bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thioredoxin-1 regulates self-renewal and differentiation of murine hematopoietic stem cells through p53 tumor suppressor
Authors: Jabbar Shaima , Mathews Parker , Wang Xiaobei , Sundaramoorthy Pasupathi , Chu Emily , Piryani Sadhna O. , Ding Shengli , Shen Xiling , Doan Phuong L. , Kang Yubin 
Published: October 2022

Abstract
Background
Thioredoxin-1 (TXN1) is one of the major cellular antioxidants in mammals and is involved in a wide range of physiological cellular responses. However, little is known about the roles and the underlying molecular mechanisms of TXN1 in the regulation of hematopoietic stem/progenitor cells (HSPCs).

Methods
TXN1 conditional knockout mice (ROSA-CreER-TXN1fl/fl) and TXN1fl/fl control mice were used. The mice were treated with tamoxifen and the number and biological functions of HSPCs were measured by flow cytometry, PCR and western blot. Limiting dilution competitive transplantation with sorted HSCs and serial transplantations were performed to assess the effects of TXN1 knockout on HSC self-renewal and long-term reconstitutional capacity. RNA sequencing (RNA-seq) was performed to investigate the downstream molecular pathways of TXN1 deletion in murine HSPCs. CRISPR/Cas9 knockout experiments were performed in vitro in EML murine hematopoietic stem/progenitor cell line to investigate the effects of TXN1 and/or TP53 deletion on cell survival, senescence and colony forming units. TP53 protein degradation assay, CHiP PCR and PGL3 firefly/renilla reporter assay were performed. The effects of TXN1 on various molecular pathways relevant to HSC radiation protection were examined in vitro and in vivo.

Results
TXN1-TP53 tumor suppressor axis regulates HSPC biological fitness. Deletion of TXN1 in HSPCs using in vivo and in vitro models activates TP53 signaling pathway, and attenuates HSPC capacity to reconstitute hematopoiesis. Furthermore, we found that knocking out of TXN1 renders HSPCs more sensitive to radiation and treatment with recombinant TXN1 promotes the proliferation and expansion of HSPCs.

Conclusions
Our findings suggest that TXN1-TP53 axis acts as a regulatory mechanism in HSPC biological functions. Additionally, our study demonstrates the clinical potential of TXN1 for enhancing hematopoietic recovery in hematopoietic stem cell transplant and protecting HSPCs from radiation injury.
Anti-SEZ6L2 antibodies in paraneoplastic cerebellar syndrome: case report and review of the literature
Authors: Kather Annika , Holtbernd Florian , Brunkhorst Robert , Hasan Dimah , Markewitz Robert , Wandinger Klaus-Peter , Wiesmann Martin , Schulz Jörg B. , Tauber Simone C. 
Published: October 2022

AbstractSeizure Related 6 Homolog Like 2 (SEZ6L2) protein has been shown to have implications in neuronal and especially motor function development. In oncology, overexpression of SEZ6L2 serves as a negative prognostic marker in several tumor entities. Recently, few cases of anti-SEZ6L2 antibody mediated cerebellar syndromes were reported. In this article, we present a case of a 70-year-old woman with subacute onset of gait disturbance, dysarthria and limb ataxia. Serum anti-SEZ6L2 antibodies were markedly increased, and further diagnostic workup revealed left sided breast cancer. Neurological symptoms and SEZ6L2 titer significantly improved after curative tumor therapy. This is a very rare and educationally important report of anti-SEZ6L2 autoimmune cerebellar syndrome with a paraneoplastic etiology. Additionally, we performed a review of the current literature for SEZ6L2, focusing on comparing the published cases on autoimmune cerebellar syndrome.
18F-FDG PET–CT dual-time imaging in detection and characterization of recurrent lesions in patients with testicular cancer
Authors: Nasr Ibrahim Mansour , Talaat Omnia Mohamed , Rezk Mahmoud Aly , Ali Ismail Mohamed 
Published: October 2022

Abstract
Background
Testicular cancer is the second most frequent form of male genital tumors. Globally, testicular malignancy has risen over the last forty years. Among malignant testicular tumors, germ cell tumors represent approximately 95% of all tumors. They are classified into seminomatous and non-seminomatous tumors as they differ in clinical features, therapy, and prognosis. Despite the increasing value of whole-body fluorodeoxyglucose positron emotion tomography/computerized tomography (18FDG-PET/CT) for all malignancies, the practical function of this imaging method in testicular germ cell tumors is still unknown. We aim to assess the diagnostic performance of18FDG-PET/CT dual-time-point imaging (DTPI) in the detection and characterization of recurrent testicular cancer lesions.

Results
18FDG-PET/CT DTPI showed higher specificity (SP) in lesions' delectability and characterization for local, nodal, and distant lesions than the single-time-point imaging (STPI) (97.6%, 93.8%, and 97% versus 95.2%, 68.8%, and 84.8%, respectively) and higher sensitivity (SN) for nodal and distant lesions (97% and 93.8% versus 87.8% and 87.5%, respectively). The mean SUVmaxD and the RI values—not the SUVmaxE—of the malignant lesions were significantly greater than the benign lesions (p 0.001*).

Conclusions
18FDG-PET/CT DTPI and its related indices (SUVmaxD and the RI) are more accurate, sensitive, and specific than the STPI in the characterization of recurrent lesions in testicular cancer patients.
Impact of Clinical Practice Gaps on the Implementation of Personalized Medicine in Advanced Non–Small-Cell Lung Cancer
Authors: Sadik Helen , Pritchard Daryl , Keeling Derry-Mae , Policht Frank , Riccelli Peter , Stone Gretta , Finkel Kira , Schreier Jeff , Munksted Susanne 
Published: October 2022

PURPOSE Personalized medicine presents new opportunities for patients with cancer. However, many patients do not receive the most effective personalized treatments because of challenges associated with integrating predictive biomarker testing into clinical care. Patients are lost at various steps along the precision oncology pathway because of operational inefficiencies, limited understanding of biomarker strategies, inappropriate testing result usage, and access barriers. We examine the impact of various clinical practice gaps associated with diagnostic testing-informed personalized medicine strategies on the treatment of advanced non–small-cell lung cancer (aNSCLC). METHODS Using Diaceutics' Data Repository, a multisource database including commercial and Medicare claims and laboratory data from over 500,000 patients with non–small-cell lung cancer in the United States, we analyzed the number of patients with newly diagnosed aNSCLC who could have, but did not, benefit from a personalized treatment. The analysis focuses on the independent and cumulative impacts of gaps occurring during seven steps of the precision oncology pathway, from diagnosis to treatment. RESULTS For every 1,000 patients in the study cohort, 497 (49.7%) are lost to precision oncology because of factors associated with getting biomarker test results. Among the 503 of 1,000 patients who did receive results from a biomarker test, 147 (29.2%) did not receive appropriate targeted treatments. Thus, approximately 64% of potentially eligible patients with aNSCLC are not benefiting from precision oncology therapies appropriate for their disease. CONCLUSION Most patients with aNSCLC eligible for precision oncology treatments do not benefit from them because of clinical practice gaps. This finding is likely reflective of similar gaps in other cancer types. An increased understanding of the impact of each practice gap can inform strategies to improve the delivery of precision oncology, helping to fully realize the promise of personalized medicine.
Data Mining Framework for Discovering and Clustering Phenotypes of Atypical Diabetes
Authors: Parikh Hemang M , Remedios Cassandra L , Hampe Christiane S , Balasubramanyam Ashok , Fisher-Hoch Susan P , Choi Ye Ji , Patel Sanjeet , McCormick Joseph B , Redondo Maria J , Krischer Jeffrey P 
Published: October 2022

Abstract

Context
Some individuals present with forms of diabetes that are “atypical” (AD), which do not conform to typical features of either type 1 diabetes (T1D) or type 2 diabetes (T2D). These forms of AD display a range of phenotypic characteristics that likely reflect different endotypes based on unique etiologies or pathogenic processes.

Objective
To develop an analytical approach to identify and cluster phenotypes of AD.

Methods
We developed Discover Atypical Diabetes (DiscoverAD), a data mining framework, to identify and cluster phenotypes of AD. DiscoverAD was trained against characteristics of manually classified patients with AD among 278 adults with diabetes within the Cameron County Hispanic Cohort (CCHC) (Study A). We then tested DiscoverAD in a separate population of 758 multiethnic children with T1D within the Texas Children's Hospital Registry for New-Onset Type 1 Diabetes (TCHRNO-1) (Study B).

Results
We identified an AD frequency of 11.5% in the CCHC (Study A) and 5.3% in the pediatric TCHRNO-1 (Study B). Cluster analysis identified 4 distinct groups of AD in Study A: cluster 1, positive for the 65 kDa glutamate decarboxylase autoantibody (GAD65Ab), adult-onset, long disease duration, preserved beta-cell function, no insulin treatment; cluster 2, GAD65Ab negative, diagnosed at age ≤21 years; cluster 3, GAD65Ab negative, adult-onset, poor beta-cell function, lacking central obesity; cluster 4, diabetic ketoacidosis (DKA)–prone participants lacking a typical T1D phenotype. Applying DiscoverAD to the pediatric patients with T1D in Study B revealed 2 distinct groups of AD: cluster 1, autoantibody negative, poor beta-cell function, lower body mass index (BMI); cluster 2, autoantibody positive, higher BMI, higher incidence of DKA.

Conclusion
DiscoverAD can be adapted to different datasets to identify and define phenotypes of participants with AD based on available clinical variables.
Microtubule-associated ROP interactors affect microtubule dynamics and modulate cell wall patterning and root hair growth
Authors: Feiguelman Gil , Cui Xiankui , Sternberg Hasana , Hur Eliran Ben , Higa Takeshi , Oda Yoshihisa , Fu Ying , Yalovsky Shaul 
Published: October 2022

ABSTRACT
Rho of plant (ROP) proteins and the interactor of constitutively active ROP (ICR) family member ICR5/MIDD1 have been implicated to function as signaling modules that regulate metaxylem secondary cell wall patterning. Yet, loss-of-function mutants of ICR5 and its closest homologs have not been studied and, hence, the functions of these ICR family members are not fully established. Here, we studied the functions of ICR2 and its homolog ICR5. We show that ICR2 is a microtubule-associated protein that affects microtubule dynamics. Secondary cell wall pits in the metaxylem of Arabidopsis icr2 and icr5 single mutants and icr2 icr5 double mutants are smaller than those in wild-type Col-0 seedlings; however, they are remarkably denser, implying a complex function of ICRs in secondary cell wall patterning. ICR5 has a unique function in protoxylem secondary cell wall patterning, whereas icr2, but not icr5, mutants develop split root hairs, demonstrating functional diversification. Taken together, our results show that ICR2 and ICR5 have unique and cooperative functions as microtubule-associated proteins and as ROP effectors.
Reduction of nucleolar NOC1 leads to the accumulation of pre-rRNAs and induces Xrp1, affecting growth and resulting in cell competition
Authors: Destefanis Francesca , Manara Valeria , Santarelli Stefania , Zola Sheri , Brambilla Marco , Viola Giacomo , Maragno Paola , Signoria Ilaria , Viero Gabriella , Pasini Maria Enrica , Penzo Marianna , Bellosta Paola 
Published: October 2022

ABSTRACT
NOC1 is a nucleolar protein necessary in yeast for both transport and maturation of ribosomal subunits. Here, we show that Drosophila NOC1 (annotated CG7839) is necessary for rRNAs maturation and for a correct animal development. Its ubiquitous downregulation results in a dramatic decrease in polysome level and of protein synthesis. NOC1 expression in multiple organs, such as the prothoracic gland and the fat body, is necessary for their proper functioning. Reduction of NOC1 in epithelial cells from the imaginal discs results in clones that die by apoptosis, an event that is partially rescued in a Minute/+ background, suggesting that reduction of NOC1 induces the cells to become less fit and to acquire a ‘loser’ state. NOC1 downregulation activates the pro-apoptotic Eiger–JNK pathway and leads to an increase of Xrp1, which results in the upregulation of DILP8, a member of the insulin/relaxin-like family known to coordinate organ growth with animal development. Our data underline NOC1 as an essential gene in ribosome biogenesis and highlight its novel functions in the control of growth and cell competition.
The Preference Survey Module: A Validated Instrument for Measuring Risk, Time, and Social Preferences
Authors: Falk Armin , Becker Anke , Dohmen Thomas , Huffman David , Sunde Uwe 
Published: October 2022

Incentivized choice experiments are a key approach to measuring preferences in economics but are also costly. Survey measures are a low-cost alternative but can suffer from additional forms of measurement error due to their hypothetical nature. This paper seeks to leverage the strengths of both approaches by proposing a new survey module on risk aversion, time discounting, trust, altruism, positive and negative reciprocity, in which survey items are selected based on ability to predict choices in corresponding, incentivized experiments. The methodology and results provided in the paper can also potentially provide a model for researchers who have specific requirements and want to design their own modules. This paper was accepted by Yan Chen, behavioral economics and decision analysis. Funding: The project received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7-2007-2013) [Grant 209214]. A. Falk and T. Dohmen acknowledge funding from the Deutsche Forschungsgemeinschaft (German Research Foundation) [Grant CRC TR 224 (Project A01)] and Germany’s Excellence Strategy [Grant EXC 2126/1-390838866]. Supplemental Material: Data and the online appendices are available at https://doi.org/10.1287/mnsc.2022.4455 .
CEO Succession Roulette
Authors: Cvijanović Dragana , Gantchev Nickolay , Li Rachel 
Published: October 2022

Despite intense scrutiny from investors, markets, and regulators, many public companies have no formal succession plans. Anecdotal evidence links succession risk to significant value destruction, but there is limited academic research evaluating the effects of succession planning on chief executive officer (CEO) turnover outcomes. We provide evidence that succession planning reduces the cost of management transitions by improving their efficiency. Firms with succession plans experience not only lower uncertainty around turnover events but also a faster reduction in uncertainty over the incoming CEO’s tenure, consistent with faster learning about CEO-firm fit. Succession planning also raises the quality of the CEO-firm match, as evidenced by longer CEO tenure, and improves the board’s readiness to replace an underperforming CEO, increasing turnover performance sensitivity. This paper was accepted by Suraj Srinivasan, accounting. Supplemental Material: The data are available at https://doi.org/10.1287/mnsc.2022.4572 .
Establishing the inter-rater and test–retest reliability of the levator scapulae index in women with chronic mechanical neck pain: a reliability study
Authors: Mishra Arushi , Goyal Manu , Sharma Sunita , Kumar Parveen , Ahmed Sohel 
Published: October 2022

Background/aims The levator scapulae is an important postural muscle that tends to shorten or become tight because of overactivity and bad posture, leading to neck and shoulder pain. Therefore, it is important to measure its length to effectively address dysfunction. The aim of this study was to measure the length of the levator scapulae using the levator scapulae index and examine this tool's inter-rater and test–retest reliability in women with chronic mechanical neck pain. Methods A total of 130 women aged between 18 to 30 years, with a body mass index between 18.5 and 24.9 kg/m2 and experiencing chronic mechanical neck pain, participated in this study. The length of the participants' levator scapulae was measured with a digital Vernier calliper and with the women in a standing position. Measurements were taken twice on the same day in the afternoon, with a 1 hour resting time between trials. The test–retest reliability of the levator scapulae index was measured for each participant. The procedure was repeated by two researchers after a 1-hour interval, and a mean value was obtained. Variability in body height was normalised by using the levator scapulae index (levator scapulae length [cm]/subject's height [cm]×100) Results Spearman's rank correlation coefficient test was used to establish the test–retest reliability (rho=0.96). Inter-rater reliability was established by intra-class correlation coefficient (rater A: 1.0, rater B: 0.98) with Cronbach's alpha (0.99). Conclusions The findings demonstrated the excellent reliability of the levator scapulae index for the measurement of levator scapulae length in females with chronic mechanical neck pain. This study helps to establish a reliable method for levator scapulae length measurement, which helps clinicians to plann more efficient treatment protocols for patients with chronic mechanical neck pain.
Impact of gender mismatch on corneal graft rejection and rejection-related graft failure in repeat penetrating keratoplasty
Authors: Chuckpaiwong Varintorn , Jongkhajornpong Passara , Rajsirisongsri Pongthep , Sontichai Vachira , Nijvipakul Sarayut , Lekhanont Kaevalin 
Published: October 2022

Purpose
To explore the impact of gender mismatch on corneal allograft rejection and rejection-related graft failure in patients with repeat penetrating keratoplasty (PK).

Methods
A retrospective cohort was conducted at Ramathibodi Hospital, Bangkok, Thailand. Patients with repeat PK and follow-up period of at least 6 months were recruited. Demographic data, pre-operative ocular findings and donor information were collected. Patients were divided into 2 groups according to gender mismatch between donor and recipient (male to female vs others). Survival analysis was performed using the Kaplan-Meier method. The association between risk factors and the outcomes of graft rejection and rejection-related graft failure were analyzed using Cox proportional hazards regression.

Results
Of 68 patients with repeat PK, 26 patients (38.2%) were gender mismatched. There was no difference in 3-year rejection-free survival and graft survival between patients with gender mismatch and others (p = 0.698 and p = 0.402, respectively). Younger recipients (< 40 years) showed a significantly higher rejection rate compared to older recipients (hazard ratio; HR = 3.14, 95% confidence interval; CI 1.15 to 8.58), while patients with multiple PK (> 2 times) were found to be significantly associated with higher rejection-related graft failure compared to patients with 2 times or less PK (HR = 2.72, 95% CI 1.03 to 7.21). After multivariate analysis, only younger recipients demonstrated a statistical significance on graft rejection (adjusted HR = 2.86, 95% CI 1.04 to 7.84).

Conclusions
Gender mismatch might not impact corneal graft rejection or rejection-related graft failure in patients with repeat PK. Younger age was found to be a strong factor associated with graft rejection. Gender matching might not be compulsory for repeat PK.
A simplified model for prophylactic transarterial chemoembolization after resection for patients with hepatocellular carcinoma
Authors: Lin Nanping , Wang Lei , Huang Qizhen , Zhou Weiping , Liu Xiaolong , Liu Jingfeng 
Published: October 2022

Background
Prophylactic transarterial chemoembolization (p-TACE) is frequently conducted for patients with hepatocellular carcinoma (HCC) in China, but the question of who could benefit from it remains controversial. Hence, we wanted to establish a nomogram model to identify patients eligible for p-TACE.

Methods
Data from HCC patients receiving R0 resection with or without p-TACE between January 2013 and December 2014 were identified, using primary liver cancer big data, to establish a nomogram model to predict overall survival (OS). Based on the model, Patients receiving R0 resection between January 2015 and December 2015 were divided into three subgroups, and survival curves were constructed using the Kaplan–Meier method and analyzed by the log-rank test among patients in each subgroup.

Results
A nomogram integrating the neutrophil to lymphocyte ratio, AFP, tumor diameter, and microvascular invasion was developed to predict the OS of patients with HCC receiving R0 resection, and significant differences were observed in the median OS of the subgroups of low-risk (≤20), intermediate-risk (20~120), and high-risk (>120) identified by the current model. This model showed good calibration and discriminatory power in the validation cohort and the external cohort (c-index of 0.669 and 0.676, respectively). In the external cohort, the Kaplan–Meier curves showed that p-TACE could only significantly prolong the median OS of high-risk patients (25.6 vs. 33.7 months, P<0.05), but no differences were observed in any subgroups stratified by the current staging systems (all P>0.05).

Conclusion
This readily available nomogram model could help guide decisions about p-TACE, but it needs further validation.
Dp71 and intellectual disability in Indonesian patients with Duchenne muscular dystrophy
Authors: Iskandar Kristy , Triono Agung , Sunartini  , Dwianingsih Ery Kus , Indraswari Braghmandita Widya , Kirana Ignatia Rosalia , Ivana Gabriele , Sutomo Retno , Patria Suryono Yudha , Herini Elisabeth Siti , Gunadi  
Published: October 2022

Introductions
Duchenne muscular dystrophy (DMD) is an X-linked recessive progressive muscular disease marked by developmental delays due to mutations in the DMD gene, which encodes dystrophin. Brain comorbidity adds to the burden of limited mobility and significantly impacts patients’ quality of life and their family. The changes of expression of dystrophin isoforms in the brain due to DMD gene mutations are thought to be related to the cognitive and neurobehavior profiles of DMD.

Objectives
This cross-sectional study aimed to characterize cognitive and neurodevelopmental profiles of patients with DMD and to explore underlying genotype-phenotype associations.

Methods
Patients with DMD aged 5–18 years from Dr Sardjito Hospital and Universitas Gadjah Mada Academic Hospital from 2017–2022 were included. Multiplex ligation-dependent probe amplification and whole exome sequencing were used to determine mutations in the DMD genes. Cognitive function was measured by intelligence quotient testing using the Wechsler Intelligence Scale for Children and adaptive function tests with Vineland Adaptive Behavior Scales. The Autism Mental Status Exam and Abbreviated Conner’s Rating Scale were used to screen for autism spectrum disorder (ASD) and attention deficit and hyperactivity disorder (ADHD), respectively.

Results
The mean total IQ score of DMD patients was lower than that of the general population (80.6 ± 22.0 vs 100 ± 15), with intellectual disability observed in 15 boys (29.4%). Of the 51 patients with DMD, the Dp71 group had the lowest cognitive performance with a total IQ score (46 ± 24.8; p = 0.003), while the Dp427 group and Dp140 group’s total IQ scores were 83.0 ± 24.6 and 84.2 ± 17.5 respectively. There were no DMD patients with ASD, while 4 boys (7.8%) had comorbidity with ADHD.

Conclusion
Boys with DMD are at higher risk of intellectual disability. The risk appears to increase with mutations at the 3’ end of the gene (Dp71 disruption). Moreover, Dp71 disruption might not be associated with ADHD and ASD in patients with DMD.