bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from UBE2C-mediated Autophagy Inhibition via Ubiquitination of SIRT1 Contributes to Endometrial Cancer Progression
Authors: Zhao Rong , Liu Yan , Wang Ziwei , Zhang Jun , Zhang Wei , Zhou Xing , Tsedendorj Sevjid , Enkhtur Amarsanaa , Feng Dilu , Wang Hongbo
Published: June 2023

Abstract
Recent studies have shown that autophagy plays an important role in gynecologic tumors, and ubiquitin modification of autophagy regulatory components is essential to regulate autophagic flux. In this study, we found that the ubiquitin-conjugating enzyme E2C (UBE2C) affects endometrial cancer cell apoptosis and proliferation by inhibiting autophagy. Electron microscopy observation of cell ultrastructure and experimental biochemical analysis showed that endometrial cancer cells with UBE2C expression knocked down display typical autophagic characteristics. Cells were cotreated with the autophagy pharmacologic inhibitors chloroquine and/or bafilomycin A1, and mRFP-GFP-LC3 assays were performed to monitor autophagic flux and determine whether UBE2C suppresses the autophagy program. Investigation of the corresponding mechanism by which UBE2C inhibits autophagy revealed that UBE2C induces K48-linked SIRT1 ubiquitination and promotes ubiquitination-dependent degradation of SIRT1, subsequently reducing H4K16 deacetylation levels and epigenetically inhibiting the expression of autophagy-related genes. The results of cell counting kit-8, Hoechst staining, and immunofluorescence assays further indicated that deletion of the autophagy-related gene BECN1 significantly attenuates UBE2C knockdown–induced cell apoptosis. Moreover, overexpression of UBE2C promoted tumor growth in the xenograft mice model. While, the introduction of rapamycin, an agonist of autophagy, successfully reversed tumor growth and apoptosis inhibition mediated by UBE2C overexpression in vitro and in vivo. Taken together, our results suggested that UBE2C-mediated ubiquitination and degradation of SIRT1 contribute to the malignant progression of endometrial cancer through epigenetic inhibition of autophagy.
Implications:
Our study highlights the tumorigenic role and regulatory mechanism of UBE2C in endometrial cancer; UBE2C inhibits endometrial cancer cell apoptosis through autophagy-related mechanisms and our findings provide new insights into the treatment of endometrial cancer.
Data from FOXA1 Reprogramming Dictates Retinoid X Receptor Response in ESR1-Mutant Breast Cancer
Authors: Wu Yang , Li Zheqi , Wedn Abdalla M. , Casey Allison N. , Brown Daniel , Rao Shalini V. , Omarjee Soleilmane , Hooda Jagmohan , Carroll Jason S. , Gertz Jason , Atkinson Jennifer M. , Lee Adrian V. , Oesterreich Steffi
Published: June 2023

Abstract
Estrogen receptor alpha (ER/ESR1) mutations occur in 30% to 40% of endocrine resistant ER-positive (ER+) breast cancer. Forkhead box A1 (FOXA1) is a key pioneer factor mediating ER–chromatin interactions and endocrine response in ER+ breast cancer, but its role in ESR1-mutant breast cancer remains unclear. Our previous FOXA1 chromatin immunoprecipitation sequencing (ChIP-seq) identified a large portion of redistributed binding sites in T47D genome-edited Y537S and D538G ESR1–mutant cells. Here, we further integrated FOXA1 genomic binding profile with the isogenic ER cistrome, accessible genome, and transcriptome data of T47D cell model. FOXA1 redistribution was significantly associated with transcriptomic alterations caused by ESR1 mutations. Furthermore, in ESR1-mutant cells, FOXA1-binding sites less frequently overlapped with ER, and differential gene expression was less associated with the canonical FOXA1–ER axis. Motif analysis revealed a unique enrichment of retinoid X receptor (RXR) motifs in FOXA1-binding sites of ESR1-mutant cells. Consistently, ESR1-mutant cells were more sensitive to growth stimulation with the RXR agonist LG268. The mutant-specific response was dependent on two RXR isoforms, RXR-α and RXR-β, with a stronger dependency on the latter. In addition, T3, the agonist of thyroid receptor (TR) also showed a similar growth-promoting effect in ESR1-mutant cells. Importantly, RXR antagonist HX531 blocked growth of ESR1-mutant cells and a patient-derived xenograft (PDX)-derived organoid with an ESR1 D538G mutation. Collectively, our data support the evidence for a stronger RXR response associated with FOXA1 reprograming in ESR1-mutant cells, suggesting development of therapeutic strategies targeting RXR pathways in breast tumors with ESR1 mutation.
Implications:
It provides comprehensive characterization of the role of FOXA1 in ESR1-mutant breast cancer and potential therapeutic strategy through blocking RXR activation.
Data from BLEACH&STAIN 15-marker Multiplexed Imaging in 3,098 Human Carcinomas Reveals Six Major PD-L1–driven Immune Phenotypes with Distinct Spatial Orchestration
Authors: Bady Elena , Möller Katharina , Mandelkow Tim , Raedler Jonas B. , Yang Cheng , Ebner Julia , Lurati Magalie C.J. , Simon Ronald , Vettorazzi Eik , Büscheck Franziska , Luebke Andreas M. , Dum David , Menz Anne , Sauter Guido , Höflmayer Doris , Weidemann Sören , Fraune Christoph , Uhlig Ria , Bernreuther Christian , Jacobsen Frank , Clauditz Till S. , Wilczak Waldemar , Burandt Eike , Steurer Stefan , Minner Sarah , Lennartz Maximilian , Blessin Niclas C.
Published: June 2023

Abstract
Multiplex fluorescence IHC (mfIHC) approaches were yet either limited to six markers or limited to a small tissue size that hampers translational studies on large tissue microarray cohorts. Here we have developed a BLEACH&STAIN mfIHC method that enabled the simultaneous analysis of 15 biomarkers (PD-L1, PD-1, CTLA-4, panCK, CD68, CD163, CD11c, iNOS, CD3, CD8, CD4, FOXP3, CD20, Ki67, and CD31) in 3,098 tumor samples from 44 different carcinoma entities within one week. To facilitate automated immune checkpoint quantification on tumor and immune cells and study its spatial interplay an artificial intelligence–based framework incorporating 17 different deep-learning systems was established. Unsupervised clustering showed that the three PD-L1 phenotypes (PD-L1+ tumor and immune cells, PD-L1+ immune cells, PD-L1−) were either inflamed or noninflamed. In inflamed PD-L1+patients, spatial analysis revealed that an elevated level of intratumoral M2 macrophages as well as CD11c+ dendritic cell (DC) infiltration (P < 0.001 each) was associated with a high CD3+ CD4± CD8± FOXP3± T-cell exclusion and a high PD-1 expression on T cells (P < 0.001 each). In breast cancer, the PD-L1 fluorescence intensity on tumor cells showed a significantly higher predictive performance for overall survival (OS; AUC, 0.72, P < 0.001) compared with the commonly used percentage of PD-L1+ tumor cells (AUC, 0.54). In conclusion, our deep-learning–based BLEACH&STAIN framework facilitates rapid and comprehensive assessment of more than 60 spatially orchestrated immune cell subpopulations and its prognostic relevance.
Implications:
The development of an easy-to-use high-throughput 15+1 multiplex fluorescence approach facilitates the in-depth understanding of the immune tumor microenvironment (TME) and enables to study the prognostic relevance of more than 130 immune cell subpopulations.
Supplementary Fig. S3 from Metabolomic, DNA Methylomic, and Transcriptomic Profiling of Suberoylanilide Hydroxamic Acid Effects on LPS-Exposed Lung Epithelial Cells
Authors: Chou Pochung Jordan , Sarwar Md Shahid , Wang Lujing , Wu Renyi , Li Shanyi , Hudlikar Rasika R. , Wang Yujue , Su Xiaoyang , Kong Ah-Ng
Published: June 2023

Supplementary Fig. S3 shows the correlation between RNA-seq gene expression and DNA-seq CpG methylation.
Effectors Enabling Adaptation to Mitochondrial Complex I Loss in Hürthle Cell Carcinoma
Authors: Gopal Raj K. , Vantaku Venkata R. , Panda Apekshya , Reimer Bryn , Rath Sneha , To Tsz-Leung , Fisch Adam S. , Cetinbas Murat , Livneh Maia , Calcaterra Michael J. , Gigliotti Benjamin J. , Pierce Kerry A. , Clish Clary B. , Dias-Santagata Dora , Sadow Peter M. , Wirth Lori J. , Daniels Gilbert H. , Sadreyev Ruslan I. , Calvo Sarah E. , Parangi Sareh , Mootha Vamsi K.
Published: June 2023

Oncocytic (Hürthle cell) carcinoma of the thyroid (HCC) is genetically characterized by complex I mitochondrial DNA mutations and widespread chromosomal losses. Here, we utilize RNA sequencing and metabolomics to identify candidate molecular effectors activated by these genetic drivers. We find glutathione biosynthesis, amino acid metabolism, mitochondrial unfolded protein response, and lipid peroxide scavenging to be increased in HCC. A CRISPR–Cas9 knockout screen in a new HCC model reveals which pathways are key for fitness, and highlights loss of GPX4, a defense against lipid peroxides and ferroptosis, as a strong liability. Rescuing complex I redox activity with the yeast NADH dehydrogenase (NDI1) in HCC cells diminishes ferroptosis sensitivity, while inhibiting complex I in normal thyroid cells augments ferroptosis induction. Our work demonstrates unmitigated lipid peroxide stress to be an HCC vulnerability that is mechanistically coupled to the genetic loss of mitochondrial complex I activity.

Significance:

HCC harbors abundant mitochondria, mitochondrial DNA mutations, and chromosomal losses. Using a CRISPR–Cas9 screen inspired by transcriptomic and metabolomic profiling, we identify molecular effectors essential for cell fitness. We uncover lipid peroxide stress as a vulnerability coupled to mitochondrial complex I loss in HCC.

See related article by Frank et al., p. 1884.

This article is highlighted in the In This Issue feature, p. 1749
Resistance to Immune Checkpoint Blockade: IFNγ or MHC-I?
Authors: Haugh Alexandra , Daud Adil
Published: June 2023

Resistance to immune checkpoint blockade (ICB), a subject of increasing interest and relevance in the current cancer treatment landscape, is likely induced by several different and incompletely understood mechanisms, including host T-cell dysfunction/exhaustion, T-cell exclusion from the tumor microenvironment, and tumor-specific changes that dampen the antitumor immune response. In this issue, Kawase and colleagues examine tumor-specific changes that might contribute to anti–PD-1 resistance with a particular focus on reduced MHC class I expression as a potential mechanism of innate and acquired resistance to ICB.

See related article by Kawase et al., p. 895 (1).
Аnalysis of the influence of basic acrylic plastics "Ftoraks" and "Villacryl H Plus" on the main hematological parameters in the experiment
Authors: Rosolovska S. О. , Kindiy D. D. , Hasiuk P. A. , Kindiy V. D. , Vorobets A. B. , Demkovych A. Ye. , Kindiy P. D.
Published: June 2023

Summary. The effectiveness of orthopedic treatment significantly depends on the properties of the basic plastics used in the manufacture of dentures.

The aim of the study – to study the effect of acrylic plastics "Ftoraks" and "Villacryl H Plus", the polymerization of which was carried out by different methods, on the main hematological parameters.

Materials and Methods. The study and comparative characterization of the possible toxic effects of dental base acrylic plastics "Ftoraks" and "Villacryl H Plus", which were polymerized by different methods, on the main hematological parameters were performed on white outbred rats, which implanted samples of these materials in periodontal tissue.

Results and Discussion. As a result of the study, it was found that animals implanted with samples of the above acrylic plastics polymerized in a "water bath" methodic in the blood had a decrease of hemoglobin, leukocytosis, increased number of band and segment nuclear neutrophils, increase in the number of eosinophils and decrease of basophils in comparison with the control and other groups of animals. In the study of samples polymerized in the apparatus for dry polymerization under pressure and in the apparatus for molding plastics, it was found that fluctuations in the content of the main hematological parameters are within the physiological norm and do not differ significantly from the control.

Сonclusions. Dental basic acrylic plastics "Ftoraks" and "Villacryl H Plus" polymerization of which was carried out by the method of dry polymerization with pressure and in the apparatus for foundry pressing of plastics cause less toxic effects on hematological parameters of the blood.
LEVEL OF SATISFACTION WITH THE PROFESSION OF A FAMILY MEDICINE AMBULATORY NURSE
Authors: Kotsaba Yu. Ya.
Published: June 2023

The profession of a family medicine nurse plays a key role in preserving the health of each individual citizen and society as a whole. Therefore, studying the level of satisfaction with one’s work as a family nurse is necessary for improving the work of family medicine. The article presents the results of a study during which the level of professional self-realization among nurses of a family medicine outpatient clinic was studied.
ОЦІНКА ТА РЕЗУЛЬТАТИ ФІЗИЧНОЇ ТЕРАПІЇ У ПАЦІЄНТІВ ІЗ РОЗСІЯНИМ СКЛЕРОЗОМ
Authors: Голяченко А. О. , Гаврилюк О. І. , Голяченко О. А.
Published: June 2023

У статті йдеться про розсіяний склероз – широковідоме хронічне захворювання центральної нерво­вої системи. Він характеризується демієлінізацією нервових волокон, що, у свою чергу, призво­дить до порушення нормального функціонування організму. Дуже важливу роль у лікуванні розсіяного склерозу відіграє реабілітація. Правильно підібрані програма реабілітації і частота курсів реабілітаційного лікування можуть сприяти значному покращенню функції ходи, повсякденної діяльності та відновленню втрачених рухових функцій.
КОМПЛЕКСНЕ ЗАСТОСУВАННЯ ТРАДИЦІЙНИХ І НЕТРАДИЦІЙНИХ МЕТОДІВ ФІЗИЧНОЇ РЕАБІЛІТАЦІЇ ПРИ НЕВРОЛОГІЧНИХ ПРОЯВАХ ОСТЕОХОНДРОЗУ ХРЕБТА
Authors: Пасічник Т. М. , Голяченко А. О.
Published: June 2023

У статті описано результати застосування традиційних і нетрадиційних методів реабілітації та їх ефективність. Використання лікувальної фізичної культури, фізіотерапії і вправ постізометричної релаксації зменшує больовий синдром, сприяє нормалізації тонусу м’язів, поліпшує крово- та лімфообіг. Реабілітація пацієнтів з остеохондрозом повинна бути комплексною, спрямованою на усунення болю, профілактику прогресування захворювання, розтягнення і розслаблення перенапружених м’язів та включати в себе різні форми і засоби фізичної реабілітації.
Роботична хірургія в Україні: перший досвід та перспектива розвитку
Authors: Стасишин А. Р. , Гураєвський А. А. , Дворакевич А. О. , Шевчук Д. В. , Калінчук О. О. , Гураєвський А.-Д. А. , Стасишин О. А.
Published: June 2023

Мета роботи: проаналізувати власний досвід виконання роботичних операцій.

Матеріали і методи. На базі Першого територіального медичного об’єднання м. Львова Лікарня Святого Пантелеймона та кафедри хірургії, пластичної хірургії та ендоскопії ФПДО Львівського національного медичного університету імені Данила Галицького проведено 45 роботичних операції за допомогою системи da Vinci S з грудня 2020 р. до лютого 2023 р. Дорослих пацієнтів було 31, дітей – 14.

Результати досліджень та їх обговорення. Середня тривалість операції – (210±15) хв, середній ліжкодень – (2±1,2) дня. Не було жодних інтраопераційних ускладнень та конверсій. Перевагами виконання роботичних операцій, на нашу думку, були: стабілізований тривимірний стереоскопічний контроль операційного поля, підвищена чіткість зображення та сприйняття глибини поза стандартним лапароскопічним монітором, цифрове 20-кратне збільшення високої чіткості забезпечувало більшу впевненість у точності хірургічних маніпуляцій, підвищена маневреність інструментів створила додатковий ступінь свободи від п’яти рухів до семи у хірургічному полі в пацієнтів з тяжкою хірургічною патологією. Це дозволяє значно зменшити число інтраопераційних ускладнень (кровотечі, ушкодження інших органів).
Політравма: причини та реабілітація на пізніх стадіях травматичної хвороби
Authors: Костюк В. П. , Цвях А. І.
Published: June 2023

Мета роботи: вивчити основні клініко-епідеміологічні показники за ознаками механізмів та обставин отримання ушкоджень серед пацієнтів із політравмою на пізньому етапі травматичної хвороби.

Матеріали і методи. Проаналізовано масив пацієнтів із полісистемними ушкодженнями (114 карт стаціонарного хворого), котрі перебували на реабілітаційному лікування із застосуванням класичних загальноприйнятих методик у травматологічному відділі комунального некомерційного підприємства “Більче-Золотецька обласна лікарня реабілітації імені В. Г. Вершигори” Тернопільської обласної ради впродовж 2010–2019 рр. Серед пацієнтів 61,4 % (n=70) складали чоловіки, і 38,6 % (n=44) – жінки. Вік пацієнтів – від 18 до 79 років (середній вік склав 41,7 року).

Результати досліджень та їх обговорення. Серед пацієнтів більшість склали постраждалі віком 25–60 років, люди працездатного віку (69,30 %). Особи, старші 60 років, склали 10,5 % вибірки, серед них переважали жінки (9 осіб або 75,0 %); віком до 25 років – 11,40 %. У групі до 25 років більшість склала чоловіки – 15 осіб (65,20 %). Найбільша питома вага припала на дорожньо-транспортний травматизм – 1 рангове місце та 40,40 % випадків, друге рангове посіли політравми внаслідок падіння з висоти (34,20 %). Серед людей старшого та похилого віку з однаковою частотою спостерігалися обставини виникнення політравми при падінні та при дорожньо-транспортному травматизмі (водій/пасажир) по 50,0 % випадків політравми. Між ознаками віку та виду травматизму існує позитивний виражений вірогідний звʼязок. Пацієнти з ушкодженнями двох анатомо-функціональних областей склали більшість досліджуваного масиву – 76,32 % (87 випадків), трьох анатомо-функціональних областей – 21,93 % (25 випадків), а чотирьох анатомо-функціональних областей – 1,75 % (2 випадки).
ВИКОРИСТАННЯ ІНТЕРАКТИВНИХ ЗАСОБІВ НАВЧАННЯ ПРИ ВИКЛАДАННІ АНАТОМІЇ ЛЮДИНИ
Authors: Стравський Т. Я. , Герасимюк І. Є. , Галицька-Хархаліс О. Я.
Published: June 2023

Анотація. Випробування галузі освіти, спричинені пандемією COVID-19, а в Україні і війною, матимуть довготривалий вплив на систему, підхід та принципи викладання. Навчальні заклади вимушено перейшли на дистанційну або ж змішану форми навчання, що безумовно склало певні труднощі, зокрема для галузі медичної освіти. За таких умов важливим завданням вищої школи стало забезпечення співіснування різних підходів щодо навчання – традиційного та інноваційного. Невід’ємним у підготовці майбутнього лікаря є знання анатомії людини, яка складає основу для формування клінічного мислення майбутнього спеціаліста. Важливим компонентом компетентнісного підходу при проведенні занять анатомії людини є впровадження та використання можливостей сучасних засобів інтерактивного навчання. Одним із критеріїв вибору оптимальної платформи для викладання була її доступність, що визначалася можливістю роботи на вже наявних технічних засобах (комп’ютери, сенсорні панелі), а також і вартість програмного забезпечення. Враховуючи можливість запуску у web-браузері та відсутність обов’язкової реєстрації, нашим вибором для вивчення кісткової системи стала безкоштовна онлайн-платформа Anatomy Standard. Для доповнення знань стосовно м’язової системи, беручи до уваги відносну доступність (недорога підписка) та широкий функціонал, нашим вибором стало рішення від Visible Body’s Human Anatomy. Незамінним компонентом при вивченні анатомії людини є досвід препарування анатомічних структур. Найбільш інформативним інтерактивним  доповненням  даної методики є рішення від компанії Anatomage, проте його вартість та відсутність локальних сервісів підтримки змусили нас провести пошук більш доступних програм. Наш вибір склав комплекс “Anatomy & physiology revealed 3.0: an interactive cadaver dissection experience”, що дозволяє вивчати пошарову будову тіла на прикладі реальних анатомічних зрізів.  Досвід використання засобів інтерактивного навчання в комбінації з безкоштовними онлайн-платформами показує, що навіть при незначних витратах, використовуючи сильні сторони кожного застосунку, прослідковується висока ефективність їх застосування під час проведення практичних занять анатомії людини.
ВПЛИВ РОБОТИ СТУДЕНТІВ В ЕКСПЕРИМЕНТАЛЬНИХ ОПЕРАЦІЙНИХ НА ЗАСВОЄННЯ НАВЧАЛЬНОГО МАТЕРІАЛУ З КЛІНІЧНОЇ АНАТОМІЇ ТА ОПЕРАТИВНОЇ ХІРУРГІЇ
Authors: Гнатюк М. С. , Монастирська Н. Я. , Слабий О. Б.
Published: June 2023

Анотація. Сьогодні в медичній освіті постійно йде пошук нових технологій, навчання, розробка ефективних навчальних програм, які дозволять істотно покращити підготовку висококваліфікованих спеціалістів з якісно новим ступенем сучасних медичних знань. Мета дослідження – вивчити вплив роботи студентів медичного факультету в експериментальних операційних на засвоєння навчального матеріалу з клінічної анатомії та оперативної хірургії. Досліджено вплив роботи студентів-медиків в експериментальних операційних на засвоєння навчального матеріалу з клінічної анатомії та оперативної хірургії. Встановлено, що студенти, в яких не було пропусків практичних занять у навчальних операційних, засвоювали навчальну дисципліну найкраще, що підтверджувалося відсотком відмінних і добрих оцінок та якісною успішністю. Засвоєння навчального матеріалу з клінічної анатомії та оперативної хірургії найгіршим виявилося у студентів, які з поважних причин пропустили половину практичних занять, що проводилися в операційних.

Отримані результати проведеного дослідження свідчать, що регулярне та систематичне проведення практичних занять зі студентами медичного факультету в експериментальних операційних дозволяє досконало освоїти необхідні практичні навички, сприяє інтенсифікації навчального процесу, розвиває ініціативність, елементи творчості та самостійності при вирішенні нестандартних завдань, стимулює студента систематично звертатися за необхідною для навчання інформацією і сприяє суттєвому покращанню засвоєння клінічної анатомії та оперативної хірургії.
LEGAL COMPETENCE AS A NECESSARY COMPONENT OF PROFESSIONAL COMPETENCE OF THE FUTURE MEDICAL WORKERS
Authors: Humenna N. V. , Kalyniuk N. M.
Published: June 2023

Abstract. The article examines the relevance of the formation of legal competence of future medical workers as a component of professional competence.  The analysis of definitions of legal competence and its structural components in modern psychological and pedagogical literature is carried out. A description of the professional competence of future doctors is given and its components are singled out.
Results of the research showed that the legal competence of the future medical workers is considered in modern psychological and pedagogical literature as an integrative professional and personal qualitative characteristic of the subject of professional medical activi­ty, which consists in theoretical-legal readiness and practical ability to perform professional medical activities and solve legal issues in the field of health care in accordance with the legislation. There such distinguished components of the legal competence: motivational, cognitive, active, as well as can be distinguished reflexive-evaluative and acmeological components.
The article emphasizes the need to introduce into educational process the academic disciplines, which would ensure the acquisition of legal knowledge; legal disciplines taught in the institutions of higher medical education should be professionally oriented and stay in connection with special disciplines.
It was determined that тhe application of legal situational tasks in the educational process, which at the same time stimulate integrative thinking of students based on the knowledge of the materials of the disciplines studied earlier is one of the most effective means of formation of the legal competence of the future medical worker, and provide problematic professionally oriented study of legal aspects of professional activity. The author focuses attention on the importance of learning the norms of professional ethics for the development of the legal competence of future specialists in the field of health care. It is noted that the development of legal competence of future medical workers should be based on understanding and awareness of general cultural and professional values ​​as the norm of professional relations; should be ensured by systematic study of legal knowledge and norms, methods of law-abiding behavior and interaction; should be ensured by formation of stable legal beliefs, development of legal activity and responsibility.
ВИКОРИСТАННЯ ІНТЕЛЕКТУАЛЬНИХ МЕТОДІВ АНАЛІЗУ ДЛЯ ОЦІНЮВАННЯ ЯКОСТІ БЕЗПЕРЕРВНОГО ПРОФЕСІЙНОГО РОЗВИТКУ ЛІКАРІВ В ЕЛЕКТРОННОМУ ПОРТФОЛІО
Authors: Суханова О. О.
Published: June 2023

Розглянуто питання аналізу багатовимірної інформації, що представляє дані безперервного професійного розвитку лікарів, відображені у портфоліо. Показано, що для забезпечення справедливого механізму оцінювання багатовимірної інформації у портфоліо лікарів корисним буде використання сучасних інтелектуальних методів аналізу великих даних (Big Data). Визначено передумови для створення якісної веб-орієнтованої технології шляхом застосування методів інтелектуального аналізу багатовимірної інформації, що вноситься в портфоліо. При використанні ансамблів алгоритмів інтелектуального аналізу портфоліо може стати ефективним засобом об'єктивізації і кількісного визначення освітнього та професійного зростання під час безперервного професійного розвитку лікаря. Враховуючи, що на сьогодні жоден із алгоритмів не може забезпечити валідне оцінювання професійного зростання спеціаліста пропонується використовувати ансамблі методів (поєднання декількох алгоритмів, що одночасно навчаються та виправляють помилки один одного). Портфоліо має великий потенціал, проте його подальше вдосконалення в повній мірі вимагає використання нових підходів, у першу чергу, пов'язаних із вирішенням питання оцінювання динаміки показників професійного зростання лікаря.
Fixos da saúde e fluxos na difusão e atendimento de pacientes com Covid-19 em São Luís, Maranhão, Brasil
Authors: Oliveira Allison Bezerra , Silva Adriana Maria Bernardes da
Published: June 2023

Este trabalho discute a dinâmica de difusão da Covid-19 no Maranhão a partir dos fluxos desencadeados durante a pandemia, por pessoas buscando atendimento em São Luís. Discute também a seletividade com que o território maranhense é usado por empresas de saúde, resultando em zonas de densidade, como São Luís, e zonas de rarefação, como a maior parte dos demais centros do estado. Na pandemia, essa particularidade regional gerou fluxos de pessoas em busca de diagnóstico e tratamento, ampliando áreas de contágio e fragilizando o sistema de saúde. Metodologicamente, o trabalho analisa a distribuição de equipamentos médico-hospitalares e de fixos da saúde para discutir a mobilidade de pessoas, agravada pela pandemia. Os dados advêm sobretudo do Sistema de Informações de Saúde e do Cadastro Nacional dos Estabelecimentos de Saúde do Brasil (ambos do Datasus, Ministério da Saúde) e da Secretaria de Estado da Saúde do Maranhão. Os resultados indicam que a Covid-19 intensificou fluxo de pessoas para São Luís, ampliando a área de contágio e o número de óbitos na capital.
A pluviometria da região da Serra do Caraça e a influência no Quadrilátero Ferrífero, Minas Gerais
Authors: Fernandes Antoniel Silva , Moreira Alecir Antonio Maciel
Published: June 2023

A pesquisa analisa sobretudo o comportamento e a distribuição das chuvas na Serra do Caraça e a interação com seu entorno, a região do Quadrilátero Ferrífero, evidenciando o papel da orografia. Utilizou-se da climatologia geográfica e da análise espacial, com técnicas estatísticas como ferramentas de interpretação dos dados e visando extrair a dinâmica e os ritmos climáticos. Os resultados demonstraram que o conjunto serrano, principalmente na borda leste (Serra do Caraça), influencia a dinâmica da circulação geral e das correntes que provocam distúrbios nos ventos (W/NW e S/SE). Essas correntes concorrem com a precipitação, que pode ultrapassar os 2.500 mm. Constatou-se que há variabilidade na distribuição da chuva no interior do Quadrilátero Ferrífero (bordas N/E apresentam volumes de chuvas mais expressivos que bordas W/S). Quanto à variabilidade espacial e temporal, entre 1984-92, registraram-se as maiores ocorrências de chuva, e, nos anos de 1998-2003 e 2013-16, as menores, no arco de tempo analisado.
A geografia e a ciência aberta
Authors: Juliasz Paula Cristiane Strina
Published: June 2023

Editorial
CD47 Activation by Thrombospondin-1 in Lymphatic Endothelial Cells Suppresses Lymphangiogenesis and Promotes Atherosclerosis
Authors: Singla Bhupesh , Aithbathula Ravi Varma , Pervaiz Naveed , Kathuria Ishita , Swanson Mallory , Ekuban Frederick Adams , Ahn WonMo , Park Frank , Gyamfi Maxwell , Cherian-Shaw Mary , Singh Udai P. , Kumar Santosh
Published: June 2023

Background:

TSP1 (thrombospondin-1)—a well-known angiogenesis inhibitor—mediates differential effects via interacting with cell surface receptors including CD36 (cluster of differentiation) and CD47. However, the role of TSP1 in regulating lymphangiogenesis is not clear. Our previous study suggested the importance of cell-specific CD47 blockade in limiting atherosclerosis. Further, our experiments revealed CD47 as a dominant TSP1 receptor in lymphatic endothelial cells (LECs). As the lymphatic vasculature is functionally linked to atherosclerosis, we aimed to investigate the effects of LEC TSP1-CD47 signaling inhibition on lymphangiogenesis and atherosclerosis.

Methods:

Murine atherosclerotic and nonatherosclerotic arteries were utilized to investigate TSP1 expression using Western blotting and immunostaining. LEC-specific knockout mice were used to determine the in vivo role of LEC
Cd47
in lymphangiogenesis and atherosclerosis. Various in vitro cell-based assays, in vivo Matrigel plug implantation, molecular biological techniques, and immunohistological approaches were used to evaluate the underlying signaling mechanisms.

Results:

Elevated TSP1 expression was observed in mouse atherosclerotic aortic tissue compared with nonatherosclerotic control tissue. TSP1 at pathological concentrations suppressed both in vitro and in vivo lymphangiogenesis. Mechanistically, TSP1 inhibited VEGF (vascular endothelial growth factor)-C–induced AKT and eNOS activation in LEC and attenuated NO (nitric oxide) production. Further,
CD47
silencing in LEC prevented the effects of TSP1 on lymphangiogenic AKT-eNOS signaling and lymphangiogenesis. Atheroprone AAV (adeno-associated virus) 8-
PCSK9
–injected LEC-specific
Cd47
knockout mice (
Cd47
ΔLEC
) had reduced atherosclerosis in both aorta and aortic root compared with control mice (
Cd47
ΔWT
). However, no differences in metabolic parameters including body weight, plasma total cholesterol levels, and fasting blood glucose were observed. Additional immunostaining experiments performed on aortic root cross-sections indicated higher lymphatic vessel density in
Cd47
ΔLEC
mice in comparison to controls.

Conclusions:

These findings demonstrate that TSP1 inhibits lymphangiogenesis via activation of CD47 in LEC, and loss of LEC
Cd47
attenuates atherosclerotic lesion formation. Collectively, these results identify LEC CD47 as a potential therapeutic target in atherosclerosis.
Omega‐3 Fatty Acids and Heart Rhythm, Rate, and Variability in Atrial Fibrillation
Authors: Baumgartner Philipp , Reiner Martin F. , Wiencierz Andrea , Coslovsky Michael , Bonetti Nicole R. , Filipovic Mark G. , Aeschbacher Stefanie , Kühne Michael , Zuern Christine S. , Rodondi Nicolas , Oberle Jolanda , Moschovitis Giorgio , Lüscher Thomas F. , Camici Giovanni G. , Osswald Stefan , Conen David , Beer Jürg H. ,   the SWISS‐AF Investigators
Published: June 2023

Background

Previous randomized control trials showed mixed results concerning the effect of omega‐3 fatty acids (n‐3 FAs) on atrial fibrillation (AF). The associations of n‐3 FA blood levels with heart rhythm in patients with established AF are unknown. The goal of this study was to assess the associations of total and individual n‐3 FA blood levels with AF type (paroxysmal versus nonparoxysmal), heart rate (HR), and HR variability in patients with AF.

Methods and Results

Total n‐3 FAs, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, and alpha‐linolenic acid blood levels were determined in 1969 patients with known AF from the SWISS‐AF (Swiss Atrial Fibrillation cohort). Individual and total n‐3 FAs were correlated with type of AF, HR, and HR variability using standard logistic and linear regression, adjusted for potential confounders. Only a mild association with nonparoxysmal AF was found with total n‐3 FA (odds ratio [OR], 0.97 [95% CI, 0.89–1.05]) and docosahexaenoic acid (OR, 0.93 [95% CI, 0.82–1.06]), whereas other individual n‐3 FAs showed no association with nonparoxysmal AF. Higher total n‐3 FAs (estimate 0.99 [95% CI, 0.98–1.00]) and higher docosahexaenoic acid (0.99 [95% CI, 0.97–1.00]) tended to be associated with slower HR in multivariate analysis. Docosapentaenoic acid was associated with a lower HR variability triangular index (0.94 [95% CI, 0.89–0.99]).

Conclusions

We found no strong evidence for an association of n‐3 FA blood levels with AF type, but higher total n‐3 FA levels and docosahexaenoic acid might correlate with lower HR, and docosapentaenoic acid with a lower HR variability triangular index.
Plasma Pro‐Enkephalin A and Incident Cognitive Impairment: The Reasons for Geographic and Racial Differences in Stroke Cohort
Authors: Short Samuel A. P. , Wilkinson Katherine , Schulte Janin , Renteria Miguel Arce , Cheung Katharine L. , Nicoli Charles D. , Howard Virginia J. , Cushman Mary
Published: June 2023

Background

Cardiovascular disease is a risk factor for cognitive impairment. Evidence links both lower and higher concentration of the circulating opioid pro‐enkephalin A (PENK‐A) with stroke risk. We studied the association of plasma PENK‐A with incident cognitive impairment.

Methods and Results

REGARDS (Reasons for Geographic and Racial Differences in Stroke) is a prospective cohort study of 30 239 adults enrolled from 2003 to 2007. Baseline PENK‐A was measured in a nested case–control study of 462 participants who developed cognitive impairment over 4.7 years, and 556 controls. Logistic regression and spline plots adjusted for confounders estimated odds ratios (ORs) of cognitive impairment by baseline PENK‐A. Interaction terms tested for differences in associations by age, sex, and race. Baseline PENK‐A was comparable between cases and controls. There were significant differences in the association of PENK‐A with cognitive impairment by sex and age (adjusted
P
=0.003 and 0.06, respectively). In women but not men, spline plots showed that higher and lower PENK‐A were associated with decreased odds of cognitive impairment (ORs for 10th and 90th percentiles versus median, 0.65 [95% CI, 0.43–0.96] and 0.64 [95% CI, 0.41–0.99]), with no difference by age. In men ≥65 years of age but not younger men, higher PENK‐A was associated with decreased odds for cognitive impairment (OR for fourth versus first quartile 0.47 [95% CI, 0.22–0.99]); this pattern was not confirmed with spline plotting.

Conclusions

High and low levels of circulating opioid PENK‐A were associated with decreased odds of future cognitive impairment in specific subgroups. Additional research is warranted to understand the biology underlying this association and the observed differences by sex.
Complex Mapping between Neural Response Frequency and Linguistic Units in Natural Speech
Authors: Zhang Yuran , Zou Jiajie , Ding Nai
Published: June 2023

When listening to connected speech, the human brain can extract multiple levels of linguistic units, such as syllables, words, and sentences. It has been hypothesized that the time scale of cortical activity encoding each linguistic unit is commensurate with the time scale of that linguistic unit in speech. Evidence for the hypothesis originally comes from studies using the frequency-tagging paradigm that presents each linguistic unit at a constant rate, and more recently extends to studies on natural speech. For natural speech, it is sometimes assumed that neural encoding of different levels of linguistic units is captured by the neural response tracking speech envelope in different frequency bands (e.g., around 1 Hz for phrases, around 2 Hz for words, and around 4 Hz for syllables). Here, we analyze the coherence between speech envelope and idealized responses, each of which tracks a single level of linguistic unit. Four units, that is, phones, syllables, words, and sentences, are separately considered. We show that the idealized phone-, syllable-, and word-tracking responses all correlate with the speech envelope both around 3–6 Hz and below ∼1 Hz. Further analyses reveal that the 1-Hz correlation mainly originates from the pauses in connected speech. The results here suggest that a simple frequency-domain decomposition of envelope-tracking activity cannot separate the neural responses to different linguistic units in natural speech.
Differential and Overlapping Effects between Exogenous and Endogenous Attention Shape Perceptual Facilitation during Visual Processing
Authors: Landry Mathieu , da Silva Castanheira Jason , Jerbi Karim
Published: June 2023

Visuospatial attention is not a monolithic process and can be divided into different functional systems. In this framework, exogenous attention reflects the involuntary orienting of attention resources following a salient event, whereas endogenous attention corresponds to voluntary orienting based on the goals and intentions of individuals. Previous work shows that these attention processes map onto distinct functional systems, yet evidence suggests that they are not fully independent. In the current work, we investigated the differential and overlapping effects of exogenous and endogenous attention on visual processing. We combined spatial cueing of visuospatial attention, EEG, and multivariate pattern analysis to examine where and when the effects of exogenous and endogenous attention were maximally different and maximally similar. Critically, multivariate pattern analysis provided new insights by examining whether classifiers trained to decode the cueing effect for one attention process (e.g., exogenous attention) can successfully decode the cueing effect for the other attention process (e.g., endogenous attention). These analyses uncovered differential and overlapping effects between exogenous and endogenous attention. Next, we combined principal component analyses, single-trial ERPs, and mediation analysis to determine whether these effects facilitate perception, as indexed by the behavioral spatial cueing effects of exogenous and endogenous attention. This approach revealed that three EEG components shape the cueing effects of exogenous and endogenous attention at various times after target onset. Altogether, our study provides a comprehensive account about how overlapping and differential processes of endogenous and exogenous relate to perceptual facilitation in the context of visuospatial attention.
One-Child Policy, Marriage Distortion, and Welfare Loss
Authors: Huang Wei , Pan Yinghao , Zhou Yi
Published: June 2023

We investigate how exposure to the One-Child Policy (OCP) during early adulthood affects marriage and fertility in China. Exploring fertility penalties across provinces over time and the different implementations by ethnicity, we show that the OCP significantly increases the unmarried rate among the Han ethnicity but not among the minorities. The OCP increases Han-minority marriages in regions where Han-minority couples are allowed for an additional child, but the impact is smaller in other regions. Finally, the deadweight loss caused by lower fertility accounts for 10 percent of annual household incomes, and policy-induced fewer marriages contribute to 30 percent of the fertility decline.
Do Homelessness Prevention Programs Prevent Homelessness? Evidence from a Randomized Controlled Trial
Authors: Phillips David C. , Sullivan James X.
Published: June 2023

This paper provides the first evidence from a randomized controlled trial isolating the impact of financial assistance to prevent homelessness. In this study individuals and families at imminent risk of homelessness were offered temporary financial assistance, averaging nearly $2,000 for those assigned to treatment. Our results show that this assistance significantly reduces homelessness by 3.8 percentage points from a base rate of 4.1 percent. The effects are larger for people with a history of homelessness and no children. Despite concerns about cost-effectiveness due to difficulty targeting, our estimates suggest that the benefits to homelessness prevention exceed costs.
Does a Spoonful of Sugar Levy Help the Calories Go Down? An Analysis of the UK Soft Drinks Industry Levy
Authors: Dickson Alex , Gehrsitz Markus , Kemp Jonathan
Published: June 2023

This study evaluates the effects of the 2018 UK Soft Drinks Industry Levy. We combine novel electronic point of sale data with longitudinal nutritional information and a variety of event-study specifications. All but a few global soft drinks brands reduced sugar content and hence avoided the tiered levy. For brands that maintained their recipes, the levy was on average over-shifted resulting in substantial retail price increases and reductions in consumption, particularly for colas. The levy is responsible for a reduction in intake of about 6,600 calories per year per UK resident, 80% of which is attributable to reformulation by manufacturers.
Boldness behavior and ecological adaptability of stone moroko (Pseudorasbora parva) in open-field testing
Authors: Zheng Yuchen , Zeng Yu , Li Jin , Gong Jianhan , Lv Zhenyu
Published: June 2023

Boldness is closely related to fish species’ adaptative strategies and invasiveness and has become the focus of fish personality research. However, due to the lack of studies on behavioral stages, the ecological functions of certain behaviors remain unclear. To better understand the link between boldness and invasiveness in stone moroko (Pseudorasbora parva), an invasive Asian fish species, we exposed the fish to an open-field environment for 60 min and assessed their behavioral patterns, profiles, and stages. The results show that the boldness behavior of stone moroko was characterized by high activity, low average velocity, and diverse swimming postures. Five behavioral stages with significant differences were revealed: outbreak, inhibition, slow swimming, exploration, and adaptation. These observations suggest that stone moroko can quickly habituate to new environments. In addition, stone moroko spent more energy on exploring the living area and less on environmental risk assessment, as revealed by an analysis of their energy trade-off strategy. The behavioral strategies of stone moroko may explain their extremely high environmental adaptability and ability to invade multiple environments.
Complementary Pathways as “Genuine and Effective Access to Means of Legal Entry” in the Reasoning of the European Court of Human Rights
Authors: Bratanova van Harten Emiliya
Published: June 2023

Complementary pathways are often viewed as an entirely political matter. While there is no legal obligation for states to introduce such, this article shows that their presence or absence has a bearing on how the ECtHR assesses compliance with the prohibition of collective expulsion of aliens. This concrete interaction between complementary pathways and human rights law has been introduced through the requirement of “genuine and effective access to means of legal entry” in the case law of the ECtHR. This article clarifies this requirement and assesses its general significance for the role of complementary pathways as a promotor of or a hindrance to human rights protection.
Gathered by the Word: Latin Pentecostal Migrant Congregations in the Nordic Countries
Authors: Alves Leonardo Marcondes
Published: June 2023

Migration from Portuguese and Spanish-speaking countries has produced over two hundred Evangelical/Pentecostal congregations in the Nordic region during the early twenty-first century. These churches attract people of diverse backgrounds, demanding ongoing negotiations to keep their distinctive existence. I argue that their existence is owed to shared interpretative practices of the Bible and migration experiences, shaping each other, and forming interpretive communities. Based on an ethnographic investigation, five significant themes characterize Latin congregations in the Nordics as interpretive communities, 1) family worship, 2) incubating churches, 3) intercultural families, 4) transnational connection, and 5) hermeneutics of prophecy. These close-knit, connected, and family-like congregations represent a form of migrant self-theologizing for a Christian witness in a pluralistic Nordic region.
The Language of the Protection of Civilians Mandate and the Primary Responsibility of the State: A Legal Norm for Peace and Security
Authors: Morris Tamer
Published: June 2023

When the Security Council mandates the protection of civilians mandate in UN peacekeeping missions, it inadvertently forms an obligation on States involved with UN peace missions. To affirm the concept of State sovereignty, the Security Council constantly references ‘the primary responsibility of the State to protect’ within their resolutions. This developing norm, beginning within the protection of civilians mandate, is an expansion of existing obligations under ihl and ihrl. Within the text of Security Council resolutions there is an obligation that States who are a party to a niac are responsible for peace and security. Therefore, force should be used for peace and security, rather than for “triumphing” in the conflict or entrenching power. As such, a State can achieve its obligations under ihl when governments take all reasonable steps to conclude the conflict, for any hostilities within civilian areas by its very nature is a breach of a State’s obligation and responsibility to protect their own civilians.
Development of Innovation Districts: A Performance Assessment
Authors: Rapetti Carina , Pique Josep M. , Etzkowitz Henry , Miralles Francesc , Duran Jorge
Published: June 2023

Global challenges demand more competitiveness from cities, calling for quick adaptation to changes brought about by the current knowledge economy. Innovation Districts (ID) stand out as the most favourable ecosystems to create economic, urban, social and governance solutions proactively and at the speed demanded by this rapid renewal of knowledge. Effective assessment is important in these areas to ensure efforts are guided to achieve the objectives set. Following validation by a panel of 17 experts through an international Fuzzy Delphi survey, and 15 experts in the DEMATEL multi-criteria decision-making approach, this study builds a conceptual framework in four dimensions (Urban, Economic, Social and Governance), with a set of 37 indicators identified as relevant to assess performance in ID and the power of influences among them. The resulting multidimensional innovation assessment framework is a powerful tool, being useful in determining the key impact indicators of existing innovation districts.
Two new species of hairy crabs (Pilumnidae) and the first record of Crinitocinus alcocki (Borradaile, 1900) (Acidopsidae) (Crustacea: Brachyura) from Taiwan
Authors: NG PETER K.L. , LIN CHIA-WEI
Published: June 2023

Two new species of pilumnid crabs, Heteropilumnus planus n. sp. and Pseudolitochira taiwang n. sp., are described from reefs in Taiwan. Heteropilumnus planus n. sp. is most similar to H. hirsutior (Lanchester, 1900) from Singapore and Japan, but can easily be distinguished by its distinctly flatter carapace, different anterolateral carapace armature, longer ambulatory legs, and male first gonopod structure. Pseudolitochira taiwang n. sp. is most similar to P. crinita Ng & Clark, 2022, from Papua New Guinea but can easily be separated by its carapace physiognomy, armature of the anterolateral carapace margin and proportionately shorter ambulatory legs. Heteropilumnus setosus (A. Milne-Edwards, 1873) is also transferred to Pseudolitochira; and compared with P. taiwang n. sp. The rarely reported acidopsid, Crinitocinus alcocki (Borradaile, 1900) is also recorded from Taiwan for the first time, substantially extending its known range northwards.