bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-Sensitivity Mutation Analysis of Cell-Free DNA for Disease Monitoring in Endometrial Cancer
Authors: Ashley Charles W. , Selenica Pier , Patel Juber , Wu Michelle , Nincevic Josip , Lakhman Yulia , Zhou Qin , Shah Ronak H. , Berger Michael F. , Da Cruz Paula Arnaud , Brown David N. , Marra Antonio , Iasonos Alexia , Momeni-Boroujeni Amir , Alektiar Kaled M. , Long Roche Kara , Zivanovic Oliver , Mueller Jennifer J. , Zamarin Dmitriy , Broach Vance A. , Sonoda Yukio , Leitao Mario M. , Friedman Claire F. , Jewell Elizabeth , Reis-Filho Jorge S. , Ellenson Lora H. , Aghajanian Carol , Abu-Rustum Nadeem R. , Cadoo Karen , Weigelt Britta 
Published: August 2022

Abstract

Purpose:
We sought to determine whether sequencing analysis of circulating cell-free DNA (cfDNA) in patients with prospectively accrued endometrial cancer captures the mutational repertoire of the primary lesion and allows for disease monitoring.

Experimental Design:
Peripheral blood was prospectively collected from 44 newly diagnosed patients with endometrial cancer over a 24-month period (i.e., baseline, postsurgery, every 6 months after). DNA from the primary endometrial cancers was subjected to targeted next-generation sequencing (NGS) of 468 cancer-related genes, and cfDNA to a high-depth NGS assay of 129 genes with molecular barcoding. Sequencing data were analyzed using validated bioinformatics methods.

Results:
cfDNA levels correlated with surgical stage in endometrial cancers, with higher levels of cfDNA being present in advanced-stage disease. Mutations in cfDNA at baseline were detected preoperatively in 8 of 36 (22%) patients with sequencing data, all of whom were diagnosed with advanced-stage disease, high tumor volume, and/or aggressive histologic type. Of the 38 somatic mutations identified in the primary tumors also present in the cfDNA assay, 35 (92%) and 38 (100%) were detected at baseline and follow-up, respectively. In 6 patients with recurrent disease, changes in circulating tumor DNA (ctDNA) fraction/variant allele fractions in cfDNA during follow-up closely mirrored disease progression and therapy response, with a lead time over clinically detected recurrence in two cases. The presence of ctDNA at baseline (P &lt; 0.001) or postsurgery (P = 0.014) was significantly associated with reduced progression-free survival.

Conclusions:
cfDNA sequencing analysis in patients with endometrial cancer at diagnosis has prognostic value, and serial postsurgery cfDNA analysis enables disease and treatment response monitoring.
See related commentary by Grant et al., p. 305
Enhanced Costimulatory Signaling Improves CAR T-cell Effector Responses in CLL
Authors: Collins McKensie A. , Jung In-Young , Zhao Ziran , Apodaca Kimberly , Kong Weimin , Lundh Stefan , Fraietta Joseph A. , Kater Arnon P. , Sun Clare , Wiestner Adrian , Melenhorst J. Joseph 
Published: August 2022

CD19-redirected chimeric antigen receptor (CAR) T cells have shown remarkable activity against B-cell cancers. While second-generation CARs induce complete remission in &gt;80% of patients with acute lymphoblastic leukemia, similar monotherapy induces long-term remissions in only 26% of patients with chronic lymphocytic leukemia (CLL). This disparity is attributed to cell-intrinsic effector defects in autologous CLL-derived T cells. However, the mechanisms by which leukemic cells impact CAR T-cell potency are poorly understood. Herein we describe an in vitro assay that recapitulates endogenous CLL-mediated T-cell defects in healthy donor CAR T cells. Contact with CLL cells insufficiently activates, but does not irreversibly impair, CAR T-cell function. This state is rescuable by strong antigenic stimulation or IL2, and is not driven by immune suppression. Rather, this activation defect is attributable to low levels of costimulatory molecules on CLL cells, and exogenous costimulation enhanced CAR T-cell activation. We next assessed the stimulatory phenotype of CLL cells derived from different niches within the same patient. Lymph node (LN)-derived CLL cells had a strong costimulatory phenotype and promoted better CAR T-cell degranulation and cytokine production than matched peripheral blood CLL cells. Finally, in vitro CD40L-activated CLL cells acquired a costimulatory phenotype similar to the LN-derived tumor and stimulated improved CAR T-cell proliferation, cytokine production, and cytotoxicity. Together, these data identify insufficient activation as a driver of poor CAR T-cell responses in CLL. The costimulatory phenotype of CLL cells drives differential CAR T-cell responses, and can be augmented by improving costimulatory signaling.Significance:CLL cells insufficiently activate CAR T cells, driven by low levels of costimulatory molecules on the tumor. LN-derived CLL cells are more costimulatory and mediate enhanced CAR T-cell killing. This costimulatory phenotype can be modeled via CD40 L activation, and the activated tumor promotes stronger CAR T-cell responses.
Inhibition of the Renin-Angiotensin System Fails to Suppress β-Aminopropionitrile–Induced Thoracic Aortopathy in Mice—Brief Report
Authors: Sawada Hisashi , Ohno-Urabe Satoko , Ye Dien , Franklin Michael K. , Moorleghen Jessica J. , Howatt Deborah A. , Mullick Adam E. , Daugherty Alan , Lu Hong S. 
Published: August 2022

Background:
Cross-linking of lysine residues in elastic and collagen fibers is a vital process in aortic development. Inhibition of lysyl oxidase by BAPN (β-aminopropionitrile) leads to thoracic aortopathies in mice. Although the renin-angiotensin system contributes to several types of thoracic aortopathies, it remains unclear whether inhibition of the renin-angiotensin system protects against aortopathy caused by the impairment of elastic fiber/collagen crosslinking.

Methods:
BAPN (0.5% wt/vol) was started in drinking water to induce aortopathies in male C57BL/6J mice at 4 weeks of age for 4 weeks. Five approaches were used to investigate the impact of the renin-angiotensin system. Bulk RNA sequencing was performed to explore potential molecular mechanisms of BAPN-induced thoracic aortopathies.

Results:
Losartan increased plasma renin concentrations significantly, compared with vehicle-infused mice, indicating effective angiotensin II type 1 receptor inhibition. However, losartan did not suppress BAPN-induced aortic rupture and dilatation. Since losartan is a surmountable inhibitor of the renin-angiotensin system, irbesartan, an insurmountable inhibitor, was also tested. Although increased plasma renin concentrations indicated effective inhibition, irbesartan did not ameliorate aortic rupture and dilatation in BAPN-administered mice. Thus, BAPN-induced thoracic aortopathies were refractory to angiotensin II type 1 receptor blockade. Next, we inhibited angiotensin II production by pharmacological or genetic depletion of AGT (angiotensinogen), the unique precursor of angiotensin II. However, neither suppressed BAPN-induced thoracic aortic rupture and dilatation. Aortic RNA sequencing revealed molecular changes during BAPN administration that were distinct from other types of aortopathies in which angiotensin II type 1 receptor inhibition protects against aneurysm formation.

Conclusions:
Inhibition of either angiotensin II action or production of the renin-angiotensin system does not attenuate BAPN-induced thoracic aortopathies in mice.
From a Uniform to a Multiform Understanding of Church. Foundations of Exchange in the Preconciliar Missiology of Jean Bruls
Authors: Ooms Toon 
Published: August 2022

Abstract
During the first half of the 20th century, genuine exchange between the churches within Roman Catholicism was virtually non-existent. Church was conceived of as the one Roman Catholic Church, and the relationship between churches was one of a Western unilateralism. Shortly after the Second World War, the Belgian Catholic missiologist Jean Bruls (1911–1982), editor-in-chief of the missiological journal Église Vivante, pointed to the necessity of an exchange (“échange”) between the Western church and the non-Western churches. This article argues that Bruls’ early attention to interchurch exchange was the result of a new conceptualization of Church. The article shows to what extent Bruls’ missiology was an anticipation of the mission doctrine of the Second Vatican Council (1962–1965).
Description of a new pseudoscorpion species, Dactylochelifer zaragozai n. sp. (Pseudoscorpiones: Cheliferidae) from North Caucasian region of European Russia
Authors: Nassirkhani Mahrad , Snegovaya Nataly , Chumachenko Yu.A. 
Published: August 2022

Abstract
A new pseudoscorpion species, Dactylochelifer zaragozai
n. sp., belonging to the family Cheliferidae Risso, 1827 is described from Republic Adygeya, Russia (North Caucasus) and its diagnostic characters are illustrated. The specimens were extracted from litter collected from oak-hornbeam hazel forest.
Impact of oral chemotherapy pharmacists on cost avoidance of oral oncolytics in an integrated health system
Authors: Nguyen Analia L 
Published: August 2022

Background While the impact of oncology pharmacist interventions on patient outcomes has been well-documented in previous studies, there is a scarcity of articles relating to oncology pharmacists’ impact on cost avoidance of oral oncolytics within an integrated health care system. Cost savings and cost avoidance studies are needed to help promote the expansion of clinical services provided by the oncology pharmacy department. Objective The primary objective of this study was to analyze interventions made by oncology pharmacists in the Oral Chemotherapy Treatment Program (OCTP) at the Kaiser Permanente—San Diego Service Area and determine the direct cost avoidance effects over one year. A secondary objective was to evaluate oncologists’ satisfaction with OCTP. Methods This was a retrospective, observational, single-arm study where the drug cost avoidance impact resulting from oncology pharmacists’ interventions was calculated. A report containing all documented oncology pharmacist interventions made in OCTP from 1 January to 31 December 2021 were reviewed for study inclusion. A retrospective chart review was conducted to verify that the interventions were made by the oncology pharmacists. The average wholesale price of drugs listed on Lexicomp as of 1 November 2021 was used to calculate drug cost avoidance values. Results A total of 238 OCTP oncology pharmacist interventions associated with direct drug cost avoidance values were identified, amounting to a total cost avoidance of $2,521,844 and an annual return on investment of 440%.
A Study on Victims of Intimate Partner Violence Reported to Colombo North Teaching Hospital, Sri Lanka During 2019-2021
Authors: Muthulingam Thanushan , Edirisinghe Patikirige Anuruddhi Samanthika , Wijewardhane Handun Pathirannehelage , Thivaharan Yalini , Jayasundara Mudiyanselage Maleesha Sawaneeth , Borukgama Nirmal , Kulathunga Deshan Lakshitha , Alwis Dula Nuwanthi , Govinnage Pawanthi Samudini , Kitulwatte Indira Deepthi Gamage 
Published: August 2022

Introduction: Intimate partner violence (IPV) is a common issue in any society and the reported cases are just the tip of an iceberg as most of the victims are reluctant to come to the criminal justice system. Forensic experts are often encountering the victims who chose to seek justice. Evaluation of the nature, consequences, and underlying factors are needed in planning preventive measures. Objectives: To describe the patterns and associated factors of IPV among victims who reported to Office of the Judicial Medical Officer of Colombo North Teaching Hospital and to specifically describe the patterns prior and during the COVID-19 pandemic. Methods: A retrospective descriptive study based on 471 medicolegal records of the victims who had undergone medicolegal examination following IPV during last two years (March 2019 to February 2021). Results: Out of 471, 206 cases were reported prepandemic and 265 reported postpandemic periods. Even though majority were females there were 21 males. Types of abuse were complex and often interrelated. There were 463 who had experienced physical injuries while there were 20 who had been subjected to sexual violence. Face was the commonest target of assault (63%). Substance abuse was identified as the commonest predisposing factor (56%). Even though repeated abuse was common, 42.5% of the victims had never made any complaints to the police. Despite multiple complains, 39.7% had experienced repeated violence. Conclusion: Victims of IPV are silently suffering for many long years. Failure in the response from authorities was identified. COVID-19 pandemic has become an additional risk factor for IPV. Strengthening of legal and social responses is the need of the hour.
Carotid pseudoaneurysm in a kitten after accidental puncture with a needle
Authors: Sterman Allyson , Dickerson Vanna , Voges Andra , Milliron Sarai , Wiener Dominique , Thieman Mankin Kelley M 
Published: August 2022

Case summary A 3-month-old intact male domestic shorthair kitten’s cervical region was inadvertently punctured during routine subcutaneous fluid administration. A swelling rapidly developed on the left lateral neck and continued to grow, despite compression. An emergency facility evaluated the kitten 48 h later and the swelling was determined to be blood. Fine-needle aspiration of the swelling resulted in further swelling of the mass on the neck. The kitten began showing signs of systemic shock, necessitating a blood transfusion. The kitten was referred to a tertiary facility 24 h later for further diagnostics and treatment. CT of the head and neck revealed a large fluid-filled mass with progressive contrast enhancement noted during the filling phase, consistent with active hemorrhage. A carotid pseudoaneurysm was suspected and surgery was recommended. The left carotid artery was ligated proximal to the pseudoaneurysm; hemorrhage continued and the swelling was further explored. A small connection to the carotid artery within the medial aspect of the swelling was identified and ligated. The kitten required autotransfusion and massive allotransfusion during surgery due to blood loss. Recovery was uneventful. A head tilt and Horner’s syndrome were noted postoperatively and improved over the following months. Histopathology was consistent with pseudoaneurysm. Relevance and novel information This is the first reported case of pseudoaneurysm in a kitten that was treated surgically, with massive blood transfusion and minimal complications. Early surgical intervention can result in excellent prognosis. The need for blood product administration should be anticipated.
Effect of Intraoperative Tranexamic Acid on Perioperative Major Hemorrhage Requiring Transfusion in Patients Undergoing Elective Spine Surgery: A Propensity Score-Matched Analysis Using a National Inpatient Database
Authors: Honda Akira , Iizuka Yoichi , Michihata Nobuaki , Uda Kazuaki , Mieda Tokue , Takasawa Eiji , Ishiwata Sho , Kakuta Yohei , Tomomatsu Yusuke , Ito Shunsuke , Inomata Kazuhiro , Matsui Hiroki , Fushimi Kiyohide , Yasunaga Hideo , Chikuda Hirotaka 
Published: August 2022

Study Design Retrospective cohort study. Objectives This study aimed to examine whether the use of intravenous TXA in elective spine surgery is associated with reduced perioperative massive hemorrhage requiring transfusion. Methods We extracted all patients who underwent decompression with or without fusion surgery for the cervical, thoracic, and lumbar spine between April 2012 and March 2019. The primary outcome was the occurrence of massive hemorrhage requiring transfusion, defined as at least 560 mL of blood transfusion within 2 days of spine surgery or the requirement of additional blood transfusion from 3-7 days postoperatively. Secondary outcomes were the occurrence of thrombotic complications (pulmonary embolism, acute coronary syndrome, and stroke) and postoperative hematoma requiring additional surgery. Results We identified 83,821 eligible patients, with 9747 (12%) patients in the TXA group. Overall, massive hemorrhage requiring transfusion occurred in 781 (.9%) patients. Propensity score matching yielded 8394 pairs. In the matched cohort, the TXA group had a lower proportion of massive hemorrhage requiring transfusion than the control group (.7% vs 1.1%; P = .002). There was no significant difference in the occurrence of thrombotic complications and postoperative hematoma requiring additional surgery between both groups. The multivariable regression analysis also showed that the use of TXA was associated with significantly lower proportions of massive hemorrhage requiring transfusion (odds ratio, .62; 95% confidence interval, .43-.90; P = .012). Conclusions In this analysis using real-world data, TXA use in elective spinal surgery was associated with reduced perioperative massive hemorrhage requiring transfusion without increasing thrombotic complications. Level of evidence Prognostic Level Ⅲ
Impact of integrating out-of-hours services into Emergency Medical Services Copenhagen: a descriptive study of transformational years
Authors: Zinger Nienke D. , Blomberg Stig Nikolaj , Lippert Freddy , Krafft Thomas , Christensen Helle Collatz 
Published: August 2022

Abstract
Background
Many emergency medical services and out-of-hours systems are facing an increasing demand for primary, ambulance, and secondary care services caused by population aging and a higher prevalence of long-term and complex conditions. In order to ensure safety and efficiency for future demands, many systems are changing their dispersed healthcare services towards a more integrated care system. Therefore, an evaluation of the production and performance over time of such a unified system is desirable.

Methods
This retrospective quantitative study was performed with dispatch and financial accounting data of Copenhagen Emergency Medical Services for the period 2010–2019. Copenhagen Emergency Medical Services operates both an emergency number and a medical helpline for out-of-hours services. The number of calls to the emergency number, the centralized out-of-hours medical helpline, the number of dispatches, and the annual expenditure of the system are described for both the periods before and after the major reforms. Production of the emergency number and the centralized medical helpline were analyzed separately.

Results
The average number of dispatches increased from 328 per 10,000 inhabitants in 2010 to 361 per 10,000 inhabitants in 2019. The newly initiated medical helpline received 533 calls per 10,000 inhabitants in its first year and 5 years later 548 calls per 10,000 inhabitants. A cost increase of 10% was observed in the first year after the reforms, but it decreased again to 8% in the following year.

Conclusions
There is a population demand for a centralized telephone access point for (semi-)emergency medical services. A more integrated EMS system is promising for a sustainable healthcare provision for a growing population with complex healthcare demands and multi-morbidities.
Efficacy of pramipexole on quality of life in patients with Parkinson’s disease: a systematic review and meta-analysis
Authors: Li Tao , Zou Shuang , Zhang Zijuan , Liu Meiruo , Liang Zhanhua 
Published: August 2022

AbstractBackgroundQuality of life (QoL) in patients with Parkinson’s disease (PD) is increasingly used as an efficacy outcome in clinical studies of PD to evaluate the impact of treatment from the patient’s perspective. Studies demonstrating the treatment effect of pramipexole on QoL remain inconclusive. This study aims to evaluate the effect of pramipexole on QoL in patients with PD by conducting a systematic review and meta-analysis of existing clinical trials.MethodsA systematic literature search of PubMed, Embase and the Cochrane Library was performed from inception to 30 April 2022 to identify randomised, placebo-controlled trials of patients with idiopathic PD receiving pramipexole, who reported a change from baseline in their QoL as measured by the 39-item Parkinson’s Disease Questionnaire (PDQ-39). Risk of bias was independently assessed by two reviewers using the Cochrane Collaboration’s tool for bias assessment.ResultsOf 80 eligible articles screened, six trials consisting of at least 2000 patients with early or advanced PD were included. From the synthesis of all six selected trials, a significant mean change from baseline in the PDQ-39 total score of –2.49 (95% CI, –3.43 to –1.54;p < 0.0001) was observed with pramipexole compared with placebo. A trend toward improvement in QoL was consistently observed among patients who received optimal doses of pramipexole (≥ 80% of the study population on 1.5 mg dosage), regardless of disease severity (advanced versus early) or baseline QoL levels.ConclusionThis meta-analysis provides evidence for the potential treatment benefit of pramipexole in improving QoL in patients with PD.
Characteristics of non-stenotic carotid plaque in embolic stroke of undetermined source compared with cardiogenic embolism: a retrospective cross-sectional observational study
Authors: Zhang Lihao , Guo Yikun , Zhou Wang , Zhu Shumin , Chen Zhuoyou , Dong Guanzhong , Cao Yin 
Published: August 2022

Abstract
Background
Non-stenotic carotid plaque is considered an important etiology of embolic stroke of undetermined source (ESUS). However, only a few previous studies included a negative control group, and the characteristics of non-stenotic carotid plaque in ESUS have yet to be investigated. The objective of this study is to explore the clinical characteristics of ESUS and the correlation between non-stenotic carotid plaque and ESUS.

Methods
This is a single-center, retrospective cross-sectional observational study conducted to compare differences in clinical information among ESUS, CE, and large-artery atherosclerosis (LAA), as well as the prevalence of non-stenotic carotid plaque and non-stenotic carotid plaque with low echo between patients with ESUS and CE in Changzhou No.2 People’s Hospital from January 2020 to January 2022. Ultrasound was used to evaluate the characteristics of non-stenotic carotid plaque and vulnerable carotid plaque was defined as plaque with low echo. The binary logistic regression model was used to analyze the relationship between the characteristics of non-stenotic carotid plaque and ESUS. The receiver-operating characteristic curve was used to evaluate the diagnostic efficiency of the characteristics of non-stenotic carotid plaque for ESUS.

Results
We had a final studying population of 280 patients including 81 with ESUS, 37 with CE, and 162 with LAA. There were no differences in clinical features between ESUS and LAA, but in the comparison of CE and ESUS, there were differences in age, smoking, hypertension, levels of triglyceride, total cholesterol, and low density lipoprotein cholesterol. In ESUS, the prevalence of non-stenotic carotid plaque was more common on the ipsilateral side of stroke than in CE [55 (67.90%) vs. 18 (48.65%), p = 0.046], so was the prevalence of non-stenotic carotid plaque with low echo [38 (46.91%) vs. 5 (13.51%), p < 0.001]. Logistic regression analysis showed that the prevalence of non-stenotic carotid plaque (OR: 4.19; 95% CI: 1.45–12.11; p = 0.008) and the prevalence of non-stenotic carotid plaque with low echo (OR: 5.12; 95% CI: 1.55–16.93; p = 0.007) were, respectively, the independent predictors of ESUS. The results receiver-operating characteristic (ROC) curve showed that the combination of age, hypertension, and ipsilateral non-stenotic carotid plaque with low echo had the best diagnostic efficiency for ESUS (0.811; 95%CI: 0.727–0.896; p < 0.001).

Conclusion
Our results suggest that ipsilateral vulnerable non-stenotic carotid plaque is associated with ESUS in anterior circulation infarction.