bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract SP066: Omitting radiotherapy in select situations
Authors: Jagsi R 
Published: February 2021

Abstract
Advances in breast imaging, surgery, pathology, and systemic therapy have rendered certain patients with breast cancer at sufficiently low risk of local recurrence that they may reasonably consider the omission of radiation therapy to reduce toxicity and burden. For decades, clinical trials have been conducted to try to identify the population of patients in whom the risk of recurrence in the absence of radiotherapy is sufficiently small that omission of radiotherapy might reasonably be considered after breast conserving surgery. Although trials to date, including ER+ patients selected based upon clinicopathologic characteristics alone, have largely proven unsuccessful, guidelines do currently identify older women with early-stage, node-negative, hormone receptor-positive disease to be candidates for radiotherapy omission after lumpectomy. This talk will review historical trials evaluating the role of radiotherapy after breast conserving surgery as well as exciting ongoing trials leveraging our growing appreciation of tumor biology to identify a population of patients who may reasonably consider omitting radiotherapy after breast conserving surgery.
Citation Format: R Jagsi. Omitting radiotherapy in select situations [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP066.
Abstract SP069: Strategies to reduce cardiac toxicity
Authors: Jimenez R 
Published: February 2021

Abstract
Approximately 60-70% of breast cancer (BC) patients receive radiation therapy (RT) as part of their care. Breast or chest wall RT improves locoregional control for BC and also improves BC survival in select populations. However, RT to the cardiac silhouette can be cardiotoxic and radiation induced cardiac toxicity (RIC) affects many breast cancer survivors. The likelihood of RIC is radiation dose dependent and can manifest in multiple forms including cardiovascular disease, heart failure, and/or pericarditis. The risk of cardiovascular disease among patients receiving RT for breast cancer increases linearly with mean heart dose exposure, with no minimum safe threshold. Prior studies have shown an increased risk of both major coronary events and heart failure within 5 years of RT among women with breast cancer, though the latency can be pronounced (10-20 years from exposure) and is further influenced by patient age at treatment as well as pre-existing cardiac risk factors. Therefore, the purpose of this talk is to: 1) discuss the nature and timing of RIC, including those patients most at risk of developing RIC, 2) review national and international cardiology-based guidelines for patient management after chest radiotherapy and 3) detail advances in cardiac sparing radiation techniques intended to reduce the risk of RIC. Ongoing research regarding novel detection and prevention strategies will be highlighted.
Citation Format: R Jimenez. Strategies to reduce cardiac toxicity [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP069.
Abstract SP087: Epigenetic therapy against high-risk breast cancer
Authors: Lupien M 
Published: February 2021

Abstract
Standard-of-care therapy in high-risk stage II-III ER+/HER2-negative and Triple-Negative Breast Cancer (TNBC) includes neoadjuvant chemotherapy (NAC) prior to surgery, which is then followed by adjuvant endocrine (for ER+) +/- salvage chemotherapy (for TNBC). These treatments are delivered with limited stratification by disease histology and, while many patients are cured, more than one third of those in whom invasive disease remains in the breast at the time of surgery experience early relapses of metastatic disease within the first few years. The poor survival rate stems from incomplete response to NAC and the lack of alternative tailored therapy against the chemo-resistant disease that recurs. Hence, there is an urgent need for new therapies to treat recurrence and improve outcome. Tumor progression following standard-of-care therapy arises from pre-existing resistant and/or adapting persister cancer cells committing to an expansion phase. These differ from treatment sensitive cells in the epigenetic landscape of their genome, regulating the on/off state of genes for instance. This underlies epigenetic variants, akin to genetic variants, that define vulnerabilities to new treatment strategies. Here, we demonstrate the value of epigenetic therapy in preclinical settings against high-risk breast cancer, putting forward new treatment options to be tested in clinical trials.
Citation Format: M Lupien. Epigenetic therapy against high-risk breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP087.
Maturation Block in Childhood Cancer
Authors: Behjati Sam , Gilbertson Richard J. , Pfister Stefan M. 
Published: February 2021

Abstract

Summary:
The key differences between tumors arising in children and those in adults stem from the cellular origin of cancer at different ages, with adult cancers arising within aging cell hierarchies, as a consequence of accumulated damage and mutagenesis, in contrast to childhood tumors that are born in aberrantly developing tissues. A distinct biological property of childhood tumor cells—a block of developmental maturation—may hold the key to advancing the treatment of childhood cancer beyond cytotoxic strategies.
Клініко-генетичний та міжгенетичний кореляційний аналіз за експресією miR-29a у хворих на плеоморфні аденоми слинних залоз
Authors: Brodetsky I. S. 
Published: February 2021

Резюме. Найбільш поширеною пухлиною слинних залоз залишається плеоморфна аденома (ПА) – 60–90 % від усіх доброякісних пухлин слинних залоз. Сучасним генетичним напрямком у діагностиці пухлин є вивчення ролі молекул мікроРНК. МікроРНК – це малі некодуючі РНК, які регулюють контроль клітинного циклу, апоптоз, метаболізм, розвиток та диференціацію клітин. Найбільший інте­рес серед них становить проапотозна miR-29a. Вона експресується у 84 % плеоморфних аденом слинних залоз. Статей, в яких описано клініко-генетичні та міжгенетичні кореляції miR-29a в інших біоптатах, окрім пухлини, – прилегла до пухлини тканина слинної залози, інтактна залоза (група контролю), та кров, не знайдено.
Мета дослідження – провести клініко-генетичний та міжгенетичний (за експресією miR-29a) кореляційний аналіз у тканинах плеоморфних аденом великих слинних залоз, тканині слинної залози, прилеглій до пухлини та в інтактній тканині слинної залози, що не мала зв’язку з пухлиною, та венозній крові.
Матеріали і методи. Матеріалом дослідження було 22 хворих на доброякісні пухлини великих слинних залоз (плеоморфні аденоми). Експресію miR-29a оцінювали за допомогою зворотної транскрипції та кількісної полімеразної ланцюгової реакції (qPCR) у режимі реального часу.
Результати досліджень та їх обговорення. Проведений аналіз рівня експресії 29а мікроРНК виявив, що серед 4-х груп показників (тканина пухлини, тканина слинної залози, прилегла до пухлини, інтактна тканина слинної залози, що не мала зв’язку з пухлиною, та венозна кров) у пацієнтів із плеоморфними аденомами великих слинних залоз найбільша експресія відмічалась у групі – тканина слинної залози, прилегла до пухлини, – 111,93±56,97.
Висновки. Проведений кореляційний аналіз клінічних (вік, тривалість захворювання, розмір пухлини, відстань від поверхні шкіри до пухлини) та генетичних показників за рівнем експресії miR-29a в різних біологічних тканинах (тканина пухлини, тканина слинної залози, прилегла до пухлини, інтактна тканина слинної залози, що не мала зв’язку з пухлиною, та венозна кров) у хворих на ПА великих слинних залоз виявив наявність однієї статистично­значущої асоціації (miR-29a). При проведенні міжгенетичного кореляційного аналізу хворих на ПА великих слинних залоз за експресією miR-29a з різними фрагментами біопсійного матеріалу інших статистично значимих асоціацій не виявлено.
Значення параметра та особливості структури біоширини навколо дентальних імплантатів: ретроспективний аналіз даних
Authors: Goncharuk-Khomyn M. Yu. , Boychuk M. M. , Krichfalushij S. I. , Voytovich V. I. , Kinash O. B. , Mykhailiuk I. A. , Mykhailiuk V. M. 
Published: February 2021

Резюме. Доказово доведено, що для формування надійного м᾽якотканинного бар᾽єра в периімплантатній ділянці необхідно забезпечити умови для біологічної організації мінімальних геометричних параметрів біоширини. Дефіцит останніх асоційований із ризиком розвитку патологічних резорбтивних процесів із редукцією рівня навколишнього кісткового гребня, та низкою поступових ускладнень.
Мета дослідження – проаналізувати значення та особливості структури біологічної ширини навколо дентальних імплантатів на основі доступних даних наукової літератури.
Матеріали і методи. Формування первинної вибірки наукових публікацій, що стосувалися теми дослідження, проводилося з використанням пошукової системи Google Scholar (https://scholar.google.com/) та бази даних PubMed (https://pubmed.ncbi.nlm.nih.gov/) із застосуванням відповідних ключових слів («biowidth», «biological width», «dental implants») та Mesh-термінів (алгоритм пошуку: («biology»[MeSH Terms] OR «biology»[All Fields] OR «biological»[All Fields]) AND width[All Fields] AND («dental implants»[MeSH Terms] OR («dental»[All Fields] AND «implants»[All Fields]) OR «dental implants»[All Fields])).
Результати досліджень та їх обговорення. В результаті проведеного аналізу вдалось виокремити такі основні характеристики зони комплексу біологічної ширини навколо дентальних імплантатів: апікальну частину епітеліальної складової, що характеризується мінімальною товщиною з формуванням навколо поверхні імплантату тонких гемідесмосомних структур; сполучнотканинну складову, яка характеризується наявністю безпосереднього контакту з поверхнею імплантату без ознак вираженого функціонального прикріплення; зону безпосереднього контакту, що характеризується відсутністю кровоносних судин та великою кількістю клітин фібробластів у структурі між колагеновими волокнами; латеральніше вищезгаданої зони відмічається зменшення кількості фібробластів та паралельне зростання величини колагенових волокон і кількісного складу судинних структур.
Висновки. Більшість досліджень, асоційованих із вивченням різних аспектів формування комплексу біологічної ширини навколо дентальних імплантатів, проводилася на тваринних моделях, що певною мірою обмежує можливості для безпосередньої інтерпретації отриманих результатів у клінічній стоматологічній практиці. Дані, отримані в ході як лабораторних, так і клінічних досліджень, свідчать про те, що вихідний дефіцит товщини м᾽яких тканин у периімплантатній ділянці пов᾽язаний із процесом редукції рівня кісткового гребеня задля забезпечення формування необхідних параметрів біоширини.
Common Medications and Intracerebral Hemorrhage: The ARIC Study
Authors: Sharma Richa , Matsushita Kunihiro , Wu Aozhou , Jack Clifford R. , Griswold Michael , Mosley Thomas H. , Fornage Myriam , Gottesman Rebecca F. 
Published: February 2021

Background
Antiplatelets, anticoagulants, and statins are commonly prescribed for various indications. The associations between these medications and the risk of intracerebral hemorrhage (ICH) and cerebral microbleeds (CMBs) are unclear.

Methods and Results
We performed a retrospective study of the ARIC (Atherosclerosis Risk in Communities) study cohort, recruited from 4 US communities in 1987 to 1989 with follow‐up. In 2011 to 2013, a subset (N=1942) underwent brain magnetic resonance imaging with CMB evaluation. Time‐varying and any antiplatelet, anticoagulant, or statin use was evaluated at subsequent study visits in participants not on each medication at baseline. To determine the hazard of ICH and odds of CMB by medication use, logistic and Cox proportional hazard models were built, respectively, adjusting for the propensity to take the medication, concomitant use of other medications, and cognitive, genetic, and radiographic data. Of 15 719 individuals during up to 20 years of follow‐up, 130 participants experienced an ICH. The adjusted hazard of ICH was significantly lower among participants taking an antiplatelet at the most recent study visit before ICH versus nonusers (hazard ratio [HR], 0.53; 95% CI, 0.30–0.92). Statin users had a significantly lower hazard of an ICH compared with nonusers (adjusted HR, 0.13; 95% CI, 0.05–0.34). There was no association of CMB and antiplatelet, anticoagulant, or statin use in adjusted models.

Conclusions
In this US community‐based study, antiplatelet and statin use were associated with lower ICH hazard, whereas no association was noted between CMBs and antiplatelets, anticoagulants, and statins. Further study is needed to understand the differential roles of these medications in cerebral microhemorrhages and macrohemorrhages.
Small Dense Low‐Density Lipoprotein Cholesterol Is the Most Atherogenic Lipoprotein Parameter in the Prospective Framingham Offspring Study
Authors: Ikezaki Hiroaki , Lim Elise , Cupples L. Adrienne , Liu Ching‐Ti , Asztalos Bela F. , Schaefer Ernst J. 
Published: February 2021

Background
Elevated plasma levels of direct low‐density lipoprotein cholesterol (LDL‐C), small dense LDL‐C (sdLDL‐C), low‐density lipoprotein (LDL) triglycerides, triglycerides, triglyceride‐rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, and lipoprotein(a) have all been associated with incident atherosclerotic cardiovascular disease (ASCVD). Our goal was to assess which parameters were most strongly associated with ASCVD risk.

Methods and Results

Plasma total cholesterol, triglycerides, high‐density lipoprotein cholesterol, direct LDL‐C, sdLDL‐C, LDL triglycerides, remnant lipoprotein particle cholesterol, triglyceride‐rich lipoprotein cholesterol, and lipoprotein(a) were measured using standardized automated analysis (coefficients of variation, <5.0%) in samples from 3094 fasting subjects free of ASCVD. Of these subjects, 20.2% developed ASCVD over 16 years. On univariate analysis, all ASCVD risk factors were significantly associated with incident ASCVD, as well as the following specialized lipoprotein parameters: sdLDL‐C, LDL triglycerides, triglycerides, triglyceride‐rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, and direct LDL‐C. Only sdLDL‐C, direct LDL‐C, and lipoprotein(a) were significant on multivariate analysis and net reclassification after adjustment for standard risk factors (age, sex, hypertension, diabetes mellitus, smoking, total cholesterol, and high‐density lipoprotein cholesterol). Using the pooled cohort equation, many specialized lipoprotein parameters individually added significant information, but no parameter added significant information once sdLDL‐C (hazard ratio, 1.42;
P
<0.0001) was in the model. These results for sdLDL‐C were confirmed by adjusted discordance analysis versus calculated non–high‐density lipoprotein cholesterol, in contrast to LDL triglycerides.

Conclusions
sdLDL‐C, direct LDL‐C, and lipoprotein(a) all contributed significantly to ASCVD risk on multivariate analysis, but no parameter added significant risk information to the pooled cohort equation once sdLDL‐C was in the model. Our data indicate that small dense LDL is the most atherogenic lipoprotein parameter.
TNFRSF13B
c.226G>A (p.Gly76Ser) as a Novel Causative Mutation for Pulmonary Arterial Hypertension
Authors: Shinya Yoshiki , Hiraide Takahiro , Momoi Mizuki , Goto Shinichi , Suzuki Hisato , Katsumata Yoshinori , Kurebayashi Yutaka , Endo Jin , Sano Motoaki , Fukuda Keiichi , Kosaki Kenjiro , Kataoka Masaharu 
Published: February 2021

Background
Recently, some studies reported the pulmonary artery hypertension (PAH)–associated genes. However, a majority of patients with familial or sporadic PAH lack variants in the known pathogenic genes. In this study, we investigated the new causative gene variants associated with PAH.

Methods and Results

Whole‐exome sequencing in 242 Japanese patients with familial or sporadic PAH identified a heterozygous substitution change involving c.226G>A (p.Gly76Ser) in tumor necrotic factor receptor superfamily 13B gene (
TNFRSF13B
) in 6 (2.5%) patients.
TNFRSF13B
controls the differentiation of B cell and secretion of inflammatory cytokines and may be involved in vascular inflammation. In silico structural analysis simulation demonstrated the structural instability of the N‐terminal region of the protein synthesized from
TNFRSF13B
p.Gly76Ser variant. These suggest that the
TNFRSF13B
p.Gly76Ser variant may be involved in the development of PAH via aberrant inflammation in pulmonary vessels.

Conclusions

TNFRSF13B
p.Gly76Ser variant is a candidate of novel causative gene variant for PAH.
<p><strong><em>Cyathea gratissima</em>, a new name for a Neotropical tree fern (Cyatheaceae, Polypodiopsida)</strong></p>
Authors: TEJEDOR ADRIAN , CALATAYUD GLORIA 
Published: February 2021

Domin, C. (1930) The species of the genus Cyathea J.Sm. Acta Botanica Bohemica 9: 85–174.Hooker, W.J. & Baker, J.G. (1874) Synopsis Filicum, ed. 2. R. Hardwicke, London. https://doi.org/10.5962/bhl.title.41433Tejedor, A. & Calatayud, G. (2018) Six new scaly tree ferns (Cyathea: Cyatheaceae) from Northern Peru. American Fern Journal 108(4): 117–138. https://doi.org/10.1640/0002-8444-108.4.117Weigend, M. (2002) Observations on the biogeography of the Amotape-Huancabamba Zone in northern Peru. The Botanical Review 68: 38–54. https://doi.org/10.1663/0006-8101(2002)068[0038:OOTBOT]2.0.CO;2
Twenty-five years of triptans – a nationwide population study
Authors: Davidsson Olafur B , Olofsson Isa A , Kogelman Lisette JA , Andersen Michael Asger , Rostgaard Klaus , Hjalgrim Henrik , Olesen Jes , Hansen Thomas Folkmann 
Published: February 2021

Background The efficacy of triptans as the main acute treatment strategy for migraine headache at the population-wide level needs to be understood to inform clinical decision-making. We summarise key trends in triptan use using more than 25 years of Danish nationwide data. Methods We conducted a nationwide register-based cohort study based on all Danish residents with access to public healthcare between 1 January 1994 and 31 October 2019 and summarise informative trends of all purchases of triptans in Denmark in the same period. Complete purchase records of Sumatriptan, Naratriptan, Zolmitriptan, Rizatriptan, Almotriptan, Eletriptan, and Frovatriptan were used. Findings Over a 25-year period, triptan use increased from 345 to 945 defined daily doses (DDD) per 1000 inhabitants per year and the yearly prevalence of triptan use increased from 5.17 to 14.57 per 1000 inhabitants. Between 2014 and 2019, 12.3% of the Danish migraine population purchased a triptan. Following their initial purchase, 43% of patients had not repurchased triptans within 5 years. At most, 10% of patients indicating triptan discontinuation tried more than one triptan. The prevalence of triptan overuse, defined as having purchased at least 20 DDDs of triptans per month for 3 consecutive months, increased in parallel with the prevalence of triptan use, prevalent in 56 of every 1000 triptan users every year between 2014 and 2019. Interpretation In a cohort with access to free clinical consultations and low medication costs, we observed low rates of triptan adherence, likely due to disappointing efficacy and/or unpleasant side effects rather than economic considerations. Triptan success continues to be hindered by poor implementation of clinical guidelines and high rates of treatment discontinuance.
Simultaneous bilateral or sequential DCR? What to choose?
Authors: Weinberger Yehonatan , Soudry Ethan , Avisar Inbal 
Published: February 2021

Background: Dacryocystorhinostomy is used to treat nasolacrimal duct obstruction when conservative measures fail. It may be performed via an external or endoscopic-endonasal approach. The aim of this study was to compare the outcomes of patients with nasolacrimal duct obstruction treated with simultaneous bilateral or unilateral dacryocystorhinostomy. Methods: The database of a tertiary medical center was retrospectively reviewed for all patients treated for nasolacrimal duct obstruction in 2012–2017. The study sample was divided into six groups by surgery type and approach: adults (>18 years) – external or endoscopic-endonasal sequential unilateral or simultaneous bilateral dacryocystorhinostomy (four subgroups); children (18 years) – endoscopic-endonasal unilateral or simultaneous bilateral dacryocystorhinostomy (two subgroups). Data were collected on patient age and sex, surgery and anesthesia type and duration, and complications. Results: The cohort included 95 adults and 27 children who underwent 111 and 41 surgical procedures, respectively. Among the adults, the durations of anesthesia and surgery were significantly longer in the external bilateral dacryocystorhinostomy group than the others, but no such differences were found between simultaneous bilateral endonasal dacryocystorhinostomy and unilateral dacryocystorhinostomy by either approach. Among the children, there was no significant between-group difference in surgery duration. In neither age population was bilateral endoscopic surgery associated with an excess of intraoperative or postoperative complications of hemorrhage, infection, and epiphora. Conclusion: The lack of intergroup differences in clinical, surgical, and outcome parameters suggests that in cases of bilateral nasolacrimal duct obstruction in adults and children, simultaneous bilateral endoscopic-endonasal dacryocystorhinostomy may yield excellent therapeutic results.
Inhibition of ACE2 Expression by Ascorbic Acid Alone and its Combinations with Other Natural Compounds
Authors: Ivanov Vadim , Goc Anna , Ivanova Svetlana , Niedzwiecki Aleksandra , Rath Matthias 
Published: February 2021

Background: Angiotensin-converting enzyme II or ACE2 is an integral membrane protein present on many types of cells, including vascular endothelial cells and lung alveolar epithelial cells. This receptor serves as the entry point for SARS-coronaviruses (SARS-CoVs), including a novel coronavirus 2019-nCoV. Limited availability of these receptors can thwart cellular entry of this virus. Methods: We tested the effects of ascorbic acid (vitamin C) on cellular expression of ACE2 at the protein and RNA levels in human small alveolar epithelial cells and microvascular endothelial cells. In addition, we investigated whether combinations of ascorbic acid with other natural compounds can affect ACE2 expression. Results: The results show that ascorbic acid itself has moderate but consistent lowering effects on ACE2 expression at the cellular, protein, and RNA levels. Some natural compounds were effective in lowering ACE2 cellular expression, with the highest inhibitory effects observed for baicalin (75%) and theaflavin (50%). Significantly, combinations of these and other test compounds with ascorbic acid further decreased ACE2 expression. The highest impact of ascorbate on ACE2 expression was noted when combined with theaflavin (decrease from 50% to 87%), zinc (decrease from 22% to 62%), and with 10-undecenoic acid (from 18% to 53%). Ascorbic acid showed moderate additional benefits in decreasing ACE2 expression when combined with N-acetylcysteine and baicalin. Conclusion: Our study provides valuable experimental confirmation of the efficacy of micronutrients in controlling ACE2 expression—the coronavirus cellular “entry” point. It further validates the importance of nutrient interactions in various aspects of cellular metabolism and in considering potential therapeutic applications of nutrient-based approaches. The study shows that ascorbic acid and its combination with some natural compounds could be included in developing preventive and therapeutic approaches toward the current pandemic.