bluuebunny/crossref_metadata_2025 huggingface dataset:
Why Does Not Nanotechnology Go Green? Bioprocess Simulation and Economics for Bacterial-Origin Magnetite Nanoparticles
Authors: Correa Tarcisio , Presciliano Rogério , Abreu Fernanda
Published: August 2021

Nanotechnological developments, including fabrication and use of magnetic nanomaterials, are growing at a fast pace. Magnetic nanoparticles are exciting tools for use in healthcare, biological sensors, and environmental remediation. Due to better control over final-product characteristics and cleaner production, biogenic nanomagnets are preferable over synthetic ones for technological use. In this sense, the technical requirements and economic factors for setting up industrial production of magnetotactic bacteria (MTB)-derived nanomagnets were studied in the present work. Magnetite fabrication costs in a single-stage fed-batch and a semicontinuous process were US$ 10,372 and US$ 11,169 per kilogram, respectively. Depending on the variations of the production process, the minimum selling price for biogenic nanomagnets ranged between US$ 21 and US$ 120 per gram. Because these prices are consistently below commercial values for synthetic nanoparticles, we suggest that microbial production is competitive and constitutes an attractive alternative for a greener manufacturing of magnetic nanoparticles nanotools with versatile applicability.
Information-Theoretic Quantification of Dedifferentiation in the Aging of Motor and Executive Functions
Authors: Chang Erik Chihhung
Published: August 2021

A central account of cognitive aging is the dedifferentiation among functions due to reduced processing resources. Previous reports contrasting trends of aging across cognitive domains mostly relied on transformed scores of heterogeneous measures. By quantifying the computational load with information entropy in tasks probing motor and executive functions, this study uncovered interaction among age, task, and load as well as associations among the parametric estimates of these factors at the individual level. Specifically, the linear functions between computational load and performance time differed significantly between motor and executive tasks in the young group but not in the elderly group and showed stronger associations for parameters within and between tasks in the elderly group than in the young group. These findings are in line with the dedifferentiation hypothesis of cognitive aging and provide a more principled approach in contrasting trends of cognitive aging across different domains from the information-theoretic perspective.
Abnormal Neural Activity in Different Frequency Bands in Parkinson’s Disease With Mild Cognitive Impairment
Authors: Rong Siming , Zhang Piao , He Chentao , Li Yan , Li Xiaohong , Li Ruitao , Nie Kun , Huang Sifei , Wang Limin , Wang Lijuan , Zhang Yuhu
Published: August 2021

Background: Abnormal spontaneous neural activity is often found in patients with Parkinson’s disease with mild cognitive impairment (PD-MCI). However, the frequency dependence of neuronal interaction activities, especially the fractional amplitude of low-frequency fluctuation (fALFF) and degree centrality (DC), in PD-MCI is still unclear. Thus, this study aimed to explore the frequency dependence of PD-MCI based on fALFF and DC maps.

Methods: Twenty-four patients with PD-MCI, 42 PD patients with normal cognition (PD-NC), and 33 healthy controls (HCs) were enrolled. Neuropsychological assessments and resting-state functional MRI (rs-fMRI) were performed. The fALFF and DC values in the conventional, slow4 and slow5 frequency bands were compared among the groups.

Results: In the conventional frequency band, the DC value in the left precentral area was decreased in PD-MCI patients, while that in the right fusiform area was increased in PD-NC patients compared with HCs. Regarding fALFFs, both the PD-MCI and PD-NC patients had decreased values in the right precentral area compared with those of the HCs. The fALFFs did not differ between PD-MCI and PD-NC patients. The fALFF results in the slow4 subfrequency band were consistent with those in the conventional frequency band. In the slow5 band, the DC value in the left middle temporal lobe was higher in PD-MCI patients than in PD-NC patients and was positively correlated with the performance of the PD-MCI patients on the Montreal Cognitive Assessment (MoCA). Additionally, both PD-MCI and PD-NC patients showed lower fALFF values in the bilateral putamen than the HCs, and the fALFF in the bilateral putamen was negatively correlated with the Hoehn and Yahr stages of PD-MCI. The fALFF in the left putamen was negatively correlated with the scores of PD-MCI patients on the Movement Disorder Society-Unified Parkinson Disease Rating Scale Part III (MDS-UPRDS-III).

Conclusion: Our results suggested that abnormal neuronal activities, such as fALFF and DC, are dependent on frequency in PD-MCI. Some subfrequency bands could distinguish PD-MCI from PD. Our findings may be helpful for further revealing the frequency-dependent resting functional disruption in PD-MCI.
Anticipatory 50-kHz Precontact Ultrasonic Vocalizations and Sexual Motivation: Characteristic Pattern of Ultrasound Subtypes in an Individual Analyzed Profile
Authors: Bogacki-Rychlik Wiktor , Rolf Mateusz , Bialy Michal
Published: August 2021

We verified the hypothesis of the existence of forms of individual-specific differences in the emission of anticipatory precontact vocalization (PVs) indicating individualization related to sexual experience and motivation in male rats. Long-Evans males were individually placed in a chamber and 50-kHz ultrasounds were recorded during 5-min periods. In experiment 1, PVs were recorded before the introduction of a female in four consecutive sessions during the acquisition of sexual experience. In experiment 2, PVs were analyzed in three groups of sexually experienced males: with the highest, moderate, and the lowest sexual motivation based on previous copulatory activity. In both experiments, the total number of ultrasounds, as well as 14 different specific subtypes, was measured. The ultrasound profiles for each male were created by analyzing the proportions of specific dominant subtypes of so-called 50-kHz calls. We decided that the dominant ultrasounds were those that represented more than 10% of the total recorded signals in a particular session. The number of PVs was positively correlated with the acquisition of sexual experience and previous copulatory efficiency (measured as the number of sessions with ejaculation). Furthermore, PVs showed domination of the frequency modulated signals (complex and composite) as well as flat and short with upward ramp ultrasounds with some individual differences, regardless of the level of sexual motivation. The results show a characteristic pattern of PVs and confirm the hypothesis that the number of PVs is a parameter reflecting the level of sexual motivation.
Older Adults Automatically Detect Age of Older Adults’ Photographs: A Visual Mismatch Negativity Study
Authors: Csizmadia Petra , Petro Bela , Kojouharova Petia , Gaál Zsófia Anna , Scheiling Katalin , Nagy Boglárka , Czigler István
Published: August 2021

The human face is one of the most frequently used stimuli in vMMN (visual mismatch negativity) research. Previous studies showed that vMMN is sensitive to facial emotions and gender, but investigations of age-related vMMN differences are relatively rare. The aim of this study was to investigate whether the models’ age in photographs were automatically detected, even if the photographs were not parts of the ongoing task. Furthermore, we investigated age-related differences, and the possibility of different sensitivity to photographs of participants’ own versus different ages. We recorded event-related potentials (ERPs) to faces of young and old models in younger (N= 20; 18–30 years) and older groups (N= 20; 60–75 years). The faces appeared around the location of the field of a tracking task. In sequences the young or the old faces were either frequent (standards) or infrequent (deviants). According to the results, a regular sequence of models’ age is automatically registered, and faces violating the models’ age elicited the vMMN component. However, in this study vMMN emerged only in the older group to same-age deviants. This finding is explained by the less effective inhibition of irrelevant stimuli in the elderly, and corresponds to own-age bias effect of recognition studies.
GABAB Receptor Agonist R-Baclofen Reverses Altered Auditory Reactivity and Filtering in the Cntnap2 Knock-Out Rat
Authors: Möhrle Dorit , Wang Wenxuan , Whitehead Shawn N. , Schmid Susanne
Published: August 2021

Altered sensory information processing, and auditory processing, in particular, is a common impairment in individuals with autism spectrum disorder (ASD). One prominent hypothesis for the etiology of ASD is an imbalance between neuronal excitation and inhibition. The selective GABAB receptor agonist R-Baclofen has been shown previously to improve social deficits and repetitive behaviors in several mouse models for neurodevelopmental disorders including ASD, and its formulation Arbaclofen has been shown to ameliorate social avoidance symptoms in some individuals with ASD. The present study investigated whether R-Baclofen can remediate ASD-related altered sensory processing reliant on excitation/inhibition imbalance in the auditory brainstem. To assess a possible excitation/inhibition imbalance in the startle-mediating brainstem underlying ASD-like auditory-evoked behaviors, we detected and quantified brain amino acid levels in the nucleus reticularis pontis caudalis (PnC) of rats with a homozygous loss-of-function mutation in the ASD-linked gene Contactin-associated protein-like 2 (Cntnap2) and their wildtype (WT) littermates using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (MALDI MS). Abnormal behavioral read-outs of brainstem auditory signaling in Cntnap2 KO rats were accompanied by increased levels of GABA, glutamate, and glutamine in the PnC. We then compared the effect of R-Baclofen on behavioral read-outs of brainstem auditory signaling in Cntnap2 KO and WT rats. Auditory reactivity, sensory filtering, and sensorimotor gating were tested in form of acoustic startle response input-output functions, short-term habituation, and prepulse inhibition before and after acute administration of R-Baclofen (0.75, 1.5, and 3 mg/kg). Systemic R-Baclofen treatment improved disruptions in sensory filtering in Cntnap2 KO rats and suppressed exaggerated auditory startle responses, in particular to moderately loud sounds. Lower ASR thresholds in Cntnap2 KO rats were increased in a dose-dependent fashion, with the two higher doses bringing thresholds close to controls, whereas shorter ASR peak latencies at the threshold were further exacerbated. Impaired prepulse inhibition increased across various acoustic prepulse conditions after administration of R-Baclofen in Cntnap2 KO rats, whereas R-Baclofen did not affect prepulse inhibition in WT rats. Our findings suggest that GABAB receptor agonists may be useful for pharmacologically targeting multiple aspects of sensory processing disruptions involving neuronal excitation/inhibition imbalances in ASD.
Effect of Body Mass Index on the Prognosis of Liver Cirrhosis
Authors: Yin Yue , Li Yiling , Shao Lichun , Yuan Shanshan , Liu Bang , Lin Su , Yang Yida , Tang Shanhong , Meng Fanping , Wu Yunhai , Chen Yu , Li Bimin , Zhu Qiang , Qi Xingshun
Published: August 2021

Objective: At present, the association of body mass index (BMI) with the prognosis of liver cirrhosis is controversial. Our retrospective study aimed to evaluate the impact of BMI on the outcome of liver cirrhosis.

Methods: In the first part, long-term death was evaluated in 436 patients with cirrhosis and without malignancy from our prospectively established single-center database. In the second part, in-hospital death was evaluated in 379 patients with cirrhosis and with acute gastrointestinal bleeding (AGIB) from our retrospective multicenter study. BMI was calculated and categorized as underweight (BMI <18.5 kg/m2), normal weight (18.5 ≤ BMI < 23.0 kg/m2), and overweight/obese (BMI ≥ 23.0 kg/m2).

Results: In the first part, Kaplan–Meier curve analyses demonstrated a significantly higher cumulative survival rate in the overweight/obese group than the normal weight group (p = 0.047). Cox regression analyses demonstrated that overweight/obesity was significantly associated with decreased long-term mortality compared with the normal weight group [hazard ratio (HR) = 0.635; 95% CI: 0.405–0.998; p = 0.049] but not an independent predictor after adjusting for age, gender, and Child–Pugh score (HR = 0.758; 95%CI: 0.479–1.199; p = 0.236). In the second part, Kaplan–Meier curve analyses demonstrated no significant difference in the cumulative survival rate between the overweight/obese and the normal weight groups (p = 0.094). Cox regression analyses also demonstrated that overweight/obesity was not significantly associated with in-hospital mortality compared with normal weight group (HR = 0.349; 95%CI: 0.096-1.269; p = 0.110). In both of the two parts, the Kaplan–Meier curve analyses demonstrated no significant difference in the cumulative survival rate between underweight and normal weight groups.

Conclusion: Overweight/obesity is modestly associated with long-term survival in patients with cirrhosis but not an independent prognostic predictor. There is little effect of overweight/obesity on the short-term survival of patients with cirrhosis and with AGIB.
Shifting of Physicochemical and Biological Characteristics of Coffee Roasting Under Ultrasound-Assisted Extraction
Authors: Duangjai Acharaporn , Saokaew Surasak , Goh Bey-Hing , Phisalprapa Pochamana
Published: August 2021

Ultrasound-assisted extraction (UAE) is an effective tool for the extraction of natural antioxidants. Thus, differentially roasted Arabica-coffee beans known as light (LC), medium (MC), and dark coffee (DC) were prepared and extracted under the influence of UAE. Following that, they were examined specifically on theirs physicochemical and biological characteristics: nutritional values, pH, °Brix, antioxidant activities, polyphenol content, caffeine, and chlorogenic-acid levels. Various parameters, such as extraction temperatures (20, 40, and 80°C) and extraction time periods (5, 10, and 20 min), were examined. DC extract was less acidic than those on MC and LC extracts. LC showed higher moisture content than the MC and DC (1.56, 1.3, and 0.92%, respectively). MC displayed the highest polyphenol content and potent antioxidant activity. Caffeine and chlorogenic acid contents trend to decrease during roasting. The maximum caffeine level was found in MC at 80°C for 5 min (27.65 mg/g extract). The highest chlorogenic acid content was in LC at 80°C for 10 min (16.67 mg/g extract). The caffeine and chlorogenic acid contents were related to the polyphenol content and depended on the roasting and extraction conditions. These results suggest that the UAE at various temperature and extraction time period may alter the physicochemical and biological characteristics of different coffee roasts.
Identification of Eleven Novel BRCA Mutations in Tunisia: Impact on the Clinical Management of BRCA Related Cancers
Authors: Hamdi Yosr , Mighri Najah , Boujemaa Maroua , Mejri Nesrine , Ben Nasr Sonia , Ben Rekaya Mariem , Messaoud Olfa , Bouaziz Hanen , Berrazega Yosra , Rachdi Haifa , Jaidane Olfa , Daoud Nouha , Zribi Aref , Ayari Jihene , El Benna Houda , Labidi Soumaya , Ben Hassouna Jamel , Haddaoui Abderazzek , Rahal Khaled , Benna Farouk , Mrad Ridha , Ben Ahmed Slim , Boussen Hamouda , Boubaker Samir , Abdelhak Sonia
Published: August 2021

Background

Breast cancer is the world’s most common cancer among women. It is becoming an increasingly urgent problem in low- and middle-income countries (LMICs) where a large fraction of women is diagnosed with advanced-stage disease and have no access to treatment or basic palliative care. About 5-10% of all breast cancers can be attributed to hereditary genetic components and up to 25% of familial cases are due to mutations in BRCA1/2 genes. Since their discovery in 1994 and 1995, as few as 18 mutations have been identified in BRCA genes in the Tunisian population. The aim of this study is to identify additional BRCA mutations, to estimate their contribution to the hereditary breast and ovarian cancers in Tunisia and to investigate the clinicopathological signatures associated with BRCA mutations.

Methods

A total of 354 patients diagnosed with breast and ovarian cancers, including 5 male breast cancer cases, have been investigated for BRCA1/2 mutations using traditional and/or next generation sequencing technologies. Clinicopathological signatures associated with BRCA mutations have also been investigated.

Results

In the current study, 16 distinct mutations were detected: 10 in BRCA1 and 6 in BRCA2, of which 11 are described for the first time in Tunisia including 3 variations that have not been reported previously in public databases namely BRCA1_c.915T>A; BRCA2_c.-227-?_7805+? and BRCA2_c.249delG. Early age at onset, family history of ovarian cancer and high tumor grade were significantly associated with BRCA status. BRCA1 carriers were more likely to be triple negative breast cancer compared to BRCA2 carriers. A relatively high frequency of contralateral breast cancer and ovarian cancer occurrence was observed among BRCA carriers and was more frequent in patients carrying BRCA1 mutations.

Conclusion

Our study provides new insights into breast and ovarian cancer genetic landscape in the under-represented North African populations. The prevalence assessment of novel and recurrent BRCA1/2 pathogenic mutations will enhance the use of personalized treatment and precise screening strategies by both affected and unaffected North African cancer cases.
Prognostic Role of Programmed Death Ligand-1 on Tumor-Infiltrating Immune Cells in “High-Risk” Patients Following Radical Cystectomy: A Retrospective Cohort Study
Authors: Lee Chung Un , Lee Dong Hyeon , Song Wan
Published: August 2021

Purpose

The aim of this study is to investigate the prognostic role of programmed death ligand-1 (PD-L1) on tumor-infiltrating immune cells (TIICs) in patients after radical cystectomy (RC) for bladder cancer (BCa).

Materials and Methods

We retrospectively reviewed 92 “high-risk” (≥pT3a and/or pN+) patients who underwent RC for BCa, without adjuvant chemotherapy (AC), between April 2014 and December 2019. PD-L1 on TIICs was measured only using the VENTANA (SP-142) immunohistochemistry assay. Patients were categorized into three groups based to the percentage of the tumor area covered by PD-L1 on TIICs: IC0 (<1%), IC1 (≥1% and <5%), and IC2/3 (≥5%). Positive PD-L1 was defined as IC2/3 (≥5%). Kaplan–Meier survival analysis was used to illustrate recurrence-free survival (RFS), and Cox proportional hazard models were used to identify predictive factors of tumor recurrence.

Results

Within the cohort, the proportions of PD-L1 IC0, IC1, and IC2/3 were 21.7%, 23.9%, and 54.4%, respectively. At follow-up (mean 31.3 months), tumor recurrence was identified in 49 patients (53.3%). Using multivariable analysis, tumor stage (pT4; P=0.005), positive lymph nodes (P=0.021), and positive PD-L1 on TIICs (P=0.010) were independent predictors of tumor recurrence. The 2- and 3-year RFS rates were 67.7% and 64.2% in negative PD-L1 on TIICs, while 27.8% and 22.3% in positive PD-L1 on TIICs, respectively.

Conclusions

Positive PD-L1 on TIICs was significantly associated with poorer RFS in “high-risk” patients after RC without AC. Our results support the use of adjuvant immunotherapy in “high-risk” patients with positive PD-L1 on TIICs after RC.
Diagnosis of Invasive Meningioma Based on Brain-Tumor Interface Radiomics Features on Brain MR Images: A Multicenter Study
Authors: Xiao Dongdong , Zhao Zhen , Liu Jun , Wang Xuan , Fu Peng , Le Grange Jehane Michael , Wang Jihua , Guo Xuebing , Zhao Hongyang , Shi Jiawei , Yan Pengfei , Jiang Xiaobing
Published: August 2021

Background

Meningioma invasion can be preoperatively recognized by radiomics features, which significantly contributes to treatment decision-making. Here, we aimed to evaluate the comparative performance of radiomics signatures derived from varying regions of interests (ROIs) in predicting BI and ascertaining the optimal width of the peritumoral regions needed for accurate analysis.

Methods

Five hundred and five patients from Wuhan Union Hospital (internal cohort) and 214 cases from Taihe Hospital (external validation cohort) pathologically diagnosed as meningioma were included in our study. Feature selection was performed from 1,015 radiomics features respectively obtained from nine different ROIs (brain-tumor interface (BTI)2–5mm; whole tumor; the amalgamation of the two regions) on contrast-enhanced T1-weighted imaging using least-absolute shrinkage and selection operator and random forest. Principal component analysis with varimax rotation was employed for feature reduction. Receiver operator curve was utilized for assessing discrimination of the classifier. Furthermore, clinical index was used to detect the predictive power.

Results

Model obtained from BTI4mm ROI has the maximum AUC in the training set (0.891 (0.85, 0.932)), internal validation set (0.851 (0.743, 0.96)), and external validation set (0.881 (0.833, 0.928)) and displayed statistically significant results between nine radiomics models. The most predictive radiomics features are almost entirely generated from GLCM and GLDM statistics. The addition of PEV to radiomics features (BTI4mm) enhanced model discrimination of invasive meningiomas.

Conclusions

The combined model (radiomics classifier with BTI4mm ROI + PEV) had greater diagnostic performance than other models and its clinical application may positively contribute to the management of meningioma patients.
Effect and Safety of Therapeutic Regimens for Patients With Germline BRCA Mutation-Associated Breast Cancer: A Network Meta-Analysis
Authors: Jiang Ying , Meng Xiang-Yu , Deng Ning-Ning , Meng Chen , Li Lu-Hui , He Zi-Kang , Wang Xing-Yun , Song Zhe-Yao , Cui Rong-Jun
Published: August 2021

Purpose

Breast cancer type 1 susceptibility (BRCA) mutations not only increase breast cancer (BC) risk but also result in poor survival and prognosis for BC patients. This study will analyze the effect and safety of therapeutic regimens for the treatment of BC patients with germline BRCA (gBRCA) mutations by network meta-analysis.

Methods

Public databases were searched from inception to 29 April 2021. Frequentist network meta-analysis was conducted to analyze the benefit of chemotherapy and targeted drug-related strategies.

Results

Seventeen articles were included in the analysis. For progression-free survival (PFS), olaparib (hazard ratio (HR): 0.58; 95% confidence interval (CI): 0.43 – 0.79), platinum (HR: 0.45; 95% CI: 0.22 – 0.89), and talazoparib (HR: 0.54; 95% CI: 0.41 – 0.71) were significantly better than platinum-free chemotherapy (Chemo). The results based on indirect comparisons showed that veliparib (Vel) + platinum + Chemo was also significantly better than Chemo (HR: 0.37; 95% CI: 0.20 – 0.69). For overall survival (OS), olaparib was significantly better than Chemo only in the population who did not receive prior chemotherapy. For pathologic complete response (pCR), bevacizumab+Chemo had a significant advantage over platinum agents (OR: 3.64; 95% CI: 1.07 - 12.39). Olaparib and talazoparib both showed significantly higher objective response rates (ORRs) than Chemo.

Conclusion

The PFS results suggested that olaparib, talazoparib, and Vel+platinum agent+Chemo were ideal regimens for overall, TNBC, and advanced BC patients with gBRCA mutations. Whether PARPis are suitable for patients with gBRCA mutations who have received prior platinum therapy still needs to be clarified.
Bibliometric Analysis of Bronchopulmonary Dysplasia in Extremely Premature Infants in the Web of Science Database Using CiteSpace Software
Authors: Zhou Qin , Kong Hai-Bo , He Bao-Mei , Zhou Su-Ya
Published: August 2021

Objectives: To review the literature related to bronchopulmonary dysplasia in extremely pre-mature infants, summarize research direction, and report trends.

Methods: CiteSpace is a Java application which supports visual exploration with knowledge discovery in bibliographic databases. Relevant articles from 2008 to 2020 were retrieved from the Web of Science Core Collection database, and we extracted the following data: title, abstract, year, keywords, author, organization, journal and cited literature. We downloaded the data into CiteSpace (version 5.7.R3) to summarize countries, institutions, journals, and authors. We visualized the data with a knowledge map, collaborative network analysis, cluster analysis, and burst keyword analysis.

Results: We identified 610 articles on bronchopulmonary dysplasia in extremely pre-mature infants. The United States had the most articles on this topic (302 articles), followed by Canada (49 articles) and Germany (44 articles). The top three institutions, high-yield journals, and authors were all from the United States. The most common keywords were neurodevelopmental disorders, active perinatal care, mechanical ventilation, inflammation, pulmonary hypertension, low-dose hydrocortisone, development, and patent ductus arteriosus.

Conclusions: This study illustrates the trends and frontiers in the study of bronchopulmonary dysplasia in extremely pre-mature infants. The current research direction is to identify the risk factors in developing bronchopulmonary dysplasia in extremely pre-mature infants.
Real-World Treatment Patterns and Outcomes of Growth Hormone Treatment Among Children in Israel Over the Past Decade (2004–2015)
Authors: Ben-Ari Tal , Chodick Gabriel , Shalev Varda , Goldstein Dalit , Gomez Roy , Landau Zohar
Published: August 2021

Objective: To assess a decade of growth hormone (GH) treatment patterns and outcomes in a real-world setting in Israel using a state-of-the-art computerized database.

Methods: This large retrospective database study included 2,379 children initiating GH treatment in Maccabi Healthcare Services (between January 2004 and December 2014). Good adherence with therapy (proportion of days covered >80%) was assessed during follow-up.

Results: At GH treatment initiation: 62.1% were boys; height standard deviation score (SDS) was −2.36 ± 0.65 (mean ± SD); age was 9.8 ± 3.1 years; and time from short stature diagnosis to first GH purchase was 4.8 ± 3.3 years. Mean treatment period was 3.5 ± 0.95 years; 79.4% of children were treated for more than 3 years. The two main indications for GH therapy were idiopathic short stature (ISS) (n = 1,615, 67.9%) and GH deficiency (GHD) (n = 611, 25.7%). Children in the highest socio-economic-status (SES) tertile comprised 61.3% of ISS and 59.7% of GHD. After 3 years, mean height gain SDS was 1.09 ± 0.91 for GHD and 0.96 ± 0.57 for ISS (p = 0.0004). Adult height (age 15 for girls and 17 for boys) was recorded for 624 patients (26.2%) with better outcomes for GHD than ISS (−1.0±0.82 vs. −1.28±0.93, respectively; p = 0.0002). Good adherence was achieved in 78.2% of the cohort during the first year and declined thereafter to 68.1% during the third year of the treatment.

Conclusions: Children who initiate GH therapy are predominantly male, belong mainly to the upper SES, commence treatment a long period after initial recognition of short stature, and have suboptimal adherence. Appropriate referral, diagnosis, and follow-up care may result in better treatment outcomes with GH therapy.
The Efficacy and Safety of Rituximab for Childhood Steroid-Dependent Nephrotic Syndrome: A Systematic Review and Meta-Analysis
Authors: Liu Sidi , Gui Chuying , Lu Zhenzhen , Li Huijie , Fu Zhike , Deng Yueyi
Published: August 2021

Objectives: Rituximab (RTX), a possible alternative treatment option, is recognized as a new therapeutic hope for the treatment of steroid-dependent nephrotic syndrome (SDNS) in children. However, the efficacy and safety of RTX in the treatment of childhood SDNS are still controversial. The objective of this study was to evaluate the efficacy and safety of RTX treatment in children with SDNS.

Study Design: Six randomized controlled trials (RCTs) and one retrospective comparative control study data from studies, performed before January 2021 were collected, from PubMed, Cochrane Library, Embase, and Web of Science. The studies evaluating the efficacy and safety of RTX in childhood SDNS were included.

Results: Six RCTs and one retrospective comparative control study were included in our analysis. Compared with the control group, the RTX treatment group achieved a higher complete remission rate (OR = 5.21; 95% CI, 3.18–8.54; p < 0.00001), and we found significant differences between the two groups on serum albumin level (MD = 0.88; 95% CI, 0.43–1.33; p = 0.0001) and estimated glomerular filtration rate (MD = 6.43; 95% CI, 2.68–10.19; p = 0.0008). However, RTX treatment did not significantly lower serum creatinine levels nor did it significantly reduce the occurrence of proteinuria. In addition, we found no advantages with RTX on treatment safety.

Conclusions: RTX has shown satisfactory characteristics in terms of efficacy and may be a promising treatment method for SDNS in children. However, the long-term effects have not been fully evaluated and should be further studied through randomized clinical trials.
An Insight on Multicentric Signaling of Angiotensin II in Cardiovascular system: A Recent Update
Authors: Verma Kanika , Pant Malvika , Paliwal Sarvesh , Dwivedi Jaya , Sharma Swapnil
Published: August 2021

The multifaceted nature of the renin-angiotensin system (RAS) makes it versatile due to its involvement in pathogenesis of the cardiovascular disease. Angiotensin II (Ang II), a multifaceted member of RAS family is known to have various potential effects. The knowledge of this peptide has immensely ameliorated after meticulous research for decades. Several studies have evidenced angiotensin I receptor (AT1 R) to mediate the majority Ang II-regulated functions in the system. Functional crosstalk between AT1 R mediated signal transduction cascades and other signaling pathways has been recognized. The review will provide an up-to-date information and recent discoveries involved in Ang II receptor signal transduction and their functional significance in the cardiovascular system for potential translation in therapeutics. Moreover, the review also focuses on the role of stem cell-based therapies in the cardiovascular system.
Impact of Transcutaneous Auricular Vagus Nerve Stimulation on Large-Scale Functional Brain Networks: From Local to Global
Authors: Rings Thorsten , von Wrede Randi , Bröhl Timo , Schach Sophia , Helmstaedter Christoph , Lehnertz Klaus
Published: August 2021

Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel non-invasive brain stimulation technique considered as a potential supplementary treatment option for a wide range of diseases. Although first promising findings were obtained so far, the exact mode of action of taVNS is not fully understood yet. We recently developed an examination schedule to probe for immediate taVNS-induced modifications of large-scale epileptic brain networks. With this schedule, we observed short-term taVNS to have a topology-modifying, robustness- and stability-enhancing immediate effect on large-scale functional brain networks from subjects with focal epilepsies. We here expand on this study and investigate the impact of short-term taVNS on various local and global characteristics of large-scale evolving functional brain networks from a group of 30 subjects with and without central nervous system diseases. Our findings point to differential, at first glance counterintuitive, taVNS-mediated alterations of local and global topological network characteristics that result in a reconfiguration of networks and a modification of their stability and robustness properties. We propose a model of a stimulation-related stretching and compression of evolving functional brain networks that may help to better understand the mode of action of taVNS.
A Multidisciplinary Comparison of Different Techniques Among Skilled Water Treaders
Authors: van Duijn Tina , Button Chris , Masters Rich S. W.
Published: August 2021

In an immersion incident, a person may be required to tread water for extended periods of time in order to survive. Treading water, or maintaining a stable head position above the water surface, can be achieved in several different ways. Determining which treading water techniques are economic (energetically and cognitively) is an important first step in approaching evidence-based water safety instruction. The present study investigated the cognitive and metabolic demands associated with four main techniques for treading water in experienced water treaders. Skilled water treaders (n=21) performed four common treading techniques for 3min each: “running” in the water, “flutter kick” with hands sculling, “upright breaststroke,” and “egg-beater.” Self-reported rate of perceived exertion (RPE) and task load index (TLX) score, as well as objective measures of probe reaction time (PRT; i.e., response to auditory cues while treading), oxygen consumption and heart rate were assessed. The “egg-beater” technique and the “upright breaststroke” technique were linked to significantly lower cognitive and energetic demands compared to the other techniques (VO2: p<0.001 – “Running” M=29.02, SD=7.40/“Flutter kick” M=29.37, SD=8.56, “Breaststroke” M=23.47, SD=7.28, and “Eggbeater” M=23.18, SD=6.31). This study lays the groundwork for future research that may establish the ideal movement behavior in drowning situations and investigate movement instruction to less experienced treaders.
Extrahepatic Surgery in Cirrhosis Significantly Increases Portal Pressure in Preclinical Animal Models
Authors: Chang Johannes , Meinke Jonathan , Geck Moritz , Hebest Marc , Böhling Nina , Dolscheid-Pommerich Ramona , Stoffel-Wagner Birgit , Kristiansen Glen , Overhaus Marcus , Peyman Leon O. , Klein Sabine , Uschner Frank E. , Brol Maximilian J. , Vilz Tim O. , Lingohr Philipp , Kalff Jörg C. , Jansen Christian , Strassburg Christian P. , Wehner Sven , Trebicka Jonel , Praktiknjo Michael
Published: August 2021

Background: Liver cirrhosis is a relevant comorbidity with increasing prevalence. Postoperative decompensation and development of complications in patients with cirrhosis remains a frequent clinical problem. Surgery has been discussed as a precipitating event for decompensation and complications of cirrhosis, but the underlying pathomechanisms are still obscure. The aim of this study was to analyze the role of abdominal extrahepatic surgery in cirrhosis on portal pressure and fibrosis in a preclinical model.

Methods: Compensated liver cirrhosis was induced using tetrachlormethane (CCL4) inhalation and bile duct ligation (BDL) models in rats, non-cirrhotic portal hypertension by partial portal vein ligation (PPVL). Intestinal manipulation (IM) as a model of extrahepatic abdominal surgery was performed. 2 and 7 days after IM, portal pressure was measured in-vivo. Hydroxyproline measurements, Sirius Red staining and qPCR measurements of the liver were performed for evaluation of fibrosis development and hepatic inflammation. Laboratory parameters of liver function in serum were analyzed.

Results: Portal pressure was significantly elevated 2 and 7 days after IM in both models of cirrhosis. In the non-cirrhotic model the trend was the same, while not statistically significant. In both cirrhotic models, IM shows strong effects of decompensation, with significant weight loss, elevation of liver enzymes and hypoalbuminemia. 7 days after IM in the BDL group, Sirius red staining and hydroxyproline levels showed significant progression of fibrosis and significantly elevated mRNA levels of hepatic inflammation compared to the respective control group. A progression of fibrosis was not observed in the CCL4 model.

Conclusion: In animal models of cirrhosis with continuous liver injury (BDL), IM increases portal pressure, and development of fibrosis. Perioperative portal pressure and hence inflammation processes may be therapeutic targets to prevent post-operative decompensation in cirrhosis.
QTL for Main Stem Node Number and Its Response to Plant Densities in 144 Soybean FW-RILs
Authors: Li Wen-Xia , Wang Ping , Zhao Hengxing , Sun Xu , Yang Tao , Li Haoran , Hou Yongqin , Liu Cuiqiao , Siyal Mahfishan , Raja veesar Rameez , Hu Bo , Ning Hailong
Published: August 2021

Although the main stem node number of soybean [Glycine max (L.) Merr. ] is an important yield-related trait, there have been limited studies on the effect of plant density on the identification of quantitative trait loci (QTL) for main stem node number (MSNN). To address this issue, here, 144 four-way recombinant inbred lines (FW-RILs) derived from Kenfeng 14, Kenfeng 15, Heinong 48, and Kenfeng 19 were used to identify QTL for MSNN with densities of 2.2 × 105 (D1) and 3 × 105 (D2) plants/ha in five environments by linkage and association studies. As a result, the linkage and association studies identified 40 and 28 QTL in D1 and D2, respectively, indicating the difference in QTL in various densities. Among these QTL, five were common in the two densities; 36 were singly identified for response to density; 12 were repeatedly identified by both response to density and phenotype of two densities. Thirty-one were repeatedly detected across various methods, densities, and environments in the linkage and association studies. Among the 24 common QTL in the linkage and association studies, 15 explained a phenotypic variation of more than 10%. Finally, Glyma.06G094400, Glyma.06G147600, Glyma.19G160800.1, and Glyma.19G161100 were predicted to be associated with MSNN. These findings will help to elucidate the genetic basis of MSNN and improve molecular assistant selection in high-yield soybean breeding.
Transcriptome Analysis of Melocactus glaucescens (Cactaceae) Reveals Metabolic Changes During in vitro Shoot Organogenesis Induction
Authors: Torres-Silva Gabriela , Correia Ludmila Nayara Freitas , Batista Diego Silva , Koehler Andréa Dias , Resende Sheila Vitória , Romanel Elisson , Cassol Daniela , Almeida Ana Maria Rocha , Strickler Susan R. , Specht Chelsea Dvorak , Otoni Wagner Campos
Published: August 2021

Melocactus glaucescens is an endangered cactus highly valued for its ornamental properties. In vitro shoot production of this species provides a sustainable alternative to overharvesting from the wild; however, its propagation could be improved if the genetic regulation underlying its developmental processes were known. The present study generated de novo transcriptome data, describing in vitro shoot organogenesis induction in M. glaucescens. Total RNA was extracted from explants before (control) and after shoot organogenesis induction (treated). A total of 14,478 unigenes (average length, 520 bases) were obtained using Illumina HiSeq 3000 (Illumina Inc., San Diego, CA, USA) sequencing and transcriptome assembly. Filtering for differential expression yielded 2,058 unigenes. Pairwise comparison of treated vs. control genes revealed that 1,241 (60.3%) unigenes exhibited no significant change, 226 (11%) were downregulated, and 591 (28.7%) were upregulated. Based on database analysis, more transcription factor families and unigenes appeared to be upregulated in the treated samples than in controls. Expression of WOUND INDUCED DEDIFFERENTIATION 1 (WIND1) and CALMODULIN (CaM) genes, both of which were upregulated in treated samples, was further validated by real-time quantitative PCR (RT-qPCR). Differences in gene expression patterns between control and treated samples indicate substantial changes in the primary and secondary metabolism of M. glaucescens after the induction of shoot organogenesis. These results help to clarify the molecular genetics and functional genomic aspects underlying propagation in the Cactaceae family.
Silicon Application Modulates the Growth, Rhizosphere Soil Characteristics, and Bacterial Community Structure in Sugarcane
Authors: Deng Quanqing , Yu Taobing , Zeng Zhen , Ashraf Umair , Shi Qihan , Huang Suihua , Lian Tengxiang , Chen Jianwen , Muzaffar Wardah , Shen Wankuan
Published: August 2021

Silicon (Si) deficiency, caused by acidic soil and rainy climate, is a major constraint for sugarcane production in southern China. Si application generally improves sugarcane growth; however, there are few studies on the relationships between enhanced plant growth, changes in rhizosphere soil, and bacterial communities. A field experiment was conducted to measure sugarcane agronomic traits, plant nutrient contents, rhizosphere soil enzyme activities and chemical properties, and the rhizosphere bacterial community diversity and structure of three predominant sugarcane varieties under two Si treatments, i.e., 0 and 200 kg of silicon dioxide (SiO2) ha−1 regarded as Si0 and Si200, respectively. Results showed that Si application substantially improved the sugarcane stalk fresh weight and Si, phosphorus (P), and potassium (K) contents comparing to Si0, and had an obvious impact on rhizosphere soil pH, available Si (ASi), available P (AP), available K (AK), total phosphorus (TP), and the activity of acid phosphatase. Furthermore, the relative abundances of Proteobacteria showed a remarkable increase in Si200, which may be the dominant group in sugarcane growth under Si application. Interestingly, the AP was noticed as a major factor that caused bacterial community structure differences between the two Si treatments according to canonical correspondence analysis (CCA). In addition, the association network analysis indicated that Si application enriched the rhizosphere bacterial network, which could be beneficial to sugarcane growth. Overall, appropriate Si application, i.e., 200 kg SiO2 ha−1 promoted sugarcane growth, changed rhizosphere soil enzyme activities and chemical properties, and bacterial community structures.
Light-Induced Dynamic Change of Phytochrome B and Cryptochrome 1 Stabilizes SINATs in Arabidopsis
Authors: Hu Jin , Hu Yinmeng , Yang Mengran , Hu Xiaotong , Wang Xuelu
Published: August 2021

Ubiquitin-dependent protein degradation plays an important role in many plant developmental processes. We previously identified a class of SINA RING-type E3 ligases of Arabidopsis thaliana (SINATs), whose protein levels decrease in the dark and increase in red and blue light, but the underlying mechanism is unclear. In this study, we created transgenic lines carrying point mutations in SINAT genes and photoreceptors-NLS or -NES transgenic plants to investigate the regulatory mechanism of SINAT protein stability. We demonstrated that the degradation of SINATs is self-regulated, and SINATs interact with photoreceptors phytochrome B (phyB) and cryptochrome 1 (CRY1) in the cytoplasm, which leads to the degradation of SINATs in the dark. Furthermore, we observed that the red light-induced subcellular localization change of phyB and blue light-induced the dissociation of CRY1 from SINATs and was the major determinant for the light-promoted SINATs accumulation. Our findings provide a novel mechanism of how the stability and degradation of the E3 ligase SINATs are regulated by an association and dissociation mechanism through the red light-induced subcellular movement of phyB and the blue light-induced dissociation of CRY1 from SINATs.
Genome-Wide Association Studies Provide Insights into the Genetic Determination of Flower and Leaf Traits of Actinidia eriantha
Authors: Liao Guanglian , Zhong Min , Jiang Zhiqiang , Tao Junjie , Jia Dongfeng , Qu Xueyan , Huang Chunhui , Liu Qing , Xu Xiaobiao
Published: August 2021

Kiwifruit (Actinidia eriantha) is a dioecious vine, and the pollen of its male cultivars has a direct effect on the quality of its fruits. In this study, to facilitate molecular breeding and gene identification, we performed genome-wide association studies (GWAS) on 11 traits of flower and leaf. A total of 946,337 highly consistent SNP markers were obtained in the whole genome. Phylogenetic tree analysis and population structure analysis showed that the 143 germplasms can be divided into two groups. The linkage disequilibrium analysis showed that A. eriantha have a relatively fast attenuation rate, and that the average attenuation distance of LD was 0.1–0.3 Kb. The MLM (QK) model was determined as best for correlation analysis, and eight and three SNPs associated with flower- and leaf-related traits were identified, respectively, at 0.01 significance level. However, SNP markers associated with stamen number per flower, pollen viability, total chlorophyll content, and total flavonoid content were not identified at the 0.01 significant level, although it is worth noting that one, one, five, and two SNPs were identified to be associated with these traits at the 0.05 significant level. This study provides insights into the complex flower- and leaf-related biology, and identifies genes controlling important traits in A. eriantha through GWAS, which extends the genetic resources and basis for facilitating molecular breeding in kiwifruits.
Validity and Reliability of the Urdu Version of the McLean Screening Instrument for Borderline Personality Disorder
Authors: Munawar Khadeeja , Aqeel Muhammad , Rehna Tasnim , Shuja Kanwar Hamza , Bakrin Faizah Safina , Choudhry Fahad Riaz
Published: August 2021

Introduction: Although the translation and the validation of the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) are performed in various languages and samples, no study has established the validity and reliability of the Urdu version of MSI-BPD in individuals with cardiac problems.

Materials and Methods: The Urdu version of the MSI-BPD was prepared through the standard back-translation method. The translation and adaption were completed in four steps: forward translation, adaption and translation, back translation and committee approach, and cross-language validation. The sample, selected through the purposive sampling method, comprised of 150 adults with cardiac problems (men = 75 and women = 75), with an age range of 23–78 years (M = 55, SD = 10.6). The Cronbach alpha reliability and factorial validity of the MSI-BPD were assessed through confirmatory factor analysis (CFA) and Pearson correlation analyses. Internal consistency and test–retest reliability (at 2 weeks' interval) were used to evaluate the reliability. Statistical analyses were performed, using SPSS (version 22) and Structural Equation Modeling (SEM) software.

Results: Preliminary analysis revealed that the overall instrument had good internal consistency (Urdu MSI-BPD α = 0.79; English MSI-BPD α = 0.77) as well as test–retest correlation coefficients for 15 days (r = 0.94).

Conclusions: Findings suggested that the MSI-BPD, with important limitations, can be used as an effective preliminary screening tool to measure BPD in Urdu-speaking adults with cardiac problems. Further validations should be conducted to make the translated version of the MSI-BPD an appropriate tool to screen BPD in hospitals and mental health care settings.