bluuebunny/crossref_metadata_2025_split huggingface dataset:
TP53 mutations in myelodysplastic syndromes and secondary AML confer an immunosuppressive phenotype
Authors: Sallman David A. , McLemore Amy F. , Aldrich Amy L. , Komrokji Rami S. , McGraw Kathy L. , Dhawan Abhishek , Geyer Susan , Hou Hsin-An , Eksioglu Erika A. , Sullivan Amy , Warren Sarah , MacBeth Kyle J. , Meggendorfer Manja , Haferlach Torsten , Boettcher Steffen , Ebert Benjamin L. , Al Ali Najla H. , Lancet Jeffrey E. , Cleveland John L. , Padron Eric , List Alan F. 
Published: July 2020

Abstract
Somatic gene mutations are key determinants of outcome in patients with myelodysplastic syndromes (MDS) and secondary AML (sAML). In particular, patients with TP53 mutations represent a distinct molecular cohort with uniformly poor prognosis. The precise pathogenetic mechanisms underlying these inferior outcomes have not been delineated. In this study, we characterized the immunological features of the malignant clone and alterations in the immune microenvironment in patients with TP53-mutant and wild-type MDS or sAML. Notably, PDL1 expression is significantly increased in hematopoietic stem cells of patients with TP53 mutations, which is associated with MYC upregulation and marked downregulation of MYC’s negative regulator miR-34a, a p53 transcription target. Notably, patients with TP53 mutations display significantly reduced numbers of bone marrow–infiltrating OX40+ cytotoxic T cells and helper T cells, as well as decreased ICOS+ and 4-1BB+ natural killer cells. Further, highly immunosuppressive regulatory T cells (Tregs) (ie, ICOShigh/PD-1−) and myeloid-derived suppressor cells (PD-1low) are expanded in cases with TP53 mutations. Finally, a higher proportion of bone marrow–infiltrating ICOShigh/PD-1− Treg cells is a highly significant independent predictor of overall survival. We conclude that the microenvironment of TP53 mutant MDS and sAML has an immune-privileged, evasive phenotype that may be a primary driver of poor outcomes and submit that immunomodulatory therapeutic strategies may offer a benefit for this molecularly defined subpopulation.
A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study
Authors: Tam Constantine S. , Opat Stephen , D'Sa Shirley , Jurczak Wojciech , Lee Hui-Peng , Cull Gavin , Owen Roger G. , Marlton Paula , Wahlin Björn E. , Sanz Ramón Garcia , McCarthy Helen , Mulligan Stephen , Tedeschi Alessandra , Castillo Jorge J. , Czyz Jaroslaw , Fernández de Larrea Carlos , Belada David , Libby Edward , Matous Jeffrey V. , Motta Marina , Siddiqi Tanya , Tani Monica , Trneny Marek , Minnema Monique C. , Buske Christian , Leblond Veronique , Trotman Judith , Chan Wai Y. , Schneider Jingjing , Ro Sunhee , Cohen Aileen , Huang Jane , Dimopoulos Meletios 
Published: July 2020

Abstract
Bruton tyrosine kinase (BTK) inhibition is an effective treatment approach for patients with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of ibrutinib, a first-generation BTK inhibitor, with zanubrutinib, a novel highly selective BTK inhibitor, in patients with WM. Patients with MYD88L265P disease were randomly assigned 1:1 to treatment with ibrutinib or zanubrutinib. The primary end point was the proportion of patients achieving a complete response (CR) or a very good partial response (VGPR) by independent review. Key secondary end points included major response rate (MRR), progression-free survival (PFS), duration of response (DOR), disease burden, and safety. A total of 201 patients were randomized, and 199 received ≥1 dose of study treatment. No patient achieved a CR. Twenty-nine (28%) zanubrutinib patients and 19 (19%) ibrutinib patients achieved a VGPR, a nonstatistically significant difference (P = .09). MRRs were 77% and 78%, respectively. Median DOR and PFS were not reached; 84% and 85% of ibrutinib and zanubrutinib patients were progression free at 18 months. Atrial fibrillation, contusion, diarrhea, peripheral edema, hemorrhage, muscle spasms, and pneumonia, as well as adverse events leading to treatment discontinuation, were less common among zanubrutinib recipients. Incidence of neutropenia was higher with zanubrutinib, although grade ≥3 infection rates were similar in both arms (1.2 and 1.1 events per 100 person-months). These results demonstrate that zanubrutinib and ibrutinib are highly effective in the treatment of WM, but zanubrutinib treatment was associated with a trend toward better response quality and less toxicity, particularly cardiovascular toxicity.
Bendamustine and rituximab as induction therapy in both transplant-eligible and -ineligible patients with mantle cell lymphoma
Authors: Villa Diego , Sehn Laurie H. , Savage Kerry J. , Toze Cynthia L. , Song Kevin , den Brok Wendie D. , Freeman Ciara L. , Scott David W. , Gerrie Alina S. 
Published: July 2020

Abstract
Rituximab-containing chemotherapy regimens constitute standard first-line therapy for mantle cell lymphoma (MCL). Since June 2013, 190 patients ≥18 years of age with MCL in British Columbia have been treated with bendamustine and rituximab (BR). The overall response rate to BR was 88% (54% complete response). Of these, 61 of 89 patients (69%) aged ≤65 years received autologous stem cell transplantation and 141 of 190 patients (74%) from the entire cohort received maintenance rituximab. Twenty-three patients (12%) had progressive disease, associated with high risk per the Mantle Cell Lymphoma International Prognostic Index (MIPI), Ki-67 ≥50%, and blastoid/pleomorphic histology. Outcomes were compared with a historical cohort of 248 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; January 2003 to May 2013). Treatment with BR was associated with significant improvements in progression-free survival (PFS), but not overall survival (OS), compared with R-CHOP in the whole cohort (3-year PFS, 66% BR vs 51% R-CHOP, P = .003; 3-year OS, 73% BR vs 66% R-CHOP, P = .054) and in those &gt;65 years of age (3-year PFS, 56% BR vs 35% R-CHOP, P = .001; 3-year OS, 64% BR vs 55% R-CHOP, P = .063). Outcomes in transplanted patients were not statistically significantly different compared with R-CHOP (3-year PFS, 85% BR vs 76% R-CHOP, P = .135; 3-year OS, 90% BR vs 88% R-CHOP, P = .305), although in multivariate analyses, treatment with BR was associated with improved PFS (hazard ratio, 0.40 [95% confidence interval, 0.17-0.94]; P = .036) but not OS. BR is an effective first-line option for most patients with MCL, however, outcomes are suboptimal for those with high-risk features and further studies integrating novel agents are warranted.
RETRACTED ARTICLE: Contribution of
anthocyanin pathways to fruit flesh coloration in pitayas
Authors: Fan Ruiyi , Sun Qingming , Zeng Jiwu , Zhang Xinxin 
Published: July 2020

Abstract
Background
Color formation in Hylocereus
spp. (pitayas) has been ascribed to the accumulation of
betalains. However, several studies have reported the presence of anthocyanins
in pitaya fruit and their potential role in color formation has not yet been
explored. In this study, we profiled metabolome and transcriptome in fruit of
three cultivars with contrasting flesh colors (red, pink and white) to
investigate their nutritional quality and the mechanism of color formation
involving anthocyanins.

Results
Results revealed that pitaya fruit is enriched in amino acid, lipid,
carbohydrate, polyphenols, vitamin and other bioactive components with
significant variation among the three cultivars. Anthocyanins were detected in
the fruit flesh and accumulation levels of Cyanidin 3-glucoside, Cyanidin
3-rutinoside, Delphinidin 3-O-(6-O-malonyl)-beta-glucoside-3-O-beta-glucoside
and Delphinidin 3-O-beta-D-glucoside 5-O-(6-coumaroyl-beta-D-glucoside)
positively correlated with the reddish coloration. Transcriptome data showed
that the white cultivar tends to repress the anthocyanin biosynthetic pathway
and divert substrates to other competing pathways. This perfectly contrasted
with observations in the red cultivar. The pink cultivar however seems to keep a
balance between the anthocyanin biosynthetic pathway and the competing pathways.
We identified several active transcription factors of the MYB and bHLH families
which can be further investigated as potential regulators of the anthocyanin
biosynthetic genes.

Conclusions
Collectively, our results suggest that anthocyanins partly
contribute to color formation in pitaya fruit. Future studies aiming at
manipulating the biosynthetic pathways of anthocyanins and betalains will better
clarify the exact contribution of each pathway in color formation in pitayas.
This will facilitate efforts to improve pitaya fruit quality and appeal.
A colonic mass revealing a disseminated crystal storing histiocytosis secondary to indolent multiple myeloma: a case report with literature review
Authors: Contejean Adrien , Larousserie Frédérique , Bouscary Didier , Dohan Anthony , Deau-Fischer Bénédicte , Szwebel Tali-Anne , Dhooge Marion , Terris Benoit , Vignon Marguerite 
Published: July 2020

Abstract
Background
Crystal storing histiocytosis is a rare disorder associated with monoclonal gammopathy. In this disease, monoclonal heavy and light chains accumulate in the lysosome of macrophages, leading to histiocytic reaction in different organs. It is secondary to the presence of a small B-cell clone, responsible for monoclonal immunoglobulin production. Histological diagnosis is a challenge and differential diagnoses include fibroblastic and histiocytic neoplasm. Clinical manifestations depend on the involved organs, rarely including peritoneum or digestive tract.

Case presentation
We present a case of a 75-year-old with a medical history of colonic carcinoma. She presented with abdominal pain and inflammatory syndrome revealing a colonic mass. Hemicolectomy was performed. Initial diagnosis was fibroblastic tumour. The patient worsened, and diagnosis of a diffuse crystal storing histiocytosis was finally done. Haematological exploration found an indolent IgG-kappa multiple myeloma. The initial treatment with conventional chemotherapy did not permit an improvement of the patient condition. Immunotherapy with anti-CD38 monoclonal antibody (daratumumab) was proposed with a clinical and biological response.

Conclusion
This case report emphasizes the histopathological challenge of histiocytic tumours which may involve digestive track. It focuses on the concept of monoclonal gammopathy of clinical significance, which can have a large spectrum of manifestations.
Prevalence and risk factors of paradoxical tuberculosis associated immune reconstitution inflammatory syndrome among HIV-infected patients in Beijing, China
Authors: Xue Ming , Xie Ruming , Pang Yu , Yan Shuo , Du Yanni , Guan Chunshuang , Chen Budong 
Published: July 2020

Abstract
Background
In this study, we aimed to describe the prevalence, clinical presentation and risk factors of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) cases in China.

Methods
We performed a descriptive analysis of demographic and clinical data of HIV/TB coinfected patients receiving ART at Beijing Ditan Hospital between January 2014 and October 2018.

Results
Of 199 patients included, 45 (22.6%) developed paradoxical TB-IRIS, and 19 (9.5%) TB-IRIS cases presented miliary TB. The pre-ART CD4 count lower than 50 cells/mm3 was found to be significantly associated with development of TB-IRIS. Similarly, patients with higher than 4-fold increase in CD4 cell count after antiretroviral therapy (ART) had significantly higher odds of having TB-IRIS. When patients aged 25–44 years were utilized as the control group, youths (< 25 years old) were more likely to have miliary TB. No significant difference was observed in the intervals from initiation of ART to IRIS presentation between miliary and non-miliary group.

Conclusions
In conclusion, our data demonstrate that approximate one quarter of patients coinfected with TB and HIV develop paradoxical TB-IRIS after initial of ART therapy in China. Lower baseline CD4 count and rapid increase in CD4 count are the major risk factors associated with the occurrence of paradoxical TB-IRIS.
Association studies of dopamine synthesis and metabolism genes with multiple phenotypes of heroin dependence
Authors: Li Yunxiao , Zhu Yongsheng , Lai Jianghua , Shi Xugang , Chen Yuanyuan , Zhang Jinyu , Wei Shuguang 
Published: July 2020

Abstract
Background
Heroin dependence is a complex disease with multiple phenotypes. Classification of heroin users into more homogeneous subgroups on the basis of these phenotypes could help to identify the involved genetic factors and precise treatments. This study aimed to identify the association between genetic polymorphisms of DA synthesis and metabolism genes, including tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), solute carrier family 6 member 3 (SLC6A3) and DA beta-hydroxylase (DBH), with six important phenotypes of heroin dependence.

Methods
A total of 801 heroin dependent patients were recruited and fourteen potential functional single nucleotide polymorphisms (SNPs) were genotyped by SNaPshot. Associations between SNPs with six phenotypes were mainly assessed by binary logistic regression. Generalized multifactor dimensionality reduction was used to analyze the gene-by-gene and gene-by-environment interactions.

Results
We found that DBH rs1611114 TT genotype had a protective effect on memory impairment after heroin dependence (P = 0.002, OR = 0.610). We also found that the income-rs12666409-rs129915-rs1611114 interaction yielded the highest testing balance accuracy and cross-validation consistency for memory change after heroin dependence.

Conclusions
Our results suggest that the memory change after heroin dependence was a result of a combination of genetics and environment. This finding could lead to a better understanding of heroin dependence and further improve personalized treatment.
Ultrasound diagnosis and follow-up of a locked thumb metacarpophalangeal joint caused by radial sesamoid entrapment: a case report
Authors: Ahn Kyung-Sik , Choi In Cheul , Kang Chang Ho , Park Jong Woong 
Published: July 2020

Abstract
Background
A locked thumb metacarpophalangeal joint is a rare condition that presents as restricted joint motions with mild hyperextension deformity, usually after a relatively minor hyperextension injury. Owing to the limitations of radiographs, computed tomography is a useful diagnostic imaging modality for assessing sesamoid displacement. However, despite its convenience, ultrasound findings of the locked thumb have rarely been reported. Here, we report a case of a locked thumb metacarpophalangeal joint diagnosed and followed-up using ultrasound.

Case presentation
A 15-year-old boy with a locked thumb metacarpophalangeal joint presented to our hospital. On physical examination, the 1st metacarpophalangeal joint was found to be hyperextended, and active and passive flexions were not possible. While radiographs were inconclusive, ultrasound revealed radial sesamoid entrapment at the 1st metacarpophalangeal joint causing locking. After closed manual reduction, metacarpophalangeal motions recovered. Success of the reduction was also confirmable by ultrasound.

Conclusions
Ultrasound can be a feasible modality to diagnose a locked thumb metacarpophalangeal joint and immediately judge the success or failure of the reduction.
Experiential learning for children’s dental anxiety: a cluster randomized trial
Authors: Zhu Minmin , Yu Hongbing , Xie Bo , Li Hongwen , He Qian , Li Huimin , Su Jing , Li Xueqi 
Published: July 2020

AbstractBackgroundDental anxiety (DA) has an impact on the quality of dental treatment and may have long-lasting implications for children. A recent study introducing experiential learning (EL) into children’s oral health promotion resulted in better oral hygiene. The purpose of the study is to evaluate whether EL can reduce children’s DA.MethodsIn September 2018, we recruited 988 children aged 7–8 years from 24 classes to participate in a cluster-randomized trial. Classes were randomly assigned to EL (in which children received a lively presentation on oral health and participated in a role play in a simulated dental clinic in the classroom) or the Tell-Show-Do (TSD) group (in which children received a conventional TSD behavior management). The primary outcome was the prevalence of high DA after the procedure of pit and fissure sealant (PFS), assessed by a modified Children’s Fear Survey Schedule-Dental Subscale. Secondary outcomes were changes in blood pressures (BP) and pulse rates (PR) before and after the PFS procedure. The intervention effects were estimated by means of mixed effect models, which included covariates of gender and school (and baseline value for BP and PR only), and a random cluster effect.ResultsIn 396 children of the EL group who received the PFS treatment, the prevalence of high DA (score ≥ 38) was 18.5%, compared with 24.3% in 391 children of the TSD group (OR = 0.65; 95% confidence interval, 0.46–0.93;P = 0.019). The increases in BP and PR after the PFS were also significantly less in the EL group.ConclusionSchool-based experiential learning intervention before a dental visit is feasible and effective in reducing children’s dental anxiety during PFS.Trial registrationThe trial was registered in Chinese Clinical Trial Registry on 5 January 2020 (No.:ChiCTR2000028878, retrospectively registered).
HOXA-AS2 promotes type I endometrial carcinoma via miRNA-302c-3p-mediated regulation of ZFX
Authors: Song Ning , Zhang Ying , Kong Fanfei , Yang Hui , Ma Xiaoxin 
Published: July 2020

Abstract
Background
HOXA cluster antisense RNA2 (HOXA-AS2), a long-chain non-coding RNA, plays an important role in the behavior of various malignant tumors. The roles of HOXA-AS2 in endometrial cancer remain unclear.

Methods
We test expression levels of HOXA-AS2, miRNA-302c-3p, the transcription factor zinc finger X-chromosomal protein (ZFX), and the chitinase-like protein YKL-40 in endometrial carcinoma by qRT-PCR and western blotting. Luciferase reporter and qRT-PCR assays were conducted to identify potential binding sites of HOXA-AS2 to miRNA-302c-3p. Cell cycle, migration and invasion ability of endometrial cancer cells were investigated using flow-cytometric analysis, CCK-8 and transwell assays, respectively.

Results
HOXA-AS2 levels were significantly increased in endometrial cancer specimens compared to normal endometrial specimens. Upregulated HOXA-AS2 promoted invasion and proliferation of type I endometrial cancer cells. HOXA-AS2 silenced miRNA-302c-3p by binding to it. MiRNA-302c-3p negatively regulates ZFX and YKL-40. Thus HOXA-AS2 promotes the development of type I endometrial cancer via miRNA-302c-3p-mediated regulation of ZFX.

Conclusions
These findings suggest that HOXA-AS2 can act as a new therapeutic target for type I endometrial cancer.
Measuring ventilation in different typologies of rural Gambian houses: a pilot experimental study
Authors: Knudsen Jakob B. , Pinder Margaret , Jatta Ebrima , Jawara Musa , Yousuf Mahamed A. , Søndergaard Amalie T. , Lindsay Steve W. 
Published: July 2020

Abstract
Background
African houses are frequently too hot and uncomfortable to use a bed net at night. Indoor thermal comfort is often evaluated by measuring temperature and humidity, ignoring ventilation. This study explored ways to measure ventilation in single-roomed rural Gambian houses during the malaria transmission season and evaluated building designs that could increase airflow at night and help keep the occupants comfortable.

Methods
Two identical mud-walled houses were constructed with a metal roof, three doors and closed eaves. Experiment 1 compared five methods for measuring ventilation in a building: (1) using a blower door, (2) increasing carbon dioxide (CO2) levels indoors using an artificial source of CO2 and then measuring the rate of gas decay, (3) using a similar approach with a natural source of CO2, (4) measuring the rise of CO2 when people enter a building and (5) using hot-wire anemometers. Experiment 2 used CO2 data loggers to compare ventilation in a reference metal-roofed house with closed eaves and badly-fitting doors with a similar house with (1) thatched roof and open eaves, (2) eaves tubes, (3) screened doors and (4) screened doors and windows.

Results
In experiment 1, CO2 data loggers placed indoors in two identical houses showed similar changes in airflow (p > 0.05) for all three methods recording either decreasing or increasing CO2. Blower doors were unable to measure airflow in houses with open eaves or screened windows and the anemometers broke down under field conditions. In experiment 2, open eaves in thatched houses, screened doors alone, and screened doors and windows increased indoor ventilation compared to the reference metal-roofed house with closed eaves and badly fitting doors (p < 0.05). Eaves tubes did not increase ventilation in comparison to the reference house.

Conclusion
CO2 data loggers proved to be a simple and efficient method for measuring ventilation in rural houses at night. Ventilation of metal-roofed houses can be improved by adding two screened doors and windows on opposite walls. Improved ventilation will result in increased thermal comfort making it more likely that people will sleep under a bed net.
“They look at us like junkies”: influences of drug use stigma on the healthcare engagement of people who inject drugs in New York City
Authors: Muncan Brandon , Walters Suzan M. , Ezell Jerel , Ompad Danielle C. 
Published: July 2020

Abstract
Background
People who inject drugs (PWID) are a medically and socially vulnerable population with a high incidence of overdose, mental illness, and infections like HIV and hepatitis C. Existing literature describes social and economic correlations to increased health risk, including stigma. Injection drug use stigma has been identified as a major contributor to healthcare disparities for PWID. However, data on this topic, particularly in terms of the interface between enacted, anticipated, and internalized stigma, is still limited. To fill this gap, we examined perspectives from PWID whose stigmatizing experiences impacted their views of the healthcare system and syringe service programs (SSPs) and influenced their decisions regarding future medical care.

Methods
Semi-structured interviews conducted with 32 self-identified PWID in New York City. Interviews were audio recorded and transcribed. Interview transcripts were coded using a grounded theory approach by three trained coders and key themes were identified as they emerged.

Results
A total of 25 participants (78.1%) reported at least one instance of stigma related to healthcare system engagement. Twenty-three participants (71.9%) reported some form of enacted stigma with healthcare, 19 participants (59.4%) described anticipated stigma with healthcare, and 20 participants (62.5%) reported positive experiences at SSPs. Participants attributed healthcare stigma to their drug injection use status and overwhelmingly felt distrustful of, and frustrated with, medical providers and other healthcare staff at hospitals and local clinics. PWID did not report internalized stigma, in part due to the availability of non-stigmatizing medical care at SSPs.

Conclusions
Stigmatizing experiences of PWID in formal healthcare settings contributed to negative attitudes toward seeking healthcare in the future. Many participants describe SSPs as accessible sites to receive high-quality medical care, which may curb the manifestation of internalized stigma derived from negative experiences in the broader healthcare system. Our findings align with those reported in the literature and reveal the potentially important role of SSPs. With the goal of limiting stigmatizing interactions and their consequences on PWID health, we recommend that future research include explorations of mechanisms by which PWID make decisions in stigmatizing healthcare settings, as well as improving medical care availability at SSPs.