bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extrachromosomal DNA Amplification Contributes to Small Cell Lung Cancer Heterogeneity and Is Associated with Worse Outcomes
Authors: Pongor Lőrinc Sándor , Schultz Christopher W. , Rinaldi Lorenzo , Wangsa Darawalee , Redon Christophe E. , Takahashi Nobuyuki , Fialkoff Gavriel , Desai Parth , Zhang Yang , Burkett Sandra , Hermoni Nadav , Vilk Noa , Gutin Jenia , Gergely Rona , Zhao Yongmei , Nichols Samantha , Vilimas Rasa , Sciuto Linda , Graham Chante , Caravaca Juan Manuel , Turan Sevilay , Tsai-wei Shen , Rajapakse Vinodh N. , Kumar Rajesh , Upadhyay Deep , Kumar Suresh , Kim Yoo Sun , Roper Nitin , Tran Bao , Hewitt Stephen M. , Kleiner David E. , Aladjem Mirit I. , Friedman Nir , Hager Gordon L. , Pommier Yves , Ried Thomas , Thomas Anish 
Published: January 2023

AbstractSmall-cell lung cancer (SCLC) is an aggressive neuroendocrine lung cancer. Oncogenic MYC amplifications drive SCLC heterogeneity, but the genetic mechanisms of MYC amplification and phenotypic plasticity, characterized by neuroendocrine and nonneuroendocrine cell states, are not known. Here, we integrate whole-genome sequencing, long-range optical mapping, single-cell DNA sequencing, and fluorescence in situ hybridization to find extrachromosomal DNA (ecDNA) as a primary source of SCLC oncogene amplifications and driver fusions. ecDNAs bring to proximity enhancer elements and oncogenes, creating SCLC transcription-amplifying units, driving exceptionally high MYC gene dosage. We demonstrate that cell-free nucleosome profiling can noninvasively detect ecDNA amplifications in plasma, facilitating its genome-wide interrogation in SCLC and other cancers. Altogether, our work provides the first comprehensive map of SCLC ecDNA and describes a new mechanism that governs MYC-driven SCLC heterogeneity. ecDNA-enabled transcriptional flexibility may explain the significantly worse survival outcomes of SCLC harboring complex ecDNA amplifications.Significance:MYC drives SCLC progression, but the genetic basis of MYC-driven SCLC evolution is unknown. Using SCLC as a paradigm, we report how ecDNA amplifications function as MYC-amplifying units, fostering tumor plasticity and a high degree of tumor heterogeneity.This article is highlighted in the In This Issue feature, p. 799
Imaging Factors Associated With Poor Outcome in Patients With Basilar Artery Occlusion Treated With Endovascular Thrombectomy
Authors: Heit Jeremy J. , Mlynash Michael , Cereda Carlo W. , Yuen Nicole , Lansberg Maarten G. , Bianco Giovanni , Christensen Soren , Qureshi Abid Y. , Hinduja Archana , Dehkharghani Seena , Goldman‐Yassen Adam E. , Hsieh Kevin Li‐Chun , Giurgiutiu Dan‐Victor , Gibson Dan , Carrera Emmanuel , Alemseged Fana , Faizy Tobias D. , Fiehler Jens , Pileggi Marco , Campbell Bruce , Albers Gregory W. 
Published: January 2023

Background
Acute ischemic stroke attributed to basilar artery occlusion (BAO) results in high rates of death and significant morbidity. Endovascular thrombectomy an effective treatment for BAO, but imaging parameters that predict a favorable response to thrombectomy are not well defined. We determined which imaging parameters were associated with poor outcome in patients with BAO treated by thrombectomy.

Methods
We performed a retrospective cohort study of patients with BAO who underwent thrombectomy at multiple international stroke centers. All patients underwent computed tomography or magnetic resonance perfusion imaging before treatment. Clinical and imaging variables were measured and correlated to poor functional outcomes (modified Rankin scale score ≥4) after thrombectomy. Imaging variables included the following: Critical Area Perfusion Score, Posterior Circulation Alberta Stroke Program Early Computed Tomography Score, ischemic core volume (30% cerebral blood flow on computed tomography perfusion or diffusion‐weighted imaging), and volume of time to maximum >10 seconds. Clinical and imaging variables associated with poor functional outcome were assessed by a multivariable binary logistic regression analysis.

Results

A total of 102 patients were included in the study. Median patient age was 66.5 years (interquartile range [IQR], 55–78), median presentation National Institutes of Health Stroke Scale score was 14 (IQR, 7–23), and the median time from last seen normal was 4 hours (IQR, 1:52–9:20). Patient age (odds ratio [OR], 1.37 per 5‐year increment [95% CI, 1.08–1.72]; P=0.008), presentation National Institutes of Health Stroke Scale score (OR, 1.11 [95% CI, 1.04–1.18]; P=0.001), successful reperfusion after thrombectomy (OR, 0.03 [95% CI, 0.003–0.25]; P=0.002), Posterior Circulation Alberta Stroke Program Early Computed Tomography Score ≤6 (OR, 11.40 [95% CI, 1.73–75]; P=0.011), and Critical Area Perfusion Score >3 (OR, 26.22 [95% CI, 1.07–642];
P
=0.045) independently predicted poor outcome after BAO thrombectomy. Ischemic core volume (30% cerebral blood flow) and volume of time to maximum >10 seconds did not predict poor outcome.

Conclusion
Age, National Institutes of Health Stroke Scale presentation, unsuccessful reperfusion, Critical Area Perfusion Score >3, and Posterior Circulation Alberta Stroke Program Early Computed Tomography Score ≤6 are independently associated with poor outcome after BAO thrombectomy.
Concomitant Mitral Valve Repair vs Replacement During Surgical Ventricular Restoration for Ischemic Cardiomyopathy
Authors: Arafat Amr A. , Alghamdi Rawan , Alfonso Juan J. , Shalaby Mostafa A. , Alotaibi Khaled , Pragliola Claudio 
Published: January 2023

There is no consensus regarding mitral valve management during surgical ventricular restoration (SVR) for ischemic cardiomyopathy. We compared the impact of SVR with mitral valve repair (MVr) vs replacement (MVR) on postoperative outcomes and long-term survival in ischemic cardiomyopathy and mitral regurgitation patients. This study included 112 patients who underwent SVR from 2009 to 2018 with MVr (n = 75) or MVR (n = 37). Patients who had MVR had higher Euro SCORE II, dyspnea class, a lower ejection fraction, higher pulmonary artery systolic pressure, higher grade of preoperative mitral and tricuspid regurgitation, and higher end-diastolic and end-systolic diameters. Intra-aortic balloon pump was more commonly used in patients with MVR. Hospital mortality occurred in 7 (9.33%) patients in the MVr group vs 3 (8.11%) in the MVR group (P > .99). Freedom from rehospitalization at 1, 5, and 7 years was 87%, 76%, and 70% in the MVr group and 83%, 61%, and 52% in the MVR group (P = .191). Survival at 1, 5, and 7 years was 88%, 78%, and 74% in the MVr group and 88%, 56%, and 56% in the MVR group (P = .027). Adjusted survival did not differ between groups. MVr or MVR are valid options in patients undergoing SVR, with good long-term outcomes.
Survival of patients with severe mental disorders: Influence of social functioning
Authors: Vázquez-Reyes Antonio , Martín-Rodríguez Agustín , Pérez-San-Gregorio María Ángeles , Vázquez-Morejón Antonio J. 
Published: January 2023

Background: Patients with severe mental disorders have a high risk of premature death due to the interaction of various factors. Social functioning is a strategic functional factor in understanding the course of psychotic disorders. Aim: Analyze the relationship between social functioning and its various dimensions and survival during a 10-year follow-up. Method: The Social Functioning Scale (SFS) was administered to 163 close relatives of patients under treatment at a Community Mental Health Unit. Survival was described by Kaplan–Meier analysis and any differences in survival by level of social functioning were found by long-rank analysis. Finally, Cox regression was used to predict premature mortality. Results: Significant differences in mortality were identified in the interpersonal behavior dimension of social functioning, while there were no significant gender or diagnostic differences in the rest of the dimensions. The interpersonal behavior dimension and age were found to be factors predicting premature death. Conclusion: These findings show the protective effect of social functioning retained by patients with psychotic disorders on their survival, and the need to apply evidence-based psychotherapy focused on recovery of social functioning in the early stages of the disorder.
Affiliate stigma and caregiving burden among family caregivers of persons with schizophrenia in rural China
Authors: Wang Yi-Zhou , Meng Xian-Dong , Zhang Tian-Ming , Weng Xue , Li Ming , Luo Wei , Huang Yi , Thornicroft Graham , Ran Mao-Sheng 
Published: January 2023

Background: Although stigma and caregiving burden are important in relation to mental health recovery, few studies have been conducted on affiliate stigma and caregiving burden among family caregivers of persons with schizophrenia (FCPWS) in rural China. Aims: This study aimed to examine the severity level of affiliate stigma and caregiving burden, and identify the correlates among FCPWS in rural China. Methods: A mental health survey was conducted ( N = 253 FCPWS) in Xinjin county, Sichuan province, China. Affiliate Self-Stigma Scale and Zarit Burden Interview Short Form were used. The regression analysis was performed to explore the correlates of stigma and burden. Results: Most FCPWS reported experiencing high and severe level of affiliate stigma (78.66%) and caregiving burden (95.26%). Family caregivers who were middle aged, unemployed, with high caregiving burden and low quality of life (QoL), showed more severe affiliate stigma. Family caregivers who were female, older, with low income, high affiliate stigma and low QoL, experienced greater caregiving burden. Conclusions: The large majority of FCPWS in rural China experienced severe affiliate stigma, caregiving burden and poor QoL. It is crucial to develop culture-specific anti-stigma interventions to reduce caregivers’ stigma and caregiving burden, and improve QoL. Specific risk factors of family caregivers’ affiliate stigma and caregiving burden should be considered for development of health policy and community-based mental health services.
A Review of Intervention Strategies for Areca Nut Use Cessation
Authors: Dhingra Kriti , Jhanjee Sonali 
Published: January 2023

Background: Areca nut (AN) is one of the world’s most widely used drugs, especially in Asia-Pacific, causing dependence and multiple adverse health impacts. The International Agency for Research on Cancer (IARC) has classified it as a type-1 carcinogen. Despite evidence of harms, its use is culturally ingrained in many regions worldwide; harm perception is low; and the availability of intervention strategies is limited. Methods: To identify the range and efficacy of interventional studies on AN use cessation, a narrative review of studies published between 1990 and 2021 was undertaken using selected electronic databases (PubMed, Embase, and Scopus). Results: Three types of interventions were identified: educational, psychological, and pharmacological. Overall, educational interventions significantly enhanced knowledge regarding harms related to AN use. Some psychological interventions reported enhancement of motivation to quit as well as helped in reduction/cessation of AN use. Two pharmacological studies on psychiatric patients with depressive disorders and AN use found that antidepressants helped in reducing/cessation of AN use. Conclusion: Overall, the number of interventional studies on AN cessation is limited, and most studies have measured the short-term effects of the intervention. The role of pharmacotherapeutic interventions needs to be evaluated for AN cessation, and evidence-based psychosocial interventions need to be developed for AN cessation. Furthermore, longitudinal research using adequate sample sizes and longer follow-up durations are needed to establish interventions in this important area.
Moral distress and patients who forego care due to cost
Authors: Keilman Linda , Jolaei Soudabeh , Olsen Douglas P 
Published: January 2023

Background In the US, many patients forgo recommended care due to cost. The ANA Code of Ethics requires nurses to give care based on need. Therefore, US nurses are compelled to practice in a context which breaches their professional ethical code. Research Objectives This study sought to determine if nurses do care for patients who forgo treatment due to cost (PFTDC) and if so, does this result in an experience of moral distress (MD). Research Design Semi-structured interviews were transcribed and analyzed using a qualitative content analysis. Participants and Research Context A convenience sample of 20 nurses in practice for at least one year from a variety of health care setting participated. Ethical Considerations This project was approved by the Michigan State University Biomedical Institutional Review Board. Results There were 19 female and one male nurse-participants, averaging 47 years old with an average of 10 years in practice. 18 reported caring for PFTDC. These 17 nurse-participants experienced a moderate degree of MD as a result, averaging 5.4 of 10 on the Moral Distress Thermometer. In the interviews, the following themes were identified, strategies to help PFTDC, and the broken US health care system which had the subthemes of preference for business over patient-oriented benefit, PFTDC using the emergency department, and limited support for treatment/management of PFTDC. Conclusions The existence of this phenomenon places the profession of nursing in the US in a position of moral compromise and threatens to corrupt the institution of nursing in the US.
Addiction experts: The discrepancy between expectations and reality of generalist psychiatry training
Authors: Lundin Robert M , Hill Harry , Rao Ranjini , Maud Catherine 
Published: January 2023

Objective The generalist psychiatrist is recognised in Australia as a specialist in the management of addiction. However, generalist training does not adequately prepare psychiatrists to take on this expert role. This problem is exacerbated by the lack of consensus around core competencies and training pathways. This article conceptualises the status of addiction training in generalist psychiatry training, outlines current gaps and worrying trends and provides suggestions for how these can be addressed. Conclusion Limited international leadership in the field provides an opportunity for psychiatry training in Australia and New Zealand to set a gold standard for training general psychiatrists to hold core competencies in addiction psychiatry. Key strategies will include: the identification and monitoring of addiction rotations; providing a formal training module in addiction; specifying a set proportion of addiction exam questions; and obtain consensus on core competencies.
A Pilot Study of the Serious Illness Conversation Guide in a Dialysis Clinic
Authors: Mandel Ernest I. , Maloney Francine L. , Pertsch Nathan J. , Gass Jonathon D. , Sanders Justin J. , Bernacki Rachelle E. , Block Susan D. 
Published: January 2023

Clinician-led conversations about future care priorities occur infrequently with end-stage renal disease (ESRD) patients on dialysis. This was a pilot study of structured serious illness conversations using the Serious Illness Conversation Guide (SICG) in a single dialysis clinic to assess acceptability of the approach and explore conversation themes and potential outcomes among patients with ESRD. Twelve individuals with ESRD on dialysis from a single outpatient dialysis clinic participated in this study. Participants completed a baseline demographics survey, engaged in a clinician-led structured serious illness conversation, and completed an acceptability questionnaire. Conversations were recorded, transcribed and thematically analyzed. The average age of participants was 68.8 years. The conversations averaged 20:53 in length. Ten participants (83%) felt that the conversation was held at the right time in their clinical course and eleven participants (91%) felt that it was worthwhile. Most participants (73%) reported neutral feelings about clinician use of a printed guide. Eleven participants (91%) reported no change in anxiety about their illness following the conversation, and five participants (42%) reported that the conversation increased their hopefulness about future quality of life. Thematic analysis revealed common perspectives on dialysis including that participants view in-center hemodialysis as temporary, compartmentalize their kidney disease, perceive narrowed life experiences and opportunities, and believe dialysis is their only option. This pilot study suggests that clinician-led structured serious illness conversations may be acceptable to patients with ESRD on dialysis. The themes identified can inform future serious illness conversations with dialysis patients.
Implanted blood vessel external support device for the treatment of distal hypoperfusion ischemic syndrome in arteriovenous fistulas and high-frame-rate Vector Flow quality assessment
Authors: Franchin Marco , Goddi Alfredo , Muscato Paola , Cervarolo Maria Cristina , Piffaretti Gabriele , Tozzi Matteo 
Published: January 2023

Introduction: Distal hypoperfusion ischemic syndrome (DHIS) is a complication occurring after arteriovenous fistula (AVF) creation. Different surgical alternatives haves been proposed in case of severe DHIS. Aim of the present paper is to present a new technique for DHIS treatment. Material and methods: Between the 1st of January 2021 and the 31st December 2021 all the patients referred to our center for DHIS grade 2–4 were treated with a new surgical technique. It consists of AVF remodeling using an external nitinol support (VasQ®) to reduce the risk of outflow vein enlargement and DHIS recurrence. To better appreciate the hemodynamic effects of the surgery, a new ultrasound technique called high-frame-rate Vector Flow (HiFR-VF) was used. Results: Seven patients (M:F 1:3; mean age 43 ± 12 years, range 29–65) were included in this study. Central line was never necessary, and technical success was 100% at 12 months. The comparison with historical data demonstrated lower recurrence of symptoms in comparison to simple artery-to-vein redo (p 0.50). The HiFR-VF showed flow with limited turbulent characteristics at the anastomosis site. Discussion and conclusion: The new technique proposed demonstrated to be safe and effective for treatment of DHIS, preventing symptoms recurrence. Ultrasound examination and HiFR-VF can be considered a valuable method to evaluate complex flows at the levels of vascular anastomosis.
Autism spectrum disorder and personality disorders: How do clinicians carry out a differential diagnosis?
Authors: Allely Clare S , Woodhouse Emma , Mukherjee Raja AS 
Published: January 2023

Although it is recognised that autism spectrum disorder (ASD) and personality disorders (PDs) have a variety of factors in common, the exact nature of the relationship between ASD and the PDs remains unclear. The overlapping symptom profiles and complexities in developmental trajectories in ASD and PDs can lead to diagnostic uncertainty and to challenges in determining differential diagnoses. Features of ASD and PD can be misattributed and easily lead to misdiagnosis or missed diagnoses in patients who have a diagnosis of ASD, which may impact therapeutic pathways. Since differentiating between ASD and PD is such a complex task with implications for therapeutic approaches, it has been argued that there is a need for additional understanding and markers for facilitating diagnostic procedures. There is an urgent need to explore how clinicians make diagnostic decisions and the challenges they face in forming diagnostic conclusions. Where overlaps exist, it is important to consider how clinicians interpret and attribute certain characteristics within the context of ASD and/or PD diagnoses. Lay Abstract It is now recognised that autism spectrum disorder (ASD) and personality disorders (PDs) have a variety of factors in common. However, the exact nature of the relationship between ASD and the PDs remains unclear. The overlapping symptom profiles of ASD and PDs can lead to diagnostic uncertainty – features of ASD and PD can be misattributed and easily lead to misdiagnosis of ASD patients. Since differentiating between ASD and PD is such a complex task, it has been argued that there is a need for additional understanding and markers for facilitating diagnostic procedures. There is an urgent need to explore, first, how clinicians make diagnostic decisions and, second, how to effectively deal with the challenges and difficulties they face when making decisions. Also, where there are clear overlaps, how do clinicians choose how to attribute labels in order to understand the person.
Temporal trends in minor and major lower extremity amputation in people with type 2 diabetes: The Fremantle Diabetes Study
Authors: Hamilton Emma J , Davis Wendy A , Baba Mendel , Davis Timothy ME 
Published: January 2023

Aims To determine whether incident minor and major lower extremity amputations (LEAs) have declined in recent decades in type 2 diabetes. Methods Participants with type 2 diabetes from the community-based Fremantle Diabetes Study Phases I (FDS1; n = 1,296, mean age 64.0 years, recruited 1993–1996) and II (FDS2; n = 1,509, mean age 65.4 years, recruited 2008–2011) were followed from entry to incident minor/major LEA, death or five years. Cox regression determined hazard ratios (HRs) for each outcome for FDS2 versus FDS1 and independent predictors of incident minor and major LEA in the combined cohort. Results Age- and sex-adjusted HRs (95% CIs) in FDS2 versus FDS1 for incident minor and major LEA were, respectively, 0.60 (0.27, 1.35) and 0.59 (0.22, 1.59). Higher glycated haemoglobin, urine albumin: creatinine (uACR) ratio and peripheral sensory neuropathy (PSN) were independent predictors of incident minor LEA. Higher fasting serum glucose, peripheral arterial disease (PAD), end-stage kidney disease and prior diabetes-related minor LEA were associated with incident major LEA. Conclusions There were non-significant reductions of approximately 40% in incident minor and major LEA in community-based people with type 2 diabetes during the 15 years between FDS Phases. Predictors of minor/major LEA confirm distinct high-risk patient groups with implications for clinical management.
Hydromethanolic Root Extract of Gnidia Kraussiana Demonstrates Anti-Inflammatory Effect Through Anti-Oxidant Activity Enhancement in a Rodent Model of Gout
Authors: Dadaya Elizé , Koubala Benoit , Ndjonka Dieudonné , Zingué Stéphane , Laya Alphonse , Atsang Gisèle 
Published: January 2023

Gout is a metabolic arthritis that originates from increased accumulation of monosodium urate (MSU) crystals in joints. This work aimed to evaluate the antioxidant and anti-inflammatory activities of the hydromethanolic extract of Gnidia kraussiana (HEGK) using model of Gouty arthritis on mice. The total polyphenol, flavonoid, tannin content and the antioxidant activity of HEGK were also evaluated. MSU-injected mice were treated daily for 3 days with HEGK (25, 50 and 100 mg/kg). Indomethacin and colchicin were used as reference drugs. Paw oedema and body temperature were measured at different time intervals post-injection. Malondialdehyde, acid phosphatase, β-Galactosidase, catalase, superoxide dismutase and glutathione levels were evaluated. HEGK is rich in polyphenol (129.93 mg/100 g), flavonoid (67.78 mg/100 g) and tannin conferring it a high antioxidant activity. Acute oral toxicity of HEGK resulted in LD50 greater than 2000 mg/kg. Oral administration of HEGK induced a significant decrease in the oedema of legs injected with urate crystals and reduced the release of acid phosphatase and β-Galactosidase. A model of oxidative damage was successfully established, revealing a significant increase in malondialdehyde and inhibition of antioxidants, including superoxide dismutase, catalase and glutathione activity. Thus, HEGK can actively inhibit the effect of inflammatory mediators in gouty arthritis.