bluuebunny/crossref_metadata_2025 huggingface dataset:
Smartphone-based behaviour analysis for challenging behaviour in intellectual and developmental disabilities and autism spectrum disorder – Study protocol for the ProVIA trial
Authors: Geissler Julia , Buchholz Hanna , Meerson Rinat , Kammerer Klaus , Göster Manuel , Schobel Johannes , Ratz Christoph , Taurines Regina , Pryss Rüdiger , Romanos Marcel
Published: October 2022

Background

Challenging behaviour (CB) comprises various forms of aggressive and problematic behaviours frequently occurring in children with intellectual and developmental disability (IDD) or autism spectrum disorder (ASD). CB often arises from impaired communication or problem solving skills. It is often met with coercive measure due to a lack of alternative strategies on the part of the caregiver, while it also impacts on the caregivers due to the exposure to physical harm and high levels of stress. Within the ProVIA project we developed a smartphone-based tool for caregivers of children with IDD and/or ASD to prevent and modify CB. The ProVIA app systematically helps caregivers to identify specific causes of CB and provides individualised practical guidance to prevent CB and consecutive coercive measures, thus aiming to improve the health and well-being of the children and caregivers.

Methods

In this uncontrolled open trial we will enrol N = 25 caregivers of children aged 3–11 years with a diagnosis of IDD and/or ASD. Participants will use the ProVIA-Kids app for 8 weeks. During the intervention phase, participants will conduct behaviour analyses after each instance of CB. The app will summarise the identified putative causes for the CB in each situation, and provide recommendations regarding the handling and prevention of CB. Furthermore, the app will aggregate data from all available behaviour analyses and identify the most relevant (i.e., most frequently reported) risk factors. Measurement points are at baseline (T0), after the intervention (T1) and 12 weeks after the end of the intervention (follow-up; T2). The primary outcome is the absolute change in parental stress (EBI total scale) between T0 and T1. Further aspects of interest are changes in CB severity and frequency, caregiver mood, satisfaction with the parenting role (EFB-K total scale) and experienced parenting competence (FKE total scale). Pre-post comparisons will be analysed with paired sample t-tests.

Discussion

ProVIA is pioneering structured behaviour analysis via smartphone, assessing predefined causes of CB and providing feedback and recommendations. If this approach proves successful, the ProVIA-Kids app will be a valuable tool for caregivers to prevent CB and improve their own as well as the children’s quality of life.

Trial registration

The study is registered at https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_IDDRKS00029039 (registered May 31, 2022).
Statistical image properties predict aesthetic ratings in abstract paintings created by neural style transfer
Authors: Geller Hannah Alexa , Bartho Ralf , Thömmes Katja , Redies Christoph
Published: October 2022

Artificial intelligence has emerged as a powerful computational tool to create artworks. One application is Neural Style Transfer, which allows to transfer the style of one image, such as a painting, onto the content of another image, such as a photograph. In the present study, we ask how Neural Style Transfer affects objective image properties and how beholders perceive the novel (style-transferred) stimuli. In order to focus on the subjective perception of artistic style, we minimized the confounding effect of cognitive processing by eliminating all representational content from the input images. To this aim, we transferred the styles of 25 diverse abstract paintings onto 150 colored random-phase patterns with six different Fourier spectral slopes. This procedure resulted in 150 style-transferred stimuli. We then computed eight statistical image properties (complexity, self-similarity, edge-orientation entropy, variances of neural network features, and color statistics) for each image. In a rating study, we asked participants to evaluate the images along three aesthetic dimensions (Pleasing, Harmonious, and Interesting). Results demonstrate that not only objective image properties, but also subjective aesthetic preferences transferred from the original artworks onto the style-transferred images. The image properties of the style-transferred images explain 50 – 69% of the variance in the ratings. In the multidimensional space of statistical image properties, participants considered style-transferred images to be more Pleasing and Interesting if they were closer to a “sweet spot” where traditional Western paintings (JenAesthetics dataset) are represented. We conclude that NST is a useful tool to create novel artistic stimuli that preserve the image properties of the input style images. In the novel stimuli, we found a strong relationship between statistical image properties and subjective ratings, suggesting a prominent role of perceptual processing in the aesthetic evaluation of abstract images.
The role of Gadd45b in neurologic and neuropsychiatric disorders: An overview
Authors: Shen Xiao-yue , Shi Shu-han , Li Heng , Wang Cong-cong , Zhang Yao , Yu Hui , Li Yan-bin , Liu Bin
Published: October 2022

Growth arrest and DNA damage-inducible beta (Gadd45b) is directly intertwined with stress-induced DNA repair, cell cycle arrest, survival, and apoptosis. Previous research on Gadd45b has focused chiefly on non-neuronal cells. Gadd45b is extensively expressed in the nervous system and plays a critical role in epigenetic DNA demethylation, neuroplasticity, and neuroprotection, according to accumulating evidence. This article provided an overview of the preclinical and clinical effects of Gadd45b, as well as its hypothesized mechanisms of action, focusing on major psychosis, depression, autism, stroke, seizure, dementia, Parkinson’s disease, and autoimmune diseases of the nervous system.
WNK3 kinase maintains neuronal excitability by reducing inwardly rectifying K+ conductance in layer V pyramidal neurons of mouse medial prefrontal cortex
Authors: Sinha Adya Saran , Wang Tianying , Watanabe Miho , Hosoi Yasushi , Sohara Eisei , Akita Tenpei , Uchida Shinichi , Fukuda Atsuo
Published: October 2022

The with-no-lysine (WNK) family of serine-threonine kinases and its downstream kinases of STE20/SPS1-related proline/alanine-rich kinase (SPAK) and oxidative stress-responsive kinase-1 (OSR1) may regulate intracellular Cl− homeostasis through phosphorylation of cation-Cl− co-transporters. WNK3 is expressed in fetal and postnatal brains, and its expression level increases during development. Its roles in neurons, however, remain uncertain. Using WNK3 knockout (KO) mice, we investigated the role of WNK3 in the regulation of the intracellular Cl− concentration ([Cl−]i) and the excitability of layer V pyramidal neurons in the medial prefrontal cortex (mPFC). Gramicidin-perforated patch-clamp recordings in neurons from acute slice preparation at the postnatal day 21 indicated a significantly depolarized reversal potential for GABAA receptor-mediated currents by 6 mV, corresponding to the higher [Cl−]i level by ~4 mM in KO mice than in wild-type littermates. However, phosphorylation levels of SPAK and OSR1 and those of neuronal Na+-K+-2Cl− co-transporter NKCC1 and K+-Cl− co-transporter KCC2 did not significantly differ between KO and wild-type mice. Meanwhile, the resting membrane potential of neurons was more hyperpolarized by 7 mV, and the minimum stimulus current necessary for firing induction was increased in KO mice. These were due to an increased inwardly rectifying K+ (IRK) conductance, mediated by classical inwardly rectifying (Kir) channels, in KO neurons. The introduction of an active form of WNK3 into the recording neurons reversed these changes. The potential role of KCC2 function in the observed changes of KO neurons was investigated by applying a selective KCC2 activator, CLP290. This reversed the enhanced IRK conductance in KO neurons, indicating that both WNK3 and KCC2 are intimately linked in the regulation of resting K+ conductance. Evaluation of synaptic properties revealed that the frequency of miniature excitatory postsynaptic currents (mEPSCs) was reduced, whereas that of inhibitory currents (mIPSCs) was slightly increased in KO neurons. Together, the impact of these developmental changes on the membrane and synaptic properties was manifested as behavioral deficits in pre-pulse inhibition, a measure of sensorimotor gating involving multiple brain regions including the mPFC, in KO mice. Thus, the basal function of WNK3 would be the maintenance and/or development of both intrinsic and synaptic excitabilities.
PXF-1 promotes synapse development at the neuromuscular junction in Caenorhabditis elegans
Authors: Lamb Reagan , Dhar Bithika , Cherra Salvatore J.
Published: October 2022

Guanine nucleotide exchange factors (GEFs) are a family of proteins that modulate small G protein signaling. Mutations in a subfamily of GEFs that act on Rap, known as RapGEFs, have been associated with neurological disorders, and knockout mice display impairments in neuronal activity. However, the precise functions of RapGEFs in the nervous system remain unclear. Here, we have used the Caenorhabditis elegans neuromuscular junction, to investigate how the RapGEF homolog, PXF-1, regulates synaptic function. We found that loss of function mutations in pxf-1 reduced cholinergic activity at the neuromuscular junction. We observed that PXF-1 is expressed in the nervous system, and its expression in neurons is sufficient to promote synaptic activity. In pxf-1 mutant animals, there is a reduction in the levels of synaptic vesicles in cholinergic motor neurons but no change in the overall synapse numbers. In addition to synaptic vesicles proteins, we also found that filamentous actin, a scaffold for nascent synapses, was reduced at developing cholinergic synapses in pxf-1 mutant animals. Our studies indicate that PXF-1 regulates neuromuscular function by promoting the formation of actin filaments to support the development of motor neuron synapses.
Seizure-induced overexpression of NPY induces epileptic tolerance in a mouse model of spontaneous recurrent seizures
Authors: Drexel Meinrad , Sperk Günther
Published: October 2022

Epileptic seizures result in pronounced over-expression of neuropeptide Y (NPY).In vivoandin vitrostudies revealed that NPY exerts potent anticonvulsive actions through presynaptic Y2 receptors by suppressing glutamate release from principal neurons. We now investigated whether seizure-induced over-expression of NPY contributes to epileptic tolerance induced by preceding seizures. We used a previously established animal model based on selective inhibition of GABA release from parvalbumin (PV)-containing interneurons in the subiculum in mice. The animals present spontaneous recurrent seizures (SRS) and clusters of interictal spikes (IS). The frequency of SRS declined after five to six weeks, indicating development of seizure tolerance. In interneurons of the subiculum and sector CA1, SRS induced over-expression of NPY that persisted there for a prolonged time despite of a later decrease in SRS frequency. In contrast to NPY, somatostatin was not overexpressed in the respective axon terminals. Contrary to interneurons, NPY was only transiently expressed in mossy fibers. To demonstrate a protective function of endogenous, over-expressed NPY, we injected the selective NPY-Y2 receptor antagonist JNJ 5207787 simultaneously challenging the mice by a low dose of pentylenetetrazol (PTZ, 30 or 40 mg/kg, i.p.). In control mice, neither PTZ nor PTZ plus JNJ 5207787 induced convulsions. In mice with silenced GABA/PV neurons, PTZ alone only modestly enhanced EEG activity. When we injected JNJ 5207787 together with PTZ (either dose) the number of seizures, however, became significantly increased. In addition, in the epileptic mice CB1 receptor immunoreactivity was reduced in terminal areas of basket cells pointing to reduced presynaptic inhibition of GABA release from these neurons. Our experiments demonstrate that SRS result in overexpression of NPY in hippocampal interneurons. NPY overexpression persists for several weeks and may be related to later decreasing SRS frequency. Injection of the Y2 receptor antagonist JNJ 5207787 prevents this protective action of NPY only when release of the peptide is triggered by injection of PTZ and induces pronounced convulsions. Thus, over-expressed NPY released “on demand” by seizures may help terminating acute seizures and may prevent from recurrent epileptic activity.
Preparation and characterization of sequilhos-type biscuits added with almond flour of Acrocomia intumescens
Authors: Silva Maria Michele Alves da , Feitosa Maria Karine de Sá Barreto , Palitot Lúcia Emanuele Barros Teixeira , Coutinho Henrique Douglas Melo , Vasconcelos John Eversong Lucena de , Santos Francisco Antonio Vieira dos , Lisbôa Cícera Gomes Cavalcante de , Raposo António , Alfheeaid Hani A. , Alsharari Zayed D. , Alturki Hmidan A. , Alhaji Jwaher Haji , Sousa Erlânio Oliveira de
Published: October 2022

Acrocomia intumescens (“macaúba”) is a species that during processing generates a large amount of waste. The use of this residue for the production of flour for incorporation into food products is a way to minimize the cost and nutritionally enrich the final product. This work aimed to develop and analyze, in terms of physico-chemical and microbiological properties, cookies with macaúba almond cake residual flour. Sequilhos formulations were obtained using three different proportions of flour (2, 4 and 6%). The analysis of the flour allowed to find 4.29% of moisture, 1.13% of acidity, 5.33 of pH, 44.46% of carbohydrates, 28.74% of lipids, 20.06% of proteins and 2.45% of ash. In the analysis of the sequilhos formulations, the following values were found: moisture (5.03 to 8.13%), acidity (0.10 to 0.14%), pH (5.52 to 5.93), carbohydrates (67.17 to 73.37%), lipids (18.77 to 31.77%), proteins (0.85 to 1.92%), ash (0.83 to 0.94%) and total energy value (137.57 to 172,50 Kcal/100g). In microbiological analyzes it was highlighted that the sequilhos presented adequate sanitary conditions. The results indicate almond flour as an ingredient to be incorporated in the preparation of sequilhos, which in turn, presented satisfactory physico-chemical properties and microbiological results.
A preliminary study of the chemical composition and bioactivity of Bombax ceiba L. flower and its potential mechanism in treating type 2 diabetes mellitus using ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry and network pharmacology analysis
Authors: Yin Kehong , Yang Jinmei , Wang Fang , Wang Zhenxing , Xiang Ping , Xie Xing , Sun Jian , He Xuemei , Zhang Xuechun
Published: October 2022

This study aimed to preliminary investigate the phytochemistry, bioactivity, hypoglycemic potential, and mechanism of action of Bombax ceiba L. flower (BCF), a wild edible and food plant in China. By using methanol extraction and liquid-liquid extraction, the crude extract (CE) of BCF and its petroleum ether (PE), dichloromethane (DCM), ethyl acetate (EtOAc), n-butanol (n-BuOH), and aqueous (AQ) fractions were obtained, and their chemical components and biological activities were evaluated. Further high-performance liquid chromatography (HPLC) analysis was carried out to identify and quantify the active constituents of BFC and its five fractions, and the phytochemical composition of the best-performing fraction was then analyzed by ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC/Q-TOF-MS). Finally, a network pharmacology strategy based on the chemical profile of this fraction was applied to speculate its main hypoglycemic mechanism. Results revealed the excellent biological activities of BCF, especially the EtOAc fraction. In addition to the highest total flavonoid content (TFC) (367.72 μg RE/mg E) and total phenolics content (TPC) (47.97 μg GAE/mg E), EtOAc showed the strongest DPPH⋅ scavenging ability (IC50 value = 29.56 μg/mL), ABTS⋅+ scavenging ability (IC50 value = 84.60 μg/mL), and ferric reducing antioxidant power (FRAP) (889.62 μg FeSO4/mg E), which were stronger than the positive control BHT. EtOAc also exhibited the second-best α-glucosidase inhibitory capacity and second-best acetylcholinesterase (AChE) inhibitory capacity with the IC50 values of 2.85 and 3.27 mg/mL, respectively. Also, EtOAc inhibited HepG2, MCF-7, Raw264.7, and A549 cell with IC50 values of 1.08, 1.62, 0.77, and 0.87 mg/mL, which were the second or third strongest in all fractions. Additionally, HPLC analysis revealed significant differences in the compounds’ abundance between different fractions. Among them, EtOAc had the most detected compounds and the highest content. According to the results of UPLC/Q-TOF-MS, 38 compounds were identified in EtOAc, including 24 phenolic acids and 6 flavonoids. Network pharmacological analysis further confirmed 41 potential targets of EtOAc in the treatment of type 2 diabetes, and intracellular receptor signaling pathways, unsaturated fatty acid, and DNA transcription pathways were the most possible mechanisms. These findings suggested that BCF was worthwhile to be developed as an antioxidant and anti-diabetic food/drug.
The effect of omega-3 fatty acids and its combination with statins on lipid profile in patients with hypertriglyceridemia: A systematic review and meta-analysis of randomized controlled trials
Authors: Yang Yunjiao , Deng Wen , Wang Yanmei , Li Tongyi , Chen Yiding , Long Cong , Wen Qing , Wu Yue , Chen Qiu
Published: October 2022

Background/Aim

Omega-3 fatty acids (OM3-FA), a promising treatment for high triglycerides, have gradually attracted public attention. However, some studies showed that their application presented tricky problems, like increasing low-density lipoprotein cholesterol (LDL-C) levels. This study aimed to systematically evaluate the effect of OM3-FA or their combination with statins on the lipid profile in patients with hypertriglyceridemia.

Materials and methods

This study followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA 2020) guidelines. PubMed, Embase, Web of science, and Cochrane library were searched up to May 15, 2022. The random-effects model was applied to calculate the mean difference (MD) and associated 95% confidence intervals (CI).

Results

This meta-analysis included 32 studies with 15,903 subjects. When OM3-FA was used as monotherapy compared with placebo, it significantly decreased TG (MD: −39.81, 95% CI: −54.94 to −24.69; p < 0.001), TC (MD: −2.98, 95% CI: −5.72 to −0.25, p = 0.03), very low-density lipoprotein cholesterol (VLDL-C) (MD: −25.12, 95% CI: −37.09 to −13.14; p < 0.001), and non-high-density lipoprotein cholesterol (non-HDL-C) levels (MD: −5.42, 95% CI: −8.06 to−2.78; p < 0.001), and greatly increased LDL-C (MD: 9.10, 95% CI: 4.27 to 13.94; p < 0.001) and HDL levels (MD: 1.60, 95% CI: 0.06 to 3.15; p = 0.04). Regarding apolipoprotein B (Apo-B) and apolipoprotein AI (Apo-AI), no significant effect was identified. When OM3-FA was combined with statins, significant reductions were observed in the concentrations of TG (MD: −29.63, 95% CI: −36.24 to −23.02; p < 0.001), TC (MD: −6.87, 95% CI: −9.30 to −4.45, p < 0.001), VLDL-C (−20.13, 95% CI: −24.76 to −15.50; p < 0.001), non-HDL-C (MD: −8.71, 95% CI: −11.45 to −5.98; p < 0.001), Apo-B (MD: −3.50, 95% CI: −5.37 to −1.64; p < 0.001), and Apo-AI (MD: −2.01, 95% CI: −3.07 to −0.95; p < 0.001). However, the combined therapy did not exert significant changes on the levels of high-density lipoprotein cholesterol (HDL-C) and LDL-C compared to control group.

Conclusion

The use of OM3-FA either as monotherapy or in combination with statins may potentially reduce the levels of TG, TC, VLDL-C, non-HDL-C, Apo-B, and Apo-AI while increasing the levels of LDL-C and HDL-C. Nevertheless, the effects of OM3-FA observed in this review should be interpreted with caution due to the high heterogeneity between the included studies.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022329552].
Nutritional composition, heavy metal content and in vitro effect on the human gut microbiota of Talitrus saltator, an underutilized crustacean from the Atlantic coast
Authors: Lopez-Santamarina Aroa , Cardelle-Cobas Alejandra , Lamas Alexandre , Mondragon-Portocarrero Alicia , Cepeda Alberto , Miranda Jose Manuel
Published: October 2022

In this study, an undervalued marine crustacean (Talitrus saltator) was characterized in terms of nutritional and heavy metal composition and its potential to affect human gut microbiota. Nutritional analysis of this crustacean revealed that it complies with the criteria established in European legislation to include nutritional claims in their labeling, such as “source of fiber,” “low in fat,” “low in sugars” and “high in protein.” The analysis of the heavy metal content did not reveal any risk derived from the presence of Cd, Hg, or Pb, whereas essential metals contained in 100 g exceeded the minimum daily requirements recommended in Europe for Zn (19.78 mg/kg), Cu (2.28 mg/kg), and Fe (32.96 mg/kg). Using an in vitro system, the effect of T. saltator on the human colonic microbiota shows some beneficial effects, such as fermentation-maintained populations of Bifidobacterium or Lactobacillus, did not increase Firmicutes phylum counts, decreased the Firmicutes/Bacteroidetes ratio, and stimulated 11 metabolic pathways with respect to baseline. These results are unusual in a high protein content-food. However, negative effects were also found in gut microbiota relative proportions, such as an increase in the Proteobacteria phylum and especially some opportunistic bacteria from this phylum, probably due to the antimicrobial effect of chitin on other groups more sensitive to its effect. This work shows for the first time the effect of T. saltator on human colonic microbiota using and in vitro system. The presence of chitin in its composition could provide some beneficial effects by modulating the microbiota, but as T. saltator is a high-protein food, more studies should be carried out showing these benefits.
AI-based chest CT semantic segmentation algorithm enables semi-automated lung cancer surgery planning by recognizing anatomical variants of pulmonary vessels
Authors: Chen Xiuyuan , Xu Hao , Qi Qingyi , Sun Chao , Jin Jian , Zhao Heng , Wang Xun , Weng Wenhan , Wang Shaodong , Sui Xizhao , Wang Zhenfan , Dai Chenyang , Peng Muyun , Wang Dawei , Hao Zenghao , Huang Yafen , Wang Xiang , Duan Liang , Zhu Yuming , Hong Nan , Yang Fan
Published: October 2022

Background

The recognition of anatomical variants is essential in preoperative planning for lung cancer surgery. Although three-dimensional (3-D) reconstruction provided an intuitive demonstration of the anatomical structure, the recognition process remains fully manual. To render a semiautomated approach for surgery planning, we developed an artificial intelligence (AI)–based chest CT semantic segmentation algorithm that recognizes pulmonary vessels on lobular or segmental levels. Hereby, we present a retrospective validation of the algorithm comparing surgeons’ performance.

Methods

The semantic segmentation algorithm to be validated was trained on non-contrast CT scans from a single center. A retrospective pilot study was performed. An independent validation dataset was constituted by an arbitrary selection from patients who underwent lobectomy or segmentectomy in three institutions during Apr. 2020 to Jun. 2021. The golden standard of anatomical variants of each enrolled case was obtained via expert surgeons’ judgments based on chest CT, 3-D reconstruction, and surgical observation. The performance of the algorithm is compared against the performance of two junior thoracic surgery attendings based on chest CT.

Results

A total of 27 cases were included in this study. The overall case-wise accuracy of the AI model was 82.8% in pulmonary vessels compared to 78.8% and 77.0% for the two surgeons, respectively. Segmental artery accuracy was 79.7%, 73.6%, and 72.7%; lobular vein accuracy was 96.3%, 96.3%, and 92.6% by the AI model and two surgeons, respectively. No statistical significance was found. In subgroup analysis, the anatomic structure-wise analysis of the AI algorithm showed a significant difference in accuracies between different lobes (p = 0.012). Higher AI accuracy in the right-upper lobe (RUL) and left-lower lobe (LLL) arteries was shown. A trend of better performance in non-contrast CT was also detected. Most recognition errors by the algorithm were the misclassification of LA1+2 and LA3. Radiological parameters did not exhibit a significant impact on the performance of both AI and surgeons.

Conclusion

The semantic segmentation algorithm achieves the recognition of the segmental pulmonary artery and the lobular pulmonary vein. The performance of the model approximates that of junior thoracic surgery attendings. Our work provides a novel semiautomated surgery planning approach that is potentially beneficial to lung cancer patients.
Pretreatment plasma fibrinogen and serum albumin levels predict therapeutic efficacy of concurrent radiochemotherapy for esophageal squamous cell cancer
Authors: Wang Jijin , Huang Di , Wang Yuanyuan , Yuan Qianqian , Chen Xue , Cheng Yufeng
Published: October 2022

Purpose

Evidence implies that plasma fibrinogen and serum albumin level (FA score) based on plasma fibrinogen and serum albumin is related to cancer prognosis. However, the association between the FA score and therapeutic efficacy of concurrent radiochemotherapy in esophageal squamous cell carcinoma (ESCC) has not yet been evaluated. This study aimed to assess the role of pretreatment FA score in predicting the therapeutic efficacy of concurrent radiochemotherapy for patients with esophageal squamous cell cancer.

Methods

This retrospective study evaluated 154 patients with ESCC who underwent concurrent radiochemotherapy. Receiver operating characteristic curve (ROC) analysis was used to determine the appropriate cut-off values, and multivariate analysis and Kaplan-Meier curve were used to evaluate prognosis.

Results

FA score was significantly associated with the N stage and M stage (P = 0.015 and 0.042, respectively). Chi-square analysis/Fisher’s exact tests revealed a correlation between the FA score and curative effect (P < 0.001), and higher FA score was associated with poorer treatment effect. Multivariate analysis indicated that FA score (P < 0.001) was predictor of overall survival (OS). Kaplan-Meier curve demonstrated that pretreatment FA score was significantly associated with the OS of ESCC: Patient with higher FA score has lower median OS.

Conclusions

The FA score is a reliable prognostic predictor that could assess the curative effect and OS benefit of concurrent radiochemotherapy in patients with ESCC.
Recent advances in the diagnostic and therapeutic roles of microRNAs in colorectal cancer progression and metastasis
Authors: Liang Chen , Yang Jing-Bo , Lin Xin-Yi , Xie Bi-Lan , Xu Yun-Xian , Lin Shu , Xu Tian-Wen
Published: October 2022

Colorectal cancer (CRC) is the third most common malignancy in the world and one of the leading causes of cancer death; its incidence is still increasing in most countries. The early diagnostic accuracy of CRC is low, and the metastasis rate is high, resulting in a low survival rate of advanced patients. MicroRNAs (miRNAs) are a small class of noncoding RNAs that can inhibit mRNA translation and trigger mRNA degradation, and can affect a variety of cellular and molecular targets. Numerous studies have shown that miRNAs are related to tumour progression, immune system activity, anticancer drug resistance, and the tumour microenvironment. Dysregulation of miRNAs occurs in a variety of malignancies, including CRC. In this review, we summarize the recent research progress of miRNAs, their roles in tumour progression and metastasis, and their clinical value as potential biomarkers or therapeutic targets for CRC. Furthermore, we combined the roles of miRNAs in tumorigenesis and development with the therapeutic strategies of CRC patients, which will provide new ideas for the diagnosis and treatment of CRC.
CircHADHA-augmented autophagy suppresses tumor growth of colon cancer by regulating autophagy-related gene via miR-361
Authors: Shi Ying , Li Jinying , Tang Ming , Liu Jingwen , Zhong Yalu , Huang Wei
Published: October 2022

Colon cancer undergoes a traditional pathway from colon polyps to colon cancer. It is of great significance to investigate the key molecules involved in carcinogenesis from polyps to malignancies. Circular RNAs (circRNAs) are stably expressed in human body fluids such as plasma. Here, we demonstrated a differential expression pattern of plasma circRNAs in healthy individuals, colon polyp patients and colon cancer patients using circRNA Arraystar microarray. We explored that circRNA HADHA (circHADHA) was upregulated in plasma from polyp patients, whereas it was downregulated in plasma from colon cancer patients. Overexpression of circHADHA promoted autophagy in colon epithelial cells. Moreover, in colon cancer cells, overexpression of circHADHA promoted autophagy, whereas it inhibited cell proliferation and colony formation. CircHADHA increased the expression of ATG13 via miR-361 in both colon epithelial and cancer cells. ATG13 knockdown reduced autophagy even in the presence of circHADHA in colon cancer cells. Furthermore, the growth of circHADHA-overexpressing colon cancer cell-derived xenograft tumors was significantly decreased compared with control tumors in nude mice. In conclusion, circHADHA was differentially expressed in the plasma of healthy individuals, colon polyp patients and colon cancer patients. CircHADHA promoted autophagy by regulating ATG13 via miR-361 in both colon epithelial and cancer cells. CircHADHA suppressed tumor growth by inducing cell autophagy in colon cancer cells. CircHADHA potentially serves as a biomarker for screening of precursor colon cancer and a therapeutic target for colon cancer treatment.
Cutaneous verrucous carcinoma: A clinicopathological study of 21 cases with long-term clinical follow-up
Authors: Ye Qian , Hu Li , Jia Meng , Deng Li-Jia , Fang Sheng
Published: October 2022

Background

Cutaneous verrucous carcinoma (CVC) is a rare variant of squamous cell carcinoma and sometimes shares similar clinical and histopathological features with other verrucous lesions.

Methods

We performed a retrospective study of 21 patients diagnosed with CVC between 2012 and 2022 by reviewing clinical and histopathological data. We also compared the clinicopathological features of patients with CVC, giant condyloma acuminatum (GCA), and pseudoepitheliomatous hyperplasia (PEH). We obtained follow-up data by reviewing medical records and telephone interviews.

Results

The average age of patients with CVC was 63.6 years, with a male predominance. The location of disease is mostly found in the foot, followed by the lower legs. Histologically, CVC is characterized by an exo-endophytic growth pattern with severe keratinization and a blunted rete ridge with pushing margins. Clinical features including exudation and crusting, induration, irregular borders, and warty surface, as well as pathological features including growth pattern, koilocytotic cells, depth and morphologic features of acanthosis, severe keratinization, and degree of dermal inflammation, were significant in distinguishing cutaneous CVC, GCA, and PEH.

Conclusion

Identification of the clinicopathological features is essential to distinguish CVC from its mimics and to make an early diagnosis. Because of the potential for recurrence and metastasis, CVC requires aggressive treatment.
Chronic hepatitis C infection is associated with higher incidence of extrahepatic cancers in a Canadian population based cohort
Authors: Darvishian Maryam , Tang Terry , Wong Stanley , Binka Mawuena , Yu Amanda , Alvarez Maria , Alexander Velásquez García Héctor , Adu Prince Asumadu , Jeong Dahn , Bartlett Sofia , Karamouzian Mohammad , Damascene Makuza Jean , Wong Jason , Ramji Alnoor , Woods Ryan , Krajden Mel , Janjua Naveed , Bhatti Parveen
Published: October 2022

Introduction

Chronic infection with hepatitis C virus (HCV) is an established risk factor for liver cancer. Although several epidemiologic studies have evaluated the risk of extrahepatic malignancies among people living with HCV, due to various study limitations, results have been heterogeneous.

Methods

We used data from the British Columbia Hepatitis Testers Cohort (BC-HTC), which includes all individuals tested for HCV in the Province since 1990. We assessed hepatic and extrahepatic cancer incidence using data from BC Cancer Registry. Standardized incidence ratios (SIR) comparing to the general population of BC were calculated for each cancer site from 1990 to 2016.

Results

In total, 56,823 and 1,207,357 individuals tested positive and negative for HCV, respectively. Median age at cancer diagnosis among people with and without HCV infection was 59 (interquartile range (IQR): 53-65) and 63 years (IQR: 54-74), respectively. As compared to people living without HCV, a greater proportion of people living with HCV-infection were men (66.7% vs. 44.7%, P-value <0.0001), had comorbidities (25.0% vs. 16.3%, P-value <0.0001) and were socially deprived (35.9% vs. 25.0%, P-value <0.0001). The SIRs for liver (SIR 33.09; 95% CI 29.80-36.39), anal (SIR: 2.57; 95% CI 1.52-3.63), oesophagus (SIR: 2.00; 95% CI 1.17-2.82), larynx (SIR: 3.24; 95% CI 1.21-5.27), lung (SIR: 2.20; 95% CI 1.82-2.58), and oral (SIR: 1.78; 95% CI 1.33-2.23) cancers were significantly higher among individuals living with HCV. The SIRs for bile duct and pancreatic cancers were significantly elevated among both individuals living with (SIR; 95% CI: 2.20; 1.27-3.14; 2.18; 1.57-2.79, respectively) and without HCV (SIR; 95% CI: 2.12; 1.88-2.36; 1.20; 1.11-1.28, respectively).

Discussion/Conclusion

In this study, HCV infection was associated with increased incidence of several extrahepatic cancers. The elevated incidence of multiple cancers among negative HCV testers highlights the potential contributions of screening bias and increased cancer risks associated with factors driving acquisition of infection among this population compared to the general population. Early HCV diagnosis and treatment as well as public health prevention strategies are needed to reduce the risk of extrahepatic cancers among people living with HCV and potentially populations who are at higher risk of HCV infection.
Location matters: LAG3 levels are lower in renal cell carcinoma metastatic sites compared to primary tumors, and expression at metastatic sites only may have prognostic importance
Authors: Schoenfeld David A. , Merkin Ross D. , Moutafi Myrto , Martinez Sandra , Adeniran Adebowale , Kumar Deepika , Jilaveanu Lucia , Hurwitz Michael , Rimm David L. , Kluger Harriet M.
Published: October 2022

While great strides have been made in the treatment of advanced renal cell carcinoma (RCC) with the emergence of immune checkpoint inhibitors (ICIs) and VEGFR-targeting drugs, sizable proportions of patients still do not respond to upfront therapy and long-term responses only occur in a minority of patients. There is therefore a great need for the development of better predictors of response and an increased understanding of mechanisms of resistance to these therapies. Alternative immune checkpoints outside the PD-1/PD-L1 axis, such as LAG3, have been implicated as one mechanism of resistance to ICIs. These checkpoints thus represent attractive therapeutic targets, and indeed the LAG3 inhibitor relatlimab was recently approved for the treatment of metastatic melanoma in combination with anti-PD-1 therapy. LAG3 inhibitors are being evaluated for RCC as well. In this context, a better understanding of LAG3 expression patterns in RCC and how they relate to clinicopathologic features of disease and response to immunotherapy may give insight into mechanisms of resistance to PD-1 inhibitors and aid in the identification of subgroups of patients more likely to benefit from certain drug regimens. In this study, we assessed LAG3 protein levels in leukocytes in normal kidney adjacent to RCC, primary RCC tumors, and matched metastatic tumors, including large numbers of brain metastases. We found that LAG3 protein levels are on average lower at metastatic sites compared to matched primary tumors, and that the difference was more pronounced in patients with high-risk clinical characteristics, including those with larger primary tumor size, grade 4 tumors, IMDC poor-risk disease, and initial presentation with brain metastases. We further saw that the prognostic value of LAG3 levels varies depending on the tissue site queried (i.e., primary tumor versus metastases), and that relatively higher LAG3 levels at metastatic sites may predict a better response to immunotherapy and longer overall survival after the development of metastatic disease. These findings may have important implications for the design of future studies involving LAG3 or other immunotherapies in RCC.
Comparison of clinical efficacy of single-incision and traditional laparoscopic surgery for colorectal cancer: A meta-analysis of randomized controlled trials and propensity-score matched studies
Authors: Li Fang-han , Zeng De-xin , Chen Li , Xu Cheng-fei , Tan Ling , Zhang Pan , Xiao Jiang-wei
Published: October 2022

Background

Single-incision laparoscopy surgery (SILS) is a new laparoscopic technique that has emerged in the past decade. Whether it has advantages over conventionl laparoscopy surgery (CLS) is inconclusive. This article aimed to compare the short- and long-term outcomes of single-incision laparoscopic surgery and conventional laparoscopic surgery for colorectal cancer through high-quality literature text mining and meta-analysis.

Methods

Relevant articles were searched on the PubMed, Embase, and Cochrane Library databases from January 2012 to November 2021. All data was from randomized controlled trials (RCTs) in order to increase the confidence of the analytical results.The main outcomes were intraoperative and postoperative complications.

Results

A total of 10 RCTs were included, involving 1609 patients. The quality of the included studies was generally high. No significant difference was found between SILS and CLS in the postoperative complications, operation time, postoperative hospital stay, number of lymph nodes removed, readmission, reoperation, complication level I- II, complication level IIIa, complication level IIIb, prolonged Ileus, blood loss, infection, anastomotic leakage and operation time. The results showed that SILS group had a higher rate of intraoperative complications, but it had lower incision length and better cosmetic effects.

Conclusion

These results indicate that SILS did not have a comprehensive and obvious advantage over the CLS. On the contrary, SILS has higher intraoperative complications, which may be related to the more difficulty of SILS operation, but SILS still has better cosmetic effects, which is in line with the concept of surgical development. Therefore, the SILS needs to be selected in patients with higher cosmetic requirements and performed by more experienced surgeons.
A novel 3D deep learning model to automatically demonstrate renal artery segmentation and its validation in nephron-sparing surgery
Authors: Zhang Shaobo , Yang Guanyu , Qian Jian , Zhu Xiaomei , Li Jie , Li Pu , He Yuting , Xu Yi , Shao Pengfei , Wang Zengjun
Published: October 2022

Purpose

Nephron-sparing surgery (NSS) is a mainstream treatment for localized renal tumors. Segmental renal artery clamping (SRAC) is commonly used in NSS. Automatic and precise segmentations of renal artery trees are required to improve the workflow of SRAC in NSS. In this study, we developed a tridimensional kidney perfusion (TKP) model based on deep learning technique to automatically demonstrate renal artery segmentation, and verified the precision and feasibility during laparoscopic partial nephrectomy (PN).

Methods

The TKP model was established based on convolutional neural network (CNN), and the precision was validated in porcine models. From April 2018 to January 2020, TKP model was applied in laparoscopic PN in 131 patients with T1a tumors. Demographics, perioperative variables, and data from the TKP models were assessed. Indocyanine green (ICG) with near-infrared fluorescence (NIRF) imaging was applied after clamping and dice coefficient was used to evaluate the precision of the model.

Results

The precision of the TKP model was validated in porcine models with the mean dice coefficient of 0.82. Laparoscopic PN was successfully performed in all cases with segmental renal artery clamping (SRAC) under TKP model’s guidance. The mean operation time was 100.8 min; the median estimated blood loss was 110 ml. The ischemic regions recorded in NIRF imaging were highly consistent with the perfusion regions in the TKP models (mean dice coefficient = 0.81). Multivariate analysis revealed that the feeding lobar artery number was strongly correlated with tumor size and contact surface area; the supplying segmental arteries number correlated with tumor size.

Conclusions

Using the CNN technique, the TKP model is developed to automatically present the renal artery trees and precisely delineate the perfusion regions of different segmental arteries. The guidance of the TKP model is feasible and effective in nephron-sparing surgery.
Current and emerging adjuvant therapies in biliary atresia
Authors: Fligor Scott C. , Hirsch Thomas I. , Tsikis Savas T. , Adeola Andrew , Puder Mark
Published: October 2022

Following Kasai hepatic portoenterostomy (HPE), most patients with biliary atresia will eventually require liver transplantation due to progressive cirrhosis and liver failure. Preventing liver transplantation, or even delaying eventual liver transplantation, is the key to improving long-term outcomes. This review first examines the commonly used adjuvant therapies in post-HPE biliary atresia and the strength of the evidence supporting these therapies. Next, it examines the evolving frontiers of management through a comprehensive evaluation of both recently completed and ongoing clinical trials in biliary atresia. Promising therapies used in other cholestatic liver diseases with potential benefit in biliary atresia are discussed. Improving post-HPE management is critical to prevent complications, delay liver transplantation, and ultimately improve the long-term survival of patients with biliary atresia.
Population pharmacokinetics of mycophenolate mofetil in pediatric patients early after liver transplantation
Authors: Wei Yinyi , Wu Dongni , Chen Yiyu , Dong Chunqiang , Qi Jianying , Wu Yun , Cai Rongda , Zhou Siru , Li Chengxin , Niu Lulu , Wu Tingqing , Xiao Yang , Liu Taotao
Published: October 2022

Objective: To investigate the factors influencing the pharmacokinetics of mycophenolate mofetil (MMF) in pediatric patients after liver transplantation, and to establish a population pharmacokinetics model, which can provide a reference for clinical dosage adjustment.

Methods: A prospective study in a single center was performed on pediatric patients who were administrated with mycophenolate mofetil dispersible tablets (MMFdt) for at least 4 days after liver transplantation continuously. Blood samples were collected in ethylene diamine tetraacetic acid anticoagulant tubes before dosing and 0.5, 1, 2, 4, 8, and 12 h after the morning intake of MMFdt. The concentrations of mycophenolic acid (MPA) in plasma were assayed with a validated reverse-phase high-performance liquid chromatography method. UGT1A8 518C > G, UGT1A9 -275T > A, UGT1A9 -2152C > T, UGT2B7 211G > T, SLC O 1B1 521T > C polymorphism were determined by Sanger sequencing. Nonlinear mixed effects modeling was used to establish the population pharmacokinetics (PPK) model. The predictability and stability of the model were internally evaluated by the goodness of fit plots, visual prediction check, normalized prediction errors, and bootstraps.

Results: A two-compartment model with first-order absorption and first-order elimination was established with 115 MPA concentrations from 20 pediatric patients. The final model were: CL/F (L/h) = 14.8×(WT/7.5)0.75×(DOSE/11.16)0.452×е0.06, Ka (h−1) = 2.02×(WT/7.5)−0.25, Vc/F (L) = 6.01×(WT/7.5), Vp/F (L) = 269 (fixed), Q/F (L/h) = 15.4×(WT/7.5)0.75×е1.39. Where CL/F was the apparent clearance rate, Ka was the absorption rate constant, Vc/F was the apparent distribution volume of the central compartment, Vp/F was the apparent distribution volume of the peripheral compartment, Q/F was the atrioventricular clearance rate, WT was the body weight of the subject, and DOSE was the MMFdt administered dose. The model indicated there was large inter-individual variability in CL/F and Q/F after multiple dosing of MMFdt. Internal evaluation results showed that the final model had good stability and prediction performance.

Conclusion: A stable and predictive population pharmacokinetic model of MMFdt in pediatric patients after the early stage of liver transplantation was established. The pediatric patient’s weight and the dose of MMFdt can be a reference to adjust the MMFdt dose.
Integrated network pharmacology and serum metabolomics approach deciphers the anti-colon cancer mechanisms of Huangqi Guizhi Wuwu Decoction
Authors: Pan Boyu , Xia Yafei , Fang Senbiao , Ai Jun , Wang Kunpeng , Zhang Jian , Du Chunshuang , Chen Yuzhou , Liu Liren , Yan Shu
Published: October 2022

Huangqi Guizhi Wuwu Decoction (HGWD), as a classic Chinese herbal decoction, has been widely used in treating various diseases for hundreds of years. However, systematically elucidating its mechanisms of action remains a great challenge to the field. In this study, taking advantage of the network pharmacology approach, we discovered a potential new use of HGWD for patients with colon cancer (CC). Our in vivo result showed that orally administered HGWD markedly inhibited the growth of CC xenografts in mice. The subsequent enrichment analyses for the core therapeutic targets revealed that HGWD could affect multiple biological processes involving CC growth, such as metabolic reprogramming, apoptosis and immune regulation, through inhibiting multiple cell survival-related signalings, including MAPK and PI3K-AKT pathways. Notably, these in silico analysis results were most experimentally verified by a series of in vitro assays. Furthermore, our results based on serum metabolomics showed that the lipid metabolic pathways, including fatty acid biosynthesis and cholesterol metabolism, play key roles in delivery of the anti-CC effect of HGWD on tumor-bearing mice, and that cytochrome P450 family 2 subfamily E member 1 (CYP2E1) is a potential therapeutic target. Together, our integrated approach reveals a therapeutic effect of HGWD on CC, providing a valuable insight into developing strategies to predict and interpret the mechanisms of action for Chinese herbal decoctions.