bluuebunny/crossref_metadata_2025 huggingface dataset:
One-Year Follow-Up of Corneal Biomechanical Changes After Accelerated Transepithelial Corneal Cross-Linking in Pediatric Patients With Progressive Keratoconus
Authors: Jian Weijun , Tian Mi , Zhang Xiaoyu , Sun Ling , Shen Yang , Li Meiyan , Zhou Xingtao
Published: July 2021

Aims: This study aimed to investigate the corneal biomechanical changes and topographic outcomes of accelerated transepithelial corneal cross-linking (ATE-CXL) in pediatric progressive keratoconus.

Methods: In this prospective longitudinal study, 31 eyes of 28 pediatric patients with keratoconus (21 boys and 7 girls; mean age, 14.35 ± 2.68 years) undergoing ATE-CXL (epithelium-on procedure with 45 mW/cm2 for 320 s) were included. Corvis ST was used to measure dynamic corneal response parameters at baseline and at 12 month after ATE-CXL. Corneal keratometry and corneal thickness were measured using Pentacam pre-operatively and 1, 6, and 12 month post-operatively.

Results: No serious complications occurred during or after ATE-CXL. The maximum keratometry values were 60.10 ± 7.51 D pre-operatively and 61.42 ± 8.92, 61.17 ± 7.96, and 60.02 ± 7.58 D at 1, 6, and 12 month after ATE-CXL (P > 0.05), respectively. Corneal thickness remained stable during the 12-month follow-up (P > 0.05). At post-operative 12 month, first applanation time (P < 0.001), first applanation length (P = 0.004), second applanation velocity (P = 0.014), highest concavity time (P = 0.022), and radius of curvature at highest concavity (P = 0.031) increased significantly. The value of stiffness parameter at first applanation was significantly increased from 57.70 ± 27.57 pre-operatively to 63.36 ± 27.09 at 12 months after ATE-CXL (P = 0.018).

Conclusions: ATE-CXL is safe and effective in stabilizing the progression of pediatric keratoconus. Changes in corneal biomechanical response consistent with stiffening following ATE-CXL were observed in pediatric patients with keratoconus.
Risk Potential for Organ Dysfunction Associated With Sodium Bicarbonate Therapy in Critically Ill Patients With Hemodynamic Worsening
Authors: Wang Tiehua , Yi Lingxian , Zhang Hua , Wang Tianhao , Xi Jingjing , Zeng Lin , He Junlin , Zhang Zhongheng , Ma Penglin
Published: July 2021

Background: The role of sodium bicarbonate therapy (SBT) remains controversial. This study aimed to investigate whether hemodynamic status before SBT contributed to the heterogeneous outcomes associated with SBT in acute critically ill patients.

Methods: We obtained data from patients with metabolic acidosis from the Medical Information Mart for Intensive Care (MIMIC)-III database. Propensity score matching (PSM) was applied to match the SBT group with the control group. Logistic regression and Cox regression were used to analyze a composite of newly “developed or exacerbated organ dysfunction” (d/eOD) within 7 days of ICU admission and 28-day mortality associated with SBT for metabolic acidosis.

Results: A total of 1,765 patients with metabolic acidosis were enrolled, and 332 pairs obtained by PSM were applied to the final analyses in the study. An increased incidence of newly d/eOD was observed in the SB group compared with the control group (54.8 vs. 44.6%, p < 0.01). Multivariable logistic regression indicated that the adjusted OR of SBT for this composite outcome was no longer significant [OR (95% CI): 1.39 (0.9, 1.85); p = 0.164]. This effect of SBT did not change with the quintiles stratified by pH. Interestingly, SBT was associated with an increased risk of the composite of newly d/eOD in the subgroup of patients with worsening hemodynamics before SBT [adjusted OR (95% CI): 3.6 (1.84, 7.22), p < 0.001]. Moreover, the risk potential for this composite of outcomes was significantly increased in patients characterized by both worsening [adjusted OR (95% CI): 2.91 (1.54, 5.47), p < 0.001] and unchanged hemodynamics [adjusted OR (95% CI): 1.94 (1.01, 3.72), p = 0.046] compared to patients with improved hemodynamics before SBT. Our study failed to demonstrate an association between SBT and 28-day mortality in acute critically ill patients with metabolic acidosis.

Conclusions: Our findings did not demonstrate an association between SBT and outcomes in critically ill patients with metabolic acidosis. However, patients with either worsening or unchanged hemodynamic status in initial resuscitation had a significantly higher risk potential of newly d/eOD subsequent to SBT.
Effects of Roxadustat on the Anemia and Iron Metabolism of Patients Undergoing Peritoneal Dialysis
Authors: Hirai Keiji , Nonaka Hiroaki , Ueda Moeka , Morino Junki , Kaneko Shohei , Minato Saori , Mutsuyoshi Yuko , Yanai Katsunori , Ishii Hiroki , Matsuyama Momoko , Kitano Taisuke , Aomatsu Akinori , Miyazawa Haruhisa , Ito Kiyonori , Ueda Yuichiro , Ookawara Susumu , Morishita Yoshiyuki
Published: July 2021

Background: We investigated the effects of roxadustat on the anemia, iron metabolism, peritoneal membrane function, and residual renal function; and determined the factors associated with the administration of roxadustat in patients who were undergoing peritoneal dialysis.

Methods: We retrospectively analyzed the changes in hemoglobin, serum ferritin, transferrin saturation (TSAT), 4-h dialysate/plasma creatinine, and renal weekly urea clearance over the 24 weeks following the change from an erythropoiesis-stimulating agent (ESA) to roxadustat in 16 patients who were undergoing peritoneal dialysis and had anemia (Roxadustat group). Twenty-three peritoneal dialysis patients who had anemia and continued ESA served as a control group (ESA group).

Results: There were no significant differences in hemoglobin, serum ferritin, TSAT, 4-h dialysate/plasma creatinine, or renal weekly urea clearance between the two groups at baseline. The hemoglobin concentration was significantly higher in the Roxadustat group than in the ESA group after 24 weeks (11.6 ± 1.0 g/dL vs. 10.3 ± 1.1 g/dL, p < 0.05), whereas the ferritin concentration and TSAT were significantly lower (139.5 ± 102.0 ng/mL vs. 209.2 ± 113.1 ng/mL, p < 0.05; and 28.1 ± 11.5% vs. 44.8 ± 10.4%, p < 0.05, respectively). The changes in 4-h dialysate/plasma creatinine and renal weekly urea clearance did not differ between the two groups. Linear regression analysis revealed that the serum potassium concentration correlated with the dose of roxadustat at 24 weeks (standard coefficient = 0.580, p = 0.019).

Conclusion: Roxadustat may improve the anemia and reduce the serum ferritin and TSAT of the peritoneal dialysis patients after they were switched from an ESA, without association with peritoneal membrane function or residual renal function.
Attitudes Toward COVID-19 Vaccines in Chinese Adolescents
Authors: Cai Hong , Bai Wei , Liu Shou , Liu Huanzhong , Chen Xu , Qi Han , Liu Rui , Cheung Teris , Su Zhaohui , Ng Chee H. , Xiang Yu-Tao
Published: July 2021

Background: As COVID-19 vaccination programs are being implemented widely, it is important to examine the attitudes of adolescents toward the COVID-19 vaccine and its uptake. The aim of this study was to examine the acceptance of and attitudes toward COVID-19 vaccines, and their associated factors among adolescents in China.

Methods: This was a cross-sectional, observational study conducted between November 27, 2020 and March 12, 2021 using snowball sampling method. Basic sociodemographic characteristics, health-related information, severity of depressive and anxiety symptoms, and attitudes and behavior toward COVID-19 vaccines were assessed.

Results: Overall, 1,057 adolescents participated in this study, yielding a response rate of 89.3%. There were 799 (75.59%) [95% Confidence Interval (CI) 73.00–78.18%] adolescents who would accept future COVID-19 vaccination. Binary logistic regression analysis revealed that adolescents who previously heard about COVID-19 vaccines (P = 0.001, odds ratio (OR) = 1.90, 95%CI:1.32–2.74), who thought that COVID-19 vaccines could protect them from COVID-19 infection (P = 0.002, OR = 2.93, 95%CI: 1.49–5.70), and those who encouraged their family members and friends to get vaccinated (P < 0.001, OR = 12.19, 95%CI: 6.78–21.92) and who believed that vaccines are safe (P = 0.012, OR = 3.94, 95%CI: 1.36–11.44) were more likely to accept future COVID-19 vaccination. In addition, younger adolescents (P = 0.003, OR = 0.93, 95%CI: 0.89–0.98) were more likely to accept future COVID-19 vaccines than older adolescents.

Conclusions: In conclusion, Chinese adolescents appeared to have positive attitudes toward COVID-19 vaccines. It is important to increase public confidence and knowledge regarding the efficacy and safety of COVID-19 vaccines to maximize the success of vaccination programs.
Breaking Therapeutic Inertia With Alirocumab in an 80-Year-Old Patient With Severe Hypercholesterolemia: A Case Report
Authors: Dardano Angela , Daniele Giuseppe , Penno Giuseppe , Miccoli Roberto , Del Prato Stefano
Published: July 2021

Background: Therapeutic inertia, defined as the failure to initiate or intensify therapy in a timely manner as per evidence-based clinical guidelines, is an important barrier limiting optimal care in the elderly. Therefore, overcoming therapeutic inertia is the core challenge when dealing with geriatric patients.

Case Description: The patient was an 80-year-old man that attended our Outpatient Lipid Clinic (Pisa University Hospital) because of persistent high LDL cholesterol (LDLc) levels in a setting of a statin contraindication. He underwent five percutaneous coronary angioplasties with drug-eluting stents. In 2014, upon starting treatment with rosuvastatin for LDLc level of 7.59 mmol/L, the patient was admitted to the Emergency Room for a presumptive diagnosis of rhabdomyolysis (creatine kinase 6685 U/L) secondary to statin. Patient developed acute kidney injury treated with dialysis. After resolution, he was discharged with ezetimibe (10 mg daily). This treatment however failed to effectively reduce LDLc levels that ranged between 5.9 and 6.6 mmol/L for the ensuing 4-years. In 2018, at the time of our evaluation, in consideration of the age, we performed a comprehensive geriatric assessment that showed good functional and mental status supporting a reliable treatment with a proprotein convertase subtilisin–kexin type 9 inhibitor. Therefore, alirocumab was prescribed as add-on to ezetimibe. At 24-month follow-up, the geriatric assessment showed no significant changes, and alirocumab was well-tolerated. LDLc was 82% lower as compared to baseline values (from 6.6 to 1.2 mmol/L).

Conclusions: This report describes a case of therapeutic inertia despite a very high-risk profile. It is also instrumental in highlightening that appropriate intensification of therapy in an elderly patient at high cardiovascular risk, by means of a patient-centered approach, may allow reaching therapeutic targets and overcoming the condition of therapeutic inertia.
Post-keratoplasty Infectious Keratitis: Epidemiology, Risk Factors, Management, and Outcomes
Authors: Song Anna , Deshmukh Rashmi , Lin Haotian , Ang Marcus , Mehta Jodhbir S. , Chodosh James , Said Dalia G. , Dua Harminder S. , Ting Darren S. J.
Published: July 2021

Post-keratoplasty infectious keratitis (PKIK) represents a unique clinical entity that often poses significant diagnostic and therapeutic challenges. It carries a high risk of serious complications such as graft rejection and failure, and less commonly endophthalmitis. Topical corticosteroids are often required to reduce the risk of graft rejection but their use in PKIK may act as a double-edged sword, particularly in fungal infection. The increased uptake in lamellar keratoplasty in the recent years has also led to complications such as graft-host interface infectious keratitis (IIK), which is particularly difficult to manage. The reported incidence of PKIK differs considerably across different countries, with a higher incidence observed in developing countries (9.2–11.9%) than developed countries (0.02–7.9%). Common risk factors for PKIK include the use of topical corticosteroids, suture-related problems, ocular surface diseases and previous corneal infection. PKIK after penetrating keratoplasty or (deep) anterior lamellar keratoplasty is most commonly caused by ocular surface commensals, particularly Gramme-positive bacteria, whereas PKIK after endothelial keratoplasty is usually caused by Candida spp. Empirical broad-spectrum antimicrobial treatment is the mainstay of treatment for both PKIK, though surgical interventions are required in medically refractory cases (during the acute phase) and those affected by visually significant scarring (during the late phase). In this paper, we aim to provide a comprehensive overview on PKIK, encompassing the epidemiology, risk factors, causes, management and outcomes, and to propose a treatment algorithm for systematically managing this challenging condition.
The Effect of Secondary Metabolites Produced by Serratia marcescens on Aedes aegypti and Its Microbiota
Authors: Heu Katy , Romoli Ottavia , Schönbeck Johan Claes , Ajenoe Rachel , Epelboin Yanouk , Kircher Verena , Houël Emeline , Estevez Yannick , Gendrin Mathilde
Published: July 2021

Serratia marcescens is a bacterial species widely found in the environment, which very efficiently colonizes mosquitoes. In this study, we isolated a red-pigmented S. marcescens strain from our mosquito colony (called S. marcescens VA). This red pigmentation is caused by the production of prodigiosin, a molecule with antibacterial properties. To investigate the role of prodigiosin on mosquito-S. marcescens interactions, we produced two white mutants of S. marcescens VA by random mutagenesis. Whole genome sequencing and chemical analyses suggest that one mutant has a nonsense mutation in the gene encoding prodigiosin synthase, while the other one is deficient in the production of several types of secondary metabolites including prodigiosin and serratamolide. We used our mutants to investigate how S. marcescens secondary metabolites affect the mosquito and its microbiota. Our in vitro tests indicated that S. marcescens VA inhibits the growth of several mosquito microbiota isolates using a combination of prodigiosin and other secondary metabolites, corroborating published data. This strain requires secondary metabolites other than prodigiosin for its proteolytic and hemolytic activities. In the mosquito, we observed that S. marcescens VA is highly virulent to larvae in a prodigiosin-dependent manner, while its virulence on adults is lower and largely depends on other metabolites.
The Compressed Vocabulary of Microbial Life
Authors: Caetano-Anollés Gustavo
Published: July 2021

Communication is an undisputed central activity of life that requires an evolving molecular language. It conveys meaning through messages and vocabularies. Here, I explore the existence of a growing vocabulary in the molecules and molecular functions of the microbial world. There are clear correspondences between the lexicon, syntax, semantics, and pragmatics of language organization and the module, structure, function, and fitness paradigms of molecular biology. These correspondences are constrained by universal laws and engineering principles. Macromolecular structure, for example, follows quantitative linguistic patterns arising from statistical laws that are likely universal, including the Zipf’s law, a special case of the scale-free distribution, the Heaps’ law describing sublinear growth typical of economies of scales, and the Menzerath–Altmann’s law, which imposes size-dependent patterns of decreasing returns. Trade-off solutions between principles of economy, flexibility, and robustness define a “triangle of persistence” describing the impact of the environment on a biological system. The pragmatic landscape of the triangle interfaces with the syntax and semantics of molecular languages, which together with comparative and evolutionary genomic data can explain global patterns of diversification of cellular life. The vocabularies of proteins (proteomes) and functions (functionomes) revealed a significant universal lexical core supporting a universal common ancestor, an ancestral evolutionary link between Bacteria and Eukarya, and distinct reductive evolutionary strategies of language compression in Archaea and Bacteria. A “causal” word cloud strategy inspired by the dependency grammar paradigm used in catenae unfolded the evolution of lexical units associated with Gene Ontology terms at different levels of ontological abstraction. While Archaea holds the smallest, oldest, and most homogeneous vocabulary of all superkingdoms, Bacteria heterogeneously apportions a more complex vocabulary, and Eukarya pushes functional innovation through mechanisms of flexibility and robustness.
High Prevalence of Extended-Spectrum Beta-Lactamases in Escherichia coli Strains Collected From Strictly Defined Community-Acquired Urinary Tract Infections in Adults in China: A Multicenter Prospective Clinical Microbiological and Molecular Study
Authors: Jia Peiyao , Zhu Ying , Li Xue , Kudinha Timothy , Yang Yang , Zhang Ge , Zhang Jingjia , Xu Yingchun , Yang Qiwen
Published: July 2021

Objective

The objective of the study was to investigate the antimicrobial susceptibility and extended-spectrum beta-lactamase (ESBL) positive rates of Escherichia coli from community-acquired urinary tract infections (CA-UTIs) in Chinese hospitals.

Materials and Methods

A total of 809 E. coli isolates from CA-UTIs in 10 hospitals (5 tertiary and 5 secondary hospitals) from different regions in China were collected during the period 2016–2017 according to the strict inclusion criteria. Antimicrobial susceptibility testing was carried out by standard broth microdilution method. Isolates were categorized as ESBL-positive, ESBL-negative, and ESBL-uncertain groups according to the CLSI recommended phenotypic screening method. ESBL and AmpC genes were amplified and sequenced on ESBL-positive and ESBL-uncertain isolates.

Results

The antimicrobial agents with susceptibility rates of greater than 95% included imipenem (99.9%), colistin (99.6%), ertapenem (98.9%), amikacin (98.3%), cefmetazole (97.9%), nitrofurantoin (96%), and fosfomycin (95.4%). However, susceptibilities to cephalosporins (varying from 58.6% to 74.9%) and levofloxacin (48.8%) were relatively low. In the phenotypic detection of ESBLs, ESBL-positive isolates made up 38.07% of E. coli strains isolated from CA-UTIs, while 2.97% were ESBL-uncertain. Antimicrobial susceptibilities of imipenem, cefmetazole, colistin, ertapenem, amikacin, and nitrofurantoin against ESBL-producing E. coli strains were greater than 90%. The percentage of ESBL-producing strains was higher in male (53.6%) than in female patients (35.2%) (p < 0.001). CTX-M-14 (31.8%) was the major CTX-M variant in the ESBL-producing E. coli, followed by CTX-M-55 (23.4%), CTX-M-15 (17.5%), and CTX-M-27 (13.3%). The prevalence of carbapenem-resistant E. coli among CA-UTI isolates was 0.25% (2/809).

Conclusion

Our study indicated high prevalence of ESBL in E. coli strains from strictly defined community-acquired urinary tract infections in adults in China. Imipenem, colistin, ertapenem, amikacin, and nitrofurantoin were the most active antimicrobials against ESBL-positive E. coli isolates. blaCTX–M–14 is the predominant esbl gene in ESBL-producing and ESBL-uncertain strains. Our study indicated that the use of cephalosporins and fluoroquinolone needs to be restricted for empirical treatment of CA-UTIs in China.
Phenotypic and Genotypic Co-receptor Tropism Testing in HIV-1 Epidemic Region of Tanzania Where Multiple Non-B Subtypes Co-circulate
Authors: Judicate George P. , Barabona Godfrey , Kamori Doreen , Mahiti Macdonald , Tan Toong Seng , Ozono Seiya , Mgunya Amina Shaban , Kuwata Takeo , Matsushita Shuzo , Sunguya Bruno , Lyamuya Eligius , Tokunaga Kenzo , Ueno Takamasa
Published: July 2021

HIV human immunodeficiency virus type I (HIV-1) entry inhibitor potency is dependent on viral co-receptor tropisms and thereby tropism determination is clinically important. However, phenotypic tropisms of HIV-1 non-B subtypes have been poorly investigated and the genotypic prediction algorithms remain insufficiently validated. To clarify this issue, we recruited 52 treatment-naïve, HIV-1-infected patients in Tanzania, where multiple HIV-1 non-B subtypes co-circulate. Sequence analysis of 93 infectious envelope clones isolated from their plasma viral RNA revealed the co-circulation of subtypes A1, C, D, and inter-subtype recombinant forms (isRFs). Phenotypic tropism assays revealed that lentivirus reporters pseudotyped with 75 (80.6%) and 5 (5.4%) envelope clones could establish infection toward U87.CD4 cells expressing CCR5 (R5) and CXCR4 (X4), respectively; whereas the remaining 13 (14%) clones could infect both cells. Genotypic analyses by widely used algorithms including V3 net charge, Geno2pheno, WebPSSM, and PhenoSeq showed that almost all phenotypic X4-tropic clones and only 15 of 75 phenotypic R5-tropic clones were concordantly predicted. However, the remaining 60 phenotypic R5-tropic clones were discordantly predicted by at least one algorithm. In particular, 2 phenotypic R5-tropic clones were discordantly predicted by all algorithms tested. Taken together, the results demonstrate the limitation of currently available genotypic algorithms for predicting co-receptor inference among co-circulating multiple non-B subtypes and emerging isRFs. Also, the phenotypic tropism dataset presented here could be valuable for retraining of the widely used genotypic prediction algorithms to enhance their performance.
High Expression Levels of CDK1 and CDC20 in Patients With Lung Squamous Cell Carcinoma are Associated With Worse Prognosis
Authors: Deng Huan , Hang Qingqing , Shen Dijian , Ying Hangjie , Zhang Yibi , Qian Xu , Chen Ming
Published: July 2021

Purpose: Progress related to the early detection and molecular targeted therapy of lung squamous cell carcinoma (LUSC) remains limited. The goal of our study was to identify key candidate indicators of LUSC.

Methods: Three microarray datasets (GSE33532, GSE30219 and GSE19188) were applied to find differentially expressed genes (DEGs). Functional enrichment analyses of DEGs were carried out, and their protein-protein interaction (PPI) network was established. Hub genes were chosen from the PPI network according to their degree scores. Then, overall survival (OS) analyses of hub genes were carried out using Kaplan-Meier plotter, and their GSEA analyses were performed. Public databases were used to verify the expression patterns of CDK1 and CDC20. Furthermore, basic experiments were performed to verify our findings.

Results: A total of 1,366 DEGs were identified, containing 669 downregulated and 697 upregulated DEGs. These DEGs were primarily enriched in cell cycle, chromosome centromeric region and nuclear division. Seventeen hub genes were selected from PPI network. Survival analyses demonstrated that CDK1 and CDC20 were closely associated with OS. GSEA analyses revealed that cell cycle, DNA replication, and mismatch repair were associated with CDK1 expression, while spliceosome, RNA degradation and cell cycle were correlated with CDC20 expression. Based on The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (THPA) databases, CDK1 and CDC20 were upregulated in LUSC at the mRNA and protein levels. Moreover, basic experiments also supported the obvious upregulation of CDK1 and CDC20 in LUSC.

Conclusion: Our study suggests and validates that CDK1 and CDC20 are potential therapeutic targets and prognostic biomarkers of LUSC.
Waste Clearance in the Brain
Authors: Kaur Jasleen , Fahmy Lara M. , Davoodi-Bojd Esmaeil , Zhang Li , Ding Guangliang , Hu Jiani , Zhang Zhenggang , Chopp Michael , Jiang Quan
Published: July 2021

Waste clearance (WC) is an essential process for brain homeostasis, which is required for the proper and healthy functioning of all cerebrovascular and parenchymal brain cells. This review features our current understanding of brain WC, both within and external to the brain parenchyma. We describe the interplay of the blood-brain barrier (BBB), interstitial fluid (ISF), and perivascular spaces within the brain parenchyma for brain WC directly into the blood and/or cerebrospinal fluid (CSF). We also discuss the relevant role of the CSF and its exit routes in mediating WC. Recent discoveries of the glymphatic system and meningeal lymphatic vessels, and their relevance to brain WC are highlighted. Controversies related to brain WC research and potential future directions are presented.
Performance of the Rowland Universal Dementia Assessment Scale for the Detection of Mild Cognitive Impairment and Dementia in a Diverse Cohort of Illiterate Persons From Rural Communities in Peru
Authors: Custodio Nilton , Montesinos Rosa , Diaz Monica M. , Herrera-Perez Eder , Chavez Kristhy , Alva-Diaz Carlos , Reynoso-Guzman Willyams , Pintado-Caipa Maritza , Cuenca José , Gamboa Carlos , Lanata Serggio
Published: July 2021

Background: The accurate diagnosis of neurocognitive disorders in illiterate Peruvian populations is challenging, largely owing to scarcity of brief cognitive screening tools (BCST) validated in these diverse populations. The Peruvian version of the Rowland Universal Dementia Assessment Scale (RUDAS-PE) is a BCST that relies minimally on educational attainment and has shown good diagnostic accuracy in an urban illiterate population in Peru, yet its psychometric properties in illiterate populations in rural settings of the country have not been previously investigated.

Objectives: To establish the diagnostic accuracy of the RUDAS-PE compared to expert clinical diagnosis using the Clinical Dementia Rating (CDR) Scale in healthy and cognitively impaired illiterate persons living in two culturally and geographically distinct rural communities of Peru.

Methods: A cross-sectional, population-based study of residents ≥ 50 years of age living in the Peruvian rural communities of Santa Clotilde and Chuquibambilla. A total of 129 subjects (76 from Santa Clotilde and 53 from Chuquibambilla) were included in this study. Gold standard diagnostic neurocognitive evaluation was based on expert neurological history and examination and administration of the CDR. Receiver operating characteristics, areas under the curve (AUC), and logistic regression analyses were conducted to determine the performance of RUDAS-PE compared to expert gold standard diagnosis.

Results: Compared to gold standard diagnosis, the RUDAS-PE was better at correctly discriminating between MCI and dementia than discriminating between MCI and controls in both sites (97.0% vs. 76.2% correct classification in Chuquibambilla; 90.0% vs. 64.7% in Santa Clotilde). In Chuquibambilla, the area under the curve (AUC) of the RUDAS to discriminate between dementia and MCI was 99.4% (optimal cutoff at <18), whereas between MCI and controls it was 82.8% (optimal cutoff at <22). In Santa Clotilde, the area under the curve (AUC) of the RUDAS to discriminate between dementia and MCI was 99.1% (optimal cutoff at <17), whereas between MCI and controls it was 75.5% (optimal cutoff at <21).

Conclusions: The RUDAS-PE has acceptable psychometric properties and performed well in its ability to discriminate MCI and dementia in two cohorts of illiterate older adults from two distinct rural Peruvian communities.
Cerebrovascular Function in Hormonal Migraine: An Exploratory Study
Authors: Dzator Jemima S. A. , Howe Peter R. C. , Griffiths Lyn R. , Coupland Kirsten G. , Wong Rachel H. X.
Published: July 2021

Background: Migraineurs, particularly young premenopausal women, are at increased risk of cerebrovascular disease; however, there is currently limited evidence as to whether hormonal migraine is associated with poor cerebrovascular function.

Objectives: The objectives of this study were to: (1) investigate the potential association of cerebrovascular function with hormonal migraine and (2) determine whether abnormalities of cerebrovascular function in hormonal migraineurs are associated with migraine-related disability and/or quality of life.

Method: A cross-sectional study was undertaken in 50 hormonal migraineurs (mean age: 38.7 ± 1.2 years) and 29 controls (mean age: 35.6 ± 1.8 years). Data were collected at a single point in time from all participants during the inter-ictal period when they were free from migraine and not menstruating. Transcranial Doppler ultrasound was used to measure resting blood flow velocity and cerebrovascular responsiveness (CVR) to hypercapnia and cognitive stimulation (neurovascular coupling) in the left and right middle cerebral artery (MCA). Additionally, hormonal migraineurs completed three questionnaires to assess migraine-related disability and quality of life as well as migraine frequency and intensity: Headache Impact Test-6™, Migraine-Specific Quality of Life and Migraine Disability Assessment.

Results: Hormonal migraineurs had lower resting mean blood flow velocity (MBFV) (P = 0.009) and neurovascular coupling during cognitive stimulation (P = 0.010) in the left MCA than controls. No such differences were found in the right MCA. Additionally, heart rate (P = 0.004) was higher in hormonal migraineurs than controls. However, no differences in CVR to hypercapnia were found between hormonal migraineurs and controls. Multi-variate analysis revealed age to be a significant (P = 0.012) predictor of MBFV in the left MCA. Negative correlations between headache frequency and CVR to hypercapnia in the left (P = 0.026) and right MCA (P = 0.044) were found. Additionally, negative correlations between neurovascular coupling during the 2-Back 1.5 s task in the right MCA and the MSQoL emotional (P = 0.013) and role-function restrictive (P = 0.039) domains were found.

Conclusions: This is the first study to show that hormonal migraineurs have poorer cerebrovascular function, as represented by lower resting MBFV and impaired neurovascular coupling in the left MCA. Future studies should investigate whether improving cerebrovascular function can prevent hormonal migraine and improve quality of life.

Clinical Trial Registration: ACTRN12618001230246.
A Machine Learning Approach for Detecting Vicarious Trial and Error Behaviors
Authors: Miles Jesse T. , Kidder Kevan S. , Wang Ziheng , Zhu Yiru , Gire David H. , Mizumori Sheri J. Y.
Published: July 2021

Vicarious trial and error behaviors (VTEs) indicate periods of indecision during decision-making, and have been proposed as a behavioral marker of deliberation. In order to understand the neural underpinnings of these putative bridges between behavior and neural dynamics, researchers need the ability to readily distinguish VTEs from non-VTEs. Here we utilize a small set of trajectory-based features and standard machine learning classifiers to identify VTEs from non-VTEs for rats performing a spatial delayed alternation task (SDA) on an elevated plus maze. We also show that previously reported features of the hippocampal field potential oscillation can be used in the same types of classifiers to separate VTEs from non-VTEs with above chance performance. However, we caution that the modest classifier success using hippocampal population dynamics does not identify many trials where VTEs occur, and show that combining oscillation-based features with trajectory-based features does not improve classifier performance compared to trajectory-based features alone. Overall, we propose a standard set of features useful for trajectory-based VTE classification in binary decision tasks, and support previous suggestions that VTEs are supported by a network including, but likely extending beyond, the hippocampus.
Genetic Variations in the Transforming Growth Factor-β1 Pathway May Improve Predictive Power for Overall Survival in Non-small Cell Lung Cancer
Authors: Zhang Hong , Wang Weili , Pi Wenhu , Bi Nan , DesRosiers Colleen , Kong Fengchong , Cheng Monica , Yang Li , Lautenschlaeger Tim , Jolly Shruti , Jin Jianyue , Kong Feng-Ming (Spring)
Published: July 2021

Purpose:Transforming growth factor-β1 (TGF-β1), a known immune suppressor, plays an important role in tumor progression and overall survival (OS) in many types of cancers. We hypothesized that genetic variations of single nucleotide polymorphisms (SNPs) in the TGF-β1 pathway can predict survival in patients with non-small cell lung cancer (NSCLC) after radiation therapy.

Materials and Methods:Fourteen functional SNPs in the TGF-β1 pathway were measured in 166 patients with NSCLC enrolled in a multi-center clinical trial. Clinical factors, including age, gender, ethnicity, smoking status, stage group, histology, Karnofsky Performance Status, equivalent dose at 2 Gy fractions (EQD2), and the use of chemotherapy, were first tested under the univariate Cox's proportional hazards model. All significant clinical predictors were combined as a group of predictors named “Clinical.” The significant SNPs under the Cox proportional hazards model were combined as a group of predictors named “SNP.” The predictive powers of models using Clinical and Clinical + SNP were compared with the cross-validation concordance index (C-index) of random forest models.

Results:Age, gender, stage group, smoking, histology, and EQD2 were identified as significant clinical predictors: Clinical. Among 14 SNPs, BMP2:rs235756 (HR = 0.63; 95% CI:0.42–0.93;p= 0.022), SMAD9:rs7333607 (HR = 2.79; 95% CI 1.22–6.41;p= 0.015), SMAD3:rs12102171 (HR = 0.68; 95% CI: 0.46–1.00;p= 0.050), and SMAD4: rs12456284 (HR = 0.63; 95% CI: 0.43–0.92;p= 0.016) were identified as powerful predictors of SNP. After adding SNP, the C-index of the model increased from 84.1 to 87.6% at 24 months and from 79.4 to 84.4% at 36 months.

Conclusion:Genetic variations in the TGF-β1 pathway have the potential to improve the prediction accuracy for OS in patients with NSCLC.
Drug Repurposing of Pantoprazole and Vitamin C Targeting Tumor Microenvironment Conditions Improves Anticancer Effect in Metastatic Castration-Resistant Prostate Cancer
Authors: Li Zhoulei , He Peng , Long Yali , Yuan Gang , Shen Wanqing , Chen Zhifeng , Zhang Bing , Wang Yue , Yue Dianchao , Seidl Christof , Zhang Xiangsong
Published: July 2021

The effective and economical therapeutic strategy for metastatic castration-resistant prostate cancer (mCRPC) is still requested from patients, who are not available for Lu-177 or Ra-223 treatment. Drug repurposing as a cost-effective and time-saving alternative to traditional drug development has been increasingly discussed. Proton pump inhibitors (PPIs) such as pantroprazole, which are commonly used as antacids, have also been shown to be effective in cancer chemoprevention via induction of apoptosis in multiple cancer cell lines. Vitamin C is an essential micronutrient for human body, has been proposed as a potential anti-cancer agent. In this context, have we investigated the combination of vitamin C and pantoprazole for the management of metastatic castration-resistant prostate cancer (mCRPC). Six chosen human adenocarcinoma cell lines were used to investigate the influence of pantoprazole on the microenvironment of cancer cells (extracellular pH and production of exosomes). Tumor growth and tumor 18F-FDG uptake in PC3 xenografts were analyzed following varied treatment. Our in vitro Results have suggested that pantoprazole enhanced the cytotoxic activity of vitamin C by regulating pH values and production of exosomes in cancer cells. Moreover, the synergistic effect of pantoprazole and vitamin C was pH-dependent since pantoprazole was more effective at a slightly acidic pH. In vivo, the combined treatment using pantoprazole and vitamin C produced better therapeutic outcomes than treatment with vitamin C or pantoprazole alone, as demonstrated via tumor growth and uptake of 18F-FDG. Therefore, we suggest that pantoprazole combined with vitamin C could be as a possible strategy to manage mCRPC.
Cancer Preventive and Therapeutic Potential of Banana and Its Bioactive Constituents: A Systematic, Comprehensive, and Mechanistic Review
Authors: Mondal Arijit , Banerjee Sabyasachi , Bose Sankhadip , Das Partha Pratim , Sandberg Elise N. , Atanasov Atanas G. , Bishayee Anupam
Published: July 2021

Background

The banana (Musa spp.) plant produces elongated and edible fruit. The two main parthenocarpic species of banana are Musa accuminata Colla and Musa balbisiana Colla. There are several health-promoting and disease-preventing effects of Musa accuminata Colla, which are attributed to its important bioactive compounds, including phenolics, carotenoids, biogenic amines, phytosterols, and volatile oils, found in the stem, fruit, pseudostem, leaf, flower, sap, inner trunk, root, and inner core. Banana possesses numerous pharmacological activities, such as antioxidant, immunomodulatory, antimicrobial, antiulcerogenic, hypolipidemic, hypoglycemic, leishmanicidal, anthelmintic, and anticancer properties. Various individual studies have reported anticancer effects of different components of the banana plant. However, according to our understanding, an up-to-date, systematic, and critical analysis of existing scientific results has not yet been carried out.

Objectives

This review aims to include a thorough assessment of banana and its phytochemicals for cancer prevention and therapy with a focus on cellular and molecular mechanisms of action.

Methods

The available research studies on anticancer activities of banana extracts, fractions and pure compounds were collected using various scholarly databases, such as PubMed, ScienceDirect, and Scopus, based on predetermined selection criteria.

Results

Various banana extracts, fractions, and phytoconstituents, including ferulic acid, protocatechualdehyde, 2-pentanone, 4-epicyclomusalenone, cycloeucalenol acetate, and chlorogenic acid, have been shown to exhibit cancer preventative and anticancer activities in breast, cervical, colorectal, esophageal, hepatic, oral, prostate, and skin cancers. Bioactive components present in bananas have exhibited antiproliferative, cell cycle arrest-inducing, apoptotic, anti-adhesive, anti-invasive, and antiangiogenic effects through modulation of diverse, dysregulated oncogenic signaling pathways.

Conclusion

Based on the critical analysis of available literature, banana products and phytoconstituents show enormous potential for future development of drugs for cancer prevention and therapy. However, more mechanistic studies and well-designed clinical trials should be performed to establish its efficacy.
Neutrophil-Lymphocyte Ratio and Circulating Tumor Cells Counts Predict Prognosis in Gastrointestinal Cancer Patients
Authors: Qian Chengcheng , Cai Renjie , Zhang Wenying , Wang Jiongyi , Hu Xiaohua , Zhang Yanjie , Jiang Bin , Yuan Haihua , Liu Feng
Published: July 2021

Purpose

The purpose of this study is to explore the prognostic value of associating pre-treatment neutrophil–lymphocyte ratio (NLR) with circulating tumor cells counts (CTCs) in patients with gastrointestinal cancer.

Materials and Methods

We collected the related data of 72 patients with gastric cancer (GC) and colorectal cancer (CRC) who received different therapies from August 2016 to October 2020, including age, gender, primary tumor location, TNM stage, tumor-differentiation, NLR, CTCs, disease-free survival (DFS) and overall survival (OS). We chose the optimal cut-off value of NLR >3.21 or NLR ≤3.21 and CTC >1 or CTC ≤1 by obtaining receiver operating characteristic (ROC) curve. The Kaplan–Meier survival analysis and Cox regression analysis were used to analyze DFS and OS. To clarify the role of the combination of NLR and CTCs counts in predicting the prognosis, we analyzed the DFS and OS when associated NLR and CTCs counts.

Results

A high NLR (>3.21) was associated with shorter DFS (P <0.0001) and OS (P <0.0001). Patients with high CTCs level (>1) had shorter DFS (P = 0.001) and OS (P = 0.0007) than patients with low CTCs level. Furthermore, patients who had both higher NLR and higher CTCs counts had obvious shorter DFS (P <0.0001) and OS (P <0.0001).

Conclusions

Patients with higher NLR and more CTCs respectively tended to have poor prognosis with shorter DFS and OS, which might be regarded as predictors of gastrointestinal cancer. In particular, associating NLR and CTCs counts might be a reliable predictor in patients with gastrointestinal cancer.
Case Report: Prenatal and Postnatal Management for Fetal Bronchogenic Cysts During the COVID-19 Pandemic
Authors: Cheng Lin , Duan Jie , Wang Mei , Lu Dan , Li Huan , Ma Jianhong , Liu Juan , Wang Cheng , Zhang Yuanzhen
Published: July 2021

Background: A fetal bronchogenic cyst (BC) is a rare congenital anomaly with an incidence of 0.147–0.238‰. The coronavirus disease 2019 (COVID-19) pandemic, as a particular situation, hindered pregnant women from receiving periodic prenatal checkups.

Case Description: Until 34+6 weeks of gestation, a fetal case of the intrathoracic cyst was found by ultrasound examination. Further, MRI examination confirmed the diagnosis of the congenital mediastinal cystic lesion, probably a BC. Genetic testing was not conducted due to the COVID-19 pandemic. At 38+5 weeks of gestation with maternal COVID-19 testing negative, a live girl was delivered by cesarean section. Five months later, the child underwent bronchocystectomy, and the postoperative pathological lesions confirmed a (right upper mediastinum) BC.

Conclusion: Herein, we reported the prenatal and postnatal management for a rare case of the congenital BC by multidisciplinary approaches during the COVID-19 pandemic. Fetal MRI and screening for fetal chromosomal abnormalities are especially recommended. This case contributes to the awareness that the COVID-19 pandemic interferes with regular follow-up schedules during pregnancy and may interfere with timely performed additional tests; which leads to more accurate genetic counseling. A combination of multidisciplinary approaches, including radiology, infection control, genetic counseling, obstetrics, and pediatric surgery, is pivotal for managing fetal BC during the COVID-19 pandemic.
The Effects of Elaeagnus angustifolia L. on the Thyroid-Stimulating Hormone, Dehydroepiandrosterone-Sulfate, Prolactin and Cortisol Levels in Post-Menopausal Women: A Double-Blind, Randomized, and Placebo-Controlled Study
Authors: Jalalvand Fatemeh , Rezaei Arezou , Badehnoosh Bita , Yaseri Mehdi , Qorbani Mostafa , Emaminia Farzaneh , Shabani Mahzad
Published: July 2021

Menopause is the last menstrual period associated with a decline in ovarian steroid secretion and follicular loss. Hormone profile changes during menopause include a decrease in the production of estrogen, dehydroepiandrosterone (DHEA), and prolactin (PRL), and an increase in thyroid-stimulating hormone (TSH) and cortisol. Herbal medicines are considered as alternatives to hormone therapy. The studies on postmenopausal women have shown that Elaeagnus angustifolia L. (called “Senjed” in Persian) has some efficacy in improving sex hormone and lipid profiles, joint pain, and cardiovascular function, as the decrease in luteinizing hormone, low-density lipoprotein, and heart rate was significant. The aim of the present study was to evaluate the effects of E. angustifolia on TSH, DHEA-S, PRL, and cortisol levels and their ratios in postmenopausal women. It is assumed that the eventual effects of hormones on the brain and other tissues are determined by the balance between interdependent hormones. In the present randomized double-blinded placebo-controlled trial (https://en.irct.ir/search/result?query=IRCT20170227032795N4), fifty-eight postmenopausal women were randomly assigned to one of two medicinal herb (15 g of the whole E. angustifolia fruit powder) and placebo (7.5 g isomalt + 7.5 g cornstarch) groups. After 10 weeks of the treatment, the serum levels of TSH, DHEA-S, PRL, cortisol hormones, and their ratios were measured. The increase in the TSH, and cortisol levels, and cortisol/DHEA-S ratio and the decrease in prolactin and DHEA-S and the PRL/TSH, PRL/cortisol, and DHEA-S/TSH ratios after E. angustifolia consumption were significant only based on within-group but not on the between-group analysis. Based on between-group analyses, the changes in the hormone profile were not significant in the placebo group. According to Iranian tradition and folklore, E. angustifolia fruit is a symbol of female fertility. Therefore, its consumption is highly recommended to maintain health in the elderly, especially women. However, the observed outcomes about the effect of E. angustifolia on menopause were not completely in line with the Iranian folklore. E. angustifolia consumption did not significantly affect the hormone profile and ratios at the end of the ten-week trial, possibly due to the small sample size, short time, and the fact that our participants were postmenopausal women.
Suppression of FGF5 and FGF18 Expression by Cholesterol-Modified siRNAs Promotes Hair Growth in Mice
Authors: Zhao Jungang , Lin Haojie , Wang Lusheng , Guo Keke , Jing Rongrong , Li Xuenan , Chen Yu , Hu Zhenlin , Gao Shuang , Xu Nuo
Published: July 2021

FGF5 and FGF18 are key factors in the regulation of the hair follicle cycle. FGF5 is overexpressed during the late anagen phase and serves as a crucial regulatory factor that promotes the anagen-to-catagen transition in the hair follicle cycle. FGF18, which is overexpressed during the telogen phase, mainly regulates the hair follicle cycle by maintaining the telogen phase and inhibiting the entry of hair follicles into the anagen phase. The inhibition of FGF5 may prolong the anagen phase, whereas the inhibition of FGF18 may promote the transition of the hair follicles from the telogen phase to the anagen phase. In the present study, we used siRNA to suppress FGF5 or FGF18 expression as a way to inhibit the activity of these genes. Using qPCR, we showed that FGF5-targeting siRNA modified by cholesterol was more effective than the same siRNA bound to a cell-penetrating peptide at suppressing the expression of FGF5 both in vitro and in vivo. We then investigated the effects of the cholesterol-modified siRNA targeting either FGF5 or FGF18 on the hair follicle cycle in a depilated area of the skin on the back of mice. The cholesterol-modified siRNA, delivered by intradermal injection, effectively regulated the hair follicle cycle by inhibiting the expression of FGF5 and FGF18. More specifically, intradermal injection of a cholesterol-modified FGF5-targeted siRNA effectively prolonged the anagen phase of the hair follicles, whereas intradermal injection of the cholesterol-modified FGF18-targeted siRNA led to the mobilization of telogen follicles to enter the anagen phase earlier. The inhibitory effect of the cholesterol-modified FGF18-targeted siRNA on FGF18 expression was also evaluated for a topically applied siRNA. Topical application of a cream containing the cholesterol-modified FGF18-targeted siRNA on a depilated area of the skin of the back of mice revealed comparable inhibition of FGF18 expression with that observed for the same siRNA delivered by intradermal injection. These findings suggested that alopecia could be prevented and hair regrowth could be restored either through the intradermal injection of cholesterol-modified siRNA targeting FGF5 or FGF18 or the topical application of FGF18 siRNA.