bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer
Authors: Yaeger Rona , Mezzadra Riccardo , Sinopoli Jenna , Bian Yu , Marasco Michelangelo , Kaplun Esther , Gao Yijun , Zhao HuiYong , Paula Arnaud Da Cruz , Zhu Yingjie , Perez Almudena Chaves , Chadalavada Kalyani , Tse Edison , Chowdhry Sudhir , Bowker Sydney , Chang Qing , Qeriqi Besnik , Weigelt Britta , Nanjangud Gouri J. , Berger Michael F. , Der-Torossian Hirak , Anderes Kenna , Socci Nicholas D. , Shia Jinru , Riely Gregory J. , Murciano-Goroff Yonina R. , Li Bob T. , Christensen James G. , Reis-Filho Jorge S. , Solit David B. , de Stanchina Elisa , Lowe Scott W. , Rosen Neal , Misale Sandra 
Published: November 2022

Abstract

With the combination of KRASG12C and EGFR inhibitors, KRAS is becoming a druggable target in colorectal cancer. However, secondary resistance limits its efficacy. Using cell lines, patient-derived xenografts, and patient samples, we detected a heterogeneous pattern of putative resistance alterations expected primarily to prevent inhibition of ERK signaling by drugs at progression. Serial analysis of patient blood samples on treatment demonstrates that most of these alterations are detected at a low frequency except for KRASG12C amplification, a recurrent resistance mechanism that rises in step with clinical progression. Upon drug withdrawal, resistant cells with KRASG12C amplification undergo oncogene-induced senescence, and progressing patients experience a rapid fall in levels of this alteration in circulating DNA. In this new state, drug resumption is ineffective as mTOR signaling is elevated. However, our work exposes a potential therapeutic vulnerability, whereby therapies that target the senescence response may overcome acquired resistance.

Significance:
Clinical resistance to KRASG12C–EGFR inhibition primarily prevents suppression of ERK signaling. Most resistance mechanisms are subclonal, whereas KRASG12C amplification rises over time to drive a higher portion of resistance. This recurrent resistance mechanism leads to oncogene-induced senescence upon drug withdrawal and creates a potential vulnerability to senolytic approaches.
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Dissociable Neural Mechanisms for Human Inference Processing Predicted by Static and Contextual Language Models
Authors: Uchida Takahisa , Lair Nicolas , Ishiguro Hiroshi , Dominey Peter Ford 
Published: November 2022

Abstract
Language models (LMs) continue to reveal non-trivial relations to human language performance and the underlying neurophysiology. Recent research has characterized how word embeddings from an LM can be used to generate integrated discourse representations in order to perform inference on events. The current research investigates how such event knowledge may be coded in distinct manners in different classes of LMs and how this maps onto different forms of human inference processing. To do so, we investigate inference on events using two well-documented human experimental protocols from Metusalem et al. (2012) and McKoon and Ratcliff (1986), compared with two protocols for simpler semantic processing. Interestingly, this reveals a dissociation in the relation between local semantics versus event-inference depending on the LM. In a series of experiments, we observed that for the static LMs (word2vec/GloVe), there was a clear dissociation in the relation between semantics and inference for the two inference tasks. In contrast, for the contextual LMs (BERT/RoBERTa), we observed a correlation between semantic and inference processing for both inference tasks. The experimental results suggest that inference as measured by Metusalem and McKoon rely on dissociable processes. While the static models are able to perform Metusalem inference, only the contextual models succeed in McKoon inference. Interestingly, these dissociable processes may be linked to well-characterized automatic versus strategic inference processes in the psychological literature. This allows us to make predictions about dissociable neurophysiological markers that should be found during human inference processing with these tasks.
The Tibetan Plateau’s Far-Reaching Impacts on Arctic and Antarctic Climate: Seasonality and Pathways
Authors: Wang Liping , Yang Haijun , Wen Qin , Liu Yimin , Wu Guoxiong 
Published: November 2022

Abstract
As the highest and most extensive plateau in the world, the Tibetan Plateau (TP) has remarkable effects on global climate. Through coupled model sensitivity experiments with and without the TP, we show that the TP can affect the Arctic directly via orography-forced stationary waves, and influence the Antarctic indirectly via stationary waves forced by sea surface temperature (SST) in the Indian Ocean. These far-reaching impacts occur mainly in wintertime. The fast atmospheric processes play an important role; particularly, the midlatitude westerly flow, which is stronger and closer to the equator in winter, provides a favorable condition for the eastward and poleward energy propagation of the forced waves. In the Northern Hemisphere, removing the TP causes a wave train traveling from the Asian continent to the North America–Atlantic Ocean region, resulting in intensified westerlies and thus an enhancement of stratospheric polar vortex and Arctic cooling. The pathways are northeastward directly in the upper level due to the background westerlies, while they are eastward and then northeastward in the lower level, modulated by the winter monsoon. To the south, the TP perturbation causes an anomalous cross-equatorial flow, leading to an anomalous SST dipole pattern in the Indian Ocean in the austral winter; this generates stationary waves propagating energy southeastward from the tropical Indian Ocean to the Antarctic, resulting in a Rossby wave train circulating around the Antarctic. Our study identifies the seasonality and pathways of the TP affecting the polar regions, which may help to understand the role of the TP in the future climate changes in polar regions.
The impact of burnout on turnover intention among Chinese general practitioners: The mediating effect of job satisfaction and the moderating effect of professional identity
Authors: Feng Jing , Sang Wenyuan , Lei Zihui , Qu Ge , Li Xinyan , Ferrier Adamm , Jiang Heng , Pu Bo , Gan Yong 
Published: November 2022

Background: Turnover among general practitioners (GPs) has become a significant public health concern worldwide. Aims: This study aimed to investigate the interrelationships between job satisfaction, professional identity, burnout, and turnover intention among GPs in China and to assess the mediating effect of job satisfaction on the association between burnout and turnover intention and the moderating effect of professional identity on the association between burnout and job satisfaction. Method: A cross-sectional study was conducted to collect data from 3,236 GPs in eastern, central, and western China between October 2017 and February 2018 using a self-administered questionnaire. Pearson’s correlation analysis and hierarchical regression were used to identify the relationships between job satisfaction, professional identity, burnout, and turnover intention among Chinese GPs. Results: Among these respondents, 65.02% reported a medium or high level of emotional exhaustion (EE), 35.38% reported a moderate or high level of depersonalization (DP), and 62.05% reported reduced personal achievement (PA). Overall, 71.08% of GPs expressed a relatively high intention to seek another position (turnover intention). We found all 3 dimensions of burnout contributed to job dissatisfaction while turnover intention arising from burnout was associated with EE and DP. Job satisfaction had a direct negative impact on turnover intention and partially mediated the impact of EE and DP on turnover intention. Professional identity played a partial moderated role between EE and job satisfaction. Conclusions: The prevalence of burnout and turnover intention among GPs is high in China. The effect of EE and DP on turnover intention is mediated by job satisfaction, and the effect of EE on job satisfaction is moderated by professional identity.
Lived experiences of mental health conditions in Singapore: A constructivist grounded theory study
Authors: Kuek Jonathan Han Loong , Raeburn Toby , Chow Melissa Yan Zhi , Wand Timothy 
Published: November 2022

Background: Since the 1990s, the mental healthcare field has begun shifting to conceptualisations of personal mental health recovery, emphasising the heterogeneous nature of how people develop and overcome the difficulties associated with mental ill health. Despite three decades of research on the topic, most recovery-oriented studies have been conducted in predominantly Western cultures, lacking the necessary nuances when applied in Asian settings. Aims: We sought to contribute to a growing body of research to fill this gap by exploring the experiences of people who experience mental ill-health in Singapore. Method: We adopted a constructivist grounded theory approach and interviewed 21 people who had been diagnosed as experiencing a mental health condition. Results: The core category emerging from interview participant perspectives was a ‘roller coaster ride of confusion’. This overarching category was made up of the following four sub-categories – ‘not understanding what was happening’, ‘losing control over self’, ‘unpacking the root of challenges’ and ‘trying to make sense of the situation’. Conclusions: Taken together, the journey of a person experiencing mental health recovery in Singapore is filled with obstacles and uncertainty due to various social and cultural influences such as family pressures, the competitiveness of society and the high-pressure nature of Singapore’s educational system. Future research needs to better understand if these are generalisable experiences, and interventions to mitigate their impact need to be explored. Given the strong societal influences, change will take time. Still, this study gives a voice to the lived experiences of people who face mental health challenges in Singapore in the hope that their insights may assist future generations in developing a more mentally healthy society.
Palliative care for adolescents and young adults with advanced illness: A scoping review
Authors: Abdelaal Mohamed , Avery Jonathan , Chow Ronald , Saleem Nasreen , Fazelzad Rouhi , Mosher Pamela , Hannon Breffni , Zimmermann Camilla , al-Awamer Ahmed 
Published: November 2022

Background: Age-related complex medical conditions have been commonly reported among adolescents and young adults with advanced life-limiting illness. There is increasing interest in exploring their palliative care needs and end-of-life experiences. Aim: This scoping review aimed to explore the available literature about providing palliative and end-of-life care to adolescents and young adults with advanced life-limiting illnesses. Design: Scoping review. This review was registered on Open Science Framework ( https://doi.org/10.17605/OSF.IO/SPTD7 ). Data sources: Electronic databases (MEDLINEALL, Embase, Emcare, Cochrane Central Register of Controlled Trial CENTRAL, Scopus, PsycINFO, Cochrane Database of Systematic Reviews), Google Scholar and reference lists were searched up to October 2021. We included studies reporting on adolescents and/or young adults with advanced life-limiting illnesses. There were no limitations concerning location, type of illness or study design. Results: We identified 51 studies published between 2002 and 2021. Most studies were published in the United States ( n = 34, 67%), and nine studies (18%) reported exclusively on patients with non-malignant illnesses. Two thirds of the identified studies were case reports and retrospective chart reviews ( n = 33). Three main topics were identified: Physical symptom burden ( n = 26, 51%), Psychological and social needs ( n = 33, 65%), and end-of-life care ( n = 30, 59%). Twenty-six studies (51%) were focused only on one topic, and the age range used to identify adolescents and young adults varied based on the study location. Conclusion: The findings of this review shed light on the different palliative care experiences and knowledge gaps related to adolescents and young adults as an underserved and vulnerable patient population. Further research needs to be dedicated toward palliative care programs tailored for adolescents and young adults.
A basic study for the molecular imaging of dual-energy CT in diagnosing anterior cruciate ligament injury of knee joint
Authors: Bai Rui , He Xiaohua , Huang Juncheng 
Published: November 2022

Background Anterior cruciate ligament (ACL) injury is a common disease in clinical practice that seriously affects the daily life of patients. Purpose To explore the molecular imaging basis of “diminution sign on dual-energy colour mapping” for the diagnosis of ACL injury by dual-energy computed tomography (DECT). Material and Methods The hydroxylysine and hydroxyproline reagents were prepared in different concentrations. The grouping was shown as follows: a simple concentration change group of an amino acid (group 1/2); a mixed solution group with the concentration increasing synchronously (group 3); a mixed solution group with the concentration reverse increasing and decreasing (group 4); and a mixed solution group that fix one amino acid with increasing concentration of the other (group 5/6). The samples were scanned by DECT. The solution CT value and image signal-to-noise ratio were analyzed. Results In group 1/2, the brightness of the dual-energy color mapping of each test tube solution and the CT value increased with increasing the concentration of amino acid. In group 6, there was no significant change in the brightness and brilliance of the dual-energy color mapping and the CT value. The remaining three groups showed an increase in the brightness and brilliance of the dual-energy color mapping and the CT value, and this increase was positively associated with the hydroxylysine concentration. Conclusion The dual-energy staining of the DECT imaging in “tendon” mode is related to hydroxylysine and hydroxyproline. Moreover, the degree of dual-energy color mapping is positively correlated with the change of CT value.
Transcriptomic and proteomic characteristics of the di(2-ethylhexyl) phthalate-induced sperm dna damage mouse model
Authors: Zhang Chenming , Wang Zulong , Chen Rubing , Wang Shiqi , Zhang Hao , Ma Sicheng , Hua Zhong 
Published: November 2022

Di(2-ethylhexyl) phthalate (DEHP) is one of the most common organic pollutants and is added to various plastic products as a plasticizer. DEHP oxidative metabolite content in the human body is associated with DNA damage in sperm and decreased testosterone levels in blood. In this study, a DEHP-induced sperm DNA damage mouse model was replicated and improved, and the transcriptomic and proteomic characteristics of the model were observed. Male mice in the two groups were exposed to DEHP 1 g/kg/d or the same amount of normal saline for 60 days, and the sperm DNA fragmentation index (DFI) was detected by a sperm chromatin structure assay (SCSA). The mRNA and protein expression profiles of the testis were detected by RNA-seq and data-independent acquisition (DIA). The sperm DFI of the DEHP group was significantly increased. Compared with the control group, 111 differentially expressed genes (DEGs) and 2147 differentially expressed proteins (DEPs), such as Lamb2, Ahnak, Tkt, Dnah8 and Tbl2, were found in the DEHP group. These genes were mainly enriched in metabolic pathways, pathways in cancer and the PI3K-Akt signaling pathway. Our results showed that DEHP 1 g/kg/d can induce sperm DNA damage in a male mouse model after 60 days of intragastric administration. The reproductive toxicity of DEHP may be related to metabolic pathways in cancer and the PI3K-Akt signaling pathway.
Under-Documented or Under-Recognized? Comorbid ADHD in Emergency Department Patients With Addictive Disorders
Authors: Hale Elijah W. , Coyle Tyler D. 
Published: November 2022

Objectives: We sought to examine rates of comorbid ADHD and SUD/AUD using a nationally representative dataset, and to compare this data with established estimates. We hoped to increase available research on ADHD within patients with SUD/AUD. Methods: This study is a retrospective secondary analysis of cross-sectional data collected in the National Hospital Ambulatory Medical Care Survey (NHAMCS). Results: The data showed less than 1% of comorbid ADHD in either AUD or SUD, and prevalence of 0.6% in patients with both. Our estimated prevalence of ADHD among SUD/AUD patients is more than 30-fold smaller than the 25% consensus. Conclusion: The stark difference between our data and prior research indicates a need for further examination of the prevalence of ADHD within acute care. This finding of a large reservoir of ADHD that is unrecognized or undocumented indicates a substantive need for ADHD-focused education with opportunity for improvement in patient treatment.
The effect of trunnionosis on the risk of re-revision following femoral head exchange in hip arthroplasty
Authors: Osan Jessica , Pabbruwe Moreica , Kop Alan , Joyce Alex , Vlaskovsky Phil , Salasi Mobin , Kuster Markus 
Published: November 2022

Background: Fretting corrosion at modular junctions contributes to arthroplasty failure. Currently, no evidence-based guidelines are available regarding the acceptable level of trunnion corrosion that can occur in vivo. We aimed to examine the relationship between trunnion corrosion and risk of re-revision to assist surgeons with intraoperative decision making. Method: Grading by 3 independent examiners of revised and re-revised head components was performed using a modified Goldberg corrosion scale. Samples were separated into low-grade (LG) and high-grade (HG) corrosion. Mechanical testing determined the relationship between corrosion severity and pull-off strength at the head-stem junction. Results: 529 retrieved femoral heads were analysed. A positive association was detected between males and HG corrosion (OR 2.07; 95% CI, 1.45–2.94; p < 0.001). No difference between the survivorship of LG and HG heads was detected ( p-value = 0.247). In the re-revised sample, the first implant had a time in situ that was on average 7.97 years longer (95% CI, 5.4–10.6) than that of the subsequent re-revised femoral head. Severe corrosion on the first head was associated with a 37.5 (95% CI, 4.00–1944) fold increase of HG on the subsequent head ( p < 0.001). Femoral disassembly force had a positive correlation with stem taper corrosion grade ( p = 0.001). Conclusions: A well-fixed stem with corrosion may remain in situ.
Use of drug-eluting, balloon-expandable resolute onyx coronary stent as a novel treatment strategy for vertebral artery ostial stenosis: Case series
Authors: Lim Jaims , Baig Ammad A , Aguirre Alexander O , Cappuzzo Justin M , Vakharia Kunal , Rho Kyungduk , Waqas Muhammad , Monteiro Andre , Fretz Thomas J , Levy Elad I , Siddiqui Adnan H 
Published: November 2022

Introduction Vertebral artery (VA) ostial stenosis is notoriously difficult to treat using bare-metal stents owing to high rates of restenosis and stent kinking and breakage. We investigated the safety and effectiveness of treatment with a drug-eluting, balloon-expandable coronary stent (Resolute Onyx, Medtronic). Methods Our prospectively maintained database was retrospectively searched for consecutive patients diagnosed with VA ostial stenosis who underwent Resolute Onyx stenting with/without angioplasty between January 1, 2015 and January 1, 2022. Patient demographics and clinical and radiographic presentations were recorded. Occlusion location, stenosis severity, contralateral disease, devices used, and intraprocedural and postprocedural complications were noted. Outcomes were assessed based on new or recurrent stroke, transient ischemic attack (TIA), or intracranial hemorrhage (ICH). Patients were followed up clinically and with radiographic imaging for in-stent stenosis. Results Twenty-six patients were included in our study (21 men [80.8%]; mean age 70.3 ± 9.8 years). Symptomatic patients presented with TIA (11/26, 42.3%) and stroke (10/26; 38.5%). Mean stenosis in the study cohort was 74.9 ± 13.0%. One (3.8%) intraprocedural complication was encountered whereby the stent failed to open despite several attempts and was exchanged with a new one without issues. No in-hospital postprocedure stroke, TIA, or mortality was reported. During a mean 16.2 ± 13.6 months’ follow up, two patients developed symptomatic in-stent restenosis that was treated with balloon angioplasty. Conclusions We report the first case series of Resolute Onyx drug-eluting stenting including 30-day postprocedure stroke/TIA rates and clinical/radiographic follow up and demonstrate safe and effective treatment of symptomatic and asymptomatic VA ostial stenosis.
Contemporary review of heart transplant immunology and immunosuppressive therapy
Authors: Anbalakan Kamalesh , Chew Kenneth M , Loh Julian K , Sim David , Lai Siang Hui , Teo Loon Yee Louis 
Published: November 2022

Background Survival after heart transplantation (HT) has improved considerably since the first HT was performed in 1967 in Cape Town, South Africa. Understanding immunology behind organ rejection has paved way for advances in the assessment of pre-transplant compatibility, development of newer and more specific immunosuppressive drugs, and management of rejection. Objectives Unlike medical therapy for heart failure, transplant protocols vary considerably between different centers. These variations in protocols generally reflect unique population characteristics and the availability of resources. This review article aims to provide a consolidated update on contemporary cardiac transplant medicine. We also aim to highlight local practice and its difference from our international counterparts. Methods A literature search was performed on Pubmed and Cochrane Central Register of Controlled Trials to identify trials and review articles that discussed heart transplant immunology and protocols. The International Society for Heart and Lung Transplant (ISHLT) guidelines were also reviewed. We focused on risk factors, prevention strategies, and treatment of cardiac rejection. Results A total of 48 articles were selected to provide a comprehensive overview of the contemporary practice of cardiac transplant immunosuppressive therapy. Comparisons were made with local data and practice protocols to highlight key differences. Conclusion Heart transplant covers a small subset of cardiac patients and much of the evidence is derived from empirical observations and retrospective analysis. This accounts for the heterogeneity in care and treatment protocols. More studies are needed to select best practices from around the world to further improve outcomes.