bluuebunny/crossref_metadata_2025_split huggingface dataset:
Realigning Expectations With Reality: A Case Study on Maternal Mental Health During a Difficult Breastfeeding Journey
Authors: Elder Mason , Murphy Lorann , Notestine Stacy , Weber Ashley 
Published: July 2021

Introduction: Many mothers have the goal to breastfeed. However, more than 50% will have breastfeeding difficulty by the 3rd day of life. Mothers who are unable to meet their breastfeeding goals are at higher risk for anxiety, depression, embarrassment, and guilt. Those who stop breastfeeding need support and help resolving these feelings. This case study aims to describe one woman’s difficulty with mental health surrounding breastfeeding, her decision to bottle feed, and her successful transition back to direct breastfeeding. Main Issue: Barriers to the participant’s success with breastfeeding were pre-existing history of depression/anxiety, forceps delivery, uncontrolled perineal pain, infant physical trauma, and nipple/flow confusion. The decision to discontinue direct breastfeeding and start bottle feeding came after 2 months of anxiety, frustration, and persistence. Management: The participant followed her healthcare team’s recommendations of triple feeding, lactation support groups, pediatric chiropractic adjustments, and prescribed galactagogues. After 2 months of exhaustion and deliberation, she made the difficult decision to stop breastfeeding for nutritional benefits and switched to breastfeeding only for her infant’s pleasure and comfort. Lowered expectations allowed the dyad to heal and her son to transition to nearly exclusive breastfeeding at 4 months of life. Conclusion: Clinicians must be aware of the delicate balance between promoting breastfeeding for its nutritional value and health benefits and supporting a struggling mother with mental health needs.
The Italian version of the Unité Rhumatologique des Affections de la Main (URAM) for Dupuytren’s disease: The URAM-I(10)
Authors: Lanfranchi E , Fairplay T , Arcuri P , Lando M , Marinelli F , Pillastrini P , Vanti C 
Published: July 2021

Introduction Several general hand functional assessment tools for Dupuytren’s disease have been reported, but none of the patient-reported-outcome measures specific to Dupuytren’s disease-associated disabilities are available in the Italian language. The purpose of this study was to culturally adapt the Unité Rhumatologique des Affections de la Main (URAM) into Italian (URAM-I) and determine its measurement properties. Methods Cross-cultural adaptation was performed according to the current guidelines. Construct validity (convergent and divergent validity) was measured by comparing the URAM-I with the Pain-Rated Wrist/Hand Evaluation (PRWHE-I), Short-Form 36 (SF-36-I) scale and finger range of motion, respectively. Factor analysis was used to investigate the URAM-I’s internal structure. Reliability was assessed by internal consistency (Cronbach’s alpha) and test-retest reliability by Intra-Class Correlation Coefficient (ICC). Results This study included 96 patients (males = 85%, age = 66.8 ± 9.3). Due to the cultural adaptation, we divided the original item #1 into two separate items, thus generating the URAM-I(10). Convergent validity analysis showed a strong positive (r = 0.67), significant (p < 0.01) Pearson’s correlation with the PRWHE-I. Divergent validity analysis showed a weak, negative (r < 0.3) and not significant correlation with the SF-36-I subscales, except for the physical pain subscale (r = −0.21, p < 0.05). Factor analysis revealed a 2-factor, 4-item solution that explained 76% of the total variance. The URAM-I(10) demonstrated high internal consistency (α = 0.94) and high test-retest reliability (ICC = 0.97). Conclusion The URAM-I(10) demonstrates moderate construct validity, high internal consistency and test-retest reliability, and showed a 2-factor internal structure. Its evaluative use can be suggested for the Italian Dupuytren’s population.
Phase 2 study of danicopan in patients with paroxysmal nocturnal hemoglobinuria with an inadequate response to eculizumab
Authors: Kulasekararaj Austin G. , Risitano Antonio M. , Maciejewski Jaroslaw P. , Notaro Rosario , Browett Peter , Lee Jong Wook , Huang Mingjun , Geffner Michael , Brodsky Robert A. 
Published: July 2021

Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by uncontrolled terminal complement activation and subsequent intravascular hemolysis (IVH). C5 inhibitors prevent membrane attack complex formation, but patients may experience extravascular hemolysis (EVH) and continue to require blood transfusions. Danicopan, an oral proximal complement inhibitor of alternative pathway factor D (FD), is designed to control IVH and EVH. In a phase 2 dose-finding trial, eculizumab-treated transfusion-dependent patients with PNH (n = 12) received danicopan, 100 to 200 mg thrice daily, in addition to their eculizumab regimen for 24 weeks. End points included hemoglobin (Hgb) change vs baseline at week 24 (primary), reduction in blood transfusions, and patient-reported outcomes. Safety, tolerability, and pharmacokinetics/pharmacodynamics were measured. Twelve patients received ≥1 danicopan dose; 1 patients discontinued from a serious adverse event deemed unlikely related to danicopan. Eleven patients completed the 24-week treatment period. Addition of danicopan resulted in a mean Hgb increase of 2.4 g/dL at week 24. In the 24 weeks prior to danicopan, 10 patients received 31 transfusions (50 units) compared with 1 transfusion (2 units) in 1 patient during the 24-week treatment period. Mean Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score increased by 11 points from baseline to week 24. The most common adverse events were headache, cough, and nasopharyngitis. Addition of danicopan, a first-in-class FD inhibitor, led to a meaningful improvement in Hgb and reduced transfusion requirements in patients with PNH who were transfusion-dependent on eculizumab. These benefits were associated with improvement of FACIT-Fatigue. This trial was registered at www.clinicaltrials.gov as #NCT03472885.
Repeated oxytocin prevents central sensitization by regulating synaptic plasticity via oxytocin receptor in a chronic migraine mouse model
Authors: Wang Yunfeng , Pan Qi , Tian Ruimin , Wen Qianwen , Qin Guangcheng , Zhang Dunke , Chen Lixue , Zhang Yixin , Zhou Jiying 
Published: July 2021

Abstract
Background
Central sensitization is one of the characters of chronic migraine (CM). Aberrant synaptic plasticity can induce central sensitization. Oxytocin (OT), which is a hypothalamic hormone, plays an important antinociceptive role. However, the antinociceptive effect of OT and the underlying mechanism in CM remains unclear. Therefore, we explored the effect of OT on central sensitization in CM and its implying mechanism, focusing on synaptic plasticity.

Methods
A CM mouse model was established by repeated intraperitoneal injection of nitroglycerin (NTG). Von Frey filaments and radiant heat were used to measure the nociceptive threshold. Repeated intranasal OT and intraperitoneal L368,899, an oxytocin receptor (OTR) antagonist, were administered to investigate the effect of OT and the role of OTR. The expression of calcitonin gene-related peptide (CGRP) and c-fos were measured to assess central sensitization. N-methyl D-aspartate receptor subtype 2B (NR2B)-regulated synaptic-associated proteins and synaptic plasticity were explored by western blot (WB), transmission electron microscope (TEM), and Golgi-Cox staining.

Results
Our results showed that the OTR expression in the trigeminal nucleus caudalis (TNC) of CM mouse was significantly increased, and OTR was colocalized with the postsynaptic density protein 95 (PSD-95) in neurons. Repeated intranasal OT alleviated the NTG-induced hyperalgesia and prevented central sensitization in CM mouse. Additionally, the OT treatment inhibited the overexpression of phosphorylated NR2B and synaptic-associated proteins including PSD-95, synaptophysin-1 (syt-1), and synaptosomal-associated protein 25 (snap25) in the TNC of CM mouse and restored the abnormal synaptic structure. The protective effect of OT was prevented by L368,899. Furthermore, the expression of adenylyl cyclase 1 (AC1)/ protein kinase A (PKA)/ phosphorylation of cyclic adenosine monophosphate response element-binding protein (pCREB) pathway was depressed by OT and restored by L368,899.

Conclusions
Our findings demonstrate that repeated intranasal OT eliminates central sensitization by regulating synaptic plasticity via OTR in CM. The effect of OT has closely associated with the down-regulation of AC1/PKA/pCREB signaling pathway, which is activated in CM model. Repeated intranasal OT may be a potential candidate for CM prevention.
Mixture toxic impacts and the related mechanism of aflatoxin B1 and deoxynivalenol on embryonic zebrafish (Danio rerio)
Authors: Wang Yanhua , Wang Qiang , Ji Chun , Guo Xiaoxuan , Yang Guiling , Wang Dou , Weng Hongbiao , Qian Yongzhong , Chen Chen 
Published: July 2021

AbstractBackgroundAlthough humans and animals are often simultaneously exposed to a variety of mycotoxins via feed and food consumption, in which aflatoxin B1 (AFB1) and deoxynivalenol (DON) is one of the most prevalent combination of mycotoxins. Many toxicological studies have merely focused on the impacts of single mycotoxins. In the present study, the combined toxicity and the related mechanism of AFB1 and DON to zebrafish (Danio rerio) were investigated.ResultsResults exhibited that DON had lower toxicity to embryonic zebrafish with a 7-day LC50of 218.3 mg a.i. L−1in comparison to AFB1 (0.031 mg a.i. L−1). The mixture of AFB1 and DON elicited an additive combined effect on zebrafish embryos. The levels of CAT, caspase-3, and T4 markedly varied in most single and mixture groups. The expressions of four genes (cas3,apaf-1,cc-chem,andcyp19a) associated with oxidative stress, cellular apoptosis, immune system, and endocrine system were markedly varied upon the mixture exposure in comparison to the corresponding single exposure of AFB1 or DON.ConclusionsOur results revealed that the impacts of a mixture could not be estimated solely based on toxicities of the single mycotoxins. Taken together, our comprehensive investigation on the mycotoxin mixtures and their potential mechanisms could better reflect the reality of mycotoxin contamination in food and feed.
Determination of genetic effects and functional SNPs of bovine HTR1B gene on milk fatty acid traits
Authors: Cao Mingyue , Shi Lijun , Peng Peng , Han Bo , Liu Lin , Lv Xiaoqing , Ma Zhu , Zhang Shengli , Sun Dongxiao 
Published: July 2021

Abstract
Background
Our previous genome-wide association study (GWAS) on milk fatty acid traits in Chinese Holstein cows revealed, the SNP, BTB-01556197, was significantly associated with C10:0 at genome-wide level (P = 0.0239). It was located in the down-stream of 5-hydroxytryptamine receptor 1B (HTR1B) gene that has been shown to play an important role in the regulation of fatty acid oxidation. Hence, we considered it as a promising candidate gene for milk fatty acids in dairy cattle. In this study, we aimed to investigate whether the HTR1B gene had significant genetic effects on milk fatty acid traits.

Results
We re-sequenced the entire coding region and 3000 bp of 5′ and 3′ flanking regions of HTR1B gene. A total of 13 SNPs was identified, containing one in 5′ flanking region, two in 5′ untranslated region (UTR), two in exon 1, five in 3′ UTR, and three in 3′ flanking region. By performing genotype-phenotype association analysis with SAS9.2 software, we observed that 13 SNPs were significantly associated with medium-chain saturated fatty acids such as C6:0, C8:0 and C10:0 (P < 0.0001 ~ 0.042). With Haploview 4.1 software, linkage disequilibrium (LD) analysis was performed. Two haplotype blocks formed by two and ten SNPs were observed. Haplotype-based association analysis indicated that both haplotype blocks were strongly associated with C6:0, C8:0 and C10:0 as well (P < 0.0001 ~ 0.0071). With regards to the missense mutation in exon 1 (g.17303383G > T) that reduced amino acid change from alanine to serine, we predicted that it altered the secondary structure of HTR1B protein with SOPMA. In addition, we predicted that three SNPs in promoter region, g.17307103A > T, g.17305206 T > G and g.17303761C > T, altered the binding sites of transcription factors (TFs) HMX2, PAX2, FOXP1ES, MIZ1, CUX2, DREAM, and PPAR-RXR by Genomatix. Of them, luciferase assay experiment further confirmed that the allele T of g.17307103A > T significantly increased the transcriptional activity of HTR1B gene than allele A (P = 0.0007).

Conclusions
In conclusion, our findings provided first evidence that the HTR1B gene had significant genetic effects on milk fatty acids in dairy cattle.
Dynamic changes of miRNAs in skeletal muscle development at New Zealand rabbits
Authors: Jing Jing , Jiang Xichun , Zhu Cuiyun , Zheng Qi , Ji Qianyun , Yin Huiqun , Huang Jingtong , Zhu Yixiao , Wang Jiao , Qin Shuaiqi , Ling Yinghui 
Published: July 2021

Abstract
Background
miRNA is one of the crucial roles in the complex and dynamic network that regulates the development of skeletal muscle. The landscape of skeletal muscle miRNAs from fetus to adult in New Zealand rabbits has not been revealed yet.

Results
In this study, nine RNA-seq libraries of fetus, child and adult rabbits’ leg muscles were constructed. A total of 278 differentially expressed miRNAs (DEmiRNAs) were identified. In the fetus vs. child group, the main functional enrichments were involved in membrane and transport. Pathway enriched terms of up-regulated DEmiRNAs were connected with the differentiation and hypertrophy of skeletal muscle, and down-regulated ones were related to muscle structure and metabolic capacity. In the child vs. adult group, functions were associated to positioning and transportation, and pathways were relevant to ECM, muscle structure and hypertrophy. Finally, ocu-miR-185-3p and ocu-miR-370-3p, which had the most target genes, were identified as hub-miRNAs in these two groups.

Conclusions
In short, we summarized the highly expressed and uniquely expressed DEmiRNAs of fetus, child and adult rabbits’ leg muscles. Besides, the potential functional changes of miRNAs in two consecutive stages have been explored. Among them, the ocu-miR-185-3p and ocu-miR-370-3p with the most target genes were selected as hub-miRNAs. These data improved the understanding of the regulatory molecules of meat rabbit development, and provided a novel perspective for molecular breeding of meat rabbits.
Hemogram-derived ratios as prognostic markers of ICU admission in COVID-19
Authors: Velazquez Sara , Madurga Rodrigo , Castellano José María , Rodriguez-Pascual Jesús , de Aguiar Diaz Obregon Santiago Ruiz , Jimeno Sara , Montero Juan Ignacio , Wichner Paula Sol Ventura , López-Escobar Alejandro 
Published: July 2021

Abstract
Background
The vast impact of COVID-19 call for the identification of clinical parameter that can help predict a torpid evolution. Among these, endothelial injury has been proposed as one of the main pathophysiological mechanisms underlying the disease, promoting a hyperinflammatory and prothrombotic state leading to worse clinical outcomes. Leukocytes and platelets play a key role in inflammation and thrombogenesis, hence the objective of the current study was to study whether neutrophil-to-lymphocyte ratio (NLR), platelets-to-lymphocyte ratio (PLR), the systemic immune-inflammation index (SII) as well as the new parameter neutrophil-to-platelet ratio (NPR), could help identify patients who at risk of admission at Intensive Care Units.

Methods
A retrospective observational study was performed at HM Hospitales including electronic health records from 2245 patients admitted due to COVID-19 from March 1 to June 10, 2020. Patients were divided into two groups, admitted at ICU or not.

Results
Patients who were admitted at the ICU had significantly higher values in all hemogram-derived ratios at the moment of hospital admission compared to those who did not need ICU admission. Specifically, we found significant differences in NLR (6.9 [4–11.7] vs 4.1 [2.6–7.6], p <  0.0001), PLR (2 [1.4–3.3] vs 1.9 [1.3–2.9], p = 0.023), NPR (3 [2.1–4.2] vs 2.3 [1.6–3.2], p <  0.0001) and SII (13 [6.5–25.7] vs 9 [4.9–17.5], p <  0.0001) compared to those who did not require ICU admission. After multivariable logistic regression models, NPR was the hemogram-derived ratio with the highest predictive value of ICU admission, (OR 1.11 (95% CI: 0.98–1.22, p = 0.055).

Conclusions
Simple, hemogram-derived ratios obtained from early hemogram at hospital admission, especially the novelty NPR, have shown to be useful predictors of risk of ICU admission in patients hospitalized due to COVID-19.
Heme oxygenase-1 and neopterin plasma/serum levels and their role in diagnosing active and latent TB among HIV/TB co-infected patients: a cross sectional study
Authors: Uwimaana Esther , Bagaya Bernard S. , Castelnuovo Barbara , Kateete David P. , Godwin Anguzu , Kiwanuka Noah , Whalen Christopher C. , Joloba Moses L. 
Published: July 2021

Abstract
Background
Tuberculosis (TB) diagnosis in the context of HIV co-infection remains challenging. Heme oxygenase 1 (HO-1) and neopterin have been validated as potential biomarkers for TB diagnosis. Latent TB infection (LTBI) is diagnosed using tuberculin skin test (TST) and interferon gamma release assays (T-Spot and QuantiFERON TB gold tests, respectively). However, these tests have shown challenges and yet diagnosing LTBI is important for the overall control of TB. This study was conducted to determine the levels of H0–1 and neopterin, and their role in the diagnosis of TB among individuals enrolled in the Community Health and Social Network of Tuberculosis (COHSONET) study and the Kampala TB Drug Resistance Survey (KDRS).

Methods
This was a nested cross-sectional study. Plasma and serum samples collected from 140 patients at Mulago National Referral Hospital, Kampala Uganda were used. M.tb culture was performed on sputum to confirm active TB(ATB) and QuantiFERON TB gold test to confirm latent TB infection (LTBI). ELISAs were performed to determine the levels of HO-1 and neopterin. Data analysis was done using t-test and Receiver Operating Characteristic curves to determine the diagnostic accuracy.

Results
HO-1 levels among active tuberculosis (ATB)/HIV-infected patients and LTBI/HIV-infected patients were 10.7 ng/ml (IQR: 7.3–12.7 ng/ml) and 7.5 ng/ml (IQR: 5.4–14.1 ng/ml) respectively. Neopterin levels among ATB/HIV-positive patients and LTBI/HIV-positive patients were 11.7 ng/ml (IQR: 5.2.4 ng/ml) and 8.8 ng/ml (IQR: 2.4–19.8 ng/ml), respectively. HO-1 showed a sensitivity of 58.57% and a specificity of 67.14% with area under the curve (AUC) of 0.57 when used to discriminate between ATB and LTB. Neopterin showed an AUC of 0.62 with a sensitivity of 57.14% and a specificity of 60.0% when used to distinguish ATB from LTB.

Conclusion
There was no in significant difference in HO-1 concentration levels of ATB individuals compared to LTB individuals. There was a significant difference in neopterin concentrations levels of ATB individuals compared to latently infected individuals. Findings from this study, show that HO-1 and neopterin have poor ability to distinguish between ATB and LTB.
A different point of view: the evaluation of motor imagery perspectives in patients with sensorimotor impairments in a longitudinal study
Authors: Gäumann Szabina , Gerber Rahel Sarah , Suica Zorica , Wandel Jasmin , Schuster-Amft Corina 
Published: July 2021

Abstract
Background
Motor imagery (MI) has been successfully applied in neurological rehabilitation. Little is known about the spontaneous selection of the MI perspectives in patients with sensorimotor impairments. What perspective is selected: internal (first-person view), or external (third-person view)? The aim was to evaluate the MI perspective preference in patients with sensorimotor impairments.

Methods
In a longitudinal study including four measurement sessions, 55 patients (25 stroke, 25 multiple sclerosis, 5 Parkinson’s disease; 25 females; mean age 58 ± 14 years) were included. MI ability and perspective preference in both visual and kinaesthetic imagery modalities were assessed using the Kinaesthetic and Visual Imagery Questionnaire-20 (KVIQ-20), the body rotation task (BRT), and mental chronometry (MC). Additionally, patients’ activity level was assessed. Descriptive analyses were performed regarding different age- (< 45, 45–64, > 64), activity levels (inactive, partially active, active), and KVIQ-20 movement classifications (axial, proximal, distal, upper and lower limb). A mixed-effects model was used to investiage the relationship between the primary outcome (MI perspective: internal, external) with the explanatory variables age, MI modality (visual, kinaesthetic), movement type (axial, proximal, distal), activity levels and the different assessments (KVIQ-20, BRT, MC).

Results
Imagery modality was not a significant predictor of perspective preference. Over the four measurement sessions, patients tended to become more consistent in their perspective selection, however, time point was not a significant predictor. Movement type was a significant predictor: imagination of distal vs. axial and proximal vs. axial movements were both associated with preference for external perspective. Patients with increased physical activity level tend to use internal imagery, however, this effect was borderline not statistically significant. Age was neither a significant precictor. Regarding the MI assessments, the KVIQ- 20 score was a significant predictor. The patients with higher test scores tend to use the external perspective.

Conclusion
It is recommended to evaluate the spontaneous MI perspective selection to design patient-specific MI training interventions. Distal movements (foot, finger) may be an indicator when evaluating the consistency of the MI perspective in patients with sensorimotor impairments.
Feasibility and effectiveness of afatinib for poor performance status patients with EGFR-mutation-positive non-small-cell lung cancer: a retrospective cohort study
Authors: Wu Chiao-En , Chang Ching-Fu , Huang Chen-Yang , Yang Cheng-Ta , Kuo Chih-Hsi Scott , Hsu Ping-Chih , Chang John Wen-Cheng 
Published: July 2021

Abstract
Background
Afatinib is one of the standard treatments for patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). However, data on the use of afatinib in patients with poor performance status (PS ≥ 2) are limited. This study aimed to retrospectively review the clinical outcomes and safety of afatinib treatment in EGFR-mutation-positive (EGFRm+) NSCLC patients with PS ≥ 2.

Methods
The data for 62 patients who were treated at Linkou Chang Gung Memorial Hospital from January 2010 to August 2019 were retrospectively reviewed. Patients’ clinicopathological features were obtained, and univariate and multivariate analyses were performed to identify possible prognostic factors. Data on adverse events were collected to evaluate general tolerance for afatinib therapy.

Results
Until February 2020, the objective response rate, disease control rate, median progression-free survival (PFS), and overall survival (OS) were 58.1% (36/62), 69.4% (43/62), 8.8 months, and 12.9 months, respectively. The absence of liver metastasis (PFS: p = 0.044; OS: p = 0.061) and good disease control (p < 0.001 for PFS and OS) were independent favorable prognostic factors for PFS and OS. Bone metastasis (p = 0.036) and dose modification (reduction/interruption, p = 0.021) were predictors of disease control.

Conclusion
Afatinib demonstrated acceptable efficacy and safety in the current cohort. This study provided evidence to support the use of afatinib as a first-line treatment in EGFRm+ NSCLC patients with poor PS.