bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applying CRISPR-Cas9 screens to dissect hematological malignancies
Authors: Iyer Deepak Narayanan , Schimmer Aaron D. , Chang Hong 
Published: November 2022

Abstract
Bit by bit, over the last few decades, functional genomic tools have been piecing together the molecular puzzle driving tumorigenesis in human patients. Nevertheless, our understanding of the role of several genes and regulatory elements that drive critical cancer-associated physiological processes from disease development to progression to spread is very limited, which significantly affects our ability of applying these insights in the context of improved disease management. The recent advent of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)–based technology and its application in cancer genomics has, however, allowed the generation of a wealth of knowledge that has helped decipher several critical questions associated with translational cancer research. Precisely, the high-throughput capability coupled with a high level of technological plasticity associated with the CRISPR-Cas9 screens have expanded our horizons from a mere struggle to appreciate cancer as a genetic disease to observing the integrated genomic/epigenomic network of numerous malignancies and correlating it with our present knowledge of drugging strategies to develop innovative approaches for next-generation precision cancer medicine. Specifically, within blood cancers, current CRISPR screens have specifically focused on improving our understanding of drug resistance mechanisms, disease biology, the development of novel therapeutic approaches, and identifying the molecular mechanisms of current therapies, with an underlying aim of improving disease outcomes. Here, we review the development of the CRISPR-Cas9 genome-editing strategy, explicitly focusing on the recent advances in the CRISPR-Cas9–based screening approaches, its current capabilities, limitations, and future applications in the context of hematological malignancies.
Positive selection-driven fixation of a hominin-specific amino acid mutation related to dephosphorylation in IRF9
Authors: Chen Jianhai , He Xuefei , Jakovlić Ivan 
Published: November 2022

AbstractThe arms race between humans and pathogens drives the evolution of the human genome. It is thus expected that genes from the interferon-regulatory factors family (IRFs), a critical family for anti-viral immune response, should be undergoing episodes of positive selection. Herein, we tested this hypothesis and found multiple lines of evidence for positive selection on the amino acid site Val129 (NP_006075.3:p.Ser129Val) of human IRF9. Interestingly, the ancestral reconstruction and population distribution analyses revealed that the ancestral state (Ser129) is conserved among mammals, while the derived positively selected state (Val129) was fixed before the “out-of-Africa” event ~ 500,000 years ago. The motif analysis revealed that this young amino acid (Val129) may serve as a dephosphorylation site of IRF9. Structural parallelism between homologous genes further suggested the functional effects underlying the dephosphorylation that may affect the immune activity of IRF9. This study provides a model in which a strong positive Darwinian selection drives a recent fixation of a hominin-specific amino acid leading to molecular adaptation involving dephosphorylation in an immune-responsive gene.
Exogenous ABA and IAA modulate physiological and hormonal adaptation strategies in Cleistocalyx operculatus and Syzygium jambos under long-term waterlogging conditions
Authors: Cisse El-Hadji Malick , Zhang Juan , Li Da-Dong , Miao Ling-Feng , Yin Li-Yan , Yang Fan 
Published: November 2022

Abstract
Background
The mechanisms of abscisic acid (ABA) and auxin (IAA) in inducing adventitious root (AR) formation, biomass accumulation, and plant development under long-term waterlogging (LT-WL) conditions are largely unexplored. This study aimed to determine the roles of exogenous application of ABA and IAA in two woody plants (Cleistocalyx operculatus and Syzygium jambos) under LT-WL conditions. A pot experiment was conducted using a complete randomized design with two factors: (i) LT-WL and (ii) application of exogenous phytohormones (ABA and IAA) for 120 d.

Results
Results revealed that exogenous ABA and IAA promoted LT-WL tolerance in both species. In C. operculatus and S. jambos, plant height, the number of blades, leaf area, and fresh shoot weight were increased by exogenous IAA under LT-WL. However, exogenous ABA affected more the adventitious and primary root in C. operculatus compared to S. jambos. LT-WL decreased drastically the photosynthetic activities in both species, but adding moderate amounts of exogenous ABA or IAA protected the photosynthesis apparatus under LT-WL. Exogenous phytohormones at certain levels decreased the superoxide anion level and malondialdehyde accumulation in plants under LT-WL. Also, the increase of the peroxidases and superoxide dismutase activities by exogenous phytohormones was more marked in C. operculatus compared to S. jambos. Meanwhile, the catalase activity was down-regulated in both species by exogenous phytohormones. Exogenous ABA or IAA positively regulated the jasmonic acid content in ARs under LT-WL. Moderate application of exogenous ABA or IAA in plants under LT-WL decreased the ABA content in the leaves. Lower accumulation of IAA and ABA in the leaves of C. operculatus under LT-WL was positively correlated with a decrease in antioxidant activity.

Conclusions
Lastly, C. operculatus which has greater morphology indexes was more tolerant to waterlogging than S. jambos. Moreover, the adaptive strategies via exogenous ABA were more built around the below-ground biomass indexes particularly in C. operculatus, while exogenous IAA backed the above-ground biomass in both species. Overall, the exogenous hormones applied (spraying or watering) influenced differentially the plant’s responses to LT-WL. The phytohormonal profile of plants exposed to waterlogging stress varied depending on the species’ tolerance level.
Association between serum liver enzymes and hypertension using propensity score matching analysis: evidence from a large kurdish prospective cohort study
Authors: Fard Mina Tahmasebi , Najafi Farid , Rezaeian Shahab , Kohsari Maryam , Moradinazar Mehdi 
Published: November 2022

Abstract
Background
The association between liver enzymes and hypertension (HTN) has been reported in some studies and the findings are inconsistent. This study was conducted to evaluate the association of liver enzymes with HTN among the Iranian Kurdish population.

Methods
This prospective cohort study was a part of the 5-years (2017–2021) follow-up phase of the Ravansar Non-Communicable Disease (RaNCD) cohort study in Kermanshah province, western Iran.The association between alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glut amyl transferase (GGT), and alkaline phosphatase (ALP) and HTN was investigated by Cox proportional-hazard model (CPHM). We used one-to-one Propensity score matching (PSM) analysis to minimize the effects of confounding factors on the relationship between liver enzymes and HTN .

Results
The full population included a total of 8267 participants. According to PSM, for liver enzyme GGT a total of 3664 participants were analyzed. The results of multivariate CPHM showed there is a relationship between participants with high level of GGT and had a higher risk of HTN (HR 1.34; 95% CI: 1.11–1.63). After PSM analysis, the effect of GGT on HTN remained positive and significant (HR 1.48; 95% CI: 1.22–1.78). The 5-years incidence rate of HTN in men and women were 1.27 and 0.81 (person-year), respectively.GGT had the greatest accuracy, which demonstrated an AUROC of 0.7837.

Conclusion
Results of this study showed GGT could be a potential biomarker among liver enzymes for early detection of HTN. Therefore, monitoring GGT levels is helpful in the early detection of HTN.
The predictive effect of direct-indirect bilirubin ratio on clinical events in acute coronary syndrome: results from an observational cohort study in north China
Authors: Li Jiayu , Xin Yanguo , Li Jingye , Meng Meng , Zhou Li , Qiu Hui , Chen Hui , Li Hongwei 
Published: November 2022

Abstract
Background:
Patients with extremely high-risk ASCVD usually suffered poor prognosis, bilirubin is considered closely related to cardiovascular outcomes. However, there is controversy over the relationship between bilirubin and coronary artery disease. This study aimed to evaluate the predictive value of the DIBIL ratio in patients with extremely high-risk ASCVD.

Methods:
10,260 consecutive patients with extremely high-risk ASCVD were enrolled in this study. All patients were divided into three groups according to their DIBIL ratio. The incidence of MACCEs was recorded, and in a competing risk regression, the incidence of MACCEs and their subgroups were recorded. The direct-indirect bilirubin ratio (DIBIL ratio) was calculated by the direct bilirubin (umol/L)/indirect bilirubin (umol/L) ratio, all laboratory values were obtained from the first fasting blood samples during hospitalization.

Results:
The area under the ROC curve of the DIBIL ratio to predict the occurrence of all-cause death was 0.668, the cut-off value of which is 0.275. Competing risk regression indicated that DIBIL ratio was positively correlated with all-cause death [1.829 (1.405–2.381), p < 0.001], CV death [1.600 (1.103, 2.321), p = 0.013]. The addition of DIBIL ratio to a baseline risk model had an incremental effect on the predictive value for all-cause death [IDI 0.004(0, 0.010), p < 0.001; C-index 0.805(0.783–0.827), p < 0.001].

Conclusion:
The DIBIL ratio was an excellent tool to predict poor prognosis, suggesting that this index may be developed as a biomarker for risk stratification and prognosis in extremely ASCVD patients.
Evaluation of index of cardiac-electrophysiological balance in patients with subarachnoid hemorrhage
Authors: Yücetas Seyho Cem , Kaya Hakan , Kafadar Safiye , Kafadar Huseyin , Tibilli Hakan , Akcay Ahmet 
Published: November 2022

Abstract
Background
Various electrocardiographic (ECG) changes occur after subarachnoid hemorrhage (SAH). Prolonged QT and corrected QT (QTc) intervals are notable changes. QT, QTc, T peak-to-end T(p-e) intervals, and Tp-e/QTc ratio are used as ventricular arrhythmia indices. In recent publications, the cardiac electrophysiological balance index (ICEB), which provides more information than other ECG parameters (QT, QTc, etc.), is recommended in predicting the risk of ventricular arrhythmia. This study aims to assess ICEB in aneurysmal SAH patients.

Methods
The study included 50 patients diagnosed with aneurysmal SAH and 50 patients diagnosed with hypertension without end-organ damage as the control group. All patients’ Fisher scores and Glasgow Coma Scale (GCS) scores were recorded. Both groups were given 12-lead ECGs. QT, QTc, Tp-e intervals, QRS duration, ICEB (QT/QRS), ICEBc (QTc/QRS), and T(p-e)/QTc values were calculated and analyzed between groups.

Results
Compared to the control group; QT (426,64 ± 14,62 vs. 348,84 ± 12,24 ms, p < 0,001), QTc (456,24 ± 28,84 vs. 392,48 ± 14,36 ms, p < 0,001), Tp-e (84,32 ± 3,46 vs. 70,12 ± 3,12, p < 0,001), Tp-e/QTc (0,185 ± 0,08 vs. 0,178 ± 0,02, p < 0,001), ICEB (4,53 ± 0,78 vs. 3,74 ± 0,28, p < 0,001) and ICEBc (4,86 ± 0,86 vs. 4,21 ± 0,24, p < 0,001) were significantly higher in patients with aneurysmal SAH. QT, QTc and Tp-e interval, Tp-e/QTc ratio, ICEB (QT/QRS) and ICEBc (QTc/QRS) were positively correlated with the Fisher score and were negatively correlated with the GCS. According to linear regression analyses, the ICEBc (QTc/QRS) found to be independently associated with the Fisher score.

Conclusion
The values of the ICEB and ICEBc were significantly increased in patients with aneurysmal SAH. The severity of SAH was positively correlated with the ICEB and ICEBc. The ICEBc (QTc/QRS) independently associated with the Fisher score. This may that SAH suggest may predispose to malignant ventricular arrhythmias.
An integrated skin cancer education program in renal transplant recipients and patients with glomerular disease
Authors: Thet Zaw , Lam Alfred King-yin , Ng Shu-Kay , Aung Soe Yu , Han Thin , Ranganathan Dwarakanathan , Newsham Stephanie , Borg Jennifer , Pepito Christine , Khoo Tien K. 
Published: November 2022

AbstractSun-protective strategies focusing on skin cancer awareness are needed in immunosuppressed patients at risk of skin cancers. The study aims to determine the effect of an integrated skin cancer education program on skin cancer awareness and sun-protective behaviours in renal transplant recipients (RTRs) and patients with glomerular disease (GD) treated with long-term immunosuppressants. A pilot prospective cohort study in Central Queensland, Australia was undertaken among adult RTRs and patients with GD, who completed survey questionaries on skin cancer and sun-health knowledge (SCSK), sun-protection practices and skin examination pre- and post-education. Fifty patients (25 RTRs, 25 patients with GD) participated in the study. All of them completed questionnaires at pre-, 3-month post-education and 92%(n = 46) at 6-month post-education. There was a significant increase in SCSK scores from baseline at 3-months (p < 0.001) and 6-months post-intervention (p < 0.01). Improved knowledge was retained for 6 months after education. There were changes in 2 of 8 photoprotective behaviours at 6 months. Interventional education enhanced regular self-skin examination rate (p < 0.001) as well as the frequency of full skin checks by general practitioners (GPs) (p < 0.001). Overall, RTRs had better compliance with sun-protective methods and higher skin examination rates by themselves and/ or GPs before and after the intervention of education compared to patients with GD. To conclude, an integrated skin cancer education program improved knowledge of skin cancer and skin health as well as the frequency of self-skin examination and formal skin assessments. However, improvement in patient compliance did not extend to other sun-protective practices.
Effects of deficient mismatch repair on the prognosis of patients with stage II and stage III colon cancer during different postoperative periods
Authors: Zhang Chunze , Zhan Yixiang , Ni Kemin , Liu Zhaoce , Xin Ran , Han Qiurong , Li Guoxun , Ping Hangyu , Liu Yaohong , Zhao Xuanzhu , Wang Wanting , Yan Suying , Sun Jing , Zhang Qinghuai , Wang Guihua , Zhang Zili , Zhang Xipeng , Hu Xia 
Published: November 2022

AbstractBackgroundWe evaluated the prognostic role of deficient mismatch repair (dMMR) systems in stage II and stage III colon cancer patients during different postoperative periods. We also assessed whether patients aged ≥75 could benefit from chemotherapy.MethodsThis retrospective study was conducted across three medical centers in China. Kaplan–Meier survival methods and Cox proportional hazards models were used to evaluate the differences in overall survival (OS) and disease-free survival (DFS) rates. Propensity score matching was performed to reduce imbalances in the baseline characteristics of the patients. Landmark analysis was performed to evaluate the role of dMMR during different postoperative periods.ResultsThe median follow-up time for all patients was 45.0 months (25–75 IQR: 38.0–82.5). There was no significant OS (p = 0.350) or DFS (p = 0.752) benefit associated with dMMR for stage II and III patients during the first postoperative year. However, significant OS (p < 0.001) and DFS (p < 0.001) benefits were observed from the second postoperative year until the end of follow-up. These differences remained after propensity score matching. Moreover, chemotherapy produced no OS (HR = 0.761, 95% CI: 0.43–1.34,p = 0.341) or DFS (HR = 0.98, 95% CI: 0.51–1.88,p = 0.961) benefit for patients aged ≥75 years.ConclusionThe benefits of dMMR in stage III patients were observed from the second postoperative year until the end of follow-up. However, the prognosis of patients with dMMR is not different from that of patients with proficient mismatch repair (pMMR) during the first postoperative year. In addition, elderly patients aged ≥75 years obtained no significant survival benefits from postoperative chemotherapy.
Early outcomes of anterior segment parameters after implantable collamer lens V4c implantation
Authors: Lin Qinghong , Yang Dong , Zhou Xingtao 
Published: November 2022

Abstract
Background
This study investigated the early outcomes of anterior segment parameters after implanting an implantable collamer lens with a central hole (ICL V4c) in patients with myopia and determined the earliest follow-up time for detecting potential complications.

Methods
Sixty-two patients were included, and the following parameters were measured at baseline (preoperative), 1 day, 1 week, and 1, 3, and 6 months after the operation: intraocular pressure (IOP), endothelial cell density (ECD), central anterior chamber depth (CACD), anterior chamber volume (ACV), nasal and temporal anterior chamber angle (n-ACA and t-ACA), horizontal corneal diameter (white-to-white, WTW), and axial length (AL). The vault was measured at each post-operative timepoint.

Results
The postoperative IOP and ECD at the 6 months were both statistically similar to the baseline. The post-operative CACD and ACV were significantly less at all timepoints compared with the baseline (P < 0.001) and stayed stable from 1 day and 1 month after the operation, respectively. Postoperative n-ACA and t-ACA decreased significantly at 1 day and 1 week compared with the baseline (P < 0.001), while tended to stabilization at 1, 3, and 6 months. The vault kept decreasing significantly at 1 day, 1 week, and 1 month, but stayed stable at 3 and 6 months. The postoperative n-ACA and t-ACA positively correlated with the baseline ACA, CACD, and ACV.

Conclusions
The anterior chamber parameters tended to stabilization early after the operation. Thus, it is essential to evaluate patients’ anterior segment status at earlier timepoints and prevent complications with prompt and non-invasive intervention.
Clinical significance of serum and vitreous soluble interleukin-2 receptor in patients with intraocular lymphoma
Authors: Suzuki Kayo , Namba Kenichi , Kase Satoru , Ogino Yo , Hase Keitaro , Iwata Daiju , Mizuuchi Kazuomi , Hiraoka Miki , Kitaichi Nobuyoshi , Ishida Susumu 
Published: November 2022

AbstractBackgroundIntraocular lymphoma (IOL) is a masquerade syndrome that mimics uveitis, making diagnosis difficult. The serum soluble interleukin-2 receptor (sIL-2R), which is cleaved by matrix metalloproteinase (MMP) -2 and MMP-9, has been recognized as a tumor-related biomarker of malignant lymphomas. The aim of this study was to review the reliability of serum and vitreous sIL-2R for distinguishing IOL from uveitis.MethodsPatients who underwent diagnostic vitrectomy for marked vitreous haze at Hokkaido University Hospital between April 2014 and June 2019 were enrolled. The patients were divided into an IOL group and a uveitis group, according to the pathology of their vitreous samples. The IOL group was further divided at the time of vitrectomy into patients who already had extraocular involvement (IOL with extraocular involvement group) and patients with no evidence of having extraocular involvement (IOL without extraocular involvement group). Serum sIL-2R, and intravitreal sIL-2R, MMP-2, and MMP-9 levels were assessed.ResultsTwenty-five eyes of 25 patients, and 15 eyes of 15 patients were included in the IOL group and uveitis group, respectively. The serum sIL-2R levels were significantly lower in the IOL group than in the uveitis group (P < 0.05), and 20.0% and 66.7% in the IOL and the uveitis group showed high sIL-2R value above the normal range. Vitreous sIL-2R tended to be higher in the IOL group than in the uveitis group (P = 0.80). Serum sIL-2R was significantly lower in the IOL without extraocular involvement group than in the IOL with extraocular involvement group (P < 0.05); 5.9% in the IOL without extraocular involvement group and 50.0% in the IOL with extraocular involvement group showed high sIL-2R value above the normal range. Vitreous sIL-2R, MMP-2, and MMP-9 tended to be higher in the IOL with extraocular involvement group than in the IOL without extraocular involvement group (P = 0.30, < 0.05, 0.16).ConclusionsSerum sIL-2R is often within the normal range in IOL patients. Even if it is within the normal range, the possibility of IOL should be considered. Serum sIL-2R is not a reliable biomarker for IOL, whereas vitreous sIL-2R may be useful for the diagnosis of IOL.
Characteristics of paediatric foot arches according to body mass among primary school students in Wrocław, Poland
Authors: Górna Sara , Pazdro-Zastawny Katarzyna , Basiak-Rasała Alicja , Kolator Mateusz , Krajewska Joanna , Zatoński Tomasz 
Published: November 2022

Abstract
Background
The purpose of this study, conducted within the framework of the project entitled ‘Let’s get the kids moving’, was to determine the associations between children’s longitudinal and transverse foot arch and their weight, gender and age.

Method
The pro-health initiative ‘Let’s get the kids moving’ was created by researchers of the Medical University and the Run for Health Foundation. A total of 655 children (51.5% boys) aged 7 to 10 years from primary schools in south-western Poland participated in the study. The mean age of the subjects was 8.7 ± 0.8 years. In all the children, we assessed anthropometric measurements (weight and height) and the longitudinal and transverse arch of the foot under the load of their weight. A two-dimensional foot scanner (Sensor Medica, Italy) was used to examine the plantar part of the children’s feet.

Results
The data collected from the 655 subjects revealed that excessive weight predisposed them to less longitudinal and transverse arching. The foot shape was not differentiated by gender or age.

Conclusions
Screening school-aged children’s footprints can detect abnormalities in the shape of children’s feet early on, which allows for early diagnosis of functional or structural flatfoot in children.