bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reasonable access: important characteristics and perceived quality of legal and illegal sources of cannabis for medical purposes in Canada
Authors: Capler N. Rielle , Balneaves Lynda G. , Buxton Jane A. , Kerr Thomas 
Published: June 2023

Abstract
Background
Throughout the past two decades of legal medical cannabis in Canada, individuals have experienced challenges related to accessing legal sources of cannabis for medical purposes. The objective of our study was to examine the sources of cannabis accessed by individuals authorized to use medical cannabis and to identify possible reasons for their use of illegal sources.

Methods
Individuals who participated in the Cannabis Access Regulations Study (CANARY), a national cross-sectional survey launched in 2014, and indicated they were currently authorized to use cannabis for medical purposes in Canada were included in this study. We assessed differences between participants accessing cannabis from only legal sources versus from illegal sources in relation to sociodemographic characteristics, health-related factors, and characteristics of medical cannabis they considered important. A secondary analysis assessed differences in satisfaction with various dimensions of cannabis products and services provided by legal versus illegal sources.

Results
Half of the 237 study participants accessed cannabis from illegal sources. Individuals accessing cannabis from illegal sources were significantly more likely to value pesticide-free products, access to a variety of strains, ability to select strain and dosage, ability to observe and smell cannabis, availability in a dispensary, and availability in small quantities than did individuals accessing cannabis from only legal sources (all p < 0.05). Additionally, participants gave significantly higher satisfaction scores to illegal sources than to legal sources on service-related dimensions of cannabis access (all p < 0.05).

Conclusion
Our findings contribute to an understanding of reasonable access to medical cannabis from a patient perspective and how to assess whether it has been achieved. Characteristics of cannabis products and services valued by patients and appropriate to their needs should be incorporated into legal medical cannabis programs to promote the use of legal medical sources. While pertaining specifically to medical use of cannabis in Canada, the findings of this study may also be instructive for understanding the use of illegal cannabis sources for non-medical purposes in Canada and provide insight for other jurisdictions implementing cannabis regulations for both medical and non-medical purposes.
A comprehensive assessment of VCAN transcriptional expression and evaluation as an effective prognostic biomarker against breast cancer: in silico study
Authors: Shovon Md. Hasan Jafre , Khan Dhrubo Ahmed , Tareq Md. Mohaimenul Islam , Imtiaz Md. , Zilani Md Nazmul Hasan , Hasan Md. Nazmul 
Published: June 2023

Abstract
Background
The VCAN gene provides instructions for making a protein called versican which is a type of protein known as a proteoglycan. Versican is a key ingredient of the extracellular matrix, and due to its widespread expression in the body, versican is involved in cell adhesion, proliferation, and migration. Mutations or alterations of this protein could result in the disintegration of the fine-tuned molecular machinery which can lead to uncontrolled cell proliferation.

Results
VCAN is a novel prognostic marker for multiple cancers, and it showed tremendous results on breast cancer prognosis based on the data available on multiple websites. So, we targeted VCAN to analyze the expression and the outcome of breast cancer. This is a server-based study, and the expression of VCAN shows upregulation in breast cancer subtypes as compared to the normal tissue. The promoter methylation analysis suggested that overexpression of VCAN may be due to hypomethylation. Mutation analysis showed a positive correlation with VCAN expression where missense-type mutation has the highest percentage (77.33%), truncating (17.33%), and splice (4%) and somatic mutation frequency is 1.8%. VCAN was closely related to ten different genes and coexpressed with five of the genes among them. Five distinct compounds are linked to the methylation and mutagenesis of VCAN, according to the gene–drug interaction.

Conclusions
The upregulation of VCAN is closely correlated with promoter methylation and the clinical features of breast cancer patients. The whole study suggests that the breast cancer patient’s survival rate gets lower when the VCAN expression level gets higher. We anticipated that these findings will lead to further improvements in breast cancer prognosis and the significance of VCAN as a biomarker for breast cancer prognosis.
Case report on successful treatment for brain abscess in a Japanese monkey (Macaca fuscata)
Authors: Kimura Tohru 
Published: June 2023

Abstract
Background
A brain abscess in human beings is a focal infection of the central nervous system frequently characterized by areas of localized cerebritis and central necrosis surrounded by a well vascularized capsule. A brain abscess, although sporadically reported, is relatively rare disease in domestic animals (horses, cattle, goats and alpacas), companion animals (dogs and cats) and laboratory nonhuman primates. Brain abscesses are life threatening disease that needs early and aggressive veterinary therapy.

Case presentation
The purpose of this study on a brain abscess in a Japanese monkey was to report the investigational and therapeutic processes including clinical observations, hematological and serum biochemical profiles, and magnetic resonance imaging (MRI) features, probiotic and antibiotic therapy. In clinical observation, the monkey presented with slowly progressive gentle and depressed behavioral change. Hematological findings showed that slightly declined platelet counts gradually increased in the course of the treatment. Serum biochemical profiles revealed initial markedly elevated. A series of chemotherapy provide prominent relief from the influence of the brain abscess. MRI images illustrated that a brain abscess was located in the right frontal lobe and the mass was delineated by a thick rim, indicating the capsule formation stage. The lesion chronologically decreased in size over the course of treatment. Until 11 weeks after treatment of the brain abscess, the size of brain abscess continued to reduce, leaving an organized lesion trace. To the best of my knowledge, this is the first report on successful treatment for a brain abscess in a Japanese monkey (Macaca fuscata).

Conclusions
Medical management of simian brain abscesses is possible based on the controlled and resolving nature of the lesions as determined by MRI and completion of a of chemical antibiotic treatment presented in this study.
De-implementing public health policies: a qualitative study of the process of implementing and then removing body mass index (BMI) report cards in Massachusetts public schools
Authors: Poole Mary Kathryn , Lee Rebekka M. , Kinderknecht Kelsey L. , Kenney Erica L. 
Published: June 2023

Abstract
Background
This study explored reasons for the adoption of a policy to distribute report cards to parents about children’s weight status (“BMI report cards”) in Massachusetts (MA) public schools in 2009 and the contextual factors influencing the policy removal in 2013.

Methods
We conducted semi-structured, qualitative interviews with 15 key decision-makers and practitioners involved with implementing and de-implementing the MA BMI report card policy. We analyzed interview data using a thematic analytic approach guided by the Consolidated Framework for Implementation Research (CFIR) 2.0.

Results
Primary themes were that (1) factors other than scientific evidence mattered more for policy adoption, (2) societal pressure spurred policy adoption, (3) problems with the policy design contributed to inconsistent implementation and dissatisfaction, and (4) media coverage, societal pressure, and organizational politics and pressure largely prompted de-implementation.

Conclusions
Numerous factors contributed to the de-implementation of the policy. An orderly process for the de-implementation of a policy in public health practice that manages drivers of de-implementation may not yet exist. Public health research should further focus on how to de-implement policy interventions when evidence is lacking or there is potential for harm.
Using qualitative comparative analysis to understand the conditions that produce successful PrEP implementation in family planning clinics
Authors: Piper Kaitlin N. , Anderson Katherine M. , Kokubun Caroline W. , Sheth Anandi N. , Sales Jessica 
Published: June 2023

AbstractBackgroundTitle X-funded family planning clinics have been identified as optimal sites for delivery of pre-exposure prophylaxis (PrEP) for HIV prevention to U.S. women. However, PrEP has not been widely integrated into family planning services, especially in the Southern U.S., and data suggest there may be significant implementation challenges in this setting.MethodsTo understand contextual factors that are key to successful PrEP implementation in family planning clinics, we conducted in-depth qualitative interviews with key informants from 38 family planning clinics (11 clinics prescribed PrEP and 27 did not). Interviews were guided by constructs from the Consolidated Framework for Implementation Research (CFIR), and qualitative comparative analysis (QCA) was used to uncover the configurations of CFIR factors that led to PrEP implementation.ResultsWe identified 3 distinct construct configurations, or pathways, that led to successful PrEP implementation: (1) high “Leadership Engagement” AND high “Available Resources”; OR (2) high “Leadership Engagement” AND NOT located in the Southeast region; OR (3) high “Access to Knowledge and Information” AND NOT located in the Southeast region. Additionally, there were 2 solution paths that led to absence of PrEP implementation: (1) low “Access to Knowledge and Information” AND low “Leadership Engagement”; OR (2) low “Available Resources” AND high “External Partnerships”.DiscussionWe identified the most salient combinations of co-occurring organizational barriers or facilitators associated with PrEP implementation across Title X clinics in the Southern U.S. We discuss implementation strategies to promote pathways that led to implementation success, as well as strategies to overcome pathways to implementation failure. Notably, we identified regional differences in the pathways that led to PrEP implementation, with Southeastern clinics facing the most obstacles to implementation, specifically substantial resource constraints. Identifying implementation pathways is an important first step for packaging multiple implementation strategies that could be employed by state-level Title X grantees to help scale up PrEP.
Imaging point diffractors using a low-rank approximation method
Authors: Chen Wei , Oboué Yapo Abolé Serge Innocent , Saad Omar M. , Yang Liuqing , Wang Hang , Chen Yangkang 
Published: June 2023

Diffraction separation plays a critical role in obtaining high-resolution images of subsurface diffractors by eliminating the diffractions’ contribution from reflections. It is usually based on the difference in spatial coherency between seismic reflection and diffraction energy in the time domain. Methods based on local slope differences, e.g., plane-wave destruction (PWD) method, tend to separate point and line diffractors simultaneously. This paper applies a rank-based diffraction separation method, known as the localized rank-reduction (LRR) method, to distinguish point diffractors in poststack data sets from line diffractors, thereby obtaining a higher resolution when characterizing point discontinuities such as karst caves. To make the LRR method more adaptive, a novel rank determination method based on a newly defined accumulated singular value ratio sequence is developed. The effectiveness of the proposed method is proved via a variety of 2D/3D synthetic and real data examples and a detailed discussion of its practical potential. Despite a larger computational cost compared to the PWD method, the proposed method helps interpretation by enabling us to distinguish between line and point diffractors.
Safety analysis of lurbinectedin versus topotecan in elderly patients.
Authors: Subbiah Vivek , Lorusso Domenica , Trigo Perez Jose Manuel Manuel , Leary Alexandra , Moreno Victor , Kristeleit Rebecca , Vergote Ignace , Lopez-Vilariño Jose Antonio , Fernandez Cristian Marcelo , Siguero Mariano , Kahatt Carmen Maria , Zeaiter Ali Hassan , Boni Valentina , Navarro Alejandro , Gutierrez Calderon Vanesa , Pardo Beatriz , Berton Dominique , Scambia Giovanni 
Published: June 2023

e20632 Background: Lurbinectedin is a selective inhibitor of oncogenic transcription. The US FDA granted accelerated approval for lurbinectedin as monotherapy (3.2 mg/m2 q3wk) for relapsed small cell lung cancer (SCLC) based on a phase 2 basket trial (NCT02454972). The ATLANTIS trial (NCT02566993) investigated lurbinectedin 2.0 mg/m2 plus doxorubicin 40.0 mg/m2 q3wk versus topotecan or CAV in relapsed SCLC. The CORAIL trial (NCT02421588) evaluated lurbinectedin (3.2 mg/m2 i.v. q3wk) compared to pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer. The elderly population is usually under-represented in clinical trials despite its interest due to the increased frailty and high comorbidity. Methods: Data from Basket and CORAIL trials were included in an integrated safety analysis to evaluate lurbinectedin safety profile at the approved regimen (3.2 mg/m2 q3wk). This post hoc safety analysis compares the outcomes of lurbinectedin in elderly population (n = 207 patients ≥65 years old; Basket n = 113 and CORAIL n = 94) versus topotecan (n = 75 patients ≥65 years old; ATLANTIS n = 45 and CORAIL n = 30). Results: Treatment-related adverse events (AEs) and laboratory abnormalities regardless of relationship occurring in > 10% of patients, were: Compared with topotecan, lurbinectedin showed lower frequency of treatment-related grade ≥3 AEs (53.1% vs. 85.3%; p < 0.01) and grade ≥3 serious adverse events (SAEs) (19.8% vs. 34.7%; p = 0.01) and a trend for less AEs leading to treatment discontinuation (5.3% vs. 8.0%; p = 0.40) or deaths (1.4% vs. 5.3%; p = 0.08). Use of supportive treatments was significantly lower with lurbinectedin: G-CSF (17.9% vs. 29.3%; p < 0.05), red blood cells transfusions (20.8% vs. 56.0%; p < 0.01) or erythropoietin (2.4% vs. 14.7%; p < 0.01). Conclusions: Lurbinectedin is well tolerated in elderly patients and has a predictable and manageable safety profile. No new safety signals were observed. With the limitations of cross-trial comparisons, lurbinectedin shows a clear advantage in terms of hematological toxicity compared with topotecan in patients ≥ 65 years old. Furthermore, fewer elderly patients treated with lurbinectedin had severe AEs, SAEs, treatment discontinuations and deaths compared to elderly patients treated with topotecan. Clinical trial information: NCT02454972 , NCT02566993 , NCT02421588 . [Table: see text]
Apollo: A randomized phase II double-blind study of olaparib versus placebo following curative intent therapy in patients with resected pancreatic cancer and a pathogenic BRCA1, BRCA2, or PALB2 mutation—ECOG-ACRIN EA2192.
Authors: Reiss Kim Anna , Hong Sung Chul , Kasi Anup , O'Reilly Eileen Mary , Maithel Shishir K. , Yao Xin , Hamilton Stanley R. , Boursi Ben , Pishvaian Michael J. , Klempner Samuel J , Domchek Susan M. , Catalano Paul J. , Chiorean E. Gabriela , Philip Philip Agop , O'Dwyer Peter J. 
Published: June 2023

TPS4202 Background: A meaningful subset of PDAC is characterized by a homologous recombination deficiency (HRD). The most well-defined patients within this group are those with pathogenic variants in BRCA1, BRCA2 and PALB2. In the metastatic setting, PARP inhibitor maintenance provides a progression-free survival benefit after a period of platinum based chemotherapy1,2, but the role of PARP inhibitors in the curative intent setting is undefined. The OlympiA study established one year of olaparib as the standard of care for patients with BRCA-related, early stage breast cancer who completed all other curative-intent treatment3. Therefore, we have designed a randomized, phase II double-blind study of one year of olaparib vs placebo in patients with pancreatic cancer and a germline or somatic variant in BRCA or PALB2 who have completed all curative intent therapy. Methods: We have enrolled and treated 29 of 152 planned patients on study NCT 04858334/EA2192. Eligibility criteria include: a pathogenic germline or somatic variant in BRCA1, BRCA2 or PALB2 as determined by local laboratory (central review required); completion of curative-intent resection and ≥ three months of multi-agent chemotherapy; no evidence of recurrent disease. At enrollment, patients must be within 12 weeks of their last anti-cancer intervention. Patients are randomized 2:1 to receive oral olaparib 300 mg twice daily or placebo for 12 28-day cycles. The primary endpoint is relapse-free survival. Overall survival is a secondary endpoint. Tumor tissue, fecal material (for microbiome analysis) and serial ctDNA samples are being collected. 1) Golan T, Locker GY, Kindler HL: Maintenance Olaparib for Metastatic Pancreatic Cancer. Reply. N Engl J Med 381:1492-1493, 2019. 2) Reiss KA, Mick R, O'Hara MH, et al: Phase II Study of Maintenance Rucaparib in Patients With Platinum-Sensitive Advanced Pancreatic Cancer and a Pathogenic Germline or Somatic Variant in BRCA1, BRCA2, or PALB2. J Clin Oncol 39:2497-2505, 2021. 3) Tutt ANJ, Garber JE, Geyer CE, Jr.: Adjuvant Olaparib in BRCA-Mutated Breast Cancer. Reply. N Engl J Med 385:1440, 2021. Clinical trial information: NCT04858334 .
Alliance A021806: A phase III trial evaluating perioperative versus adjuvant therapy for resectable pancreatic cancer.
Authors: Chawla Akhil , Shi Qian , Ko Andrew H. , Beg Shaalan , Varghese Anna M. , Behrman Stephen W , Bloomston Mark , Ahmed Firas Salem , Frankel Wendy L. , Dixon Jesse G. , Carrero Xiomara W. , Shergill Ardaman , Crawley Jamie , Akin Oguz , Renouf Daniel John , Zogopoulos George , Hubbard Joleen M. , Meyerhardt Jeffrey A. , O'Reilly Eileen Mary , Ferrone Cristina R. 
Published: June 2023

TPS4204 Background: The role of neoadjuvant chemotherapy in resectable pancreatic cancer has yet to be defined. Recent phase II trial results demonstrate a median overall survival time (mOS) of only 22.4 months after treatment with perioperative modified FOLFIRINOX (mFOLFIRINOX) with 36% not reaching surgery due to disease progression during neoadjuvant therapy. While potential benefits and shortcomings of neoadjuvant chemotherapy have been well documented, to date, no phase III trial has directly compared a perioperative versus an adjuvant chemotherapy strategy in resectable pancreatic cancer. Alliance for Clinical Trials in Oncology A021806 is an actively accruing randomized controlled phase III trial evaluating the efficacy of perioperative chemotherapy with mFOLFIRINOX in patients with resectable pancreatic cancer. Methods: To qualify for enrollment, patients must have biopsy-proven localized resectable pancreatic adenocarcinoma as defined by the National Comprehensive Cancer Network. Patients must have good performance status (ECOG 0 or 1) and be candidates to receive mFOLFIRINOX treatment. All patients enrolled undergo central radiologic eligibility review for quality control and are then randomized to either Arm 1 which consists of 8 cycles of neoadjuvant mFOLFIRINOX followed by 4 cycles of adjuvant mFOLFIRINOX or Arm 2 which includes upfront surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary endpoint of the trial is overall survival with secondary endpoints evaluating disease-free survival, margin-negative resection rate, surgical complications, and chemotherapeutic adverse events. Additional correlative endpoints include quality of life and radiomic imaging assessments. A total enrollment of 352 patients is planned from the US and Canada; current enrollment for this trial is at 145 patients. An OS interim analysis will be performed when 50% of the events (124) are observed combining the two arms. If the trial continues after interim analysis, the final OS analysis will be performed with a total of 248 events (combined arms). If the Cox model (stratified by tumor location and ECOG PS) comparing OS between arms produces a one-sided p-value < 0.05, then we will conclude that the OS of the perioperative therapy arm is superior to adjuvant therapy. The Alliance A021806 phase III trial aims to define a new standard of care for patients with resectable pancreatic cancer. Clinical trial information: NCT04340141 .
Thyroid Function Tests in Children and Adolescents With Trisomy 21: Definition of Syndrome-Specific Reference Ranges
Authors: Cattoni Alessandro , Molinari Silvia , Capitoli Giulia , Masera Nicoletta , Nicolosi Maria Laura , Barzaghi Silvia , Marziali Giulia , Lazzerotti Alessandra , Gazzarri Alessandra , Vimercati Chiara , Sala Debora , Biondi Andrea , Galimberti Stefania , Fossati Chiara 
Published: June 2023

Abstract

Context
The lack of syndrome-specific reference ranges for thyroid function tests (TFT) among pediatric patients with Down syndrome (DS) results in an overestimation of the occurrence of hypothyroidism in this population.

Objective
To (a) outline the age-dependent distribution of TFT among pediatric patients with DS; (b) describe the intraindividual variability of TFT over time; and (c) assess the role of elevated thyrotropin (TSH) in predicting the future onset of overt hypothyroidism.

Methods
In this retrospective, monocentric, observational analysis, we included 548 patients with DS (0-18 years) longitudinally assessed between 1992 and 2022. Exclusion criteria were abnormal thyroid anatomy, treatments affecting TFT, and positive thyroid autoantibodies.

Results
We determined the age-dependent distribution of TSH, FT3, and FT4 and outlined the relative nomograms for children with DS. Compared with non-syndromic patients, median TSH levels were statistically greater at any age (P &lt; .001). Median FT3 and FT4 levels were statistically lower than controls (P &lt; .001) only in specific age classes (0-11 for FT3, 11-18 years for FT4). TSH levels showed a remarkable fluctuation over time, with a poor (23%-53%) agreement between the TSH centile classes at 2 sequential assessments. Finally, the 75th centile was the threshold above which TSH values predicted future evolution into overt hypothyroidism with the best statistical accuracy, with a satisfactory negative predictive value (0.91), but poor positive predictive value (0.15).

Conclusion
By longitudinally assessing TFT in a wide pediatric DS population, we outlined the syndrome-specific reference nomograms for TSH, FT3, and FT4 and demonstrated a persistent upward shift of TSH compared to non-syndromic children.