bluuebunny/crossref_metadata_2025 huggingface dataset:
SLOVENIA'S CONTRIBUTION TO AFGHANISTAN PEACE AND REINTEGRATION PROGRAMME – POLICY ADVISOR'S PERSPECTIVE
Authors: SELAN ALJOŠA
Published: February 2021

This article uses theoretical framework of the changing nature of war, peace-building and counterinsurgency as a foundation for explaining a unique disarmament, demobilization and reintegration (DDR) programme – Afghanistan Peace and Reintegration Programme. It explains basic concepts, structures and processes of the Afghanistan Peace and Reintegration Programme. Additionally, it presents the role of the Slovenian policy advisor in the International Security and Assistance Force Headquarters' Force Reintegration Cell. Main challenges and the dynamics of the unique and complex programme and of the policy advisor’s work are laid out. Afghanistan Peace and Reintegration Programme is an important internationally funded project which has removed thousands of former fighters from the field and has helped to provide support to local communities and reintegrees. The lack of adequate transparency and measurability of the Programme’s achievements has been addressed but not yet resolved. ISAF has been playing a very positive supporting, expert and facilitating role in an effort to help further develop a more effective and efficient programme. In the final analysis the overall success of the programme is significantly correlated to the Afghan authorities’ credibility and the need for improved governance. Članek izhaja iz teoretičnega okvira spreminjajoče se narave vojne, gradnje miru in protiuporniškega delovanja in je uporabljen kot temelj za razlago enotnega programa za razorožitev, demobilizacijo in reintegracijo (DDR) Programa za reintegracijo in spravo v Afganistanu. Razloženi so temeljni koncepti, strukture in procesi tega programa, predstavljena pa je tudi vloga slovenskega političnega svetovalca v Celici za reintegracijo pri poveljstvu Mednarodnih varnostnih sil za pomoč (Isaf). V prispevku so pojasnjeni glavni izzivi in dinamika enotnega in kompleksnega programa ter delovanja političnega svetovalca. Program za reintegracijo in spravo v Afganistanu je pomemben mednarodno financiran projekt, ki je pripomogel k vrnitvi tisočev nekdanjih borcev s terena ter k podpori lokalnim skupnostim in reintegraciji. Članek obravnava pomanjkanje ustrezne preglednosti in merljivosti dosežkov programa, ki še ni odpravljeno. Pri prizadevanjih za nadaljnje oblikovanje učinkovitega in smotrnega programa ima Isaf zelo pozitivno podporno, strokovno in izvršilno vlogo. Končna analiza razkriva, da je uspešnost programa tesno povezana z verodostojnostjo afganistanskih oblasti in potrebo po boljšem upravljanju.
THE NORMATIVE ROLE OF THE ALLIANCE
IN NON-CONVENTIONAL SECURITY THREATS – CYBER DEFENCE OF MEMBER STATES
Authors: DVORŠAK ADRIJANA
Published: February 2021

The role of international security organizations is to create a consensus on values, norms and rules relating to cyber warfare. NATO produces cyber policy and provides for education and the exchange of information also through publicistic activity. To a lesser extent it has also developed operational capabilities for joint cyber defence and cyber warfare.
NATO can expect initiatives for close cooperation in cyber defence and the establishment of common cyber capabilities, which are all rational responses to unconventional threats. The benefits stemming from such cooperation differ by state. The author is nonetheless convinced that the United States will benefit the most from the said cooperation as their economy is the most dependent on information and communication technology, the most globalised and allegedly the most frequent target of cyber attacks.
The Values of Character in Traditional Games Simalungun Society
Authors: Damanik Ramlan , Sinaga Warisman
Published: February 2021

Simalungun ethnic is one of the ethnic in North Sumatra, Simalungun ethnic have some traditional games, marlubuk,marsitengka, marjalengkat, batu marsiada (mardara), marultop, margala, margodok, pattik lele, pecah piring, olei,olei, margasing, jalengkat sarip, marjakop, dan marampera. Discussions with an informan and immediately held a game involve some children in Sirpang Sigodang Kecamatan Raya village, for get Simalungun traditional games’ type. Methods such as recording, documenting, interviewing have eighteen character values, among others: religious values, honesty, tolerance, discipline, hard work, creative thinking, independence / independence, democracy, curiosity, national spirit, patriotism, appreciation for achievement, hospitality, peace, love to read, protect the environment, social care, and responsibility. Simalungun traditional games can be played at school, some friends in neighborhood for form character values.
The Implementation of Child Livelihood Payment after Divorce Occurs in the Perspective of the Shafi` School of Fiqh and Positive Law (Post-Court Judgment Analysis Study in North Sumatra)
Authors: Asmuni Asmuni , Hasibuan Pagar , Rangkuti Ahmad Zuhri
Published: February 2021

As many as 80% of the judges' verdicts at the North Sumatra Religious Court (PA Sumut) were ignored by their former husbands, excluding education and health costs. This study aims: (1) to find out how to pay for children's livelihoods after divorce, from the perspective of the Syāfi`ī school of jurisprudence, (2) to find out how to pay for child support after divorce, with a positive legal perspective (3) to find out how to determine children's livelihoods after divorce from the perspective of the fiqh school of thought Shafi`ī PA North Sumatra. This research uses field research methods by collecting primary data with direct interview respondents, direct observation in North Sumatra PA, collecting closely related data and information, supported by library research methods. This type of research is field research. This research approach is sociological juridical. The nature of the research is descriptive-analysis. The data sources were obtained from primary, secondary and tertiary legal materials. Data collection methods by means of interviews and documentation. Research conclusions: (1) how to pay for child support after divorce from the perspective of the Syāfi`ī school of jurisprudence, namely a) asking or taking the method directly according to the local urf, b) giving it directly by the ex-husband or through a representative according to the local urf, c) filing a lawsuit. (2) The method of paying for children's livelihoods after divorce from a positive legal perspective, namely: a), handing over directly to the mother, b) the Court's decision due to divorce or sue (3) The way North Sumatra PA determines children's livelihoods after divorce, namely through: a) the child's mother, b) a verdict, c) filing a lawsuit.
OWNERSHIP STRUCTURE OF FAMILY BUSINESS GROUPS
Authors: Xavier Wlamir , Camilo Silvio Parodi Oliveira , Marcon Rosilene , Greene Frederick
Published: February 2021

This study seeks to analyze the relationship between the ownership structure of Family Business Groups and the institutional environment. Family Business Groups prevail in emerging countries as diverse organizational structures that aggregate various companies under the control of a family or a reduced number of people. This economically relevant structure is responsible for a significant share of countries' Gross Domestic Product and frequently congregates the largest private companies in their respective countries. Institutional reforms have been implemented in emerging economies in order to support the integration of other nations from a trade perspective. This paper contributes to the literature by developing propositions on the effect of institutional reforms on the ownership structure of Family Business Groups.
Humic substances and their effects on the micropropagation of banana
Authors: Buttrós Victor Hugo Teixeira , Pereira Maysa Mathias Alves , Martins Adalvan Daniel , Rodrigues Filipe Almendagna , Pasqual Moacir , Dória Joyce
Published: February 2021

The growing concern to promote sustainable agriculture, seeking environmental preservation and, at the same time, increased productivity resulted in the search for technologies for the implementation of agricultural production systems, with ecological approaches and responsible use of natural resources, in the economic, political and social contexts in each region. One of the potential alternatives to achieve these results would be the use of humic substances, considering their direct and indirect mechanisms aimed at increasing agricultural production. Thus, the objective of this work was to evaluate the bioactivity of humic and fulvic acids, as well as to promote improvements in the phytotechnical attributes of banana cv. Prata-Anã micropropagated. The treatments consisted of five doses of humic acid and fulvic acid (2; 5; 10; 20 and 40 mg L-1) and a control without humic substances. Higher values ​​for the length of the aerial part and the larger root were obtained with the use of 40 mg L-1 fulvic acid. The results prove the ability of fulvic acid to improve the in vitro development of banana explants.
Dynamics of experimental infection with Leptospira serogroup Pomona in different sheep breed
Authors: Costa Diego Figueiredo da , Morais Davidianne de Andrade , Silva Aline Ferreira da , Borges Ismael Lira , Ferreira Jefferson da Silva , Bezerra Camila de Sousa , Pimenta Carla Lauise Rodrigues Menezes , Silva Maria Luana Cristiny Rodrigues , Azevedo Sergio Santos de , Alves Clebert José
Published: February 2021

Most of the information about leptospirosis was obtained from experimental infections with rodents, which in spite of being relevant, do not provide all the answers about the disease in animals and human beings, given the variability of interactions which exist between the agent and the different hosts. Therefore, the objective of the present study was to verify the pathogenesis of the infection in native breeds of sheep of Brazil challenged with a strain of the serogroup Pomona.  A total of 10 sheep were divided into two groups with five animals according to the breed. In each group four sheep were challenged by intraperitoneal route with a strain of the serogroup Pomona and one was used as control. Sheep were monitored for 60 days, with collection of blood for serologic diagnosis, as well as vaginal fluid and urine for microbiological and molecular analyses. After this period the animals were submitted to euthanasia and necropsy, with collection of tissues for microbiological, molecular and histopathologic diagnosis. All the challenged sheep presented anti-Leptospira antibodies. Crossbred sheep presented a lower concentration of titers and the antibodies were detected for a shorter period of time when compared to the Santa Inês sheep, with statistical difference in the concentration of the titers on the days 15 (p<0.05), 45 (p<0.05) and 60 (p<0.05) post-infection. There was no significant difference between the groups when comparing the positivity rates of the microscopic agglutination test (MAT) (p>0.05). Eight positive reactions in the urine and vaginal fluid PCR were detected in both groups, being four (50%) in urine and four (50%) in the vaginal fluid, however without statistical difference (p>0.05). In both groups there was a greater proportion of PCR positive samples in kidneys (71.4%) in relation to uterus (28.6%), however without significant difference (p>0.05). There was no significant difference between the groups when comparing the positivity rates of the PCR (p>0.05). The isolation of leptospires from the urine and kidney of a crossbred sheep was possible. Therefore, it is possible that the native sheep, especially the crossbred, may have a relation of resistance with strains of the serogroup Pomona. However the intensity and duration of this relation need to be elucidated and longer-lasting investigations of natural and experimental infections are necessary in order to determine the epidemiological nature of this relation.
Liga Acadêmica de Nutrição Funcional e Esportiva: uma iniciativa para contribuição na formação dos estudantes de Graduação em Nutrição
Authors: Ferreira Wagner Andrade , Sobral Pamela de Aguiar , Leal Paula Mendonça , Brotto Lais Irencio , Schallitz Tatiane , Santana Isabelle
Published: February 2021

A Liga Acadêmica de Nutrição Funcional e Esportiva (LANFE) foi fundada por acadêmicos com propósito de aprimorar o conhecimento teórico-prático sobre nutrição funcional e esportiva. O objetivo deste estudo foi relatar a experiência de criação e implantação de um projeto de extensão da 1ª liga acadêmica (LA) em um curso de nutrição de uma universidade pública do Estado do Rio de Janeiro, discorrer sobre as atividades realizadas e avaliar seu impacto. Trata-se de um estudo quali-quantitativo, descritivo, do tipo relato de experiência da criação e primeiro ano de atividades da liga. Na avaliação de questionários aplicados à comunidade interna e externa da universidade, observou-se que 99,2% dos participantes (n=123) acreditavam na importância da criação de uma LA para o Curso de Nutrição. Quanto às atividades realizadas pela LANFE, 100% dos participantes (n=15) do Workshop de gastronomia funcional sobre cacau consideraram o nível de qualidade do evento como “muito bom”, bem como o suporte às dúvidas e preocupações expostas. Além disso, 85,3% dos participantes do I Simpósio da LANFE (n = 34) demonstraram um grau de satisfação “muito bom”. Desta forma, a liga acadêmica mostrou-se um importante instrumento de ensino e aprendizagem, mobilizando estudantes e profissionais em prol da construção e do compartilhamento de conhecimentos científicos, contribuindo assim, para a formação dos estudantes de graduação em nutrição.
Histological analysis of the tongue, esophagus and crop of Southern Carcará (Polyborus plancus)
Authors: Franzo Vanessa Sobue , Oliveira Leiny Paula de , Viana Ana Carolina Pôssas , Ramos Adriano Tony , Bertolino Jéssica Fernanda , Adorno Barbara Ataide , Araújo Diego Pereira de , Amoroso Lizandra , Vulcani Valcinir Aloisio Scalla
Published: February 2021

The Southern Caracara is a bird of prey, of the family Falconidae, inhabits all the Brazilian territory, they are omnivorous birds adapted for hunting. The digestive system of the predators presents differences in their morphology due to their eating habits. Knowing the importance of the gastrointestinal system, this study aims to carry out a histological study of the tongue, esophagus and the crop of Polyborus plancus. For this purpose, eight avian of both sexes, with different body weights and ages were used, they were euthanized and the organs were collected, fixed, dehydrated and stained with hematoxylin-eosin. It was noted that the tongue has stratified squamous epithelium with mucous glands and with different degrees of keratinization. The esophagus and crop have four well developed muscle layers and mucous glands. Additionally, in the crop there is presence of an adventitious layer that consists of loose connective tissue. We conclude that the tongue, the esophagus and the crop of the Southern Caracara have similar histological organization of several birds like the Pekin Ducks, ostriches, domestic chicken and partridges.
Anatomia encefálica comparativa de primatas humanos e não-humanos: uma revisão
Authors: Pereira Dayane Kelly Sabec , Araújo Eugênio Gonçalves de , Pereira Kleber Fernando , Vulcani Valcinir Aloisio Scalla
Published: February 2021

O estudo anatômico de primatas não-humanos, tem exercido função importante para intervenções clínicas e cirúrgicas em atendimento da medicina veterinária. Sabe-se que o modelo experimental mais conhecido na área científica é a Macaca mulatta, popularmente conhecido como macaco Rhesus e o que a literatura tem demonstrado são novos modelos experimentais que possam suprir estudos sobre o sistema nervoso central, sendo necessário para essas descobertas um aprofundamento maior na área da anatomia comparativa. O objetivo desta revisão de literatura é promover uma visão ampla sobre os aspectos anatômicos do encéfalo de primatas humanos e não-humanos em termos comparativos. Observou-se nesta revisão algumas particularidades em primatas não-humanos referentes ao trajeto dos vasos sanguíneos no encéfalo, assim como a presença de diferentes seios venosos da dura-máter quando comparados ao primata humano. A importância do estudo morfológico no que se refere a anatomia do telencéfalo, assim como os mecanismos de revestimento, irrigação arterial encefálica e drenagem dos seios venosos da dura-máter, possibilita informações sobre a organização encefálica dos primatas não-humanos, dados esses escassos na literatura científica, mas que geram subsídios para compreensão de outras áreas de investigações etológicas e funcionais, quando comparados ao primata humano.
A cultura do sorgo sacarino: revisão
Authors: Oliveira Taniele Carvalho de
Published: February 2021

O sorgo sacarino é uma gramínea de grande importância agrícola, apresenta ciclo anual, colmos eretos e suculentos com teores de açúcares elevados, podendo ser cultivada em regiões tropicais e subtropicais do todo o mundo. A cultura se apresenta como uma das fontes renováveis capaz de contribuir para o aumento na produção de etanol, podendo ser usada como cultura complementar à cana-de-açúcar. Nesse contexto, objetivou-se revisar a literatura disponível sobre as potencialidades de cultivo da cultura do sorgo sacarino. O estudo apresentado é de natureza qualitativa e trata-se de uma revisão de literatura e com objetivos de reunir informações sobre o cultivo e utilização de sorgo sacarino e sintetizá-los em um documento, principalmente para uso didático. Diante das observações e pesquisas realizadas foi possível constatar que apesar do sorgo sacarino apresentar potencial para a produção de etanol, a cultura ainda pouco utilizada no país. Essas pesquisas mostraram que a produção de biocombustíveis está em constante evolução, com isso o cultivo de sorgo sacarino auxiliará no desenvolvimento desse cenário. A avaliação de novas possibilidades com o uso do sorgo sacarino na produção de etanol é estrategicamente importante para o país, pois promove o avanço na geração de conhecimentos, melhoria da qualidade dos produtos e incorporação de processos produtivos de menor impacto ambiental, permitindo o fortalecimento do sistema de produção de etanol, bem como a sua diversificação.
Algesthesia after epileptic seizure
Authors: Mareš J , Rokyta R
Published: February 2021

The consequences of epileptic seizures related to postictal
inhibition in early postictal period include postictal analgesia. We
studied this phenomenon over 96 h following flurothyl-induced
seizures in adult male Wistar rats. Nociception of control (no
seizure) and seizured groups were tested using the plantar and
von Frey hair tests. We determined latency of forepaw and hind
paw reactions using plantar tests and the number of von Frey
hairs reactions. Shortly after seizures, longer plantar test
latencies were seen relative to the control group. Before the
seizures the plantar test reaction times were significantly shorter
in forepaws than in hind paws. The effect disappeared postseizure and surprisingly, it also disappeared at the corresponding
time in controls; it reappeared after 48 h in the seizure group
and after 24 h in controls. Differences in the von Frey hairs test
occurred at 5 and 60 min post-seizure, however, these
differences could not be explained by limb anatomy; although,
different thermal and mechanical nociception mechanisms could
be significant. The unexpected reactions in controls could be
related to brief social and physical interactions between the two
groups.
A non-invasive method for detecting the metabolic stress response in rodents: characterization and disruption of the circadian corticosterone rhythm
Authors: Thanos PK , Cavigelli SA , Michaelides M , Olvet DM , Patel U , Diep MN , Volkow ND
Published: February 2021

Plasma corticosterone (CORT) measures are a common
procedure to detect stress responses in rodents. However, the
procedure is invasive and can influence CORT levels, making it
less than ideal for monitoring CORT circadian rhythms. In the
current paper, we examined the applicability of a non-invasive
fecal CORT metabolite measure to assess the circadian rhythm.
We compared fecal CORT metabolite levels to circulating CORT
levels, and analyzed change in the fecal circadian rhythm
following an acute stressor (i.e. blood sampling by tail veil
catheter). Fecal and blood samples were collected from male
adolescent rats and analyzed for CORT metabolites and
circulating CORT respectively. Fecal samples were collected
hourly for 24 h before and after blood draw. On average, peak
fecal CORT metabolite values occurred 7-9 h after the plasma
CORT peak and time-matched fecal CORT values were well
correlated with plasma CORT. As a result of the rapid blood
draw, fecal production and CORT levels were altered the next
day. These results indicate fecal CORT metabolite measures can
be used to assess conditions that disrupt the circadian CORT
rhythm, and provide a method to measure long-term changes in
CORT production. This can benefit research that requires longterm glucocorticoid assessment (e.g. stress mechanisms
underlying health).
Spreading of Helminths Detected in Private Poultry Farms by Regions of Azerbaijan
Authors: Bairamov S.
Published: February 2021

Of the helminths detected during these studies, the intensity of the invasions with Ascaridia galli in the Aran region, Heterakis gallinarum — on the Absheron, Syngamus trachea, Capillaria obsignata — in Lankaran-Astara, Raillietina tetragona — in Kuba-Khachmaz, and on the basis of studies carried out during autopsy of carcasses the intensity of invasions with heterakises, railietins in the Aran region, Ascaridia in Kuba-Khachmaz, and with singamuses and capillaries in Lankaran-Astara was high. Along with the fact that in the summer period there was observed high extensiveness and intensity of invasions among the studies carried out by seasons of the year, the prevalence of Ascaridia, heterakises, singamuses in Sheki-Zagatala region, railietins in Kuba-Khachmaz, and capillaries in Lankaran–Astara in comparison with other regions was high. The intensity of the invasions with Ascaridia in Kuba-Khachmaz, heterakises, singamuses, railietins, and capillaries in Aran came up to a high level.
Обмежена осудність: перспективи вдосконалення законодавчої регламентації
Authors: Зайцев O.B.
Published: February 2021

З урахуванням досягнутого рівня науки кримінального права та судової психіатрії проведено аналіз положень про обмежену осудність у проекті КК України. Висловлено додаткові аргументи на користь визнання медичним критерієм виключно психічних розладів. Запропоновано змінити підхід у визначені психологічного критерію. Приділено увагу факультативному значенню обмеженої осудності при пом’якшенні покарання. Звернуто увагу на неприйнятності збереження примусової психіатричної допомоги до цієї категорії злочинців.
Реформа системи органів міського самоврядування на території Галичини в другій половині ХІХ століття
Authors: Бутирін Є. О.
Published: February 2021

У статті здійснено історико-правовий аналіз реформи міського самоврядування на території Галичини в другій половині ХІХ століття. Зроблені висновки, що в заможних громад таких крупних міст, як: Дрогобич, Коломия, Краків, Львів, Станіслав, Стрий, Тернопіль ‒ можливостей для реалізації власних потенцій було більше, утім і маленькі міста та містечка, отримавши право на залишення у своєму розпорядженні частини прибутків і податків та дбайливого їх використання для власних потреб, отримали відчутний ефект. Навіть попри те що система гмінного самоврядування мала свої недоліки, громади ставали заможнішими, їх можливості зростали, а громадська діяльність в органах місцевого самоврядування виявлялася корисною школою суспільного життя.
Ґенеза адміністративно-правового забезпечення житлового будівництва в Україні (з часів існування СРСР і до сьогодні)
Authors: Тарасюк Ю.В.
Published: February 2021

Стаття присвячена здійсненню історико-правового аналізу становлення та розвитку адміністративно-правового забезпечення житлового будівництва в Україні з часів існування СРСР в і до сьогодні. Обґрунтовано, що за роки панування в Україні радянського режиму було сформовано досить розгалужену систему нормативно-правових актів із питань будівництва, що складалася із загальносоюзних та республіканських актів, деякі з яких є і досі чинними. Під час аналізу сучасного етапу розвитку адміністративно-правового забезпечення будівельної сфері було з’ясовано, що основним питанням, яке слід вирішити законодавцю, є забезпечення здійснення систематизації законодавства у вказаній сфері, з метою його приведення у єдину, злагоджену систему з чітко виз наченим стрижневим галузевим Законом.
Правове забезпечення екологічного відновлення міст на постконфліктних територіях
Authors: Трегуб О.А.
Published: February 2021

Стаття присвячена обґрунтуванню пропозицій щодо вдосконалення правового забезпечення екологічного відновлення міст на постконфліктних територіях. Для зменшення обсягів накопичення на цих територіях небезпечних відходів витрати на їх перевезення до місць утилізації запропоновано тимчасово фінансувати за рахунок бюджетних коштів. Аргументовано, що застосування принципу наближеності до джерел утворення відходів потребує обмеження щодо зон, які прилягають до лінії розмежування та перебувають під загрозою ураження внаслідок бойових дій. Запропоновано визначити особливості моніторингу довкілля на постконфліктних територіях iз використанням космічних технологій.
Сучасний стан та проблеми розслідування злочинів у сфері фінансових ресурсів держави
Authors: Комишнюк Ю. О.
Published: February 2021

Стаття присвячена проблемним питанням організації розслідування злочинів у сфері фінансових ресурсів держави, що потребують відповідних знань у галузі економіки, оподаткування, бухгалтерського обліку тощо. З урахуванням потреб практики розслідування злочинів та ґрунтуючись на статистичних даних правоохоронних органів, наведено низку факторів як об’єктивного, так і суб’єктивного характеру, що впливають на ефективність організації розслідування таких злочинів; запропоновано можливі напрями їх вирішення. Наголошується на необхідності підбору якісного кадрового складу, який здатен розслідувати такі кримінальні правопорушення, його належної підготовки й підвищення кваліфікації.
Актуальне дослідження проблем теорії та практики кримінального процесуального доказування при застосуванні заходів забезпечення кримінального провадження слідчим суддею та судом
Authors: Лоскутов Т.О.
Published: February 2021

Рецензія підготовлена на монографію «Особливості доказування при за-стосуванні заходів забезпечення кримінального провадження слідчим суддею та судом: теорія і практика», автором якої є кандидат юридичних наук, старший викладач кафедри кримінального процесу, детективної та оперативно-розшукової діяльності Національного університету «Одеська юридична академія». У монографії розкрито питання щодо рішення про застосування заходів забезпечення кримінального провадження в системі кримінально-процесуальних актів, кримінального процесуального доказування при розгляді слідчим суддею клопотань про застосування заходів забезпечення кримі-нального провадження в досудовому провадженні, особливостей доказування при застосуванні заходів забезпечення кримінального провадження в судовому провадженні.
SOME CLASSES OF q-ANALYTIC FUNCTIONS AND THE q-GREEN'S FORMULA
Authors: GENÇTÜRK İlker , HÖKELEKLİ Şermin , KOCA Kerim
Published: February 2021

In this paper, we first give two new definitions for q-analytic functions. We also define a new line q-integral. Finally, using these q-integrals we obtain a version of complex q-Green's formula.
Case Study: Influence of Three Gorges Reservoir Impoundment on Hydrological Regime of the Acipenser sinensis Spawning Ground, Yangtze River, China
Authors: Zhou Yinjun , Li Zhijing , Yao Shiming , Shan Miner , Guo Chao
Published: February 2021

After the construction of the Three Gorges Dam (TGD) in China, the downstream has been affected by the reduction in sediment discharge and regulation of flow processes, which have resulted in severe scouring and changes hydrological regime. Consequently, the spawning ground of Chinese sturgeon distributed along the downstream Yichang reach could be affected. This study examined the effects of TGD on the streamflow, sediment load and channel morphology downstream based on in situ measured data. Results showed that, after the impoundment of the TGD, sediment load at the downstream Yichang hydrological station decreased significantly, and the Yichang reach continued to be scoured. The distribution of erosion was uneven, and the scouring mainly occurred in the branching channels. The channel gradient and riverbed roughness increased with the erosion of the river cross section. After more than 10 years of erosion, the riverbed scouring and armouring in the Yichang reach was basically completed, thus we expected that the spawning grounds of Chinese sturgeon could be retain as the riverbed tends to be stable. The findings in this work have implications in the protection of the critically endangered Chinese sturgeon.
Crossed Entorhino-Dentate Projections Form and Terminate With Correct Layer-Specificity in Organotypic Slice Cultures of the Mouse Hippocampus
Authors: Hildebrandt-Einfeldt Lars , Yap Kenrick , Paul Mandy H. , Stoffer Carolin , Zahn Nadine , Drakew Alexander , Lenz Maximilian , Vlachos Andreas , Deller Thomas
Published: February 2021

The entorhino-dentate projection, i.e., the perforant pathway, terminates in a highly ordered and laminated fashion in the rodent dentate gyrus (DG): fibers arising from the medial entorhinal cortex (MEC) terminate in the middle molecular layer, whereas fibers arising from the lateral entorhinal cortex (LEC) terminate in the outer molecular layer of the DG. In rats and rabbits, a crossed entorhino-dentate projection exists, which originates from the entorhinal cortex (EC) and terminates in the contralateral DG. In contrast, in mice, such a crossed projection is reportedly absent. Using single and double mouse organotypic entorhino-hippocampal slice cultures, we studied the ipsi- and crossed entorhino-dentate projections. Viral tracing revealed that entorhino-dentate projections terminate with a high degree of lamina-specificity in single as well as in double cultures. Furthermore, in double cultures, entorhinal axons arising from one slice freely intermingled with entorhinal axons originating from the other slice. In single as well as in double cultures, entorhinal axons exhibited a correct topographical projection to the DG: medial entorhinal axons terminated in the middle and lateral entorhinal axons terminated in the outer molecular layer. Finally, entorhinal neurons were virally transduced with Channelrhodopsin2-YFP and stimulated with light, revealing functional connections between the EC and dentate granule cells. We conclude from our findings that entorhino-dentate projections form bilaterally in the mouse hippocampus in vitro and that the mouse DG provides a permissive environment for crossed entorhinal fibers.
Prognostic and Predictive Value of Integrated Qualitative and Quantitative Magnetic Resonance Imaging Analysis in Glioblastoma
Authors: Verduin Maikel , Primakov Sergey , Compter Inge , Woodruff Henry C. , van Kuijk Sander M. J. , Ramaekers Bram L. T. , te Dorsthorst Maarten , Revenich Elles G. M. , ter Laan Mark , Pegge Sjoert A. H. , Meijer Frederick J. A. , Beckervordersandforth Jan , Speel Ernst Jan , Kusters Benno , de Leng Wendy W. J. , Anten Monique M. , Broen Martijn P. G. , Ackermans Linda , Schijns Olaf E. M. G. , Teernstra Onno , Hovinga Koos , Vooijs Marc A. , Tjan-Heijnen Vivianne C. G. , Eekers Danielle B. P. , Postma Alida A. , Lambin Philippe , Hoeben Ann
Published: February 2021

Glioblastoma (GBM) is the most malignant primary brain tumor for which no curative treatment options exist. Non-invasive qualitative (Visually Accessible Rembrandt Images (VASARI)) and quantitative (radiomics) imaging features to predict prognosis and clinically relevant markers for GBM patients are needed to guide clinicians. A retrospective analysis of GBM patients in two neuro-oncology centers was conducted. The multimodal Cox-regression model to predict overall survival (OS) was developed using clinical features with VASARI and radiomics features in isocitrate dehydrogenase (IDH)-wild type GBM. Predictive models for IDH-mutation, 06-methylguanine-DNA-methyltransferase (MGMT)-methylation and epidermal growth factor receptor (EGFR) amplification using imaging features were developed using machine learning. The performance of the prognostic model improved upon addition of clinical, VASARI and radiomics features, for which the combined model performed best. This could be reproduced after external validation (C-index 0.711 95% CI 0.64–0.78) and used to stratify Kaplan–Meijer curves in two survival groups (p-value < 0.001). The predictive models performed significantly in the external validation for EGFR amplification (area-under-the-curve (AUC) 0.707, 95% CI 0.582–8.25) and MGMT-methylation (AUC 0.667, 95% CI 0.522–0.82) but not for IDH-mutation (AUC 0.695, 95% CI 0.436–0.927). The integrated clinical and imaging prognostic model was shown to be robust and of potential clinical relevance. The prediction of molecular markers showed promising results in the training set but could not be validated after external validation in a clinically relevant manner. Overall, these results show the potential of combining clinical features with imaging features for prognostic and predictive models in GBM, but further optimization and larger prospective studies are warranted.
Interplay between the Gut Microbiota and Inflammatory Mediators in the Development of Colorectal Cancer
Authors: Heo Gwangbeom , Lee Yunna , Im Eunok
Published: February 2021

Inflammatory mediators modulate inflammatory pathways during the development of colorectal cancer. Inflammatory mediators secreted by both immune and tumor cells can influence carcinogenesis, progression, and tumor metastasis. The gut microbiota, which colonize the entire intestinal tract, especially the colon, are closely linked to colorectal cancer through an association with inflammatory mediators such as tumor necrosis factor, nuclear factor kappa B, interleukins, and interferons. This association may be a potential therapeutic target, since therapeutic interventions targeting the gut microbiota have been actively investigated in both the laboratory and in clinics and include fecal microbiota transplantation and probiotics.
Adoptive Immunotherapy beyond CAR T-Cells
Authors: Titov Aleksei , Zmievskaya Ekaterina , Ganeeva Irina , Valiullina Aygul , Petukhov Alexey , Rakhmatullina Aygul , Miftakhova Regina , Fainshtein Michael , Rizvanov Albert , Bulatov Emil
Published: February 2021

Adoptive cell immunotherapy (ACT) is a vibrant field of cancer treatment that began progressive development in the 1980s. One of the most prominent and promising examples is chimeric antigen receptor (CAR) T-cell immunotherapy for the treatment of B-cell hematologic malignancies. Despite success in the treatment of B-cell lymphomas and leukemia, CAR T-cell therapy remains mostly ineffective for solid tumors. This is due to several reasons, such as the heterogeneity of the cellular composition in solid tumors, the need for directed migration and penetration of CAR T-cells against the pressure gradient in the tumor stroma, and the immunosuppressive microenvironment. To substantially improve the clinical efficacy of ACT against solid tumors, researchers might need to look closer into recent developments in the other branches of adoptive immunotherapy, both traditional and innovative. In this review, we describe the variety of adoptive cell therapies beyond CAR T-cell technology, i.e., exploitation of alternative cell sources with a high therapeutic potential against solid tumors (e.g., CAR M-cells) or aiming to be universal allogeneic (e.g., CAR NK-cells, γδ T-cells), tumor-infiltrating lymphocytes (TILs), and transgenic T-cell receptor (TCR) T-cell immunotherapies. In addition, we discuss the strategies for selection and validation of neoantigens to achieve efficiency and safety. We provide an overview of non-conventional TCRs and CARs, and address the problem of mispairing between the cognate and transgenic TCRs. Finally, we summarize existing and emerging approaches for manufacturing of the therapeutic cell products in traditional, semi-automated and fully automated Point-of-Care (PoC) systems.
PD-L1 Expression after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancers Is Associated with Aggressive Residual Disease, Suggesting a Potential for Immunotherapy
Authors: Grandal Beatriz , Mangiardi-Veltin Manon , Laas Enora , Laé Marick , Meseure Didier , Bataillon Guillaume , El-Alam Elsy , Darrigues Lauren , Dumas Elise , Daoud Eric , Vincent-Salomon Anne , Talagrand Laure-Sophie , Pierga Jean-Yves , Reyal Fabien , Hamy Anne-Sophie
Published: February 2021

The consequences of neoadjuvant chemotherapy (NAC) for PD-L1 activity in triple-negative breast cancers (TNBC) are not well-understood. This is an important issue as PD-LI might act as a biomarker for immune checkpoint inhibitors’ (ICI) efficacy, at a time where ICI are undergoing rapid development and could be beneficial in patients who do not achieve a pathological complete response. We used immunohistochemistry to assess PD-L1 expression in surgical specimens (E1L3N clone, cutoff for positivity: ≥1%) on both tumor (PD-L1-TC) and immune cells (PD-L1-IC) from a cohort of T1-T3NxM0 TNBCs treated with NAC. PD-L1-TC was detected in 17 cases (19.1%) and PD-L1-IC in 14 cases (15.7%). None of the baseline characteristics of the tumor or the patient were associated with PD-L1 positivity, except for pre-NAC stromal TIL levels, which were higher in post-NAC PD-L1-TC-positive than in negative tumors. PD-L1-TC were significantly associated with a higher residual cancer burden (p = 0.035) and aggressive post-NAC tumor characteristics, whereas PD-L1-IC were not. PD-L1 expression was not associated with relapse-free survival (RFS) (PD-L1-TC, p = 0.25, and PD-L1-IC, p = 0.95) or overall survival (OS) (PD-L1-TC, p = 0.48, and PD-L1-IC, p = 0.58), but high Ki67 levels after NAC were strongly associated with a poor prognosis (RFS, p = 0.0014, and OS, p = 0.001). A small subset of TNBC patients displaying PD-L1 expression in the context of an extensive post-NAC tumor burden could benefit from ICI treatment after standard NAC.
Synergistic Impact of Alpha-Fetoprotein and Tumor Burden on Long-Term Outcomes Following Curative-Intent Resection of Hepatocellular Carcinoma
Authors: Tsilimigras Diamantis I. , Hyer J. Madison , Diaz Adrian , Bagante Fabio , Ratti Francesca , Marques Hugo P. , Soubrane Olivier , Lam Vincent , Poultsides George A. , Popescu Irinel , Alexandrescu Sorin , Martel Guillaume , Workneh Aklile , Guglielmi Alfredo , Hugh Tom , Aldrighetti Luca , Endo Itaru , Pawlik Timothy M.
Published: February 2021

Introduction: The prognostic role of tumor burden score (TBS) relative to pre-operative α -fetoprotein (AFP) levels among patients undergoing curative-intent resection of HCC has not been examined. Methods: Patients who underwent curative-intent resection of HCC between 2000 and 2017 were identified from a multi-institutional database. The impact of TBS on overall survival (OS) and cumulative recurrence relative to serum AFP levels was assessed. Results: Among 898 patients, 233 (25.9%) patients had low TBS, 572 (63.7%) had medium TBS and 93 (10.4%) had high TBS. Both TBS (5-year OS; low TBS: 76.9%, medium TBS: 60.9%, high TBS: 39.1%) and AFP (>400 ng/mL vs. <400 ng/mL: 48.5% vs. 66.1%) were strong predictors of outcomes (both p < 0.001). Lower TBS was associated with better OS among patients with both low (5-year OS, low–medium TBS: 68.0% vs. high TBS: 47.7%, p < 0.001) and high AFP levels (5-year OS, low–medium TBS: 53.7% vs. high TBS: not reached, p < 0.001). Patients with low–medium TBS/high AFP had worse OS compared with individuals with low–medium TBS/low AFP (5-year OS, 53.7% vs. 68.0%, p = 0.003). Similarly, patients with high TBS/high AFP had worse outcomes compared with patients with high TBS/low AFP (5-year OS, not reached vs. 47.7%, p = 0.015). Patients with high TBS/low AFP and low TBS/high AFP had comparable outcomes (5-year OS, 47.7% vs. 53.7%, p = 0.24). The positive predictive value of certain TBS groups relative to the risk of early recurrence and 5-year mortality after HCC resection increased with higher AFP levels. Conclusion: Both TBS and serum AFP were important predictors of prognosis among patients with resectable HCC. Serum AFP and TBS had a synergistic impact on prognosis following HCC resection with higher serum AFP predicting worse outcomes among patients with HCC of a certain TBS class.
Whole-Genome Sequencing of Retinoblastoma Reveals the Diversity of Rearrangements Disrupting RB1 and Uncovers a Treatment-Related Mutational Signature
Authors: Davies Helen R. , Broad Kevin D. , Onadim Zerrin , Price Elizabeth A. , Zou Xueqing , Sheriff Ibrahim , Karaa Esin Kotiloğlu , Scheimberg Irene , Reddy M. Ashwin , Sagoo Mandeep S. , Ohnuma Shin-ichi , Nik-Zainal Serena
Published: February 2021

The development of retinoblastoma is thought to require pathological genetic changes in both alleles of the RB1 gene. However, cases exist where RB1 mutations are undetectable, suggesting alternative pathways to malignancy. We used whole-genome sequencing (WGS) and transcriptomics to investigate the landscape of sporadic retinoblastomas derived from twenty patients, sought RB1 and other driver mutations and investigated mutational signatures. At least one RB1 mutation was identified in all retinoblastomas, including new mutations in addition to those previously identified by clinical screening. Ten tumours carried structural rearrangements involving RB1 ranging from relatively simple to extremely complex rearrangement patterns, including a chromothripsis-like pattern in one tumour. Bilateral tumours obtained from one patient harboured conserved germline but divergent somatic RB1 mutations, indicating independent evolution. Mutational signature analysis showed predominance of signatures associated with cell division, an absence of ultraviolet-related DNA damage and a profound platinum-related mutational signature in a chemotherapy-exposed tumour. Most RB1 mutations are identifiable by clinical screening. However, the increased resolution and ability to detect otherwise elusive rearrangements by WGS have important repercussions on clinical management and advice on recurrence risks.
miR-582-5p Is a Tumor Suppressor microRNA Targeting the Hippo-YAP/TAZ Signaling Pathway in Non-Small Cell Lung Cancer
Authors: Zhu Bowen , V Mitheera , Finch-Edmondson Megan , Lee Yaelim , Wan Yue , Sudol Marius , DasGupta Ramanuj
Published: February 2021

The Hippo-YAP/TAZ signaling pathway is an evolutionarily conserved signaling pathway involved in a broad spectrum of biological processes, including tumorigenesis. Whilst aberrant Hippo-YAP/TAZ signaling is frequently reported in various cancers, the genetic alterations of this pathway are relatively rare, suggesting regulation at the post-transcriptional level. MicroRNAs play key role in tumorigenesis by regulating gene expression post-transcriptionally. Amongst the cancer-relevant microRNAs, miR-582-5p suppresses cell growth and tumorigenesis by inhibiting the expression of oncogenes, including AKT3, MAP3K2 and NOTCH1. Given the oncogenic role of YAP/TAZ in solid tumors, we scrutinized the possible interplay between miR-582-5p and Hippo-YAP/TAZ signaling. Correlation analysis in NSCLC cells revealed a positive relationship between the expression of mature miR-582-5p and the proportion of phosphorylated YAP/TAZ. Intriguingly, YAP/TAZ knockdown reduced the expression of mature miR-582-5p but increased that of primary miR-582. Overexpression of miR-582-5p resulted in increased phosphorylation of YAP/TAZ with a concomitant reduction in cell proliferation and enhanced apoptosis. Mechanistically, we find that miR-582-5p targets actin regulators NCKAP1 and PIP5K1C, which may be responsible for the observed alteration in F-actin, known to modulate YAP/TAZ. We postulate that regulation of the actin cytoskeleton by miR-582-5p may attenuate YAP/TAZ activity. Altogether, this study reveals a novel mechanism of YAP/TAZ regulation by miR-582-5p in a cytoskeleton-dependent manner and suggests a negative feedback loop, highlighting the therapeutic potential of restoring miR-582-5p expression in treating NSCLC.
Dedicated Axillary MRI-Based Radiomics Analysis for the Prediction of Axillary Lymph Node Metastasis in Breast Cancer
Authors: Samiei Sanaz , Granzier Renée W. Y. , Ibrahim Abdalla , Primakov Sergey , Lobbes Marc B. I. , Beets-Tan Regina G. H. , van Nijnatten Thiemo J. A. , Engelen Sanne M. E. , Woodruff Henry C. , Smidt Marjolein L.
Published: February 2021

Radiomics features may contribute to increased diagnostic performance of MRI in the prediction of axillary lymph node metastasis. The objective of the study was to predict preoperative axillary lymph node metastasis in breast cancer using clinical models and radiomics models based on T2-weighted (T2W) dedicated axillary MRI features with node-by-node analysis. From August 2012 until October 2014, all women who had undergone dedicated axillary 3.0T T2W MRI, followed by axillary surgery, were retrospectively identified, and available clinical data were collected. All axillary lymph nodes were manually delineated on the T2W MR images, and quantitative radiomics features were extracted from the delineated regions. Data were partitioned patient-wise to train 100 models using different splits for the training and validation cohorts to account for multiple lymph nodes per patient and class imbalance. Features were selected in the training cohorts using recursive feature elimination with repeated 5-fold cross-validation, followed by the development of random forest models. The performance of the models was assessed using the area under the curve (AUC). A total of 75 women (median age, 61 years; interquartile range, 51–68 years) with 511 axillary lymph nodes were included. On final pathology, 36 (7%) of the lymph nodes had metastasis. A total of 105 original radiomics features were extracted from the T2W MR images. Each cohort split resulted in a different number of lymph nodes in the training cohorts and a different set of selected features. Performance of the 100 clinical and radiomics models showed a wide range of AUC values between 0.41–0.74 and 0.48–0.89 in the training cohorts, respectively, and between 0.30–0.98 and 0.37–0.99 in the validation cohorts, respectively. With these results, it was not possible to obtain a final prediction model. Clinical characteristics and dedicated axillary MRI-based radiomics with node-by-node analysis did not contribute to the prediction of axillary lymph node metastasis in breast cancer based on data where variations in acquisition and reconstruction parameters were not addressed.