bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a women’s empowerment index for Tanzania from the demographic and health surveys of 2004–05, 2010, and 2015–16
Authors: Mganga Andrew Evarist , Renju Jenny , Todd Jim , Mahande Michael Johnson , Vyas Seema 
Published: October 2021

Abstract
Background
Women’s empowerment is a multidimensional construct which varies by context. These variations make it challenging to have a concrete definition that can be measured quantitatively. Having a standard composite measure of empowerment at the individual and country level would help to assess how countries are progressing in efforts to achieve gender equality (SDG 5), enable standardization across and within settings and guide the formulation of policies and interventions. The aim of this study was to develop a women’s empowerment index for Tanzania and to assess its evolution across three demographic and health surveys from 2004 to 2016.

Results
Women’s empowerment in Tanzania was categorized into six distinct domains namely; attitudes towards violence, decision making, social independence, age at critical life events, access to healthcare, and property ownership. The internal reliability of this six-domain model was shown to be acceptable by a Cronbach’s α value of 0.658. The fit statistics of the root mean squared error of approximation (0.05), the comparative fit index (0.93), and the standardized root mean squared residual (0.04) indicated good internal validity. The structure of women’s empowerment was observed to have remained relatively constant across three Tanzanian demographic and health surveys.

Conclusions
The use of factor analysis in this research has shown that women’s empowerment in Tanzania is a six-domain construct that has remained relatively constant over the past ten years. This could be a stepping stone to reducing ambiguity in conceptualizing and operationalizing empowerment and expanding its applications in empirical research to study different women related outcomes in Tanzania.
Treatment of hepatitis C virus infection with direct-acting antiviral agent-based regimens in Iranian patients with hereditary bleeding disorders
Authors: Sharafi Heidar , Behnava Bita , Azizi-saraji Alireza , Namvar Ali , Anvar Ali , Salimi Shima , Alavian Seyed Moayed 
Published: October 2021

AbstractBackgroundChronic hepatitis C (CHC) is one of the most important comorbidities in patients with hereditary bleeding disorders (HBD). The present study aimed at evaluating the effectiveness of direct-acting antiviral agent (DAA)-based interferon-free HCV antiviral regimens in patients with HBD.Patients and methodsThe present study was performed on the patients with HBD and CHC between 2015 and 2019. Sofosbuvir-based interferon-free regimens with or without ribavirin were prescribed to treat HCV infection. The main endpoint of the study was to determine the sustained virologic response (SVR), assessed 12 weeks after the completion of treatment.ResultsA total of 147 patients with a mean age of 41.1 years were enrolled in the study; 4.1% of them were co-infected with HIV, 25.2% had cirrhosis, and 76.9% of them were diagnosed with hemophilia A. HCV genotype-1 includes the largest number (68.1%) of patients. 46.3% of patients were treatment-naïve and others had a treatment history with interferon-based regimens. Out of 147 patients, 15 patients were lost to follow-up during treatment or for SVR evaluation or discontinued treatment. 132 subjects completed treatment and were evaluated for SVR, 12 weeks after the completion of treatment. All of the patients achieved SVR 12 (SVR rate: 100%, 95% CI 97.2–100%).ConclusionHepatitis C DAA-based regimens are the effective treatments for CHC in patients with HBD, regardless of the treatment modifiers such as previous treatment experience, cirrhosis, HIV co-infection, and HCV genotype.
Axial variation in flexural stiffness of plant stem segments: measurement methods and the influence of measurement uncertainty
Authors: Martin-Nelson Nathanael , Sutherland Brandon , Yancey Michael , Liao Chung Shan , Stubbs Christopher J. , Cook Douglas D. 
Published: October 2021

Abstract
Background
Flexural three-point bending tests are useful for characterizing the mechanical properties of plant stems. These tests can be performed with minimal sample preparation, thus allowing tests to be performed relatively quickly. The best-practice for such tests involves long spans with supports and load placed at nodes. This approach typically provides only one flexural stiffness measurement per specimen. However, by combining flexural tests with analytic equations, it is possible to solve for the mechanical characteristics of individual stem segments.

Results
A method is presented for using flexural tests to obtain estimates of flexural stiffness of individual segments. This method pairs physical test data with analytic models to obtain a system of equations. The solution of this system of equations provides values of flexural stiffness for individual stalk segments. Uncertainty in the solved values for flexural stiffness were found to be strongly dependent upon measurement errors. Row-wise scaling of the system of equations reduced the influence of measurement error. Of many possible test combinations, the most advantageous set of tests for performing these measurements were identified. Relationships between measurement uncertainty and solution uncertainty were provided for two different testing methods.

Conclusions
The methods presented in this paper can be used to measure the axial variation in flexural stiffness of plant stem segments. However, care must be taken to account for the influence of measurement error as the individual segment method amplifies measurement error. An alternative method involving aggregate flexural stiffness values does not amplify measurement error, but provides lower spatial resolution.
New bakuchiol dimers from Psoraleae Fructus and their inhibitory activities on nitric oxide production
Authors: Xu Qingxia , lv Qian , Liu Lu , Zhang Yingtao , Yang Xiuwei 
Published: October 2021

Abstract
Background
Dried fruits of Psoralea corylifolia L. (Psoraleae Fructus) is one of the most popular traditional Chinese medicine with treatment for nephritis, spermatorrhea, pollakiuria, asthma, and various inflammatory diseases. Bakuchiol is main meroterpenoid with bioactive diversity from Psoraleae Fructus. This study was designed to seek structural diverse bakuchiol derivants with anti-inflammatory activities from this plant.

Methods
Various column chromatography methods were used for isolation experiment. Structures and configurations of these compounds were determined by spectroscopic methods and single-crystal X-ray diffraction. Their inhibition on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were evaluated by the Griess reaction.

Results
Twelve unpresented bakuchiol dimmers, bisbakuchiols M–U (1–9) and bisbakuchiol ethers A–C (10–12), along with five known compounds (13–17), were isolated from the fruits of Psoralea corylifolia L. Compounds 1–3, 10–12, 16 and 17 exhibited inhibitory activities against LPS-induced NO production in RAW264.7 macrophages, and the inhibition of compound 1 (half maximal inhibitory concentration (IC50) value = 11.47 ± 1.57 μM) was equal to that of L-N(6)-(1-iminoethyl)-lysine (IC50 = 10.29 ± 1.10 μM) as a positive control.

Conclusions
Some compounds exhibited inhibitory activities against NO production, and the study of structure–activity relationship suggested that uncyclized compounds with oxygen substitution at C-12/12′ showed strong inhibitory activities, and carbonyl units contributed to enhanced activities.
Comparative metabolic profiling of posterior parietal cortex, amygdala, and hippocampus in conditioned fear memory
Authors: Jeon Yoonjeong , Lim Yun , Yeom Jiwoo , Kim Eun-Kyoung 
Published: October 2021

AbstractFear conditioning and retrieval are suitable models to investigate the biological basis of various mental disorders. Hippocampus and amygdala neurons consolidate conditioned stimulus (CS)-dependent fear memory. Posterior parietal cortex is considered important for the CS-dependent conditioning and retrieval of fear memory. Metabolomic screening among functionally related brain areas provides molecular signatures and biomarkers to improve the treatment of psychopathologies. Herein, we analyzed and compared changes of metabolites in the hippocampus, amygdala, and posterior parietal cortex under the fear retrieval condition. Metabolite profiles of posterior parietal cortex and amygdala were similarly changed after fear memory retrieval. While the retrieval of fear memory perturbed various metabolic pathways, most metabolic pathways that overlapped among the three brain regions had high ranks in the enrichment analysis of posterior parietal cortex. In posterior parietal cortex, the most perturbed pathways were pantothenate and CoA biosynthesis, purine metabolism, glutathione metabolism, and NAD+ dependent signaling. Metabolites of posterior parietal cortex including 4′-phosphopantetheine, xanthine, glutathione, ADP-ribose, ADP-ribose 2′-phosphate, and cyclic ADP-ribose were significantly regulated in these metabolic pathways. These results point to the importance of metabolites of posterior parietal cortex in conditioned fear memory retrieval and may provide potential biomarker candidates for traumatic memory-related mental disorders.
Intratumor heterogeneity: the hidden barrier to immunotherapy against MSI tumors from the perspective of IFN-γ signaling and tumor-infiltrating lymphocytes
Authors: Wu Wantao , Liu Yihan , Zeng Shan , Han Ying , Shen Hong 
Published: October 2021

AbstractIn this era of precision medicine, with the help of biomarkers, immunotherapy has significantly improved prognosis of many patients with malignant tumor. Deficient mismatch repair (dMMR)/microsatellite instability (MSI) status is used as a biomarker in clinical practice to predict favorable response to immunotherapy and prognosis. MSI is an important characteristic which facilitates mutation and improves the likelihood of a favorable response to immunotherapy. However, many patients with dMMR/MSI still respond poorly to immunotherapies, which partly results from intratumor heterogeneity propelled by dMMR/MSI. In this review, we discuss how dMMR/MSI facilitates mutations in tumor cells and generates intratumor heterogeneity, especially through type II interferon (IFN-γ) signaling and tumor-infiltrating lymphocytes (TILs). We discuss the mechanism of immunotherapy from the perspective of dMMR/MSI, molecular pathways and TILs, and we discuss how intratumor heterogeneity hinders the therapeutic effect of immunotherapy. Finally, we summarize present techniques and strategies to look at the tumor as a whole to design personalized regimes and achieve favorable prognosis.
An exploration of changes in plantar pressure distributions during walking with standalone and supported lateral wedge insole designs
Authors: Tse Calvin T. F. , Ryan Michael B. , Dien Jason , Scott Alex , Hunt Michael A. 
Published: October 2021

AbstractBackgroundLateral wedge insoles (LWI), standalone or with medial arch support (supported‐LWI), have been thoroughly investigated for their effects on modifying gait biomechanics for people with knee osteoarthritis. However, plantar pressure distribution between these insole types has not been investigated and could provide insight towards insole prescription with concomitant foot symptoms taken into consideration.MethodsIn a sample of healthy individuals (n = 40), in‐shoe plantar pressure was measured during walking with LWI, with or without medial arch support (variable‐ and uniform‐stiffness designs), and a flat control insole condition. Pressure data from the plantar surface of the foot were divided into seven regions: medial/lateral rearfoot, midfoot, medial/central/lateral forefoot, hallux. Plantar pressure outcomes assessed were the medial‐lateral pressure index (MLPI) for the whole foot, and the peak pressure, pressure‐time integral (PTI), and contact area in each plantar region. Comfort in each insole condition was rated as a change relative to the flat control insole condition. Repeated‐measures analyses of variance were calculated to compare the plantar pressure outcomes between insole conditions.ResultsRegionally, medial rearfoot and forefoot pressure were reduced by all wedged insoles, with the variable‐stiffness supported‐wedge showing greater reductions than the standalone wedge. Lateral rearfoot and forefoot pressure were reduced by both supported‐LWI, but unchanged by the standalone wedge. In the midfoot, the standalone wedge maintained pressure but reduced regional contact area, while both supported‐LWI increased midfoot pressure and contact area. All LWI increased the MLPI, indicating a lateral shift in plantar pressure distribution throughout the weightbearing phase of gait. Comfort ratings were not significantly different between insole conditions.ConclusionsRegional differences in plantar pressure may help determine an appropriate lateral wedge insole variation to avoid exacerbation of concomitant foot symptoms by minimizing pressure in symptomatic regions. Lateral shifts in plantar pressure distribution were observed in all laterally wedged conditions, including one supported‐LWI that was previously shown to be biomechanically ineffective for modifying knee joint load distribution. Thus, shifts in foot centre of pressure may not be a primary mechanism by which LWI can modify knee joint load distribution for people with knee osteoarthritis.
Identification and clinical significance of somatic oncogenic mutations in epithelial ovarian cancer
Authors: Watanabe Takafumi , Nanamiya Hideaki , Endo Yuta , Kojima Manabu , Nomura Shinji , Furukawa Shigenori , Soeda Shu , Tamura Hirosumi , Ryufuku Masae , Tanaka Daisuke , Isogai Takao , Imai Jun-ichi , Watanabe Shinya , Fujimori Keiya 
Published: October 2021

Abstract
Objective
Epithelial ovarian cancer (EOC) is a heterogeneous disease with diverse clinicopathological features and behaviors, and its heterogeneity may be concerned with the accumulation of multiple somatic oncogenic mutations. The major goals of this study are to systematically perform the comprehensive mutational profiling in EOC patients, and investigate the associations between somatic mutations and clinicopathological characteristics.

Methods
A total of 80 surgical specimens were obtained from EOC patients who had previously undergone primary debulking surgery, and genomic DNAs were extracted from fresh-frozen tissues. We investigated mutational status in hot spot regions of 50 cancer-related genes by targeted next-generation sequencing using an Ion AmpliSeq Cancer Hotspot Panel v2 Kit.

Results
Validated mutations were detected in 66 of the 80 tumors (82.5%). The five most frequently mutated genes were TP53 (43.8%), PIK3CA (27.5%), KRAS (23.8%), PTEN (10%) and CTNNB1 (10%). PTEN and CTNNB1 mutations were associated with younger age. PIK3CA1, KRAS and CTNNB1 mutations were observed in early-stage, whereas TP53 mutations were more common in advanced stage. Significant associations were observed between TP53 mutation and serous carcinoma, and between KRAS mutation and mucinous carcinoma. Both PIK3CA mutation and CTNNB1 mutation were also significantly associated with endometrioid and clear cell carcinoma. The patients with PIK3CA and KRAS mutations were significantly associated with favorable progression free survival (PFS). In particular, PIK3CA mutations had more significant associations with favorable PFS than PIK3CA wild-type in the endometrioid subtype (P = 0.012). Patients with mutations only in TP53 were significantly associated with worse PFS.

Conclusion
EOCs were heterogeneous at the genomic level and harbored somatic oncogenic mutations. Our molecular profiling may have the potential for becoming a novel stratification within histological subtypes of EOC. Further studies are needed to define molecular classification for improved clinical outcomes and treatment of EOC patients in future.
Hemoglobin life-threatening value (1.9 g/dl) in good general condition: a pediatric case-report
Authors: Parodi Emilia , Riboldi Lorenzo , Ramenghi Ugo 
Published: October 2021

AbstractBackgroundWe report a pediatric patient presenting in good general condition despite a hemoglobin value of 1,9 g/dL, which is normally regarded as life-threatening.Case presentationAn African 5 years-old girl presented to our Emergency Department (ED) for worsening asthenia, within a clinical picture of good general condition. The hemoglobin value at admission was 1,9 g/dL. The subsequent diagnostic-therapeutic pathway highlighted the presence of two different causes, both well known to be responsible for chronic anemia (with slow reduction of hemoglobin values): iron deficiency anemia (IDA) due to a very low dietary intake of iron-rich foods, and homozygous sickle cell disease (HbSS). She received transfusions of packed red blood cells (overall 15 ml/kg) and subsequently intravenous iron preparations (total amount 200 mg) followed by oral iron supplements. The Hb value at discharge, 10 days after the admission, was 9.8 g/dL.ConclusionsWhen approaching a picture of severe anemia, we suggest pediatricians take into consideration clinical conditions rather than laboratory values and to take advantage of detailed anamnestic data in order to make the diagnosis.
Differential regulation of mRNA fate by the human Ccr4-Not complex is driven by coding sequence composition and mRNA localization
Authors: Gillen Sarah L. , Giacomelli Chiara , Hodge Kelly , Zanivan Sara , Bushell Martin , Wilczynska Ania 
Published: October 2021

Abstract
Background
Regulation of protein output at the level of translation allows for a rapid adaptation to dynamic changes to the cell’s requirements. This precise control of gene expression is achieved by complex and interlinked biochemical processes that modulate both the protein synthesis rate and stability of each individual mRNA. A major factor coordinating this regulation is the Ccr4-Not complex. Despite playing a role in most stages of the mRNA life cycle, no attempt has been made to take a global integrated view of how the Ccr4-Not complex affects gene expression.

Results
This study has taken a comprehensive approach to investigate post-transcriptional regulation mediated by the Ccr4-Not complex assessing steady-state mRNA levels, ribosome position, mRNA stability, and protein production transcriptome-wide. Depletion of the scaffold protein CNOT1 results in a global upregulation of mRNA stability and the preferential stabilization of mRNAs enriched for G/C-ending codons. We also uncover that mRNAs targeted to the ER for their translation have reduced translational efficiency when CNOT1 is depleted, specifically downstream of the signal sequence cleavage site. In contrast, translationally upregulated mRNAs are normally localized in p-bodies, contain disorder-promoting amino acids, and encode nuclear localized proteins. Finally, we identify ribosome pause sites that are resolved or induced by the depletion of CNOT1.

Conclusions
We define the key mRNA features that determine how the human Ccr4-Not complex differentially regulates mRNA fate and protein synthesis through a mechanism linked to codon composition, amino acid usage, and mRNA localization.
Mapping and modeling the genomic basis of differential RNA isoform expression at single-cell resolution with LR-Split-seq
Authors: Rebboah Elisabeth , Reese Fairlie , Williams Katherine , Balderrama-Gutierrez Gabriela , McGill Cassandra , Trout Diane , Rodriguez Isaryhia , Liang Heidi , Wold Barbara J. , Mortazavi Ali 
Published: October 2021

AbstractThe rise in throughput and quality of long-read sequencing should allow unambiguous identification of full-length transcript isoforms. However, its application to single-cell RNA-seq has been limited by throughput and expense. Here we develop and characterize long-read Split-seq (LR-Split-seq), which uses combinatorial barcoding to sequence single cells with long reads. Applied to the C2C12 myogenic system, LR-split-seq associates isoforms to cell types with relative economy and design flexibility. We find widespread evidence of changing isoform expression during differentiation including alternative transcription start sites (TSS) and/or alternative internal exon usage. LR-Split-seq provides an affordable method for identifying cluster-specific isoforms in single cells.
The challenge of equipoise in trials with a surgical and non-surgical comparison: a qualitative synthesis using meta-ethnography
Authors: Davies Loretta , Beard David , Cook Jonathan A. , Price Andrew , Osbeck Ida , Toye Francine 
Published: October 2021

Abstract
Background
Randomised controlled trials in surgery can be a challenge to design and conduct, especially when including a non-surgical comparison. As few as half of initiated surgical trials reach their recruitment target, and failure to recruit is cited as the most frequent reason for premature closure of surgical RCTs. The aim of this qualitative evidence synthesis was to identify and synthesise findings from qualitative studies exploring the challenges in the design and conduct of trials directly comparing surgical and non-surgical interventions.

Methods
A qualitative evidence synthesis using meta-ethnography was conducted. Six electronic bibliographic databases (Medline, Central, Cinahl, Embase and PsycInfo) were searched up to the end of February 2018. Studies that explored patients’ and health care professionals’ experiences regarding participating in RCTs with a surgical and non-surgical comparison were included. The GRADE-CERQual framework was used to assess confidence in review findings.

Results
In total, 3697 abstracts and 49 full texts were screened and 26 published studies reporting experiences of patients and healthcare professionals were included. The focus of the studies (24/26) was primarily related to the challenge of recruitment. Two studies explored reasons for non-compliance to treatment allocation following randomisation. Five themes related to the challenges to these types of trials were identified: (1) radical choice between treatments; (2) patients’ discomfort with randomisation: I want the best treatment for me as an individual; (3) challenge of equipoise: patients’ a priori preferences for treatment; (4) challenge of equipoise: clinicians’ a priori preferences for treatment and (5) imbalanced presentation of interventions.

Conclusion
The marked dichotomy between the surgical and non-surgical interventions was highlighted in this review as making recruitment to these types of trials particularly challenging. This review identified factors that increase our understanding of why patients and clinicians may find equipoise more challenging in these types of trials compared to other trial comparisons. Trialists may wish to consider exploring the balance of potential factors influencing patient and clinician preferences towards treatments before they start recruitment, to enable issues specific to a particular trial to be identified and addressed. This may enable trial teams to make more efficient considered design choices and benefit the delivery of such trials.