bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world pan-cancer landscape of frameshift mutations and their role in predicting responses to immune checkpoint inhibitors in cancers with low tumor mutational burden
Authors: Florou Vaia , Floudas Charalampos S , Maoz Asaf , Naqash Abdul Rafeh , Norton Carter , Tan Aik Choon , Sokol Ethan S , Frampton Garrett , Soares Heloisa P , Puri Sonam , Swami Umang , Wilky Breelyn , Hosein Peter , Trent Jonathan , Lopes Gilberto de Lima , Park Wungki , Garrido-Laguna Ignacio 
Published: August 2023

BackgroundPembrolizumab is FDA approved for tumors with tumor mutational burden (TMB) of ≥10 mutations/megabase (mut/Mb). However, the response to immune checkpoint inhibitors (ICI) varies significantly among cancer histologies. We describe the landscape of frameshift mutations (FSs) and evaluated their role as a predictive biomarker to ICI in a clinical cohort of patients.MethodsComprehensive genomic profiling was performed on a cohort of solid tumor samples examining at least 324 genes. The clinical cohort included patients with metastatic solid malignancies who received ICI monotherapy and had tumor sequencing. Progression-free survival (PFS), overall survival, and objective response rates (ORR) were compared between the groups.ResultsWe analyzed 246,252 microsatellite stable (MSS) and 4561 samples with microsatellite instability across solid tumors. Histologies were divided into groups according to TMB and FS. MSS distribution: TMB-L (<10 mut/Mb)/FS-A (absent FS) (N=111,065, 45%), TMB-H (≥10 mut/Mb)/FS-A (N=15,313, 6%), TMB-L/FS-P (present ≥1 FS) (N=98,389, 40%) and TMB-H/FS-P (N=21,485, 9%). FSs were predominantly identified in the p53 pathway. In the clinical cohort, 212 patients were included. Groups: TMB-L/FS-A (N=80, 38%), TMB-H/FS-A (N=36, 17%), TMB-L/FS-P (N=57, 27%), TMB-H/FS-P (N=39, 18%). FSs were associated with a higher ORR to ICI, 23.8% vs 12.8% (p=0.02). TMB-L/FS-P had superior median PFS (5.1 months) vs TMB-L/FS-A (3.6 months, p<0.01). The 12-month PFS probability was 34% for TMB-L/FS-P vs 17.1% for TMB-L/FS-A.ConclusionsFSs are found in 47% of patients with MSS/TMB-L solid tumors in a pan-cancer cohort. FS may complement TMB in predicting immunotherapy responses, particularly for tumors with low TMB.
Concurrent bacterial endocarditis is associated with worse inpatient outcomes for large vessel occlusions
Authors: Ramsay Ian A , Elarjani Turki , Govindarajan Vaidya , Silva Michael A , Abdelsalam Ahmed , Burks Joshua D , Starke Robert M , Luther Evan 
Published: August 2023

BackgroundNeurological complications of bacterial endocarditis (BE) are common, including acute ischemic stroke (AIS). Although mechanical thrombectomy (MT) is effective for large vessel occlusion (LVO) stroke, data are limited on MT for LVOs in patients with endocarditis. We assess outcomes in patients treated with thrombectomy for LVOs with concurrent BE.MethodsThe National Inpatient Sample (NIS) was used. The NIS was queried from October 2015–2019 for patients receiving MT for LVO of the middle cerebral artery. Odds ratios (OR) were calculated using a multivariate logistic regression model.ResultsA total of 635 AIS with BE patients and 57 420 AIS only patients were identified undergoing MT. AIS with BE patients had a death rate of 26.8% versus 10.2% in the stroke alone cohort, and were also less likely to have a routine discharge (10.2% vs 20.9%, both P<0.0001). AIS with BE patients had higher odds of death (OR 3.94) and lower odds of routine discharge (OR 0.23). AIS with BE patients also had higher rates of post-treatment cerebral hemorrhage, 39.4% vs 23.7%, with an OR of 2.20 (P<0.0001 for both analyses). These patients also had higher odds of other complications, including hydrocephalus, respiratory failure, acute kidney injury, and sepsis.ConclusionWhile MT can be used to treat endocarditis patients with LVOs, these patients have worse outcomes. Additional investigations should be undertaken to better understand their clinical course, and further develop treatments for endocarditis patients with stroke.
Effect of statin treatment on clinical outcomes in cardioembolic stroke with endovascular thrombectomy
Authors: Gong Chen , Liu Chang , Wang You , Chen Liyuan , Yuan Jinxian , Zhang Jie , Xiaoming Li , Chen Yanru , Huang Liping , Xu Tao , Chen Yangmei 
Published: August 2023

BackgroundWhile statins have been widely used in patients with large-artery atherosclerotic stroke, their effectiveness in patients with cardioembolic large vessel occlusion (CE-LVO) undergoing endovascular treatment (EVT) remains unclear. This study aimed to evaluate whether combining statin therapy with EVT could improve clinical outcomes in patients with acute ischemic stroke caused by CE-LVO in the anterior circulation.MethodsWe performed a retrospective screening on patients with CE-LVO in the anterior circulation who underwent EVT in 27 hospitals across China between 2018 and 2021. The primary outcome measure was functional independence, defined as a 90-day modified Rankin Scale (mRS) score of 0 to 2. Safety outcomes included 90-day mortality and symptomatic intracranial hemorrhage (sICH).ResultsA total of 510 patients with CE-LVO in the anterior circulation undergoing EVT were included in this study. Of these, 404 (79.2%) patients received statin treatment (statin group), while 106 (20.8%) did not (non-statin group). Statin treatment was significantly associated with improved functional independence (adjusted OR (aOR) 2.072, 95% CI 1.197 to 3.586, P=0.009). Moreover, statin use was associated with a lower rate of 90-day mortality (aOR 0.343, 95% CI 0.197 to 0.596, P<0.001) and a lower rate of sICH (aOR 0.153, 95% CI 0.072 to 0.325, P<0.001).ConclusionStatin treatment was associated with improved clinical outcomes and reduced risks of mortality and sICH in patients with CE-LVO in the anterior circulation undergoing EVT.
Impact of COVID-19 pandemic on treatment and outcomes of cerebral arteriovenous malformations
Authors: Ramsay Ian A , Govindarajan Vaidya , Elarjani Turki , Abdelsalam Ahmed , Silva Michael , Starke Robert M , Luther Evan 
Published: August 2023

Background
There has been a recent decrease in interventional management of cerebral arteriovenous malformations (AVMs). The objective of our study was to evaluate the changing patterns in management of AVMs in the first year of the COVID-19 pandemic.

Methods
The National Inpatient Sample (NIS) database was used. From 2016 to 2020, patients with an International Classification of Diseases, 10th revision (ICD-10) diagnosis code for a cerebral AVM were included. An intervention was defined as ICD-10 code for surgical, endovascular, or stereotactic radiosurgery treatment. Odds ratios (ORs) were calculated using a logistic regression model with covariates deemed to be clinically relevant.

Results

63 610 patients with AVMs were identified between 2016 and 2020, 14 340 of which were ruptured. In 2020, patients had an OR of 0.69 for intervention of an unruptured AVM (P<0.0001) compared with 2016–19. The rate of intervention for unruptured AVMs decreased to 13.5% in 2020 from 17.6% in 2016–19 (P<0.0001). The rate of AVM rupture in 2020 increased to 23.9% from 22.2% in 2016–19 (P<0.0001). In 2020, patients with ruptured AVMs had an OR for inpatient mortality of 1.72 compared with 2016–19. Linear regression analysis from 2016 to 2020 showed an inverse relationship between intervention rate and rupture rate (slope −0.499, R
2
=0.88, P=0.019).

Conclusion
In 2020, the rate of intervention for unruptured cerebral AVMs decreased compared with past years, with an associated increase in the rate of rupture. Patients with ruptured AVMs also had a higher odds of mortality.
Seasonal variation in trophic structure and community niche dynamics of an Arctic coastal community of marine vertebrates
Authors: Fuirst Matthew , Elliott Kyle H. , Ferguson Steven H. , Fisk Aaron T. , Harris Les N. , Hedges Kevin J. , Jacobs Kevin B. , Johnson Kelsey F. , Loewen Tracey N. , Matthews Cory J. D. , Mundy C.J. , Niemi Andrea , Ogloff Wesley R. , Watt Cortney A. , Yurkowski David J. 
Published: August 2023

Temporal variation in food web structure is widespread among highly seasonal environments, such as the Arctic, and is driven by changes in resource availability. Variation in resource availability can lead to species differences in diet composition, isotopic niche width, and trophic position (TP) across seasons. Here, we used tissue samples that represent two distinct turnover rates for diet (liver = shorter term, muscle = longer term) from 18 fish and three marine mammal species to investigate seasonal (i) variation in TPs within the Southampton Island marine ecosystem of Hudson Bay, (ii) variation in consumer isotopic niche width within this part of the food web, and (iii) variation in community niche dynamics among a fish and marine mammal community using stable carbon (δ13C) and nitrogen (δ15N) isotope analyses. Many zooplanktivores and piscivores increased in TP in summer (i.e., shorter-term turnover period), whereas benthic feeders dependent on ice-obligate prey decreased in TP. Most isotopic niche widths and community metrics (δ15N range, total ellipse area, mean centroid distance) were higher in liver than muscle. Our findings demonstrate seasonal changes in TPs, which suggests that Arctic communities may be differentially affected by longer ice-free periods and earlier onset of primary production due to accelerated climate change.
Ruptured Large Gastrointestinal Stromal Tumor: A Case Report and Review of Literature
Authors: Jabbar Javereeya Abdul , Elmekresh Amr , Eltayeb Yousif 
Published: August 2023

Gastrointestinal stromal tumors (GIST) account for the majority of non-epithelial, mesenchymal tumors occurring in the gastrointestinal tract. Usually, the tumor measures a few centimeters, and cases larger than 15 cm are rare. Here, we report a rare case of a previously healthy 50-year-old woman, with generalized abdominal pain and increased abdominal girth for over nine months. Imaging showed a very large cystic lesion (

21

cm
×
15

cm
×
24

cm

) arising from the greater curvature of the stomach with rupture of the lesion into the intraperitoneal space. The patient was taken for exploratory laparotomy, which revealed a ruptured large cystic mass (

21

cm
×
15

cm
×
24

cm

) occupying the upper abdomen and encompassing the greater curvature of the stomach, body, and tail of the pancreas, as well as part of the spleen.
ATM-Inhibitor AZD1390 Is a Radiosensitizer for Breast Cancer CNS Metastasis
Authors: Tew Ben Yi , Kalfa Alex J. , Yang Zeyi , Hurth Kyle M. , Simon Thomas , Abnoosian Eric , Durant Stephen T. , Hamerlik Petra , Salhia Bodour 
Published: August 2023

Abstract

Purpose:
Limited effective treatments are currently available for central nervous system (CNS) metastasis (CM). This is largely driven by the inability of current therapeutics to penetrate the blood brain barrier (BBB) and the lack of preclinical models for testing new therapies. Here we study the efficacy of AZD1390, a BBB penetrating ataxia-telangiectasia mutated inhibitor, as a radiosensitizer for breast cancer CM treatment.

Experimental Design:
Three patient-derived xenograft (PDX) tumors including 2 HER2+ and 1 triple-negative breast cancer harboring DNA damage response (DDR) gene mutations, were implanted subcutaneously in the flank of mice to assess tumor growth inhibition by AZD1390 combined with radiation. Animal survival was further assessed by implanting the best responding PDX model orthotopically in the brain.

Results:
Pretreatment with AZD1390 followed by radiation therapy inhibited growth of PDX tumors implanted in the flank, and improved survival in orthotopic models with average survival of 222 days compared with 123 days in controls. Administration of AZD1390 posttreatment for 21 days had no further benefits. While the combination therapy resulted in sustained tumor inhibition, sporadic regrowth was observed in some mice 50 to 100 days posttreatment in all models. Gene expression comparing these tumors with complete responders demonstrated changes in upregulation of oncogenic proteins, which are potential drivers of tumor growth after treatment.

Conclusions:
Our results demonstrate that AZD1390 effectively sensitizes breast cancer CM to radiation therapy in DDR mutant tumors. This study demonstrates the potential of using AZD1390 as a novel therapeutic agent for patients with breast cancer CM.
Phase I Results of Bromodomain and Extra-Terminal Inhibitor PLX51107 in Combination with Azacitidine in Patients with Relapsed/Refractory Myeloid Malignancies
Authors: Senapati Jayastu , Fiskus Warren C. , Daver Naval , Wilson Nathaniel R. , Ravandi Farhad , Garcia-Manero Guillermo , Kadia Tapan , DiNardo Courtney D. , Jabbour Elias , Burger Jan , Short Nicholas J. , Alvarado Yesid , Jain Nitin , Masarova Lucia , Issa Ghayas C. , Qiao Wei , Khoury Joseph D. , Pierce Sherry , Miller Darla , Sasaki Koji , Konopleva Marina , Bhalla Kapil N. , Borthakur Gautam , Pemmaraju Naveen 
Published: August 2023

Abstract

Purpose:
Treatment outcomes in patients with relapsed/refractory (R/R) myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) remains dismal. On the basis of both extensive preclinical data and emerging clinical data, treatment with bromodomain and extra-terminal domain inhibitors (BETi) is a potential approach for patients with high-risk myeloid malignancies.

Patients and Methods:
We conducted a phase I trial to study the safety and efficacy of PLX51107 (BETi) and azacitidine combination therapy in patients with R/R AML and high-risk (HR) MDS and studied mechanisms of resistance to the combination therapy.

Results:
Thirty-seven patients with HR R/R MDS (n = 4) and R/R AML (n = 33) were treated. Sixteen patients (43%) had MECOM gene rearrangement and 7 other patients had TP53 mutation. Median prior number of therapies was three (range 1–9); 97% had received prior hypomethylating agent and 84% prior venetoclax. Overall response rate was 8/37 (22%): complete remission with incomplete platelet recovery (n = 1); morphologic leukemia-free state (n = 2); hematologic improvement (n = 5). The most common nonhematologic toxicities were febrile neutropenia and pneumonia in 12 (32%) patients each; 6 patients (17%) had severe hyperbilirubinemia. RNA-sequencing analysis of mononuclear cells harvested on treatment (day 3) versus pretreatment showed significant changes in mRNA expressions in responders: downregulation of MYC, BCL2, IL7R, and CDK6 and upregulation of HEXIM1, CD93, DCXR, and CDKN1A. Immunoblot analyses confirmed reduction in protein levels of c-Myc, CDK6, BCL2, and BCL-xL, and induction of BRD4 and HEXIM1 protein levels in responders.

Conclusions:
In a heavily pretreated patient cohort with R/R MDS and AML, PLX51107+ azacitidine was well-tolerated and resulted in modest clinical benefit.
High Self‐Reported Levels of Pain 1 Year After a Myocardial Infarction Are Related to Long‐Term All‐Cause Mortality: A SWEDEHEART Study Including 18 376 Patients
Authors: Vixner Linda , Hambraeus Kristina , Äng Björn , Berglund Lars 
Published: August 2023

Background
Pain increases the risk for cardiovascular diseases, including myocardial infarction (MI). However, the impact of pain on mortality after MI has not yet been investigated in large studies with long‐term follow‐up periods. Thus, we aimed to examine various levels of pain severity 1 year after an MI as a potential risk for all‐cause mortality.

Methods and Results
We collected data from 18 376 patients, aged <75 years, who had a registered MI event during the period from 2004 to 2013 and with measurements of potential cardiovascular risk indicators at hospital discharge from the Swedish quality register SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies). Self‐reported levels of experienced pain according to EuroQol‐5 dimension instrument were recorded in secondary prevention clinics 1 year after hospital discharge. We collected all‐cause mortality data up to 8.5 years (median, 3.4 years) after the 1‐year visit. The Cox proportional hazard regression was used to estimate hazard ratio (HR) and 95% CI. Moderate pain and extreme pain were reported by 38.2% and 4.5%, respectively, of included patients. There were 1067 deaths. Adjusted HR was 1.35 (95% CI, 1.18–1.55) and 2.06 (95% CI, 1.63–2.60) for moderate and extreme pain, respectively. Pain was a stronger mortality predictor than smoking.

Conclusions
Pain 1 year after MI is highly prevalent, and its effect on mortality 1 year after MI was found to be more pronounced than smoking. Clinicians managing patients after MI should recognize the need to consider experienced pain when making prognosis or treatment decisions.
TREAT‐AIS: A Multicenter National Registry
Authors: Tang Sung‐Chun , Hsieh Yi‐Chen , Lin Chun‐Jen , Chen Yu‐Wei , Lin Kuan‐Hung , Sung Pi‐Shan , Hsieh Meng‐Tsang , Tang Chih‐Wei , Chu Hai‐Jui , Tsai Kun‐Chang , Chou Chao‐Liang , Wei Cheng‐Yu , Yen Shang‐Yih , Chen Po‐Lin , Yeh Hsu‐Ling , Chan Lung , Sung Sheng‐Feng , Liu Hon‐Man , Lin Ching‐Huang , Lee Chung‐Wei , Lee I‐Hui , Chen Chi‐Jen , Lin Chien‐Jen , Chang Yu‐Ming , Ou Chang‐Hsien , Lai Yen‐Jun , Lin Cheng‐Huai , Chen Chih‐Hao , Chou Chung‐Hsing , Lien Li‐Ming , Chiou Hung‐Yi , Lee Jiunn‐Tay , Jeng Jiann‐Shing ,   the nationwide TREAT‐AIS (Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke) investigators
Published: August 2023

Background
Endovascular thrombectomy (EVT) is the standard therapy for patients with acute ischemic stroke secondary to large‐artery occlusion. In January 2019, the Taiwan Stroke Society established a nationwide TREAT‐AIS (Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke). Here, we provide the study design, current progress, and baseline data of TREAT‐AIS.

Methods
TREAT‐AIS is a multicenter prospective registration program in Taiwan. Patients aged ≥20 years who underwent EVT for acute ischemic stroke were recruited. The key items on the registration form were divided into general stroke demographics and EVT‐related sections. The main outcome of effectiveness was functional independence (modified Rankin Scale score, 0–2) at 3 months. The influence of sex on post‐EVT outcomes was also analyzed in the presented study.

Results

By the end of June 2022, there were 10 medical centers and 9 community hospitals participating in the TREAT‐AIS and a total of 1522 patients (mean±SD age, 71.2±13.6 years; men, 55.6%) being enrolled. The median National Institutes of Health Stroke Scale score on admission was 18 (interquartile range, 12–23). The major cause of stroke was cardioembolism (43.6%), followed by large‐artery atherosclerosis (36.8%) and an undetermined cause (15.4%). Functional independence at 3 months poststroke was achieved in 36.2% of the patients. Male patients were more likely to have functional independence at 3 months compared with female patients (40.4% versus 30.8%;
P
<0.001). However, the sex difference in functional independence became nonsignificant (odds ratio, 1.12 [95% CI, 0.96–1.46] in men compared with women) after adjusting for age, National Institutes of Health Stroke Scale score at admission, and recanalization status after EVT.

Conclusions
This study demonstrated the current progress of the TREAT‐AIS in capturing real‐world EVT data in Taiwan. The TREAT‐AIS will provide valuable insights into the real‐world practice of EVT in patients with acute stroke and the related quality of care in Asian patients.
Jesuits in Modern Far East
Authors: Pieragastini Steven 
Published: August 2023

Abstract
This special issue of the Journal of Jesuit Studies explores the “new” Jesuit mission to China, established in the 1840s. This, following the Society’s suppression in Europe and the broader banishment of Christianity in China. The introduction provides a snapshot of the critical themes threading through the essays. These include the dynamic interplay between the “old” and “new” Jesuit missions to China, featuring intriguing discussions on cultural “accommodation” and indigenization. The unique role of Shanghai as a vital Jesuit hub in East Asia is examined, underscoring its strategic importance. Furthermore, the issue delves into the transference and circulation of ideologies, texts, and visual media within East Asia, highlighting the region’s interconnectedness. The collection presents a comprehensive view of the Jesuits’ complex, transformative journey in the East.
Jesuit Louis Antoine de Poirot’s Translation of the Bible: A Comparative Approach to Translation and Rhetoric
Authors: Yu Ya-Ting 
Published: August 2023

Abstract
A critical study of the history of the use of language reveals that ideology, religion, and language have usually been intimately linked; this also applies to the topic of “mutual encounters and linguistic exchanges” between China and the West. At the same time, we can affirm that each Chinese encounter with the West represented an encounter with Christians and Christianity. Within this context, this article examines how Jesuit Louis Antoine de Poirot (He Qingtai 賀清泰, 1735–1814), who worked for Emperor Qianlong, composed Guxin shengjing 古新聖經 (Old and New Testament), a translation of the Bible in both vernacular Chinese and Manchu, in the second half of the eighteenth century. Specifically, it focuses on how de Poirot used rhetoric in shaping the language the Jesuits adopted for translating the Bible, as well as for addressing readers in Qing China. This article is part of the special issue of the Journal of Jesuit Studies, “Jesuits in Modern Far East,” guest edited by Steven Pieragastini.
Gaoli Zhiming Shilüe: An Intercultural, Interlaced Text between the Jesuits in Shanghai and the Missions Etrangères de Paris in Seoul
Authors: Soh Jeanhyoung 
Published: August 2023

Abstract
In 1900, as the Boxer Uprising raged in China, two Chinese translations of the work Histoire de l’Eglise de Corée (Gaoli zhiming shilüe and Gaoli zhuzheng) were published to encourage Chinese Catholics, given the difficult history of persecutions faced by Korean Catholics. A close examination of these translations, along with the translator of Gaoli zhiming shilüe’s earlier work on the history of Korean martyrs, reveals that they relied on different Korean source texts and even embellished the original narrative in places. These modifications, in turn, demonstrate the complex chain of translation and information within East Asian missions, working between several languages and incorporating a variety of sources for information. In particular, a study of these texts highlights connections between the Catholic mission in Shanghai and Korea throughout a period when both faced intense opposition and the latter outright suppression. This article is part of the special issue of the Journal of Jesuit Studies, “Jesuits in Modern Far East,” guest edited by Steven Pieragastini.