bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crosstalk between MUC1 and VEGF in angiogenesis and metastasis: a review highlighting roles of the MUC1 with an emphasis on metastatic and angiogenic signaling
Authors: Khodabakhsh Farnaz , Merikhian Parnaz , Eisavand Mohammad Reza , Farahmand Leila 
Published: April 2021

AbstractVEGF and its receptor family (VEGFR) members have unique signaling transduction system that play significant roles in most pathological processes, such as angiogenesis in tumor growth and metastasis. VEGF-VEGFR complex is a highly specific mitogen for endothelial cells and any de-regulation of the angiogenic balance implicates directly in endothelial cell proliferation and migration. Moreover, it has been shown that overexpressing Mucin 1 (MUC1) on the surface of many tumor cells resulting in upregulation of numerous signaling transduction cascades, such as growth and survival signaling pathways related to RTKs, loss of cell-cell and cell-matrix adhesion, and EMT. It promotes gene transcription of pro-angiogenic proteins such as HIF-1α during periods of oxygen scarcity (hypoxia) to enhance tumor growth and angiogenesis stimulation. In contrast, the cytoplasmic domain of MUC1 (MUC1-C) inhibits apoptosis, which in turn, impresses upon cell fate. Besides, it has been established that reduction in VEGF expression level correlated with silencing MUC1-C level indicating the anti-angiogenic effect of MUC1 downregulation. This review enumerates the role of MUC1-C oncoprotein and VEGF in angiogenesis and metastasis and describes several signaling pathways by which MUC1-C would mediate the pro-angiogenic activities of cancer cells.
The patient enablement instrument for back pain: reliability, content validity, construct validity and responsiveness
Authors: Molgaard Nielsen A. , Hartvigsen J. , Kongsted A. , Öberg B. , Enthoven P. , Abbott A. , Lauridsen H. H. 
Published: April 2021

Abstract
Background
Currently, there are no outcome measures assessing the ability of people with non-specific low back pain to self-manage their illness. Inspired by the ‘Patient Enablement Instrument’, we developed the Patient Enablement Instrument for Back Pain (PEI-BP). The aim of this study was to describe the development of the Patient Enablement Instrument for Back Pain (PEI-BP) and investigate content validity, construct validity, internal consistency, test–retest reliability, measurement error, responsiveness and floor and ceiling effects.

Methods
The PEI-BP consists of 6 items that are rated on a 0–10 Numeric Rating Scale. Measurement properties were evaluated using the COSMIN taxonomy and were based on three cohorts from primary care with low back pain: The content validity cohort (N = 14) which participated in semi-structured interviews, the GLA:D® Back cohort (N = 272) and the test–retest cohort (N = 37) which both completed self-reported questionnaires. For construct validity and responsiveness, enablement was compared to disability (Oswestry Disability Index), back pain beliefs (Brief Illness Perception Questionnaire), fear avoidance (Fear-Avoidance Beliefs Questionnaire—physical activity), mental health (SF-36), educational level and number of previous episodes of low back pain.

Results
The PEI-BP was found to have acceptable content validity, construct validity, reliability (internal consistency, test–retest reliability and measurement error) and responsiveness. The Smallest Detectable Change was 10.1 points illustrating that a patient would have to change more than 1/6 of the scale range for it to be a true change. A skewed distribution towards the high scores were found at baseline indicating a potentially problematic ceiling effect in the current population.

Conclusions
The PEI-BP can be considered a valid and reliable tool to measure enablement on people seeking care for non-specific LBP. Further testing of the PEI-BP in populations with more severe LBP is recommended.
Trial registration: Not applicable.
A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors
Authors: Ghimire Dibya , KC Yuvraj , Timilsina Uddhav , Goel Kriti , Nitz T. J. , Wild Carl T. , Gaur Ritu 
Published: April 2021

Abstract
Background
Maturation inhibitors (MIs) potently block HIV-1 maturation by inhibiting the cleavage of the capsid protein and spacer peptide 1 (CA-SP1). Bevirimat (BVM), a highly efficacious first-in-class MI against HIV-1 subtype B isolates, elicited sub-optimal efficacy in clinical trials due to polymorphisms in the CA-SP1 region of the Gag protein (SP1:V7A). HIV-1 subtype C inherently contains this polymorphism thus conferring BVM resistance, however it displayed sensitivity to second generation BVM analogs.

Results
In this study, we have assessed the efficacy of three novel second-generation MIs (BVM analogs: CV-8611, CV-8612, CV-8613) against HIV-1 subtype B and C isolates. The BVM analogs were potent inhibitors of both HIV-1 subtype B (NL4-3) and subtype C (K3016) viruses. Serial passaging of the subtype C, K3016 virus strain in the presence of BVM analogs led to identification of two mutant viruses—Gag SP1:A1V and CA:I201V. While the SP1:A1V mutant was resistant to the MIs, the CA:I120V mutant displayed partial resistance and a MI-dependent phenotype. Further analysis of the activity of the BVM analogs against two additional HIV-1 subtype C strains, IndieC1 and ZM247 revealed that they had reduced sensitivity as compared to K3016. Sequence analysis of the three viruses identified two polymorphisms at SP1 residues 9 and 10 (K3016: N9, G10; IndieC1/ZM247: S9, T10). The N9S and S9N mutants had no change in MI-sensitivity. On the other hand, replacing glycine at residue 10 with threonine in K3016 reduced its MI sensitivity whereas introducing glycine at SP1 10 in place of threonine in IndieC1 and ZM247 significantly enhanced their MI sensitivity. Thus, the specific glycine residue 10 of SP1 in the HIV-1 subtype C viruses determined sensitivity towards BVM analogs.

Conclusions
We have identified an association of a specific glycine at position 10 of Gag-SP1 with an MI susceptible phenotype of HIV-1 subtype C viruses. Our findings have highlighted that HIV-1 subtype C viruses, which were inherently resistant to BVM, may also be similarly predisposed to exhibit a significant degree of resistance to second-generation BVM analogs. Our work has strongly suggested that genetic differences between HIV-1 subtypes may produce variable MI sensitivity that needs to be considered in the development of novel, potent, broadly-active MIs.

Graphic abstract
Parachute mitral valve associated with reticular chordae tendineae in an adult: case report
Authors: Duan Qun-Jun , Duan Cui-Ting , Dong Ai-Qiang , Cheng Hai-Feng 
Published: April 2021

AbstractBackgroundParachute mitral valve with reticular chordae tendineae is an extremely rare anomaly.Case presentationWe present a case of parachute mitral valve associated with distinctive reticular chordae tendineae in an adult. It was diagnosed from the echocardiogram. The patient was referred for surgery. Valve analysis showed thickened mitral valve leaflets and commissures. The chordae tendinae were lengthy and thick. All the chordae tendinae merged into a solitary papillary muscle. A distinctive reticular fibrous tissue was found on mitral valve apparatus as the chordae tendinae intermixed each other. The only functional communication between the left atrium and the left ventricle was through the reticular spaces. This anomaly was considered to be unrepairable and was replaced with a mechanical valve.ConclusionsAn extremely rare and unique case of parachute mitral valve associated with reticular chordae tendineae was reported. Mitral valve replacement is a reasonable choice in patients with parachute mitral valve with reticular chordae tendineae.
Currarino syndrome: a comprehensive genetic review of a rare congenital disorder
Authors: Dworschak Gabriel C. , Reutter Heiko M. , Ludwig Michael 
Published: April 2021

Abstract
Background
The triad of a presacral mass, sacral agenesis and an anorectal anomaly constitutes the rare Currarino syndrome (CS), which is caused by dorsal–ventral patterning defects during embryonic development. The major causative CS gene is MNX1, encoding a homeobox protein.

Main body
In the majority of patients, CS occurs as an autosomal dominant trait; however, a female predominance observed, implies that CS may underlie an additional mode(s) of inheritance. Often, the diagnosis of CS is established solely by clinical findings, impacting a detailed analysis of the disease. Our combined data, evaluating more than 60 studies reporting patients with CS-associated mutations, revealed a slightly higher incidence rate in females with a female-to-male ratio of 1.39:1. Overall, MNX1 mutation analysis was successful in only 57.4% of all CS patients investigated, with no mutation detected in 7.7% of the familial and 68% of the sporadic patients. Our studies failed to detect the presence of an expressed MNX1 isoform that might explain at least some of these mutation-negative cases.

Conclusion
Aside from MNX1, other genes or regulatory regions may contribute to CS and we discuss several cytogenetic studies and whole-exome sequencing data that have implicated further loci/genes in its etiology.
Psychometric properties of the Thai Mood and Feelings Questionnaire (MFQ) for adolescent depression
Authors: Fuseekul Nanthaka , Orchard Faith , Reynolds Shirley 
Published: April 2021

Abstract
Background
The Mood and Feelings Questionnaire (MFQ) is a widely used screening tool for child and adolescence depression but has not been validated with young people in Thailand. This study aimed to assess the reliability and validity and to determine the optimal clinical cut-off of the Thai MFQ.

Methods
The Thai MFQ was evaluated in two parts. In part 1, The MFQ was translated and back translated into the Thai language and piloted on a small number of Thai adolescents. Then 1275 young people aged 12–18 years from three secondary schools in Thailand completed the MFQ and related measures of depression. In part 2, 138 students were invited to take part in a structured diagnostic interview (the Thai translation of the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children -Present and Lifetime Version (the K-SADS-PL). Of those, 103 students were interviewed and completed the Thai MFQ a second time to assess test–retest reliability. Receiver Operating Characteristics (ROC) analyses were conducted to evaluate diagnosis accuracy and examine the optimal cut-off score of the Thai MFQ.

Results
The Thai MFQ had excellent internal consistency (α = 0.92) and good to moderate test–retest reliability in 2-week and 4-week intervals. The Thai MFQ also had good convergent validity with related measures of depression. The ROC analyses demonstrated that the Thai MFQ also had excellent accuracy distinguishing between depressed and non-depressed adolescents [AUC = 0.95, 95% CI [0.92, 0.99]. A total score of 28 on the Thai MFQ was the optimal cut-off score (sensitivity was 0.97 and specificity was 0.83).

Discussion
The Thai MFQ demonstrated excellent psychometric properties and accurately distinguished between depressed and non-depressed adolescents. It is appropriate to use as a screening measure to identify adolescents with depression in community settings in Thailand.
Rates and risk factors for amputation in people with diabetes in Japan: a historical cohort study using a nationwide claims database
Authors: Kaneko Masanori , Fujihara Kazuya , Harada Mayuko Yamada , Osawa Taeko , Yamamoto Masahiko , Kitazawa Masaru , Matsubayashi Yasuhiro , Yamada Takaho , Seida Hiroyasu , Kodama Satoru , Sone Hirohito 
Published: April 2021

AbstractBackgroundThe prevalence of diabetes is rising, and diabetes develops at a younger age in East Asia. Although lower limb amputation negatively affects quality of life and increases the risk of cardiovascular events, little is known about the rates and predictors of amputation among persons with diabetes from young adults to those in the “young‐old” category (50–72 y).MethodsWe analyzed data from a nationwide claims database in Japan accumulated from 2008 to 2016 involving 17,288 people with diabetes aged 18–72 y (mean age 50.2 y, HbA1c 7.2%). Amputation occurrence was determined according to information from the claims database. Cox regression model identified variables related to lower limb amputation.ResultsThe mean follow‐up time was 5.3 years, during which time 16 amputations occurred (0.17/1000 person‐years). Multivariate Cox regression analysis showed that age (hazard ratio [HR] 1.09 [95% confidence intervals] 1.02–1.16, p = 0.01) and HbA1c (HR 1.46 [1.17–1.81], p < 0.01) were independently associated with amputations. Compared with those aged < 60 years with HbA1c < 8.0%, the HR for amputation was 27.81 (6.54–118.23) in those aged ≥60 years and HbA1c ≥8.0%.ConclusionsAge and HbA1c were associated with amputations among diabetic individuals, and the rates of amputation were significantly greater in those ≥60 years old and with HbA1c ≥8.0%.
Evaluation of the online-based self-help programme “Selfapy” in patients with unipolar depression: study protocol for a randomized, blinded parallel group dismantling study
Authors: Krämer Rico , Köhler Stephan 
Published: April 2021

Abstract
Background
Patients with mild to moderate depressive symptoms can have limited access to regular treatment; to ensure appropriate care, low-threshold treatment is needed. Effective online interventions could increase the supply of low-threshold treatment. Further research is needed to evaluate the effectiveness of online interventions. This study aims to evaluate the online-based self-help programme “Selfapy” on a sample of depressive subjects and compares the impact of the programme’s unaccompanied version with its therapeutic accompanied version.

Methods
A sample of 400 subjects that have a mild to severe depressive episode (Becks Depression Inventory - II and Hamilton Depression Scale) will be used. Subjects are randomly assigned to immediate access to an unaccompanied course (no support from psychologist via weekly phone calls), immediate access to an accompanied course (support from a psychologist via weekly phone calls) or a waiting list control group (access to the intervention after 24 weeks). The intervention will last for a period of 12 weeks. Depressive symptoms as a primary parameter, as well as various secondary parameters, such as life satisfaction, therapeutic relationships, social activation, self-esteem, attitudes towards Internet interventions and drop-out rates, are recorded at four different points in time: at baseline (T1), 6 weeks after the start of the intervention (T2), 12 weeks after the start of the intervention (T3) and 3 months after completion of the treatment follow-up (T4).

Conclusion
This randomized and controlled, blinded study will make use of a “dismantled” approach to adequately compare the accompanied and unaccompanied versions of the intervention. Positive and meaningful results are expected that could influence the acceptance and implementation of online interventions.

Trial registration
German Clinical Trials Register DRKS00017191. Registered on 14 June 2019
Comparison of various organic acids for xylo-oligosaccharide productions in terms of pKa values and combined severity
Authors: Cao Rou , Liu Xinlu , Guo Jianming , Xu Yong 
Published: April 2021

Abstract
Background
Methods to produce XOS have been intensively investigated, including enzymatic hydrolysis, steam explosion, and acid hydrolysis. Acid hydrolysis is currently the most widely used method to produce XOS due to its advantages of fewer processing steps, stronger raw material adaptability, higher yield, and better reproducibility. Especially, organic acids such as acetic acid, formic acid and xylonic acid work better as compared with mineral acids. However, the catalytic mechanism of different organic acids has been little studied. In this paper, four different organic acids, including formic acid, glycolic acid, lactic acid, and acetic acid were selected to compare their hydrolytic effects.

Results
Using pKa values as the benchmark, the yield of xylo-oligosaccharide (XOS) increased with the increasing value of pKa. The yield of XOS was 37% when hydrolyzed by 5% acetic acid (pKa = 4.75) at 170 ℃ for 20 min. Combined severity (CS), a parameter associated with temperature and reaction time was proposed, was proposed to evaluate the hydrolysis effect. The results of CS were consistent with that of pKa values on both the yield of XOS and the inhibitor.

Conclusion
The results based on pKa values and combined severity, a parameter associated with temperature and reaction time, concluded that acetic acid is a preferred catalyst. Combining the techno-economic analysis and environmental benefits, acetic acid hydrolysis process has lower factory production costs, and it is also an important metabolite and a carbon source for wastewater anaerobic biological treatment. In conclusion, production of xylo-oligosaccharides by acetic acid is an inexpensive, environment-friendly, and sustainable processing technique.
Bioprospecting of wild type ethanologenic yeast for ethanol fuel production from wastewater-grown microalgae
Authors: Romero-Frasca Enrique , Velasquez-Orta Sharon B. , Escobar-Sánchez Viviana , Tinoco-Valencia Raunel , Orta Ledesma María Teresa 
Published: April 2021

Abstract
Background
Wild-type yeasts have been successfully used to obtain food products, yet their full potential as fermenting microorganisms for large-scale ethanol fuel production has to be determined. In this study, wild-type ethanologenic yeasts isolated from a secondary effluent were assessed for their capability to ferment saccharified microalgae sugars.

Results
Yeast species in wastewater were identified sequencing the Internal Transcribed Spacers 1 and 2 regions of the ribosomal cluster. Concurrently, microalgae biomass sugars were saccharified via acid hydrolysis, producing 5.0 ± 0.3 g L−1 of fermentable sugars. Glucose consumption and ethanol production of yeasts in hydrolyzed-microalgae liquor were tested at different initial sugar concentrations and fermentation time. The predominant ethanologenic yeast species was identified as Candida sp., and glucose consumption for this strain and S. cerevisiae achieved 75% and 87% of the initial concentration at optimal conditions, respectively. Relatively similar ethanol yields were determined for both species, achieving 0.45 ± 0.05 (S. cerevisiae) and 0.46 ± 0.05 g ethanol per g glucose (Candida sp.).

Conclusion
Overall, the results provide a first insight of the fermentation capacities of specific wild-type Candida species, and their potential role in ethanol industries seeking to improve their cost-efficiency.
Identification of the major fermentation inhibitors of recombinant 2G yeasts in diverse lignocellulose hydrolysates
Authors: Vanmarcke Gert , Demeke Mekonnen M. , Foulquié-Moreno Maria R. , Thevelein Johan M. 
Published: April 2021

Abstract
Background
Presence of inhibitory chemicals in lignocellulose hydrolysates is a major hurdle for production of second-generation bioethanol. Especially cheaper pre-treatment methods that ensure an economical viable production process generate high levels of these inhibitory chemicals. The effect of several of these inhibitors has been extensively studied with non-xylose-fermenting laboratory strains, in synthetic media, and usually as single inhibitors, or with inhibitor concentrations much higher than those found in lignocellulose hydrolysates. However, the relevance of individual inhibitors in inhibitor-rich lignocellulose hydrolysates has remained unclear.

Results
The relative importance for inhibition of ethanol fermentation by two industrial second-generation yeast strains in five lignocellulose hydrolysates, from bagasse, corn cobs and spruce, has now been investigated by spiking higher concentrations of each compound in a concentration range relevant for industrial hydrolysates. The strongest inhibition was observed with industrially relevant concentrations of furfural causing partial inhibition of both D-glucose and D-xylose consumption. Addition of 3 or 6 g/L furfural strongly reduced the ethanol titer obtained with strain MD4 in all hydrolysates evaluated, in a range of 34 to 51% and of 77 to 86%, respectively. This was followed by 5-hydroxymethylfurfural, acetic acid and formic acid, for which in general, industrially relevant concentrations caused partial inhibition of D-xylose fermentation. On the other hand, spiking with levulinic acid, 4-hydroxybenzaldehyde, 4-hydroxybenzoic acid or vanillin caused little inhibition compared to unspiked hydrolysate. The further evolved MD4 strain generally showed superior performance compared to the previously developed strain GSE16-T18.

Conclusion
The results highlight the importance of individual inhibitor evaluation in a medium containing a genuine mix of inhibitors as well as the ethanol that is produced by the fermentation. They also highlight the potential of increasing yeast inhibitor tolerance for improving industrial process economics.
Age at menarche, age at natural menopause, and risk of rheumatoid arthritis — a Mendelian randomization study
Authors: Zhu Jingjing , Niu Zheng , Alfredsson Lars , Klareskog Lars , Padyukov Leonid , Jiang Xia 
Published: April 2021

AbstractBackgroundHormonal reproductive factors have been suggested to play an important role in the etiology of rheumatoid arthritis (RA), an autoimmune inflammatory disorder affecting primarily women. We conducted a two-sample Mendelian randomization (MR) study examining three relevant exposures, age at menarche (AAM), age at natural menopause (ANM), and age at first birth (AFB) with the risk of RA.MethodsWe collected summary statistics from the hitherto largest GWAS conducted in AAM (N = 329,345), ANM (N = 69,360), AFB (N = 251,151), and RA (Ncase = 14,361,Ncontrol = 43,923), all of European ancestry. We constructed strong instruments using hundreds of exposure-associated genetic variants and estimated causal relationship through different MR approaches including an inverse-variance weighted method, an MR-Egger regression and a weighted median method. We conducted a multivariable MR to control for pleiotropic effect acting in particular through obesity and socioeconomic status. We also performed important sensitivity analyses to verify model assumptions.ResultsWe did not find any evidence in support for a causal association between genetically predicted reproductive factors and risk of RA (ORper-SD increment in AAM = 1.06 [0.98–1.15]; ORper-SD increment in ANM = 1.05 [0.98–1.11], ORper-SD increment in AFB = 0.85 [0.65–1.10]). Results remained consistent after removing palindromic SNPs (ORper-SD increment in AAM = 1.06 [0.97–1.15], ORper-SD increment in ANM = 1.05 [0.98–1.13], ORper-SD increment in AFB = 0.81 [0.61–1.07]) or excluding SNPs associated with potential confounding traits (ORper-SD increment in AAM = 1.03 [0.94–1.12], ORper-SD increment in ANM = 1.04 [0.95–1.14]). No outlying instrument was identified through the leave-one-out analysis.ConclusionsOur MR study does not convincingly support a casual effect of reproductive factors, as reflected by age at menarche, age at menopause, and age at first birth, on the development of RA. Despite the largely augmented set of instruments we used, these instruments only explained a modest proportion of phenotypic variance of exposures. Our knowledge regarding this topic is still insufficient and future studies with larger sample size should be designed to replicate or dispute our findings.