bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of epilepsy and its treatment on brain metastasis from solid tumors: A retrospective study
Authors: Maschio Marta , Maialetti Andrea , Giannarelli Diana , Koudriavtseva Tatiana , Galiè Edvina , Fabi Alessandra
Published: October 2022

Introduction

Retrospective observational study on medical records of patients with epilepsy related brain metastases (BM) to evaluate efficacy, safety and possible interaction with cancer treatment of different anti-seizure medications (ASMs) and the risk of seizures.

Materials and methods

We consecutively reviewed all medical records of epilepsy-related BM patients from 2010 to 2020 who were followed for at least one month at the Brain Tumour-related Epilepsy Center of the IRCCS Regina Elena National Cancer Institute Rome, Italy.

Results

We selected 111 cancer patients. Of these, only 42 had at least undergone a second neurological examination. In the whole population, 95 (85.2%) had seizures and 16 patients had no seizures (14.4%). The most frequently first ASM prescribed was LEV (40.5%). We observed a significant correlation between tumor site and probability of having seizures, but not between seizure type and age (>65 or <65 years). Among 42 patients, 26 were administered levetiracetam, followed by oxcarbazepine. Until the last follow-up, 19 never changed the first ASM, maintained the same dosage and remained seizure free. After a median of 7 months, 16 (38.1%) required changes in therapeutic treatment due to inefficacy. At the last follow-up, 24 patients (57.1%) were seizure free. Eighteen patients (42.8%) never achieved freedom from seizures despite had at least 2 therapy changes. Two patients changed ASM due to adverse events and 1 to phenobarbital owing to the interaction with cancer treatment. The mean daily dose of first ASM in all 42 patients was very close to the Defined Daily Dose (DDD).

Conclusion

In BM patients seizure incidence could be underestimated; a team evaluation performed by oncologist and neurologist together, could guarantee an accurate taking care of both oncological illness and epilepsy, in this fragile patient population. More than 50% of our patients respond to monotherapy with new generation ASMs. Furthermore we deemed in patients receiving chemotherapy the choice of ASM should consider possible interactions with antitumor therapies, for this reason newer generation ASMs should be the preferred choice. It is necessary to get close to the DDD before considering an ASM ineffective in seizure control.
Fronto-parietal cortex activation during walking in patients with Parkinson's disease adopting different postural strategies
Authors: Zhang Xinyuan , Wang Yue , Lu Jiewei , Wang Jin , Shu Zhilin , Cheng Yuanyuan , Zhu Zhizhong , Liu PeiPei , Yu Yang , Yu Ningbo , Han Jianda , Wu Jialing
Published: October 2022

Background

Cortical activation patterns in patients with Parkinson's disease (PD) may be influenced by postural strategies, but the underlying neural mechanisms remain unclear. Our aim is to examine the role of the fronto-parietal lobes in patients with PD adopting different postural strategies and the effect of dual task (DT) on fronto-parietal activation.

Methods

Two groups of patients with PD adopting either the posture first strategy (PD-PF) or the posture second strategy (PD-PS) were examined respectively when in the “OFF” state while single-walking task (SW) and DT. Frontal and parietal lobe activity was assessed by functional near infrared spectroscopy (fNIRS) and measuring gait parameters. Linear mixed models were used for analyses.

Results

Patients with PD who adopted PS had greater cortical activation than those who adopted PF, and there was no difference between PF and PS in the behavioral parameters. For oxyhemoglobin levels, the task condition (SW vs. DT) had a main effect in fronto-parietal lobes. Postural strategy (PD-PF vs. PD-PS) a main effect in the left prefrontal cortex (LPFC), left parietal lobe (LPL), and right parietal lobe (RPL) regions. In the task of walking with and without the cognitive task, patients with PD adopting PS had higher activation in the LPL than those adopting PF. In DT, only PD patients who adopted PS had elevated oxyhemoglobin levels in the LPFC, right prefrontal cortex (RPFC), and LPL compared with the SW, whereas patients with PD who adopted PF showed no differences in any region.

Conclusion

Different patterns of fronto-parietal activation exist between PD-PF and PD-PS. This may be because PD-PS require greater cortical functional compensation than those adopting PF.
Metabolic regulation of the neural stem cell fate: Unraveling new connections, establishing new concepts
Authors: Angelopoulos Ioannis , Gakis Georgios , Birmpas Kyriakos , Kyrousi Christina , Habeos Evagelia Eva , Kaplani Konstantina , Lygerou Zoi , Habeos Ioannis , Taraviras Stavros
Published: October 2022

The neural stem cell niche is a key regulator participating in the maintenance, regeneration, and repair of the brain. Within the niche neural stem cells (NSC) generate new neurons throughout life, which is important for tissue homeostasis and brain function. NSCs are regulated by intrinsic and extrinsic factors with cellular metabolism being lately recognized as one of the most important ones, with evidence suggesting that it may serve as a common signal integrator to ensure mammalian brain homeostasis. The aim of this review is to summarize recent insights into how metabolism affects NSC fate decisions in adult neural stem cell niches, with occasional referencing of embryonic neural stem cells when it is deemed necessary. Specifically, we will highlight the implication of mitochondria as crucial regulators of NSC fate decisions and the relationship between metabolism and ependymal cells. The link between primary cilia dysfunction in the region of hypothalamus and metabolic diseases will be examined as well. Lastly, the involvement of metabolic pathways in ependymal cell ciliogenesis and physiology regulation will be discussed.
High-resolution spatiotemporal analysis of single serotonergic axons in an in vitro system
Authors: Hingorani Melissa , Viviani Adele M. L. , Sanfilippo Jenna E. , Janušonis Skirmantas
Published: October 2022

Vertebrate brains have a dual structure, composed of (i) axons that can be well-captured with graph-theoretical methods and (ii) axons that form a dense matrix in which neurons with precise connections operate. A core part of this matrix is formed by axons (fibers) that store and release 5-hydroxytryptamine (5-HT, serotonin), an ancient neurotransmitter that supports neuroplasticity and has profound implications for mental health. The self-organization of the serotonergic matrix is not well understood, despite recent advances in experimental and theoretical approaches. In particular, individual serotonergic axons produce highly stochastic trajectories, fundamental to the construction of regional fiber densities, but further advances in predictive computer simulations require more accurate experimental information. This study examined single serotonergic axons in culture systems (co-cultures and monolayers), by using a set of complementary high-resolution methods: confocal microscopy, holotomography (refractive index-based live imaging), and super-resolution (STED) microscopy. It shows that serotonergic axon walks in neural tissue may strongly reflect the stochastic geometry of this tissue and it also provides new insights into the morphology and branching properties of serotonergic axons. The proposed experimental platform can support next-generation analyses of the serotonergic matrix, including seamless integration with supercomputing approaches.
Choroid plexus epithelium and its role in neurological diseases
Authors: Liu Ruizhen , Zhang Zhiping , Chen Yibing , Liao Junbo , Wang Yuchang , Liu Jingping , Lin Zhixiong , Xiao Gelei
Published: October 2022

Choroid plexus epithelial cells can secrete cerebrospinal fluid into the ventricles, serving as the major structural basis of the selective barrier between the neurological system and blood in the brain. In fact, choroid plexus epithelial cells release the majority of cerebrospinal fluid, which is connected with particular ion channels in choroid plexus epithelial cells. Choroid plexus epithelial cells also produce and secrete a number of essential growth factors and peptides that help the injured cerebrovascular system heal. The pathophysiology of major neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, as well as minor brain damage diseases like hydrocephalus and stroke is still unknown. Few studies have previously connected choroid plexus epithelial cells to the etiology of these serious brain disorders. Therefore, in the hopes of discovering novel treatment options for linked conditions, this review extensively analyzes the association between choroid plexus epithelial cells and the etiology of neurological diseases such as Alzheimer's disease and hydrocephalus. Finally, we review CPE based immunotherapy, choroid plexus cauterization, choroid plexus transplantation, and gene therapy.
Mortality prediction of the nutrient profile of the Chilean front-of-pack warning labels: Results from the Seguimiento Universidad de Navarra prospective cohort study
Authors: Bullón-Vela Vanessa , Sayón-Orea Carmen , Gómez-Donoso Clara , Martínez J. A. , Martínez-González Miguel A. , Bes-Rastrollo Maira
Published: October 2022

Background and aims

Front-of-Pack (FoP) nutrition labelling has been established as a policy, empowering consumers to choose healthy food options for preventing diet-related non-communicable diseases. This study aimed to evaluate the association between the nutrient profile underlying the Chilean warning label score and all-cause mortality and to conduct a calibration with the Nutri-Score in a large cohort of Spanish university graduates.

Materials and methods

This prospective cohort study analysed 20,666 participants (8,068 men and 12,598 women) with a mean (standard deviation) age of 38 years (±12.4) from the SUN cohort. Dietary food intake was assessed by a validated semi-quantitative food-frequency questionnaire at baseline and after 10 years of follow-up. The warning label score was calculated by considering the threshold of nutrients (sugar, saturated fat, and sodium) and energy density per 100 g/ml of product, as established by Chilean Legislation. Participants were classified according to quartiles of consumption of daily label score: Q1 (≤5.0), Q2 (>5.0–7.1), Q3 (>7.1–9.8), and Q4 (>9.8). Time-dependent, multivariable-adjusted Cox models were applied. To compare the performance of the warning label score and Nutri-Score to predict mortality, we used the Akaike information criterion (AIC) and Bayesian information criterion (BIC) methods.

Results

During a median of 12.2 years of follow-up, 467 deaths were identified. A higher score in the warning label values (lower nutritional quality) was associated with an increased risk of all-cause mortality [HR (95% CI) Q4 vs. Q1: 1.51 (1.07–2.13); p-trend = 0.010] and cancer mortality [HR (95% CI) Q4 vs. Q1: 1.91 (1.18–3.10); p-trend = 0.006]. However, no statistically significant association was found for cardiovascular mortality. Furthermore, the warning label score and Nutri-Score exhibited comparable AIC and BIC values, showing similar power of prediction for mortality.

Conclusion

A diet with a higher warning label score (>9.8 per day) was a good predictor of all cases and cancer mortality in a large Spanish cohort of university graduates. Also, the warning label score was capable to predict mortality as well as the Nutri-Score. Our findings support the validity of the warning label score as a FoP nutrition labelling policy since it can highlight less healthy food products.
Embryonal tumors with multilayered rosettes, C19MC-altered or not elsewhere classified: Clinicopathological characteristics, prognostic factors, and outcomes of 17 children from 2018 to 2022
Authors: Xu Kailun , Sun Zhaoyun , Wang Lifeng , Guan Wenbin
Published: October 2022

Objective

Embryonal tumors with multilayered rosettes (ETMRs) are a histologically heterogeneous entity and gather embryonal tumors with abundant neuropil and true rosettes (ETANTRs), ependymoblastoma, and medulloepithelioma. ETMRs are highly aggressive and associated with poorer clinical courses. However, cases of this entity are rare, and advances in molecular genetics and therapy are minor. The purpose of our study was to retrospectively analyze the clinical, pathological features, and prognostic factors of ETMRs.

Methods

Our cohort consisted of 17 patients diagnosed with ETMRs in our hospital from 2018 to 2022, and two of them were lost to follow-up. Clinical data were retrieved, and immunohistochemistry and genetic analyses were performed.

Results

Among 17 cases, 16 were ETANTRs, and one was medulloepithelioma. Morphologically, tumor cells of ETANTRs could transform into anaplasia and lose the biphasic architecture during tumor progression. Immunohistochemistry of LIN28A revealed positive expression in 17 cases, and the expression of LIN28A was more intense and diffuse in the recurrent lesions than in primaries. The increased N-MYC copy numbers were detected in the primary tumor and recurrence of patient 8. Moreover, the incidence of metastatic disease was 100% in patients aged > 4 years and 18% in the younger group. For patients receiving chemotherapy, the median overall survival time was 7.4 months, while that of those who didn’t receive it was 1.2 months. Nevertheless, surgical approaches, radiotherapy, age at presentation, gender, tumor location, and metastatic status were not associated with independent prognosis.

Conclusion

ETANTR might not present as the typical morphologies during tumor progression, so analyses of C19MC amplification and Lin28A antibody are indispensable for diagnosing ETMRs accurately. Children aged > 4 years tend to have a higher rate of metastasis in ETMRs. Chemotherapy is the only prognostic factor for ETMRs patients with a favorable prognosis. The biological nature and clinical patterns for recurrent diseases need to be further demonstrated to predict prognosis and guide treatment.
HER2 expression in urothelial carcinoma, a systematic literature review
Authors: Scherrer Emilie , Kang Ashley , Bloudek Lisa M. , Koshkin Vadim S.
Published: October 2022

Background

Urothelial carcinoma (UC) is a common malignancy with significant associated mortality. Recent clinical trials suggest an emerging role for HER2-targeted therapy. Testing for HER2 expression in UC is not part of current routine clinical practice. In consequence, the prevalence of HER2 expression in UC is not well defined.

Methods

A systematic literature review (SLR) was conducted to characterize HER2 expression in both locally advanced unresectable or metastatic (LA/mUC) and earlier stage UC, classified as HER2+, HER2-low, HER2-. HER2+ was defined as an immunohistochemistry (IHC) score of 3+ or IHC 2+ and ISH/FISH+. HER2-low was defined as an IHC score of 2+ and ISH/FISH- or IHC 1+. HER2- was defined as an IHC score of 0. Weighted averages were calculated to generate an estimate of the population prevalence.

Results

A total of 88 studies were identified, with 45, 30, and 13 studies investigating LA/mUC, earlier stage UC, and mixed stage/unspecified, respectively. The most common assays used were Dako HercepTest and Ventana Pathway anti-HER2/neu (4B5) for IHC to assess HER2 protein expression; Abbott PathVysion HER-2 DNA Probe Kit, FoundationOne CDx, and Guardant360 CDx for assessing HER2 gene amplification. The most frequently cited scoring guidelines were ASCO/CAP guidelines for breast cancer and gastric cancer, though most studies defined their own criteria for HER2 expression. Using the pre-specified definition, HER2+ prevalence ranged from 6.7% to 37.5% with a weighted average of 13.0% in LA/mUC. Only 1 study presented data that could be classified as HER2+ based on pre-specified criteria in earlier stage UC patients, and this study represented a likely outlier, at 76.0%.

Conclusion

The results from this SLR help to shed light on HER2 expression in UC, a potentially clinically relevant biomarker-driven subpopulation for emerging HER2-directed regimens. Results of this SLR illuminate the variability in how HER2+ status expression levels are being assessed and how HER2+ is defined. Consensus on standardized HER2 testing and scoring criteria is paramount to better understand the clinical relevance in patients with UC.
3D renal model for surgical planning of partial nephrectomy: A way to improve surgical outcomes
Authors: Bianchi Lorenzo , Cercenelli Laura , Bortolani Barbara , Piazza Pietro , Droghetti Matteo , Boschi Sara , Gaudiano Caterina , Carpani Giulia , Chessa Francesco , Lodi Simone , Tartarini Lorenzo , Bertaccini Alessandro , Golfieri Rita , Marcelli Emanuela , Schiavina Riccardo , Brunocilla Eugenio
Published: October 2022

Objective

to evaluate the impact of 3D model for a comprehensive assessment of surgical planning and quality of partial nephrectomy (PN).

Materials and methods

195 patients with cT1-T2 renal mass scheduled for PN were enrolled in two groups: Study Group (n= 100), including patients referred to PN with revision of both 2D computed tomography (CT) imaging and 3D model; Control group (n= 95), including patients referred to PN with revision of 2D CT imaging. Overall, 20 individuals were switched to radical nephrectomy (RN). The primary outcome was the impact of 3D models-based surgical planning on Trifecta achievement (defined as the contemporary absence of positive surgical margin, major complications and ≤30% postoperative eGFR reduction). The secondary outcome was the impact of 3D models on surgical planning of PN. Multivariate logistic regressions were used to identify predictors of selective clamping and Trifecta’s achievement in patients treated with PN (n=175).

Results

Overall, 73 (80.2%) patients in Study group and 53 (63.1%) patients in Control group achieved the Trifecta (p=0.01). The preoperative plan of arterial clamping was recorded as clampless, main artery and selective in 22 (24.2%), 22 (24.2%) and 47 (51.6%) cases in Study group vs. 31 (36.9%), 46 (54.8%) and 7 (8.3%) cases in Control group, respectively (p<0.001). At multivariate logistic regressions, the use of 3D model was found to be independent predictor of both selective or super-selective clamping and Trifecta’s achievement.

Conclusion

3D-guided approach to PN increase the adoption of selective clamping and better predict the achievement of Trifecta.
Inflammation-related parameter serve as prognostic biomarker in esophageal squamous cell carcinoma
Authors: Xu Xiaoqin , Jing Jiexian
Published: October 2022

Objective

The aim of this study was to explore the predictive role of inflammation-related parameters in prognosis of esophageal squamous cell carcinoma (ESCC).

Methods

A total of 370 ESCC patients subjected to curative surgery were enrolled. All patients had complete medical records and did not receive preoperative adjuvant therapy. Preoperative systemic immune-inflammation index (SII) was calculated as platelet count × neutrophil count/lymphocyte count, prognostic nutrition index (PNI) as albumin concentration (g/L) + 5 × total lymphocyte count (109/L), and systemic inflammation response index (SIRI) as neutrophil count × monocyte count/lymphocyte count. The optimal cut‐off values of preoperative SII, neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), PNI, and SIRI were determined via receiver operating characteristic (ROC) analysis, and their correlations with clinical parameters and survival analyzed.

Results

NLR was associated with gender (P = 0.022), and PLR (P = 0.037), PNI (P = 0.017) was associated with survival status, LMR was related with gender (P = 0.034) and survival status (P = 0.01), SIRI was correlated with gender (P = 0.000), smoking history (P = 0.000) and drinking history (P = 0.004). Survival analysis indicated that high PLR (P = 0.042), low LMR (P = 0.001), and low PNI (P = 0.007) were predictive of poor prognosis of ESCC. Stratified analysis revealed the prognostic predictor roles of distinct markers in different ESCC subgroups. SII and SIRI were predominantly correlated with the clinical outcome in the lymphatic metastasis subgroup. Further univariate analysis disclosed that T stage, smoking history, lymphatic metastasis, TNM staging, PLR, LMR, and PNI potentially serve as influencing factors(P < 0.05). Multivariate analysis identified T stage (HR = 1.781, P = 0.002), TNM staging (HR = 8.617, P = 0.001) and LMR (HR = 0.504, P = 0.001) as independent predictors for outcomes of ESCC.

Conclusions

Low LMR could serve as an independent marker of poor prognosis in patients with ESCC. Inflammation-related markers have distinct predictive roles in ESCC subgroups with different features.
Optimization of a method for the clinical detection of serum exosomal miR-940 as a potential biomarker of breast cancer
Authors: Gu Zhiyun , Yin Haojie , Zhang Haiwei , Zhang Hui , Liu Xiaoyu , Zeng Xiaohua , Zheng Xiaodong
Published: October 2022

Serum exosomal microRNAs (miRNAs) are potential biomarkers for tumor diagnosis. Clinically, reverse transcription-quantitative polymerase chain reaction (RT−qPCR) can be used to determine the expression of exosomal miRNAs in the serum of breast cancer patients. The prerequisites for obtaining meaningful serum exosomal miRNA data of breast cancer patients include a suitable extraction method for exosomes and RT−qPCR data standardized by internal reference genes. However, the appropriate methods for the extraction of exosomes and the applicability of reference genes for analyzing exosomal miRNAs in breast cancer patients remain to be studied. This study compared the effects of three exosome extraction methods as well as the expression of exosomal miRNA in different initial serum amounts and at different serum states to identify the selection of the best method for serum exosome extraction. Five candidate reference genes including miR-16, miR-484, miR-1228, miR-191 and miR-423 for standardizing serum exosomal miRNAs were screened using five algorithms and were used for the quantification of serum exosomal miR-940. Significant downregulation of serum exosomal miR-940 expression in breast cancer was detected using miR-191 and miR-1228, whereas no significant down or up regulation was observed with miR-484, miR-423 and miR-16. Previous studies have shown that the expression level of miR-940 is downregulated in breast cancer tissues. The absolute quantitative results showed that miR-940 was significantly downregulated in breast cancer serum exosomes, which was consistent with the results from the analysis using miR-191 or miR-1228 as reference genes. Therefore, miR-191 and miR-1228 could serve as reference genes for the relative quantification of serum exosomal miRNAs. This finding indicated the importance of rigorously evaluating the stability of reference genes and standardization for serum exosomal miRNA expression. Moreover, the level of serum exosomal miR-940 in breast cancer could reflect the presence of lymph node metastasis and the status of HER2/neu, which indicates its potential as a biomarker for breast cancer metastasis. In summary, an optimized protocol for the detection of serum exosomal miR-940 as a breast cancer marker was preliminarily established.
Clinical impact of soluble Neuropilin-1 in ovarian cancer patients and its association with its circulating ligands of the HGF/c-MET axis
Authors: Klotz Daniel Martin , Kuhlmann Jan Dominik , Link Theresa , Goeckenjan Maren , Hofbauer Lorenz C. , Göbel Andy , Rachner Tilman D. , Wimberger Pauline
Published: October 2022

Background

Neuropilin (NRP) is a transmembrane protein, which has been shown to be a pro-angiogenic mediator and implicated as a potential driver of cancer progression. NRP-1 up-regulation in ovarian cancer tissue predicts poor prognosis. However, the clinical relevance of the soluble form of NRP-1 (sNRP-1) as a circulating biomarker in ovarian cancer patients is unknown.

Methods/patients cohort

sNRP-1 levels were quantified in a cohort of 88 clinically documented ovarian cancer patients by a commercially available sNRP-1 enzyme-linked immunosorbent assay (ELISA) kit (Biomedica, Vienna, Austria). Patients (81.8% with FIGOIII/IV) received primary cytoreductive surgery with the aim of macroscopic complete resection (achieved in 55.7% of patients) and the recommendation of adjuvant chemotherapy in line with national guidelines.

Results

Higher levels of sNRP-1 reflected more advanced disease (FIGO III/IV) and indicated a trend towards suboptimal surgical outcome, i.e. any residual tumor. sNRP-1 was neither related to the patients’ age nor the BRCA1/2 mutational status. Patients with higher sNRP-1 levels at primary diagnosis had a significantly reduced progression-free survival (PFS) (HR = 0.541, 95%CI: 0.304 - 0.963; p = 0.037) and overall survival (OS) (HR = 0.459, 95%CI: 0.225 - 0.936; p = 0.032). Principal component analysis showed that sNRP-1 levels were unrelated to the circulating hepatocyte growth factor (HGF) and the soluble ectodomain of its receptor the tyrosine kinase mesenchymal–epithelial transition (c-MET), suggesting that there is no proportional serological concentration gradient of soluble components of the NRP-1/HGF/c-MET signaling axis.

Conclusions

In line with the previously shown tissue-based prognostic role, we demonstrated for the first time that sNRP-1 can also act as a readily accessible, prognostic biomarker in the circulation of patients with ovarian cancer at primary diagnosis. Given its known role in angiogenesis and conferring resistance to the poly ADP-ribose polymerase (PARP) inhibitor olaparib in vitro, our results encourage more detailed investigation into sNRP-1 as a potential predictive biomarker for bevacizumab and/or PARP-inhibitor treatment.
Case report and literature review: Novel compound heterozygous FIG4 variants causing both of peripheral and central nervous system defects
Authors: Yu Yonglin , Yin Hongwei , Ma Changli , Jia Xiaoyi , Chen Wencong , Li Haifeng , Wu Ke
Published: October 2022

Background

Pathogenic variants in the FIG4 gene have been described to be associated with a diverse spectrum of syndromes, such as autosomal recessive bilateral temporooccipital polymicrogyria (OMIM 612691), autosomal dominant amyotrophic lateral sclerosis-11 (ALS11; OMIM 612577), autosomal recessive Charcot-Marie-Tooth disease, type 4J (CMT4J; OMIM 611228), and autosomal recessive Yunis-Varon syndrome (YVS; OMIM 216340). Heterozygous FIG4 variants are responsible for ALS11 characterized by progressive muscular weakness, atrophy, and bulbar palsy. CMT4J is a disorder of peripheral nervous system defects mainly presenting with a highly variable onset of proximal and/or distal muscle weakness. YVS is a disorder of severe neurological involvement with central nervous system (CNS) dysfunction and extensive skeletal anomalies.

Case Presentation

We reported two Chinese siblings born with a weakness in all limbs. They experienced rapidly progressive weakness in distal limbs. At the age of 6 years, the elder brother presented with severe scoliosis and cervical kyphosis. They both had global developmental delay and a CNS involvement with cognitive deficits and swallowing problems. Genetic screening in the patients' family for inherited diseases was recommended. Novel compound heterozygous variants in the FIG4 gene (c.2148delTinsAA and c.317A > G) were found by whole-exome sequencing in the patients. These variants were confirmed by Sanger sequencing in family members.

Conclusions

Herein, we reported two Chinese male patients with CMT4J who presented with abnormal CNS features. CMT4J with CNS involvement has been very rarely reported. We hoped this study could expand the phenotypic and genetic spectrum of FIG4-related diseases. And we helped physicians to understand the genotype–phenotype correlation.
Update on prognosis driven classification of pediatric AKI
Authors: Patel Mital , Gbadegesin Rasheed A.
Published: October 2022

Acute kidney injury (AKI) affects a large proportion of hospitalized children and increases morbidity and mortality in this population. Initially thought to be a self-limiting condition with uniformly good prognosis, we now know that AKI can persist and progress to acute kidney disease (AKD) and chronic kidney disease (CKD). AKI is presently categorized by stage of injury defined by increase in creatinine, decrease in eGFR, or decrease in urine output. These commonly used biomarkers of acute kidney injury do not change until the injury is well established and are unable to detect early stage of the disease when intervention is likely to reverse injury. The kidneys have the ability to compensate and return serum creatinine to a normal or baseline level despite nephron loss in the setting of AKI possibly masking persistent dysfunction. Though these definitions are important, classifying children by their propensity for progression to AKD and CKD and defining these risk strata by other factors besides creatinine may allow for better prognosis driven discussion, expectation setting, and care for our patients. In order to develop a classification strategy, we must first be able to recognize children who are at risk for AKD and CKD based on modifiable and non-modifiable factors as well as early biomarkers that identify their risk of persistent injury. Prevention of initial injury, prompt evaluation and treatment if injury occurs, and mitigating further injury during the recovery period may be important factors in decreasing risk of AKD and CKD after AKI. This review will cover presently used definitions of AKI, AKD, and CKD, recent findings in epidemiology and risk factors for AKI to AKD to CKD progression, novel biomarkers for early identification of AKI and AKI that may progress to CKD and future directions for improving outcome in children with AKI.
Abnormalities in microbial composition and function in infants with necrotizing enterocolitis: A single-center observational study
Authors: Huang Huan , Peng Qian , Zhang Yuli , Li Ying , Huang Nanqu , Duan Miao , Huang Bo
Published: October 2022

Objective

To investigate the features and functions of the intestinal microbiota in neonates with necrotizing enterocolitis (NEC) in a single center in China.

Methods

We collected clinical information and stool samples from 19 participants in our center, including 9 infants with necrotizing enterocolitis and 10 control infants. DNA was extracted from the samples, and 16S rRNA gene sequencing was used to analyse the participants' gut microbiota. Functional prediction was achieved using PICRUSt2.

Results

Alpha diversity analysis found that similar levels of bacterial richness and diversity were found in the gut microbiota of infants with NEC and control infants (P = 0.1800), whereas beta diversity analysis suggested that the overall structures of the gut microbiota were significantly different (P = 0.0020). The Mann–Whitney U test of bacterial composition and abundance analysis revealed that the abundance levels of Proteobacteria (P = 0.03049) and Firmicutes (P = 0.01011) significantly differed between the two groups at the phylum level. Proteobacteria was the most abundant phylum in the NEC group. At the genus level, the abundance levels of Enterococcus (P = 0.0003), Streptococcaceae (P = 0.0109) and Lactobacillales (P = 0.0171) were significantly decreased in infants with NEC. Furthermore, the linear discriminant analysis effect size (LEfSe) method showed 12 bacterial taxa with significant differences in relative abundances in the two groups. Interestingly, members of Proteobacteria were enriched in NEC samples. In addition, functional prediction suggested that the microbial changes observed in infants with NEC resulted in a decline in galactose metabolism, the pentose phosphate pathway, fructose and mannose metabolism, amino sugar and nucleotide sugar metabolism, glycolysis/gluconeogenesis, starch and sucrose metabolism, and phosphotransferase system (PTS) pathways (P < 0.05).

Conclusions

Our study shows the compositional and functional alterations of the intestinal microbiota in NEC, which will help demonstrate the relationship between the gut microbiota and NEC pathogenesis.
Safety and efficacy of compound methyl salicylate liniment for topical pain: A multicenter real-world study in China
Authors: Guo Jie , Hu Xiaolei , Wang Jing , Yu Bin , Li Juan , Chen Jianting , Nie Xiaoli , Zheng Zhijian , Wang Shixuan , Qin Qun
Published: October 2022

Compound methyl salicylate liniment (Ammeltz) is composed of various components, such as methyl salicylate, menthol, camphor, chlorpheniramine maleate, and thymol. It was approved for listing in China in 2011. The purpose of this phase Ⅳ clinical trial was to evaluate the safety and efficacy of Ammeltz in a real-life environment in China. Adverse events and adverse drug reactions were used to assess the safety of the monitored drugs. Visual analog scale (VAS) scores were evaluated to assess the severity of pain and the pain relief rate was used to evaluate the efficacy of the study drug. Of 3,600 subjects enrolled, 3,515 (97.64%) subjects completed the study and 85 (2.36%) terminated the study prematurely. A total of 277 adverse events occurred in 258 subjects (7.28%). The most common adverse events included upper respiratory infections (130 cases, 3.67%), local pruritus (17 cases, 0.48%), and diarrhea (12 cases, 0.34%). A total of 50 (1.41%) subjects experienced 58 adverse drug reactions. The most common adverse drug reactions included local pruritus (17 cases, 0.48%), a burning sensation at the application site (10 cases, 0.28%), and irritation at the application site (local) (7 cases, 0.2%). No adverse reactions were identified as new adverse drug reactions. The majority of adverse drug reactions were mild (48 cases, 1.36%), and no severe adverse drug reactions occurred. The subjects experienced significant pain relief after using Ammeltz (mean VAS scores: 5.34 vs. 2.79; Day 7 ± 1 vs. Baseline; p < 0.0001). The pain relief rate was 47.11% ± 23.13%, and in 2,769 cases (78.31%) the drug was effective in pain relief. After excluding subjects who used drugs that could affect the efficacy of the study drug, the subgroups of subjects experienced significant pain relief after using Ammeltz (mean VAS scores: 5.31 vs 2.77; Day 7 ± 1 vs Baseline; p < 0.0001). The pain relief rate was 47.34% ± 23.00%, and 2,612 subjects (78.75%) experienced effective pain relief. In conclusion, Ammeltz is safe and effective in real-life use. It can significantly relieve soft tissue pain caused by shoulder and neck pain, back pain, or muscle pain. No new adverse drug reactions were found in our multicenter real-world study.

Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT05489939?cond=Safety+and+efficacy+of+compound+methyl+salicylate+liniment+for+topical+pain%3A+A+multicenter+real-world+study+in+China&draw=2&rank=1, identifier NCT05489939
Identification of the effect and mechanism of Yiyi Fuzi Baijiang powder against colorectal cancer using network pharmacology and experimental validation
Authors: Xiang Bin , Geng Ruiman , Zhang Zhengkun , Ji Xuxu , Zou Jiaqiong , Chen Lihong , Liu Ji
Published: October 2022

Background: Yiyi Fuzi Baijiang powder (YFBP) is a traditional Chinese medicine used to treat colorectal cancer, although its bioactivity and mechanisms of action have not been studied in depth yet. The study intended to identify the potential targets and signaling pathways affected by YFBP during the treatment of colorectal cancer through pharmacological network analysis and to further analyze its chemical compositions and molecular mechanisms of action.

Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID), HitPredict (HIT), and Search Tool for Interactions of Chemicals (STITCH) databases were used to screen the bioactive components and promising targets of YFBP. Targets related to colorectal cancer were retrieved from the GeneCards and Gene Ontology databases. Cytoscape software was used to construct the “herb–active ingredient–target” network. The STRING database was used to construct and analyze protein–protein interactions (PPIs). Afterward, the R packages clusterProfiler and Cytoscape Hub plug-in were used to perform Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of target genes. The results of the network pharmacological analysis were also experimentally validated.

Results: In total, 33 active components and 128 target genes were screened. Among them, 46 target genes were considered potential therapeutic targets that crossed the CRC target genes. The network pharmacology analysis showed that the active components of YFBP were correlated positively with CRC inflammatory target genes such as TLR4, TNF, and IL-6. The inflammation-related signaling pathways affected by the active components included the TNF-α, interleukin-17, and toll-like receptor signaling pathways. The active ingredients of YFBP, such as luteolin, β-sitosterol, myristic acid, and vanillin, may exert anti-tumor effects by downregulating SMOX expression via anti-inflammatory signaling and regulation of the TLR4/NF-κB signaling pathway.

Conclusion: In the present study, the potential active components, potential targets, and key biological pathways involved in the YFBP treatment of CRC were determined, providing a theoretical foundation for further anti-tumor research.
Peroxisome proliferator-activated receptor gamma and its natural agonists in the treatment of kidney diseases
Authors: Sharma Vinesh , Patial Vikram
Published: October 2022

Kidney disease is one of the leading non-communicable diseases related to tremendous health and economic burden globally. Diabetes, hypertension, obesity and cardiovascular conditions are the major risk factors for kidney disease, followed by infections, toxicity and autoimmune causes. The peroxisome proliferator-activated receptor gamma (PPAR-γ) is a ligand-activated nuclear receptor that plays an essential role in kidney physiology and disease. The synthetic agonists of PPAR-γ shows a therapeutic effect in various kidney conditions; however, the associated side effect restricts their use. Therefore, there is an increasing interest in exploring natural products with PPARγ-activating potential, which can be a promising solution to developing effective and safe treatment of kidney diseases. In this review, we have discussed the role of PPAR-γ in the pathophysiology of kidney disease and the potential of natural PPAR-γ agonists in treating various kidney diseases, including acute kidney injury, diabetic kidney disease, obesity-induced nephropathy, hypertension nephropathy and IgA nephropathy. PPAR-γ is a potential target for the natural PPAR-γ agonists against kidney disease; however, more studies are required in this direction.
Therapeutic potential of topical administration of acriflavine against hypoxia-inducible factors for corneal fibrosis
Authors: Zhu Shuyan , Shan Huimin , Li Jianqiao , Pan Lijie , Wang Shudan , Zhu Jing , Guo Hui , Mi Fenghua , Wu Xinyi , Yin Jia , Pang Kunpeng
Published: October 2022

Transdifferentiation of keratocytes into fibroblasts or further into myofibroblasts, which produced denser and more disorganized extracellular matrix, is the major cause of corneal fibrosis and scarring, leading to corneal blindness. TGF-β1 is the critical cytokine for the myofibroblast’s transdifferentiation and survival. Hypoxia Inducible Factor (HIF) was found to play an important role in promoting fibrosis in lung, kidney, and dermal tissues recently. Our preliminary study demonstrated that topical administration of the acriflavine (ACF), a drug inhibiting HIF dimerization, delayed corneal opacity and neovascularization after the alkali burn. To know whether ACF could prevent corneal fibrosis and improve corneal transparency, we created a mouse mechanical corneal injury model and found that topical administration of ACF significantly inhibited corneal fibrosis at day 14 post-injury. The reduction of myofibroblast marker α-SMA, and fibronectin, one of the disorganized extracellular matrix molecules, in the corneal stroma were confirmed by the examination of immunohistochemistry and real-time PCR. Furthermore, the ACF inhibited the expression of α-SMA and fibronectin in both TGF-β1 stimulated or unstimulated fibroblasts in vitro. This effect was based on the inhibition of HIF signal pathways since the levels of the HIF-1α downstream genes including Slc2a1, Bnip3 and VEGFA were downregulated. To our knowledge, this is the first time to implicate that HIFs might be a new treatment target for controlling corneal fibrosis in mechanical corneal injuries.
Hawkes processes for understanding heterogeneity in information propagation on Twitter
Authors: Wang Liwen , Zhang Lin
Published: October 2022

Social platforms make information propagation anywhere anytime. Large quantity data recording information spreading is available for further understanding the intrinsic mechanism within these stochastic processes. Based on the empirical spreading trees of tweets on Twitter, the heterogeneity of Twitter users is explored, turning out the burstiness in the spreading process. A few super spreaders can significantly change the trends of information spreading. Moreover, an improved Hawkes process is designed in this study to better investigate users’ heterogeneity during information propagation. Verification is provided for accuracy and stability of the improved Hawkes model in simulating propagation patterns revealed in empirical sequential data, predicting spreading trends, and predicting probability of information outbreaks. Our improved Hawkes model is an effective spreading model for detecting and quantifying super spreaders during the propagation process, which may shed light on the control and prediction of information spreading in social media.
Non-carbonic buffer power of whole blood is increased in experimental metabolic acidosis: An in-vitro study
Authors: Krbec Martin , Waldauf Petr , Zadek Francesco , Brusatori Serena , Zanella Alberto , Duška František , Langer Thomas
Published: October 2022

Non-carbonic buffer power (βNC) of blood is a pivotal concept in acid-base physiology as it is employed in several acid-base evaluation techniques, including the Davenport nomogram and the Van Slyke equation used for Base excess estimation in blood. So far, βNC has been assumed to be independent of metabolic acid-base status of blood, despite theoretical rationale for the contrary. In the current study, we used CO2 tonometry to assess βNC in blood samples from 10 healthy volunteers, simultaneously analyzing the electrolyte shifts across the red blood cell membrane as these shifts translate the action of intracellular non-carbonic buffers to plasma. The βNC of the blood was re-evaluated after experimental induction of metabolic acidosis obtained by adding a moderate or high amount of either hydrochloric or lactic acid to the samples. Moreover, the impact of βNC and pCO2 on the Base excess of blood was examined. In the control samples, βNC was 28.0 ± 2.5 mmol/L. In contrast to the traditional assumptions, our data showed that βNC rose by 0.36 mmol/L for each 1 mEq/l reduction in plasma strong ion difference (p < 0.0001) and was independent of the acid used. This could serve as a protective mechanism that increases the resilience of blood to the combination of metabolic and respiratory acidosis. Sodium and chloride were the only electrolytes whose plasma concentration changed relevantly during CO2 titration. Although no significant difference was found between the electrolyte shifts in the two types of acidosis, we observed a slightly higher rate of chloride change in hyperchloremic acidosis, while the variation of sodium was more pronounced in lactic acidosis. Lastly, we found that the rise of βNC in metabolic acidosis did not induce a clinically relevant bias in the calculation of Base excess of blood and confirmed that the Base excess of blood was little affected by a wide range of pCO2.
Rainbow trout integrated response after recovery from short-term acute hypoxia
Authors: García-Meilán Irene , Tort Lluis , Khansari Ali Reza
Published: October 2022

Overcoming a stress situation, such as hypoxia episodes, which involve an allostatic load, will depend on the ability of fish to modulate physiological and biochemical systems to maintain homeostasis. The aim of the study was to determine the integrated stress response after acute hypoxia of the rainbow trout considering the different elements and areas of the stress response: systemic and mucosal, local and global, and from the systemic hypothalamic–pituitary–interrenal axis to skin mucosa. For this purpose, trout were subjected to acute hypoxia (dissolved O2 down to 2 mg/L) for 1 h and then recovered and sampled at 1, 6, and 24 h after reoxygenation. Physiological responses were significantly affected by hypoxic stress and their interaction with time after the challenge, being significant for plasma lactate and cortisol levels, in both plasma and skin mucus. At the central brain level, only trh expression was modulated 1 h after hypoxia which indicates that brain function is not heavily affected by this particular stress. Unlike the brain, the head kidney and skin were more affected by hypoxia and reoxygenation. In the head kidney, an upregulation in the expression of most of the genes studied (gr, il1β, il6, tgfβ1, lysozyme, caspase 3, enolase, hif-1, myoglobin, sod2, gpx, gst, and gsr) took place 6 h after recovery, whereas only hsp70 and il10 were upregulated after 1 h. On the contrary, in the skin, most of the analyzed genes showed a higher upregulation during 1 h after stress suggesting that, in the skin, a local response took place as soon as the stressor was detected, thus indicating the importance of the skin in the building of a stress response, whereas the interrenal tissue participated in a later time point to help prevent further alteration at the central level. The present results also show that, even though the stressor is a physical/environmental stressor, all components of the biological systems participate in the regulation of the response process and the recovery process, including neuroendocrine, metabolism, and immunity.