bluuebunny/crossref_metadata_2025 huggingface dataset:
Managing the shortage: A quantitative-qualitative study on the scale and effects of the severe lack in sign language interpreting resource in the German market
Authors: Maaß Laura Marie
Published: December 2024

This study provides an insight into the extent of the shortage of sign language interpreters in Germany and the impact this has on the co-operation and workflows between hearing sign language interpreters and their deaf clients. There is a considerable lack in sign language interpreters in Germany; on average, each deaf person can only receive around 18 hours of interpreting services per year. In the context of growing demands for participation and inclusion, for example in education, and the accessibility of events of all kinds, we see a growing tension between the two groups. With almost 800 respondents, this study provides insight in the relationship between hearing sign language interpreters and their deaf clients. It focusses on various application scenarios and shows, among other things, that the shortage is currently reflected in the area of acute medical emergencies and that the current free market will not cover this shortage.
TÍNH DỰ BÁO TRONG THI PHÁP KỊCH ALFRED DE MUSSET
Authors: Phạm Duy Khuê
Published: December 2024

Thường thì hiện thực nào, nghệ thuật ấy. Nhưng nghệ thuật phản ánh hiện thực không giống như chiếc gương soi “viết tô” đời sống, mà thông qua lăng kính chủ quan của nghệ sĩ. Nghệ sĩ thực hiện “nhào nặn”, khái quát hoá, điển hình hoá nội dung vấn đề hiện thực được phản ánh theo cảm thức, suy cảm, hưng phấn thẩm mỹ từ những quan điểm cá nhân của mình. Nói cách khác, nghệ sĩ phản ánh hiện thực bởi thi pháp nghệ thuật của mình. Sáng tác kịch của Alfred de Musset không ngoài những vấn đề có tính lý luận chung này. Song, điều đáng nói, đó là cái riêng - “tính dự báo” trong thi pháp nghệ thuật kịch của ông.
Lipova în timpul lui Gabriel Báthory (1608-1613)
Authors:   Complexul Muzeal Arad, Bulboacă Sorin Ovidiu
Published: December 2024

The article aims to present, based on the investigation of sources and specialized literature, the evolution of Lipova from a social and political point of view in the years 1608–1613, during the reign of the prince of Transylvania, Gabriel Báthory (1608–1613), a controversial personality but who paid special attention to the city of Lipova. Prince Gabriel Báthory was concerned about the situation of the city of Lipova, an important strategic point in the Mureș valley, which prospered in the years 1608–1613. The center of Arad county during these years was in Lipova. In 1608 and 1611 Gabriel Báthory reconfirmed the privileges of the city of Lipova but did not take serious measures regarding the restoration and strengthening of Lipova’s fortifications. As early as 1612, a pretender to the princely throne – Andrei Géczy – promised the Turks that he would cede the fortress and the city of Lipova to them. The gate even asks the sitting prince – Gabriel Báthory – to give up the border fortresses of Lipova, Ineu and Caransebeș in favor of the Turks. The maintenance of Lipova within the borders of the Principality of Transylvania becomes uncertain in 1613 in the context in which Gabriel Bethlen, the new pretender to the throne and later prince, promises the sultan to hand over Lipova.
Le domaine de Maisons sur Seine et ses constructions d’origine
Authors:   Centre des Monuments Nationaux, France, Ember Andreea
Published: December 2024

The estate of Maisons-sur-Seine, inherited by René de Longueil in 1629, became one of the most beautiful in France thanks to the construction of a new castle, entrusted to François Mansart. This vast property included several pavilions, stables, moats, and beautifully landscaped gardens. The monumental entrances, ornate iron gates, and decorated retaining walls testified to the elegance and wealth of the estate. The gardens, celebrated by poets, featured long perspectives and refined plantings. René expanded the estate by purchasing adjacent fiefs, creating a vast territory almost surrounding the royal domain of Saint-Germain. He made Maisons-sur-Seine a luxurious residence, hosting the king and the court. The château, richly furnished and adorned with works of art, reflected his taste for tapestries, porcelains, and orange trees. Powerful and influential, René de Longueil made Maisons-sur-Seine a symbol of his status and refinement, passing on an important heritage and the title of marquis to his descendants.
Considerații privind studenții Facultății de Drept din București în perioada 1864-1918
Authors:   Facultatea de Istorie, Universitatea din București, Gudin Cristina
Published: December 2024

Since its inception, the Faculty of Law at the University of Bucharest enrolled the largest number of students compared to the rest of the faculties in the mentioned period and benefited from the most consistent teaching staff. The constant increase in the number of students represented evidence of the increasingly pronounced interest in legal studies, a fact that justified the expansion of the educational offer in order to train the most competent specialists. This material focuses on the particularities of the students, but tangentially also takes into account the changes recorded in terms of educational offer, material endowments or involvement in political life. As expected, the quality of being a student, even at the most attractive faculty, was accompanied by challenges that resulted both from the high standards set by the professors, but also from the way in which aspects such as political-military events or economic evolution interfered with the dynamics of the institution and the instructional process itself.
Si vis pacem para belum!
Apărarea pasivă a orașului Alba Iulia în perioada interbelică
Authors:   Muzeul Național al Unirii Alba Iulia, Mircea Ionela Simona
Published: December 2024

In the interwar period, the defense of the countryʼs territorial integrity against Hungaryʼs vindictive tendencies required the Romanian government to adopt a firm position in the League of Nations. Internally action were taken in the direction of strengthening and equipping in the Romanian Army with military equipment, with border defense projects and plans being developed. Also, measures were taken to organize the territory and prepare the population for the eventuality of a war. In the Alba Iulia Citty Hall, a special office was organized whose object of activity was the passive defense of the city. Between 1936-1949, the office operated based on the instructions of the Directorate of the Office of Mobilization and Organization of the Nation Territory, within the Ministry of the Interior. After the elaboration of the Regulation for the apllication of the administrative law of November 18, 1939, the MONT Office became a service. Since the establishment of the MONT Office, the pasive defense of the city has represented an important segment in the activity of the local administration, the foreshadowing of a new war imposing the need to prepare the population and the city in this regarde.
Istoricul Baroului Hunedoara
Authors:   Muzeul Civilizației Dacice și Romane Deva, Boda Gherghina
Published: December 2024

The legal phenomenon has accompanied human society at all stages of its development, which has required the establishment of specific bodies to regulate people’s misconduct, as well as punitive means associated with each violation of social rules. Each historical period is characterized by a legal system that met the requirements of the time and that, like society, has been constantly perfected and improved. Bars appeared in the second period of the 19th century, first in Bucharest, then in Iași, Dolj-Jiu, and in Deva in 1923.
Ripensia în Divizia Naţională (1932-1933)
Authors:   Facultatea de Litere, Istorie, Teologie, Universitatea de Vest din Timişoara, Narai Eusebiu
Published: December 2024

Journalists from the West analyzed, pertinently, the preliminary draft of the National Division, constituted according to the Italian model, preliminary draft sent by the Federal Office to the profile leagues in the country. Ripensia has maintained its practice of organizing several friendly matches before international matches. In the pages of the Banat daily, the actions of some groups from Oradea (C.A.O., Crişana) and Bucharest (C.F.R., Macabi) to illegally ,,borrow” players of a certain value, taking advantage of certain provisions of the regulation regarding the certification of players, were also captured. Before the tournament in France, Ripensia was forced to acquire experienced players who came either from other teams from Timişoara, such as Kadima or R.G.M.T., or from the renowned Cluj team University. The participation of Ripensia in the National Division required the granting of a separate regime to the professional teams, which would allow the team from Timişoara to cover the financial deficit. In 1932, there were quite dangerous value fluctuations of the Ripensia team in the matches played in the National Division. Many times, the technicality of the professional team from the city of Timişoara was not enough to defeat the aggressive and fast game of some teams from Bucharest. Unfortunately, many times, through various methods, the initiators of the National Division protected the clubs from the Capital, a fact that deeply displeased the management of the Ripensia club and generated vehement criticism in the pages of the daily the West. The quality of Ripensias matches sometimes depended on refereeing errors or the hostile atmosphere created by other teams. At the end of 1932, there was an interpenetration of political and sports life, at least at the football level. In 1932, Ripensia also participated in the Hutchinson Cup, but its results were below expectations, because the team was not sufficiently welded following the latest changes in the official team. In 1933, Ripensia won most of the matches played, achieving an impressive goal difference, thanks to the stability of the team and the maintenance of the style of play. Almost every time they lined up: Zombory-Bürger, Hoksary-Deheleanu, Kotormany, Lakatos II-Bindea, Al. Schwartz, Ciolac, Raffinsky, Dobay. The practice of friendly, domestic and international matches, as well as participation in the Hutchinson Cup, continued. The amendment of the sports legislation allowed the recovery of Ripensia's income. King Carol II was among Ripensia's ardent fans. In the middle of November 1933, the rules for legitimizing the players were radically changed, drawing a ,,red line” between amateurism and professionalism, with beneficial effects on Ripensia.'
Amatorismul cultural ca tip de conservare a identității naționale a românilor din Serbia
(1945-1952)
Authors:   Școala de Studii Înalte pentru Educatori „Mihailo Palov”, Vârșeț, Serbia, Măran Mircea
Published: December 2024

The first post-war years caused major changes in the cultural movement of Romanians in the Yugoslav Banat, which primarily consisted in the introduction of ideological content in all cultural activities at the country level. Even before the end of the war, the new communist authorities tried to neutralize the influence of the Romanian Orthodox Church and all pre-war factors, especially the ASTRA association from the Yugoslav Banat, which they considered a collaborator of the German occupation regime during the Second World War II. In order to introduce new ideological contents and direct the cultural development of Romanians in the direction proposed by the communist regime, the agitrpop apparatus took a series of measures to use the cultural movement of Romanians from Banat in the interests of the new authorities, with the main aim of including Romanians in the new order that was being formed. They tried to achieve this by establishing the Cultural Union of Romanians, in 1945, and from 1948 all cultural activities came under the control of the Union of Cultural-Instructive Societies of Voivodina – Section for Romanians.
Grebenaţ – sat păstrător al tradițiilor românilor din Banatul Sârbesc
Authors:   Casa de Presă și Editura Libertatea, Panciova, Serbia, Petroi Adriana
Published: December 2024

One of the most specific localities in the Serbian Banat, with an ancient autochthonous population, is the village of Grebenaț, found near the town of Biserica Albă (Bela Crkva). In the Middle Ages, this settlement, together with the surrounding settlements, belonged to the Wallachian Haram district, proof of the antiquity of the Romanian population in this geographical space. In the 18th century, the number of inhabitants increased through colonization, Grebenațul preserving its specificity among Romanians from the Serbian Banat in speech, customs and port. In this locality there is the oldest Romanian church building in the Serbian Banat and one of the oldest in general in this geographical area, dating back to 1722. The most specific traditional custom, which continues to this day, is the, during which the ancient dance of the gaggles takes place.
Mind-Body Interactıon
Authors:   Department of Anesthesiology and Intensive Care, Pain Medicine, Traditional and Complementary Medicine, Tekirdag Namik Kemal University, Turkey, Mordeniz Cengiz
Published: December 2024

The human mind–body possesses an innate ability, based upon the
evolutionarily conserved brain and body systems to promote health
and healing. Since there is a bidirectional influence of psychological
and physiological variables on health, modern allopathic medicine,
that addresses the disease in the body and disorder in the mind,
should be reconceptualized for more holistic wellness. The mind-body
dualism is re-evaluated in the light of different scientific findings such
as energy and electromagnetic wave, information, quantum theories,
and placebo effect.
USO RACIONAL Y EFICIENTE DE LA ENERGÍA PARA ILUMINAR EN ARGENTINA (1979-2024). ¿POLÍTICAS PÚBLICAS O BUENAS INTENCIONES?
Authors: Ruiz Verónica , Rodriguez Roberto Germán , Pattini Andrea
Published: December 2024

The environmental worsening, an excessive exploitation of finite resources, and climate change are some of the urgent challenges humanity faces today, and energy cuts across all of them. The rational and efficient use of energy (REUE) includes various actions where energy consumption is the final result of a chain of specific decisions for each socioeconomic context in which they are taken.
This article reviews the history and evolution of the Argentine energy system between 1945 and 2024. Various REUE initiatives promoted by the State as organizer and administrator of this strategic resource are presented, particularly those related to the residential sector, responsible in 2023 for the 27% of the country's energy consumption, with lighting occupying 2% of it.
A well-trodden path is observed in relation to the rational and efficient use of energy since 1979, based on initiatives that do not necessarily constitute public policies. Argentina has a path of good intentions, built on solid foundations that it has not always managed to execute effectively and efficiently.
ACCURATE DETERMINATION OF THE RELATIVE DENSITY OF SLM ADDITIVELY MANUFACTURED PARTS
Authors: Kloppers Cornelius Petrus , de Beer Deon
Published: December 2024

Additive manufacturing (AM) is a disruptive technology that provides design freedom, fast turnaround times, and a digital workflow. However, reliable mechanical and material properties are crucial for medical implants and devices produced by AM. The laser powder bed fusion (LPBF) echnique is a reliable method for producing high-quality parts with excellent mechanical properties. The presence of internal porosity, however, is one of the most significant problems in SLM part production. This study aimed to determine the relative density of components produced by LPBF and to develop a method for accurately quantifying the relative density. Three powders were used to evaluate the efficacy of three different quantification methods. The OR-Laser Creator LPBF unit was used to manufacture them. After production, all nine samples were polished on a lathe, and the relative density was measured using three different quantification methods. The results of this study showed that the Archimedes principle is the most accurate and reliable method for determining the density of materials used in LPBF. The findings of this study should help to ensure that the quality of parts produced by SLM is reliable and accurate. This should increase confidence in the use of LPBF in the medical industry and other industries where AM components have a significant advantage.
Od wyroku w sprawie Pierre Fabre do decyzji w sprawie Guess. Próba zdefiniowania status quo co do pewnych ograniczeń nakładanych w związku z prowadzeniem dystrybucji selektywnej w Internecie w oczekiwaniu na wynik przeglądu rozporządzenia blokowego
Authors: Banaś Marta Dominika , Piaskowski Mikołaj
Published: December 2024

Wraz ze wzrostem popularności systemów dystrybucji selektywnej coraz bardziej aktualną staje się ocena dopuszczalności i ryzyka prawnego związanego z ograniczeniami, w szczególności w Internecie, nakładanymi przez dostawców na dystrybutorów. Niniejszy artykuł analizuje podejście do tego tematu organów ochrony konkurencji i sądów począwszy od sprawy Pierre Fabre do ostatnio rozstrzygniętej sprawy Guess i podejmuje próbę wskazania najistotniejszych kwestii, które powinny zostać podjęte w ramach konsultacji publicznych prowadzonych przez KE dotyczących rozporządzenia Komisji (UE) nr 330/2010 oraz wytycznych wydanych do tego rozporządzenia.
Modele dystrybucji treści elektronicznych na przykładzie rynku e-booków
Authors: Łyszczarz Wojciech
Published: December 2024

E-booki mogą być dystrybuowane przez platformy internetowe w dwóch zasadniczych modelach. Z jednej strony, może być stosowany model hurtowy, w ramach którego e-booki są sprzedawane detalistom po cenie hurtowej do odsprzedaży po cenie swobodnie przez nich ustalanej. Z drugiej strony, może być stosowany model agencyjny, w ramach którego detalista działała jako pośrednik w sprzedaży e-booków i pobiera prowizję od wydawcy. Doświadczenia amerykańskich I europejskich organów ochrony konkurencji wykazują, że stosowanie lub zmiana modelu dystrybucyjnego e-booków może wywoływać negatywne konsekwencje w obszarze prawa konkurencji. Artykuł przedstawia problemy dystrybucji e-booków na przykładzie firmy Apple i tzw. wielkiej piątki wydawców e-booków.
Ograniczenia sprzedaży przez Internet w porozumieniach franczyzowych
Authors: Elżanowski Fabian
Published: December 2024

Artykuł koncentruje się na problematyce antymonopolowej oceny porozumień franczyzowych w prawie unijnym. W publikacji została przedstawiona gospodarcza istota systemów dystrybucji franczyzowej oraz aktualnie obowiązujące w tym zakresie reguły antymonopolowe. Artykuł analizuje doktrynę niezbędnych ograniczeń w zakresie, w jakim znajduje ona zastosowanie do porozumień franczyzowych oraz postulowany sposób jej zastosowania do ograniczeń sprzedaży przez Internet w porozumieniach franczyzowych.
Umowy dystrybucyjne na obszar Unii Europejskiej: ograniczenia konkurencji w postanowieniach o prawach własności intelektualnej
Authors: Kruk-Kubarska Joanna
Published: December 2024

Artkuł omawia typowe postanowienia dotyczące praw własności intelektualnej, które pojawiają się w umowach dystrybucyjnych na obszar Unii Europejskiej, a które mogą stanowić ograniczenie konkurencji. Uwzględniono m.in. przyjęty sposób analizy nakładających się regulacji krajowych z zakresu prawa własności intelektualnej oraz unijnego prawa ochrony konkurencji, a także warunki wyłączenia spod zakazu porozumień ograniczających konkurencję. Celem artykułu jest przybliżenie problematyki w świetle praktyki decyzyjnej Komisji Europejskiej i sądów unijnych.
Zobowiązanie do ujawienia istotnych informacji przed zawarciem umowy franczyzy (pre-contractual disclosure obligation). Analiza prawnoporównawcza na tle ustawodawstwa polskiego oraz wybranych jurysdykcji
Authors: Kowalczuk-Szymańska Magdalena
Published: December 2024

Artykuł koncentruje się na przedstawieniu zagadnienia pre-contractual disclosure obligation w relacjach franczyzodawca – franczyzobiorca i systemie dystrybucji opartym na umowie franczyzy. Autorka przedstawia nie tylko ujęcie tego tematu w prawie polskim, lecz także regulacje obowiązujące w różnych jurysdykcjach, tak w Europie, jak i na świecie. Zróżnicowane ustawodawstwa krajowe, niekiedy również na szczeblu wewnątrzkrajowym, jak ma to miejsce w Stanach Zjednoczonych Ameryki, dają możliwość oceny, który z modeli wydaje się najbardziej odpowiadać pożądanej zasadzie fair play w biznesie, równoważąc interesy obu stron projektowanej relacji franczyzowej.
Rozwiązywanie umów dystrybucyjnych
Authors: Sztejnert-Roszak Olga
Published: December 2024

Przedmiotem artykułu jest analiza zagadnienia możliwości i trybu rozwiązania umowy dystrybucyjnej zawartej pod prawem polskim, będącej umową nienazwaną w rozumieniu polskiego prawa cywilnego. Umowy dystrybucyjne, często zawierane w sposób nieformalny, nie przewidują przesłanek ich rozwiązania czy to z zachowaniem terminu wypowiedzenia, czy w trybie natychmiastowym. Ich rozwiązanie jest jednak możliwe, choć sporne w polskim piśmiennictwie jest na przykład czy także dystrybucyjna umowa terminowa może zostać rozwiązana za wypowiedzeniem przed upływem okresu, na jaki została zawarta oraz czy przepisy ogólne kodeksu cywilnego stwarzają możliwość zakończenia umowy dystrybucyjnej w trybie natychmiastowym, a w szczególności – czy jest możliwe odstąpienie od takiej umowy. Artykuł zawiera odniesienia do jurysdykcji europejskich co do rozsądnego terminu wypowiedzenia umowy dystrybucyjnej oraz przesłanek, w oparciu o które należy taki termin wyznaczać oraz zauważa wpływ Draft Common Frame of Reference na kształtowanie praw i obowiązków stron umowy dystrybucyjnej.
Obowiązki operatorów systemów dystrybucyjnych elektroenergetycznych i gazowych w zakresie rozwoju infrastruktury ładowania drogowego transportu publicznego
Authors:   Uniwersytet im. Adama Mickiewicza w Poznaniu, Greser Jarosław
Published: December 2024

Artykuł porusza problematykę budowy infrastruktury niezbędnej do zwiększenia liczby pojazdów napędzanych paliwami alternatywnymi. Zgodnie z decyzją ustawodawcy kluczową rolę w realizacji tego zadania będą odgrywać operatorzy systemów dystrybucyjnych elektroenergetycznych i gazowych, którzy będą odpowiedzialni za budowę wskazanej w ustawie liczby punktów. Jednocześnie miejsca ich lokalizacji wyznaczane są przez inne podmioty, takie jak: gminy, GDDKiA czy zarządcy portów. W artykule zostaną poruszone kwestie obowiązków OSD w zakresie przygotowania planów i programów budowy stacji i punktów ładowania we wszystkich przypadkach przewidzianych w ustawie o elektromobilności i paliwach alternatywnych.
Public opinion as an indicator of the political crisis in the UK: migration track
Authors: Serbina Anna Stepanovna
Published: December 2024

The subject of this study is the change in migration regulation and public discourse on immigration in the UK after leaving the European Union. On the basis of official statistical data and survey data conducted by the largest companies in the field of marketing research and national centers for sociological research, the degree of influence of Brexit on the transformation of migration processes in the UK and the change in British public opinion on the issue of the country's immigration policy is analyzed. Brexit changed the structure of migration in the UK, the growth of net migration was provided by the outflow of European citizens and immigration from non-EU countries. The public perception of migration processes is opportunistic and depends on the political preferences of citizens and the degree of speculation on the migration topic in the media. The theoretical basis of the research is neofunctionalism as a theory of disintegration applicable to European integration. The methodological basis of the study is a systematic approach and predictive methods using inductive algorithms, which were expressed in the construction of a scenario of post-integration interaction between London and Brussels in the field of migration regulation. Content analysis was used to study regulatory documents. It is concluded that any British government is faced with the usual compromise between the needs of the economy and migration policy, which is non-systemic and adapts to public opinion. It has been revealed that the migration issue is being resolved not from a legal, but from a political point of view, acting as an instrument of the electoral struggle between Conservatives and Labour. The dynamics of public opinion regarding the economic and cultural consequences of immigration is positive, but a drastic reduction in public discontent is possible only when solving systemic problems of migration policy. The author concludes that a way out of the political crisis is possible, including through a return to free movement with the EU, which in the short term is a taboo topic for the Labour government.
Human birth tissue products as a non-opioid medicine to inhibit post-surgical pain
Authors: Zhang Chi , Huang Qian , Ford Neil C , Limjunyawong Nathachit , Lin Qing , Yang Fei , Cui Xiang , Uniyal Ankit , Liu Jing , Mahabole Megha , He Hua , Wang Xuewei , Duff Irina , Wang Yiru , Wan Jieru , Zhu Guangwu , Raja Srinivasa N , Jia Hongpeng , Yang Dazhi , Dong Xinzhong , Cao Xu , Tseng Scheffer C , He Shaoqiu , Guan Yun
Published: December 2024

Pain after surgery causes significant suffering. Opioid analgesics cause severe side effects and accidental death. Therefore, there is an urgent need to develop non-opioid therapies for managing post-surgical pain. Local application of Clarix Flo (FLO), a human amniotic membrane (AM) product, attenuated established post-surgical pain hypersensitivity without exhibiting known side effects of opioid use in mice. This effect was achieved through direct inhibition of nociceptive dorsal root ganglion (DRG) neurons via CD44-dependent pathways. We further purified the major matrix component, the heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) from human AM that has greater purity and water solubility than FLO. HC-HA/PTX3 replicated FLO-induced neuronal and pain inhibition. Mechanistically, HC-HA/PTX3-induced cytoskeleton rearrangements to inhibit sodium current and high-voltage activated calcium current on nociceptive DRG neurons, suggesting it is a key bioactive component mediating pain relief. Collectively, our findings highlight the potential of naturally derived biologics from human birth tissues as an effective non-opioid treatment for post-surgical pain. Moreover, we unravel the underlying neuronal mechanisms of pain inhibition induced by FLO and HC-HA/PTX3.
Autologous P63+ lung progenitor cell transplantation in idiopathic pulmonary fibrosis: a phase 1 clinical trial
Authors: Zhang Shiyu , Zhou Min , Shao Chi , Zhao Yu , Liu Mingzhe , Ni Lei , Bao Zhiyao , Zhang Qiurui , Zhang Ting , Luo Qun , Qu Jieming , Xu Zuojun , Zuo Wei
Published: December 2024

In idiopathic pulmonary fibrosis (IPF) patients, alveolar epithelium architectures are persistently lost and lung gas transfer function would decline over time, which cannot be rescued by conventional anti-fibrotic therapy. P63+ airway basal progenitor cells are previously reported to have great potential to repair damaged lung epithelium. Here, we successfully cloned and expanded the autologous P63+ progenitor cells from IPF patients to manufacture the cell therapeutic product REGEND001, which were further characterized by cell morphology and single-cell transcriptomic analysis. Subsequently, an open-label, dose-escalation autologous progenitor cell transplantation clinical trial (CTR20210349) was conducted. The primary outcome was the incidence and severity of the cell therapy-related adverse events (AEs); secondary outcome included other safety and efficacy evaluation in each dose groups. We treated 12 patients with ascending doses of cells: 0.6x, 1x, 2x and 3.3× 10
6
cells/kg bodyweight. The data revealed that P63+ basal progenitor cell was safe and well tolerated at all doses, with no dose-limiting toxicity or cell therapy-related severe adverse events observed. Patients in the three higher dose groups showed statistically significant improvement of lung gas transfer function as well as exercise ability after REGEND001 therapy. Resolution of honeycomb lesion was also observed in patients of higher dose groups. Altogether these results indicated that REGEND001 has high safety profile and meanwhile encourages further efficacy exploration in IPF patients.
Systematic creation and phenotyping of Mendelian disease models in C. elegans: towards large-scale drug repurposing
Authors: O’Brien Thomas J , Barlow Ida L , Feriani Luigi , Brown André EX
Published: December 2024

There are thousands of Mendelian diseases with more being discovered weekly and the majority have no approved treatments. To address this need, we require scalable approaches that are relatively inexpensive compared to traditional drug development. In the absence of a validated drug target, phenotypic screening in model organisms provides a route for identifying candidate treatments. Success requires a screenable phenotype, however the right phenotype and assay may not be obvious for pleiotropic neuromuscular disorders. Here we show that high-throughput imaging and quantitative phenotyping can be conducted systematically on a panel of
C. elegans
disease model strains. We used CRISPR genome-editing to create 25 worm models of human Mendelian diseases and phenotyped them using a single standardised assay. All but two strains were significantly different from wild-type controls in at least one feature. The observed phenotypes were diverse, but mutations of genes predicted to have related functions in their human orthologs led to similar behavioural differences in worms. As a proof-of-concept, we performed a drug repurposing screen of an FDA approved compound library, and identified two compounds that rescued the behavioural phenotype of a model of UNC80 deficiency. Our results show that a single assay to measure multiple phenotypes can be applied systematically to diverse Mendelian disease models. The relatively short time and low cost associated with creating and phenotyping multiple strains suggests that high-throughput worm tracking could provide a scalable approach to drug repurposing commensurate with the number of Mendelian diseases.
Progesterone induces meiosis through two obligate co-receptors with PLA2 activity
Authors: Nader Nancy , Assaf Lama , Zarif Lubna , Halama Anna , Yadav Sharan , Dib Maya , Attarwala Nabeel , Chen Qiuying , Suhre Karsten , Gross Steven S , Machaca Khaled
Published: December 2024

The steroid hormone progesterone (P4) regulates multiple aspects of reproductive and metabolic physiology. Classical P4 signaling operates through nuclear receptors that regulate transcription. In addition, P4 signals through membrane P4 receptors (mPRs) in a rapid nongenomic modality. Despite the established physiological importance of P4 nongenomic signaling, the details of its signal transduction cascade remain elusive. Here, using
Xenopus
oocyte maturation as a well- established physiological readout of nongenomic P4 signaling, we identify the lipid hydrolase ABHD2 (α/β hydrolase domain-containing protein 2) as an essential mPRβ co-receptor to trigger meiosis. We show using functional assays coupled to unbiased and targeted cell-based lipidomics that ABHD2 possesses a phospholipase A2 (PLA2) activity that requires mPRβ. This PLA2 activity bifurcates P4 signaling by inducing clathrin-dependent endocytosis of mPRβ, resulting in the production of lipid messengers that are G-protein coupled receptors agonists. Therefore, P4 drives meiosis by inducing an ABHD2 PLA2 activity that requires both mPRβ and ABHD2 as obligate co-receptors.
Olfactory ensheathing cells from adult female rats are hybrid glia that promote neural repair
Authors: Phelps Patricia E , Ha Sung Min , Khankan Rana R , Mekonnen Mahlet A , Juarez Giovanni , Ingraham Dixie Kaitlin L , Chen Yen-Wei , Yang Xia
Published: December 2024

Olfactory ensheathing cells (OECs) are unique glial cells found in both central and peripheral nervous systems where they support continuous axonal outgrowth of olfactory sensory neurons to their targets. Previously we reported that following severe spinal cord injury, OECs transplanted near the injury site modify the inhibitory glial scar and facilitate axon regeneration past the scar border and into the lesion. To better understand the mechanisms underlying the reparative properties of OECs, we used single-cell RNA-sequencing of OECs from adult rats to study their gene expression programs. Our analyses revealed five diverse OEC subtypes, each expressing novel marker genes and pathways indicative of progenitor, axonal regeneration, secreted molecules, or microglia-like functions. We found substantial overlap of OEC genes with those of Schwann cells, but also with microglia, astrocytes, and oligodendrocytes. We confirmed established markers on cultured OECs, and localized select top genes of OEC subtypes in olfactory bulb tissue. We also show that OECs secrete Reelin and Connective tissue growth factor, extracellular matrix molecules which are important for neural repair and axonal outgrowth. Our results support that OECs are a unique hybrid glia, some with progenitor characteristics, and that their gene expression patterns indicate functions related to wound healing, injury repair and axonal regeneration.
Single-cell transcriptomics of vomeronasal neuroepithelium reveals a differential endoplasmic reticulum environment amongst neuronal subtypes
Authors: Devakinandan GVS , Terasaki Mark , Dani Adish
Published: December 2024

Specialized chemosensory signals elicit innate social behaviors in individuals of several vertebrate species, a process that is mediated via the accessory olfactory system (AOS). The AOS comprising the peripheral sensory vomeronasal organ has evolved elaborate molecular and cellular mechanisms to detect chemo signals. To gain insight into the cell types, developmental gene expression patterns, and functional differences amongst neurons, we performed single-cell transcriptomics of the mouse vomeronasal sensory epithelium. Our analysis reveals diverse cell types with gene expression patterns specific to each, which we made available as a searchable web resource accessed from https://www.scvnoexplorer.com. Pseudo-time developmental analysis indicates that neurons originating from common progenitors diverge in their gene expression during maturation with transient and persistent transcription factor expression at critical branch points. Comparative analysis across two of the major neuronal subtypes that express divergent GPCR families and the G-protein subunits Gnai2 or Gnao1, reveals significantly higher expression of endoplasmic reticulum (ER) associated genes within Gnao1 neurons. In addition, differences in ER content and prevalence of cubic membrane ER ultrastructure revealed by electron microscopy, indicate fundamental differences in ER function.
Hybrid transformer-CNN and LSTM model for lung disease segmentation and classification
Authors: Shafi Syed Mohammed , Chinnappan Sathiya Kumar
Published: December 2024

According to the World Health Organization (WHO) report, lung disorders are the third leading cause of mortality worldwide. Approximately three million individuals are affected with various types of lung disorders annually. This issue alarms us to take control measures related to early diagnostics, accurate treatment procedures, etc. The precise identification through the assessment of medical images is crucial for pulmonary disease diagnosis. Also, it remains a formidable challenge due to the diverse and unpredictable nature of pathological lung appearances and shapes. Therefore, the efficient lung disease segmentation and classification model is essential. By taking this initiative, a novel lung disease segmentation with a hybrid LinkNet-Modified LSTM (L-MLSTM) model is proposed in this research article. The proposed model utilizes four essential and fundamental steps for its implementation. The first step is pre-processing, where the input lung images are pre-processed using median filtering. Consequently, an improved Transformer-based convolutional neural network (CNN) model (ITCNN) is proposed to segment the affected region in the segmentation process. After segmentation, essential features such as texture, shape, color, and deep features are retrieved. Specifically, texture features are extracted using modified Local Gradient Increasing Pattern (LGIP) and Multi-texton analysis. Then, the classification step utilizes a hybrid model, the L-MLSTM model. This work leverages two datasets such as the COVID-19 normal pneumonia-CT images dataset (Dataset 1) and the Chest CT scan images dataset (Dataset 2). The dataset is crucial for training and evaluating the model, providing a comprehensive basis for robust and generalizable results. The L-MLSTM model outperforms several existing models, including HDE-NN, DBN, LSTM, LINKNET, SVM, Bi-GRU, RNN, CNN, and VGG19 + CNN, with accuracies of 89% and 95% at learning percentages of 70 and 90, respectively, for datasets 1 and 2. The improved accuracy achieved by the L-MLSTM model highlights its capability to better handle the complexity and variability in lung images. This hybrid approach enhances the model’s ability to distinguish between different types of lung diseases and reduces diagnostic errors compared to existing methods.
A novel optimization method for hazardous materials vehicle routing with temperature-based time windows
Authors: Ding Lu , Zhang Fangwei , Ye Jun , Kong Fanyi , Jiao Minhui
Published: December 2024

As a concrete achievement of sharing economy, sharing intermediate bulk containers (IBCs) have emerged and developed in recent years. Meanwhile, high temperature is one of the essential factors in routing optimal problems for vehicles with hazardous material (hazmat). Therefore, to address the above issue, a variant of the hazmat vehicle routing problem of sharing IBCs is proposed. Correspondingly, a mixed non-linear integer programming model is refined considering temperature-based time windows. Specifically, the given problem is solved by using a novel adaptive large neighborhood search (ALNS) algorithm. The main innovation points are as follows. Firstly, temperature-based time windows are quantified and integrated into the proposed hazmat vehicle routing optimal model. Secondly, novel heuristic operators are introduced in the ALNS algorithm. Finally, 18 numerical examples for the Solomon set demonstrate that the proposed algorithm is suitable to solve this kind of hazmat vehicle routing optimal problem.
The association between fibroblast growth factor 21 with diabetes retinopathy among type 2 diabetes mellitus patients: a systematic review, meta-analysis, and meta-regression
Authors: Basir Herni , Nugrahani Annisa Salsabilla Dwi , Aman Andi Makbul , Bakri Syakib , Rasyid Haerani , Umar Husaini , H. P. Faridin , Ichsan Andi Muhammad , Zainuddin Andi Alfian
Published: December 2024

Background

Diabetic retinopathy (DR), a leading cause of vision loss worldwide, is a common complication of type 2 diabetes mellitus (T2DM) driven by chronic hyperglycemia and microvascular damage. Fibroblast growth factor 21 (FGF21) is crucial in blood sugar regulation and has been linked to DR incidence and severity. While some studies suggest that FGF21 levels may contribute to the DR incidence, others propose a protective role. This discrepancy necessitates further analysis, prompting this study to evaluate the association between FGF21 levels and DR incidence and severity in T2DM patients.

Methods

A systematic search was conducted through MEDLINE, Web of Science, Scopus, and Embase up to May 2024 for studies evaluating the association between FGF21 and DR incidence and severity. A random-effect model meta-analysis was performed to calculate the pooled standardized mean difference (SMD) and 95% confidence intervals (CI). A univariate meta-regression was performed to analyze factors influencing pooled size estimates. All statistical analyses were performed using STATA 17 software.

Result

This systematic review and meta-analysis of 5,852 participants revealed that FGF21 was positively correlated with DR (SMD 3.11; 95% CI [0.92–5.30], p = 0.005) and sight-threatening DR (STDR) incidence (SMD 3.61; 95% CI [0.82–6.41], p = 0.01). There was no significant difference in FGF21 levels in DR vs STDR (p = 0.79). Subgroup analysis revealed a significant difference in DR incidence between LDL groups, with higher DR incidence in the group with low-density lipoprotein (LDL) levels >100 (P < 0.00001). Meta-regression revealed no variables significantly influenced the pooled size estimates.

Conclusion

A higher level of FGF21 was associated with higher DR and STDR incidence among T2DM patients, highlighting its potential utilization as a biomarker for DR detection and enabling the exploration of FGF21-based treatment strategies. However, variables independently predicting DR among patients with elevated FGF21 levels shall be explored further.

PROSPERO ID

CRD42024559142.
Pepper power: short-term impact of pepper consumption on the gut bacteriome composition in healthy volunteers
Authors: Owolo Oluwafayoke , Audu Haruna J. , Afolayan Ayorinde O. , Ayeni Funmilola A.
Published: December 2024

Background

Pepper from Capsicum species is a well-established spice with a rich history of culinary use. Some observations have linked its consumption to gastrointestinal discomfort and alterations in stool patterns while it is considered beneficial in some cultures. However, there is lack of information on the direct effect of pepper consumption on human gut microbiota, we conducted dietary intervention studies to assess the impact of pepper on gut bacteriome composition in humans.

Methods

Ten healthy volunteers were recruited, and each person received 200 ml of 0.14 g/ml fresh Habanero Pepper (Capsicum chinense) daily over a 4-day period after which they abstained from pepper consumption for the subsequent 4 days before resumption of their normal diet. Stool samples were collected at baseline, after pepper consumption, after 4 days without pepper and after 4- and 6-days resumption of normal diet. We sequenced the V3-V4 region of the 16S rRNA gene and analyzed microbial diversity and composition using the QIIME2 pipeline and relevant R packages.

Results

Consumption of pepper over a 4-day period led to a higher abundance of Verrucomicrobia, a phylum rarely found in significant proportions at other time points. There was a gradual depletion of Shigella and Staphylococcus spp. from baseline untill the end of the study. Other taxa showed timepoint specific associations, emphasizing the potential impact of short-term dietary interventions on the relative abundance of these genera.

Conclusions

Our study adds nuance to the understanding of diet-microbiota interactions, highlighting the intricate relationship between pepper consumption and gut bacteriome composition. Further exploration of these dynamics holds promise for personalized dietary recommendations and targeted interventions to support gut microbial health.
The Role of Financial Education in Preventing Credit Card Debt: A Framework for Schools and Communities
Authors: ABU Jacob Kehinde,
Published: December 2024

Many individuals, particularly young adults and those in underserved communities, lack essential financial education, leaving them ill-equipped to manage credit cards and other financial products. The study examined the role of financial education in preventing credit card debt: a comprehensive framework for schools and communities. The study’s specific objectives were to: examine the importance of financial education in mitigating credit card debt among young adults and underserved communities; develop a framework for incorporating credit card management education into school curricula and community initiatives; ascertain the long-term advantages of early financial education on responsible credit card usage and overall financial well-being, thereby supporting the broader strategy of promoting financial literacy and demonstrating expertise in creating targeted educational programs. Descriptive survey research design was adopted on a sample respondents of 100 credit card users in Mississippi, USA. Primary data were collected using structured questionnaire. After the descriptive analysis conducted through mean and frequency, the hypothesis were tested using one-sample t-test. The findings of the study revealed that: financial education is significantly important in mitigating credit card debt among young adults and underserved communities (t-value = 6.401; p = 0.000); the proposed framework will significantly help in incorporating credit card management education into school curricula and community initiatives (t-value = 6.653; p = 0.000); there are significant long-term advantages of early financial education on responsible credit card usage and overall financial well-being (t-value of 8.646; p = 0.000). In conclusion, by equipping individuals with the knowledge and skills to manage credit responsibly, financial education can help reduce the risk of debt accumulation and foster healthier financial habits. The study recommends among others that financial education organizations and curriculum developers should prioritize early financial education initiatives to promote responsible credit card usage and long-term financial well-being.
Evaluation of Fungicides Efficacy for the Control of Yellow Rust (Puccinia striiformis f.s.tritici) Disease on Bread Wheat, Arsi Highlands of Ethiopia
Authors: Zerihun Alemu Ayele , Abebele Getnet Muche
Published: December 2024

Two new verification test fungicides namely Cayunis EC 325 (Bixafen 75g/L +Spiroxamine 150g/L + Trifloxystrobin 100g/L), and Tridium 70 WG (Mancozeb59.7%+Azoxystrobin 4.7%+Tebuconazole 5.6%WG and evaluated with standard checks called Nativo SC 300(trifloxystrobin 100 gm/lt + tebuconazol 200 gm/lt) were evaluated the efficacies in controlling the yellow (stripe) rust. The objective of the study was to evaluate and verify the efficacy of new fungicides against yellow rust disease control and recommend for registration. The trial was conducted in non-replicated with replication of sites at Meraro substation and Kulumsa agricultural research center, and Boru Chilalo farmers’ field. The test fungicides of Cayunis 325 EC and Tridium 70WG had decreased the disease severity to the lowest level of 20% at all locations but 60% to 90% disease severity was recoded on the unsprayed treatment. The highest grain yield was recorded from cayunis 325 EC treatment was recorded 5861, 6428, 5398kgha-1 whereas Tridium 70 WG was recorded 2878, 6035 and 3224kgha-1at Kulumsa, Meraro and Boru chilalo respectively. Although the differences of test fungicides were not statistically significant, treated plots consistently produced higher yields, thousand kernel weights, and hectolitre weights than untreated plots. The result revealed that Bixafen 75g/L +Spiroxamine 150g/L + Trifloxystrobin 100g/L), and Mancozeb59.7%+Azoxystrobin 4.7%+Tebuconazole 5.6%WG fungicides were effective in controlling yellow rust disease and improving high grain yield than trifloxystrobin 100 gm/lt + tebuconazol 200 gm/lt and unsprayed control treatments in all tested experimental sites and recommended for registration.