bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo genome-wide CRISPR screening in murine acute myeloid leukemia uncovers microenvironmental dependencies
Authors: Mercier Francois E. , Shi Jiantao , Sykes David B. , Oki Toshihiko , Jankovic Maja , Man Cheuk Him , Kfoury Youmna S. , Miller Elizabeth , He Shutao , Zhu Alexander , Vasic Radovan , Doench John , Orthwein Alexandre , Michor Franziska , Scadden David T. 
Published: July 2022

Abstract
Genome-wide CRISPR screens have been extremely useful in identifying therapeutic targets in diverse cancers by defining genes that are essential for malignant growth. However, most CRISPR screens were performed in vitro and thus cannot identify genes that are essential for interactions with the microenvironment in vivo. Here, we report genome-wide CRISPR screens in 2 in vivo murine models of acute myeloid leukemia (AML) driven by the KMT2A/MLLT3 fusion or by the constitutive coexpression of Hoxa9 and Meis1. Secondary validation using a focused library identified 72 genes specifically essential for leukemic growth in vivo, including components of the major histocompatibility complex class I complex, Cd47, complement receptor Cr1l, and the β-4-galactosylation pathway. Importantly, several of these in vivo–specific hits have a prognostic effect or are inferred to be master regulators of protein activity in human AML cases. For instance, we identified Fermt3, a master regulator of integrin signaling, as having in vivo–specific dependency with high prognostic relevance. Overall, we show an experimental and computational pipeline for genome-wide functional screens in vivo in AML and provide a genome-wide resource of essential drivers of leukemic growth in vivo.
Evaluating the impact of eligibility criteria in first-line clinical trials for follicular lymphoma: a MER/LEO cohort analysis
Authors: Luan Danny , Fatola Tolulope , Toure Ahmed , Flowers Christopher R. , Link Brian , Friedberg Jonathan W. , Cohen Jonathon B. , Kahl Brad , Lossos Izidore S. , Nastoupil Loretta , Maurer Matthew J. , Cerhan James R. , Martin Peter 
Published: July 2022

Abstract
Cancer clinical trial eligibility criteria may create patient populations studied in trials that do not reflect the patient populations treated in the real-world setting. Follicular lymphoma (FL) is an indolent lymphoma with heterogeneous presentations across a broad range of individuals, resulting in many acceptable management strategies. We evaluated how first-line clinical trial eligibility criteria impacted the demographic makeup and outcomes of patients with FL for whom systemic therapy might be considered. We compared the characteristics of 196 patients with FL from a single institution to eligibility criteria from 10 first-line FL trials on clinicaltrials.gov. Next, we tabulated eligibility criteria from 24 first-line FL protocols and evaluated their impact on 1198 patients with FL with stages II to IV disease from the prospective Molecular Epidemiology Resource (MER) and Lymphoma Epidemiology of Outcomes (LEO) cohort studies. We found that 39.8% and 52.7% of patients with FL might be excluded from clinical trials based on eligibility criteria derived from clinicaltrials.gov and protocol documents, respectively. Patients excluded because of renal function, prior malignancy, and self-reported serious health conditions tended to be older. Expanding stage requirement from III-IV to II-IV, and platelet requirement from ≥150 000 to ≥75 000 increased population size by 21% and 8%, respectively, in MER and by 16% and 13%, respectively, in LEO, without impacting patient demographics or outcomes. These data suggest that management of older individuals with FL may not be fully informed by recent clinical trials. Moreover, liberalizing stage and platelet criteria might expand the eligible population and allow for quicker trial accrual without impacting outcomes.
MRI-based random survival Forest model improves prediction of progression-free survival to induction chemotherapy plus concurrent Chemoradiotherapy in Locoregionally Advanced nasopharyngeal carcinoma
Authors: Pei Wei , Wang Chen , Liao Hai , Chen Xiaobo , Wei Yunyun , Huang Xia , Liang Xueli , Bao Huayan , Su Danke , Jin Guanqiao 
Published: July 2022

Abstract
Background
The present study aimed to explore the application value of random survival forest (RSF) model and Cox model in predicting the progression-free survival (PFS) among patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) after induction chemotherapy plus concurrent chemoradiotherapy (IC + CCRT).

Methods
Eligible LANPC patients underwent magnetic resonance imaging (MRI) scan before treatment were subjected to radiomics feature extraction. Radiomics and clinical features of patients in the training cohort were subjected to RSF analysis to predict PFS and were tested in the testing cohort. The performance of an RSF model with clinical and radiologic predictors was assessed with the area under the receiver operating characteristic (ROC) curve (AUC) and Delong test and compared with Cox models based on clinical and radiologic parameters. Further, the Kaplan-Meier method was used for risk stratification of patients.

Results
A total of 294 LANPC patients (206 in the training cohort; 88 in the testing cohort) were enrolled and underwent magnetic resonance imaging (MRI) scans before treatment. The AUC value of the clinical Cox model, radiomics Cox model, clinical + radiomics Cox model, and clinical + radiomics RSF model in predicting 3- and 5-year PFS for LANPC patients was [0.545 vs 0.648 vs 0.648 vs 0.899 (training cohort), and 0.566 vs 0.736 vs 0.730 vs 0.861 (testing cohort); 0.556 vs 0.604 vs 0.611 vs 0.897 (training cohort), and 0.591 vs 0.661 vs 0.676 vs 0.847 (testing cohort), respectively]. Delong test showed that the RSF model and the other three Cox models were statistically significant, and the RSF model markedly improved prediction performance (P < 0.001). Additionally, the PFS of the high-risk group was lower than that of the low-risk group in the RSF model (P < 0.001), while comparable in the Cox model (P > 0.05).

Conclusion
The RSF model may be a potential tool for prognostic prediction and risk stratification of LANPC patients.
Lower urinary tract symptoms in an elderly women caused by degeneration of the pubic symphysis
Authors: He Kaixing , Wang Jinguo , Zhao Haixiao , Gao Jialin 
Published: July 2022

Abstract
Background
Lower urinary tract symptoms are very common in elderly women, and transvaginal delivery and multiple deliveries have been confirmed to be risk factors. Transvaginal delivery and multiple deliveries may lead to an increase in pubic symphysis degeneration.

Case presentation
A 79-year-old woman consulted a urologist because of worsening lower urinary tract symptoms such as frequent urination and urodynia. Color ultrasound and cystoscopy suggested the possibility of a bladder mass. A lump on the anterior wall of the bladder was observed although the surface mucosa was normal. Physical examination showed obvious tenderness in the posterior area of the pubic symphysis. Further urological computed tomography (CT) and pelvic magnetic resonance imaging (MRI) showed a nodular bony protuberance in the posterior part of the pubic symphysis, which was more obvious than before, with compression changes near the anterior wall of bladder. Open pelvic surgery showed that nodular bone tissue originating from the pubic symphysis significantly oppressed the anterior wall of the bladder behind the pubic symphysis. After resection of the nodule, the lower urinary tract symptoms were relieved significantly.

Conclusions
Pubic symphysis degeneration caused by transvaginal delivery may be an important cause of lower urinary tract symptoms in women. Pelvic CT or MRI is necessary to diagnosis this condition.
Population genetics of Cryptosporidium parvum subtypes in cattle in Poland: the geographical change of strain prevalence and circulation over time
Authors: Kaupke Agnieszka , Rzeżutka Artur 
Published: July 2022

Abstract
Background
Cryptosporidium parvum (C. parvum) is a cosmopolitan parasite that infects various livestock animals including cattle. Microsatellite typing tools for identification of C. parvum subtypes are currently employed to better understand the species-specific epidemiology of cattle cryptosporidiosis. The aim of this study was to analyse the population genetics of C. parvum strains infecting cattle and recognise geographical distribution and time-span correlations in subtype prevalence in Poland. In total, 1601 faecal samples were collected from 2014 to 2018 from healthy cattle from dairy, meat and mixed breeds at the age of 1 week to 4 months. The 267 farms visited were randomly selected and represented all Polish provinces. PCR–RFLP based identification of C. parvum at the 18 small subunit ribosomal RNA (SSU rRNA) locus was performed, followed by strain subtyping by GP60-PCR.

Results
The overall prevalence of C. parvum in Polish cattle was estimated at 6.2% (100/1601). Animals below the age of 1 month were the major host for this parasite. Excluding one breed, that of dairy-meat mixed, there were no significant differences observed between breed and presence of C. parvum infections (95% TPIAll breeds: 1.67–73.53%; POPR = 0.05—0.95). Infected animals were detected in 15 out of 16 Polish provinces, with significant regional prevalence diffrences (Kruskal–Wallis rank sum test, Kruskal–Wallis χ2 = 13.46, p < 0.001). When the population genetics of C. parvum strains were analysed, 11 parasite subtypes from the IIa and IId genetic families were identified. Compared to other parasite strains, IIaA17G1R1 and IIaA17G2R1 appeared at statistically significantly higher frequency (F-test, F = 3.39; p = 0.0003). The prevalence of C. parvum subtypes in cattle was breed-related (Chi-squared test, χ2 = 143.6; p < 0.001).

Conclusions
The analysis of the population genetics of C. parvum subtypes showed that strains from the IIa subtype family predominated in the tested cattle population. However, relations in changes of subtype prevalence and circulation over time were observed. They were associated with the disappearance of some strains and emergence of new variants from the same genetic family in different geographical locations.
Low frequency vibrating magnetic field-triggered magnetic microspheres with a nanoflagellum-like surface for cancer therapy
Authors: Guo Yuliang , Yang Wenxuan , Pu Guangjin , Zhu Chunjiao , Zhu Yifan , Li Ji , Huang Yuqiao , Wang Bo , Chu Maoquan 
Published: July 2022

Abstract
Background
The magneto-mechanical force killing cancer cells is an interesting and important strategy for cancer therapy.

Results
Novel magnetic microspheres composed of a Fe3O4 nanocore, a bovine serum albumin (BSA) matrix, and a rod-like SiO2 nanoshell, which had flagellum-like surface for force-mediated cancer therapy were developed. One such magnetic microsphere (Fe3O4/BSA/rSiO2) at a cancer cell (not leave the cell surface) under a low frequency vibrating magnetic field (VMF) could generate 6.17 pN force. Interestingly, this force could induce cancer cell to generate reactive oxygen species (ROS). The force and force-induced ROS could kill cancer cells. The cell killing efficiency of Fe3O4/BSA/rSiO2 exposed to a VMF was enhanced with increasing silica nanorod length, and the microspheres with straight nanorods exhibited stronger cell killing ability than those with curled nanorods. Fe3O4/BSA/rSiO2 triggered by a VMF could efficiently inhibit mouse tumor growth, while these microspheres without a VMF had no significant effect on the cell cycle distribution, cell viability, tumor growth, and mouse health.

Conclusions
These microspheres with unique morphological characteristics under VMF have great potential that can provide a new platform for treating solid tumors at superficial positions whether with hypoxia regions or multidrug resistance.
HDAC1 regulates inflammation and osteogenic differentiation of ankylosing spondylitis fibroblasts through the Wnt-Smad signaling pathway
Authors: Zeng Yong , He Rui , Liu Yong , Luo Ting , Li Qing , He Yu , Fang Miao , Wang Taiping 
Published: July 2022

AbstractAnkylosing spondylitis (AS) is a refractory autoimmune disease, whose typical pathology is the development of inflammation to ossification and ankylosis. Histone deacetylase 1 (HDAC1) is considered to be a key factor involved in inflammatory gene transduction, but its role in AS remains unclear. The purpose of this study was to explore the role and possible mechanism of HDAC1 in AS based on the Wnt-Smad pathway. Fibroblasts were isolated from hip synovial tissues of AS patients, adeno-associated virus (AAV) was used to regulate the expression of HDAC1, DKK-1 and SIS3 was used to inhibit Wnt and Smad, respectively. The expressions of Wnt-Smad pathway-related proteins were analyzed by WB, and the TRP ion channel proteins were analyzed by immunofluorescence and WB. The proliferation of AS fibroblasts was detected by CCK-8, the expression of inflammatory cytokines was detected by ELISA, and the effects of HDAC1 on osteogenic differentiation of AS fibroblasts were investigated by alkaline phosphatase (ALP) activity, intracellular calcium concentration, mineralization and osteogenic proteins expressions. Results showed that HDAC1 significantly affected the protein expressions of the Wnt-Smad pathway in AS fibroblasts, and Wnt inhibitor DKK-1 and Smad3 inhibitor SIS3 could significantly reverse the effect of HDAC1 on the Wnt-Smad pathway. In addition, HDAC1 significantly activated the TRP ion channel and promoted the proliferation, inflammatory response and osteogenic differentiation of AS fibroblasts. DKK-1 or SIS3 treatment significantly inhibit the effect of HDAC-1 on AS fibroblasts, suggesting that the Wnt-Smad pathway is involved in the regulation of AS by HDAC1. In conclusion, HDAC1 promotes the proliferation, inflammatory response and osteogenic differentiation of AS fibroblasts through the Wnt-Smad pathway.
Identification of novel candidate biomarkers and immune infiltration in polycystic ovary syndrome
Authors: Na Zhijing , Guo Wen , Song Jiahui , Feng Di , Fang Yuanyuan , Li Da 
Published: July 2022

Abstract
Background
In this study, we aimed to identify novel biomarkers for polycystic ovary syndrome (PCOS) and analyze their potential roles in immune infiltration during PCOS pathogenesis.

Methods
Five datasets, namely GSE137684, GSE80432, GSE114419, GSE138518, and GSE155489, were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were selected from the train datasets. The least absolute shrinkage and selection operator logistic regression model and support vector machine-recursive feature elimination algorithm were combined to screen potential biomarkers. The test datasets validated the expression levels of these biomarkers, and the area under the curve (AUC) was calculated to analyze their diagnostic value. Quantitative real-time PCR was conducted to verify biomarkers’ expression in clinical samples. CIBERSORT was used to assess differential immune infiltration, and the correlations of biomarkers with infiltrating immune cells were evaluated.

Results
Herein, 1265 DEGs were identified between PCOS and control groups. The gene sets related to immune response and adaptive immune response were differentially activated in PCOS. The two diagnostic biomarkers of PCOS identified by us were HD domain containing 3 (HDDC3) and syndecan 2 (SDC2; AUC, 0.918 and 0.816, respectively). The validation of hub biomarkers in clinical samples using RT-qPCR was consistent with bioinformatics results. Immune infiltration analysis indicated that decreased activated mast cells (P = 0.033) and increased eosinophils (P = 0.040) may be a part of the pathogenesis of PCOS. HDDC3 was positively correlated with T regulatory cells (P = 0.0064), activated mast cells (P = 0.014), and monocytes (P = 0.024) but negatively correlated with activated memory CD4 T cells (P = 0.016) in PCOS. In addition, SDC2 was positively correlated with activated mast cells (P = 0.0021), plasma cells (P = 0.0051), and M2 macrophages (P = 0.038) but negatively correlated with eosinophils (P = 0.01) and neutrophils (P = 0.031) in PCOS.

Conclusion
HDDC3 and SDC2 can serve as candidate biomarkers of PCOS and provide new insights into the molecular mechanisms of immune regulation in PCOS.
Oral glucose tolerance testing at 1 h and 2 h: relationship with glucose and cardiometabolic parameters and agreement for pre-diabetes diagnosis in patients with morbid obesity
Authors: Guerreiro Vanessa , Maia Isabel , Neves João Sérgio , Salazar Daniela , Ferreira Maria João , Mendonça Fernando , Silva Maria Manuel , Borges-Canha Marta , Viana Sara , Costa Cláudia , Pedro Jorge , Varela Ana , Lau Eva , Freitas Paula , Carvalho Davide ,   AMTCO Group
Published: July 2022

Abstract
Background
One hour plasma glucose concentration (1hPG) during an oral glucose tolerance test (OGTT) may be an alternative to 2-h plasma glucose concentration (2hPG) in the identification of individuals at increased risk of hyperglycaemia, although its role is not fully understood.

Aim
We aim to investigate the relationship of these measures with other glucose parameters, as well as their relationship with cardiometabolic risk markers and the level of agreement for prediabetes mellitus diagnosis, in a sample of patients with morbid obesity.

Methods
We retrospectively evaluated 656 patients with morbid obesity without diagnosed diabetes. To define prediabetes with 2hPG, 2022 American Diabetes Association guidelines criteria were used, while for 1hPG, glucose ≥ 155 mg/dL was considered. Cohen’s Kappa coefficient was used to assess the agreement between both measures of prediabetes mellitus diagnosis.

Results
A Cohen’s Kappa coefficient of 0.405 (p < 0.001) was obtained. The 1hPG were positively correlated with homeostatic model assessment for insulin resistance (HOMA-IR) (ρ = 0.281, p < 0.001), fasting plasma glucose (FPG) (ρ = 0.581, p < 0.001), glycated haemoglobin (Hb1AC) (ρ = 0.347, p < 0.001) and were negatively correlated with homeostatic model assessment for cell-β function (HOMA-β) (ρ = −0.092, p = 0.018). 2hPG were also correlated with the same parameters, except for HOMA-β.

Conclusion
A fair agreement between 1 and 2hPG was verified. 1hPG criteria may be a useful indicator of β-cell dysfunction and insulin resistance in patients with morbid obesity without diabetes diagnosis.
The effect of karate interventions on the motor proficiency of female adolescents with developmental coordination disorder (DCD) from high and low socio-economic status
Authors: Ghadiri Farhad , O’Brien Wesley , Soltani Sana , Faraji Marzieh , Bahmani Moslem 
Published: July 2022

AbstractBackgroundThere is not a general consensus on the best type of intervention to improve the motor proficiency (MP) of adolescents with developmental coordination disorder (DCD). Considering the effect of socio-economic status (SES) in relation to the MP of adolescents with DCD, it is necessary to examine this issue further. The purpose of this study was to investigate the effect of Karate-Do interventions on the MP of adolescents with DCD from high/low SES.MethodsParticipants included 16 adolescent girls (12 to 13 years old) with DCD, and their classification into high/low SES groups was done by using appropriate previously validated questionnaire. A short form of the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition (BOT-2), was used to assess fine motor precision, fine motor integration, manual dexterity, upper limb coordination, bilateral coordination, balance, strength, speed, agility, and overall MP level of the participants. Both high/low-SES groups completed a specifically prescribed Karate-Do intervention program for 8 consecutive weeks (3 sessions per week with each session lasting for 75 min).ResultsResults from this 8-week intervention showed that the pattern of change in manual dexterity, bilateral coordination, strength and the total MP score improved over time in both groups with varied socioeconomic backgrounds. Specifically, the high-SES group performed significantly better than their low-SES counterparts during the 8-week Karate-Do intervention (p< 0.05).ConclusionsFollowing participants’ completion of the Karate-Do intervention, the existence of significant changes in the MP of adolescents’ with DCD at high/low SES confirmed our hypothesis. Compared to the low-SES group, adolescents with high SES displayed superior MP following the intervention. It seems that karate (kata) training serves as a good alternative for rehabilitation MP programs, however, an important issue concerning social infrastructure is to create a suitable exercise environment for adolescents at lower SES. Until the SES achievement gap in female adolescent MP is stable, future work is warranted to discover more practical and meaningful interventions.
The future as aesthetic experience: imagination and engagement in future studies
Authors: van Lente Harro , Peters Peter 
Published: July 2022

AbstractIn this paper, we examine the question how future studies can productively engage with the future by considering how art is engaging. This question is pertinent, as doubts about the future are increasingly urgent, while the need to engage with the future is not sufficiently addressed by the quantitative growth of future studies. In the case of climate change, for example, the future consequences of global temperature increase are well-known, but do not invoke action accordingly. While some see the use of art as an effective means to engage with the future, others criticise such usage as reducing art to an instrumental value, at the expense of aesthetic values. This raises fundamental questions about how art and imagination can be engaging and what this implies for future studies.To address the issue, we resort to a pragmatist understanding of art. We present a reading of the work of John Dewey (1859–1952). In hisArt as Experience, Dewey claimed that art can be seen as a “mode of prediction not found in charts and statistics”. He presents the experience of art as a reciprocal process that is imaginative: in our engagement with art, we experience the artwork, while the experience also produces us. The aesthetic experience is transformative. This mutual coming into existence is not a planned creation, but insinuates an open future as well as an open past.As a next step, we review the production of futures in future studies, using Dewey’s understandings on how imagination and the future connect in the aesthetic experience. First, we look at methods to produce futures: extrapolations, Delphi Surveys, surveys, simulations and scenarios. Second, we evaluate how the produced futures engage their audience, distinguishing between narratives, symbols, graphs and images.We conclude that while futures studies have been successful in showing routes to the future, they also have difficulties to relate to futures in a more open, imaginative and responsible way. They are informative but not transformative. The difficulty of future studies to engage, hinders responsible responses.