bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel gas sands characterization and improved depositional modeling of the Cretaceous Sembar Formation, Lower Indus Basin, Pakistan
Authors: Aftab Furqan , Zafar Mohammad , Hajana Muhammad Iqbal , Ahmad Waqar
Published: December 2022

The Lower Indus Basin of Pakistan has substantial hydrocarbon potential with the Cretaceous Sembar Formation as its principal source rock. While studies have identified the shale gas potential of the Sembar Formation, no extensive research has been conducted to evaluate the hydrocarbon potential of thick packages of sands encountered within it. This study is intended to fill this research gap by identifying the hidden-untapped thick packages of sands of the Sembar Formation for the first time in the Khewari and Gambat areas. We use well log and seismic reflection data to define the thickness, depth distribution, and petrophysical properties for reservoir characterization. This integrated modeling identifies favorable zones for gas production and the spatial distribution of sand packages with excellent reservoir properties in thickness (≈200 m), almost continuous sand packages suitable for hydrocarbon exploration. The Suleman-01 well has a very good hydrocarbon reservoir potential with 70% sand volume, approximately 13% effective porosity, 3.57 millidarcys average permeability, and approximately 58–60% hydrocarbon saturation. We suggest that the post-collisional tectonics of the Indian and Eurasian plates affected the depositional geometry of the Sembar Formation in such a way that it trends from shallower to deeper from western to eastern parts of the study area. Similarly, reservoir quality sands follow the positive upward trend from west to east toward the Indian shield. We propose that the approach implemented in this study is applicable to the entire Lower Indus Basin and further toward the Rajasthan Basin in India in the east and Zagros fold-and-thrust belt in Iran in the west. This approach would help assess the undeveloped hydrocarbon potential of the Sembar Formation sands and related formations in South Asia and worldwide.
Final adult height in children with central precocious puberty – a retrospective study
Authors: Knific Taja , Lazarevič Melisa , Žibert Janez , Obolnar Nika , Aleksovska Nataša , Šuput Omladič Jasna , Battelino Tadej , Avbelj Stefanija Magdalena
Published: December 2022

Background/Aims

Central precocious puberty (CPP) is due to premature activation of the hypothalamic-pituitary-gonadal axis. It predominantly affects girls. CPP leads to lower final height (FH), yet the treatment benefit in girls between 6 and 8 years is equivocal. Our main goal was to evaluate the effects of gonadotropin-releasing hormone analog (GnRHa) on FH and identify factors that predict FH.

Methods

In a retrospective study, children with CPP (12 boys, 81 girls) that reached FH were included. Their clinical data at diagnosis and up to their final height was compared by descriptive statistics among idiopathic (iCPP) (n=68) and non-idiopathic CPP (nCPP) and between GnRHa treated (n=48) and untreated (n=15) girls with iCPP. The treatment effect of body weight (BW) adjusted GnRHa dosing was evaluated. Univariate linear regression and step-wise multivariable regression including 48 girls with iCPP treated with GnRHa were performed to identify predicting factors for FH.

Results

Children with idiopathic CPP (iCPP) reached higher FH (p=0.002) than children with non-idiopathic CPP. After the diagnosis, the treated group gained 7.0 cm more than the untreated group. Yet, attributable to individualized decision-making, the FH in both groups was comparable (161.5 cm in treated, 161.0 cm in untreated girls with iCPP), although the onset of menarche was 2.5 years earlier among untreated girls. BW-adjusted dosing suppressed peak luteinizing hormone (LH) below 4.5 IU/L in 95% of children; however, bone age further advanced during therapy in 38% of patients. Predicting factors revealed by multivariable regression were bone age at diagnosis, BMI SDS at diagnosis, LH basal, age at start and cessation of treatment, predicted adult height and target height. (R2 = 0.72).

Conclusion

Children with nCPP had worse FH outcome compared to iCPP despite similar CPP onset and therapeutic characteristics. Treatment by GnRHa using BW-adjusted dosing was effective in delaying menarche onset and reaching target height in girls with iCPP. Multiple factors affecting FH outcome indicated individualized decision-making regarding therapeutic intervention remains challenging. In the treated patients, among the factors that can be influenced, height at treatment cessation most significantly influenced the outcome.
Genetic and phenotypic differences between sexes in congenital hypogonadotropic hypogonadism (CHH): Large cohort analysis from a single tertiary centre
Authors: Federici Silvia , Cangiano Biagio , Goggi Giovanni , Messetti Dario , Munari Elisabetta Veronica , Amer Myriam , Giovanelli Luca , Hrvat Faris , Vezzoli Valeria , Persani Luca , Bonomi Marco
Published: December 2022

Background

Congenital hypogonadotropic hypogonadism (CHH) is a condition with a strong genetic background, caused by a deficient production, secretion, or action of gonadotropin-releasing hormone (GnRH). Published data on CHH cohorts indicate a male predominance, although this is not supported by our current understandings.

Aims

In order to unravel the possible causes or contributors to such epidemiological sex difference, the aim of our study is to investigate differences in genetic background and clinical presentation between males and females in a large cohort of CHH patients.

Materials and methods

We enrolled 338 CHH patients with absent or arrested pubertal development, referred to our Center from 01/2016. Data collection included clinical assessment at diagnosis and genetic analysis performed by next generation sequencing (NGS), employing a custom panel of 28 candidate genes.

Results

Among 338 patients 94 were female (F) and 244 male (M), with a ratio of 1:2.6. We found that 36.09% (122/338) of patients harbored potentially pathogenic rare genetic variants (RVs) with no significant differences between sexes; on the other hand, a significantly higher frequency of oligogenicity was observed in females (F 9,57% 9/94 vs M 3,69% 9/244, P = 0.034). The prevalence of non-reproductive phenotypic features was significantly higher (P = 0.01) in males (53/228, 23.2%) than in females (10/93, 10.8%): in particular, kidney abnormalities affected only male patients and midline defects had a significantly higher prevalence in males (P = 0.010). Finally, BMI SDS was -0.04 ± 1.09 in females and 0.69 ± 1.51 in males, with a statistically significant difference between groups (P = <0.001).

Conclusion

Our data confirm the male predominance in CHH and identify some differences with regard to the clinical presentation between males and females that could indicate a variable expression of genetic rare variants and a dimorphic modulation of phenotype according to metabolic/behavioral factors, which will need to be substantiated and investigated by further studies.
Antioxidant activity of mycelia methanolic extracts of endophytic fungi BvFV and BvFIX isolated from leaves of Bauhinia variegata
Authors: Freitas Pires Daniela Gurgel de , Araújo Laíza Magalhães de , Mesquita Pedro Góes , Neves Francisco de Assis Rocha , Borin Maria de Fátima
Published: December 2022

Endophytes are considered an essential source of natural products. Skin is the body’s largest organ; its primary function is the protection of other organs, and aging is one of the most relevant problems associated with this organ. UV radiation generates reactive oxygen species (ROS), which lead to skin degeneration and consequent aging. The main endogenous antioxidants that neutralize ROS are enzymatic antioxidants such as superoxide dismutase (SOD), catalase, glutathione peroxidase, and glutathione reductase, and non-enzymatic antioxidants, such as glutathione and α-tocopherol. Nuclear receptors are involved in molecular mechanisms that control the aging process, especially peroxisome proliferator-activated receptors (PPAR), which regulate the function and expression of genes that modulate the balance between matrix metalloproteinases (MMP) activity and the expression of collagen. Some natural compounds, such as polyphenols, can activate PPAR and reduce the activation of MMP and collagen degradation. In this work, the antioxidant activity of the mycelia methanolic extracts of two endophytic fungi isolated from leaves of Bauhinia variegata, named BvFV and BvFIX, their action as PPAR agonists, and their effect on the activity of antioxidant defense system enzymes were evaluated. The mycelia methanolic extract of BvFV showed a weak agonist effect on PPARβ/δ, a high capability to inhibit lipid peroxidation, increased catalase activity, and increased superoxide dismutase activity by approximately 64%. In contrast, BvFIX increased catalase activity and increased superoxide dismutase activity in a dose-dependent manner, with an increase of 49.62% ± 7.87%, 56.64% ± 12.27%, and 240.46% ± 26.11% at concentrations of 25 µg/mL, 50 µg/mL and 100 µg/mL, respectively, in human dermal fibroblasts submitted to oxidative stress. These results suggest that the metabolites of the mycelia of endophytic fungi studied are promising to act in the chemoprevention of skin aging.
m7G-related lncRNAs are potential biomarkers for predicting prognosis and immune responses in patients with oral squamous cell carcinoma
Authors: Wang Xuefeng , Dong Wei , Zhang Yanbo , Huo Feng
Published: December 2022

Among head and neck cancers, oral squamous cell carcinoma (OSCC) is the most common malignant tumor. N-7-methylguanosine (m7G) and lncRNAs are both related to the development and progression of tumors. Therefore, this study aims to explore and establish the prognostic signal of OSCC based on m7G-related lncRNAs. In this study, RNA sequencing transcriptome data of OSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Therefore, m7G-related lncRNAs were identified as differentially expressed in OSCC. Then, univariate Cox regression analysis and LASSO regression analysis were conducted to evaluate the prognostic significance of differentially expressed lncRNAs. Consequently, the abovementioned lncRNAs were assigned five OSCC patient risk scores, with high-risk and low-risk patients assigned to each group. Different signaling pathways were significantly enriched between the two groups as determined by set enrichment analysis (GSEA). Multivariate Cox regression analysis confirmed the factors used to construct the nomogram model. Then, the prognosis of the nomogram model was evaluated. Consequently, high-risk individuals had higher immune infiltration levels. According to the results of a study that evaluated the sensitivity of different risk subgroups to antitumour drugs, the high-risk group had a high sensitivity to doxorubicin. By performing real-time polymerase chain reaction (RT‒PCR), we verified the expression of these five m7G lncRNAs. Therefore, the model based on five m7G-related lncRNAs was able to predict the overall survival rates of OSCC patients and guide their treatment. It can also spur new ideas about how to prevent and treat OSCC.
Khat use and associated factors during pregnancy in eastern Ethiopia: A community-based cross-sectional study
Authors: Misgana Tadesse , Tesfaye Dejene , Alemu Daniel , Gebremichael Berhe , Tamiru Dawit , Tariku Mandaras , Weldesenbet Adisu Birhanu , Dheresa Merga
Published: December 2022

Introduction

Women of reproductive age are increasingly using khat. The use of khat is associated with prelabor rupture of membranes, anemia among pregnant women, and other problems related to motherhood and infanthood. Most of the previous studies performed at the facility level revealed that different factors were associated with khat use among pregnant women. Lower educational status, low wealth index, and the age of the mother were the factors significantly associated with maternal khat use. Partner substance use also has a significant association with maternal khat use. However, there is limited information about khat use and its associated factors among pregnant women in the study area.

Objective

This study aims at assessing the prevalence of khat use and associated factors among pregnant women in Kersa and Haramaya Health and Demographic Surveillance System Sites, eastern Ethiopia.

Methods

A community-based cross-sectional study design was employed among randomly selected 1,015 pregnant women from an open cohort from Kersa and Haramaya Health and Demographic Surveillance System Sites in Ethiopia. Data were collected through face-to-face interviews from January 30 to April 30, 2021, using Open Data Kit (ODK) software and analyzed using SPSS v-26. Descriptive statistics were used to summarize the characteristics of pregnant women. Factors associated with khat use were identified by bivariate and multivariable logistic regression analyses; an adjusted odds ratio (AOR) with a 95% confidence interval (CI) was estimated. Statistical significance was declared atp < 0.05.

Results

The prevalence of khat use among pregnant women was 15.5% (95% CI, 13.3–17.7). Age of the pregnant women; being in the age group between 25 and 35 years (AOR = 2.27, 95% CI, 1.33–4.89) and 35 years and greater (AOR = 2.33, 95% CI, 1.29–4.20); having a chronic medical illness (AOR = 3.28, 95% CI, 1.27–8.48); and having a history of abortion (AOR = 2.87 95% CI, 1.73–4.76) significantly increased the likelihood of khat use among pregnant women.

Conclusion

The current study revealed a relatively high magnitude of khat use in pregnant women as compared with previous studies. The age of the pregnant women, history of medical illness, and history of abortion were significantly associated with khat use during pregnancy.
Alternative pre-mRNA splicing as a mechanism for terminating Toll-like Receptor signaling
Authors: Lee Frank Fang Yao , Alper Scott
Published: December 2022

While inflammation induced by Toll-like receptor (TLR) signaling is required to combat infection, persistent inflammation can damage host tissues and contribute to a myriad of acute and chronic inflammatory disorders. Thus, it is essential not only that TLR signaling be activated in the presence of pathogens but that TLR signaling is ultimately terminated. One mechanism that limits persistent TLR signaling is alternative pre-mRNA splicing. In addition to encoding the canonical mRNAs that produce proteins that promote inflammation, many genes in the TLR signaling pathway also encode alternative mRNAs that produce proteins that are dominant negative inhibitors of signaling. Many of these negative regulators are induced by immune challenge, so production of these alternative isoforms represents a negative feedback loop that limits persistent inflammation. While these alternative splicing events have been investigated on a gene by gene basis, there has been limited systemic analysis of this mechanism that terminates TLR signaling. Here we review what is known about the production of negatively acting alternative isoforms in the TLR signaling pathway including how these inhibitors function, how they are produced, and what role they may play in inflammatory disease.
Single-cell profiling of T cells uncovers a tissue-resident memory-like T-cell subset associated with bidirectional prognosis for B-cell acute lymphoblastic leukemia
Authors: Lai Wenpu , Wang Xiaofang , Liu Lian , Xu Ling , Mao Lipeng , Tan Jiaxiong , Zha Xianfeng , Zhan Huien , Lei Wen , Lan Yu , Chen Guobing , Li Yangqiu , Luo Oscar Junhong
Published: December 2022

Introduction

The character and composition of leukemia-related T cells are closely related to the treatment response and prognosis for patients. Though B cell-acute lymphoblastic leukemia (B-ALL) patients have benefited from immune-based approaches, such as chimeric antigen receptor T cells therapy, some of them still end with poor prognosis, especially for adult patients. Therefore, deep understanding of the developmental relationship between T cell subtypes in relation to B-ALL patient prognosis is urgently needed.

Methods

We analyzed the peripheral blood T cell single-cell RNA sequencing data of three B-ALL patients, using data from 11 healthy individuals as controls. In total, 16,143 and 53,701 T cells from B-ALL patients and healthy adults, respectively, were objectively analyzed for detailed delineation of 13 distinct T cell clusters. Cluster-specific genes were used as marker genes to annotate each T cell subtype.

Results

Unbiased analysis enabled the discovery of circulating CD103+ T cell (CD3+CD103+MKI67+), also defined as tissue-resident memory-like T (Trm-like) cell, populations were elevated in B-ALL patients, which expressed high level of cell proliferation and exhaustion related genes. In addition, cell fate trajectory analysis showed these Trm-like cells, which shared T-cell receptor (TCR) clonotypes with exhausted T (Tex) cells and effector T (Teff) cells, were supposed to transition into Teff cells; however, mainly transformed into Tex cells in leukemia environment. More importantly, Trm-like cells transformation into Teff cells and Tex cells potentially led to favorable or poor prognosis for B-ALL patients, respectively.

Conclusion

In sum, a circulating Trm-like cell subset with high level expression of cell proliferation and exhaustion related genes was elevated in B-ALL patients. The bidirectional developmental potential of these T cells into Teff or Tex is closely associated with favorable or poor prognosis, respectively. Together, our study provided a unique insight of alteration of leukemia related T cells, also showed a potential immunotherapy direction and prognosis assessment model for B-ALL patients.
Hypodense regions in the peripapillary region increased the risk of macular retinoschisis detected by optical coherence tomography
Authors: She Xiangjun , Zhou Congying , Liang Zhi , Xie Jin , Zhao Shixin , Tao Jiwei , Zhang Yun , Mao Jianbo , Chen Yiqi , Shen Lijun
Published: December 2022

Purpose

The purpose of the present study was to investigate the clinical features of peripapillary regions in patients with myopic macular retinoschisis (MRS) and its association with the development of retinoschisis (RS).

Methods

In this cross-sectional study, high-myopic patients with or without MRS were recruited, and the hypodense regions were analyzed in the peripapillary regions. The vitreoretinal adhesions around both macular and paravascular arcades were compared between groups. The risk factors for the development of MRS were analyzed by logistic regression.

Results

Of 88 myopic eyes, MRS was detected in 45 eyes (51%). The eyes with MRS showed a higher rate of peripapillary and paravascular retinoschisis (P < 0.001 and P = 0.006). Hypodense regions were detected in 25 eyes (20.35%). Higher rates of horizontal and vertical macular MRS were detected in the hypodense group (P = 0.012 and P = 0.002). Lower refractive error, longer axial length, and higher rates of outer retinoschisis both in horizontal and vertical macular regions were observed in the hypodense group (P = 0.012, P = 0.006, P = 0.038, and P = 0.034). Higher rates of inner and outer retinoschisis, vitreoschisis, and microfolds along superior vascular arcade were detected in the hypodense group (P = 0.005, P = 0.001, P = 0.014, and P = 0.014). Higher rates of internal limiting membrane (ILM) detachment, inner and outer RS were detected along the inferior vascular arcade in the hypodense group (P = 0.008, P = 0.001, and P = 0.028). Hypodense regions, the axial length and PICC (peripapillary intrachoroidal cavitation) were significantly correlated with the severity of MRS (Odds ratio = 0.207, P = 0.010; Odds ratio = 1.399, P = 0.016; Odds ratio = 0.142, P = 0.010).

Conclusions

The hypodense regions were likely to affect outer retinoschisis both in macular and paravascular regions. It was a risk factor for the development of MRS.
Back to basics with newer technology: Should we focus on reducing work of breathing earlier?
Authors: Sciarretta Christopher , Greenberg Jeremy , Wyatt Kara D. , Whittle Jessica S.
Published: December 2022

The typical approach to management of respiratory distress is focused on oxygen supplementation. However, additional oxygen alone does not improve outcomes, particularly in critically ill patients. Instead, supplemental oxygen can be associated with increased morbidities. We present the hypothesis that clinicians should focus on reducing the work of breathing early in the course of critical illness. Rather than simply supplementing oxygen, newer technologies including high flow nasal oxygen, may be utilized to increase the efficiency of gas exchange. By reducing the work of breathing, the cardiac workload can be reduced, thus relieving some excess physiologic stress and supporting the critically ill patient. To illustrate this point, we provided three clinical cases of respiratory failure from non-pulmonary origins; all cases displayed hemodynamic improvement due to reducing the work of breathing through high-velocity therapy prior to receiving definitive therapy for underlying pathologies.
Efficacy of prophylactic human papillomavirus vaccines on cervical cancer among the Asian population: A meta-analysis
Authors: Ren Xinyu , Hao Yubing , Wu Beike , Jia Xinhua , Niu Meili , Wang Kunbo , Li Zhifang
Published: December 2022

Objective

We conducted a meta-analysis to assess the efficacy of prophylactic human papillomavirus (HPV) vaccines against cervical cancer precursors and HPV persistent infection among Asian populations.

Methods

Randomized controlled clinical trials conducted in Asian countries were identified from three electronic databases (PubMed, EMBASE and the Cochrane Library). Publication retrieval was performed on September 1, 2022 and only those written in English were included. The data were analyzed with Cochrane Review Manager (version 5.3) and Stata/SE (15.1). Effect sizes were presented as risk ratios (RRs) and 95% confidence intervals (CIs).

Results

Ten articles were considered in the meta-analysis, without significant heterogeneity among them. The fixed-effect RRs and 95% CIs for cervical intraepithelial neoplasia grade 1 (CIN1+) and CIN2+ were 0.10 (0.05–0.21) and 0.11 (0.04–0.27), respectively. Positive effect of HPV vaccination on 6- and 12-month persistent infection were observed, with the respective pooled RRs of 0.05 (95% CI: 0.03–0.09) and 0.09 (95% CI: 0.05–0.15). HPV vaccination has a positive effect on the incidence of cytological abnormalities associated with HPV 16/18 (RR, 0.13; 95% CI (0.09–0.20)). Positive effects of HPV vaccination were also observed for HPV 16- and 18-specific immunogenicity (RR, 235.02; 95% CI (82.77–667.31) and RR, 98.24; 95% CI (50.36–191.67), respectively). Females receiving an initial vaccination showed significant decreased incidences of cervical intraepithelial neoplasia, HPV persistent infection and cytological abnormalities and a significantly higher antibody positive conversion rate compared with non-vaccination counterparts.

Conclusion

Prophylactic HPV vaccines are highly efficacious in preventing cervical cancer in Asian females. The government should accelerate the processes of vaccine introduction and vaccination implementation by prioritizing them in public health policies, which should be helpful to enhance Asian females’ awareness of receiving HPV vaccination volitionally.
The association between albumin levels and survival in patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis
Authors: Guven Deniz Can , Sahin Taha Koray , Erul Enes , Rizzo Alessandro , Ricci Angela Dalia , Aksoy Sercan , Yalcin Suayib
Published: December 2022

Background: The albumin levels may potentially be used as a prognostic biomarker in patients with cancertreated with immune checkpoint inhibitors (ICIs) due to its close relationship with nutritional and inflammatory status. However, the available data is limited with heterogeneous patient cohorts, sample sizes and variable cut-offs. Therefore, we conducted a systematic review and meta-analysis to evaluate the association between survival outcomes and albumin levels in patients treated with ICIs.

Methods: We conducted a systematic review using the PubMed, Web of Science, and Embase databases to filter the published studies up to 1 June 2022. The meta-analyses were performed with the generic inverse-variance method with a random-effects model due to the high degree of heterogeneity. The primary outcome measure was hazard ratio (HR) with 95% confidence intervals (CI). The study protocol was registered with the PROSPERO registry (Registration Number: CRD42022337746).

Results: Thirty-six studies encompassing 8406 cancer patients with advanced disease were included in the meta-analyses. Almost half of the studies were conducted in NSCLC cohorts (n = 15), and 3.5 gr/dL was the most frequently used albumin cut-off in the included studies (n = 20). Patients with lower albumin levels had a significantly increased risk of death (HR: 1.65, 95% CI: 1.52–1.80, p < 0.0001) than patients with higher albumin levels. Subgroup analyses for study location, sample size, tumor type and albumin cut-off were demonstrated consistent results. Furthermore, in the subgroup analysis of eight studies using albumin levels as a continuous prognostic factor, every 1 gr/dL decrease in albumin levels was associated with significantly increased risk of death by a factor of 10% (HR: 1.10, 95% CI: 1.05–1.16, p = 0.0002). Similar to analyses with overall survival, the patients with lower albumin levels had an increased risk of progression or death compared to patients with higher albumin levels (HR: 1.76, 95% CI: 1.40–2.21, p < 0.001).

Conclusion: The available evidence demonstrates that albumin levels may be a prognostic biomarker in advanced cancer patients treated with ICIs. Further research is needed to delineate the role of albumin levels in patients treated with ICIs in the adjuvant setting, as well as the possible benefit of therapeutic approaches to improve hypoalbuminemia.
Genetic loci, rs17817449 and rs6567160, known for obesity and the risk of stroke events among middle-aged and older Chinese people
Authors: Zhong Qiong-Qiong , Zhu Feng
Published: December 2022

Background

Fat Mass and Obesity-Associated (FTO) and the Melanocortin-4 Receptor (MC4R) genes are strongly associated with obesity, an established risk factor for stroke. We aimed to assess the associations between rs17817449 at the FTO and rs6567160 at the MC4R and the risk of stroke events in middle-aged and older Chinese people.

Materials and methods

Study data were obtained from the Guangzhou Biobank Cohort Study; a total of 148 participants with a self-reported history of stroke and an equal volume of age- and sex-matched participants were selected as the cases and the controls in a case-control study; a total of 13,967 participants at the first follow-up and all participants with fatal stroke (up to April 2021) were included in a retrospective cohort study. Conditional logistic regression and the Cox proportional hazards regression analyses were used to assess the associations of the two genetic loci with the risk of stroke events.

Results

After adjusting for age, sex, education, job, smoking, alcohol consumption, body mass index, physical activity, hypertension, diabetes, and dyslipidemia, rs17817449 and rs6567160 shared minor alleles G and C, respectively, in the case-control analyses. The genotypes GG+GT of rs17817449 at the FTO were significantly associated with a decreased risk of fatal stroke occurrence, with fatal all strokes having an adjusted hazard ratio (aHR) of 0.71 (95% confidence intervals (CI) 0.52-0.97, P = 0.04) and fatal ischemic stroke having an aHR of 0.64 (95% CI 0.41–1.00, P = 0.05), when the genotype TT was taken as a reference and a series of multiplicities were adjusted; the risk of fatal all strokes was lowered by dyslipidemia (aHR = 0.63, 95% CI 0.39–1.00, P = 0.05) and non–diabetes (aHR = 0.68, 95% CI 0.46–0.99, P = 0.049) in the retrospective cohort analyses. Significances were observed neither in the associations between rs6567160 and the risk of stroke events nor in an interaction between rs17817449 and rs6567160 in the two-stage analyses.

Conclusion

The G allele of rs17817449 at the FTO, not rs6567160 at the MC4R, was associated with a decreased risk of fatal stroke occurrence; its functional role in stroke should be explored in relatively healthy middle-aged to older Chinese people.
Long-term efficacy of dexamethasone treatment via tympanic antrum catheterization for intractable Meniere's disease
Authors: Lyu Yafeng , Guo Jia , Li Xiaofei , Jian Huirong , Li Yawei , Wang Jing , Fan Zhaomin , Wang Haibo , Zhang Daogong
Published: December 2022

Objective

To explore the long-term efficacy and safety of dexamethasone treatment via tympanic antrum catheterization (TAC) in intractable Meniere's disease (MD).

Methods

In this retrospective analysis, 60 unilateral intractable MD patients treated with TAC in our hospital from January 2020 to August 2020 were followed for 2 years. Fifty patients who underwent endolymphatic sac decompression (ESD) and 50 patients who accepted intratympanic steroids (ITS) were established as the control groups. Vertigo control, hearing level, tinnitus, aural fullness and functional level were assessed during the study.

Results

The effective vertigo control rate of intractable MD patients with TAC treatment was 76.7% (46/60) after 2 years follow-up, with a complete control rate of 58.3% (35/60) and a substantial control rate of 18.3% (11/60). The vertigo control rate of TAC was comparable to that of ESD (χ2 = 0.313, p > 0.05), and significantly higher than that of ITS (χ2 = 4.380, p < 0.05). The hearing loss rate of these patients was 10.8% (4/37), which was not significantly different from the control groups (χ2 = 2.452, p > 0.05). The tinnitus improvement rate of patients with TAC was 56.7% (34/60), which was significantly higher than that of patients with ESD (χ2 =11.962, p < 0.001) and ITS (χ2 =15.278, p < 0.001). The aural fullness improvement rate in the TAC group was 56.7% (34/60), which was significantly higher than that in the ESD (χ2 = 11.962, p < 0.001) and ITS groups (χ2 = 5.635, p < 0.05). The functional level improvement rate in the TAC group was 71.7% (43/60), which was much higher than that in the ITS group (χ2 = 17.256, p < 0.001), but there was no significant difference between TAC and ESD (χ2 = 0.410, p > 0.05). No patients had complications or adverse reactions following TAC treatment.

Conclusion

Dexamethasone treatment via TAC can effectively control vertigo attacks and improve related symptoms of intractable MD patients, providing valuable new insights into the treatment of MD.
Circ-Vps41 positively modulates Syp and its overexpression improves memory ability in aging mice
Authors: Li Yibo , Wang Hongfang , Gao Yanjing , Zhang Runjiao , Liu Qing , Xie Wenmeng , Liu Ziyu , Geng Dandan , Wang Lei
Published: December 2022

Introduction

Age is an established risk factor for neurodegenerative disorders. Aging-related cognitive decline is a common cause of memory impairment in aging individuals, in which hippocampal synaptic plasticity and hippocampus-dependent memory formation are damaged. Circular RNAs (circRNAs) have been reported in many cognitive disorders, but their role in aging-related memory impairment is unclear.

Methods: In this study, we aimed to investigate the effects of circ-Vps41 on aging-related hippocampus-dependent memory impairment and explore the potential mechanisms. Here, D-galactose was used to produce a conventional aging model resulting in memory dysfunction.

Results

Circ-Vps41 was significantly downregulated in D-galactose-induced aging in vitro and in vivo. The overexpression of circ-Vps41 could upregulate synaptophysin (Syp), thereby promoting the synaptic plasticity and alleviating cognitive impairment in aging mice. Mechanistically, we found that circ-Vps41 upregulated Syp expression by physically binding to miR-24-3p. Moreover, the miR-24-3p mimics reversed the circ-Vps41 overexpression-induced increase in Syp expression.

Discussion

Overexpression of circ-Vps41 alleviated the synaptic plasticity and memory dysfunction via the miR-24-3p/Syp axis. These findings revealed circ-Vps41 regulatory network and provided new insights into its potential mechanisms for improving aging-related learning and memory impairment.
The biological alterations of synapse/synapse formation in sepsis-associated encephalopathy
Authors: Tang Chuan , Jin Ye , Wang Huan
Published: December 2022

Sepsis-associated encephalopathy (SAE) is a common complication caused by sepsis, and is responsible for increased mortality and poor outcomes in septic patients. Neurological dysfunction is one of the main manifestations of SAE patients. Patients may still have long-term cognitive impairment after hospital discharge, and the underlying mechanism is still unclear. Here, we first outline the pathophysiological changes of SAE, including neuroinflammation, glial activation, and blood-brain barrier (BBB) breakdown. Synapse dysfunction is one of the main contributors leading to neurological impairment. Therefore, we summarized SAE-induced synaptic dysfunction, such as synaptic plasticity inhibition, neurotransmitter imbalance, and synapses loss. Finally, we discuss the alterations in the synapse, synapse formation, and mediators associated with synapse formation during SAE. In this review, we focus on the changes in synapse/synapse formation caused by SAE, which can further understand the synaptic dysfunction associated with neurological impairment in SAE and provide important insights for exploring appropriate therapeutic targets of SAE.
Case report: Peritumoral hepatic steatosis in a patient with a metastatic somatostatin-producing oligosymptomatic neuroendocrine neoplasm
Authors: Shao Yuming , Gui Yang , Cheng Yuejuan , Xu Jia , Chang Xiaoyan , Lv Ke
Published: December 2022

Neuroendocrine neoplasms (NENs) comprise a heterogeneous collection of tumors derived from various neuroendocrine cells and are divided into functioning NEN and non-functioning NEN. Some NENs present with mild symptoms and can secrete somatostatin. These neoplasms are known as somatostatin-producing oligosymptomatic NENs. In this report, we describe a case of metastatic somatostatin-producing oligosymptomatic NEN with peritumoral hepatic steatosis and review the relevant literature. The patient was a 45-year-old woman who presented with mild steatorrhea and melena. A computed tomography scan revealed an enlarged pancreas protruding into the duodenum. Pathology after total pancreatectomy showed a grade 2 pancreatic NEN with positive somatostatin immunostaining. Enlarging masses on the liver were observed after the operation. Ultrasound examination revealed several lesions in the liver, with inner hypoechoic areas that showed rapid enhancement and fast washout on contrast-enhanced ultrasonography and with outer hyperechoic areas with continuous iso-enhancement. Therefore, the inner hypoechoic areas seen on contrast-enhanced ultrasonography were suspected to be true metastases. A biopsy confirmed this suspicion and indicated that the outer areas were peritumoral liver steatosis. This case highlights the importance of the imaging pattern described in this report for accurate diagnosis of metastatic NEN to avoid incorrect estimation of tumor size or a missed diagnosis on biopsy.
Enhanced cardiac substructure sparing through knowledge-based treatment planning for non-small cell lung cancer radiotherapy
Authors: Momin Shadab , Wolf Jonathan , Roper Justin , Lei Yang , Liu Tian , Bradley Jeffrey D. , Higgins Kristin , Yang Xiaofeng , Zhang Jiahan
Published: December 2022

Radiotherapy (RT) doses to cardiac substructures from the definitive treatment of locally advanced non-small cell lung cancers (NSCLC) have been linked to post-RT cardiac toxicities. With modern treatment delivery techniques, it is possible to focus radiation doses to the planning target volume while reducing cardiac substructure doses. However, it is often challenging to design such treatment plans due to complex tradeoffs involving numerous cardiac substructures. Here, we built a cardiac-substructure-based knowledge-based planning (CS-KBP) model and retrospectively evaluated its performance against a cardiac-based KBP (C-KBP) model and manually optimized patient treatment plans. CS-KBP/C-KBP models were built with 27 previously-treated plans that preferentially spare the heart. While the C-KBP training plans were created with whole heart structures, the CS-KBP model training plans each have 15 cardiac substructures (coronary arteries, valves, great vessels, and chambers of the heart). CS-KBP training plans reflect cardiac-substructure sparing preferences. We evaluated both models on 28 additional patients. Three sets of treatment plans were compared: (1) manually optimized, (2) C-KBP model-generated, and (3) CS-KBP model-generated. Plans were normalized to receive the prescribed dose to at least 95% of the PTV. A two-tailed paired-sample t-test was performed for clinically relevant dose-volume metrics to evaluate the performance of the CS-KBP model against the C-KBP model and clinical plans, respectively. Overall results show significantly improved cardiac substructure sparing by CS-KBP in comparison to C-KBP and the clinical plans. For instance, the average left anterior descending artery volume receiving 15 Gy (V15 Gy) was significantly lower (p < 0.01) for CS-KBP (0.69 ± 1.57 cc) compared to the clinical plans (1.23 ± 1.76 cc) and C-KBP plans (1.05 ± 1.68 cc). In conclusion, the CS-KBP model significantly improved cardiac-substructure sparing without exceeding the tolerances of other OARs or compromising PTV coverage.
Approach to the child with fatigue: A focus for the general pediatrician
Authors: De Nardi Laura , Lanzetta Maria Andrea , Ghirigato Elena , Barbi Egidio , Gortani Giulia
Published: December 2022

Background

Fatigue is a common, nonspecific complaint commonly used to describe various conditions, ranging from a vague, subjective sense of weariness to muscular weakness, fatigability, exercise intolerance or excessive daytime somnolence. Despite its high frequency in the general population, literature addressing the approach to the child with fatigue from a general pediatrician perspective is poor. We herein propose a review of the available evidence on the topic, providing a practical framework to assist physicians in dealing with the issue.

Methods

Data were identified by searches of MEDLINE, UpToDate, Google Scholar and references from relevant articles. Articles published between 1990 and 2021 were considered, prioritizing systematic reviews and meta-analyses. Then, an empirically-based model of approaching the tired child was proposed according to our center experience.

Results

To correctly characterize the meaning of fatigue reporting, specific clues from history and physical examination should be emphasized. Duration, severity, and the age at onset are to be considered. Then, specific queries about everyday activities, sleep hygiene and social domain could be useful in reaching a specific diagnosis and offering an appropriate treatment.

Conclusions

We suggest a pragmatic approach to fatigue in children based on age assessment, targeted questions, physical examination clues, and some laboratory first-level tests. This could provide pediatricians with a useful tool to discriminate the broad etiology of such a complaint, disentangling between psychological and organic causes. Further studies are needed to investigate the predictive value, specificity and sensitivity of this diagnostic workflow in managing the child with fatigue.
Perinatal/maternal-fetal-infant dermatologic manifestations of SARS-CoV-2. An Overview and Implications for diagnosis, treatment, and prognosis
Authors: Young Elaine M.
Published: December 2022

Early identification of the dermatologic manifestations of SARS-CoV-2 in perinatal and maternal-fetal-infant populations is essential for early intervention in the diagnosis, treatment, and prevention of short and long term sequelae. Although cutaneous signs of SARS-CoV-2 are less common in pregnant women, neonates, and infants, the recognition of related skin lesions with regard to timing, location, duration, and pattern can lead to determining disease severity. While many pediatric patients may be asymptomatic with negative SARS-CoV-2 testing, skin lesions may be the only clue of infection. SARS-CoV-2 infection in pregnancy can lead to severe life threatening illness and by understanding the cutaneous manifestations associated with SARS-CoV-2 infection, early diagnosis can be made with improved maternal-fetal outcomes. A wide array of dermatologic presentations associated with SARS-CoV-2 are reported in the literature. This review explores the expanding reports in the literature of the dermatologic presentations of skin lesions related to SARS-CoV-2 specifically in perinatal and maternal-fetal-infant health and the implications for management. The collaboration of the specialties of dermatology, pediatrics, obstetrics/gynecology, and infectious disease in the approach to SARS-CoV-2 disease can lead to a better understanding of the scope and presentation of this disease.
No ambiguity: Chemosensory-based ayurvedic classification of medicinal plants can be fingerprinted using E-tongue coupled with multivariate statistical analysis
Authors: Jayasundar Rama , Ghatak Somenath , Kumar Dushyant , Singh Aruna , Bhosle Preeti
Published: December 2022

Background: Ayurveda, the indigenous medical system of India, has chemosensory property (rasa) as one of its major pharmacological metric. Medicinal plants have been classified in Ayurveda under six rasas/tastes—sweet, sour, saline, pungent, bitter and astringent. This study has explored for the first time, the use of Electronic tongue for studies of rasa-based classification of medicinal plants.

Methods: Seventy-eight medicinal plants, belonging to five taste categories (sweet, sour, pungent, bitter, astringent) were studied along with the reference taste standards (citric acid, hydrochloric acid, caffeine, quinine, L-alanine, glycine, β-glucose, sucrose, D-galactose, cellobiose, arabinose, maltose, mannose, lactose, xylose). The studies were carried out with the potentiometry-based Electronic tongue and the data was analysed using Principle Component Analysis, Discriminant Function Analysis, Taste Discrimination Analysis and Soft Independent Modeling of Class Analogy.

Results: Chemosensory similarities were observed between taste standards and the plant samples–citric acid with sour group plants, sweet category plants with sucrose, glycine, β-glucose and D-galactose. The multivariate analyses could discriminate the sweet and sour, sweet and bitter, sweet and pungent, sour and pungent plant groups. Chemosensory category of plant (classified as unknown) could also be identified.

Conclusion: This preliminary study has indicated the possibility of fingerprinting the chemosensory-based ayurvedic classification of medicinal plants using E-tongue coupled with multivariate statistical analysis.
The essential role of YAP in ERα36-mediated proliferation and the epithelial-mesenchymal transition in MCF-7 breast cancer cells
Authors: Park Miso , Lee Seung Hyun , Bui Quyen Thu , Kim Young-Mi , Kang Keon Wook
Published: December 2022

Purpose: Most breast cancers are hormone-receptor-positive, and thus the first-line therapy for them is an anti-estrogen medication such as tamoxifen. If metastasis occurs or resistance to tamoxifen develops, the 5-year survival rates for breast cancer patients significantly decrease. Hence, a better understanding of the molecular mechanisms that contribute to breast cancer aggressiveness is of great importance. ERα36 is an estrogen receptor variant that is known to be upregulated in breast cancer patients receiving tamoxifen treatment or in triple-negative breast cancer cells. However, the specific molecular mechanism underlying ERα36-induced tamoxifen-resistance is not yet fully understood.

Methods: ERα36-overexpressing MCF-7 cells were constructed by either plasmid transfection using ERα36 vector or retroviral infection using ERα36-V5-His vector. Target-gene expression was assessed by Western blot analysis and real-time PCR, and YAP activation was evaluated by luciferase assays and immunofluorescence. Cell proliferation and formation of three-dimensional spheroids were evaluated using the IncuCyte S3 Live Cell Analysis System.

Results: We found that the expression patterns of Hippo signaling-related genes were significantly changed in ERα36-overexpressing MCF-7 cells compared to MCF-7 cells, which were also similarly observed in tamoxifen-resistant MCF-7 cells. Specifically, the protein expression level and activity of YAP, the core downstream protein of the Hippo pathway, were significantly increased in ERα36-overexpressing MCF-7 cells compared with MCF-7 cells. The aggressive phenotypes acquired by ERα36 overexpression in MCF-7 cells were destroyed by YAP knockout. On this basis, we propose that ERα36 regulates YAP activity by a new mechanism involving Src kinase.

Conclusion: Our results suggest that YAP targeting may be a new therapeutic approach to the treatment of advanced breast cancers overexpressing ERα36.
Beneficial shift of rhizosphere soil nutrients and metabolites under a sugarcane/peanut intercropping system
Authors: Tang Xiumei , He Yonglin , Zhang Zheng , Wu Haining , He Liangqiong , Jiang Jing , Meng Weiwei , Huang Zhipeng , Xiong Faqian , Liu Jing , Zhong Ruichun , Han Zhuqiang , Wan Shubo , Tang Ronghua
Published: December 2022

Intercropping systems have been studied as a sustainable agricultural planting pattern to increase soil quality and crop yields. However, the relationships between metabolites and soil physicochemical properties remain poorly understood under sugarcane/peanut intercropping system. Thus, we determined the rhizosphere soil physicochemical properties, and analyzed rhizosphere soil metabolites and root metabolites by metabolomics method under monoculture and intercropping patterns of sugarcane and peanut. The results showed that pH, the contents of total phosphorus (P), total potassium (K), available nitrogen (N), available phosphorus (P), and available potassium (K) were higher in rhizosphere soil of intercropping peanut than monoculture peanut, and the content of total P was higher in rhizosphere soil of intercropping sugarcane than monoculture sugarcane. Sugarcane/peanut intercropping also significantly increased the activities of acid phosphatase and urease in rhizosphere soil. The metabolomics results showed that 32 metabolites, mainly organic acids and their derivatives (25.00%), nucleotides and their metabolites (18.75%), were detected in root and rhizosphere soil samples. In the MP-S (rhizosphere soil of monoculture peanut) vs. IP-S (rhizosphere soil of intercropping peanut) comparison, 47 differential metabolites (42 upregulated) were screened, including glycerolipids (19.15%), organic acids and their derivatives (17.89%), and amino acids and their metabolites (12.77%). In the MS-S (rhizosphere soil of monoculture sugarcane) vs. IS-S (rhizosphere soil of intercropping sugarcane) comparison, 51 differential metabolites (26 upregulated) were screened, including heterocyclic compounds (15.69%), glycerolipids (11.76%), and organic acids and their derivatives (9.80%). The metabolite species from MP-S, MS-S, IP-S, and IS-S were similar, but some metabolite contents were significantly different, such as adenine, adenosine, maltotriose, thermozeaxanthin-13 and PE-NMe (20:0/24:0). Adenine and adenosine were detected in root and rhizosphere soils, and their levels were increased in the intercropping treatment, which were mainly related to enhanced purine metabolism in root and rhizosphere soils under the sugarcane/peanut intercropping system. Importantly, adenine and adenosine were significantly positively correlated with total P and total K contents, acid phosphatase and urease activities, and pH. This study clarified that the sugarcane/peanut intercropping system could improve soil nutrients and enzymes and was related to purine metabolism.