bluuebunny/crossref_metadata_2025 huggingface dataset:
Canadian family medicine residency program survey of physical activity curriculum content
Authors: Lindeman Cliff , Filion Myriam , Klein Doug , Stickland Michael K. , Drummond Neil , Spence John C.
Published: March 2023

Background: Physical activity (PA) is an important contributor to the health of Canadians. However, the extent that PA is included in family medicine residents' education is largely unknown. This study surveyed curriculum experts in Canadian family medicine residency programs to understand what residents learn about PA and to what extent this varies across programs.
Methods: Seventeen family medicine residency program websites were reviewed for information pertaining to their PA curriculum. Additionally, curriculum experts were asked to complete a survey to better understand the extent that PA curriculum is included in their programs.
Results: Most (82.4%) of the eligible programs responded to the survey; of which, the majority (92.9%) indicated that residents learn that physical inactivity is a risk factor for chronic conditions, to incorporate into patient care plans, and to recommended PA as prevention for chronic diseases. However, half (50.0%) of the programs stated that they believe residents will be sufficiently prepared to incorporate PA in the care they provide patients, less than half (42.9%) teach PA guidelines, and few (21.4%) teach about PA referral to an allied health care provider or community program.
Conclusions: The instruction about PA that family physicians receive in Canadian residency programs varied depending on the program. A standard to ensure residents are sufficiently and competently prepared to recommend and advise physical activity as treatment and prevention is needed. Additional studies are needed to understand the opinions and teachings of preceptors who may have an influence over the residency training of Canadian family physicians.
Allogeneic transplantation in acute myelogenous leukemia: a comprehensive single institution's experience
Authors: Socie Gerard , Galimard Jacques-Emmanuel , Raffoux Emmanuel , Itzykson Raphael , Debureaux Pierre Edouard , Michonneau David , Lengliné Etienne , Robin Marie , De Fontbrune Flore Sicre , Sébert Marie , Xhaard Aliénor , Kim Rathana , Couprie Anne , Dhedin Nathalie , Dragani Matteo , Lemaire Pierre , Larcher Lise , Clappier Emmanuelle , Boissel Nicolas , Soulier Jean , Dombret Hervé , Fenaux Pierre , De Latour Régis Peffault , Adès Lionel
Published: March 2023

Since decades, debates on the role and timing of allogeneic transplantation HSCT in acute myelogenous leukemia (AML) persist. Time to transplant introduces an immortal time and current treatment algorithm mainly relies on the ELN’s disease risk classification. Previous studies are also limited to age groups, remission status and other ill-defined parameters. We studied all patients at diagnosis irrespective of age and comorbidities to estimate the cumulative incidence and potential benefit or disadvantage of HSCT in a single center. As a time-dependent covariate, HSCT improved overall survival in intermediate and poor risk patients (hazard ratio 0.51; p=0.004). In good risk patients only 8 were transplanted in first complete remission. Overall, the 4-year cumulative incidence of HSCT was only 21.9% but was higher (52.1%) for patients in the first age quartile (16-57) and 26.4% in older patients (57-70); p
Analisis pemakaian Variasi Bahasa Penyiar Radio Kharisma 95,6 Fm Ratu Samban Arga Makmur Bengkulu Utara (Kajian Sosiolinguistik)
Authors: Mufidah  , Basuki Rokhmat , Supadi
Published: March 2023

Tujuan penelitian ini adalah untuk mendeskripsikan pemakaian variasi bahasa penyiar radio Kharisma 95,6 FM di kaji dari segi penutur yaitu idiolek, kronolek dan sosiolek. Metode yang digunakan dalam penelitian ini adalah metode deskriptif. Data penelitian ini diperoleh melalui teknik simak. Langkah-langah analisis data adalah transkripsi data, identifikasi data, klasifikasi data, analisis data dan penyimpulan. Hasil penelitian ini menunjukkan bahwa pemakaian variasi bahasa penyiar radio Kharisma 95,6 FM terdapat 3 bentuk tuturan meliputi: (1) variasi bahasa idiolek ditemukannya pilihan kata yang berulang pada ujaran yang digunakan oleh penyiar radio yaitu “nanti kita puterin ya lagunya”(2) variasi bahasa kronolek ditemukannya pemakaian bahasa masa kini yaitu ujaran “oke, play kan, oke siaaapp, geng ciwi-ciwi, requesannya” (3) variasi bahasa sosiolek ditemukannya pemakaian katasalam salam yang digunakan oleh penyiar yaitu pada ujaran “selamat pagi, selamat siang, selamat pagi menjelang siang, dan terima kasih kembali”. Faktor- faktor yang mempengaruhi terjadinya pemakaian variasi bahasa penyiar Radio Kharisma 95,6 Fm di Arga Makmur adalah (1) variasi idiolek dipengaruhi oleh faktor sosial. (2) variasi kronolek dan sosiolek dipengaruhi oleh faktor situasional.
Nandai Pada Etnik Serawai Di Kabupaten Seluma Sebagai Sumber Pembelajaran Apresiasi Sastra Lama
Authors: Mareta Abenda , Agustina Emi , Sarwono Sarwit
Published: March 2023

This study aims (1) to inventory or collect marks on the Serawai ethnicity in Seluma Regency so that it can be a source of learning for the appreciation of old literature. (2) Finding and explaining the moral values ​​contained in the mark of the Serawai ethnicity in Seluma Regency. The method used in this research is a descriptive qualitative method. The data collection technique was carried out by (1) Observation (2) Defect technique (3) Recording (4) Documentation. Data Analysis Techniques (1) perform translation (2) find and explain moral values ​​(3) conclusions. Research Results (1). Until now, markers are still found in 5 sub-districts in Seluma district, although they are no longer told productively because it is difficult to find sources who can still mark, plus many have had health problems and died. The Nandai that was found was the Nandai ghenai which is a type of legend and fairy tale. (2) There are moral messages and values ​​that can be taken in the markings on the Serawai ethnicity such as individual moral values ​​(honest, patient, disciplined, and responsible) and social moral values ​​(respect for every human being, respect for women, respect for the opinions of others , loyal, polite, and true to promises). (3) Nandai can be used as a source of learning appreciation for old literature in Seluma district at the Junior High School, Senior High School, and General levels because it has two languages ​​(Serawai and Indonesian)and Glossary.

Keywords: Nandai Serawai Ethnic, Learning Values, Learning Resources
Scleral Lens Applications Focused on Korean Patients with Various Corneal Disorders
Authors: Lee Ko Eun , Moon Su Young , Nam Sanghyu , Jang Joon Hyuck , Kim Jae Yong , Tchah Hungwon , Lee Hun
Published: March 2023

Purpose: We aimed to report on the clinical outcomes of scleral lens applications in Korean patients with various corneal disorders.Methods: This retrospective review was conducted for 62 eyes of 47 patients who had been fitted with scleral lenses for various corneal disorders. The patients were referred for inadequate spectacle-corrected visual acuity and rigid gas permeable (RGP) or soft contact lens intolerance. Uncorrected visual acuity, habitually corrected visual acuity, best lens-corrected visual acuity, topographic indices, keratometry indices, and lens parameters were evaluated.Results: Twenty-six eyes of 19 patients with keratoconus were enrolled. Other conditions included corneal scar (13 eyes of 12 patients), phlyctenules (three eyes), laceration (four eyes), chemical burn (one eye), keratitis (one eye), Peters’ anomaly (one eye), fibrous dysplasia (one eye), ocular graft-versus-host disease (two eyes of one patient), irregular astigmatism (18 eyes of 12 patients), and corneal transplant status (five eyes of four patients). The mean topographic values of the eyes include flat keratometric value (43.0 ± 6.1 diopters [D]), steep keratometric value (48.0 ± 7.4 D), and astigmatism (4.9 ± 3.6 D). Of the eyes fitted with scleral lenses, best lens-corrected visual acuity (0.10 ± 0.22 logarithm of the minimum angle of resolution [logMAR]) was significantly better than the habitually corrected visual acuity (0.59 ± 0.62 logMAR, p < 0.001).Conclusions: Scleral contact lenses are a good alternative for patients with corneal abnormalities and those who are intolerable to RGP contact lenses, resulting in both successful visual outcomes and patient satisfaction, especially concerning keratoconus, corneal scar, and corneal transplant status.
Evaluation of bioswale efficiency in consideration of climate and design features: A case study in Hong Kong
Authors: Chen Season S , Sun Yuqing , Chen Liang , He Mingjing , Chiu Albert , Cheung William , Tsang Daniel C W
Published: March 2023

Sustainable drainage systems (SuDSs) have been increasingly implemented to mitigate the stress of urbanisation, climate change, and water scarcity. However, SuDS construction in densely populated metropolitan cities with a subtropical monsoon climate such as that of Hong Kong may encounter challenging field conditions and site constraints. This fieldscale study aimed to verify the performance of bioswale for flood resilience and water quality improvement under various simulated rainfall scenarios with different intermittency and intensity. In the six simulated rainfall events, the results showed that metal removal and flow attenuation were excellent under minor and moderate rainfall events, while the system performance was compromised during intensive rainfall events. The removal of turbidity and nutrients from the runoff was moderate owing to the low contaminant levels in the synthetic stormwater. The dry state of soil media led to more fluctuating results for water quality control. To further enhance the treatment capability under practical site constraints, the addition of appropriate soil amendments and the integrated use of different SuDS measures are recommended in order to achieve sustainable development goals and resilient water management.
Sarcopenia em idosos: conhecimento e intervenção do nutricionista no atendimento desta população
Authors: Maia Jovana de Cássia , Ribeiro Iorrana Índira dos Anjos
Published: March 2023

Este trabalho objetivou descrever as intervenções nutricionais realizadas pelo nutricionista no cuidado do idoso sarcopênico. Trata-se de um estudo de campo, de natureza observacional, de caráter transversal descritivo, com abordagem quantitativa. A pesquisa foi realizada durante os meses de dezembro de 2021 a fevereiro de 2022, com nutricionistas que atuam ou que já atuaram em clínicas e hospitais, através de um questionário online, no Google Forms, contendo 17 questões objetivas. Este, foi divulgado por e-mail, WhatsApp Messenger e Instagram. Na análise dos dados, as questões objetivas foram expostas por meio de gráficos, em que os dados coletados foram colocados em tabelas do Microsoft Excel 2013, proporcionando a comparação dos mesmos. O trabalho foi submetido à Plataforma Brasil e após ser aprovado pelo Comitê de Ética, iniciou-se a pesquisa. Dos resultados, a amostra foi constituída em sua maioria pelo sexo feminino, com faixa etária entre 31 a 50 anos. Os nutricionistas demonstraram possuir conhecimento sobre a sarcopenia e as intervenções nutricionais mais utilizadas por eles foram através de uma dieta hipercalórica, hiperproteica, normoglicídica e normolipídica, com maior destaque da suplementação de proteína, cálcio, vitamina D e ômega 3. Contudo, é importante salientar que a temática ainda é escassa, portanto, é de extrema relevância maiores estudos nessa área.
Tecnologia para produção do óleo de algodão
Authors: Queiroga Vicente de Paula , Mendes Nouglas Veloso Barbosa , Lima Denise de Castro
Published: March 2023

A verticalização do subproduto de óleo bruto de algodão poderá ser a meta de algumas empresas algodoeiras que dispõem, além das máquinas de descaroçamento e de prensa hidráulica para o enfardamento de fibra, de uma unidade de extração de óleo, mas que necessita agregar ao seu circuito produtivo agroindustrial os processos de refino para a produção de óleo comestível. Portanto, este trabalho tem por objetivo mostrar vias que possam aperfeiçoar os procedimentos de preparação das sementes de algodão, extração do óleo das amêndoas e refinamento de óleo, destacando em cada etapa dos processos envolvidos entre a chegada do algodão em rama na agroindústria até a saída dos produtos finais. Para se obter sucesso em tal empreendimento é necessário melhorar o marketing do produto (óleo refinado) pelo fato da semente de algodão possui características proteicas adequadas, que possibilita o seu uso na indústria alimentícia. Além disso, essa agregação de valor do óleo bruto de algodão irá depender da aquisição de alguns equipamentos requeridos nos processos de seu refinamento e também da qualidade inicial da semente, quando é recém-colhida e com umidade em torno de 10%, determinam a obtenção de um bom óleo.
Vida sexual depois dos 60: risco ou prevenção diante das infecções sexualmente transmissíveis?
Authors: Monnerat Isabela da Costa , Azevedo Jackson Freire Benedito de , Câmara Livia de Souza , Barbosa Renata Mendes , Gonçalves Verônica Peres , Teixeira Selma Villas Boas , Cordeiro   Benisia Maria Barbosa , Silva Leila Rangel da
Published: March 2023

A população está em franco processo de envelhecimento e com a manutenção das práticas sexuais, o risco de adquirir Infecções Sexualmente Transmissíveis torna-se elevado. O objetivo desta investigação é discutir o conhecimento e o comportamento de idosos quanto ao risco e à prevenção diante das infecções sexualmente transmissíveis. Estudo quantitativo, descritivo e transversal realizado no município de Teresópolis/RJ, no ano de 2021. Os participantes foram cinquenta idosos cadastrados em uma Unidade de Saúde da Família. Para a coleta de dados, utilizou-se um questionário estruturado autoaplicável. Entre os participantes, mais da metade é do sexo masculino, com faixa etária entre 60 e 65 anos, casados, autodeclarados brancos, católicos, com nível de escolaridade fundamental incompleto. Mais da metade não recebeu orientações de profissionais de saúde com relação à prevenção e referiram o uso da televisão como forma de adquirir informação. Quanto ao conhecimento, a maioria refere desconhecer o que seja uma doença transmitida pelo sexo, não utilizam preservativo e reconhecem o risco de contágio. Este estudo evidenciou que a população idosa enfrenta barreiras no tocante a sua sexualidade e que entre os fatores associados à suscetibilidade às infecções estão: baixa escolaridade, conhecimento limitado sobre contágio e prevenção e pouca adesão ao uso do preservativo. Conclama-se por campanhas educativas e pela participação efetiva dos profissionais de saúde no cuidado integral a fim de minimizar danos à saúde sexual dos idosos.
Potencial inseticida de caldas agroecológicas no controle do curuquerê da couve, Ascia monuste orseis (Lepidoptera: Pieridae)
Authors: Spazzin Magdalena Pomina , Cemin Marina Ferreira Rosa , Bellon Patrícia Paula
Published: March 2023

O objetivo desse trabalho foi avaliar o potencial inseticida de caldas agroecológicas no controle de Ascia monuste orseis. O experimento foi conduzido em laboratório, em delineamento experimental inteiramente casualizado, com cinco tratamentos e dez repetições, onde cada repetição foi constituída por cinco lagartas. As folhas de couve coletadas na propriedade agroecológica foram seccionadas em formato oval e mergulhadas por um tempo de 2 minutos nas respectivas caldas. Posteriormente, cinco lagartas de quinto instar, foram transferidas para cada placa contendo as folhas tratadas com as caldas. Os parâmetros avaliados foram a mortalidade das lagartas 24 e 72 h após a aplicação das caldas agroecológicas. Para as lagartas que sobreviveram após esse período de exposição as caldas, foi avaliado a fase de pupa e a emergência dos adultos. Os dados foram submetidos ao teste não paramétrico de Kruskal-Wallis ao nível de significância de 5%. Havendo diferenças significativas entre os tratamentos, as medianas foram comparadas pelo teste de Dunn a 5% de probabilidade de erro. As caldas de fumo e nim apresentaram efeito significativo na mortalidade do curuquerê da couve. Em relação a duração da fase pupal, as caldas de fumo, alho + pimenta e sálvia apresentaram diferença significativa quando comparadas com a testemunha. Quando avaliada a emergência verificou-se que todas as caldas testadas apresentaram redução na emergência dos adultos e diferiram significativamente da testemunha. Os resultados deste trabalho demonstram a eficiência, principalmente para a calda de fumo, como potencial inseticida para o controle de lagartas de Ascia monuste orseis.
NATIONAL INTERRELATIONSHIPS FROM THE VIEWPOINT OF BIOLOGIST
Authors: V. SIROTKIN ALEXANDER
Published: March 2023

This review presents an original hypothesis, which explains the existence of current nationalism in the modern globalized society by biological rules of hierarchy and competition between the genotypes. Due to its innate character, it cannot be completely deleted from the social life, but the understanding its biological origin can avoid its negative expressions in the multinational communities.
MUSICAL COMPOSITION AS METONYMY OF CULTURE AND THE SUBJECT OF MUSICOLOGICAL STUDIES
Authors: SAMOILENKO OLEXANDRA , OSADCHA SVITLANA , CHERNOIVANENKO ALLA , GRYBYNENKO JULIA , OVSYANNIKOVA-TREL OLEXANDRA
Published: March 2023

The study of musical composition as a unique artistic phenomenon remains an urgent task of modern musicology. Despite the constant use of this concept, it did not acquire a sufficiently stable categorical status. Some ambiguities in the theoretical interpretation of the concept of musical composition are due to the complex nature of this phenomenon, in which the main principles of musical form and meaning formation are focused. It is found that, on the one hand, the temporal nature of music and its impact allows us to consider musical compositions as conditional chronotopic indicators of the historical existence of culture. On the other hand, the semantic attitudes of cultural consciousness determine the typological features of a musical composition. The leading task of musicological interpretation is forming an integrative approach to the phenomenon of a musical composition. It allows combining various research criteria and proposing the most general metonymic model. The metonymic approach to a musical composition presupposes its abstract theoretical reconstruction; at the same time, this reconstruction leads to the identification of those constitutive features of the phenomenon under study that explain its specific artistic and expressive nature, coupled with sound exposure and auditory perception. In the context of art psychology, consideration of a musical composition as an artifact of cultural consciousness reveals its leading semantic properties. The metonymic aspect of this phenomenon interpretation reveals its addressing of noetic reality - the highest level of self-realization of culture semantic consciousness.
ROBUST BUDGETING IN INTERNATIONAL UNIONS
Authors: BOIAR ANDRII , KYTSYUK IRYNA , DEDELYUK KATERYNA , SKOROKHOD IRYNA , KUKHARYK VIKTORIA , ROMANIUK NATALIIA , FEDONIUK SERHII
Published: March 2023

As international economic integration advances the issue of budgeting in inter(supra)national unions becomes more and more important. To ensure stable, effective and efficient functioning of the union its budgetary system should be designed based on a number of rules. In the article we analyze budgetary structures of current international unions and combine the revealed rules into six basic principles. We describe and substantiate these principles. In addition, some theoretical tools that could be applied in scientific validation of a supranational budgetary model are proposed.
SONATA OP.13 BY L. BEETHOVEN IN THE INTERPRETATION OF OUTSTANDING PIANISTS OF THE 20TH CENTURY: TO THE PROBLEM OF PERFORMANCE STYLE
Authors: MULIAR PAVLO , KHIL OLENA , KOCHNIEV VOLODYMYR , MULIAR ANASTASIIA , ZEYU LIU
Published: March 2023

In the article, on the example of the interpretation of Beethoven's work (in particular, Sonata op. 13) in the performance of prominent pianists of the 20th century, it is shown that associativity plays a huge role in the work of the performer. At a certain stage, as a result of the accumulation of meanings, a literary text inevitably turns into a summa summarum a derivative of many other texts, interpreting them and entering into a dialogue or polemic with them: so, in Beethoven's works, his music gradually becomes a kind of “music about music” and needs deciphering its context, which, in turn, determines the need for special skill of the performer. Each composition of Beethoven is individualized, there are no templates, typical stamps. The performance of his compositions outside the concept is not able to adequately convey the spirit of the music.
STUDENT EXPERIENCES OF UNIVERSITY EDUCATION DURING THE COVID-19 PANDEMIC: EVIDENCE FROM SLOVAKIA
Authors: MAROS MILAN , KORENKOVA MARCELA , LEVICKY MICHAL , DRAGUNOVA MARIA
Published: March 2023

The aim of this study was to examine the online education of subjects with an economic focus during the COVID-19 pandemic based on the opinions and experiences of university students in the Slovak Republic. The data were collected using a questionnaire, while the research sample consisted of 358 respondents. Data analysis was performed using the Friedman test, the Nemenyi post-hoc test and the Mann-Whitney test. Students consider safety for health to be the biggest advantage and the biggest disadvantage is the lack of development of interpersonal relationships. The necessary technical equipment to implement online education is not a problem for them. We also found some differences in responses based on gender, degree of study and study results.
A MUSICAL INSTRUMENT AS AN ANTHROPOLOGICAL PHENOMENON
Authors: CHERNOIVANENKO ALLA , YU LIU , XINWEN ZHANG , MURZA SVETLANA , IVANOVA LYUDMILA
Published: March 2023

Among the philosophical discourses in the understanding of the phenomenon of music, the cultural and anthropological one is gaining increasingly more relevance. Located in the direction of the modern paradigm of art history, cultural and anthropological research, this approach expands the traditional perspectives of musicological and philosophical analysis and allows considering music and musical instruments in the context of processes occurring in the sphere of human cultural existence. In the article, music is considered as a specifically anthropological phenomenon that reflects not only the external sociocultural aspects of human existence, but also, first of all, its fundamental essential bases (thinking, feelings, cathartic outlets, etc.).
AESTHETIC FOUNDATIONS AND VALUE CRITERIA OF MODERN MUSIC STUDIES
Authors: SAMOILENKO OLEXANDRA , XIAONAN BAI , XIRAN SUN , YUHAN JIN , XIAOPAI CHEN
Published: March 2023

The purpose of this study is to analyze and theoretically substantiate the complex multidimensional value communicative system inherent in musical art in its dynamic movement and holistic form, to clarify its structure and functional formations, its main internal and external relationships, as well as to establish some ways of influencing the course of artistic processes in society, and, to a certain extent, clarifying the ability to manage them without invading them. It is shown that, for all the subjectivity of perception in the art of music, style favors the formation of conditions for objective value judgments and conclusions. The latter, in turn, form an informational thesaurus that influences the historical dynamics of public musical consciousness.
Duality, Liberty, and Realism in Entangled Political Economy
Authors: Garzarelli Giampaolo , Keeton Lyndal , Sitoe Aldo
Published: March 2023

The work concentrates on the implications of the idealistic and the political realism senses of protecting classical liberalism for entangled political economy through the economics framework of duality. It finds that entangled political economy reveals a failure of the primal problem of duality, but not of the dual one. The modeling survival of the dual problem suggests that the minimization of coercion is what can (and must) be genuinely solved to protect classical liberalism. The solution hinges on institutional design as opposed to allocative choice. And this solution implies that the relationship between liberty and coercion is itself entangled.
A Runge-Kutta numerical scheme applied in solving predator-prey fuzzy model with Holling type II functional response
Authors: Sukarsih I. , Supriatna A. K. , Carnia E. , Anggriani N.
Published: March 2023

The predator-prey model has been extensively studied, but only studies models in a certain environment, where all parameters and initial values involved in the model are assumed to be certain. In real practice, some parameters and initial values are often uncertain. To overcome this uncertainty problem, a model can be made by using a fuzzy theoretical approach. In this paper, we develop a numerical scheme for solving two predator-prey models with a Holling type II functional response by considering fuzzy parameters and initial populations. The behavior of the model was studied qualitatively using the 5th order Runge-Kutta method of which was modified for the fuzzy system using the Zadeh extension principle. The numerical simulation results show that, when the initial populations of prey and predators are fuzzy, the behavior of the fuzzy model would be qualitatively the same as the crisp model. Finally, we conclude that the resulting fuzzy behavior represents a generalization of crisp behavior. This gives more realistic results since the solution is obtained by explicitly considering the problem of uncertainty.
To investigate the correlation between normal fetal biventricular myocardial function and gestational age using velocity vector imaging
Authors: Hou Min , Duan Xiao-Jing , An Yan , You Ji-Peng , Bi Liang-Liang , Zhou Xuan , Wan Jie , Qu Yi
Published: March 2023

Objective

The aim of this study was to evaluate the left and right ventricular segmental and global myocardial function of normal fetuses using velocity vector imaging and explore the correlation between global myocardial function parameters and gestational age.

Methods

A total of 127 normal fetuses were selected and divided into five groups according to gestational age for the measurement of their left and right ventricular segmental and global velocity, strain, and strain rate. This study also explored the change trend in the global myocardial function parameters at different gestational ages and analyzed its correlation with gestational age.

Results

The peak velocities of the biventricular segments of the normal fetuses showed a decreasing trend from the basal to the middle to the apex segment, and the differences were statistically significant (P < 0.05). However, the strain and peak strain rate between adjacent segments showed no significant differences (P > 0.05). The peak global velocity of both ventricles increased with the gestational age, and it was moderately correlated with gestational age; however, the correlation of strain and peak strain rate with gestational age was not statistically significant (P > 0.05).

Conclusion

In normal fetuses, the peak myocardial velocity of the biventricular segments showed a decreasing trend from the basal to the apical segment. The global peak myocardial velocity was linearly correlated with gestational age; however, the global strain and peak strain rate did not change as gestational age increased, indicating that the myocardial deformability of the fetus' ventricles was constant in the middle and late trimesters.
Effect of a stylet on specimen sampling in thyroid fine needle aspiration: A randomized, controlled, non-inferiority trial
Authors: Luo Pengfei , Mu Xiali , Ma Wei , Jiao Dahai , Zhang Peixin
Published: March 2023

Background

There is a cost advantage in using a needle without stylet over a needle with stylet in thyroid fine needle aspiration (FNA). This study aimed to elucidate the non-inferiority of thyroid FNA without a stylet (S-) to thyroid FNA with a stylet (S+) on specimen sampling.

Methods

In this study, patients with thyroid nodules undergoing FNA were consecutively enrolled between May 2022 and July 2022. One experienced operator performed two punctures of each nodule with a stylet and without a stylet. Specimen adequacy was the primary outcome. Wald test was used for statistical analysis of the primary outcome. The difference in specimen adequacy between the two methods was expressed as a two-sided 95% confidence interval (CI). The S- method was considered non-inferior to the S+ method if the lower bound of the 95% CI of the S- minus S+ adequacy difference was greater than a predetermined non-inferiority margin of -10%.

Results

A total of 149 patients (195 nodules) were enrolled in the study. A total of 167 of 195 nodules (85.64%) and 169 of 195 nodules (86.67%) were obtained adequate specimens using the S+ and S- methods, respectively. The difference in specimen adequacy (S- minus S+) between the two methods was 1.03% (95% CI, -5.83% to 7.88%). The lower bound 95% CI of the difference in specimen adequacy (-5.83%) was greater than the predetermined non-inferiority margin of -10%. The difference in the yield for malignancy was not significantly different between the two methods.

Conclusion

Thyroid FNA without a stylet is non-inferior to thyroid FNA with a stylet on specimen sampling.
Neoepitope load, T cell signatures and PD-L2 as combined biomarker strategy for response to checkpoint inhibition immunotherapy
Authors: Borch Annie , Bjerregaard Anne-Mette , Araujo Barbosa de Lima Vinicius , Østrup Olga , Yde Christina Westmose , Eklund Aron Charles , Mau-Sørensen Morten , Barra Carolina , Svane Inge Marie , Nielsen Finn Cilius , Funt Samuel A. , Lassen Ulrik , Hadrup Sine Reker
Published: March 2023

Immune checkpoint inhibition for the treatment of cancer has provided a breakthrough in oncology, and several new checkpoint inhibition pathways are currently being investigated regarding their potential to provide additional clinical benefit. However, only a fraction of patients respond to such treatment modalities, and there is an urgent need to identify biomarkers to rationally select patients that will benefit from treatment. In this study, we explore different tumor associated characteristics for their association with favorable clinical outcome in a diverse cohort of cancer patients treated with checkpoint inhibitors. We studied 29 patients in a basket trial comprising 12 different tumor types, treated with 10 different checkpoint inhibition regimens. Our analysis revealed that even across this diverse cohort, patients achieving clinical benefit had significantly higher neoepitope load, higher expression of T cell signatures, and higher PD-L2 expression, which also correlated with improved progression-free and overall survival. Importantly, the combination of biomarkers serves as a better predictor than each of the biomarkers alone. Basket trials are frequently used in modern immunotherapy trial design, and here we identify a set of biomarkers of potential relevance across multiple cancer types, allowing for the selection of patients that most likely will benefit from immune checkpoint inhibition.
A novel natural killer cell-related signatures to predict prognosis and chemotherapy response of pancreatic cancer patients
Authors: Lan Yongting , Jia Qing , Feng Min , Zhao Peiqing , Zhu Min
Published: March 2023

Background: Natural killer (NK) cells are involved in monitoring and eliminating cancers. The purpose of this study was to develop a NK cell-related genes (NKGs) in pancreatic cancer (PC) and establish a novel prognostic signature for PC patients.

Methods: Omic data were downloaded from The Cancer Genome Atlas Program (TCGA), Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC), and used to generate NKG-based molecular subtypes and construct a prognostic signature of PC. NKGs were downloaded from the ImmPort database. The differences in prognosis, immunotherapy response, and drug sensitivity among subtypes were compared. 12 programmed cell death (PCD) patterns were acquired from previous study. A decision tree and nomogram model were constructed for the prognostic prediction of PC.

Results: Thirty-two prognostic NKGs were identified in PC patients, and were used to generate three clusters with distinct characteristics. PCD patterns were more likely to occur at C1 or C3. Four prognostic DEGs, including MET, EMP1, MYEOV, and NGFR, were found among the clusters and applied to construct a risk signature in TCGA dataset, which was successfully validated in PACA-CA and GSE57495 cohorts. The four gene expressions were negatively correlated with methylation level. PC patients were divided into high and low risk groups, which exerts significantly different prognosis, clinicopathological features, immune infiltration, immunotherapy response and drug sensitivity. Age, N stage, and the risk signature were identified as independent factors of PC prognosis. Low group was more easily to happened on PCD. A decision tree and nomogram model were successfully built for the prognosis prediction of PC patients. ROC curves and DCA curves demonstrated the favorable and robust predictive capability of the nomogram model.

Conclusion: We characterized NKGs-derived molecular subtypes of PC patients, and established favorable prognostic models for the prediction of PC prognosis, which may serve as a potential tool for prognosis prediction and making personalized treatment in PC.
Identification of copy number variants contributing to hallux valgus
Authors: Zhou Wentao , Jia Jun , Qu Hui-Qi , Ma Feier , Li Junyi , Qi Xiaohui , Meng Xinyi , Ding Zhiyong , Zheng Gang , Hakonarson Hakon , Zeng Xiantie , Li Jin , Xia Qianghua
Published: March 2023

Hallux valgus is a common form of foot deformity, and genetic factors contribute substantially to the pathogenesis of hallux valgus deformity. We conducted a genetic study on the structural variants underlying familial hallux valgus using whole exome sequencing approach. Twenty individuals from five hallux valgus families and two sporadic cases were included in this study. A total of 372 copy number variations were found and passed quality control filtering. Among them, 43 were only present in cases but not in controls or healthy individuals in the database of genomic variants. The genes covered by these copy number variations were enriched in gene sets related to immune signaling pathway, and cytochrome P450 metabolism. The hereditary CNVs demonstrate a dominant inheritance pattern. Two candidate pathogenic CNVs were further validated by quantitative-PCR. This study suggests that hallux valgus is a degenerative joint disease involving the dysregulation of immune and metabolism signaling pathways.
Mitochondrial non-coding RNA in nasopharyngeal carcinoma: Clinical diagnosis and functional analysis
Authors: Wang Feng , Li Xiaoyu , Li Cong
Published: March 2023

Background: Nasopharyngeal carcinoma is a common head and neck cancer with high incidence in Southeast Asia. Despite advances in treatment, the diagnosis of NPC remains a challenge due to its non-specific symptoms and high rate of false negatives. In this study, we aimed to identify novel non-coding RNAs (ncRNAs) as diagnostic biomarkers for NPC. Mitochondrial non-coding RNAs (mtio-ncRNAs) have been shown to play important roles in regulating various cellular processes. However, their specific functions and underlying mechanisms are largely unknown.

Methods: We investigated the expression and biological function of mtio-ncRNAs in the human NPC cell line C666-1. By using high-throughput sequencing, we identified several significantly expressed mtio-ncRNAs in C666-1 cells and analyzed their target genes and enriched pathways using tsRFUN.

Results: Our results showed that these significantly expressed mtio-ncRNAs mainly enriched in Cancer Gene Neighborhoods and targeted genes GCM1 and ACTG1. To validate the bioinformatics predictions, we synthesized two mtio-ncRNAs, t00846456 and t00048674, and transfected them into C666-1 cells. Our results showed that the expression of GCM1 was significantly increased by transfection of t00846456, while the expression of ACTG1 was significantly increased by transfection of t0048674. Additionally, the migration ability of the transfected cells was also enhanced.

Discussion: Our findings provide novel insights into the biological functions of mtio-ncRNAs and their potential applications in cancer diagnosis and treatment.
Single-cell protein activity analysis reveals a novel subpopulation of chondrocytes and the corresponding key master regulator proteins associated with anti-senescence and OA progression
Authors: Guang Zhao , Min Zhang , Jun-Tan Li , Tian-Xu Dou , Xiang Gao
Published: March 2023

Background

Osteoarthritis (OA) is a prevalent senescence-related disease with substantial joint pain, loss of joint function, and cartilage degeneration. Because of the paucity of single-cell studies of OA and the gene dropout problem of single-cell RNA sequencing, it is difficult to acquire an in-depth understanding of the molecular characteristics of various chondrocyte clusters.

Methods

Here, we aimed to provide new insights into chondrocyte senescence and a rationale for the development of effective intervention strategies for OA by using published single-cell RNA-sequencing data sets and the metaVIPER algorithm (Virtual Inference of Protein activity by Enriched Regulon). This algorithm was employed to present a proteome catalog of 62,449 chondrocytes from the cartilage of healthy individuals and OA patients at single-cell resolution. Furthermore, histopathologic analysis was carried out in cartilage samples from clinical patients and experimental mouse models of OA to validate above results.

Results

We identified 16 protein-activity-based chondrocyte clusters as well as the underlying master regulators in each cluster. By assessing the enrichment score of each cluster in bulk RNA-sequencing data, followed by gene-set variation analysis, we preliminarily identified a novel subpopulation of chondrocytes (cluster 3). This clinically relevant cluster was predicted to be the main chondrocyte cluster responsible for maintaining cellular homeostasis and anti-senescence. Specifically, we uncovered a set of the key leading-edge proteins of cluster 3 by validating the robustness of the above results using another human chondrocyte single-cell RNA-sequencing data set, consisting of 24,675 chondrocytes. Furthermore, cartilage samples from clinical patients and experimental mouse models of OA were used to evaluate the expression patterns of these leading-edge proteins, and the results indicated that NDRG2, TSPYL2, JMJD6 and HMGB2 are closely associated with OA pathogenesis and might play critical roles in modulating cellular homeostasis and anti-senescence in chondrocytes.

Conclusion

Our study revealed a novel subpopulation of chondrocytes that are critical for anti-progression of OA and the corresponding master regulator proteins, which might serve as therapeutic targets in OA.
Genetic deletion of HVEM in a leukemia B cell line promotes a preferential increase of PD-1- stem cell-like T cells over PD-1+ T cells curbing tumor progression
Authors: del Rio Maria-Luisa , de Juan Carla Yago-Diez , Roncador Giovanna , Caleiras Eduardo , Álvarez-Esteban Ramón , Pérez-Simón José Antonio , Rodriguez-Barbosa Jose-Ignacio
Published: March 2023

Introduction

A high frequency of mutations affecting the gene encoding Herpes Virus Entry Mediator (HVEM, TNFRSF14) is a common clinical finding in a wide variety of human tumors, including those of hematological origin.

Methods

We have addressed how HVEM expression on A20 leukemia cells influences tumor survival and its involvement in the modulation of the anti-tumor immune responses in a parental into F1 mouse tumor model of hybrid resistance by knocking-out HVEM expression. HVEM WT or HVEM KO leukemia cells were then injected intravenously into semiallogeneic F1 recipients and the extent of tumor dissemination was evaluated.

Results

The loss of HVEM expression on A20 leukemia cells led to a significant increase of lymphoid and myeloid tumor cell infiltration curbing tumor progression. NK cells and to a lesser extent NKT cells and monocytes were the predominant innate populations contributing to the global increase of immune infiltrates in HVEM KO tumors compared to that present in HVEM KO tumors. In the overall increase of the adaptive T cell immune infiltrates, the stem cell-like PD-1- T cells progenitors and the effector T cell populations derived from them were more prominently present than terminally differentiated PD-1+ T cells.

Conclusions

These results suggest that the PD-1- T cell subpopulation is likely to be a more relevant contributor to tumor rejection than the PD-1+ T cell subpopulation. These findings highlight the role of co-inhibitory signals delivered by HVEM upon engagement of BTLA on T cells and NK cells, placing HVEM/BTLA interaction in the spotlight as a novel immune checkpoint for the reinforcement of the anti-tumor responses in malignancies of hematopoietic origin.
Combined therapy with methotrexate nanoconjugate and dendritic cells with downregulated IL-10R expression modulates the tumor microenvironment and enhances the systemic anti-tumor immune response in MC38 murine colon carcinoma
Authors: Szczygieł Agnieszka , Węgierek-Ciura Katarzyna , Wróblewska Anna , Mierzejewska Jagoda , Rossowska Joanna , Szermer-Olearnik Bożena , Świtalska Marta , Anger-Góra Natalia , Goszczyński Tomasz M. , Pajtasz-Piasecka Elżbieta
Published: March 2023

Background

Understanding the negative impact of the tumor microenvironment on the creation of an effective immune response has contributed to the development of new therapeutic anti-cancer strategies. One such solution is combined therapy consisting of chemotherapeutic administration followed by dendritic cell (DC)-based vaccines. The use of cytostatic leads to the elimination of cancer cells, but can also modulate the tumor milieu. Moreover, great efforts are being made to increase the therapeutic outcome of immunotherapy, e.g. by enhancing the ability of DCs to generate an efficient immune response, even in the presence of immunosuppressive cytokines such as IL-10. The study aimed to determine the effectiveness of combined therapy with chemotherapeutic with immunomodulatory potential – HES-MTX nanoconjugate (composed of methotrexate (MTX) and hydroxyethyl starch (HES)) and DCs with downregulated expression of IL-10 receptor stimulated with tumor antigens (DC/shIL-10R/TAg) applied in MC38 murine colon carcinoma model.

Methods

With the use of lentiviral vectors the DCs with decreased expression of IL-10R were obtained and characterized. During in vivo studies MC38-tumor bearing mice received MTX or HES-MTX nanoconjugate as a sole treatment or combined with DC-based immunotherapy containing unmodified DCs or DCs transduced with shRNA against IL-10R (or control shRNA sequence). Tumor volume was monitored during the experiment. One week after the last injection of DC-based vaccines, tumor nodules and spleens were dissected for ex vivo analysis. The changes in the local and systemic anti-tumor immune response were estimated with the use of flow cytometry and ELISA methods.

Results and conclusions

In vitro studies showed that the downregulation of IL-10R expression in DCs enhances their ability to activate the specific anti-tumor immune response. The use of HES-MTX nanoconjugate and DC/shIL-10R/TAg in the therapy of MC38-tumor bearing mice resulted in the greatest tumor growth inhibition. At the local anti-tumor immune response level a decrease in the infiltration of cells with suppressor activity and an increase in the influx of effector cells into MC38 tumor tissue was observed. These changes were crucial to enhance the effective specific immune response at the systemic level, which was revealed in the greatest cytotoxic activity of spleen cells against MC38 cells.
Precision (repeatability and reproducibility) of papillary and peripapillary vascular density measurements using optical coherence tomography angiography in children
Authors: Chen Ruru , Liu Xinyu , Yao Mingyu , Zou Zhilin , Chen Xinyi , Li Zheng , Chen Xin , Su Mengjuan , Lian Hengli , Lu Weiwei , Yang Yizhou , McAlinden Colm , Wang Qinmei , Chen Shihao , Huang Jinhai
Published: March 2023

Importance

Optical coherence tomography angiography (OCTA) has been widely applied into children, however, few studies have assessed the repeatability and reproducibility of papillary and peripapillary VD in healthy children.

Objective

To assess the precision of papillary and peripapillary vascular density (VD) measurements using optical coherence tomography angiography (OCTA) and analyze the effects of the signal strength index (SSI) and axial length (AL) on precision estimates.

Design, setting, and participants

This was a prospective observational study. Seventy-eight children aged 6–16 years underwent 4.5 × 4.5 mm OCTA (RTVue XR Avanti) disc scans: two scans by one examiner (repeatability) and two additional scans by another examiner (reproducibility). Within-subject standard deviation (Sw), test-retest reproducibility (TRT), within-subject coefficient of variation (CoV), intraclass correlation coefficient (ICC), and Bland–Altman analysis were performed.

Main outcomes and measures

In repeatability measurement, the fluctuation ranges (minimum to maximum) of VD between intraexaminer A/B in Sw, TRT, CoV, and ICC were (1.05–2.17)% / (1.16–2.32)%, (2.9–6)% / (3.21–6.44)%, (1.9–4.47)% / (2.08–5)%, and (0.588–0.783)% / (0.633–0.803)%, respectively. In reproducibility measurement, the fluctuation ranges of VD in Sw, TRT, CoV, and ICC were 1.11–2.13%, 3.07–5.91%, 1.99–4.41%, and 0.644–0.777%, respectively. VD was negatively correlated with SSI in most sectors of the peripapillary (e.g., inferior nasal, temporal inferior, temporal superior, superior temporal, and superior nasal). AL was positively correlated with inferior temporal VD and negatively correlated with superior nasal VD.

Conclusion and relevance

Optical coherence tomography angiography showed moderate-to-good repeatability and reproducibility for papillary and peripapillary perfusion measurements in healthy children. The SSI value affects most of the peripapillary VD, while AL affects only the temporal inferior and nasal superior peripapillary VD.