou , Plug Leonie G. , Patente Thiago A. , de Jonge-Muller Eveline S. M. , Elmagd Amir Abou , van der Meulen-de Jong Andrea E. , Everts Bart , Barnhoorn Marieke C. , Hawinkels Lukas J. A. C.
Published: November 2022

Inflammatory bowel disease (IBD) is a chronic relapsing inflammation of the intestinal tract with currently not well-understood pathogenesis. In addition to the involvement of immune cells, increasing studies show an important role for fibroblasts in the pathogenesis of IBD. Previous work showed that glycolysis is the preferred energy source for fibroblasts in fibrotic diseases. 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3) is a key kinase supporting glycolysis. Increased expression of PFKFB3 in several cancers and inflammatory diseases has been previously reported, but the metabolic status of fibroblasts and the role of PFKFB3 in patients with IBD are currently unknown. Therefore, in this study, we evaluated the role of glycolysis and PFKFB3 expression in IBD. Single-sample gene set enrichment analysis (ssGSEA) revealed that glycolysis was significantly higher in IBD intestinal samples, compared to healthy controls, which was confirmed in the validation cohorts of IBD patients. Single-cell sequencing data indicated that PFKFB3 expression was higher in IBD-derived stromal cells. In vitro, PFKFB3 expression in IBD-derived fibroblasts was increased after the stimulation with pro-inflammatory cytokines. Using seahorse real-time cell metabolic analysis, inflamed fibroblasts were shown to have a higher extracellular acidification rate and a lower oxygen consumption rate, which could be reversed by inhibition of JAK/STAT pathway. Furthermore, increased expression of pro-inflammatory cytokines and chemokines in fibroblasts could be reverted by PFK15, a specific inhibitor of PFKFB3. In vivo experiments showed that PFK15 reduced the severity of dextran sulfate sodium (DSS)- and Tcell transfer induced colitis, which was accompanied by a reduction in immune cell infiltration in the intestines. These findings suggest that increased stromal PFKFB3 expression contributes to inflammation and the pathological function of fibroblasts in IBD. Inhibition of PFKFB3 suppressed their inflammatory characteristics.
Alteration of alpha and beta diversity in nekton community by extreme marine heatwave events: An example from the East China Sea
Authors: Liu Zunlei , Yang Linlin , Yan Liping , Zhang Hui , Zhang Yi , Xu Min , Jin Yan , Cheng Jiahua
Published: November 2022

In the year of 2016 to 2017, record-breaking marine heatwave (MHW) events occurred along the Chinese coast, exerting severe impacts on coastal fishes and fisheries. However, the response of the nekton community to MHW events still remains poorly understanding. Thus, to investigate the influences of the MHW events on species composition dynamics, this study conducted a survey on nekton communities in the northern East China Sea in the summers during 2014 to 2017. The recently-developed “heatwaveR” package was adopted to describe the variation characteristics of heatwaves within the study area, based on high-resolution remote-sensing sea surface temperature products. We also compared variations in the community structures of different biological groups before (2014–2015) and during the occurrence of the MHW events (2016–2017). During the MHW events, temperature increased by approximately 2.3°C in both 2016 and 2017. Compared with those before the MHW events, the biomass and dominance of several important crustaceans decreased, and the biomass of warm water affinity species increased significantly, while their richness and diversity decreased; the biomass of warm temperature affinity species declined significantly, while their diversity increased slightly. These results show the difference in the response rates of species with different thermal preferences and different species compositions to the extreme climate change. Beta diversity analysis revealed that the inter-group variation before and during the MHW event exceeded the intra-group variation, proving that MHWs changed the community structure to a certain extent. PERMANOVA test showed that the species compositions of planktivorous fish (FG1) and small-omnivorous fish (FG2) in the feeding-functional groups were significantly different before and during the MHW event, which may be attributed to the impact of MHWs on oligotrophic fishes through thermal preference and the trophic cascade effect. There was no significant change in the species compositions of other functional groups, indicating that medium-trophic and eutrophic fishes possessed certain adaptability to MHWs. Regarding fisheries management under extreme warming events, it would be advisable to diagnose temperature anomalies in the early stage, monitor changes in species abundance in the early life cycle, and then rapidly develop suitable fishing strategies.
The HMOX2 polymorphism contributes to the carotid body chemoreflex in European sea-level residents by regulating hypoxic ventilatory responses
Authors: Fabries Pierre , Drogou Catherine , Sauvet Fabien , Nespoulous Olivier , Erkel Marie-Claire , Marchandot Vincent , Bouaziz Walid , Lepetit Benoît , Hamm-Hornez Anne-Pia , Malgoyre Alexandra , Koulmann Nathalie , Gomez-Merino Danielle , Chennaoui Mounir
Published: November 2022

This study investigates whether a functional single nucleotide polymorphism of HMOX2 (heme oxygenase-2) (rs4786504 T>C) is involved in individual chemosensitivity to acute hypoxia, as assessed by ventilatory responses, in European individuals. These responses were obtained at rest and during submaximal exercise, using a standardized and validated protocol for exposure to acute normobaric hypoxia. Carriers of the ancestral T allele (n = 44) have significantly lower resting and exercise hypoxic ventilatory responses than C/C homozygous carriers (n = 40). In the literature, a hypoxic ventilatory response threshold to exercise has been identified as an independent predictor of severe high altitude-illness (SHAI). Our study shows that carriers of the T allele have a higher risk of SHAI than carriers of the mutated C/C genotype. Secondarily, we were also interested in COMT (rs4680 G > A) polymorphism, which may be indirectly involved in the chemoreflex response through modulation of autonomic nervous system activity. Significant differences are present between COMT genotypes for oxygen saturation and ventilatory responses to hypoxia at rest. In conclusion, this study adds information on genetic factors involved in individual vulnerability to acute hypoxia and supports the critical role of the ≪ O2 sensor ≫ - heme oxygenase-2 - in the chemosensitivity of carotid bodies in Humans.
Genome-wide scan for potential CD4+ T-cell vaccine candidates in Candida auris by exploiting reverse vaccinology and evolutionary information
Authors: Gupta Shishir K. , Osmanoglu Özge , Minocha Rashmi , Bandi Sourish Reddy , Bencurova Elena , Srivastava Mugdha , Dandekar Thomas
Published: November 2022

Candida auris is a globally emerging fungal pathogen responsible for causing nosocomial outbreaks in healthcare associated settings. It is known to cause infection in all age groups and exhibits multi-drug resistance with high potential for horizontal transmission. Because of this reason combined with limited therapeutic choices available, C. auris infection has been acknowledged as a potential risk for causing a future pandemic, and thus seeking a promising strategy for its treatment is imperative. Here, we combined evolutionary information with reverse vaccinology approach to identify novel epitopes for vaccine design that could elicit CD4+ T-cell responses against C. auris. To this end, we extensively scanned the family of proteins encoded by C. auris genome. In addition, a pathogen may acquire substitutions in epitopes over a period of time which could cause its escape from the immune response thus rendering the vaccine ineffective. To lower this possibility in our design, we eliminated all rapidly evolving genes of C. auris with positive selection. We further employed highly conserved regions of multiple C. auris strains and identified two immunogenic and antigenic T-cell epitopes that could generate the most effective immune response against C. auris. The antigenicity scores of our predicted vaccine candidates were calculated as 0.85 and 1.88 where 0.5 is the threshold for prediction of fungal antigenic sequences. Based on our results, we conclude that our vaccine candidates have the potential to be successfully employed for the treatment of C. auris infection. However, in vivo experiments are imperative to further demonstrate the efficacy of our design.
Case report: A prosthetic valve endocarditis caused by Legionella bozemanae in an immunocompetent patient
Authors: Fraz Mai Sasaki Aanensen , Dahle Gry , Skaug Kirsten Margrete , Jarraud Sophie , Frye Stephan , Bjørnholt Jørgen Vildershøj , Nordøy Ingvild
Published: November 2022

Extrapulmonary infections with Legionella species are rare, but important to acknowledge. We report a case of infective endocarditis (IE) with Legionella bozemanae in a 66-year-old immunocompetent man with an aortic homograft. The diagnosis was made by direct 16S rRNA gene amplification from valve material, confirmed by a targeted Legionella-PCR in serum and the detection of L. bozemanae specific antibodies. To our knowledge, this is the first confirmed case of IE with L. bozemanae as causative pathogen. The infected aortic prosthesis was replaced by a homograft, and the patient was successfully treated with levofloxacin and azithromycin for 6 weeks.
Performance evaluation of a new on-demand molecular test for the rapid identification of severe acute respiratory syndrome coronavirus 2 in pediatric and adult patients
Authors: Colagrossi Luna , Costabile Valentino , Scutari Rossana , Cento Valeria , Coltella Luana , Reale Antonino , Scilipoti Martina , Villani Alberto , Alteri Claudia , Perno Carlo Federico , Russo Cristina
Published: November 2022

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has increased the need to identify additional rapid diagnostic tests for an accurate and early diagnosis of infection. Here, we evaluated the diagnostic performance of the cartridge-based reverse transcription polymerase chain reaction (RT-PCR) test STANDARD M10 SARS-CoV-2 (SD Biosensor Inc., Suwon, South Korea), targeting the ORF1ab and E gene of SARS-CoV-2, and which can process up to eight samples in parallel in 60 min. From January 2022 to March 2022, STANDARD™ M10 assay performance was compared with Xpert® Xpress SARS-CoV-2 (Cepheid, Sunnyvale CA) on 616 nasopharyngeal swabs from consecutive pediatric (N = 533) and adult (N = 83) patients presenting at the “Istituto di Ricovero e Cura a Carattere Scientifico” (IRCCS) Ospedale Pediatrico Bambino Gesù, Roma. The overall performance of STANDARD M10 SARS-CoV-2 was remarkably and consistently comparable to the Xpert® Xpress SARS-CoV-2 with an overall agreement of 98% (604/616 concordant results), and negligible differences in time-to-result (60 min vs. 50 min, respectively). When the Xpert® Xpress SARS-CoV-2 results were considered as the reference, STANDARD™ M10 SARS-CoV-2 had 96.5% sensitivity and 98.4% specificity. STANDARD M10 SARS-CoV-2 can thus be safely included in diagnostic pathways because it rapidly and accurately identifies SARS-CoV-2 present in nasopharyngeal swabs.
Correctness and response time distributions in the MemTrax continuous recognition task: Analysis of strategies and a reverse-exponential model
Authors: Ashford J. Wesson , Clifford James O. , Anand Sulekha , Bergeron Michael F. , Ashford Curtis B. , Bayley Peter J.
Published: November 2022

A critical issue in addressing medical conditions is measurement. Memory measurement is difficult, especially episodic memory, which is disrupted by many conditions. On-line computer testing can precisely measure and assess several memory functions. This study analyzed memory performances from a large group of anonymous, on-line participants using a continuous recognition task (CRT) implemented at https://memtrax.com. These analyses estimated ranges of acceptable performance and average response time (RT). For 344,165 presumed unique individuals completing the CRT a total of 602,272 times, data were stored on a server, including each correct response (HIT), Correct Rejection, and RT to the thousandth of a second. Responses were analyzed, distributions and relationships of these parameters were ascertained, and mean RTs were determined for each participant across the population. From 322,996 valid first tests, analysis of correctness showed that 63% of these tests achieved at least 45 correct (90%), 92% scored at or above 40 correct (80%), and 3% scored 35 correct (70%) or less. The distribution of RTs was skewed with 1% faster than 0.62 s, a median at 0.890 s, and 1% slower than 1.57 s. The RT distribution was best explained by a novel model, the reverse-exponential (RevEx) function. Increased RT speed was most closely associated with increased HIT accuracy. The MemTrax on-line memory test readily provides valid and reliable metrics for assessing individual episodic memory function that could have practical clinical utility for precise assessment of memory dysfunction in many conditions, including improvement or deterioration over time.
Multiple routes to help you roam: A comparison of training interventions to improve cognitive-motor dual-tasking in healthy older adults
Authors: Downey Rachel , Bherer Louis , Pothier Kristell , Vrinceanu Tudor , Intzandt Brittany , Berryman Nicolas , Lussier Maxime , Vincent Thomas , Karelis Antony D. , Nigam Anil , Vu Thien Tuong Minh , Bosquet Laurent , Li Karen Z. H.
Published: November 2022

Cognitive-motor dual-tasking is a complex activity that predicts falls risk and cognitive impairment in older adults. Cognitive and physical training can both lead to improvements in dual-tasking; however, less is known about what mechanisms underlie these changes. To investigate this, 33 healthy older adults were randomized to one of three training arms: Executive function (EF; n = 10), Aerobic Exercise (AE; n = 10), Gross Motor Abilities (GMA; n = 13) over 12 weeks (1 h, 3×/week). Single and dual-task performance (gait speed, m/s; cognitive accuracy, %) was evaluated before and after training, using the 2-back as concurrent cognitive load. Training arms were designed to improve cognitive and motor functioning, through different mechanisms (i.e., executive functioning – EF, cardiorespiratory fitness – CRF, and energy cost of walking – ECW). Compared to baseline, we observed few changes in dual-task gait speed following training (small effect). However, dual-task cognitive accuracy improved significantly, becoming facilitated by walking (large effect). There were no differences in the magnitude of improvements across training arms. We also found that older adults with lower cognitive ability (i.e., MoCA score < 26; n = 14) improved more on the dual-task cognitive accuracy following training, compared to older adults with higher cognitive ability (i.e., MoCA ≥26; n = 18). Taken together, the results suggest that regardless of the type of intervention, training appears to strengthen cognitive efficiency during dual-tasking, particularly for older adults with lower baseline cognitive status. These gains appear to occur via different mechanisms depending on the form of intervention. Implications of this research are paramount, as we demonstrate multiple routes for improving cognitive-motor dual-tasking in older adults, which may help reduce risk of cognitive impairment.
Cortical circuit-based lossless neural integrator for perceptual decision-making: A computational modeling study
Authors: Lee Jung Hoon , Tsunada Joji , Vijayan Sujith , Cohen Yale E.
Published: November 2022

The intrinsic uncertainty of sensory information (i.e., evidence) does not necessarily deter an observer from making a reliable decision. Indeed, uncertainty can be reduced by integrating (accumulating) incoming sensory evidence. It is widely thought that this accumulation is instantiated via recurrent rate-code neural networks. Yet, these networks do not fully explain important aspects of perceptual decision-making, such as a subject’s ability to retain accumulated evidence during temporal gaps in the sensory evidence. Here, we utilized computational models to show that cortical circuits can switch flexibly between “retention” and “integration” modes during perceptual decision-making. Further, we found that, depending on how the sensory evidence was readout, we could simulate “stepping” and “ramping” activity patterns, which may be analogous to those seen in different studies of decision-making in the primate parietal cortex. This finding may reconcile these previous empirical studies because it suggests these two activity patterns emerge from the same mechanism.
Principal component analysis of photoplethysmography signals for improved gesture recognition
Authors: Ruan Yuwen , Chen Xiang , Zhang Xu , Chen Xun
Published: November 2022

In recent years, researchers have begun to introduce photoplethysmography (PPG) signal into the field of gesture recognition to achieve human-computer interaction on wearable device. Unlike the signals used for traditional neural interface such as electromyography (EMG) and electroencephalograph (EEG), PPG signals are readily available in current commercial wearable devices, which makes it possible to realize practical gesture-based human-computer interaction applications. In the process of gesture execution, the signal collected by PPG sensor usually contains a lot of noise irrelevant to gesture pattern and not conducive to gesture recognition. Toward improving gesture recognition performance based on PPG signals, the main contribution of this study is that it explores the feasibility of using principal component analysis (PCA) decomposition algorithm to separate gesture pattern-related signals from noise, and then proposes a PPG signal processing scheme based on normalization and reconstruction of principal components. For 14 wrist and finger-related gestures, PPG data of three wavelengths of light (green, red, and infrared) are collected from 14 subjects in four motion states (sitting, walking, jogging, and running). The gesture recognition is carried out with Support Vector Machine (SVM) classifier and K-Nearest Neighbor (KNN) classifier. The experimental results verify that PCA decomposition can effectively separate gesture-pattern-related signals from irrelevant noise, and the proposed PCA-based PPG processing scheme can improve the average accuracies of gesture recognition by 2.35∼9.19%. In particular, the improvement is found to be more evident for finger-related (improved by 6.25∼12.13%) than wrist-related gestures (improved by 1.93∼5.25%). This study provides a novel idea for implementing high-precision PPG gesture recognition technology.
Time-restricted eating for patients with diabetes and prediabetes: A systematic review
Authors: Lin Xiaoxiao , Guan Yihong , Wu Guomin , Huang Jinyu , Wang Shuai
Published: November 2022

Background

Several studies have explored the effect of time-restricted eating (TRE) on patients with diabetes and prediabetes. However, these studies have not been analyzed and summarized as a whole. We conducted a systematic review to summarize and analyze all studies about the efficacy and safety of TRE for patients with diabetes and prediabetes.

Methods

We conducted a comprehensive search of the Embase, PubMed and Cochrane databases and the time span was from inception to 1 May 2022. The Cochrane Collaboration’s Risk of Bias 2 (RoB2) and ROBINS-I tools were used to evaluate the quality of included studies. The effect of TRE on weight loss, insulin sensitivity, plasma glucose, and the safety of TRE were summarized and analyzed.

Results

In total, 7 studies with 326 participants including 5 articles with 217 patients with diabetes and 2 articles with 109 patients with prediabetes were included. The TRE windows were from 4 to 10 h. The percentages of females ranged from 0 to 90%. The mean age ranged from 35.2 to 67.5 years, and most of patients adhered to TRE. All studies were assessed as high quality. TRE may result in weight loss, and improvements in the insulin sensitivity and plasma glucose, with no severe AEs.

Conclusion

Time-restricted eating is a safe and feasible intervention, and may offer cardiovascular and metabolic benefits for patients with diabetes and prediabetes. Studies in this field, which should be viewed as important, are limited. Therefore, more high-quality studies are needed.
Prediction of the immunological and prognostic value of five signatures related to fatty acid metabolism in patients with cervical cancer
Authors: Zeng Qiongjing , Jiang Huici , Lu Fang , Fu Mingxu , Bi Yingying , Zhou Zengding , Cheng Jiajing , Qin Jinlong
Published: November 2022

A growing attention has been attached to the role of fatty acid metabolism (FAM) in the development of cancer, and cervical cancer (CC) is still the primary cause of cancer-associated death in women worldwide. Therefore, it is imperative to explore the possible prognostic significance of FAM in CC. In this study, CC samples and corresponding normal samples were acquired from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Single sample gene set enrichment analysis (ssGSEA) was conducted for calculating FAM-related scores (FAMRs) to screen FAM-related genes (FAMRGs). Two subtypes related to FAM were identified by consistent clustering. Among them, subtype C2 had a poor prognosis, and C1 had a high level of immune cell infiltration, while C2 had a high possibility of immune escape and was insensitive to chemotherapy drugs. Based on the differentially expressed genes (DEGs) in the two subtypes, a 5-gene signature (PLCB4, FBLN5, TSPAN8, CST6, and SERPINB7) was generated by the least absolute shrinkage and selection operator (LASSO) and Akaike information criterion (AIC). The model demonstrated a high prognostic accuracy (area under the curve (AUC)>0.7) in multiple cohorts and was one independent prognostic factor for CC patients. Accordingly, FAMRGs can be adopted as a biomarker for the prediction of CC patients’ prognosis and help guide the immunotherapy of CC.
Orchestration of mesenchymal plasticity and immune evasiveness via rewiring of the metabolic program in pancreatic ductal adenocarcinoma
Authors: Hashimoto Ari , Handa Haruka , Hata Soichiro , Hashimoto Shigeru
Published: November 2022

Pancreatic ductal adenocarcinoma (PDAC) is the most fatal cancer in humans, due to its difficulty of early detection and its high metastatic ability. The occurrence of epithelial to mesenchymal transition in preinvasive pancreatic lesions has been implicated in the early dissemination, drug resistance, and cancer stemness of PDAC. PDAC cells also have a reprogrammed metabolism, regulated by driver mutation-mediated pathways, a desmoplastic tumor microenvironment (TME), and interactions with stromal cells, including pancreatic stellate cells, fibroblasts, endothelial cells, and immune cells. Such metabolic reprogramming and its functional metabolites lead to enhanced mesenchymal plasticity, and creates an acidic and immunosuppressive TME, resulting in the augmentation of protumor immunity via cancer-associated inflammation. In this review, we summarize our recent understanding of how PDAC cells acquire and augment mesenchymal features via metabolic and immunological changes during tumor progression, and how mesenchymal malignancies induce metabolic network rewiring and facilitate an immune evasive TME. In addition, we also present our recent findings on the interesting relevance of the small G protein ADP-ribosylation factor 6-based signaling pathway driven by KRAS/TP53 mutations, inflammatory amplification signals mediated by the proinflammatory cytokine interleukin 6 and RNA-binding protein ARID5A on PDAC metabolic reprogramming and immune evasion, and finally discuss potential therapeutic strategies for the quasi-mesenchymal subtype of PDAC.
Does radiation therapy need more than two photon energies from Linac?
Authors: Zhang Xile , Zhou Fugen , Liu Bo , Xiong Tianyu , Bai Xiangzhi , Wu Qiuwen
Published: November 2022

Purpose

Modern Linacs are equipped with multiple photon energies for radiation therapy, and proper energy is chosen for each case based on tumor characteristics and patient anatomy. The aim of this study is to investigate whether it is necessary to have more than two photons energies.

Methods

The principle of photon energy synthesis is presented. It is shown that a photon beam of any intermediate energy (Esyn) can be synthesized from a linear combination of a low energy (Elow) and a high energy (Ehigh). The principle is validated on a wide range of scenarios: different intermediate photon energies on the same Linac; between Linacs from the same manufacturer or different manufacturers; open and wedge beams; and extensive photon energies available from published reference data. In addition, 3D dose distributions in water phantom are compared using Gamma analysis. The method is further demonstrated in clinical cases of various tumor sites and multiple treatment modalities. Experimental measurements are performed for IMRT plans and they are analyzed using the standard clinical protocol.

Results

The synthesis coefficients vary with energy and field size. The root mean square error (RMSE) is within 1.1% for open and wedge fields. Excellent agreement was observed for British Journal of Radiology (BJR) data with an average RMSE of 0.11%. The 3D Gamma analysis shows a good match for all field sizes in the water phantom and all treatment modalities for the five clinical cases. The minimum gamma passing rate of 95.7% was achieved at 1%/1mm criteria for two measured dose distributions of IMRT plans.

Conclusion

A Linac with two photon energies is capable of producing dosimetrically equivalent plans of any energy in-between through the photon energy synthesis, supporting the notion that there is no need to equip more than two photon energies on each Linac. This can significantly reduce the cost of equipment for radiation therapy.
Mediating effect assessment of ifosfamide on limb salvage rate in osteosarcoma: A study from a single center in China
Authors: Li Yan , Fu Yiwei , Zhang Zhaohui , Wang Zhuo , Yin Junqiang , Shen Jingnan
Published: November 2022

Osteosarcoma is one of the most prevalent primary bone malignancies in children and adolescents. Surgery and chemotherapy are the standard treatment methods of osteosarcoma. Methotrexate, adriamycin, and cisplatin, and methotrexate, adriamycin, cisplatin, and ifosfamide regimens are both first-line neoadjuvant chemotherapy regimens for osteosarcoma. Moreover, the use of ifosfamide is highly controversial. Most studies of ifosfamide focused on the overall survival rate and event-free survival rate; few studies concentrated on surgical options. We conducted this retrospective study to compare the baseline characteristic of amputation and limb salvage osteosarcoma patients. Furthermore, we analyzed the direct and indirect roles in surgical decision-making and found that ifosfamide may play a partial mediating role in the surgery option choice by mediating tumor mass volume change, tumor response, and the shortest distance from the center of main blood vessels to the margin of the tumor lesion.
COVID-19 pandemic impact on follow-up of child growth and development in Brazil
Authors: Carneiro Lucas Lima , Vieira Ed Wilson Rodrigues , Duarte Elysângela Dittz , da Rocha Najara Barbosa , Velasquez-Melendez Gustavo , Caminhas Walmir
Published: November 2022

Objectives

This study investigated the impact of the COVID-19 pandemic on the primary health care (PHC) services to follow-up the child growth and development (CGD) in Brazil.

Methods

A cross-sectional study was conducted using secondary data related visits to assess the growth and development of children up to five years between Apr-2017 to Mar-2021. Differences between monthly rate of visits (per thousand inhabitants up to five) during the pandemic (Apr-2020 to Mar-2021) and before (Apr-2017 to Mar-2020) were analyzed using paired t test and control diagrams (averages ± 1.96 standard deviation).

Results

A total of 39,599,313 visits for monitoring CGD was studied. The average monthly rate of visits dropped from 61.34 (per thousand) before the pandemic to 39.70 in the first 12 months of the pandemic (p < 0.001). In all states, except Rio Grande do Sul, there was a significant reduction, with differences ranging from −14.21% in São Paulo to −59.66% in Ceará. The Northeast region was the most impacted, being lower than expected in all 12 first months of pandemic.

Conclusions

The number of visits to follow-up the CGD in PHC in Brazil decreased during the first year of the COVID-19 pandemic, varying over the months and between states and regions.
The ABBA project (Assess Better Before Access): A retrospective cohort study of neonatal intravascular device outcomes
Authors: van Rens Matheus F. P. T. , Bayoumi Mohammad A. A. , van de Hoogen Agnes , Francia Airene L. V. , Cabanillas Irian J. , van Loon Fredericus H. J. , Spencer Timothy R.
Published: November 2022

Background

Venous access devices (VADs) play a vital role within the neonatal intensive care unit. However, there are significant risks associated with the use of VADs, with complications such as infection, thrombosis, device occlusion, and infiltration/extravasation frequently contributing to device-related failures and increasing the risk of significant patient harm or injury. This study aimed to explore the relationships between risk factors and different venous access device complications in the neonatal setting, and then use that evidence to develop an algorithm based on observational data.

Methods

This is a retrospective, single-center cohort study that was conducted in a large 112-bed neonatal intensive care unit in Qatar. We examined venous access device data from January 2016 to December 2018 for all term and preterm neonates. Descriptive statistics were used to summarize the outcomes, which included a mean and its standard deviation or median and an interquartile range for continuous variables regarding normal distribution, and absolute numbers with percentages for discrete variables.

Results

The authors recorded a total of 23,858 VADs inserted during the study period. Of these, 21,313 (89%) were peripheral intravenous catheters, 689 (3%) were extended dwell-peripheral intravenous catheters, 1,335 (6%) were epicutaneo-caval catheters, and 521 (2%) were umbilical venous catheters. In total, 51,179 catheter days were registered, with 2.17 catheter days reported per patient. Peripheral device dwell times were significantly shorter when compared with central venous catheter devices (P < 0.001), with mean dwell times of 22 days ± 23 h and 236 days ± 183 h, respectively. After insertion, a complication occurred in 11,177 (51%) of peripheral VADs and 221 (12%) of central VADs. The type of device inserted [P < 0.001, hazard ratio (HR) = 0.52, 95% confidence interval (CI): 0.50–0.54], reason/indication for intravenous therapy (P < 0.001, HR = 0.85, 95% CI: 0.82–0.87), and the side of insertion of the device (P < 0.001, HR = 1.25, 95% CI: 1.24–1.27) had a significant relationship with outcomes.

Conclusions

Four subgroups of VADs were identified (peripheral intravenous catheters, extended dwell-peripheral intravenous devices, epicutaneo-caval catheters, and umbilical venous catheters) with outcome-related differences. Central venous access devices (epicutaneo-caval catheters and umbilical venous catheters) had lower complications compared with peripheral VADs. Proper venous access device selection, early insertion, and early removal approaches remain crucial to preventing venous access device complications. Peripheral intravenous devices should be used carefully and closely watched for early detection of complications.
Mitochondrial toxicity evaluation of traditional Chinese medicine injections with a dual in vitro approach
Authors: Shen Yunfu , Guo Kaiqiang , Ma Aijun , Huang Zhe , Du Jingjing , Chen Junhe , Lin Qianyu , Wei Chengming , Wang Zi , Zhang Fuming , Zhang Juan , Lin Wanjun , Feng Na , Ma Wenzhe
Published: November 2022

Graphical Abstract

A dual in vitro mitochondrial toxicity assay approach combing the conventional “glucose/galactose” assay in HepG2 cells with the cytotoxic assay in mitochondrial respiration deficient cells was established in this study. Using this platform, we systematically assessed the mitochondrial toxicity of TCM injections for the first time. Four TCM injections were identified with potential mitochondrial toxicity. Their toxic ingredients were predicted by molecular docking and validated by the dual in vitro approach.
Astragalus and its formulas as a therapeutic option for fibrotic diseases: Pharmacology and mechanisms
Authors: Zhu Yi , Chai Yilu , Xiao Guojin , Liu Yufei , Xie Xiaohong , Xiao Wei , Zhou Pengcheng , Ma Wei , Zhang Chuantao , Li Liuying
Published: November 2022

Fibrosis is the abnormal deposition of extracellular matrix, characterized by accumulation of collagen and other extracellular matrix components, which causes organ dysfunction and even death. Despite advances in understanding fibrosis pathology and clinical management, there is no treatment for fibrosis that can prevent or reverse it, existing treatment options may lead to diarrhea, nausea, bleeding, anorexia, and liver toxicity. Thus, effective drugs are needed for fibrotic diseases. Traditional Chinese medicine has played a vital role in fibrotic diseases, accumulating evidence has demonstrated that Astragalus (Astragalus mongholicus Bunge) can attenuate multiple fibrotic diseases, which include liver fibrosis, pulmonary fibrosis, peritoneal fibrosis, renal fibrosis, cardiac fibrosis, and so on, mechanisms may be related to inhibition of epithelial-mesenchymal transition (EMT), reactive oxygen species (ROS), transforming growth factor beta 1 (TGF-β1)/Smads, apoptosis, inflammation pathways. The purpose of this review was to summarize the pharmacology and mechanisms of Astragalus in treating fibrotic diseases, the data reviewed demonstrates that Astragalus is a promising anti-fibrotic drug, its main anti-fibrotic components are Calycosin, Astragaloside IV, Astragalus polysaccharides and formononetin. We also review formulas that contain Astragalus with anti-fibrotic effects, in which Astragalus and Salvia miltiorrhiza Bunge, Astragalus and Angelica sinensis (Oliv.) Diels are the most commonly used combinations. We propose that combining active components into new formulations may be a promising way to develop new drugs for fibrosis. Besides, we expect Astragalus to be accepted as a clinically effective method of treating fibrosis.
Transcriptome and metabolome analyses of Shatian pomelo (Citrus grandis var. Shatinyu Hort) leaves provide insights into the overexpression of the gibberellin-induced gene CcGASA4
Authors: Wu Tianli , Liu Kaidong , Chen Min , Jiang Bo , Gong Qijing , Zhong Yun
Published: November 2022

The gibberellic acid (GA)-stimulated Arabidopsis (GASA) gene family is highly specific to plants and plays crucial roles in plant growth and development. CcGASA4 is a member of the GASA gene family in citrus plants; however, the current understanding of its function in citrus is limited. We used CcGASA4-overexpression transgenic citrus (OEGA) and control (CON) plants to study the role of CcGASA4 in Shatian pomelo. The RNA sequencing (RNA-seq) analysis showed that 3,522 genes, including 1,578 upregulated and 1,944 downregulated genes, were significantly differentially expressed in the CON versus OEGA groups. The Gene Ontology enrichment analysis showed that 178 of the differentially-expressed genes (DEGs) were associated with flowers. A Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEGs were enriched in 134 pathways, including “plant–pathogen interaction”, “MAPK signaling pathway-plant”, “phenylpropane biosynthesis”, “plant hormone signal transduction”, “phenylalanine, tyrosine and tryptophan biosynthesis”, and “flavonoid and flavonol biosynthesis”. The most significantly-enriched pathway was “plant–pathogen interaction”, in which 203 DEGs were enriched (126 DEGs were upregulated and 78 were downregulated). The metabolome analysis showed that 644 metabolites were detected in the OEGA and CON samples, including 294 differentially-accumulated metabolites (DAMs; 83 upregulated versus 211 downregulated in OEGA compared to CON). The metabolic pathway analysis showed that these DAMs were mainly involved in the metabolic pathways of secondary metabolites, such as phenylpropanoids, phenylalanine, flavone, and flavonol biosynthesis. Thirteen flavonoids and isoflavones were identified as DAMs in OEGA and CON. We also discovered 25 OEGA-specific accumulated metabolites and found 10 that were associated with disease resistance. CcGASA4 may therefore play a functional role in activating the expression of MAPK signaling transduction pathway and disease resistance genes, inhibiting the expression of auxin- and ethylene-related genes, and activating or inhibiting the expression of brassinosteroid biosynthesis- and abscisic acid-related genes. CcGASA4 may also play a role in regulating the composition and abundance of flavonoids, isoflavones, amino acids, purines, and phenolic compounds. This study provides new insights into the molecular mechanisms of action of CcGASA4 in citrus plants.
PacBio full-length sequencing integrated with RNA-seq reveals the molecular mechanism of waterlogging and its recovery in Paeonia ostii
Authors: Zhang Xiaoxiao , Liu Xiang , Zhou Minghui , Hu Yonghong , Yuan Junhui
Published: November 2022

Paeonia ostii, a widely cultivated tree peony species in China, is a resourceful plant with medicinal, ornamental and oil value. However, fleshy roots lead to a low tolerance to waterlogging in P. ostii. In this study, P. ostii roots were sequenced using a hybrid approach combining single-molecule real-time and next-generation sequencing platforms to understand the molecular mechanism underlying the response to this sequentially waterlogging stress, the normal growth, waterlogging treatment (WT), and waterlogging recovery treatment (WRT). Our results indicated that the strategy of P. ostii, in response to WT, was a hypoxic resting syndrome, wherein the glycolysis and fermentation processes were accelerated to maintain energy levels and the tricarboxylic acid cycle was inhibited. P. ostii enhanced waterlogging tolerance by reducing the uptake of nitrate and water from the soil. Moreover, transcription factors, such as AP2/EREBP, WRKY, MYB, and NAC, played essential roles in response to WT and WRT. They were all induced in response to the WT condition, while the decreasing expression levels were observed under the WRT condition. Our results contribute to understanding the defense mechanisms against waterlogging stress in P. ostii.
Bayesian reasoning with emotional material in patients with schizophrenia
Authors: Romero-Ferreiro Verónica , Susi Rosario , Sánchez-Morla Eva M. , Marí-Beffa Paloma , Rodríguez-Gómez Pablo , Amador Julia , Moreno Eva M. , Romero Carmen , Martínez-García Natalia , Rodriguez-Jimenez Roberto
Published: November 2022

Delusions are one of the most classical symptoms described in schizophrenia. However, despite delusions are often emotionally charged, they have been investigated using tasks involving non-affective material, such as the Beads task. In this study we compared 30 patients with schizophrenia experiencing delusions with 32 matched controls in their pattern of responses to two versions of the Beads task within a Bayesian framework. The two versions of the Beads task consisted of one emotional and one neutral, both with ratios of beads of 60:40 and 80:20, considered, respectively, as the “difficult” and “easy” variants of the task. Results indicate that patients showed a greater deviation from the normative model, especially in the 60:40 ratio, suggesting that more inaccurate probability estimations are more likely to occur under uncertainty conditions. Additionally, both patients and controls showed a greater deviation in the emotional version of the task, providing evidence of a reasoning bias modulated by the content of the stimuli. Finally, a positive correlation between patients’ deviation and delusional symptomatology was found. Impairments in the 60:40 ratio with emotional content was related to the amount of disruption in life caused by delusions. These results contribute to the understanding of how cognitive mechanisms interact with characteristics of the task (i.e., ambiguity and content) in the context of delusional thinking. These findings might be used to inform improved intervention programs in the domain of inferential reasoning.
Fear, depression, and well-being during COVID-19 in German and South African students: A cross-cultural comparison
Authors: Holm-Hadulla Rainer M. , Mayer Claude-Hélène , Wendler Hannes , Kremer Thomas L. , Kotera Yasuhiro , Herpertz Sabine C.
Published: November 2022

Various studies have shown a decrease in well-being and an increase in mental health problems during the COVID-19 pandemic; however, only a few studies have explored fear, depression, and well-being cross-culturally during this time. Accordingly, we present the results of a cross-cultural study that (1) compares these mental health scores for German and South African students, (2) compares the correlations among them, and (3) identifies COVID-19 fear, well-being, and depression predictors. German and South African societies differ from each other socio-culturally, politically, and economically. Their university systems also differ to a large extent. University students in both countries completed the Fear of COVID-19 Scale, the World Health Organization-Five Well-Being Index (WHO-5), and the Patient Health Questionnaire-9 (PHQ-9). Welch’s t-test, correlation, and multiple regression analyses were performed. (1) German students were found to have statistically lower levels of COVID-19 fear and depression, but lower levels of general well-being than South African students. (2) In both samples, fear of COVID-19 was negatively correlated with well-being and positively associated with female gender and depression. (3) Additionally, female gender, depression, and lower well-being were identified as predictors of COVID-19 fear in both samples. The findings indicate that the fear of COVID-19 is associated with and varies according to gender, depression, and well-being across cultures, and that the difference in the intensity of fear between German and South African students may be partly explained by cultural and contextual differences. These findings can create a deeper understanding of the pandemic’s impact on student communities and may be used by mental health practitioners and researchers to develop and apply culture-specific interventions.
Organizational support and job crafting with the new math teachers’ well-being: The mediating effect of basic psychological needs
Authors: Wang Limei , Peng Fuqiang , Song Naiqing
Published: November 2022

Enhancement of the teacher well-being level has grown into a general, pressing problem to be solved in the domain of education worldwide. Based on the theoretical perspective of the multi-level dynamically formed mechanical model of occupational well-being, this study initially constructed a mechanism model with the occupational well-being role of organizational support, job crafting, and the occupational well-being of new math teachers at primary and junior high schools, and conducted empirical research using structural equation modeling. The study found out that organizational support, job crafting and basic psychological needs have prominent and positive effects on the occupational well-being of the new math teachers in primary up to junior high schools. It also argues that basic psychological needs may mediate the correlation between organizational support, job crafting, and the occupational well-being of the new math teachers. To sum up, the study findings reveal the mechanisms of the role in organizational support and job crafting on the occupational well-being of new primary up to junior high school math teachers. Also, the findings may be conducive to extending the research on the factors that influence the teacher well-being, notably fostering the study on that in the math teachers in the primary up to junior high schools of China.