bluuebunny/crossref_metadata_2025 huggingface dataset:
Autophagy and Aging: Roles in Skeletal Muscle, Eye, Brain and Hepatic Tissue
Authors: Li Ping , Ma Yuanzheng , Yu Chengwei , Wu Shoutong , Wang Kai , Yi Hongyang , Liang Weizheng
Published: October 2021

Autophagy is an evolutionary conserved degradative process contributing to cytoplasm quality control, metabolic recycling and cell defense. Aging is a universal phenomenon characterized by the progressive accumulation of impaired molecular and reduced turnover of cellular components. Recent evidence suggests a unique role for autophagy in aging and age-related disease. Indeed, autophagic activity declines with age and enhanced autophagy may prevent the progression of many age-related diseases and prolong life span. All tissues experience changes during aging, while the role of autophagy in different tissues varies. This review summarizes the links between autophagy and aging in the whole organism and discusses the physiological and pathological roles of autophagy in the aging process in tissues such as skeletal muscle, eye, brain, and liver.
Targeted Bisulfite Sequencing Reveals DNA Methylation Changes in Zinc Finger Family Genes Associated With KRAS Mutated Colorectal Cancer
Authors: Pu Weilin , Qian Fei , Liu Jing , Shao Keke , Xiao Feng , Jin Qin , Liu Qingmei , Jiang Shuai , Zhang Rui , Zhang Jun , Guo Shicheng , Zhang Jianfeng , Ma Yanyun , Ju Shaoqing , Ding Weifeng
Published: October 2021

Background: Colorectal cancer (CRC) is a leading cause of cancer death, and early diagnosis of CRC could significantly reduce its mortality rate. Previous studies suggest that the DNA methylation status of zinc finger genes (ZFGs) could be of potential in CRC early diagnosis. However, the comprehensive evaluation of ZFGs in CRC is still lacking.

Methods: We first collected 1,426 public samples on genome-wide DNA methylation, including 1,104 cases of CRC tumors, 54 adenomas, and 268 para-tumors. Next, the most differentially methylated ZFGs were identified and validated in two replication cohorts comprising 218 CRC patients. Finally, we compared the prediction capabilities between the ZFGs and the SEPT9 in all CRC patients and the KRAS + and KRAS- subgroup.

Results: Five candidate ZFGs were selected: ESR1, ZNF132, ZNF229, ZNF542, and ZNF677. In particular, ESR1 [area under the curve (AUC) = 0.91] and ZNF132 (AUC = 0.93) showed equivalent or better diagnostic capability for CRC than SEPT9 (AUC = 0.91) in the validation dataset, suggesting that these two ZFGs might be of potential for CRC diagnosis in the future. Furthermore, we performed subgroup analysis and found a significantly higher diagnostic capability in KRAS + (AUC ranged from 0.97 to 1) than that in KRAS- patients (AUC ranged from 0.74 to 0.86) for all these five ZFGs, suggesting that these ZFGs could be ideal diagnostic markers for KRAS mutated CRC patients.

Conclusion: The methylation profiles of the candidate ZFGs could be potential biomarkers for the early diagnosis of CRC, especially for patients carrying KRAS mutations.
High Serum Carbohydrate Antigen (CA) 125 Level Is Associated With Poor Prognosis in Patients With Light-Chain Cardiac Amyloidosis
Authors: Li Muzheng , Wu Zhijian , Tudahun Ilyas , Liu Na , Lin Qiuzhen , Liu Jiang , Wang Yingmin , Chen Mingxian , Chen Yaqin , Qi Nenghua , Zhu Qingyi , Li JunLi , Li Wei , Tang Jianjun , Liu Qiming
Published: October 2021

Background and Aims: Patients with light-chain cardiac amyloidosis (AL-CA) are characterized by high levels of serum carbohydrate antigen 125 (CA 125). However, studies have not explored the correlation between CA 125 and AL-CA. The aim of this study was to explore the clinical implications of an increase in CA 125 in patients with AL-CA.

Methods and Results: A total of 95 patients diagnosed with AL-CA at the Second Xiangya Hospital were enrolled in this study. Out of the 95 patients with AL-CA, 57 (60%) patients had elevated serum CA 125 levels. The mean age was 59.7 ± 10.0 years with 44 (77.2%) men in the high serum CA 125 group, and 61.8 ± 9.6 years with 28 (73.7%) men in the normal group. Patients with high CA 125 showed higher rates of polyserositis (79.3% vs. 60.5%, p = 0.03), higher levels of hemoglobin (117.4 ± 21.9 g/L vs. 106.08 ± 25.1 g/L, p = 0.03), serum potassium (4.11 ± 0.47 mmol/L vs. 3.97 ± 0.40 mmol/L, p = 0.049), low-density lipoprotein-cholesterol (3.0 ± 1.6 mmol/L vs. 2.3 ± 1.10 mmol/L, p = 0.01), and cardiac troponin T (96.0 pg/mL vs. 91.9 pg/mL, p = 0.005). The median overall survival times for patients with high or normal serum CA 125 were 5 and 25 months, respectively (p = 0.045). Multivariate Cox hazard analysis showed that treatment without chemotherapy (HR 1.694, 95% CI 1.121–2.562, p = 0.012) and CA 125 (HR 1.002, 95% CI 1.000–1.004, p = 0.020) was correlated with high all-cause mortality. The time-dependent receiver operating characteristic (t-ROC) curve showed that the prediction accuracy of CA 125 was not inferior to that of cardiac troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and lactate dehydrogenase (LDH) based on the area under the curve.

Conclusions: CA 125 is a novel prognostic predictor. High serum CA 125 values are correlated with low overall survival, and the accuracy of predicting prognosis is similar to that of traditional biomarkers in AL-CA.
The Evolution of Peteroa Volcano (Chile–Argentina) Crater Lakes Between 1984 and 2020 Based on Landsat and Planet Labs Imagery Analysis
Authors: Aguilera Felipe , Caro Javiera , Layana Susana
Published: October 2021

One of the major challenges in the understanding of the crater lakes dynamics and their connection with magmatic/hydrothermal processes is the continuous tracking of the physical behavior of lakes, especially in cases of remote and poorly accessible volcanoes. Peteroa volcano (Chile–Argentina border) is part of the Planchón–Peteroa–Azufre Volcanic Complex, one of the three volcanoes in the Southern Volcanic Zone of the Andes with crater lakes. Peteroa volcano is formed by a ∼5 km diameter caldera-type crater, which hosts four crater lakes and several fumarolic fields. Peteroa volcano has a large history of eruptive activity including phreatic-and-phreatomagmatic explosions and several episodes of strong degassing from its crater lakes. Here, we used TIR and SWIR bands from Landsat TM, ETM+, and OLI images available from October 1984 to December 2020 to obtain thermal parameters such as thermal radiance, brightness temperature, and heat fluxes, and Planet Labs Inc. images (RapidEye and PlanetScope) available between May 2009 and December 2020 to obtain physical parameters such as area, color, and state (liquid or frozen) of the crater lakes. We reviewed the historical eruptive activity and compared it with thermal and physical data obtained from satellite images. We determined the occurrence of two eruptive/thermal cycles: 1) Cycle 1 includes the formation of a new fumarolic field and two active craters during a short eruptive period, which includes thermal activity in three of the four crater lakes, and a strong degassing process between October 1998 and February 2001, coincident with a peak of volcanic heat flux (Qvolc) in two craters. The cycle finished with an eruptive episode (September 2010–July 2011). 2) Cycle 2 is represented by the thermal reactivation of two crater lakes, formation and detection of thermal activity in a new nested crater, and occurrence of a new eruptive episode (October 2018–April 2019). We observed a migration of the thermal and eruptive activity between the crater lakes and the interconnection of the pathways that feed the lakes, in both cases, partially related to the presence of two deep magma bodies. The Qvolc in Peteroa volcano crater lakes is primarily controlled by volcanic activity, and seasonal effects affect it at short-term, whilst at long-term, seasonal effects do not show clear influences in the volcanic heat fluxes. The maximum Qvolc measured between all crater lakes during quiescent periods was 59 MW, whereas during unrest episodes Qvolc in single crater lakes varied from 7.1 to 38 MW, with Peteroa volcano being classified as a low volcanic heat flux system. The detection of new thermal activity and increase of Qvolc in Peteroa volcano previous to explosive unrest can be considered as a good example of how thermal information from satellite images can be used to detect possible precursors to eruptive activity in volcanoes which host crater lakes.
Highly Variable and Non-complex Diazotroph Communities in Corals From Ambient and High CO2 Environments
Authors: Geissler Laura , Meunier Valentine , Rädecker Nils , Perna Gabriela , Rodolfo-Metalpa Riccardo , Houlbrèque Fanny , Voolstra Christian R.
Published: October 2021

The ecological success of corals depends on their association with microalgae and a diverse bacterial assemblage. Ocean acidification (OA), among other stressors, threatens to impair host-microbial metabolic interactions that underlie coral holobiont functioning. Volcanic CO2 seeps offer a unique opportunity to study the effects of OA in natural reef settings and provide insight into the long-term adaptations under a low pH environment. Here we compared nitrogen-fixing bacteria (diazotrophs) associated with four coral species (Pocillopora damicornis, Galaxea fascicularis, Acropora secale, and Porites rus) collected from CO2 seeps at Tutum Bay (Papua New Guinea) with those from a nearby ambient CO2 site using nifH amplicon sequencing to characterize the effects of seawater pH on bacterial communities and nitrogen cycling. Diazotroph communities were of generally low diversity across all coral species and for both sampling sites. Out of a total of 25 identified diazotroph taxa, 14 were associated with P. damicornis, of which 9 were shared across coral species. None of the diazotroph taxa, however, were consistently found across all coral species or across all samples within a species pointing to a high degree of diazotroph community variability. Rather, the majority of sampled colonies were dominated by one or two diazotroph taxa of high relative abundance. Pocillopora damicornis and Galaxea fascicularis that were sampled in both environments showed contrasting community assemblages between sites. In P. damicornis, Gammaproteobacteria and Cyanobacteria were prevalent under ambient pCO2, while a single member of the family Rhodobacteraceae was present at high relative abundance at the high pCO2 site. Conversely, in G. fascicularis diazotroph communities were indifferent between both sites. Diazotroph community changes in response to OA seem thus variable within as well as between host species, potentially arguing for haphazard diazotroph community assembly. This warrants further research into the underlying factors structuring diazotroph community assemblages and their functional role in the coral holobiont.
Angioplasty With Stent Implantation for Portal Venous Stenosis Caused by Abdominal Tuberculosis: A Case Report and Literature Review
Authors: Quan Xin , Tai Yang , Wei Bo , Tong Huan , Wang Zhidong , Yang Yuhang , Wu Hao
Published: October 2021

Abdominal tuberculosis is one of common forms of extra-pulmonary tuberculosis. However, portal vein involvement leading to portal venous stenosis and portal hypertension is a rare complication in abdominal tuberculosis. Because of the non-specific presentations and insensitive response to anti-tuberculosis therapy of the lesions involving portal vein, it continues to be both a diagnostic and treatment challenge. We have reported a 22-year-old woman presented with massive ascites and pleural effusion, which was proved to be TB infection by pleural biopsy. After standard anti-tuberculosis therapy, her systemic symptoms completely resolved while ascites worsened with serum-ascites albumin gradient >11 g/L. Contrast-enhanced computed tomography and portal venography showed severe main portal vein stenosis from compression by multiple calcified hilar lymph nodes. Finally, the patient was diagnosed with portal venous stenosis due to lymphadenopathy after abdominal tuberculosis infection. Portal venous angioplasty by balloon dilation with stent implantation was performed and continued anti-tuberculosis therapy were administrated after discharge. The ascites resolved promptly with no recurrence occurred during the six-month follow-up. Refractory ascites due to portal venous stenosis is an uncommon vascular complication of abdominal tuberculosis. Portal venous angioplasty with stent placement could be a safe and effective treatment for irreversible vascular lesions after anti-tuberculosis therapy.
DNA-Binding Properties of YbaB, a Putative Nucleoid-Associated Protein From Caulobacter crescentus
Authors: Pal Parul , Modi Malvika , Ravichandran Shashank , Yennamalli Ragothaman M. , Priyadarshini Richa
Published: October 2021

Nucleoid-associated proteins (NAPs) or histone-like proteins (HLPs) are DNA-binding proteins present in bacteria that play an important role in nucleoid architecture and gene regulation. NAPs affect bacterial nucleoid organization via DNA bending, bridging, or forming aggregates. EbfC is a nucleoid-associated protein identified first in Borrelia burgdorferi, belonging to YbaB/EbfC family of NAPs capable of binding and altering DNA conformation. YbaB, an ortholog of EbfC found in Escherichia coli and Haemophilus influenzae, also acts as a transcriptional regulator. YbaB has a novel tweezer-like structure and binds DNA as homodimers. The homologs of YbaB are found in almost all bacterial species, suggesting a conserved function, yet the physiological role of YbaB protein in many bacteria is not well understood. In this study, we characterized the YbaB/EbfC family DNA-binding protein in Caulobacter crescentus. C. crescentus has one YbaB/EbfC family gene annotated in the genome (YbaBCc) and it shares 41% sequence identity with YbaB/EbfC family NAPs. Computational modeling revealed tweezer-like structure of YbaBCc, a characteristic of YbaB/EbfC family of NAPs. N-terminal–CFP tagged YbaBCc localized with the nucleoid and is able to compact DNA. Unlike B. burgdorferi EbfC protein, YbaBCc protein is a non-specific DNA-binding protein in C. crescentus. Moreover, YbaBCc shields DNA against enzymatic degradation. Collectively, our findings reveal that YbaBCc is a small histone-like protein and may play a role in bacterial chromosome structuring and gene regulation in C. crescentus.
Mechanical Thrombectomy for Acute Stroke Due to Large-Vessel Occlusion Presenting With Mild Symptoms
Authors: Liu Feifeng , Shen Hao , Chen Chen , Bao Huan , Zuo Lian , Xu Xiahong , Yang Yumei , Cochrane Alexia , Xiao Yaping , Li Gang
Published: October 2021

Purpose: To evaluate the safety and efficacy of mechanical thrombectomy (MT) for acute stroke due to large vessel occlusion (LVO), presenting with mild symptoms.

Methods: A prospective cohort study of patients with mild ischemic stroke and LVO was conducted. Patients were divided into two groups: MT group or best medical management (MM) group. Propensity score matching (PSM) was conducted to reduce the confounding bias between the groups. The primary outcome was functional independence at 90 days. The safety outcome was symptomatic intracranial hemorrhage (sICH). Univariate and multivariate logistic regression analyses were used to identify the independent factors associated with outcomes.

Results: Among the 105 included patients, 43 were in the MT group and 62 in the MM group. Forty-three pairs of patients were generated after PSM. There were no significant differences in sICH rates between two groups (p = 1.000). The MT group had a higher proportion of independent outcomes (83.7% MT vs. 67.4% MM; OR 2.483; 95% CI 0.886–6.959; p = 0.079) and excellent outcomes (76.7% MT vs. 51.2% MM; OR 3.150; 95% CI 1.247–7.954; p = 0.013) compared to the MM group, especially in patients with stroke of the anterior circulation (p < 0.05). Multivariate logistic regression analysis showed that small infarct core volume (p = 0.015) and MT treatment (p = 0.013) were independently associated with excellent outcomes.

Conclusions: Our results suggest that MT in stroke patients, presenting with mild symptoms, due to acute LVO in the anterior circulation may be associated with satisfactory clinical outcomes.

Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT04526756.
A Time-Course-Based Estimation of the Human Medial Olivocochlear Reflex Function Using Clicks
Authors: Boothalingam Sriram , Goodman Shawn S. , MacCrae Hilary , Dhar Sumitrajit
Published: October 2021

The auditory efferent system, especially the medial olivocochlear reflex (MOCR), is implicated in both typical auditory processing and in auditory disorders in animal models. Despite the significant strides in both basic and translational research on the MOCR, its clinical applicability remains under-utilized in humans due to the lack of a recommended clinical method. Conventional tests employ broadband noise in one ear while monitoring change in otoacoustic emissions (OAEs) in the other ear to index efferent activity. These methods, (1) can only assay the contralateral MOCR pathway and (2) are unable to extract the kinetics of the reflexes. We have developed a method that re-purposes the same OAE-evoking click-train to also concurrently elicit bilateral MOCR activity. Data from click-train presentations at 80 dB peSPL at 62.5 Hz in 13 young normal-hearing adults demonstrate the feasibility of our method. Mean MOCR magnitude (1.7 dB) and activation time-constant (0.2 s) are consistent with prior MOCR reports. The data also suggest several advantages of this method including, (1) the ability to monitor MEMR, (2) obtain both magnitude and kinetics (time constants) of the MOCR, (3) visual and statistical confirmation of MOCR activation.
Arginine and Arginine-Rich Peptides as Modulators of Protein Aggregation and Cytotoxicity Associated With Alzheimer’s Disease
Authors: Mamsa Somayra S. A. , Meloni Bruno P.
Published: October 2021

A substantial body of evidence indicates cationic, arginine-rich peptides (CARPs) are effective therapeutic compounds for a range of neurodegenerative pathologies, with beneficial effects including the reduction of excitotoxic cell death and mitochondrial dysfunction. CARPs, therefore, represent an emergent class of promising neurotherapeutics with multimodal mechanisms of action. Arginine itself is a known chaotrope, able to prevent misfolding and aggregation of proteins. The putative role of proteopathies in chronic neurodegenerative diseases such as Alzheimer’s disease (AD) warrants investigation into whether CARPs could also prevent the aggregation and cytotoxicity of amyloidogenic proteins, particularly amyloid-beta and tau. While monomeric arginine is well-established as an inhibitor of protein aggregation in solution, no studies have comprehensively discussed the anti-aggregatory properties of arginine and CARPs on proteins associated with neurodegenerative disease. Here, we review the structural, physicochemical, and self-associative properties of arginine and the guanidinium moiety, to explore the mechanisms underlying the modulation of protein aggregation by monomeric and multimeric arginine molecules. Arginine-rich peptide-based inhibitors of amyloid-beta and tau aggregation are discussed, as well as further modulatory roles which could reduce proteopathic cytotoxicity, in the context of therapeutic development for AD.
Economic Evaluation of Sacituzumab Govitecan for the Treatment of Metastatic Triple-Negative Breast Cancer in China and the US
Authors: Chen Jigang , Han Mingyang , Liu Aihua , Shi Bo
Published: October 2021

Background

The effectiveness of Sacituzumab Govitecan (SG) for metastatic triple-negative breast cancer (mTNBC) has been demonstrated. We aimed to evaluate its cost-effectiveness on mTNBC from the Chinese and United States (US) perspective.

Methods

A partitioned survival model was developed to compare the cost and effectiveness of SG versus single-agent chemotherapy based on clinical data from the ASCENT phase 3 randomized trial. Cost and utility data were obtained from the literature. The incremental cost-effectiveness ratio (ICER) was measured, and one-way and probabilistic sensitivity analyses (PSA) were performed to observe model stability. A Markov model was constructed to validate the results.

Results

In China, SG yielded an additional 0.35 quality-adjusted life-year (QALY) at an additional cost of Chinese Renminbi ¥2257842. The ICER was ¥6375856 ($924037)/QALY. In the US, SG yielded the same additional QALY at an extra cost of $175393 and the ICER was $494479/QALY. Similar results were obtained from the Markov model. One-way sensitivity analyses showed that SG price had the greatest impact on the ICER. PSA showed the probability of SG to be cost-effective when compared with chemotherapy was zero at the current willing-to-pay threshold of ¥217341/QALY and $150000/QALY in China and the US, respectively. The probability of cost-effectiveness of SG would approximate 50% if its price was reduced to ¥10.44/mg in China and $3.65/mg in the US.

Conclusion

SG is unlikely to be a cost-effective treatment of mTNBC at the current price both in China and the US.
Elevated Lactate Dehydrogenase Levels Display a Poor Prognostic Factor for Non-Hodgkin’s Lymphoma in Intensive Care Unit: An Analysis of the MIMIC-III Database Combined With External Validation
Authors: Qi Jiaqian , Gu Chengyuan , Wang Weijuan , Xiang Mengqi , Chen Xiaochen , Fu Jianhong
Published: October 2021

Background

Among the growing number of patients with hematologic neoplasms hospitalized in the intensive care unit (ICU), the largest proportion of these patients are diagnosed with lymphoma. However, less attention has been paid in the past to identifying critically ill patients and assessing the prognosis of patients in ICU. Traditional critical care-related scores have shown limitations and inaccuracy in predicting mortality risk.

Methods

Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) were searched for in the Marketplace for Information in Intensive Care Medicine III (MIMIC-III) database. We searched mortality within 28 days as the primary endpoint. Logistics regression was used to screen risk factors. A calibration curve was used for internal validation, and the ROC curve and AUC were used to compare the new model with traditional scores.

Results

405 patients with DLBCL are enrolled in the project. Multivariate analysis shows the patients with the level of lactate dehydrogenase (LDH) > 327 U/L had an increased risk of 28-day mortality in ICU than others (OR = 13.04, p<0.01). Notably, length of ICU stay, LDH, creatinine, white blood cell counts, and APS III score are independent prognostic factors for patients with DLBCL in the ICU. Then, all these independent prognostic factors are selected into our prediction model. The new model has good accuracy (C-index=0.863) and a calibration curve, which improves clinical status concerning established ratings such as IPI, NCCN-IPI score, SOFA, APS III, and LODS. The results of a multicenter external validation including 124 DLBCL patients also showed that the new model was more accurate than all other models.

Conclusions

The elevated level of LDH indicates a poor prognosis of patients with DLBCL in the ICU. Our risk score with crossed validation based on the level of LDH shows a significant prognostic value and may be a valuable tool for assessing the critically ill as well.
The Value of MicroRNA-375 Detection for Triaging Primary Human Papillomavirus Positive Women: A Cross-Sectional Study in a General Population
Authors: Wu Qiongyan , Wang Lingfang , Zhao Xiumin , Tian Qifang , Wang Fenfen , Sima Ni , Qiu Liqian , Lu Weiguo , Xie Xing , Wang Xinyu , Cheng Xiaodong
Published: October 2021

Purpose

This study aims to validate the value of microRNA (miRNA) detection for triaging human papillomavirus (HPV)-positive women in the general population.

Patients and Methods

miR-375 detection in cervical exfoliated cells has been demonstrated to have the superior value to cytology in triaging primary HPV-positive women in the hospital population. In this study, residual samples of cervical exfoliated cells from 10,951 women in a general population were used to detect miRNA. The performance efficiency of miRNA detection in identifying high-grade cervical intraepithelial neoplasia (CIN) was evaluated. Pearson chi-square test and McNemar pairing test were used to compare miRNA detection and cytology.

Results

In valid 9,972 women aged 25–65, miR-375 expression showed a downward trend along with an increase in cervical lesion severity. The expression level of miR-375 ≤1.0 × 10-3 was identified as positive. In the HPV-positive and 12 HPV genotypes other than 16/18 (HR12)-positive women, miR-375 detection showed equivalent sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to that of cytology (≥ASC-US) and higher or similar sensitivity and NPV but lower specificity and PPV than that of cytology (≥ASC-H) in identifying CIN3+ and CIN2+. In HPV 16-positive women, miR-375 positivity had higher sensitivity and NPV but lower specificity and PPV than that of cytology (≥ASC-H and HSIL) in identifying CIN3+ and CIN2+. The immediate CIN3+ risk of miR-375 positivity was 19.8% (61/308) in HPV-positive, 10.8% (22/204) in HR12-positive, and 43.5% (37/85) in HPV16-positive women, respectively.

Conclusion

The detection of miR-375 in cervical exfoliated cells may be an optional method for triaging primary HPV-positive women in population-based cervical cancer screening.
Treatment Experience of 210 Pediatric Patients With Extraordinary Daytime Urinary Frequency: A Prospective Study
Authors: Li Yan , Zhang Ying , Liu Chao , Li Xiang , Zhou Qi , Sun Chao , Zhang Lei
Published: October 2021

Background: Lactulose can be used to manage chronic constipation and children who are withholding their bowel movements, but no studies are available regarding lactulose to treat pediatric extraordinary daytime urinary frequency (PEDUF). To explore the benefits of different therapeutic regimens (non-drug treatment vs. oral lactulose) in patients with PEDUF.

Methods: This prospective study included PEDUF patients admitted to the Pediatric Center of Qilu Hospital of Shandong University (Qingdao) from January 2015 to December 2019. The patients randomized received non-drug treatment (counseling), drug treatment (lactulose), or combination therapy. A therapeutic effect was defined by a decrease of>10% of the urination frequency.

Results: A total of 210 patients were included. They were 5.9 ± 0.4 years. There were 98 boys and 112 girls. Among the 210 patients, 82.4% (173/210) of their family members reported symptoms of constipation. Among the three groups, the response rate was 61.4% (43/70) in the non-drug treatment group, 90.0% (63/70) in the drug treatment group, and 91.4% (64/70) in the combination therapy group (P < 0.0001).

Conclusion: The frequency of constipation in children with PEDUF is high. The use of a laxative, like lactulose, might achieve a high therapeutic response rate in children with PEDUF, higher than counseling alone. That might represent a valuable therapeutic strategy for PEDUF.
Global Research Trends in Pediatric Trauma From 1968 to 2021: A Bibliometric Analysis
Authors: Ahmad Tauseef , Hua Linlin , Khan Muhammad , Nabi Ghulam , Khan Suliman , Çinar İlgün Özen ,   Haroon, Jalal Sajid , Baig Mukhtiar , Jin Hui , Wang Xiaoyan
Published: October 2021

Introduction: Every year, millions of children die from preventable causes worldwide. According to World Health Organization, injuries are the leading cause of disability and death among all age groups below 60 years.

Aim: This study aimed to evaluate the global research outcomes and trends, and some key bibliometric indicators in pediatric trauma.

Methods: A descriptive bibliometric analysis study was designed. On June 14, 2021, an electronic search was performed in the Web of Science Core Collection database using the potential searching keywords “Pediatric AND Trauma” in the title field without any limitations. The search was performed using the Boolean search query method. The data were downloaded in plaintext and comma-separated values format. The required graphs were generated using OriginPro 2018. Furthermore, the data were transferred to HistCite™ software for bibliometric analysis. In addition, the obtained data were plotted for network visualization mapping using VOSviewer software version 1.6.15 for windows.

Results: A total of 2,269 documents were included in the final analysis. The included documents were authored by 7,894 authors and published in 395 research and academic journals, mainly in the English language (n = 2,222). The main document types were articles (n = 1,276, citations = 18,244), and meeting abstracts (n = 331, citations = 19). Pediatric (n = 2,269) and trauma (n = 2,257) were the most widely used keywords. The most productive year was 2019 (n = 184, citations = 527). The most prolific author was Upperman JS (n = 29, citations = 202). The most attractive journals in pediatric trauma research were The Journal of Trauma and Acute Care Surgery (n = 290, citations = 5,199) and the Journal of Pediatric Surgery (n = 256, citations = 5,088). The most active institute was the University of California System (n = 110). The most dominant country was the United States of America (USA) (n = 1,620, citations = 22,983). The USA and Canada had the highest total link strength, 103 and 70, respectively.

Conclusion: This study provides a comprehensive overview of research output in pediatric trauma. The USA continues to dominate scientific research and funding in pediatric trauma. Findings of the current study will help the researchers and clinicians to understand the recent achievements and research frontiers. Collaborative research initiative needs to be established between institutions in developed and developing countries and among researchers.
Dual Viscosity Mixture Vehicle for Intratympanic Dexamethasone Delivery Can Block Ototoxic Hearing Loss
Authors: Li Hui , Suh Myung-Whan , Oh Seung Ha
Published: October 2021

Clinically there is no effective method to prevent drug induced hearing loss in patients undergoing chemotherapy and anti-tuberculosis therapy. In this study, we developed an intratympanic (IT) local drug delivery vehicle featuring hyaluronic acid-based dual viscosity mixture encapsulation of dexamethasone (D), named dual-vehicle + D, and assessed its protective effect in ototoxic hearing loss. We assessed the residence time, biocompatibility, and treatment outcome of the novel vehicle compared with the current standard of care vehicle (saline) and control conditions. The hearing threshold and hair cell count were significantly better in the dual-vehicle + D group compared to the other two groups. The final hearing benefit in the dual-vehicle group was approximately 25–35 dB, which is significant from a clinical point of view. Morphologic evaluation of the cochlear hair cells also supported this finding. Due to the high viscosity and adhesive property of the vehicle, the residence time of the vehicle was 49 days in the dual-vehicle + D group, whereas it was less than 24 h in the saline + D group. There was no sign of inflammation or infection in all the animals. From this study we were able to confirm that dual viscosity mixture vehicle for IT D delivery can effectively block ototoxic hearing loss.
Phosphate-Dependent Regulation of Growth and Stresses Management in Plants
Authors: Bechtaoui Noura , Rabiu Muhammad Kabir , Raklami Anas , Oufdou Khalid , Hafidi Mohamed , Jemo Martin
Published: October 2021

The importance of phosphorus in the regulation of plant growth function is well studied. However, the role of the inorganic phosphate (Pi) molecule in the mitigation of abiotic stresses such as drought, salinity, heavy metal, heat, and acid stresses are poorly understood. We revisited peer-reviewed articles on plant growth characteristics that are phosphorus (P)-dependently regulated under the sufficient-P and low/no-P starvation alone or either combined with one of the mentioned stress. We found that the photosynthesis rate and stomatal conductance decreased under Pi-starved conditions. The total chlorophyll contents were increased in the P-deficient plants, owing to the lack of Pi molecules to sustain the photosynthesis functioning, particularly, the Rubisco and fructose-1,6-bisphosphatase function. The dry biomass of shoots, roots, and P concentrations were significantly reduced under Pi starvation with marketable effects in the cereal than in the legumes. To mitigate P stress, plants activate alternative regulatory pathways, the Pi-dependent glycolysis, and mitochondrial respiration in the cytoplasm. Plants grown under well-Pi supplementation of drought stress exhibited higher dry biomass of shoots than the no-P treated ones. The Pi supply to plants grown under heavy metals stress reduced the metal concentrations in the leaves for the cadmium (Cd) and lead (Pb), but could not prevent them from absorbing heavy metals from soils. To detoxify from heavy metal stress, plants enhance the catalase and ascorbate peroxidase activity that prevents lipid peroxidation in the leaves. The HvPIP and PHO1 genes were over-expressed under both Pi starvation alone and Pi plus drought, or Pi plus salinity stress combination, implying their key roles to mediate the stress mitigations. Agronomy Pi-based interventions to increase Pi at the on-farm levels were discussed. Revisiting the roles of P in growth and its better management in agricultural lands or where P is supplemented as fertilizer could help the plants to survive under abiotic stresses.
Transcriptomic Effects of Acute Ultraviolet Radiation Exposure on Two Syntrichia Mosses
Authors: Ekwealor Jenna T. B. , Mishler Brent D.
Published: October 2021

Ultraviolet radiation (UVR) is a major environmental stressor for terrestrial plants. Here we investigated genetic responses to acute broadband UVR exposure in the highly desiccation-tolerant mosses Syntrichia caninervis and Syntrichia ruralis, using a comparative transcriptomics approach. We explored whether UVR protection is physiologically plastic and induced by UVR exposure, addressing the following questions: (1) What is the timeline of changes in the transcriptome with acute UVR exposure in these two species? (2) What genes are involved in the UVR response? and (3) How do the two species differ in their transcriptomic response to UVR? There were remarkable differences between the two species after 10 and 30 min of UVR exposure, including no overlap in significantly differentially abundant transcripts (DATs) after 10 min of UVR exposure and more than twice as many DATs for S. caninervis as there were for S. ruralis. Photosynthesis-related transcripts were involved in the response of S. ruralis to UVR, while membrane-related transcripts were indicated in the response of S. caninervis. In both species, transcripts involved in oxidative stress and those important for desiccation tolerance (such as late embryogenesis abundant genes and early light-inducible protein genes) were involved in response to UVR, suggesting possible roles in UVR tolerance and cross-talk with desiccation tolerance in these species. The results of this study suggest potential UVR-induced responses that may have roles outside of UVR tolerance, and that the response to URV is different in these two species, perhaps a reflection of adaptation to different environmental conditions.
Examining Heterogeneity in the Impacts of Socio-Emotional Curricula in Preschool: A Quantile Treatment Effect Approach
Authors: Shea Zhiling Meng , Jenkins Jade Marcus
Published: October 2021

We examine treatment effect heterogeneity using data from the Head Start CARES study, in which a sample of preschool centers was randomly assigned to either one of three curricula interventions targeting socio-emotional (SE) skills (i.e., emotional knowledge, problem-solving skills, and executive functions) or to continue using their “business-as-usual” curriculum. Most existing research estimates only mean differences between treatment and control groups, and uses simple subgroup analyses to assess treatment heterogeneity, which may overlook important variation in treatment effects across the ex post outcome distribution. We use quantile treatment effects analyses to understand the impacts of these curricular interventions at various parts of the outcome distribution, from the 1st percentile to the 99th percentile, to understand who benefits most from SE curricula interventions. Results show positive impacts of the curricula interventions on emotional knowledge and problem-solving skills, but not equally across the full skill distribution. Children in the upper half of the emotional knowledge distribution and at the higher end of the problem-solving skills distribution gain more from the curricula. As in the study’s original mean-comparison analyses, we find no impacts on children’s executive function skills at any point in the skills distribution. Our findings add to the growing literature on the differential effects of curricula interventions for preschool programs operating at scale. Importantly, it provides the first evidence for the effects of SE curricula interventions on SE outcomes across children’s outcome skill levels. We discuss implications for early education programs for children with different school readiness skills.
Examining Additive and Synergistic Relations Between Preschool Self-Regulation and Executive Function Skills: Predictions to Academic Outcomes
Authors: Finders Jennifer K. , Duncan Robert J. , Korucu Irem , Bryant Lindsey B. , Purpura David J. , Schmitt Sara A.
Published: October 2021

In the present study, we examined the extent to which teacher-rated self-regulation and directly assessed executive function skills were independently, additively, or synergistically related to academic achievement during the transition to kindergarten. The sample included 126 children (42% female; Mage = 4.73 years) from families with low incomes who participated in a larger evaluation of state-funded preschool. Regression models with children nested in their respective preschool classrooms investigated main effects and moderated effects of teacher-rated self-regulation skills manifested in preschool classroom behaviors and cognitive executive function skills assessed through direct assessments on math, literacy, and vocabulary in the spring of preschool and in the fall of kindergarten. Results revealed independent but not additive relations between executive function and math in the spring of preschool and self-regulation and literacy in the fall of kindergarten. One significant interaction emerged providing evidence for synergistic relations between teacher-rated self-regulation and directly assessed executive function for literacy at both timepoints across the transition to kindergarten. Implications for policy and practice are discussed.
The Choice Point Model of Acceptance and Commitment Therapy With Inpatient Substance Use and Co-occurring Populations: A Pilot Study
Authors: Berman Brian M. , Kurlancheek Kris
Published: October 2021

Objectives: Acceptance and Commitment Therapy (ACT) is an empirically supported treatment which aims to enhance self-acceptance and a commitment to core values. The present study examined the effectiveness of the Choice Point model of ACT in a residential substance use disorder (SUD) setting. Choice Point is a contemporary approach to ACT and targets transdiagnostic processes.

Methods: This uncontrolled quasi-experimental design assessed 47 participants taking part in Choice Point for Substances (CHOPS) in order to investigate its influence on psychological inflexibility, values-based action, and self-compassion over time. The study additionally assessed for sleeper effects and associations between transdiagnostic processes and warning signs of relapse.

Results: Findings demonstrated a decrease in psychological inflexibility and increases in values-based action and self-compassion over time. Gains were maintained at follow-up, and sleeper effects were observed for psychological inflexibility and mindfulness. Correlational analysis suggested that all transdiagnostic processes were related to warning signs of relapse at follow-up.

Conclusion: These results provide preliminary evidence for the feasibility, acceptability, and effectiveness of CHOPS for SUD. Observed sleeper effects in psychological inflexibility and mindfulness indicate that CHOPS may provide longer-term benefits critical to a population where relapse is common. While encouraging, these findings should be interpreted with caution. Future research should utilize comparison groups when investigating CHOPS.
Meta-Analysis on the Association of Neuropeptide Y rs16139 Variant With the Risk of Alcoholism
Authors: Chen Biqing , Yadav Manish , Mulkalwar Madhubala , Saikrishna Lakkakula , Verma Henu , Ye Weibing , Bhaskar L. V. K. S.
Published: October 2021

Introduction: The neuropeptide-Y (NPY) is involved in the development of alcoholism through NPY receptors. A T>C mutation causes substitution of leucine to proline at codon 7 (L7P; rs16139) in the signal peptide of neuropeptide Y is known to cause a 42% increase in plasma NPY levels. Studies that analyzed the association between NPY rs16139 and alcoholism risk did not demonstrate conclusive evidence for this relationship. The present study aims to evaluate the association between NPY gene rs16139 variant and alcohol dependence.

Method: An electronic search of databases including PubMed and Google Scholar was performed to retrieve studies investigating the association between NPY rs16139 and alcoholism. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated in allelic and dominant genetic models. Sensitivity analyses and publication bias were assessed in our meta-analysis. The meta-analysis was conducted using the MetaGenyo web tool.

Result: Significant heterogeneity was observed across studies (p < 0.001). Our results have shown that there is no significant association between NPY rs16139 variant and the risk of alcoholism in allelic (OR = 0.98, 95% CI 0.70–1.38, p = 0.921) and dominant models (OR = 0.98, 95% CI 0.69–1.40, p = 0.919). Begg's funnel plot and Egger's test have not shown publication bias (p = 0.332).

Conclusion: To the best of our knowledge, this is the first meta-analysis that evaluates the relationship between the NPY rs16139 polymorphism and the risk of alcoholism. Our large-scale meta-analysis suggests that NPY rs16139 polymorphism is not associated with alcoholism. However, further studies are needed to increase our understanding of the relationship between NPY variants in alcoholism.
Causal Associations Between Educational Attainment and 14 Urological and Reproductive Health Outcomes: A Mendelian Randomization Study
Authors: Wang Menghua , Jian Zhongyu , Gao Xiaoshuai , Yuan Chi , Jin Xi , Li Hong , Wang Kunjie
Published: October 2021

Background: The impact of educational attainment (EA) on multiple urological and reproductive health outcomes has been explored in observational studies. Here we used Mendelian randomization (MR) to investigate whether EA has causal effects on 14 urological and reproductive health outcomes.

Methods: We obtained summary statistics for EA and 14 urological and reproductive health outcomes from genome-wide association studies (GWAS). MR analyses were applied to explore the potential causal association between EA and them. Inverse variance weighted was the primary analytical method.

Results: Genetically predicted one standard deviation (SD) increase in EA was causally associated with a higher risk of prostate cancer [odds ratio (OR) 1.14, 95% confidence interval (CI) 1.05–1.25, P = 0.003] and a reduced risk of kidney stone (OR 0.73, 95% CI 0.62–0.87, P < 0.001) and cystitis (OR 0.76, 95% CI 0.67–0.86, P < 0.001) after Bonferroni correction. EA was also suggestively correlated with a lower risk of prostatitis (OR 0.76, 95% CI 0.59–0.98, P = 0.037) and incontinence (OR 0.64, 95% CI 0.47–0.87, P = 0.004). For the bioavailable testosterone levels and infertility, sex-specific associations were observed, with genetically determined increased EA being related to higher levels of testosterone in men (β 0.07, 95% CI 0.04–0.10, P < 0.001), lower levels of testosterone in women (β −0.13, 95% CI−0.16 to−0.11, P < 0.001), and a lower risk of infertility in women (OR 0.74, 95% CI 0.64–0.86, P < 0.001) but was not related to male infertility (OR 0.79, 95% CI 0.52–1.20, P = 0.269) after Bonferroni correction. For bladder cancer, kidney cancer, testicular cancer, benign prostatic hyperplasia, and erectile dysfunction, no causal effects were observed.

Conclusions: EA plays a vital role in urological diseases, especially in non-oncological outcomes and reproductive health. These findings should be verified in further studies when GWAS data are sufficient.
Bradyrhizobium Inoculation of Field-Grown Kersting's Groundnut [Macrotyloma geocarpum (Harms) Marechal & Baudet] Increased Grain Yield and N2 Fixation, Measured Using the Ureide, and 15N Natural Abundance Techniques
Authors: Mohammed Mustapha , Mbah Glory C. , Sowley Elias N. K. , Dakora Felix D.
Published: October 2021

Here, we report on the symbiotic N2 fixation and water use efficiency (δ13C) of Kersting's groundnut, an important but underutilized grain legume in Africa, in response to inoculation with Bradyrhizobium strains 3267 and CB756. The 15N natural abundance and xylem ureide techniques were used to quantify N2 fixation. The landraces in this study derived variable levels of their N requirements from symbiosis, which translated into marked differences in the amounts of N-fixed by the landrace–inoculant combinations across the test locations. In most instances, the landrace-strain combinations that elicited higher shoot biomass also recorded greater N-fixed and/or ureide-N in xylem sap as well as grain yield. Although some landraces coupled increased grain yield with higher water use efficiency (shoot δ13C), a trait that could be tapped for crop improvement, others recorded lower yields despite eliciting relatively high shoot δ13C values, indicating genotypic variations in adaptation to the different environments. Grain yield of the test landraces showed marked variation and ranged from 131 to 1349.8 kg ha−1 depending on the landrace–strain combination used and the planting location. The high symbiotic dependence by landraces in this study could explain why Kersting's groundnut thrives in the low nutrient soils that are prevalent in its cultivation areas. These results provide more insights into the literature regarding the Kersting's groundnut–rhizobia symbiosis as well as the crop's water use efficiency.