bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness and safety of dupilumab and JAK-inhibitors in daily practice
Authors:   , Boesjes Celeste Mirte
Published: November 2024

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases worldwide. Until recently, adequate systemic treatment options for patients with moderate-to-severe AD were limited. Due to the increased understanding of the underlying pathophysiology of AD in the past decade, more targeted therapies for moderate-to-severe AD have been developed that address this unmet need. The advent of these new advanced systemic drugs since 2017, including biologics (i.e. dupilumab and tralokinumab) and Janus kinase (JAK)-inhibitors (i.e. baricitinib, upadacitinib and abrocitinib), therefore represents an important advancement in the therapeutic landscape for AD. In this thesis, including data from the real-life Dutch BioDay registry, we demonstrate that dupilumab treatment resulted in a significant improvement of clinical and patient-reported outcomes together with a significant decrease in severity-associated serum biomarkers and alterations in the skin microbiome moving it towards healthy skin. Effectiveness of dupilumab sustained even in the long-term use in both pediatric, adult and elderly patients as well as patients with or without pathogenic filaggrin variants, while the majority of patients was able to prolong their dosing interval. The JAK-inhibitors also showed to be effective treatment options for adult patients with moderate-to-severe AD, with upadacitinib and abrocitinib providing the highest effectiveness rates based on both physician and patients’ perspectives. Safety assessments showed that dupilumab has a favorable long-term safety profile, while the JAK-inhibitors still need to prove their safety in the long-term use.
Fostering students’ interprofessional feedback dialogues in health professions education
Authors:   , Tielemans Claudia Jeanne Maria
Published: November 2024

Interprofessional feedback helps health profession trainees collaborate and learn in the complex, ever-changing clinical workplace. Fostering interprofessional feedback processes is thus a key aim of interprofessional education, where students from different professions learn ‘with, from, and about each other’. To better understand and support interprofessional feedback education in health professions education, in this thesis, we draw from the broader field of higher education research. In the last decade, scholars in the higher education research field have been moving away from traditional definitions of feedback as information transmission, increasingly defining feedback as a process in which learners seek, make sense of, and use feedback information. Moving away from transmission-based views on feedback has led some scholars to advocate for feedback dialogue—the ongoing exchange, clarification, and alteration of ideas through asking and responding to questions—as a means to construct feedback processes. In this thesis, we argue that this dialogue perspective is especially relevant and necessary in health professions education. Drawing from contemporary insights in feedback literature, we investigate how, when, and why feedback dialogue training in the interprofessional setting works. Through this, we aim to gain insight into how to foster students’ interprofessional feedback dialogues through educational design. The overarching research question is: How can healthcare students’ interprofessional feedback dialogues be fostered in health professions education?
A molecular corset for spermatids
Authors:   , Judernatz Jo Henry
Published: November 2024

Sperm cells are highly specialized and polarized cells that deliver the paternal genome to the female oocyte. Spermiogenesis is the crucial process of sperm shaping. It involves acrosome formation, chromatin condensation, nuclear shaping, tail formation, and cytoplasm reduction; failures during these processes inevitably lead to morphology defects and infertility. During spermiogenesis, a temporal organelle called the manchette assembles and facilitates the high polarization of round spermatids to sperm cells. The manchette primarily comprises microtubules, highly dynamic, hollow biopolymers involved in many fundamental cellular processes, including cell division and cellular motility. The manchette is relevant for our understanding of microtubule regulation and stabilization, as it maintains its structural integrity for several weeks and is used as a scaffold for protein cargo. The work presented here provides fundamental new insights into the molecular mechanisms involved in manchette stabilization and function.
Chapter I provides fundamentals of sperm cell development and the molecular role of the manchette during spermiogenesis. Chapter II overviews the current state-of-the-art of cryo-ET and its applications in cell biology. Chapter III explores the stabilization of manchette microtubules, showcasing the involvement of multiple molecular players that work together to maintain the manchette integrity over a long period. The study unveils a protein (mMIP) regularly binding to the inside of the microtubule. Its binding site suggests that it is involved in the stabilization of the seam of microtubules. The seam is the most unstable part of the microtubule, and its stabilization via the mMIP likely contributes to the prolonged integrity of the manchette. Chapter IV focuses on the utilization of the manchette as a bidirectional transport scaffold and its involvement in the polarization of the spermatid. Two diverging mechanisms of cellular cargo transport are revealed. Soluble proteins are transported along the manchette microtubules via dyneins, while vesicles are transported via other transport machinery. The study further revealed actin filaments as a second biopolymer integral to the manchette. Actin filaments appear as bundles and singlets, indicating two different roles in the manchette. Chapter V presents a workflow that allows the investigation of whole spermatids with cryo-EM. The workflow enables visualization of multiple spermiogenesis-specific structures like the manchette and the acroplaxome within spermatids. Finally, Chapter VI discusses the results in the context of published data and provides a scientific outlook.
Counting the Uncounted
Authors:   , Zult Daan Bernardus
Published: November 2024

Multiple systems estimation (MSE) is an estimation method to estimate the number of unobserved population units, in case a population is observed by two or more (incomplete) samples of this population. To provide asymptotically unbiased estimates, MSE depends on a number of assumptions and conditions that are often violated in practice. When one of the assumptions or conditions is violated, there generally is a method available in literature that allows the statistician to correct for this violation. However, when more than one assumption or condition is violated, it is not always clear how these correction methods can be combined. To be more specific, an MSE assumption that is often violated, is the assumption of sample independence, which will lead to a biased estimate when only two samples are used. When more than two samples are used, this assumption can be relaxed, so the use of three or more samples is advisable. However, some of the available correction methods for other violations of assumptions or conditions, such as the assumption of perfectly identifiable population units and the condition of large enough samples, are generally developed for the case of two (independent) samples. Furthermore, when multiple samples are required, it may be that some of these samples are available with delay, while an early estimate is desired. Therefore, in this dissertation we propose methods that generalise the finite sample correction method by Chapman (1951) in case of three or more samples (Ch. 2), improve and extend the so-called linkage error correction method by Ding & Fienberg (1994, Ch. 3 & 4), and proposes two different approaches (Ch. 5 & 6) that allow the statistician to obtain early estimates, where Ch. 6 proposes a new method that is based on samples that become available periodically over time.
Catching Houdini - targeting TP53-deficient ALL
Authors:   , Cox Willem Pieter Jan
Published: November 2024

With over 90% being cures, the treatment of acute lymphoblastic leukemia (ALL) in children is a success story. Improving this cure rate even more starts with the identification of those patients at risk and defining novel treatment strategies to combat specifically the type of tumor that these patients suffer from. This study focused on a rare subgroup of leukemia, characterized by mutations in the TP53 gene, which have a dismal prognosis when treated with standard of care protocols. Doctoral candidate Willem Cox found that tumor cells that have this mutations are intrinsically resistant to nearly all of the drugs that are used in the treatment, including novel antibody-drug-conjugates. Importantly, his study also showed that these tumor cells can be re-sensitized to treatment when specific drug combinations are used, for example when an HDAC inhibitor is added to the treatment.

With novel cellular immunotherapies moving their way towards first and second-line treatment of ALL, Cox studied whether loss of TP53 changed the response to this type of treatment, called CAR T. Similar to the response to the chemotherapeutics, tumor cells with a defective TP53 gene are less responsive to CAR T treatment. Indeed, comparing the outcome of CAR T treatment in patients suffering for TP53 defective tumors to patients with a normal TP53 gene showed that CAR T treatment is ineffective against TP53 defective tumors. Cox was able to attribute this resistance to lower levels of so-called Death Receptors that are used in CAR T treatment to kill the tumor cells.

These studies underscore that tumors characterized by a defect in the TP53 gene are notoriously difficult to treat because of cell intrinsic resistance to both conventional chemotherapeutics and novel immunotherapies. It is therefore important to search for TP53 mutations at diagnosis and later when second line treatments are needed. And although Cox showed that current therapy protocols are unsuccessful, his studies provide a proof of principle that cells can be sensitized to treatment by targeted combination treatments which aid in the design of better treatment for these patients.
Leveraging Measurement Theory for Natural Language Processing Research
Authors:   , Fang Qixiang
Published: November 2024

This dissertation explores the intersection of natural language processing (NLP) and measurement theory. NLP is a field aimed at enabling machines to process and generate human languages, such as English, German, and Mandarin. These languages are complex, diverse, and full of irregularities, making them challenging for machines to handle compared to structured artificial languages, like programming languages. NLP research ranges from simple tasks, like word frequency analysis, to complex ones involving the understanding and generation of human language.

Measurement theory, traditionally applied in social sciences, addresses how we measure various properties scientifically. Key concepts include construct validity, which examines whether a measure accurately represents what it intends to measure, and reliability, which focuses on the consistency of a measure across different conditions. This dissertation argues that many challenges in NLP relate to measurement issues and suggests that principles from measurement theory can help address these challenges, particularly by providing tools to evaluate and improve the quality of NLP models.

The structure of the dissertation is as follows:

Chapter 2 offers background on NLP and measurement theory, covering essential text representation techniques in NLP, the history of measurement theory, and recent discussions on its unification across fields.

Chapters 3-5 apply measurement theory to evaluate NLP models: Chapter 3 explores the reliability of gender bias measures in NLP by using classical reliability estimators from social sciences. Chapter 4 adapts a construct validity testing framework to assess the quality of text representations for social science constructs. Chapter 5 introduces a psychometric-based benchmarking approach to evaluate large language models, demonstrated through a case study on eighth-grade math proficiency.

Chapters 6-7 focus on using measurement theory to improve NLP model performance: Chapter 6 presents a framework for designing user models based on measurement principles, achieving better-quality user representations than current methods. Chapter 7 examines how integrating human values into model training can enhance models’ ability to recognize values in human arguments.

Chapters 8 and 9 reflect on current NLP research challenges and propose future directions: Chapter 8 identifies challenges in text-based personality computing, offering potential solutions and avenues for research. Chapter 9 concludes with a summary of the dissertation’s findings and suggests future work at the intersection of measurement theory and NLP.

This work underscores the potential of measurement theory to enhance NLP research by offering frameworks for evaluating and designing more reliable and valid models. By integrating these approaches, the dissertation aims to bridge NLP and measurement theory, advancing NLP's capability to address complex measurement challenges.
Comparative Study of the Effectiveness of Pulsed and Continuous 450 nm Laser Radiation on Tissue for Layered Removal of Pigmented Nevi
Authors: Podurar S. A. , Gorbatova N. E. , Bryantsev A. V. , Stankova N. V. , Tertychnyy A. S. , Varev G. A.
Published: November 2024

Benign pigmented skin lesions, including congenital giant pigmented nevi (CGPN), are pathological formations located in various skin layers and consisting of melanocyte clusters. CGPN represent a serious psychological and medical problem associated with extensive unaesthetic changes in the patient’s skin appearance. These lesions are currently treated by various methods, including laser radiation. However, such methods often render ineffective and lead to unsatisfactory clinical and aesthetic results, with the incidence of complications in the form of scarring and recurrence sometimes reaching 41%. Therefore, the problem of effective and appropriate treatment of this pathology is relevant, deserving further research. In this work, we conduct an experimental biomedical study into the effect of blue laser radiation with a wavelength (λ) of 450 nm on the tissues of laboratory animals in order to determine its prospects in the treatment of pigmented nevi, including CGPN. Blue laser radiation (λ — 450 nm) was generated by an Lasermed 10-03 device (Russian Engineering Club, LLC, Tula, Russia). An experimental biomedical in vitro research was performed on chilled samples of the liver and muscles of mini-pigs and in vivo on the pigmented skin of live laboratory rats. The dynamics of the regenerative wound process in the exposure areas was studied at different periods, i.e., immediately after exposure and following up to 90 days. A morphometric assessment of the exposure areas was carried out in terms of penetration depth and coagulation changes. The results obtained allowed determination of optimal parameters of 450 nm blue laser radiation for a precision removal of various pigmented skin formations. Laser radiation with a wavelength of 450 nm is a promising treatment approach for pigmented skin lesions, including CGPN.
Differences in Models of Traumatic Brain Injury and the Subsequent Behavior Assessment in Rats and Mice
Authors: Chervonetsky S. A. , Paimulina A. A. , Selizarova N. O.
Published: November 2024

Traumatic brain injury (TBI) is associated with varied and unpredictable consequences, which can be manifested during both acute and long-term periods. Such consequences may lead to the development of neurodegenerative diseases years and even decades after the injury. Given the heterogeneous nature of  TBI in humans, preclinical studies need to be conducted using different test systems. Currently, preference is given to rodents due to their availability and low cost. However, the choice of test systems for research should be based not only on economic and logistical components, but also on their specific physiological characteristics.
Aspects of the Combined Use of Anticoagulant and Hemostatic Drugs in Large Joint Endoprosthetics
Authors: Golovko L. S. , Safronenko A. V. , Gantsgorn E. V. , Wehbh M. , Malleev I. M. , Baloyan A. A. , Manvelyan R. M. , Rashkova E. V.
Published: November 2024

The article presents a brief overview of the modern view on the problem of the combined use of drugs with a multidirectional spectrum of action, anticoagulants and hemostatics, in major orthopedics among patients with endoprosthetics of large joints of the lower extremities. Variable prescription regimens of anticoagulant prophylaxis against the background of using hemostatic drugs were analyzed.
Experience of Genotyping of the Class 1 Major Histocompatibility Complex Genes in a Rhesus Macaques Collection
Authors: Orlov S. V. , Agumava A. A. , Kurdyukov I. D. , Beltyukov P. P.
Published: November 2024

The utility of animal models in preclinical research depends on the completeness of our knowledge about these models. Nonhuman primates are the closest animal model to humans, available for preclinical evaluation of biotechnological products. The lack of immunogenetic characteristics of the primates used in a particular study significantly limits the possibilities of analyzing the results obtained. The availability of information about the haplotype of the major histocompatibility complex (MHC) increases the overall significance of the model. Genotyping of primates at the MHC locus by DNA analysis is excluded, since the representation of individual MHC proteins depends on the level of their expression in immune cells, rather than on their presence in the genome. Therefore, the genotyping of primates at the MHC locus is  carried out by analyzing mRNA encoding allelic variants of proteins. This work presents the results of genotyping of a sample of rhesus macaques from the collection of the Kurchatov Complex of Medical Primatology by a next-generation sequencing technology using an IonProton sequencer.
Doxorubicin Effects on Cognitive Impairment and the Microscopic View of Brain Structures in Rats
Authors: Alekseev I. V. , Miroshkina I. A. , Sorokina A. V. , Tsorin I. B. , Kolik L. G.
Published: November 2024

The creation of a validated model of the “chemical brain” in laboratory animals is an urgent task, the solution of which will optimize the search for new drugs for the prevention and pharmacological correction of delayed effects of chemotherapy on the central nervous system. The aim of the work has been to assess the effect of doxorubicin after systemic course administration on behavioral reactions and the microscopic view of the cerebral cortex and hippocampus in rats.

Doxorubicin was administered intraperitoneally to male rats at doses of 5 and 6 mg/kg, once a week, for 28 days. The behavioral reactions of the animals were assessed, and pathomorphological studies of the cerebral cortex and hippocampus were carried out.

Doxorubicin at doses of 5 and 6 mg/kg causes inhibition of motor activity in the “Open Field” test, impairment of non-spatial and spatial memory in the “New Object Recognition” and “Y-Maze” tests, respectively. Doxorubicin at these doses increases the severity of vascular congestion and perivascular edema in the cerebral cortex and hippocampus.

Doxorubicin at doses of 5 and 6 mg/kg causes impairment of cognitive functions in rats in tests assessing non-spatial and spatial memory, as well as microcirculation disorders in the cerebral cortex and hippocampus of rats.
Current Animal Models of Chemotherapy-Induced Peripheral Polyneuropathy
Authors: Prikhodko V. A. , Matuzok T. M. , Okovitiy S V.
Published: November 2024

Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication of antineoplastic chemotherapy. In a large number of patients, this complication is highly persistent to treatment. The present review is focused on current rodent CIPN models using antineoplastic agents of different groups.
Experimental Modeling of Heart Failure in Mice
Authors: Kulchanovskaya D. S. , Chernomordova A. V. , Okovitiy S. V. , Kulikov A. N.
Published: November 2024

The article presents the results of testing a heart failure model in laboratory animals by single administration of amyloidogen. White outbred mice were used as biomodels, which were divided into intact and experimental groups. Animals from the experimental group were once injected with amyloidogen containing mouse myocardial homogenate to reproduce a pronounced cardiopathic effect. Structural and functional changes of the myocardium were monitored using echocardiography. According to the results obtained, animals in the experimental group demonstrated a remodeling of the heart similar to restrictive cardiomyopathy and a myocardial disfunction of both ventricles, indicating the formation of heart failure.
A megtartott ejekciós frakcióval járó szívelégtelenség és a krónikus vesebetegség kapcsolata
Authors: Ágoston Gergely
Published: November 2024

A megtartott ejekciós frakciójú szívelégtelenség (HFpEF) heterogén etiológiájú és patomechanizmusú betegség, változó klinikai manifesztációval. Amennyiben a HFpEF krónikus vesebetegséggel (CKD) szövődik, magas morbiditással és mortalitással jár. A HFpEF és a CKD számos közös társbetegséggel és rizikófaktorral rendelkezik, mint a hypertonia, az obesitas, a diabetes vagy a metabolikus szindróma. A HFpEF a vesét elsősorban a magas centrális vénás nyomáshoz köthető patomechanizmus által károsítja, míg a CKD a proinflammatorikus miliő kialakításával indítja el a balkamra-remodellinghez vezető folyamatot. A diagnózis felállítása nem mindig egyszerű, a HFpEF tekintetében pontrendszerek állnak rendelkezésre, amelyek a klinikumot, társbetegségeket, echokardiográfiás paramétereket és az NT-proBNP-szintet veszik alapul. Kérdéses diagnózis esetén a terheléses vizsgálatoknak van egyre nagyobb létjogosultsága, hiszen jellemzően fizikai aktivitásra jelentkeznek panaszok. Kezelés tekintetében eddig az SGLT-2-gátlók bizonyították prognosztikus jelentőségüket mind a HFpEF, mind pedig a CKD tekintetében. A folyamatban lévő klinikai vizsgálatok pedig a GLP-1-agonistákkal és mineralokortikoidreceptor-antagonistákkal mutatnak biztató eredményeket. Várhatóan a HFpEF-CKD kezelésében is a több támadáspontú, kombinációs kezelés vezet majd eredményhez. A betegség egy megfelelően felépített, jól együttműködő multidiszciplináris csapatot igényel a teljes spektrumban (korai diagnózis, kezelés, hosszú távú gondozás), mivel így a betegek számára kedvezőbb életminőséget és kimenetelt biztosíthatunk.
Nanopore Sequencing of Cell-free DNA: An Emerging Liquid Biopsy Approach for Brain Tumor Molecular Profiling
Authors: Addissouky Tamer A.
Published: November 2024

Background: Brain tumors exhibit significant molecular heterogeneity, complicating diagnosis, prognosis, and treatment. Traditional tissue biopsies are invasive and often fail to capture the full tumor landscape due to intratumoral heterogeneity. Liquid biopsy, which analyzes cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA), offers a minimally invasive alternative for tumor profiling. Nanopore sequencing, a novel long-read sequencing technology, is emerging as a valuable tool in this context.

Purpose: This review explores the application of nanopore sequencing in molecular profiling of brain tumors using liquid biopsy, focusing on its ability to detect both genetic and epigenetic alterations with clinical relevance.

Main body: Brain tumors, such as gliomas and medulloblastomas, are characterized by diverse molecular profiles, which influence patient outcomes and treatment strategies. Nanopore sequencing offers unique advantages for profiling cfDNA from biofluids like cerebrospinal fluid (CSF) and plasma, including the ability to generate long reads and detect structural variants, copy number alterations, and methylation patterns. Several studies have demonstrated its potential to identify key mutations (e.g., IDH1/2, H3K27 M) and track tumor evolution through serial cfDNA monitoring. However, challenges remain, including low ctDNA fractions in biofluids and bioinformatic complexities.

Conclusion: Nanopore sequencing holds significant promise for advancing non-invasive molecular profiling of brain tumors, offering real-time insights into tumor genomics and evolution. This technology could revolutionize personalized brain tumor management, but further validation and optimization are needed before it can be routinely applied in clinical practice.
Democratic Co-Production and Co-Creation in Action: The New England Town Meeting
Authors: Rogers Sawyer
Published: November 2024

Kensington, New Hampshire, United States, is a rural community governed by the New England Town Meeting, a form of direct democracy with centuries of co-creating and co-producing public services. This paper utilizes archival documents and takes a multiple descriptive case study approach with process tracing. I have five findings regarding democratic co-creation and democratic co-production within Kensington. One, it is a bargaining process resulting in restrictions for the public’s benefit. Two, that empowerment and impact are more prominent than equity and inclusion. Three, it is supported through networks. Four, it produces substantial levels of creative problem-solving, power sharing, and resilient governance while ensuring the protection of minorities and increasing opportunities for representation. My overarching finding is that co-production and co-creation when operating with democracy, can improve each other’s democratic outcomes but are only as democratic as the bodies creating them.
Two proofs of the Riemann hypothesis
Authors: Abe Yukitaka
Published: November 2024

We prove the Riemann hypothesis by a new analytic approach. We first give a new zero-free region of $\zeta (s)$. Using this region, we prove the Riemann hypothesis by two ways. We use a lemma on Dirichlet series and the theorem of de la Vall\'ee Poussin in the first proof. The second one depends on numerical results.
Swifties Experience: Examining Taylor Swift The Eras Tour (2023) Movie as Concert Mediatization
Authors: Ambadar Alleyda Maharani
Published: November 2024

This research examines Taylor Swift’s concert documentary movie called The Eras Tour (2023) that created a shift in audience’s cinema experience by not customarily watching a movie but emerge themselves which resulting in a ‘concert-feel- like’ activity. This study shows an alternative and complement live performance and streaming technology that previously researched by Scherzinger (2019) as music distribution method. Using Hjarvard’s concept of mediatization and Harvey’s theory of the production of space, I analyze how this movie concert influences audience interactions which create a new social space within cinema. Data were collected through interviews and social media documentation to examine the watching experience of The Eras Tour (2023) movie. This research finds that this mediatized concert acts as an incomplete substitution for live performances, positioning cinema as a concert space due to the implications of mediatization. Additionally, the research reveals that audience interactions beyond merely watching the movie demonstrate an amalgamation process that fosters solidarity within the fandom. Interestingly, this phenomenon generally ‘breaks the rules’ of traditional cinema logic due to the amalgamations that occur. Thus, this research shows that the mediatized concert acts as an incomplete substitution of live performance, which contribute to modern practice of mediatization in media and music industry.
Comparative Analysis Between Sharia Pawnshops and Conventional Pawnshops in The Economic Empowerment of Indonesian Communities
Authors: Rahmadanti Nindya Ismi , Sugiarti Dian
Published: November 2024

Sharia Pawnshops and Conventional Pawnshops are two financial entities that play an important role in strengthening the empowerment of Indonesian society. For years, they have been offering credit services with the aim of improving people's financial situations. However, the two institutions operate using different principles and methodologies. The aim of this scientific work is to analyze and then determine which one is more empowering to the community, between conventional pawnshops and sharia pawnshops. This research is included in qualitative research, with data sources containing all material that can be used as a guideline for research emphasis, namely the comparison between sharia pawnshops and conventional pawnshops in empowering Indonesian society. Sharia pawnshops play a bigger and more effective role in empowering the community, especially by providing financial products based on Islamic sharia principles. Sharia pawnshops prohibit all types of interest and focus on contract terms, honesty and security required in buying and selling transactions based on Islamic law.
Pengaruh Activity Based Workplace Terhadap Kinerja Pegawai di KPP Pratama Biak
Authors: Munawir  , Hadya Rizka
Published: November 2024

Kinerja pegawai merupakan faktor kunci dalam keberhasilan sebuah organisasi. Dalam upaya meningkatkan kinerja pegawai, Activity Based Workplace (ABW) telah menjadi pendekatan yang semakin popular dalam desain ruang kerja. Penelitian ini bertujuan untuk mengetahui pengaruh penerapan (ABW) terhadap kinerja pegawai di Kantor Pelayanan Pajak (KPP) Pratama Biak selaku instansi pemerintah dibawah Kementerian Keuangan yang berpedoman pada Keputusan Menteri Keungan Nomor 453/KMK.01/2020 tentang Pedoman Pelaksanaan Activity Based Workplace Di Lingkungan Kementerian Keuangan dalam menerapkan ABW. Metode penelitian yang digunakan adalah pendekatan dengan kualitatif dengan melakukan observasi dan menganalisis laporan hasil kinerja pegawai. Hasil penelitian menunjukkan bahwa penerapan ABW berpengaruh terhadap kinerja pegawai di KPP Pratama Biak. Implikasi dari penelitian ini memberikan pemahaman lebih lanjut tentang pentingnya desain ruang kerja yang mendukung produktivitas dan kreativitas pegawai dalam konteks pelayanan publik
Analisis Pengaruh Kualitas Pelayanan Terhadap Kepuasan Pelanggan di Mixue Gerai Ruko Orange Ciangsana
Authors: Clara Shinta Dewi  , Abdillah Wildan Army
Published: November 2024

Ada banyak faktor yang dapat mempengaruhi kepuasan pelanggan salah satunya adalah kualitas pelayanan. Tujuan dalam penelitian ini adalah untuk mengetahui kualitas pelayanan di Mixue Gerai Ruko Orange Ciangsana Kabupaten Bogor, untuk mengetahui Kepuasan Pelanggan pada Mixue Gerai Ruko Orange Ciangsana Kabupaten Bogor, serta untuk mengetahui seberapa besar pengaruh Kualitas Pelayanan terhadap kepuasan pelanggan di Mixue Gerai Ruko Orange Ciangsana Kabupaten Bogor. Metode dalam penelitian ini adalah kuantitatif korelasional. Hasil penelitian yang diperoleh adalah kualitas pelayanan di Mixue Gerai Ruko Orange Ciangsana Kabupaten Bogor menurut pandangan responden dikategorikan Sangat Baik, karena nilai prosentase tersebut berada pada rentang nilai 86 % - 100 %. Kepuasan pelanggan di Mixue Gerai Ruko Orange Ciangsana Kabupaten Bogor berdasarkan jawaban angket responden dikategorikan Sangat Baik, karena nilai prosentase tersebut berada pada rentang nilai 86 % - 100 %. Sementara pengaruh kualitas pelayanan terhadap loyalitas pelanggan Mixue Gerai Ruko Orange Ciangsana Kabupaten Bogor dinyatakan Kuat, karena nilai interpretasi koefisien korelasi nilai R-nya berada pada rentang nilai 0,60 - 0,80. Selain itu kualitas pelayanan mempunyai pengaruh positif dan signifikan terhadap tingkat kepuasan pelanggan di Mixue Gerai Ruko Orange Ciangsana Kabupaten Bogor karena nilai T-hitung (11,896) lebih besar dari nilai T-tabel (1,611).
Efficacy of a polyherbal formula for controlling lice infestation in chickens and goats in backyard farming system in Romania
Authors: Coroian Mircea , Hociotă Cristinel-Cornel , Varga Erzsébet , Fülöp Ibolya , Fazakas Mihaly , Györke Adriana
Published: November 2024

Introduction

Lice infestation negatively impacts the welfare and productivity of domestic animals. This study aimed to evaluate the efficacy of a commercial polyherbal formula (PHF) containing Asarum europaeum, Lavandula angustifolia, Artemisia absinthium, and Tanacetum vulgare in managing lice infestations in chickens and goats within a backyard farming system in Romania.

Methods

The PHF was analyzed using high-performance liquid chromatography (HPLC) to determine its phytochemical composition. Chickens and goats with confirmed lice infestations were treated with the PHF by spraying it on the entire body. Treatments were administered three times at 14-day intervals for goats and at both 14- and 7-day intervals for chickens. Lice infestations were assessed in experimental groups before each treatment by counting the collected lice specimens.

Results

HPLC analysis identified key compounds in PHF: kaempferol (336.25 mg/ml), quercetin (88.38 mg/ml), epicatechin (43.98 mg/ml), and catechin (9.43 mg/ml). The PHF effectively controlled chewing lice in both chickens and goats, achieving a mortality rate of 76–98% in chickens and 96% in goats. However, the PHF was not effective against sucking lice in goats. A significant reduction in lice infestation (75% in chickens) was observed when the PHF was applied at 7-day intervals. No adverse reactions were noted in treated animals.

Discussion

The polyherbal formula demonstrated promising efficacy against chewing lice in chickens and goats, supporting its potential use as an alternative to chemical treatments, especially in organic farming settings. The findings suggest that this PHF could be a viable option for managing lice infestations in domestic animals, particularly where organic practices are prioritized.
Novosorb® BTM- history, production and application in challenging wounds
Authors: Rajaram Rohan , Zhang Min , Premaratne Gehan , Ng Sally
Published: November 2024

Novosorb® Biodegradable Temporising Matrix (BTM) is an entirely synthetic dermal matrix that is gaining popularity in the management of challenging wounds. Not only does it provide a framework in which to grow an organised neodermis, it is also especially resistant to infection. Today, the matrix is available as a 2 mm thick open cell polyurethane foam with a non-degrading sealing membrane. Its current form is the result of numerous in vitro and in vivo experiments that examined its shape, biodegradation, inflammatory response, and cytotoxicity. Clinical data on the use of BTM in a variety of cases is novel and presents early insights into its ability to foster wound healing where otherwise improbable. This review presents the history and development of Novosorb® BTM as well as all the currently available clinical data on its efficacy in difficult wounds such as: major burns, necrotising soft tissue infection, chronic wounds and in non graftable wound beds.
Biomechanical effects of different mandibular movements and torque compensations during mandibular advancement with clear aligners: a finite element analysis
Authors: Wang Ya , Daraqel Baraa , Wang Ying , Yang Dan , Dong Yihan , Hu Yun , Zheng Leilei
Published: November 2024

Introduction

This study aimed to evaluate the biomechanical effects of different mandibular movements and torque compensations during mandibular advancement with clear aligners using finite element analysis.

Methods

Models were constructed to include the mandible, teeth, periodontal ligament (PDL), and clear aligners with buccal wings. Five oral muscles (superficial masseter, deep masseter, medial temporalis, posterior temporalis, and medial pterygoid) were represented as springs. Muscle values were measured and applied during different mandibular movements, including advancement distances (1–7 mm) and occlusal opening distances (2–4 mm). Different torque compensation angles (0°, 1°, 2°, and 3°) were applied to the mandibular central incisor.

Results

When the mandibular advancement was equal to or slightly excessed the occlusal opening distance, stress on the posterior PDL decreased and became more evenly distributed. Increasing the occlusal opening distance significantly raised stress on the posterior PDL and caused grater labial inclination of the mandibular anterior teeth. As the torque compensation increased, the labial inclination of the mandibular central incisor decreased, but stress on the PDL increased. Nearly complete bodily movement of the lower central incisor was achieved with torque compensation angles of approximately 15°, 19°, and 20° in models M1-2, M2-3, and M3-4, respectively.

Conclusion

To maintain periodontal health during mandibular advancement, it is recommended that the mandibular advancement distance be equal to or slightly excessed the occlusal opening distance. Excessive occlusal opening distance increases stress on the posterior PDL and the labial inclination of mandibular anterior teeth, requiring careful control. Additionally, proper torque control of the mandibular interior teeth is crucial for optimal outcomes.
Significance of exosomes in osteosarcoma research: a systematic review and meta-analysis of a singular clinical investigation
Authors: Liu Xuehong , Ye Jingyao , Guo Wenlong , Wang Junqing
Published: November 2024

Background

Osteosarcoma is the most prevalent among primary bone malignancies, and its standard intervention involves neoadjuvant chemotherapy - surgical adjuvant chemotherapy (MAP regimen) with adriamycin, cisplatin, and high-dose methotrexate. Early-stage osteosarcoma can be effectively treated with surgical resection along with chemotherapy or radiotherapy. However, as the cancer progresses, the efficacy of chemo- and radiotherapy decreases, and the associated problems increase. The current understanding of osteosarcoma development, diagnosis, and treatment does not meet clinical demands. More recently, there has been a significant increase in exosome-associated osteosarcoma research, potentially opening up novel possibilities for osteosarcoma research.

Purpose

We comprehensively evaluated and analyzed the advancement of preclinical research related to exosome-osteosarcoma. We aimed to establish a practical, theoretical foundation for future research initiatives.

Study design

The selected design was a systematic review and meta-analysis.

Methods

Scientific databases, such as PubMed, Embase, The Cochrane Library, and Web of Science, were extensively screened for exosome and osteosarcoma articles. Two highly trained investigators separately reviewed the literature, extracted relevant information, and assessed study quality. Subsequently, we conducted a meta-analysis using Review Manager 5.4.

Results

In total, 25 animal-based randomized controlled trials (RCTs) were selected for analysis. Among them, 13 studies provided strong evidence of cellular exosomes regulating osteosarcoma development from bone marrow mesenchymal stem cells, osteosarcoma cells, and macrophages. In addition, 12 studies demonstrated the therapeutic potential of exosomes in managing osteosarcoma, among which 7 studies transplanted transfected exosomes directly into animals as drugs, and five studies employed exosomes as drug carriers, which were next transplanted into animals.

Conclusion

Based on our meta-analysis, macrophages strongly modulate osteosarcoma development, and engineered exosomes provide the most effective exosome-based osteosarcoma treatment.
Vascular endothelial growth factor facilitates the effects of telocytes on tumor cell proliferation and migration
Authors: Li Fujie , Tang Xueying , Cao Haitao , Wang Wenya , Geng Chengyue , Sun Zuyao , Shen Xiaokun , Li Shinan
Published: November 2024

Background

Telocytes, recently recognized as interstitial cells with a diverse range of potential functions, have attracted considerable attention for their involvement in tumorigenesis. Nevertheless, owing to certain challenges in the isolation and cultivation of telocytes, the research on telocytes has advanced rather slowly. Therefore, it is imperative to study the role and mechanisms of telocytes in tumors.

Methods

We improved the separation method and successfully isolated telocytes by exploiting the combination of cell adhesion and magnetic bead sorting. Telocytes conditioned medium was collected to culture tumor cells and explore the role and mechanisms of telocytes in tumors.

Results

MTT and colony formation assays demonstrated that telocytes promoted tumor cell proliferation. Wound healing experiments and transwell assays indicated that telocytes enhanced tumor cell migration. Real-time reverse transcriptase PCR analysis showed that the expression of E-cadherin was decreased, and that of Vimentin was notably increased. ELISA results revealed that telocytes secreted high levels of vascular endothelial growth factor (VEGF). And the promoting effects were alleviated by the VEGF inhibitor bevacizumab.

Conclusion

Our findings revealed that telocytes promoted tumor cell proliferation, migration, and angiogenesis through VEGF. Notably, these effects were inhibited by the addition of bevacizumab. In conclusion, our findings illuminated the role of telocytes in promoting tumor progression, and confirmed their crucial regulatory role in the growth of tumor cells.
Structural and antimicrobial properties of synthesized gold nanoparticles using biological and chemical approaches
Authors: Kalantari Hamidreza , Turner Raymond J.
Published: November 2024

This study explores the synthesis and characterization of gold nanoparticles (AuNPs) using green and chemical methods, employing ginger extract and curcumin as reducing agents, in comparison to sodium citrate reduction. The biosynthesized AuNPs synthesized with ginger extract exhibited an average hydrodynamic diameter of 15 and 10 nm for curcumin-conjugated AuNPs, while chemically synthesized AuNPs with sodium citrate displayed an average size of 10 nm. Assessments via Zeta potential measurements revealed negative surface charges across all samples, with the curcumin-conjugated AuNPs showing −36.3 mV, ginger extract-synthesized AuNPs showing −31.7 mV, and chemically produced gold nanoparticles having a surface charge of −40.4 mV. Transmission Electron Microscopy (TEM) confirmed spherical morphologies for the synthesized nanoparticles,and it revealed the presence of biomolecules embedded within the nanoparticles synthesized using biological materials, whereas chemically synthesized AuNPs lacked such features. The FTIR spectra of the biosynthesized AuNPs highlighted the presence of phenolic and aromatic compounds from the ginger extract and curcumin, indicating their role in coating the nanoparticles. Gas chromatography-mass spectrometry (GC-MS) analysis identified gingerol as a key component in the ginger extract, contributing to nanoparticle capping. The antimicrobial efficacy of the AuNPs was evaluated against P. aeruginosa, E. coli, and S. aureus, revealing superior activity for curcumin-AuNPs, with ginger-AuNPs also outperforming chemically synthesized counterparts. These findings confirm the advantages of biological approaches, using a plant extract like ginger and pure curcumin suspension, for better size distribution when used as reducing agents, along with improved antimicrobial efficacy compared to chemically produced gold nanoparticles synthesized with sodium citrate. This study also highlight the potential of green-synthesized AuNPs in biomedical applications, due to their enhanced stability from higher surface charge and the repeatability of biological methods.
Salmonella Typhi Haplotype 58 biofilm formation and genetic variation in isolates from typhoid fever patients with gallstones in an endemic setting in Kenya
Authors: Muturi Peter , Wachira Peter , Wagacha Maina , Mbae Cecilia , Kavai Susan M. , Mugo Michael M. , Mohamed Musa , González Juan F. , Kariuki Samuel , Gunn John S.
Published: November 2024

Although typhoid fever has largely been eliminated in high-income countries, it remains a major global public health concern especially among low- and middle-income countries. The causative agent, Salmonella enterica serovar Typhi (S. Typhi), is a human restricted pathogen with a limited capacity to replicate outside the human host. Human carriers, 90% of whom have gallstones in their gallbladder, continue to shed the pathogen for an ill-defined period of time after treatment. The genetic mechanisms involved in establishing the carrier state are poorly understood, but S. Typhi is thought to undergo specific genetic changes within the gallbladder as an adaptive mechanism. In the current study, we aimed to identify the genetic differences in longitudinal clinical S. Typhi isolates from asymptomatic carriers with gallstones in a typhoid endemic setting in Nairobi, Kenya. Whole-genome sequences were analyzed from 22 S. Typhi isolates, 20 from stool samples, and 2 from blood samples, all genotype 4.3.1 (H58). Out of this, 19 strains were from four patients also diagnosed with gallstones, of whom three had typhoid symptoms and continued to shed S. Typhi after treatment. All isolates had point mutations in the quinolone resistance-determining region (QRDR), and only sub-lineage 4.3.1.2.EA3 encoded multidrug resistance genes. There was no variation in antimicrobial resistance patterns among strains from the same patient/household. Non-multidrug resistant (MDR) isolates formed significantly stronger biofilms in vitro than the MDR isolates, p<0.001. A point mutation within the treB gene (treB A383T) was observed in strains isolated after clinical resolution from patients living in 75% of the households. For missense mutations in Vi capsular polysaccharide genes, tviE P263S was also observed in 18% of the isolates. This study provides insights into the role of typhoid carriage, biofilm formation, AMR genes, and genetic variations in S. Typhi during asymptomatic carriage.
Developing teamwork: transitioning between stages in human-agent collaboration
Authors: Kaelin Vera C. , Tewari Maitreyee , Benouar Sara , Lindgren Helena
Published: November 2024

Introduction

Human-centric artificial intelligence (HCAI) focuses on systems that support and collaborate with humans to achieve their goals. To better understand how collaboration develops in human-AI teaming, further exploration grounded in a theoretical model is needed. Tuckman's model describes how team development among humans evolves by transitioning through the stages of forming, storming, norming, performing, and adjourning. The purpose of this pilot study was to explore transitions between the first three stages in a collaborative task involving a human and a human-centric agent.

Method

The collaborative task was selected based on commonly performed tasks in a therapeutic healthcare context. It involved planning activities for the upcoming week to achieve health-related goals. A calendar application served as a tool for this task. This application embedded a collaborative agent designed to interact with humans following Tuckman's stages of team development. Eight participants completed the collaborative calendar planning task, followed by a semi-structured interview. Interviews were transcribed and analyzed using inductive content analysis.

Results

The results revealed that the participants initiated the storming stage in most cases (n = 7/8) and that the agent initiated the norming stage in most cases (n = 5/8). Additionally, three main categories emerged from the content analyses of the interviews related to participants' transition through team development stages: (i) participants' experiences of Tuckman's first three stages of team development; (ii) their reactions to the agent's behavior in the three stages; and (iii) factors important to the participants to team up with a collaborative agent.

Conclusion

Results suggest ways to further personalize the agent to contribute to human-agent teamwork. In addition, this study revealed the need to further examine the integration of explicit conflict management into human-agent collaboration for human-agent teamwork.