bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unexpected suppression of tumorigenesis by c-MYC via TFAP4-dependent restriction of stemness in B lymphocytes
Authors: Tonc Elena , Takeuchi Yoshiko , Chou Chun , Xia Yu , Holmgren Melanie , Fujii Chika , Raju Saravanan , Chang Gue Su , Iwamoto Masahiro , Egawa Takeshi 
Published: July 2021

Abstract
The proliferative burst of B lymphocytes is essential for antigen receptor repertoire diversification during the development and selective expansion of antigen-specific clones during immune responses. High proliferative activity inevitably promotes oncogenesis, the risk of which is further elevated in B lymphocytes by endogenous gene rearrangement and somatic mutations. However, B-cell–derived cancers are rare, perhaps owing to putative intrinsic tumor-suppressive mechanisms. We show that c-MYC facilitates B-cell proliferation as a protumorigenic driver and unexpectedly coengages counteracting tumor suppression through its downstream factor TFAP4. TFAP4 is mutated in human lymphoid malignancies, particularly in &gt;10% of Burkitt lymphomas, and reduced TFAP4 expression was associated with poor survival of patients with MYC-high B-cell acute lymphoblastic leukemia. In mice, insufficient TFAP4 expression accelerated c-MYC–driven transformation of B cells. Mechanistically, c-MYC suppresses the stemness of developing B cells by inducing TFAP4 and restricting self-renewal of proliferating B cells. Thus, the pursuant transcription factor cascade functions as a tumor suppressor module that safeguards against the transformation of developing B cells.
Differential long non-coding RNA expression profile and function analysis in primary Sjogren’s syndrome
Authors: Chen Xiaochan , Cheng Qi , Du Yan , Liu Lei , Wu Huaxiang 
Published: July 2021

Abstract
Background
Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease characterized by abnormal immune cell activation. This study aimed to investigate differentially expressed long non-coding RNA (lncRNA) in peripheral blood mononuclear cells (PBMCs) in patients with pSS to identify lncRNAs that affect pSS pathogenesis.

Methods
Total RNA was extrated from PBMCs of 30 patients with pSS and 15 healthy persons. Transcriptome sequencing was used to screen differentially expressed lncRNAs and mRNAs in 8 RNA samples from the discovery cohort. The differentially expressed mRNAs underwent functional enrichment analysis. A protein interaction relationship (PPI) and competitive endogenous RNA (ceRNA) network was constructed. Real-time PCR was used to validate screened lncRNAs in all 45 RNA samples..

Results
1180 lncRNAs and 640 mRNAs were differentially expressed in pSS patients (fold change > 2 in healthy persons). The PPI network was constructed with 640 mRNAs and a ceRNA network with four key lncRNAs (GABPB1-AS1, PSMA3-AS1, LINC00847 and SNHG1). Real-time PCR revealed that GABPB1-AS1 and PSMA3-AS1 were significantly up-regulated 3.0- and 1.4-fold in the pSS group, respectively. The GABPB1-AS1 expression level was positively correlated with the percentage of B cells and IgG levels.

Conclusions
GABPB1-AS1 was significently up-regulated in pSS patients, and its expression level is positively correlated with the percentage of B cells and IgG levels. GABPB1-AS1 may be involved in the pathogenesis of pSS and may be a promising biological marker.
Genome-wide association mapping reveals new loci associated with light-colored seed coat at harvest and slow darkening in carioca beans
Authors: de Almeida Caléo Panhoca , Santos Isabella Laporte , de Carvalho Paulino Jean Fausto , Barbosa Caio Cesar Ferrari , Pereira Cássia Cristina Augusto , Carvalho Cassia Regina Limonta , de Moraes Cunha Gonçalves Gabriel , Song Qijian , Carbonell Sérgio Augusto Morais , Chiorato Alisson Fernando , Benchimol-Reis Luciana Lasry 
Published: July 2021

AbstractBackgroundCommon bean (Phaseolus vulgarisL.) is a legume whose grain can be stored for months, a common practice among Brazilian growers. Over time, seed coats become darker and harder to cook, traits that are undesirable to consumers, who associate darker-colored beans with greater age. Like commercial pinto and cranberry bean varieties, carioca beans that have darker seeds at harvest time and after storage are subject to decreased market values.ResultsThe goal of our study was to identify the genetic control associated with lightness of seed coat color at harvest (HL) and with tolerance to post-harvest seed coat darkening (PHD) by a genome-wide association study. For that purpose, a carioca diversity panel previously validated for association mapping studies was used with 138 genotypes and 1,516 high-quality SNPs. The panel was evaluated in two environments using a colorimeter and the CIELAB scale. Shelf storage for 30 days had the most expressive results and the L* (luminosity) parameter led to the greatest discrimination of genotypes. Three QTL were identified for HL, two on chromosome Pv04 and one on Pv10. Regarding PHD, results showed that genetic control differs for L* after 30 days and for the ΔL* (final L*—initial L*); only ΔL* was able to properly express the PHD trait. Four phenotypic classes were proposed, and five QTL were identified through six significant SNPs.ConclusionsLightness of seed coat color at harvest showed an oligogenic inheritance corroborated by moderate broad-sense heritability and high genotypic correlation among the experiments. Only three QTL were significant for this trait – two were mapped on Pv04 and one on Pv10. Considering the ΔL, six QTL were mapped on four different chromosomes for PHD. The same HL QTL at the beginning of Pv10 was also associated with ΔL* and could be used as a tool in marker-assisted selection. Several candidate genes were identified and may be useful to accelerate the genetic breeding process.
The association of timing of repeat cesarean with outcomes among a cohort of Guatemalan women with a history of prior cesarean birth
Authors: Harrison Margo S. , Garces Ana , Figueroa Lester , Westcott Jamie , Hambidge Michael , Krebs Nancy F. 
Published: July 2021

Abstract
Background
The objective of this analysis was to observe whether maternal and perinatal/neonatal outcomes of birth vary by timing of repeat cesarean among women with a history of one prior cesarean birth in a Guatemalan cohort.

Methods
This secondary analysis was conducted using data from a prospective study conducted in communities in Chimaltenango, Guatemala through the Global Network for Women’s and Children’s Health Research.

Results
Between January 2017 and April 2020, 26,465 women delivered; 3,143 (11.9%) of those women had a singleton gestation and a history of prior cesarean delivery. 2,210 (79.9%) women with a history of prior cesarean birth had data available on mode of delivery and gave birth by repeat cesarean; 1312 (59.4%) were pre-labor cesareans while 896 (40.5%) were intrapartum cesarean births. Risk factors associated with an increased risk of intrapartum cesarean birth included hospital delivery as compared to “other” location (ARR 1.6 [1.2,2.1]) and dysfunctional labor (ARR 1.6 [1.4,1.9]). Variables associated with a reduced risk of intrapartum cesarean birth were hypertensive disease (ARR 0.7 [0.6,0.9]), schooling (ARR 0.9 [0.8,0.9]), and increasing age, which was associated with a very slight reduction in the outcome (ARR 0.99 [0.98,0.99]). Maternal and neonatal outcomes did not vary by type of cesarean birth.

Conclusion
Outcomes of cesarean birth do not seem to vary by timing of repeat cesarean birth, with hypertensive disease increasing the likelihood of pre-labor cesarean. This information might be useful in counseling women that outcomes after failed trial of labor do not appear worse than those after pre-labor cesarean birth.
Usefulness of readout-segmented EPI-based diffusion tensor imaging of lacrimal gland for detection and disease staging in thyroid-associated ophthalmopathy
Authors: Chen Lu , Hu Hao , Chen Wen , Wu Qian , Zhou Jiang , Chen Huan-Huan , Xu Xiao-Quan , Shi Hai-Bin , Wu Fei-Yun 
Published: July 2021

Abstract
Background
Dysfunction of lacrimal gland (LG) gains increasing attention in patients with thyroid-associated ophthalmopathy (TAO), while the underlying pathological change is still not fully established. This study aimed to evaluate the utility of readout-segmented echo-planar imaging (rs-EPI)-based diffusion tensor imaging (DTI) in non-invasively detecting microstructural alterations of LG in patients with TAO, as well as in discriminating disease activity.

Methods
Thirty TAO patients and 15 age- and sex- matched healthy controls, who underwent rs-EPI-based DTI, were retrospectively enrolled. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of LG, and clinical-endocrinological variables were collected and compared. The correlations between FA and ADC values of LG and serum thyroid biochemical markers were also assessed.

Results
TAO group showed significantly lower FA (P < 0.001) and higher ADC (P = 0.014) of LG than healthy group. Active subgroup had significantly lower FA (P < 0.001) and higher ADC (P < 0.001) than inactive subgroup. In TAO group, FA of LG was significantly and negatively correlated with TRAb (r=-0.475, P = 0.008), while ADC of LG showed no significant correlation (P > 0.05). The area under receiver operating characteristic curve of FA was significantly greater than that under curve of ADC for discriminating disease activity (0.832 vs. 0.570, P = 0.009).

Conclusions
rs-EPI-based DTI is a useful tool to characterize the microstructural change of LG in patients with TAO. The derived metrics, particularly FA, can help to reveal disease activity.
RAB33B and PCNT variants in two Pakistani families with skeletal dysplasia and short stature
Authors: Ain Noor ul , Fatima Zunaira , Naz Sadaf , Makitie Outi 
Published: July 2021

Abstract
Background
Skeletal dysplasia is a heterogeneous group of disorders resulting from different genetic variants in humans. The current study was designed to identify the genetic causes of skeletal dysplasia and short stature in two consanguineous families from Pakistan, both comprised of multiple affected individuals. Patients in one family had proportionate short stature with reduced head circumference while affected individuals in the other family had disproportionate short stature.

Methods
Clinical data were obtained and radiological examinations of the index patients were completed. Whole genome sequencing for probands from both families were performed followed by Sanger sequencing to confirm segregation of identified variants in the respective families. In-silico pathogenicity score prediction for identified variant and amino acid conservation analysis was completed.

Results
Whole Genome Sequencing identified a known biallelic variant c.6176_6189delGTCAGCTGCCGAAG; p.(Gln2060ArgfsTer48) in PCNT gene and a novel biallelic variant c.174delC; p.(Asp60ThrfsTer7) in RAB33B gene respectively in affected members of the two families. Clinical imaging revealed platyspondyly and varus deformity in the legs of the affected members in the first family. Radiographs indicated severe platyspondyly, genu valgus deformity of legs and pectus carinatum for the patients in the second family.

Conclusion
In this study we report the phenotypes and genetic variants in two unrelated families with two distinct forms of skeletal dysplasia. This study strengthens the previous findings that patients harboring PCNT variants are phenotypically homogeneous and also extends the genotypic spectrum of RAB33B variants.
Repetitive brief ischemia accelerates tibial shaft fracture healing: a 5-years prospective preliminary clinical trial (PCT)
Authors: Wang Dong , Liu Yang , Lv Wenrui , Liang Wei , Zhou Xiaobin , Ding Yin , Zhou Junlin 
Published: July 2021

Abstract
Background
This study was to evaluate the effects of repetitive brief ischemia (RBI) on bone healing in patients with tibial shaft fractures.

Methods
In this prospective clinical trial, patients with tibia shaft fractures were enrolled between January 2016 and January 2021. The intermittent pneumatic compression (IPC) device was used to make RBI on the affected limb after surgical operation 24 h. The inflation pressure was the systolic pressure of patients + 50 mmHg. Patients were received 30 s inflation/30 s deflation 30 times twice a day for 4 weeks. The primary outcome was bone healing time and the secondary outcomes were the rates of delayed union and nonunion, the rates of venous thrombosis of lower limbs, Johner-Wruhs scores, Lysholm knee score, VAS scores, postoperative complications, serum BMP-2, osteocalcin (OC) and bone specific alkaline phosphatase (BS-ALP).

Results
A total of 32 patients were enrolled finally and all were completed with a 12 months follow-up. All the fractures were healed and the bone healing time was 3(1) months in RBI group. However, the bone healing time of control group was 4(1) and there was statistical difference between the two groups (p < 0.01). No patient with fracture delayed union, nonunion and venous thrombosis of lower limbs in RBI group. 2 patients were delayed union in the control group. In RBI group, the Lysholm knee score was 83(6) at 6 months and 100(8) at 12 months. In the control group, the score was 78(4) and 90.5(17), there was statistical difference between the two groups (p < 0.01, p = 0.014, respectively). VAS scores were postoperative 2 weeks 6(1) in RBI group and 7(0.5) in the control group, there was statistical difference between the two groups (p = 0.016). There were 2 patients with intramuscular venous thrombosis of lower extremity in control group. Besides, RBI treatment increased the serum BMP-2, OC and BS-ALP at postoperative 2 weeks and 1 month.

Conclusions
RBI is a new method to accelerate bone healing in tibia shaft fracture patients and is a simple and noninvasive method.

Trial registration
Chinese clinical trial registry, ChiCTR-INR-17014208. Registered 28 December 2017—Retrospectively registered.
Do the dimensions of the hard palate have a relationship with the volumes of the upper airways and maxillary sinuses? A CBCT study
Authors: Miranda-Viana Murilo , Freitas Deborah Queiroz , Machado Alessiana Helena , Gomes Amanda Farias , Nejaim Yuri 
Published: July 2021

Abstract
Background
As the hard palate is a central structure of the skull, and its close relationship with the nasal cavity, oral cavity, and maxillary sinuses, it would be of interest to study if there is a relationship between this bone and other structures of the stomatognathic system. Thus, this study aimed to assess the dimensions of the hard palate and associate them with sex, and skeletal and breathing patterns. Also, to investigate if there is a relationship between these dimensions and the volumes of the upper airways and maxillary sinuses.

Methods
Two hundred and ninety-eight CBCT scans of patients were classified according to sex, and skeletal and breathing patterns. Then, the linear dimensions of width and height of the hard palate at the regions of the first premolars and first molars, and the volumes of the upper airways and maxillary sinuses were measured using the CS 3D Imaging and ITK-SNAP software, respectively. Data were submitted to multi-way analysis of variance and linear regression, with a significance level of 5% (α = 0.05).

Results
Sex and facial type influenced the hard palate dimensions (p < 0.05). Males had greater width and height of the hard palate than females (p < 0.0001). It was observed greater width for brachycephalics at the first premolars region (p = 0.0032), and greater height for dolichocephalics at the first premolars (p = 0.0154) and first molars (p = 0.0038) regions. Skeletal malocclusion and breathing pattern did not influence the measurements of the hard palate (p > 0.05). There was a significant relationship between the width and height of the hard palate at the premolar’s region and the total volume of the upper airways (p = 0.018, and p = 0.038), and between both dimensions of the hard palate at the molar’s region and the total volume of the maxillary sinuses (p < 0.0001).

Conclusions
The hard palate dimensions are influenced by sex and facial type, but not by skeletal malocclusion or breathing pattern. Also, there is an association between these dimensions and the volumes of the upper airways and maxillary sinuses.
Effects of Stephania hainanensis alkaloids on MSU-induced acute gouty arthritis in mice
Authors: Fan Hao-fei , Fang Xing-yue , Wu Hao-lin , Xu Yi-qian , Gong Li-chong , Yu Dao-rui , Jia Hao , Tang Xiao-liang , Liu Qi-bing 
Published: July 2021

AbstractBackgroundGout is initiated by the precipitation of monosodium urate (MSU) crystals within the joints and soft tissues, and it can eventually cause acute or chronic arthritis. MSU crystals trigger, amplify, and maintain a strong inflammatory response through promoting proinflammatory activity. In this study, the therapeutic effects ofStephania hainanensis(S. hainanensis) total alkaloid (SHA) were tested and evaluated on MSU-induced acute gouty arthritis in a mouse model.MethodsAfter oral administration of SHA (10 or 20 mg/kg) or the antigout medicine colchicine (0.5 mg/kg) once daily for 3 consecutive days, MSU crystals suspended in saline (2.5 mg/50 μl) were intradermally injected into the right paw of the mice. Then, SHA and colchicine were administered for another 2 days. During this period, swelling of the ankle and clinical scores were measured at 12, 24, and 48 h postinjection. After the mice were euthanized, inflammatory cytokine expression and paw tissue inflammation-related gene and protein expression, and a histopathological analysis was performed.ResultsSHA had obvious therapeutic effects on MSU-induced acute gouty arthritis in mice. SHA alleviated ankle swelling and inhibited the production of cytokines, such as IL-1β and TNF-α. In addition, NLRP3, Caspase-1 and IL-1β, which are activated by MSU were also suppressed by SHA. The histological evaluation showed that SHA relieved the infiltration of inflammation around the ankle.ConclusionsThese results suggest that SHA is capable of anti-inflammatory activities and may be useful for treating gouty arthritis.
Measuring patient-reported physical functioning and fatigue in myelodysplastic syndromes using a modular approach based on EORTC QLQ-C30
Authors: Regnault Antoine , Pompilus Farrah , Ciesluk Anna , Mazerolle Flora , Bejar Rafael , Fram Robert J. , Faller Douglas V. , Marquis Patrick , Bell Jill A. 
Published: July 2021

Abstract
Purpose
Physical functioning and fatigue are key patient concerns in myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). The objective of this research was to generate supportive quantitative evidence for modular physical functioning and fatigue measures based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30) and a customized selection of 10 supplemental items from the EORTC Item Library.

Methods
The 40 items were completed online cross-sectionally by 51 patients (higher risk [HR] MDS: 53%; CMML: 26%; AML: 10%). Psychometric analyses based on Rasch measurement theory (RMT) were conducted on the QLQ-C30 physical functioning and fatigue domains as well as measures combining QLQ-C30 and supplemental items. A measure of anemia-related symptoms composed of QLQ-C30 and supplemental items covering fatigue, dyspnea, and dizziness was also investigated.

Results
The QLQ-C30 physical functioning and fatigue domains showed good targeting to the sample and adequate reliability, with few conceptual gaps identified. Combining the QLQ-C30 and supplemental physical functioning and fatigue items improved the conceptual coverage and the reliability of the measures. The patient-reported anemia-related symptom measure showed good measurement performance, underpinned by a clinically meaningful characterization of severity of these symptoms over a spectrum, starting with fatigue, then dyspnea, and finally dizziness (most severe).

Conclusion
The modular measurement approach of combining EORTC QLQ-C30 and Item Library offers a promising pragmatic solution to the measurement of physical functioning and fatigue, as well as anemia-related symptoms in clinical trials conducted in HR MDS, CMML, and AML.
Quality of referrals to a rheumatology service before and after implementation of a triage system with telemedicine support
Authors: Piovesan Deise Marcela , Busato Vanessa Barrili , da Silveira Romulo Gomes , do Prado Aline Defaveri , Molina-Bastos Cynthia Goulart , Hickmann Sheila , Bongiorno Guilherme Kopik , de David Cruz Camila , Zamboni Sheron , Simon Julio César , Gonçalves Marcelo Rodrigues , Bredemeier Markus 
Published: July 2021

Abstract
Purpose
To evaluate the quality of referrals for a first Rheumatology consultation at a tertiary care center in a southern Brazilian capital (Porto Alegre, RS), having as background findings from a similar survey performed in 2007/2008. Since then, our state has implemented referral protocols and a triage system with teleconsulting support exclusively for referrals from locations outside the capital, permitting a comparison between patients screened and not screened by the new system.

Methods
Physicians of the Rheumatology Service at Hospital Nossa Senhora da Conceição prospectively collected information regarding first visits over a 6-month period (Oct 2017 to March 2018). We recorded demographic characteristics, diagnostic hypotheses, date of referral, and the municipality of origin (within the state of Rio Grande do Sul). We considered adequate referrals from primary health care when a systemic autoimmune inflammatory disease (SIRD) was suspected at first evaluation by the attending rheumatologist.

Results
Three hundred fifty-seven patients/appointments were eligible for analysis (193 from the capital and 164 from small and medium towns). In 2007/2008, suspected SIRD occurred in 76/260 (29.2%) and 73/222 (32.9%) among patients from the capital and outside counties, respectively (P = 0.387). In 2017/2018, suspected SIRD occurred in 75/193 (38.9%) and 111/164 (67.7%) in patients from the capital and outside counties, respectively (difference: 28.8, 95% CI: 19.0 to 38.9, P < 0.001), indicating a marked improvement in referrals submitted to the new triage system.

Conclusion
The quality of Rheumatology referrals in our state improved over the 10-year interval under study, particularly among patients from locations submitted to referral protocols and teleconsulting support.