bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the Growth of Algae Under Low Atmospheric Pressures for Potential Food and Oxygen Production on Mars
Authors: Cycil Leena M. , Hausrath Elisabeth M. , Ming Douglas W. , Adcock Christopher T. , Raymond James , Remias Daniel , Ruemmele Warren P.
Published: November 2021

With long-term missions to Mars and beyond that would not allow resupply, a self-sustaining Bioregenerative Life Support System (BLSS) is essential. Algae are promising candidates for BLSS due to their completely edible biomass, fast growth rates and ease of handling. Extremophilic algae such as snow algae and halophilic algae may also be especially suited for a BLSS because of their ability to grow under extreme conditions. However, as indicated from over 50 prior space studies examining algal growth, little is known about the growth of algae at close to Mars-relevant pressures. Here, we explored the potential for five algae species to produce oxygen and food under low-pressure conditions relevant to Mars. These includedChloromonas brevispina,Kremastochrysopsis austriaca,Dunaliella salina,Chlorella vulgaris, andSpirulina plantensis. The cultures were grown in duplicate in a low-pressure growth chamber at 670 ± 20 mbar, 330 ± 20 mbar, 160 ± 20 mbar, and 80 ± 2.5 mbar pressures under continuous light exposure (62–70 μmol m–2s–1). The atmosphere was evacuated and purged with CO2after sampling each week. Growth experiments showed thatD. salina, C. brevispina, andC. vulgariswere the best candidates to be used for BLSS at low pressure. The highest carrying capacities for each species under low pressure conditions were achieved byD. salinaat 160 mbar (30.0 ± 4.6 × 105cells/ml), followed byC. brevispinaat 330 mbar (19.8 ± 0.9 × 105cells/ml) andC. vulgarisat 160 mbar (13.0 ± 1.5 × 105cells/ml).C. brevispina, D. salina, andC. vulgarisall also displayed substantial growth at the lowest tested pressure of 80 mbar reaching concentrations of 43.4 ± 2.5 × 104, 15.8 ± 1.3 × 104, and 57.1 ± 4.5 × 104cells per ml, respectively. These results indicate that these species are promising candidates for the development of a Mars-based BLSS using low pressure (∼200–300 mbar) greenhouses and inflatable structures that have already been conceptualized and designed.
Genetic Characterization of Brucella spp.: Whole Genome Sequencing-Based Approach for the Determination of Multiple Locus Variable Number Tandem Repeat Profiles
Authors: Pelerito Ana , Nunes Alexandra , Grilo Teresa , Isidro Joana , Silva Catarina , Ferreira Ana Cristina , Valdezate Sylvia , Núncio Maria Sofia , Georgi Enrico , Gomes João Paulo
Published: November 2021

Brucellosis is an important zoonosis that is emerging in some regions of the world, gaining increased relevance with the inclusion of the causing agent Brucella spp. in the class B bioterrorism group. Until now, multi-locus VNTR Analysis (MLVA) based on 16 loci has been considered as the gold standard for Brucella typing. However, this methodology is laborious, and, with the rampant release of Brucella genomes, the transition from the traditional MLVA to whole genome sequencing (WGS)-based typing is on course. Nevertheless, in order to avoid a disruptive transition with the loss of massive genetic data obtained throughout the last decade and considering that the transition timings will vary considerably among different countries, it is important to determine WGS-based MLVA alleles of the nowadays sequenced genomes. On this regard, we aimed to evaluate the performance of a Python script that had been previously developed for the rapid in silico extraction of the MLVA alleles, by comparing it to the PCR-based MLVA procedure over 83 strains from different Brucella species. The WGS-based MLVA approach detected 95.3% of all possible 1,328 hits (83 strains×16 loci) and showed an agreement rate with the PCR-based MLVA procedure of 96.4% for MLVA-16. According to our dataset, we suggest the use of a minimal depth of coverage of ~50x and a maximum number of ~200 contigs as guiding “boundaries” for the future application of the script. In conclusion, the evaluated script seems to be a very useful and robust tool for the in silico determination of MLVA profiles of Brucella strains, allowing retrospective and prospective molecular epidemiological studies, which are important for maintaining an active epidemiological surveillance of brucellosis.
Putative Antimicrobial Peptides Within Bacterial Proteomes Affect Bacterial Predominance: A Network Analysis Perspective
Authors: Oulas Anastasis , Zachariou Margarita , Chasapis Christos T. , Tomazou Marios , Ijaz Umer Z. , Schmartz Georges Pierre , Spyrou George M. , Vlamis-Gardikas Alexios
Published: November 2021

The predominance of bacterial taxa in the gut, was examined in view of the putative antimicrobial peptide sequences (AMPs) within their proteomes. The working assumption was that compatible bacteria would share homology and thus immunity to their putative AMPs, while competing taxa would have dissimilarities in their proteome-hidden AMPs. A network–based method (“Bacterial Wars”) was developed to handle sequence similarities of predicted AMPs among UniProt-derived protein sequences from different bacterial taxa, while a resulting parameter (“Die” score) suggested which taxa would prevail in a defined microbiome. T he working hypothesis was examined by correlating the calculated Die scores, to the abundance of bacterial taxa from gut microbiomes from different states of health and disease. Eleven publicly available 16S rRNA datasets and a dataset from a full shotgun metagenomics served for the analysis. The overall conclusion was that AMPs encrypted within bacterial proteomes affected the predominance of bacterial taxa in chemospheres.
An lncRNA Model for Predicting the Prognosis of Hepatocellular Carcinoma Patients and ceRNA Mechanism
Authors: Zhang Hao , Liu Renzheng , Sun Lin , Hu Xiao
Published: November 2021

Liver cancer is a highly malignant tumor. Notably, recent studies have found that long non-coding RNAs (lncRNAs) play a prominent role in the prognosis of patients with liver cancer. Herein, we attempted to construct an lncRNA model to accurately predict the survival rate in liver cancer. Based on The Cancer Genome Atlas (TCGA) database, we first identified 1066 lncRNAs with differential expression. The patient data obtained from TCGA were divided into the experimental group and the verification group. According to the difference in lncRNAs, we used single-factor and multi-factor Cox regression to select the genes needed to build the model in the experimental group, which were verified in the verification group. The results showed that the model could accurately predict the survival rate of patients in the high and low risk groups. The reliability of the model was also confirmed by the area under the receiver operating characteristic curve. Our model is significantly correlated with different clinicopathological features. Finally, we built a ceRNA network based on lncRNAs, which was used to display miRNAs and mRNAs related to lncRNAs. In summary, we constructed an lncRNA model to predict the survival rate of patients with hepatocellular carcinoma.
Does Second Language Learning Promote Neuroplasticity in Aging? A Systematic Review of Cognitive and Neuroimaging Studies
Authors: Ware Caitlin , Dautricourt Sophie , Gonneaud Julie , Chételat Gael
Published: November 2021

As the population ages, understanding how to maintain older adults' cognitive abilities is essential. Bilingualism has been linked to higher cognitive reserve, better performance in executive control, changes in brain structure and function relative to monolinguals, and delay in dementia onset. Learning a second language thus seems a promising avenue for cognitive enhancement in older adults. Our review aims to determine whether learning a foreign language in later life improves cognition and promotes neuroplasticity. We screened articles from the Pubmed, Scopus, and Science Direct databases to identify interventional studies using second language training in senior participants, including either cognition or neuroimaging as outcome measures. A total of nine articles were found, with only one neuroimaging study. Results from these studies are inconsistent, but tend to suggest that second language learning is associated with improvement in attentional switching, inhibition, working memory, and increased functional connectivity. We discuss the implications of these results, and suggest new directions and methodological recommendations for future research.
Alleviative Effect of Alpha-Lipoic Acid on Cognitive Impairment in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Rats
Authors: Ko Chih-Yuan , Xu Jian-Hua , Lo Yangming Martin , Tu Rong-Syuan , Wu James Swi-Bea , Huang Wen-Chung , Shen Szu-Chuan
Published: November 2021

Background: The intricate relationship between type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) suggests that insulin is involved in modulating AD-related proteins. Alpha-lipoic acid (ALA) can improve insulin resistance (IR) in diabetic rats. However, the role of ALA in alleviating the cognitive decline of T2DM is not yet clear. This study examined the ameliorative effect of ALA on cognitive impairment, cerebral IR, and synaptic plasticity abnormalities in high-fat diet (HFD) plus streptozotocin (STZ) induced diabetic rats.

Methods: The HFD/STZ-induced T2DM male Wistar rats were orally administered with ALA (50, 100, or 200 mg/kg BW) once a day for 13 weeks. Abilities of cognition were measured with a passive avoidance test and Morris water maze. Specimens of blood and brain were collected for biochemical analysis after the rats were sacrificed. Western blotting was used to determine protein expressions in the hippocampus and cortex in the insulin signaling pathways, long-term potentiation (LTP), and synaptic plasticity-related protein expressions.

Results: Alpha-lipoic acid improved hyperinsulinemia and the higher levels of free fatty acids of the T2DM rats. Behavioral experiments showed that the administration of ALA improved cognitive impairment in HFD/STZ-induced T2DM rats. ALA ameliorated insulin-related pathway proteins [phosphoinositide 3-kinase (PI3K), phospho-protein kinase B (pAkt)/Akt, and insulin-degrading enzyme (IDE)] and the LTP pathway, as well as synaptic plasticity proteins (calmodulin-dependent protein kinase II, cyclic AMP response element-binding protein, and postsynaptic density protein-95) of the cerebral cortex or hippocampus in HFD/STZ-induced T2DM rats.

Conclusion: Our findings suggested that ALA may ameliorate cognition impairment via alleviating cerebral IR improvement and cerebral synaptic plasticity in diabetic rats.
20-HETE Participates in Intracerebral Hemorrhage-Induced Acute Injury by Promoting Cell Ferroptosis
Authors: Han Ranran , Wan Jieru , Han Xiaoning , Ren Honglei , Falck John R. , Munnuri Sailu , Yang Zeng-Jin , Koehler Raymond C.
Published: November 2021

Intracerebral hemorrhage (ICH) is a highly fatal type of stroke that leads to various types of neuronal death. Recently, ferroptosis, a form of cell death resulting from iron-dependent lipid peroxide accumulation, was observed in a mouse ICH model. N-hydroxy-N′-(4-n-butyl-2-methylphenyl)-formamidine (HET0016), which inhibits synthesis of the arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE), has shown a protective effect after ICH. However, the underlying mechanisms of the neuroprotective effect need further investigation. We explored whether 20-HETE participates in ICH-induced ferroptosis ex vivo by using hemoglobin-treated organotypic hippocampal slice cultures (OHSCs) and in vivo by using a collagenase-induced ICH mouse model. Ex vivo, we found that the 20-HETE synthesis inhibitor HET0016 and antagonist 20-6,15-HEDGE reduced hemoglobin-induced cell death, iron deposition, and lipid reactive oxygen species levels in OHSCs. Furthermore, 20-HETE inhibition in OHSCs increased the expression of glutathione peroxidase (GPX) 4, an antioxidant enzyme that serves as a main regulator of ferroptosis. In contrast, exposure of OHSCs to the 20-HETE stable mimetic 20-5,14-HEDGE induced cell death that was significantly inhibited by the ferroptosis inhibitor ferrostatin-1. In vivo, HET0016 treatment ameliorated focal deficits, reduced lesion volume, and decreased iron accumulation around the lesion at day 3 and 7 after ICH. In addition, lipid peroxidation was decreased and expression of GPX4 was increased in the HET0016-treated ICH group. The mitogen-activated protein kinase pathway also was inhibited by HET0016 in vivo. These results indicate that 20-HETE contributes to ICH-induced acute brain injury in part by activating ferroptosis pathways, thereby providing an upstream target for inhibiting ferroptosis.
DISCOHAT: An Acronym to Describe the Spectrum of Symptoms Related to Bilateral Vestibulopathy
Authors: Paredis Sophie , van Stiphout Lisa , Remmen Eva , Strupp Michael , Gerards Marie-Cecile , Kingma Herman , Van Rompaey Vincent , Fornos Angelica-Perez , Guinand Nils , van de Berg Raymond
Published: November 2021

Objective: To assess the prevalence of each symptom listed in the acronym DISCOHAT (worsening of symptoms in Darkness and/or uneven ground, Imbalance, Supermarket effect, Cognitive complaints, Oscillopsia, Head movements worsen symptoms, Autonomic complaints, and Tiredness) in patients with bilateral vestibulopathy (BVP), compared to patients with unilateral vestibulopathy (UVP).

Methods: A descriptive case-control study was performed on BVP and UVP patients who were evaluated for their vestibular symptoms by two of the authors (RvdB, MCG) at a tertiary referral center, between 2017 and 2020. During history taking, the presence of each DISCOHAT symptom was checked and included in the electronic health record. Presence of a symptom was categorized into: “present,” “not present,” and “missing.”

Results: Sixty-six BVP patients and 144 UVP patients were included in this study. Prevalence of single DISCOHAT symptoms varied from 52 to 92% in BVP patients and 18–75% in UVP patients. Patients with BVP reported “worsening of symptoms in darkness,” “imbalance,” “oscillopsia,” and “worsening of symptoms with fast head movements” significantly more than UVP patients (p ≤ 0.004).

Conclusion: The DISCOHAT acronym is able to capture a wide spectrum of symptoms related to vestibulopathy, while it is easy and quickly to use in clinic. Application of this acronym might facilitate a more thorough and uniform assessment of bilateral vestibulopathy, within and between vestibular clinics worldwide.
Study of Neuronal Apoptosis ceRNA Network in Hippocampal Sclerosis of Human Temporal Lobe Epilepsy by RNA-Seq
Authors: Yu Shengkun , Gu Yifei , Wang Tianyu , Mu Long , Wang Haiyang , Yan Shi , Wang Aoweng , Wang Jiabin , Liu Li , Shen Hong , Na Meng , Lin Zhiguo
Published: November 2021

Hippocampal sclerosis (HS) is one of the most common pathological type of intractable temporal lobe epilepsy (TLE), often characterized by hippocampal atrophy, neuronal apoptosis, and gliogenesis. However, the molecular mechanisms of neuronal apoptosis in patients with HS are still not fully understood. We therefore conducted a pilot study focusing on the neuronal apoptosis ceRNA network in the sclerotic hippocampus of intractable TLE patients. In this research, RNA sequencing (RNA-seq) was utilized to quantify the expression levels of lncRNAs, miRNAs, and mRNAs in TLE patients with HS (HS-TLE) and without HS (non-HS-TLE), and reverse transcription-quantitative PCR (qRT-PCR). The interactions of differential expression (DE) lncRNAs-miRNAs or DEmiRNAs-mRNAs were integrated by StarBase v3.0, and visualized using Cytoscape. Subsequently, we annotate the functions of lncRNA-associated competitive endogenous RNA (ceRNA) network through analysis of their interactions with mRNAs. RNA-seq analyses showed 381 lncRNAs, 42 miRNAs, and 457 mRNAs were dysregulated expression in HS-TLE compared to non-HS-TLE. According to the ceRNA hypothesis, 5 HS-specific ceRNA network were constructed. Among them, the core ceRNA regulatory network involved in neuronal apoptosis was constituted by 10 DElncRNAs (CDKN2B-AS1, MEG3, UBA6-AS1, etc.), 7 DEmiRNAs (hsa-miR-155-5p, hsa-miR-195-5p, hsa-miR-200c-3p, etc.), and 3 DEmRNAs (SCN2A, DYRK2, and MAPK8), which belonging to apoptotic and epileptic terms. Our findings established the first ceRNA network of lncRNA-mediated neuronal apoptosis in HS-TLE based on transcriptome sequencing, which provide a new perspective on the disease pathogenesis and precise treatments of HS.
Surgical Conversion for Initially Unresectable Locally Advanced Hepatocellular Carcinoma Using a Triple Combination of Angiogenesis Inhibitors, Anti-PD-1 Antibodies, and Hepatic Arterial Infusion Chemotherapy: A Retrospective Study
Authors: Zhang Jinliang , Zhang Xihao , Mu Han , Yu Ge , Xing Wenge , Wang Lu , Zhang Ti
Published: November 2021

Background

Recent research has shown that selected patients with initially unresectable hepatocellular carcinoma (HCC) are able to achieve conversion to resectable disease through systemic or local therapy. Combination regimens comprised of drugs with different mechanisms of action have shown better outcomes than single-drug or single-approach-based treatments; however, to date, combination regimens investigated as part of conversion therapy strategies have been two drug combinations with reported issues of relatively low surgical conversion and objective response rates. In this study, we investigated the efficacy and safety of triple combination therapy with angiogenesis inhibitors, programmed death-1 inhibitors and hepatic arterial infusion chemotherapy for surgical conversion of advanced HCC.

Methods

This was a single-center, retrospective, single-arm study of patients with unresectable HCC who received at least one cycle of triple combination therapy with an oral anti-angiogenic drug, programmed death-1 inhibitors and hepatic arterial infusion chemotherapy between August 2019 and August 2020. Endpoints included the overall response rate (ORR), surgical conversion rate, time to response and safety. Treatment response was assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST v1.1.

Results

In total, 34 patients were included in this study, of whom 25 completed treatment evaluation. The best ORR was 96.0% (24/25); 48.0% (n = 12) had a complete response, 48.0% (n = 12) had a partial response, and 4.0% (n = 1) had stable disease. The median time to response was 50.5 (95% CI, 31.02–64.00) days and the surgical conversion rate was 60% (15/25). Of the 25 patients, 56.0% (n = 14) received surgical resection and 28.0% (n = 7) had a pathologic complete response. Toxic side effects were manageable.

Conclusion

A triple combination therapy regimen of angiogenesis inhibitors, programmed death-1 inhibitors and hepatic arterial infusion chemotherapy showed significant therapeutic effect with an extremely high surgical conversion rate in patients with initially unresectable HCC.
The Prognostic and Predictive Role of Chromogranin A in Gastroenteropancreatic Neuroendocrine Tumors – A Single-Center Experience
Authors: Tsai Hui-Jen , Hsiao Chin-Fu , Chang Jeffrey S. , Chen Li-Tzong , Chao Ying-Jui , Yen Chia-Ju , Shan Yan-Shen
Published: November 2021

Chromogranin A (CgA) is a non-specific biomarker excreted by neuroendocrine tumor (NET) cells. Elevation of circulating CgA level can be detected in gastroenteropancreatic (GEP)-NET patients and has been shown to correlate with tumor burden. The prognostic and predictive roles of CgA level and the change of CgA level are controversial. In this study, we retrospectively analyzed 102 grade 1/2 GEP-NET patients with available baseline or serial follow-up CgA levels from the National Cheng Kung University Hospital to evaluate the association between circulating CgA level and the tumor extent, overall survival (OS), and tumor response prediction. The baseline characteristics, baseline CgA level, and change of CgA level during follow-up and their association was analyzed. Sixty cases had baseline CgA levels available prior to any treatment and ninety-four cases had serial follow-up CgA levels available during treatment or surveillance. Baseline CgA levels were associated with stage and sex. Higher baseline CgA levels were associated with worse OS after adjusting for sex, stage, grade, primary site, and functionality (hazard ratio=13.52, 95% confidence interval (CI), 1.06-172.47, P=0.045). The cross-sectional analysis for the change of CgA level during follow-up showed that a ≥ 40% increase of CgA meant a higher probability of developing tumor progression or recurrence than those with a < 40% increase of CgA level (odds ratio=5.04, 95% CI, 1.31-19.4, P=0.019) after adjusting for sex, age, grade, stage, and functionality. Our study results suggest that CgA may be a predictive marker for tumor burden, OS, and tumor progression in GEP-NET patients.
Retrospective Study on the Application of Enhanced Recovery After Surgery Measures to Promote Postoperative Rehabilitation in 50 Patients With Brain Tumor Undergoing Craniotomy
Authors: Feng SongShan , Xie Bo , Li ZhenYan , Zhou XiaoXi , Cheng Quan , Liu ZhiXiong , Tao ZiRong , Zhang MingYu
Published: November 2021

Objective

To investigate whether enhanced recovery after surgery (ERAS) can promote rehabilitation of patients after neurosurgical craniotomy.

Methods

The clinical data of 100 patients with brain tumor undergoing craniotomy in the Department of Neurosurgery, Xiangya Hospital, Central South University, from January 2018 to August 2020 were collected, including 50 patients in the ERAS group and 50 patients in the control group. t-Test, Wilcoxon’s rank sum test, and chi-square analysis were used to compare the clinical characteristics, prognosis, and hospitalization time between the two groups.

Results

There was no significant difference in gender, age, and other general clinical data between the two groups (p > 0.05). The days of antiemetic drugs applied in the ERAS group were less than those in the control group (1.00 vs. 2.00 days, p = 0.003), and the proportion of patients requiring analgesics was lower than that of the control group (30% vs. 52%, OR = 0.41, 95% CI 0.18–0.93, p = 0.031). The time of urinary catheter removal and that of patients starting ambulation in the ERAS group were shorter than those in the control group (16.00 vs. 24.00 h, and 1.00 vs. 2.00 days, p < 0.001, respectively); and the hospital length of stay (LOS) in the ERAS group was shorter than that in the control group (Total LOS, 13.00 vs. 15.50 days; Postoperative LOS, 7.00 vs. 10.00 days, p < 0.001). By analyzing the prognosis of patients in the ERAS group and control group, we found that there was no significant difference in postoperative complications and Karnofsky Performance Status (KPS) score 1 month after operation between the two groups.

Conclusion

The application of ERAS in craniotomy can accelerate the postoperative recovery of patients without increasing the perioperative risk, which is worthy of wide application. However, whether the ERAS measures can reduce the postoperative complications and improve the prognosis of patients still needs more large-scale case validation and multicenter collaborative study.
Hypofractionated Radiotherapy in Head and Neck Cancer Elderly Patients: A Feasibility and Safety Systematic Review for the Clinician
Authors: Piras Antonio , Boldrini Luca , Menna Sebastiano , Venuti Valeria , Pernice Gianfranco , Franzese Ciro , Angileri Tommaso , Daidone Antonino
Published: November 2021

Objective

Radiotherapy (RT) in the head and neck (H&N) site are undoubtedly the most challenging treatments for patients. Older and frail patients are not always able to tolerate it, and there are still no clear guidelines on the type of treatments to be preferred for them. The recommendations for Risk-Adapted H&N Cancer Radiation Therapy during the coronavirus disease 2019 (COVID-19) pandemic provided by the ASTRO-ESTRO consensus statement achieved a strong agreement about hypofractionated RT (HFRT). A systematic literature review was conducted in order to evaluate the feasibility and safety of HFRT for older patients affected by H&N malignancies.

Materials and Methods

A systematic database search was performed on PubMed and Embase according to Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guidelines. Original studies, case series, and case reports describing the use of HFRT (with at least 2.2 Gy fractions) in patients with mean age ≥65 years were included. The analysis was based on the type of study, number of patients, mean age, tumor site, histology, performance status (PS), RT details, concomitant chemotherapy (CT), and described clinical outcomes. All the reported doses have been calculated in equivalent dose in 2 Gy fractions (EQD2) and biologically effective dose (BED) using α/β = 10 Gy or α/β = 12 Gy.

Results

We selected 17 papers that met the inclusion criteria and divided them in 4 categories: 6 articles analyze HFRT performed twice daily in repeated cycles, 3 once a day in repeated cycles, 4 in alternative days, and the last 4 in consecutive days.

Conclusion

HFRT seems to be a good treatment with an acceptable prolonged disease control. In older patients fit for radical treatments, a 55 Gy in 20 fractions regimen can be proposed as a valid alternative to the standard fractionated RT, but there are a multitude of hypofractionated regimens, ranging from single fraction, quad shot, and 1-, 2-, 3-, 4-, and 5-week schedules that all may be appropriate. The correct regimen for a patient depends on many factors, and it represents the result of a more specific and complex decision.
Neuroimaging Features of Optic Nerve Hemangioblastoma Identified by Conventional and Advanced Magnetic Resonance Techniques: A Case Report and Literature Review
Authors: Duan Meihan , Yang Lie , Kang Jun , Wang Renzhi , You Hui , Feng Ming
Published: November 2021

Optic nerve hemangioblastoma is a very rare benign tumor with only 39 reported cases by now. It appears to be hyperintense on T2-weighted images with a significant enhancement on contrast scans, which are similar to glioma and meningioma. Due to the lack of specificity in MRI manifestations, optic nerve hemangioblastoma is often misdiagnosed. To provide new insights into differential diagnosis of optic nerve hemangioblastoma, we report for the first time an optic nerve hemangioblastoma case employing advanced magnetic resonance techniques including diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) maps, and magnetic resonance angiography (MRA). In addition, we have collected all reported optic nerve hemangioblastoma cases and reviewed their neuroimaging findings by MRI and angiography. Our results show that solid-type tumor is the dominant form of optic nerve hemangioblastoma and extensive edema is widely observed. These findings are surprisingly contrary to manifestations of cerebellar hemangioblastoma. Besides the structural features, quantitative indexes including ADC and relative cerebral blood volume (rCBV) ratio, which are significantly elevated in cerebellar hemangioblastoma, may also shed a light on the preoperative diagnosis of hemangioblastoma of optic nerve. Finally, we discuss the critical neuroimaging features in the differential diagnosis between optic nerve hemangioblastoma from optic pathway glioma and optic nerve sheath meningioma.
Neonatal Problems and Infancy Growth of Term SGA Infants: Does “SGA” Definition Need to Be Re-evaluated?
Authors: Abali Saygin , Beken Serdar , Albayrak Eda , Inamlik Aysegul , Bulum Burcu , Bulbul Ezgi , Eksi Gulten Zeynep , Ay Zeynep Alize , Karabay Melis , Kaya Didem , Halici Muge , Semiz Serap , Korkmaz Ayse
Published: November 2021

Introduction: The exact definition of small-for-gestational-age (SGA) infant is still controversial among clinicians. In this study, we aimed to understand which definition is better in terms of establishing both early postnatal problems and growth. In this way, we compared early neonatal problems and infancy growth of term infants with birth weight (BW) < -2 SDS and with BW between 10th percentile (−1.28 SDS) and −2 SDS.

Methods: A single center retrospective cohort study was conducted. Preterm infants, multiple gestations and newborns with any congenital anomalies were excluded from the study. Study group was defined as Group 1 (n = 37), infants BW < −2.00 SDS; Group 2 (n = 129), between −1.28 and −2.00 SDS; and Group 3 (n = 137), randomly selected newborns with optimal-for-gestational-age (BW between −0.67 and +0.67 SDS) as a control group.

Results: The incidence of severe hypoglycemia was highest in Group 1 (%10.8) and Group 2 and 3 had similar rates of severe hypoglycemia (0.8 and 0.7%, respectively). The incidence of polycythemia was 5.4% in Group 1 and was significantly higher than Group 3 (0.0%) while it was 2.3% in Group 2. Short stature (length < −2 SDS) ratio at the age of 1 and 2 years were similar in each group. Overweight/obesity ratio at the age of 1 were 9.5, 20.8 and 16.7% in each group, respectively (p = 0.509).

Conclusion: This study was planned as a pilot study to determine potential differences in the problems of hypoglycemia, polycythemia, and growth according to the differences in definition. Short term disturbances such as hypoglycemia and polycythemia are found to be higher in infants with a BW SDS below −2. From this point of view, of course, it will not be possible to change the routine applications immediately, however this study will be an initiative for discussions by making long-term studies.
Advantages of Tailored Isotretinoin Treatment in Moderate to Severe Acne: Real-Life Data
Authors: Skroza Nevena , Tolino Ersilia , Balduzzi Veronica , Bernardini Nicoletta , Mambrin Alessandra , Marchesiello Anna , Marraffa Federica , Rossi Giovanni , Volpe Salvatore , Proietti Ilaria , Potenza Concetta
Published: November 2021

This retrospective single-center study analyzes the efficacy and safety of isotretinoin for the treatment of moderate to severe acne in real-life clinical practice, particularly with regard to acne severity, isotretinoin cumulative dosage, and patients’ gender. The results suggest the opportunity of an early isotretinoin systemic treatment in patients affected by moderate acne and emphasize the importance of an appropriate dose adjustment in order to minimize adverse events.
Peptibody Based on FGFR1-Binding Peptides From the FGF4 Sequence as a Cancer-Targeting Agent
Authors: Jendryczko Karolina , Rzeszotko Jakub , Krzyscik Mateusz Adam , Szymczyk Jakub , Otlewski Jacek , Szlachcic Anna
Published: November 2021

Targeted therapies are a promising alternative to conventional chemotherapy, with an increasing number of therapeutics targeting specific molecular aberrancies in cancer cells. One of the emerging targets for directed cancer treatments is fibroblast growth factor receptors (FGFRs), which are known to be involved in the pathogenesis and progression of multiple cancer types, specially in lung, bladder, and breast cancers. Here, we are demonstrating the development of the FGFR1-targeting agent based on the interactome screening approach, based on the isolation of binding regions from ligands interacting with the receptor. The parallel analysis by FGFR1 pull-down of chymotryptic peptides coupled with MS analysis, and PepSpot analysis yielded equivalent peptide sequences from FGF4, one of the FGFR1 ligands. Three sequences served as a basis for peptibody (Fc-fusion) generation, to overcome clinical limitations of peptidic agents, and two of them showed favorable FGFR1-binding in vitro and FGFR1-dependent internalization into cells. To validate if developed FGFR1-targeting peptibodies can be used for drug delivery, similar to the well-established concept of antibody–drug conjugates (ADCs), peptibodyF4_1 was successfully conjugated with monomethylauristatin E (MMAE), and has shown significant and specific toxicity toward FGFR1-expressing lung cancer cell lines, with nanomolar EC50 values. Essentially, the development of new effective FGFR1 binders that comprise the naturally occurring FGFR-recognition peptides and Fc region ensuring high plasma stability, and long bloodstream circulation is an interesting strategy expanding targeted anticancer agents’ portfolio. Furthermore, identifying peptides effectively binding the receptor from sequences of its ligands is not limited to FGFRs and is an approach versatile enough to be a basis for a new peptide/peptibodies development strategy.
Nanotechnology for Targeted Therapy of Atherosclerosis
Authors: Hossaini Nasr Seyedmehdi , Huang Xuefei
Published: November 2021

Atherosclerosis is the major cause of heart attack and stroke that are the leading causes of death in the world. Nanomedicine is a powerful tool that can be engineered to target atherosclerotic plaques for therapeutic and diagnosis purposes. In this review, advances in designing nanoparticles with therapeutic effects on atherosclerotic plaques known as atheroprotective nanomedicine have been summarized to stimulate further development and future translation.
Detection of Drug-Induced Thrombocytopenia Signals in Children Using Routine Electronic Medical Records
Authors: Nie Xiaolu , Jia Lulu , Peng Xiaoxia , Zhao Houyu , Yu Yuncui , Chen Zhenping , Zhang Liqiang , Cheng Xiaoling , Lyu Yaqi , Cao Wang , Wang Xiaoling , Ni Xin , Zhan Siyan
Published: November 2021

Background: Drug-induced thrombocytopenia (DITP) is a severe adverse reaction and a significantly under-recognized clinical problem in children. However, for post-marketing pharmacovigilance purposes, detection of DITP signals is crucial. This study aimed to develop a signal detection model for DITP using the pediatric electronic medical records (EMR) data.

Methods: This study used the electronic medical records collected at Beijing Children’s Hospital between 2009 and 2020. A two-stage modeling method was developed to detect the signal of DITP. In the first stage, we calculated the crude incidence by mining cases of thrombocytopenia to select the potential suspected drugs. In the second stage, we constructed propensity score–matched retrospective cohorts of specific screened drugs from the first stage and estimated the odds ratio (OR) and 95% confidence interval (CI) using conditional logistic regression models. The novelty of the signal was assessed by current evidence.

Results: In the study, from a total of 839 drugs, 21 drugs were initially screened as potentially inducing thrombocytopenia. In total, we identified 18 positive DITP associations. Of these, potential DITP risk of nystatin (OR: 1.75, 95% CI: 1.37–2.22) and latamoxef sodium (OR: 1.61, 95% CI: 1.38–1.88) were two new DITP signals in both children and adults. Six associations between thrombocytopenia and drugs including imipenem (OR: 1.69, 95% CI: 1.16–2.45), teicoplanin (OR: 4.75, 95% CI: 3.33–6.78), fusidic acid (OR: 2.81, 95% CI: 2.06–3.86), ceftizoxime sodium (OR: 1.83, 95% CI: 1.36–2.45), ceftazidime (OR: 2.16, 95% CI: 1.58–2.95), and cefepime (OR: 5.06, 95% CI: 3.77–6.78) were considered as new signals in children.

Conclusion: This study developed a two-stage algorithm to detect safety signals of DITP and found eighteen positive signals of DITP, including six new signals in a pediatric population. This method is a promising tool for pharmacovigilance based on EMR data.
Influence of CaO Content on the Fly Ash–Lime System Hydrothermal Synthesis Reaction Under Autoclave Curing
Authors: Zhu Chenhui , Lou Yilong , Shen Xuemei , Xu Hesi , Yang Jie
Published: November 2021

As a substitute for traditional Portland cement, the development and research of “low-temperature-synthesized fly ash cement” has been receiving extensive attention. This study explores the effects of calcium oxide content on the fly ash–lime system hydrothermal synthesis reaction under autoclave curing, focusing on the effects of CaO content on the strength of the cement paste. The changes in phase composition, microstructure, and morphology were characterized using X-ray diffraction and scanning electron microscopy (SEM) analysis. The results show that with an increase in the CaO content, the amounts of β-C2S and C12A7 in the gelling material also increase. However, when the CaO content is very high, the amounts of β-C2S and C12A7 in the gelling material no longer increase, and the strength is lost.
An Induced Mutation in HvRECQL4 Increases the Overall Recombination and Restores Fertility in a Barley HvMLH3 Mutant Background
Authors: Arrieta Mikel , Macaulay Malcolm , Colas Isabelle , Schreiber Miriam , Shaw Paul D. , Waugh Robbie , Ramsay Luke
Published: November 2021

Plant breeding relies on the meiotic recombination or crossing over to generate the new combinations of the alleles along and among the chromosomes. However, crossing over is constrained in the crops such as barley by a combination of the low frequency and biased distribution. In this study, we attempted to identify the genes that limit the recombination by performing a suppressor screen for the restoration of fertility to the semi-fertile barley mutant desynaptic10 (des10), carrying a mutation in the barley ortholog of MutL-Homolog 3 (HvMLH3), a member of the MutL-homolog (MLH) family of DNA mismatch repair genes. des10 mutants exhibit reduced recombination and fewer chiasmata, resulting in the loss of obligate crossovers (COs) leading to chromosome mis-segregation. We identified several candidate suppressor lines and confirmed their restored fertility in an Hvmlh3 background in the subsequent generations. We focus on one of the candidate suppressor lines, SuppLine2099, which showed the most complete restoration of fertility. We characterized this line by using a target-sequence enrichment and sequencing (TENSEQ) capture array representing barley orthologs of 46 meiotic genes. We found that SuppLine2099 contained a C/T change in the anti-CO gene RecQ-like helicase 4 (RECQL4) resulting in the substitution of a non-polar glycine to a polar aspartic acid (G700D) amino acid in the conserved helicase domain. Single nucleotide polymorphism (SNP) genotyping of F3 populations revealed a significant increase in the recombination frequency in lines with Hvrecql4 in the Hvmlh3 background that was associated with the restoration of fertility. The genotyping also indicated that there was nearly double the recombination levels in homozygous Hvrecql4 lines compared to the wild type (WT). However, we did not observe any significant change in the distribution of CO events. Our results confirm the anti-CO role of RECQL4 in a large genome cereal and establish the possibility of testing the utility of increasing recombination in the context of traditional crop improvement.
Optimum Planting Density Improves Resource Use Efficiency and Yield Stability of Rainfed Maize in Semiarid Climate
Authors: Zhang Yuanhong , Xu Zonggui , Li Jun , Wang Rui
Published: November 2021

Increasing planting density is an effective strategy for improving maize productivity, but grain yield does not increase linearly with the increase in plant density, especially in semiarid environments. However, how planting density regulates the integrated utilization of key input resources (i.e., radiation, water, and nutrients) to affect maize production is not clear. To evaluate the effects of planting density and cultivar on maize canopy structure, photosynthetic characteristics, yield, and resource use efficiency, we conducted a successive field experiment from 2013 to 2018 in Heyang County (Shaanxi Province, China) using three different cultivars [i.e., Yuyu22 (C1), Zhengdan958 (C2), and Xianyu335 (C3)] at four planting densities [i.e., 52,500 (D1), 67,500 (D2), 82,500 (D3), and 97,500 (D4) plants ha–1]. Increasing planting density significantly increased the leaf area index (LAI) and the amount of intercepted photosynthetically active radiation (IPAR), thereby promoting plant growth and crop productivity. However, increased planting density reduced plant photosynthetic capacity [net photosynthetic rate (Pn)], stomatal conductance (Gc), and leaf chlorophyll content. These alterations constitute key mechanisms underlying the decline in crop productivity and yield stability at high planting density. Although improved planting density increased IPAR, it did not promote higher resource use efficiency. Compared with the D1 treatment, the grain yield, precipitation use efficiency (PUE), radiation use efficiency (RUE), and nitrogen use efficiency (NUE) increased by 5.6–12.5%, 2.8–7.1%, and −2.1 to 1.6% in D2, D3, and D4 treatments, respectively. These showed that pursuing too high planting density is not a desirable strategy in the rainfed farming system of semiarid environments. In addition, density-tolerant cultivars (C2 and C3) showed better canopy structure and photosynthetic capacity and recorded higher yield stability and resource use efficiency. Together, these results suggest that growing density-tolerant cultivars at moderate planting density could serve as a promising approach for stabilizing grain yield and realizing the sustainable development of agriculture in semiarid regions.
MdBBX21, a B-Box Protein, Positively Regulates Light-Induced Anthocyanin Accumulation in Apple Peel
Authors: Zhang Bo , Zhu Zhen-Zhen , Qu Dong , Wang Bo-Chen , Hao Ni-Ni , Yang Ya-Zhou , Yang Hui-Juan , Zhao Zheng-Yang
Published: November 2021

The red coloration of apple (Malus × domestica Borkh.) is due to the accumulation of anthocyanins in the fruit peel. Light is essential for anthocyanin biosynthesis in apple. In this study, we performed a transcriptome sequencing (RNA-seq) analysis of apple fruit exposed to light after unbagging. The identified differentially expressed genes included MdBBX21, which is homologous to Arabidopsis BBX21, suggesting it may be involved in light-induced anthocyanin biosynthesis. Additionally, MdBBX21 was localized in the nucleus and its gene was expressed earlier than MdMYB1 in apple peel treated with light. Overexpressing MdBBX21 in Arabidopsis and apple calli under light increased anthocyanin accumulation. Dual-luciferase and yeast one-hybrid assays confirmed that MdBBX21 binds to the MdHY5, MdBBX20, and MdBBX22-1/2 promoters and induces expression. At the same time, MdHY5 can also activate the expression of MdBBX21. Furthermore, bimolecular fluorescence complementation and yeast two-hybrid assays demonstrated that MdBBX21 can interact with MdHY5. This interaction can significantly enhance MdMYB1 promoter activity. These findings clarify the molecular mechanism by which MdBBX21 positively regulates light-induced anthocyanin accumulation in apple.
Arbuscular Mycorrhizal Fungus Alters Root System Architecture in Camellia sinensis L. as Revealed by RNA-Seq Analysis
Authors: Chen Weili , Ye Tao , Sun Qinyu , Niu Tingting , Zhang Jiaxia
Published: November 2021

Arbuscular mycorrhizal fungus (AMF), forming symbiosis with most terrestrial plants, strongly modulates root system architecture (RSA), which is the main characteristic of root in soil, to improve plant growth and development. So far, the studies of AMF on tea plant seedlings are few and the relevant molecular mechanism is not deciphered. In this study, the 6-month-old cutting seedlings of tea plant cultivar “Wancha No.4” were inoculated with an AMF isolate, Rhizophagus intraradices BGC JX04B and harvested after 6 months of growth. The indexes of RSA and sugar contents in root were determined. The transcriptome data in root tips of mycorrhizal and non-mycorrhizal cutting seedlings were obtained by RNA-sequence (Seq) analysis. The results showed that AMF significantly decreased plant growth, but increased the sucrose content in root and the higher classes of lateral root (LR) formation (third and fourth LR). We identified 2047 differentially expressed genes (DEGs) based on the transcriptome data, and DEGs involved in metabolisms of phosphorus (42 DEGs), sugar (39), lipid (67), and plant hormones (39) were excavated out. Variation partitioning analysis showed all these four categories modulated the RSA. In phosphorus (P) metabolism, the phosphate transport and release (DEGs related to purple acid phosphatase) were promoted by AMF inoculation, while DEGs of sugar transport protein in sugar metabolism were downregulated. Lipid metabolism might not be responsible for root branching but for AMF propagation. With respect to phytohormones, DEGs of auxin (13), ethylene (14), and abscisic acid (5) were extensively affected by AMF inoculation, especially for auxin and ethylene. The further partial least squares structural equation modeling analysis indicated that pathways of P metabolism and auxin, as well as the direct way of AMF inoculation, were of the most important in AMF promoting root branching, while ethylene performed a negative role. Overall, our data revealed the alterations of genome-wide gene expression in tea plant roots after inoculation with AMF and provided a molecular basis for the regulatory mechanism of RSA (mainly root branching) changes induced by AMF.
The Dynamics of Social Movements in Unrecognized States—A Comparative Study
Authors: Ulas Hilmi
Published: November 2021

In the political realm, our world is currently experiencing both a massive decline in democracies as well as the quality of democratic regimes in all geographical regions, and a rise in pro-democracy social change movements. Meanwhile, extant scholarly research emphasizes that social movements can contribute to changes in political regimes, such as the undermining of authoritarian ones or simply causing a circulation of the elite. Nevertheless, there is a gap in the scholarly knowledge regarding when political activism becomes effective or can even take place without total annihilation in the context of unrecognized states. To address this gap, studying cases of pro-democracy movements in unrecognized states through a comparative schema is the most effective methodology. In these cases, some variables that affect movement outcomes, such as international diplomatic relations, NGO activity, multinational company pressures, etc. are more restricted due to these states lacking official diplomatic capacity. Therefore, in unrecognized states, domestic political-economic factors are primal and their effects can be observed much more easily, which then lends some tentatively generalizable insights as well. For the purposes of this paper, I will consider the emergence and ultimate outcomes of pro-democracy movements in three unrecognized states: North Cyprus, Abkhazia, and Taiwan. All three cases in comparative perspective can shed light on the dynamics of how nonviolent, pro-democracy movements unfold under the authoritarian-leaning settings of unrecognized states with minimal international interaction or oversight.