bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pevonedistat in East Asian patients with acute myeloid leukemia or myelodysplastic syndromes: a phase 1/1b study to evaluate safety, pharmacokinetics and activity as a single agent and in combination with azacitidine
Authors: Handa Hiroshi , Cheong June-Won , Onishi Yasushi , Iida Hiroatsu , Kobayashi Yukio , Kim Hyeoung-Joon , Chiou Tzeon-Jye , Izutsu Koji , Tsukurov Olga , Zhou Xiaofei , Faessel Helene , Yuan Ying , Sedarati Farhad , Faller Douglas V. , Kimura Akiko , Wu Shang-Ju 
Published: May 2022

AbstractPevonedistat, the first small-molecule inhibitor of NEDD8-activating enzyme, has demonstrated clinical activity in Western patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). We report findings from a phase 1/1b study in East Asian patients with AML or MDS, conducted to evaluate the safety/tolerability and characterize the pharmacokinetics of pevonedistat, alone or in combination with azacitidine, in this population, and determine the recommended phase 2/3 dose for pevonedistat plus azacitidine. Twenty-three adult patients with very high/high/intermediate-risk AML or MDS were enrolled in Japan, South Korea and Taiwan. All 23 patients experienced at least one grade ≥ 3 treatment-emergent adverse event. One patient in the combination cohort reported a dose-limiting toxicity. Eighteen patients discontinued treatment; in nine patients, discontinuation was due to progressive disease. Three patients died on study of causes considered unrelated to study drugs. Pevonedistat exhibited linear pharmacokinetics over the dose range of 10–44 mg/m2, with minimal accumulation following multiple-dose administration. An objective response was achieved by 5/11 (45%) response-evaluable patients in the pevonedistat plus azacitidine arm (all with AML), and 0 in the single-agent pevonedistat arm. This study showed that the pharmacokinetic and safety profiles of pevonedistat plus azacitidine in East Asian patients were similar to those observed in Western patients as previously reported. The recommended Phase 2/3 dose (RP2/3D) of pevonedistat was determined to be 20 mg/m2 for co-administration with azacitidine 75 mg/m2 in Phase 2/3 studies, which was identical to the RP2/3D established in Western patients.Trial registration: clinicaltrials.gov: NCT02782468 25 May 2016. https://clinicaltrials.gov/ct2/show/NCT02782468
Immunogenomic intertumor heterogeneity across primary and metastatic sites in a patient with lung adenocarcinoma
Authors: Chen Runzhe , Li Jun , Fujimoto Junya , Hong Lingzhi , Hu Xin , Quek Kelly , Tang Ming , Mitra Akash , Behrens Carmen , Chow Chi-Wan , Jiang Peixin , Little Latasha D. , Gumbs Curtis , Song Xingzhi , Zhang Jianhua , Tan Dongfeng , Heymach John V. , Wistuba Ignacio , Futreal P. Andrew , Gibbons Don L. , Byers Lauren A. , Zhang Jianjun , Reuben Alexandre 
Published: May 2022

Abstract
Background
Lung cancer is the leading cause of cancer death, partially owing to its extensive heterogeneity. The analysis of intertumor heterogeneity has been limited by an inability to concurrently obtain tissue from synchronous metastases unaltered by multiple prior lines of therapy.

Methods
In order to study the relationship between genomic, epigenomic and T cell repertoire heterogeneity in a rare autopsy case from a 32-year-old female never-smoker with left lung primary late-stage lung adenocarcinoma (LUAD), we did whole-exome sequencing (WES), DNA methylation and T cell receptor (TCR) sequencing to characterize the immunogenomic landscape of one primary and 19 synchronous metastatic tumors.

Results
We observed heterogeneous mutation, methylation, and T cell patterns across distinct metastases. Only TP53 mutation was detected in all tumors suggesting an early event while other cancer gene mutations were later events which may have followed subclonal diversification. A set of prevalent T cell clonotypes were completely excluded from left-side thoracic tumors indicating distinct T cell repertoire profiles between left-side and non left-side thoracic tumors. Though a limited number of predicted neoantigens were shared, these were associated with homology of the T cell repertoire across metastases. Lastly, ratio of methylated neoantigen coding mutations was negatively associated with T-cell density, richness and clonality, suggesting neoantigen methylation may partially drive immunosuppression.

Conclusions
Our study demonstrates heterogeneous genomic and T cell profiles across synchronous metastases and how restriction of unique T cell clonotypes within an individual may differentially shape the genomic and epigenomic landscapes of synchronous lung metastases.
A decade of independent prescribing in the UK: a review of progress
Authors: Fitzpatrick Matthew TJ , Borthwick Alan M 
Published: May 2022

AbstractBackground2022 marks a decade since the profession of podiatry secured independent prescribing rights in the UK. Widely viewed as a significant milestone, its advent appeared to herald a new age of practice, with increased autonomy, a broader scope of practice and improved patient care. Access to any medicine within the British National Formulary (with a few notable exceptions) seemed to signal an end to the perennial difficulties and frequent disappointments in obtaining ease of access to medicines necessary for effective practice.Main bodyRecent attempts to expand the scope of prescribing practice to include access to a broader range of controlled drugs (CDs) have led to unanticipated complications which may even threaten existing rights. These issues highlight the limitations of current independent prescribing and the continuing inability of podiatrists to access certain key medicines, primarily controlled drugs. Reliance on specified ‘lists' of approved medicines, whether a controlled drug list for prescribers or the use of statutory exemptions by non‐prescriber podiatrists, remain inflexible and difficult to change. The data underpinning much of this paper is derived from the work undertaken by the authors as representatives of podiatry on NHS England's Chief Professions' Officers' Medicines project, in particular involving submissions to the Commission on Human Medicines and the Advisory Council on the Misuse of Medicines, spanning the years 2017–2021. It describes a complex process, and highlights a misalignment between two legislative frameworks that threaten to unravel existing rights.Short conclusionOngoing difficulties relating to controlled drugs illustrate the problematic nature of current supply, administration and prescribing rights in podiatry. Efforts to keep pace with periodic legal reclassifications of medicines are constrained by limited and inflexible legal mechanisms, and formal approval for extended access via prescribing remains unpredictable and complex. For prescriber and non‐prescriber1 (1Non‐ prescriber podiatrists are those who are neither supplementary or independent prescribers, but do enjoy existing administration and supply rights to certain medicines.) podiatrists alike, the profession of podiatry faces a new challenge to its ability to access medicines, and to realise its full clinical potential.
Smart imaging to empower brain-wide neuroscience at single-cell levels
Authors: Guo Shuxia , Xue Jie , Liu Jian , Ye Xiangqiao , Guo Yichen , Liu Di , Zhao Xuan , Xiong Feng , Han Xiaofeng , Peng Hanchuan 
Published: May 2022

AbstractA deep understanding of the neuronal connectivity and networks with detailed cell typing across brain regions is necessary to unravel the mechanisms behind the emotional and memorial functions as well as to find the treatment of brain impairment. Brain-wide imaging with single-cell resolution provides unique advantages to access morphological features of a neuron and to investigate the connectivity of neuron networks, which has led to exciting discoveries over the past years based on animal models, such as rodents. Nonetheless, high-throughput systems are in urgent demand to support studies of neural morphologies at larger scale and more detailed level, as well as to enable research on non-human primates (NHP) and human brains. The advances in artificial intelligence (AI) and computational resources bring great opportunity to ‘smart’ imaging systems, i.e., to automate, speed up, optimize and upgrade the imaging systems with AI and computational strategies. In this light, we review the important computational techniques that can support smart systems in brain-wide imaging at single-cell resolution.
Effects of inter-pregnancy intervals on preterm birth, low birth weight and perinatal deaths in urban South Ethiopia: a prospective cohort study
Authors: Jena Belayneh Hamdela , Biks Gashaw Andargie , Gete Yigzaw Kebede , Gelaye Kassahun Alemu 
Published: May 2022

Abstract
Background
Preterm birth, low birth weight and perinatal deaths are common adverse perinatal outcomes that are linked with each other, and a public health problems contributing to neonatal mortality, especially in developing countries. Although more than half of women in Ethiopia become pregnant within a short interval after the preceding childbirth, whether the short intervals increase the risk of adverse perinatal outcomes or not is understudied. We, therefore, aimed to assess the effects of inter-pregnancy intervals (IPIs) on the adverse perinatal outcomes.

Methods
A community-based prospective cohort study was conducted among 2578 pregnant women in urban South Ethiopia. Pregnant women with IPIs < 24 months (IPIs < 18 and 18–23 months) were exposed groups, and those with IPI 24–60 months were the unexposed group. A multilevel analysis (mixed-effects) was done to estimate the effect of IPIs on preterm birth and low birth weight, and a generalized linear model for a binary outcome (fixed-effect) was done for perinatal deaths, using a 95% confidence level.

Results
In this study, IPI < 18 months found to increase the risk of preterm birth (Adjusted Relative Risk (ARR) = 1.35, 95% CI: 1.02, 1.78), term low birth weight (ARR = 2.20, 95% CI: 1.35, 3.58) and perinatal deaths (ARR = 3.83, 95% CI: 1.90, 7.71) than 24–60 months. The results suggest that, about 9% of preterm birth, 21% of term low birth weight and 41% of perinatal deaths in the study population were attributed to IPI < 18 months. These could be prevented with the removal of the IPI < 18 months in the study population. IPI 18–23 months has shown no effect on the three adverse perinatal outcomes.

Conclusion
This study has shown that, IPI under 18 months has a higher risk of adverse perinatal outcomes than IPI 24–60 months. Due attention should still be given for spacing pregnancies.
Fatal haemorrhage from a lower limb varicose vein rupture: two case reports
Authors: Logrado Diana , Gomes Catarina , Sardinha Mário 
Published: May 2022

Abstract
Background
Chronic venous disease is one of the most prevalent pathologies today. In Portugal, as in other western countries, its prevalence is high, affecting around 35% of the adult population. It is a chronic and progressive condition that, despite generally benign, may course with major complications, like severe bleeding.

Case presentation
We present the cases of a 47-year-old man and of an 82-year-old woman, with chronic venous disease and obesity, whose deaths occurred from lower limb varicose vein rupture. The gathered circumstantial information, the presence of large amounts of blood on the bodies’ surfaces and clothes, and malleolus ulcers agree with the fatalities reported in scientific literature.

Conclusions
These cases are peculiar, both from a forensic pathology and from a clinical perspective. We want to raise awareness among the medical community about this major complication that is linked with a disease commonly perceived as benign, but that can result in a medical emergency. We also underline the importance of educating patients to this possible outcome.
Design of a maximum power point tracking-based PID controller for DC converter of stand-alone PV system
Authors: Mohammed Fatema A. , Bahgat Mohiy E. , Elmasry Saied S. , Sharaf Soliman M. 
Published: May 2022

AbstractStand-alone photovoltaic system (PV) produces a variance in the output voltage under variable irradiation and temperature, and variable load conditions, resulting in control challenges. The research scope is to maintain a constant output load voltage despite variations in input voltage or load. The use of a DC converter ensures that the output voltage of such systems remains constant regardless of changes in the production voltage and load. The control on a DC boost converter is employed to solve this problem. This paper presents the design of a maximum power point tracking-based (MPPT) DC converter controller for such a system. The MPPT-based PID has been proposed as a control approach and implemented to the system DC converter. Incremental Conductance (IC) algorithm has been employed as an MPPT in association with an optimized PID. The Particle Swarm optimization technique (PSO) has been used to optimize the proposed PID through selected cost function. The PV system with the loaded converter is modeled and simulated using the MATLAB/Simulink environment. The system performance is displayed using a family of curves under different operating conditions and disturbances.
National Survey on the Effect of Oncology Drug Shortages in Clinical Practice: A Hematology Oncology Pharmacy Association Survey
Authors: McBride Ali , Hudson-DiSalle Sarah , Pilz Jeff , Hamm Mark , Boring Brooke , Buie Larry W. , DeRemer David L. 
Published: May 2022

PURPOSE: Drug shortages are a clear and growing challenge. Prominent shortages included oncology medications and supportive care products essential for the care of patients with cancer. Oncology drug shortages often result in disruptions in the timing of chemotherapy treatments, alterations in the dose or regimen administered, or even missed doses when alternative agents are unavailable. The purpose of this survey was to characterize the impact of oncology drug shortages across the United States, including the experiences of health care organizations, resource implications, and the impact on patient safety, patient care, and clinical trials. METHODS: A 36-item online survey was distributed to membership of the Hematology/Oncology Pharmacy Association to gather information on shortages of oncology drugs (ie, all drugs essential in the care of patients with cancer, including supportive care agents). RESULTS: Sixty-eight US organizations participated in the survey between December 2019 and July 2020. Sixty-three percent of institutions reported one or more drug shortages per month, with a 34% increase in 2019 from 2018. Treatment delays, reduced doses, or alternative regimens were reported by 75% of respondents. The most difficult agents to obtain were vincristine, vinblastine, intravenous immunoglobulin, leucovorin, and Bacillus Calmette-Guerin. CONCLUSION: A survey of US oncology pharmacists indicated that oncology drug shortages occurred frequently in 2020. Shortages led to delays in chemotherapy and changes in treatment or omission, complicated clinical research, and increased risk of medication errors and adverse outcomes.
Proyecto ELEVAR: Evaluating the Latinx Experience With the Health Care System Through Variables on Access and Resources
Authors: Franco Idalid , Olazagasti Coral , Osman Fauzia , Duma Narjust 
Published: May 2022

PURPOSE: Hispanic/Latinx communities encounter disparities in access and availability of appropriate timely health care services, negatively affecting cancer outcomes. Limited data exist on the role of these factors in personal experiences of Hispanic/Latinx with health care systems. We aim to better understand Hispanic/Latinx experience with the health care system, focusing on the impact of the Affordable Care Act (ACA) and applications to clinical practice in patients diagnosed with cancer. METHODS: Competitively obtained data from 2010 to 2019 Association of American Medical Colleges Consumer Survey of Health Care Access (a US population–based sample of potential health care consumers needing health care at least once in the past year) were retrospectively reviewed. Descriptive statistics and univariate and multivariate comparisons of patterns pre- versus post-ACA were performed for respondents self-identifying as Hispanic/Latinx. RESULTS: In a total cohort of 53,523 respondents, Hispanic/Latinx comprised 7.5% (n = 4,094). Post-ACA demographics showed a higher proportion of female and an increase in employment, educational attainment, income, and private insurance coverage, with a decrease in uninsured. Adjusted models showed that post-ACA Hispanic/Latinx patients are less likely to use emergency room if sick or needing medical advice (odds ratio [OR] 0.33; P < .001) and more likely to report chronic conditions involving cancer (OR 2.43; P < .001) or being limited in activities because of mental or emotional problems (OR 1.36; P = .005). CONCLUSION: Although ACA implementation was associated with decreased health care access barriers in Hispanic/Latinx, they continue to experience disparities in chronic health conditions, including cancer, with higher limitations because of emotional or mental health. Ongoing efforts that build upon current strides, toward improved patient satisfaction and overall outcomes, are of paramount importance.
Progression-Free Survival in Patients With Cholangiocarcinoma With or Without FGF/FGFR Alterations: A FIGHT-202 Post Hoc Analysis of Prior Systemic Therapy Response
Authors: Bibeau Kristen , Féliz Luis , Lihou Christine F. , Ren Haobo , Abou-Alfa Ghassan K. 
Published: May 2022

PURPOSE Oncogenic fibroblast growth factor receptor (FGFR) gene alterations have been described in patients with cholangiocarcinoma (CCA). This post hoc analysis assessed progression-free survival (PFS) in patients who had received first- or second-line systemic therapy for advanced/metastatic CCA before enrollment in the phase II FIGHT-202 study (ClinicalTrials.gov identifier: NCT02924376 ). PATIENTS AND METHODS Patients with locally advanced or metastatic CCA with FGFR2 fusions/rearrangements (n = 107), other FGF/FGFR alterations (n = 20), or no FGF/FGFR alterations (n = 18) and documented disease progression after at least one systemic cancer therapy before enrollment in FIGHT-202 were assessed. Prior therapy and disease response data were collated from electronic case report forms. PFS was calculated for each prior line of systemic cancer therapy. RESULTS Among patients with FGFR2 fusions/rearrangements, other FGF/ FGFR alterations, and no FGF/ FGFR alterations, respectively, the median PFS with prior first-line systemic therapy was 5.5 months (95% CI, 4.0 to 8.0; n = 102), 4.4 months (2.7 to 7.1; n = 19), and 2.8 months (1.6 to 11.3; n = 16); the median PFS with prior second-line systemic therapy was 4.2 months (3.0 to 5.3; n = 39), 3.0 months (1.1 to 9.9; n = 8), and 5.9 months (2.4 to 12.5; n = 6). The median PFS was 7.0 months (4.9 to 11.1) for patients with FGFR2 fusions/rearrangements (n = 65) with second-line pemigatinib received during the FIGHT-202 trial. CONCLUSION In patients with CCA and FGFR2 fusions or rearrangements, second-line treatment with pemigatinib may be associated with longer PFS compared with second-line treatment with systemic therapy received before study enrollment; however, a prospective controlled trial is required to confirm this. The results support the therapeutic potential of pemigatinib previously demonstrated in FIGHT-202.
Representation of Women as Neurological Surgery Society Award Recipients
Authors: Johnson Gabrielle W. , Almgren-Bell Alison , Skidmore Alexander , Raval Dhvanii , Blow Gretchen , Mackey Kimberly A. , Groves Mari L. , Lee Hedwig , Strahle Jennifer M. 
Published: May 2022

BACKGROUND:
Women comprise more than half of medical school matriculants, but only 8.4% of US neurosurgeons. Awards given by neurosurgical societies are instrumental in shaping and advancing careers of women within academic neurosurgery, which can serve to increase the pipeline of women in the field.

OBJECTIVE:
To quantify the gender diversity of awards given by neurosurgical societies over 54 years.

METHODS:
Awards given by the American Association of Neurological Surgeons, Congress of Neurological Surgeons, and American Association of Neurological Surgeons/Congress of Neurological Surgeons joint sections were classified as research, humanitarian/achievement, or lectureships and analyzed for gender. Composite gender data were obtained from the societies. Percentage differences were calculated using comparison of proportions testing.

RESULTS:
Ninety six distinct awards granted to 1281 individuals from 1965 to 2019 were analyzed, and 9.4% were awarded to women. Seven percent of neurosurgeon awardees were women (excluding Women in Neurosurgery Section [WINS] awards). 36.1% of awards given at least 5 times were never awarded to women. Female awardees increased from 2000-2009 to 2010-2019 (5.2% difference, P = .018). The Cerebrovascular (2.0%) and Spine (2.3%) sections awarded the fewest awards to women, whereas the WINS (73.3%) and Pediatric section (20.6%) awarded the most. Spine, WINS, Pain, Cerebrovascular, and Tumor sections awarded significantly fewer awards to women than respective society demographic proportions. One-hundred percent (39 of 39) of named awards (excluding 2 from WINS) were named after men.

CONCLUSION:
Women remain underrepresented in the field of neurosurgery and as award winners. Many subspecialty sections continue to give significantly fewer awards to women than their society demographic proportions.
A culturally competent approach to teaching humanities in an international medical school: potential frameworks and lessons learned
Authors: Daher-Nashif Suhad , Kane Tanya 
Published: May 2022

Background: This paper describes the development of a culturally competent medical humanities course for second and third-year medical students at the ethnically diverse College of Medicine at Qatar University. First taught in 2016, the elective seminar “Medicine and the Arts” was restructured in 2017 to cultivate an appreciation of the symbiotic relationship between medicine, art, and humanities, and to foster cultural competence among the students.Methods: Results and tips are based on our experiences and past reports.Results: In designing a course for students immersed in an Arab-Muslim context, we encountered two challenges: the discipline’s privileging of a predominantly Western canon of arts and humanities, and the largely Euro-American-centric and unilateral framing of concepts e.g., the doctor-patient relationship, patient-centered approach, patient experiences, and meanings of health and illness. To circumvent these challenges, we followed the Purnell Model for Cultural Competence, adopted the interdisciplinary approach, and employed an intersectionality framework to build and deliver a culturally competent course exploring the nexus of arts, humanities, and medicine.In addition to these tips on which frameworks to adopt and how to structure the course, we recommend a visual literacy workshop to help them develop the ability to recognize and understand ideas conveyed through art. Furthermore, we recommend deep conversations about artistic portrayals of medicine from different cultural contexts as tools for developing cultural awareness. Lastly, we recommend that these discussions adopt a student-centered approach, where students inform about their experiences and their own health and illness determinants, in order to develop their knowledge and practice of holism and patient centered approach, and other issues related to humanities and social sciences. Conclusions:Adopting and implementing a culturally competent approach to medical education, alongside interdisciplinary and intersectionality concepts, are potential conceptual frameworks to structure a course that uses art to inform about medical humanities.