bluuebunny/crossref_metadata_2025 huggingface dataset:
Documenting the de-identification process of clinical and imaging data for AI for health imaging projects
Authors: Kondylakis Haridimos , Catalan Rocio , Alabart Sara Martinez , Barelle Caroline , Bizopoulos Paschalis , Bobowicz Maciej , Bona Jonathan , Fotiadis Dimitrios I. , Garcia Teresa , Gomez Ignacio , Jimenez-Pastor Ana , Karatzanis Giannis , Lekadir Karim , Kogut-Czarkowska Magdalena , Lalas Antonios , Marias Kostas , Marti-Bonmati Luis , Munuera Jose , Nikiforaki Katerina , Pelissier Manon , Prior Fred , Rutherford Michael , Saint-Aubert Laure , Sakellariou Zisis , Seymour Karine , Trouillard Thomas , Votis Konstantinos , Tsiknakis Manolis
Published: May 2024

Artificial intelligence (AI) is revolutionizing the field of medical imaging, holding the potential to shift medicine from a reactive “sick-care” approach to a proactive focus on healthcare and prevention. The successful development of AI in this domain relies on access to large, comprehensive, and standardized real-world datasets that accurately represent diverse populations and diseases. However, images and data are sensitive, and as such, before using them in any way the data needs to be modified to protect the privacy of the patients. This paper explores the approaches in the domain of five EU projects working on the creation of ethically compliant and GDPR-regulated European medical imaging platforms, focused on cancer-related data. It presents the individual approaches to the de-identification of imaging data, and describes the problems and the solutions adopted in each case. Further, lessons learned are provided, enabling future projects to optimally handle the problem of data de-identification.

Critical relevance statement

This paper presents key approaches from five flagship EU projects for the de-identification of imaging and clinical data offering valuable insights and guidelines in the domain.

Key Points

ΑΙ models for health imaging require access to large amounts of data.

Access to large imaging datasets requires an appropriate de-identification process.

This paper provides de-identification guidelines from the AI for health imaging (AI4HI) projects.
Paracrine- and cell-contact-mediated immunomodulatory effects of human periodontal ligament-derived mesenchymal stromal cells on CD4+ T lymphocytes
Authors: Behm Christian , Miłek Oliwia , Rausch-Fan Xiaohui , Moritz Andreas , Andrukhov Oleh
Published: May 2024

Background

Mesenchymal stromal cells (MSCs) isolated from the periodontal ligament (hPDL-MSCs) have a high therapeutic potential, presumably due to their immunomodulatory properties. The interaction between hPDL-MSCs and immune cells is reciprocal and executed by diverse cytokine-triggered paracrine and direct cell-to-cell contact mechanisms. For the first time, this study aimed to directly compare the contribution of various mechanisms on this reciprocal interaction using different in vitro co-culture models at different inflammatory milieus.

Methods

Three co-culture models were used: indirect with 0.4 μm-pored insert, and direct with or without insert. After five days of co-culturing mitogen-activated CD4+ T lymphocytes with untreated, interleukin (IL)-1β, or tumor necrosis factor (TNF)-α- treated hPDL-MSCs, the CD4+ T lymphocyte proliferation, viability, and cytokine secretion were investigated. The gene expression of soluble and membrane-bound immunomediators was investigated in the co-cultured hPDL-MSCs.

Results

Untreated hPDL-MSCs decreased the CD4+ T lymphocyte proliferation and viability more effectively in the direct co-culture models. The direct co-culture model without inserts showed a strikingly higher CD4+ T lymphocyte cell death rate. Adding IL-1β to the co-culture models resulted in substantial CD4+ T lymphocyte response alterations, whereas adding TNF resulted in only moderate effects. The most changes in CD4+ T lymphocyte parameters upon the addition of IL-1β or TNF-α in a direct co-culture model without insert were qualitatively different from those observed in two other models. Additionally, the co-culture models caused variability in the immunomediator gene expression in untreated and cytokine-triggered hPDL-MSCs.

Conclusion

These results suggest that both paracrine and cell-to-cell contact mechanisms contribute to the reciprocal interaction between hPDL-MSCs and CD4+ T lymphocytes. The inflammatory environment affects each of these mechanisms, which depends on the type of cytokines used for the activation of MSCs’ immunomodulatory activities. This fact should be considered by comparing the outcomes of the different models.
Bridging the gap between in vitro and in vivo models: a way forward to clinical translation of mitochondrial transplantation in acute disease states
Authors: Bodenstein David F. , Siebiger Gabriel , Zhao Yimu , Clasky Aaron J. , Mukkala Avinash N. , Beroncal Erika L. , Banh Lauren , Aslostovar Lili , Brijbassi Sonya , Hogan Sarah E. , McCully James D. , Mehrabian Mohadeseh , Petersen Thomas H. , Robinson Lisa A. , Walker Melanie , Zachos Constantine ,   MITO2i-MbD Mitochondrial Transplant Consortium, Viswanathan Sowmya , Gu Frank X. , Rotstein Ori D. , Cypel Marcelo , Radisic Milica , Andreazza Ana C.
Published: May 2024

Mitochondrial transplantation and transfer are being explored as therapeutic options in acute and chronic diseases to restore cellular function in injured tissues. To limit potential immune responses and rejection of donor mitochondria, current clinical applications have focused on delivery of autologous mitochondria. We recently convened a Mitochondrial Transplant Convergent Working Group (CWG), to explore three key issues that limit clinical translation: (1) storage of mitochondria, (2) biomaterials to enhance mitochondrial uptake, and (3) dynamic models to mimic the complex recipient tissue environment. In this review, we present a summary of CWG conclusions related to these three issues and provide an overview of pre-clinical studies aimed at building a more robust toolkit for translational trials.
The crucial role of HFM1 in regulating FUS ubiquitination and localization for oocyte meiosis prophase I progression in mice
Authors: Zhong Chenyi , Wang Huiyuan , Yuan Xiong , He Yuheng , Cong Jing , Yang Rui , Ma Wenjie , Gao Li , Gao Chao , Cui Yugui , Wu Jie , Tan Rongrong , Pu Danhua
Published: May 2024

Background

Helicase for meiosis 1 (HFM1), a putative DNA helicase expressed in germ-line cells, has been reported to be closely associated with premature ovarian insufficiency (POI). However, the underlying molecular mechanism has not been clearly elucidated. The aim of this study was to investigate the function of HFM1 in the first meiotic prophase of mouse oocytes.

Results

The results suggested that the deficiency of HFM1 resulting in increased apoptosis and depletion of oocytes in mice, while the oocytes were arrested in the pachytene stage of the first meiotic prophase. In addition, impaired DNA double-strand break repair and disrupted synapsis were observed in the absence of HFM1. Further investigation revealed that knockout of HFM1 promoted ubiquitination and degradation of FUS protein mediated by FBXW11. Additionally, the depletion of HFM1 altered the intranuclear localization of FUS and regulated meiotic- and oocyte development-related genes in oocytes by modulating the expression of BRCA1.

Conclusions

These findings elaborated that the critical role of HFM1 in orchestrating the regulation of DNA double-strand break repair and synapsis to ensure meiosis procession and primordial follicle formation. This study provided insights into the pathogenesis of POI and highlighted the importance of HFM1 in maintaining proper meiotic function in mouse oocytes.
Laparoscopic repair of a primary parahiatal hernia combined with gastric volvulus: a case report and literature review
Authors: Muramatsu Hirotada , Amaike Hisashi , Ogura Rena , Shirono Kouichi , Kamiya Noriyuki
Published: May 2024

Background

Parahiatal hernias present a hernial orifice at the diaphragm that is adjacent to the esophageal hiatus, differing from the paraesophageal type of hiatal hernias. Although diagnostic imaging has advanced in recent years, diagnosing parahiatal hernias remains challenging. We herein report a case in which we performed laparoscopic surgery and intraoperatively diagnosed a parahiatal hernia.

Case presentation

A 67-year-old man presented to our hospital with difficulty eating, epigastric pain, and vomiting. We suspected a paraesophageal hiatal hernia. Laparoscopic surgery was performed, and a diagnosis of parahiatal hernia was made. We closed the hernial orifice with direct simple closure using nonabsorbable threads. The patient’s postoperative recovery course was reasonable, and he was discharged on the twelfth postoperative day.

Conclusions

Parahiatal hernias are rare, and a definitive diagnosis is difficult. Laparoscopic surgery can help accurately diagnose and treat patients presenting with the condition.
Exploring the impact of aluminum oxide nanoparticles on waste transformer biodiesel blend under variable injection timing
Authors: Prabu A.
Published: May 2024

This study investigated the use of nano-blended biodiesel, made by mixing waste transformer biodiesel with nanoscale aluminum oxide particles. A fuel blend ratio containing both diesel and biodiesel components was created with 100 parts per million of alumina nanoparticles. All tests were conducted at various loads in an engine, using diesel, biodiesel, and nano-blended biodiesel fuel. The outcomes demonstrated that adding nanoparticles improved engine thermal efficiency and reduced emissions, especially at higher fuel injection timings. The greatest increase in brake thermal efficiency, 6% higher than diesel mode, was achieved with a nano-blended biodiesel formulation containing 100 ppm of aluminum oxide, at a fuel injection timing of 27 before top dead center under full load conditions. With a constant nanoparticle-blended biodiesel content and fuel injection timing of 27 before top dead center, reductions of 1.5% in smoke, 33% in hydrocarbon, and 8% in carbon monoxide emissions were observed, with a 9.7% increase in NO emissions.
Anticancer potential of four triterpenoids against NCI-60 human tumor cell lines
Authors: Irungu Beatrice Njeri , Nyangi Mary , Ndombera Fidelis Toloyi
Published: May 2024

Background

The burden of cancer incidences and mortality is rapidly increasing worldwide resulting in an increased demand for new therapies. Secondary metabolites extracted from medicinal plants have significantly contributed toward discovery of new cancer therapies some of which are in clinical use. In this study, anticancer potential of four triterpenoids, namely oleanonic acid (EK-2), 3-epi-oleanolic acid (EK-8), 1,2,3,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene (EK-4) and 2,3,22,23-tetrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene (EK-9), extracted from Ekebergia capensis Sparrm root bark was evaluated.

Results

We employed CLC-Pred to initially evaluate cytotoxicity of previously isolated compounds in silico where predictions revealed high probability of bioactivity. The compounds were then submitted to the National Cancer Institute (NCI), Developmental Therapeutics Program, for bioactivity evaluation against NCI-60 human tumor cell lines. The four compounds demonstrated a range of potencies at a concentration of 10 µM. The results revealed that EK-9 was the most potent with mean growth percent of 32.84 and cases of lethality (negative growth percent) against two leukemia cell lines (HL-60 (TB) and RPMI-8226) and HT29 (colon cancer) and SK-MEL-5 (melanoma). This molecule was further evaluated in a five-dose assay where notable growth inhibition against leukemia cells, HL-60 (TB), RPMI-8226 and K-562 was observed with growth inhibitory activity (GI50) values of 3.10, 3.74 and 5.07 µM, respectively. In addition, total growth inhibition was observed at 11.2 μM and 18.9 μM for HL-60 (TB) and RPMI-8226 cells, respectively, partly accounting for the negative growth percent.

Conclusion

The study has demonstrated anticancer properties of the four triterpenoids with compound EK-9 being the most potent overall having selective bioactivity in leukemia and breast cancer cells. Further studies focusing on elucidating its mechanism of action will be useful in exploration of the therapeutic potential of triterpenoids in general.
GCC banks liquidity and financial performance: does the type of financial system matter?
Authors: Bilal Zaroug , AlGhazali Abdullah , Samour Ahmed
Published: May 2024

This study examines whether the type of financial structure in the GCC influences the relationship between liquidity risk and banks’ performance from 2007 to 2021. By employing fixed effects and fully modified ordinary least squares (FMOLS), we find that the impact of liquidity risk on bank profitability differs among bank-based and market-based systems. Specifically, the results show that the profitability of banks operating in bank-based countries is positively influenced by the liquidity risk compared to their counterparts. The study also demonstrates that the global financial crisis increases banks’ profitability in the bank-based financial system. Furthermore, the results show that gross domestic product growth (GDPG) determines banks’ financial profitability in the banks-based market. This study offers some important implications for policymakers to consider the type of financial system to stimulate bank stability.
Signaling pathways in liver cancer: pathogenesis and targeted therapy
Authors: Xue Yangtao , Ruan Yeling , Wang Yali , Xiao Peng , Xu Junjie
Published: May 2024

Liver cancer remains one of the most prevalent malignancies worldwide with high incidence and mortality rates. Due to its subtle onset, liver cancer is commonly diagnosed at a late stage when surgical interventions are no longer feasible. This situation highlights the critical role of systemic treatments, including targeted therapies, in bettering patient outcomes. Despite numerous studies on the mechanisms underlying liver cancer, tyrosine kinase inhibitors (TKIs) are the only widely used clinical inhibitors, represented by sorafenib, whose clinical application is greatly limited by the phenomenon of drug resistance. Here we show an in-depth discussion of the signaling pathways frequently implicated in liver cancer pathogenesis and the inhibitors targeting these pathways under investigation or already in use in the management of advanced liver cancer. We elucidate the oncogenic roles of these pathways in liver cancer especially hepatocellular carcinoma (HCC), as well as the current state of research on inhibitors respectively. Given that TKIs represent the sole class of targeted therapeutics for liver cancer employed in clinical practice, we have particularly focused on TKIs and the mechanisms of the commonly encountered phenomena of its resistance during HCC treatment. This necessitates the imperative development of innovative targeted strategies and the urgency of overcoming the existing limitations. This review endeavors to shed light on the utilization of targeted therapy in advanced liver cancer, with a vision to improve the unsatisfactory prognostic outlook for those patients.
Visualization of scientific production in Caenorhabditis elegans: a bibliometric analysis (1980–2023)
Authors: Berk Şeyda , Özdemir Serkan , Pektaş Ayşe Nur
Published: May 2024

Caenorhabditis elegans (C. elegans) is a nematode and model organism whose entire genome has been mapped, which allows for easy observation of the organism’s development due to its transparent structure, and which is appealing due to its ease of crossover, ease of culture, and low cost. Despite being separated by nearly a billion years of evolution, C. elegans homologs have been identified for the vast majority of human genes and are associated with C. elegans for many biological processes such as apoptosis, cell signaling, cell cycle, cell polarity, metabolism, and aging. A detailed bibliometric study is performed here to examine publication trends in this field. Data were taken from the Web of Science database and analyzed using the bibliometric application Biblioshiny (RStudio). In terms of publication, the results indicated a gradual increase each year between 1980 and 2023. A total of 20,322 records were issued in 96 countries, the majority of which were in the USA, China, and Japan. The most prolific writers, the journals most engaged in the area, the nations, institutions, and keywords used by authors were all determined using the Web of Science database and bibliometric rules. The number of papers in the C. elegans research field is increasing exponentially, and Genetics is the journal with the highest number of articles. This study presents how research patterns have evolved throughout time. As a result, worldwide cooperation and a potential field can be developed.
Effect of blood flow restriction training on pressure pain threshold and hand function among adults with persistent neck pain: A study protocol for a randomized controlled trial
Authors: Sidiq Mohammad , Chahal Aksh , Bansal Nitesh , Alam Sajjad , Verma Rituraj , Reddy Vajrala Krishna , Sharma Jyoti , Khan Sumera , Sharma Yamini , Janakiraman Balamurugan , Hirendra Rai Richa , Malhotra Nitesh
Published: May 2024

Background Persistent neck pain is a prevalent musculoskeletal condition that affects the quality of life and functional abilities of individuals. Blood Flow Restriction Training (BFRT) is a novel therapeutic approach that involves restricting blood flow to exercising muscles to enhance strength and function. However, limited research has been conducted on the effects of BFRT on pressure pain threshold and hand function in adults with persistent neck pain. This randomized controlled trial aims to investigate the potential benefits of BFRT as a treatment intervention for this population. Methods This study will be a prospective 1:1 allocation, parallel group active controlled trail conducted at Physiotherapy Department, Galgotias University. The trial was prospectively registered with the Clinical Trial Registry India CTRI/2023/06/053439. Informed consent will be obtained from all the participants who are eligible to be included in the study. A total of 110 patients with persistent neck pain will be randomly allocated into two groups. The BFRT group will receive supervised training sessions three times a week for eight weeks, performing low-load resistance exercises with blood flow restriction applied using personalized cuff pressure. The control group will receive standard care for neck pain, which may include general advice, manual therapy, and/or home exercises without BFRT. The primary outcome measures will be the pressure pain threshold, assessed using a pressure Algometer, and hand function, evaluated using standardized tests such as Hand Grip Strength and Purdue Peg board Test. Results The data obtained will be analyzed using appropriate statistical methods, and the significance level will be set at p<0.05. Conclusion This trial will contribute valuable contribution highlighting the potential benefits of BFR training in improving pressure pain threshold and hand function in adults with persistent neck pain.
Yöneticilik ve Liderlik Açısından Merhamet Kavramının Kur’an’i Temeli: Âl-i İmrân Suresi 159. Ayet Örnekliğinde Bir Değerlendirme
Authors: Burak Emel , Avcı Hatice
Published: May 2024

Merhamet insanın olduğu tüm mecraların temelini oluşturan kadim bir kavramdır. Bu sebeple günlük hayat ve meşgaleler ile çeşitli roller ve statülerde bulunan insan, ancak merhamet dili ile insani noktada eşitlenecek ve aynı amaca hizmet için gönüllü olacaktır. İş hayatında, küreselleşme ve dijitalleşme ile zaman unsurunun hız ve tüketim kültürüne kurban edilmesi, bireysel başarı hırsını köpürtmektedir. Yapılan çalışmalar, bu durumun en önemli ve kıymetli baş etme metodu olarak insanı özüne davet eden merhamet kavramına işaret etmektedir. Bu sebeple çalışmanın amacı, yöneticilik ve liderlik kavramlarını merhamet ekseninde değerlendirmek üzere iş hayatında insanın özüne davet edilmesine katkı sunmaktır. Çalışmada yönetici, lider ve merhamet kavramlarına teorik çerçevede yer verilmiştir. Ardından yöneticilik ve liderlikte merhamet kavramının Kur’an’i temeline işaret ettiği düşünülen Âl-i İmrân suresi 159. ayet, klasik tefsir örnekleri ile değerlendirilmiştir. Sonuç kısmında ise kavramsal bir yaklaşım ile yönetimde merhamet kavramı Kur’an temelinde değerlendirilmiş, merhamet kavramının insana insanca muamele için anahtar bir rol oynadığı sonucuna ulaşılmıştır.
Le varietà tedesche dell’Alto Adige – Südtirol
Authors: Caria Marco , Autelli Erica
Published: May 2024

This article aims to describe the complex linguistic and sociolinguistic situation of Alto Adige – Südtirol, officially named Autonomous Province of Bolzano – Bozen with a focus on the varieties of German spoken there as first language. The territory, which is officially trilingual as it hosts the Ladin minority in Val Gardena and Val Badia besides the Italian speakers, became part of Italy in 1919 as “spoils of war” after Austrian defeat in the First World War. The division of the ancient historical region of Tyrol meant a subsequent difficult period of forced Italianization, imposing Italian on German in names, toponyms and daily life. Only the determination of the local population and their affection to their language and culture has preserved – even if not always with peaceful means – the survival of the Austrian dialects and traditions and has led to the modern forms of safeguarding and cohabitation which make of this province of Northern Italy one of the strongest linguistic minorities in all Europe.
“Structures of Feeling”: On Tenderness and Other Sensations in Carlos Gamerro’s Fiction
Authors: Bollig Ben
Published: May 2024

Abstract: An important aspect of Carlos Gamerro’s novels is a subtle and nuanced focus on emotions. This paper begins by outlining the “affective technique”—precise, often metaphorical descriptions, of imprecise, hard-to-describe feelings—in his early works, in a nod to the “affective turn” in Latin American studies. Gamerro’s most recent novels— Cardenio and La jaula de los onas —offer funny and provocative digressions from known historical events, but rely on moving depictions of human frailty, pleasure, and interdependence. Gamerro links these through a central emotion: tenderness. Moreover, these novels display a “structural tenderness,” and with it, a relationship between the vulnerability of this emotion and a readerly response—an uncertainty or self-doubt—of being pushed into and out of fiction. La jaula de los onas uses this depiction of mutual vulnerability to tell a moving and politically acute story of violence and cultural erasure in the far south.
In vivo endoscopic optical coherence elastography based on a miniature probe
Authors: Xu Haoxing , Xia Qingrong , Shu Chengyou , Lan Jiale , Wang Xiatian , Gao Wen , Lv Shengmiao , Lin Riqiang , Xie Zhihua , Xiong Xiaohui , Li Fei , Zhang Jinke , Gong Xiaojing
Published: May 2024

Optical coherence elastography (OCE) is a functional extension of optical coherence tomography (OCT). It offers high-resolution elasticity assessment with nanoscale tissue displacement sensitivity and high quantification accuracy, promising to enhance diagnostic precision. However, in vivo endoscopic OCE imaging has not been demonstrated yet, which needs to overcome key challenges related to probe miniaturization, high excitation efficiency and speed. This study presents a novel endoscopic OCE system, achieving the first endoscopic OCE imaging in vivo. The system features the smallest integrated OCE probe with an outer diameter of only 0.9 mm (with a 1.2-mm protective tube during imaging). Utilizing a single 38-MHz high-frequency ultrasound transducer, the system induced rapid deformation in tissues with enhanced excitation efficiency. In phantom studies, the OCE quantification results match well with compression testing results, showing the system's high accuracy. The in vivo imaging of the rat vagina demonstrated the system's capability to detect changes in tissue elasticity continually and distinguish between normal tissue, hematomas, and tissue with increased collagen fibers precisely. This research narrows the gap for the clinical implementation of the endoscopic OCE system, offering the potential for the early diagnosis of intraluminal diseases.
Inkjet-printed waveguide-coupled passive wedge-shaped microdisk resonator with refractive index tunability
Authors: van Schoonhoven Frederik , Tomishige Yoshitaka , Abazi Adrian , Sánchez-Postigo Alejandro , Chen Jinghan , Mikami Yuya , Tate Naoya , Oki Yuji , Schuck Carsten , Yoshioka Hiroaki
Published: May 2024

We incorporate a passive wedge-shaped organic microdisk supporting spatially separated whispering gallery modes into an SU-8 photonic integrated circuit (PIC) by using direct inkjet printing. This innovative method allows the mixing of multiple organic materials, enabling tunability of the refractive index of microdisks, thereby overcoming limitations of single-material resonators from conventional lithography. In this study, the microdisk resonator, with a refractive index matching that of SU-8 by mixing hyperbranched polymers, is mounted horizontally to an optical waveguide, achieving directional coupling between the microdisk and PIC at a wavelength of 1550 nm. Geometrical conditions for successful coupling were obtained by measuring the cross-sectional profile of the fabricated structure’s surface via atomic force microscopy, determining ways to adjust the coupling efficiency.
ChatOCT: embedded clinical decision support systems for optical coherence tomography in offline and resource-limited settings
Authors: Yang Jianlong , Liu Chang , Zhang Haoran , Zheng Zheng , Liu Wenjia , Gu Chengfu , Lan Qi , Zhang Weiyi
Published: May 2024

Large Language Models (LLMs) are revolutionizing various aspects of our lives. Integrating LLMs into Optical Coherence Tomography (OCT) devices could significantly assist doctors by offering diagnostic and treatment recommendations, particularly in situations where medical expertise is scarce. Unlike artificial intelligence (AI) models that provide diagnostic conclusions opaquely, LLMs enhance the safety and efficacy of AI-assisted diagnosis and treatment through interactive human-computer dialogue. However, due to the imperative to protect patient privacy and ensure data security, OCT devices in healthcare settings are commonly operated offline. This limitation prevents the implementation of LLMs in an online environment, contrasting with platforms like ChatGPT or Kimi. Additionally, the operation of current LLMs demands substantial graphics memory, posing a significant challenge for OCT devices that already require considerable graphics memory for tasks such as data acquisition, rendering, and real-time display. In this paper, we introduce ChatOCT, an embedded clinical decision support system with specialized knowledge in OCT and related medical fields, designed to operate offline and with minimal computational resources. We propose a framework for its development, encompassing OCT knowledge injection, Q&A-based clinical instruction tuning, and model compression techniques. The superiority of our models, both the original and a 79% compressed version, has been independently confirmed by ChatGPT (GPT-4) and two clinical ophthalmologists. We envision that ChatOCT could significantly elevate the intelligence and adoption of OCT technology.
Silicon integrated nanophotonic polarizers with graphene oxide 2D films
Authors: Moss David
Published: May 2024

We experimentally demonstrate waveguide and microring resonator (MRR) polarizers by integrating 2D graphene oxide (GO) films onto silicon (Si) photonic devices. The 2D GO films with highly anisotropic light absorption are on-chip integrated with precise control over their thicknesses and sizes. Detailed measurements are performed for the fabricated devices with different GO film thicknesses, coating lengths, and Si waveguide widths. The results show that a maximum polarization-dependent loss (PDL) of ~17 dB is achieved for the hybrid waveguides, and the hybrid MRRs achieved a maximum polarization extinction ratio (PER) of ~10 dB. We also characterize the wavelength- and power-dependent response for these polarizers. The former demonstrates a broad operation bandwidth of over ~100 nm, and the latter verifies performance improvement enabled by photo-thermal changes in GO films. By fitting the experimental results with theoretical simulations, we find that the anisotropy in the loss of GO films dominates the polarization selectivity of these devices. These results highlight the strong potential of 2D GO films for realizing high-performance polarization selective devices in Si photonic platform.
Community preferred drug delivery approaches for pilot roll-out of a potential novel paediatric schistosomiasis treatment option in two endemic counties of Kenya: A mixed methods study
Authors: Masaku Janet , Gachohi John M. , Sinkeet Alice , Maghanga Mary , Wakesho Florence , Omondi Wyckliff , Monnier Nora , Steinmann Peter , Reigl Lisa Sophie , Lange Isabelle L. , Winkler Andrea S. , Njenga Sammy M. , Amuyunzu-Nyamongo Mary
Published: May 2024

Treating preschool age children (PSAC) for schistosomiasis has remained a challenge due to lack of a pediatric formulation. In response to this unmet need, the Paediatric Praziquantel Consortium has developed a potential novel paediatric treatment option. In advance to its roll-out to follow regulatory response, we conducted a social science study to gather information on preferred drug delivery approaches to inform implementation. A cross-sectional study was conducted in eight villages in two purposively selected Kenyan counties. A questionnaire was administered on 690 parents/guardians of PSAC at household level. Preferred drug delivery approaches were analyzed using frequencies and proportions. We conducted key informant interviews with 17 opinion leaders and 28 healthcare workers, and 12 focus group discussions with parents/guardians of PSAC and 7 with community health volunteers (CHVs). Thematic analysis was performed on the qualitative data. Majority of the 690 respondents were women 594 (86.1%) with a mean age of 34.1 (SD = 11.3, min-max = 18–86). Community-based mass drug administration (cMDA) was the most preferred drug delivery method by 598 participants (86.7%), followed by health facility/fixed points by 398 participants (57.7%). Similarly, in the qualitative data participants indicated they prefer cMDA since the CHVs who would distribute the medication are familiar with households with PSAC and are trusted to explain the drug effects. Health facilities/fixed points were the second most preferred drug delivery approach, but some health workers we interviewed expressed concern about potential understaffing and overcrowding of facilities. Appropriate timing of the drug distribution, not to interfere with farming activities, was considered critical, irrespective of the approach used. All profiles of study participants preferred cMDA over the other delivery approaches due to the convenience of receiving drugs at home and providing explanations about the new drug. For positive outcomes, adequate planning, proper timings and community involvement are highly recommended.
Uptake of multi-level HIV interventions and HIV-related behaviours among young people in rural South Africa
Authors: Mthiyane Nondumiso , Shahmanesh Maryam , Copas Andrew , Chimbindi Natsayi , Dreyer Jaco , Zuma Thembelihle , McGrath Nuala , Baisley Kathy , Floyd Sian , Birdthistle Isolde , Sherr Lorraine , Seeley Janet , Harling Guy
Published: May 2024

Combination HIV prevention packages have reduced HIV incidence and improved HIV-related outcomes among young people. However, there is limited data on how package components interact to promote HIV-related prevention behaviours. We described the uptake of HIV prevention interventions supported by Determined, Resilient, Empowered, AIDS-free, Motivated and Safe (DREAMS) Partnership and assessed the association between uptake and HIV-related behaviours among young people in rural KwaZulu-Natal, South Africa. We analysed two cohorts followed from May 2017 to December 2019 to evaluate the impact of DREAMS, covering 13–29 year-old females, and 13–35 year-old males. DREAMS interventions were categorised as healthcare-based or social. We described the uptake of interventions and ran logistic regression models to investigate the association between intervention uptake and subsequent protective HIV-related outcomes including no condomless sex and voluntary medical male circumcision (VMMC). For each outcome, we adjusted for socio-demographics and sexual/pregnancy history and reported adjusted odds ratios (aOR) and 95% confidence intervals (CI). Among 5248 participants, uptake of healthcare interventions increased from 2018 to 2019 by 8.1% and 3.7% for males and females respectively; about half of participants reported receiving both healthcare and social interventions each year. The most utilised combinations of interventions included HIV testing and counselling, school-based HIV education and cash transfers. Participation in social interventions only compared to no intervention was associated with reduced condomless sex (aOR = 1.60, 95%CI: 1.03–2.47), while participation in healthcare interventions only was associated with increased condomless sex. The uptake of interventions did not significantly affect subsequent VMMC overall. Among adolescent boys, exposure to school-based HIV education, cash transfers and HIV testing and counselling was associated with increase in VMMC (aOR = 1.79, 95%CI: 1.04–3.07). Multi-level HIV prevention interventions were associated with an increase in protective HIV-related behaviours emphasizing the importance of accessible programs within both school and community settings for young people.
Identification of pleiotropic and specific therapeutic targets for cardio-cerebral diseases: A large-scale proteome-wide mendelian randomization and colocalization study
Authors: Zhu Yanchen , Wang Yahui , Cui Zhaorui , Liu Fani , Hu Jiqiang
Published: May 2024

Background

The cardiac-brain connection has been identified as the basis for multiple cardio-cerebral diseases. However, effective therapeutic targets for these diseases are still limited. Therefore, this study aimed to identify pleiotropic and specific therapeutic targets for cardio-cerebral diseases using Mendelian randomization (MR) and colocalization analyses.

Methods

This study included two large protein quantitative trait loci studies with over 4,000 plasma proteins were included in the discovery and replication cohorts, respectively. We initially used MR to estimate the associations between protein and 20 cardio-cerebral diseases. Subsequently, Colocalization analysis was employed to enhance the credibility of the results. Protein target prioritization was based solely on including highly robust significant results from both the discovery and replication phases. Lastly, the Drug-Gene Interaction Database was utilized to investigate protein-gene-drug interactions further.

Results

A total of 46 target proteins for cardio-cerebral diseases were identified as robust in the discovery and replication phases by MR, comprising 7 pleiotropic therapeutic proteins and 39 specific target proteins. Followed by colocalization analysis and prioritization of evidence grades for target protein, 6 of these protein-disease pairs have achieved the highly recommended level. For instance, the PILRA protein presents a pleiotropic effect on sick sinus syndrome and Alzheimer’s disease, whereas GRN exerts specific effects on the latter. APOL3, LRP4, and F11, on the other hand, have specific effects on cardiomyopathy and ischemic stroke, respectively.

Conclusions

This study successfully identified important therapeutic targets for cardio-cerebral diseases, which benefits the development of preventive or therapeutic drugs.
Trade shocks and trade diversion due to epidemic diseases: Evidence from 110 countries
Authors: Liu Naixi , Li Yu , Jiang Mingzhe , Liu Bangfan
Published: May 2024

COVID-19 has been a massive trade shock that has disrupted global trade, making the last few years a special phase. Even during normal times, epidemic diseases have acted as trade shocks in specific countries, albeit not to the same extent as COVID-19. For some trade shocks, the situation normalizes after the disease transmission is over; for some, it does not. Thus, specific countries can sometimes lose their original trade ratio due to trade diversion; that is, an epidemic disease could lead to unexpected industry restructuring. To examine this, based on data on 110 WHO members from 1996 to 2018, we use a fixed-effect panel model supported by the Hausman Test to empirically identify whether epidemic diseases can cause trade shocks and trade diversion. We find: First, epidemic disease can lead to negative shocks to a country’s trade growth and its ratio of worldwide trade. Second, with a longer epidemic, the probability of the trade diversion effect increases. Our results hold even after considering country heterogeneity. This presents a considerable concern about the shock of COVID-19 lasting further. Many countries are not just facing the problem of temporary trade shocks, but also the challenge of trade diversions. In particular, the probability of trade diversions is increasing rapidly, especially for late-developed countries due to their lack of epidemic containment and vaccine-producing capabilities. Even middle and high income countries cannot ignore global industry chain restructuring. Forward-looking policies should be implemented in advance; it may be too late when long-term trade damage is shown.
Impact through research in education and studies in human society: A review of Australian Research Council ‘high-for-impact’ case studies
Authors: Jefferson Grace , Henry Rosita , Heyeres Marion , Morgan Rhian , Tomas Louisa , Tsey Komla , Zuchowski Ines
Published: May 2024

Research impact is an important measure of the effective transmission and ongoing contribution of research beyond the scope of initial research publication outputs; however, determining what constitutes ‘high-for-impact’ research can be difficult for specific fields of study. This review of the Australian Research Council’s Engagement and Impact Assessment 2018 analyses high-for-impact case studies submitted in the fields of Education (n = 17) and Studies in Human Society (n = 11) with the aim of understanding and explicating how high impact research has been evidenced in these fields. The review was guided by three research questions that concern the identification of the key characteristics of high-for-impact case studies, their reported impacts, and the evidence researchers cite to support claims of impact. The review highlights an important limitation in how impact is defined and understood by researchers, particularly cultural and social impact. Half of the analysed case studies involved international engagement, with minimal partner collaboration in the global south and countries in the Indo-Pacific, despite the region’s strategic geo-political importance for Australia. Our findings draw into question the distribution of funding to universities and where investment might best be made for the highest potential return on research impact. Another key finding is that reported impacts across the domains of economy, society, culture, national security, public service, health, environment and quality of life offer little satisfactory evidence of impact, despite affording valuable insights into the nature of impact claimed. Accordingly, we conclude that to enhance the value of research and demonstrate impact in Education and Social Sciences, improved impact literacy is required among researchers. We assert that a better understanding of what constitutes impact and how it can be evidenced will support more impactful research designs. Wider adoption of the holistic anthropological definition of culture, which integrates values, practices and products, would enhance impact case studies by expanding their focus to include the broader cultural changes that underpin sustained social change. While the ARC engagement and impact agenda is a step in the right direction, improving the value of research for society will require a radical reconceptualisation of research and its funding, well beyond the current assessment framework. The Lowitja Institute’s research-for-impact framework [1] is proposed as an alternative approach to research priority-setting based on explicit evidence gap analysis.
Diagnostic performance of ultrasound-based artificial intelligence for predicting key molecular markers in breast cancer: A systematic review and meta-analysis
Authors: Fu Yuxia , Zhou Jialin , Li Junfeng
Published: May 2024

Background

Breast cancer (BC) diagnosis and treatment rely heavily on molecular markers such as HER2, Ki67, PR, and ER. Currently, these markers are identified by invasive methods.

Objective

This meta-analysis investigates the diagnostic accuracy of ultrasound-based radiomics as a novel approach to predicting these markers.

Methods

A comprehensive search of PubMed, EMBASE, and Web of Science databases was conducted to identify studies evaluating ultrasound-based radiomics in BC. Inclusion criteria encompassed research on HER2, Ki67, PR, and ER as key molecular markers. Quality assessment using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Radiomics Quality Score (RQS) was performed. The data extraction step was performed systematically.

Results

Our meta-analysis quantifies the diagnostic accuracy of ultrasound-based radiomics with a sensitivity and specificity of 0.76 and 0.78 for predicting HER2, 0.80, and 0.76 for Ki67 biomarkers. Studies did not provide sufficient data for quantitative PR and ER prediction analysis. The overall quality of studies based on the RQS tool was moderate. The QUADAS-2 evaluation showed that the studies had an unclear risk of bias regarding the flow and timing domain.

Conclusion

Our analysis indicated that AI models have a promising accuracy for predicting key molecular biomarkers’ status in BC patients. We performed the quantitative analysis for HER2 and Ki67 biomarkers which yielded a moderate to high accuracy. However, studies did not provide adequate data for meta-analysis of ER and PR prediction accuracy of developed models. The overall quality of the studies was acceptable. In future research, studies need to report the results thoroughly. Also, we suggest more prospective studies from different centers.
Achillea fragrantissima (Forssk.) Sch.Bip instigates the ROS/FADD/c-PARP expression that triggers apoptosis in breast cancer cell (MCF-7)
Authors: Alasmari Abdulrahman
Published: May 2024

Achillea fragrantissima is a shrub plant that belongs to the Asteraceae family in Arabia and Egypt. It is used as folk medicine and is a good source of phenolic acids, flavonoids, and some active compounds. To investigate the anti-cancer effect of A.fragrantissima on breast cancer MCF-7 cells and find the critical mechanism involved in apoptosis. The toxicity and pharmacokinetic studies of ethanolic extract of A.fragrantissima was examined for anti-breast cancer properties. In turn, cytotoxicity and cell viability were achieved by the MTT method. Furthermore, the trypan blue exclusion and microscopy examination proved the presence of apoptotic cells. Again, fluorescent staining such as AO/EtBr, DCFH-DA, Rho-123, and Hoechst-33342 reveals the cellular cytoplasmic disciplines upon A. fragrantissima effect. Moreover, cellular functioning tests like wound healing, colony formation, and Transwell invasion assay were demonstrated. In addition, the qRT-PCR technique authenticates the A. fragrantissima -induced apoptotic network genes (Caspase-3, Caspase-8, Caspase-9, Cytochrome c, BCL-2, BID, BAX, PARP, PTEN, PI3K, and Akt) expression were evaluated. Mainly, the Immunoblot technique proved the expressed level of apoptotic proteins such as cleaved PARP, CYCS, and FADD. This study confirmed that the A. fragrantissima exerts cytotoxicity at 20 μg/mL for 24 hrs in MCF-7 cells. Also, decreases cellular viability, producing apoptotic cells and damaged cellular surfaces with dead matter. Consequently, it creates ROS species accumulation, loss of mitochondrial membrane potential, and fragmentation of DNA in MCF-7 cells. Furthermore, it arrests cell migration, induces colony-forming ability loss, and suppresses cell invasion. In addition, A. fragrantissima significantly upregulates genes such as caspase-3, 9, cytochrome c, BID, BAX, and PTEN while downregulating the Pi3K/ Akt signaling. Nonetheless, A.fragrantissima induced cleaved PARP, CYCS, and FADD proteins in MCF-7 cells to avail apoptosis.
Broad-scale changes in lesser prairie-chicken habitat
Authors: Vhay Megan P. , Haukos David A. , Sullins Daniel S. , Rice Mindy B.
Published: May 2024

Lesser prairie-chicken (Tympanuchus pallidicinctus) populations of in the Sand Sagebrush Prairie Ecoregion of southwest Kansas and southeast Colorado, USA, have declined sharply since the mid-1980s. Decreased quality and availability of habitat are believed to be the main drivers of declines. Our objective was to reconstruct broad-scale change in the ecoregion since 1985 as a potential factor in population declines. We assessed temporal change from 1985–2015 in landcover types and calculated landscape metrics using Land Change Monitoring, Assessment, and Projection imagery layers. We also documented presence of anthropogenic structures including oil wells and electrical transmission lines. Landcover type composition changed little since 1990 across the Sand Sagebrush Prairie Ecoregion. However, anthropogenic structures (i.e., oil/gas wells, cell towers, wind farms, and transmission lines) notably increased, potentially causing functional habitat loss at a broad scale. Increased anthropogenic structures may have decreased habitat availability as well as the quality of existing habitat for lesser prairie-chickens, possibly contributing to recent population declines throughout the Sand Sagebrush Prairie Ecoregion.
Path of Pyrazoles from Synthetic Factors to Anti-inflammatory Potential: A Review
Authors: Vashisht Ketan , Sethi Pooja , Bansal Anshul , Tuli Hardeep Singh , Jairoun Ammar Abdulrahman , Shahwan Moyad , Ramniwas Seema , Chauhan Ritu
Published: May 2024

Pyrazoles, a class of heterocyclic compounds, have garnered considerable attention in drug development due to their intriguing properties, particularly those containing a pyrazole moiety. Pyrazole, a pivotal chemical in the creation of potent bioactive agents, encompasses five heterocyclic members. The discovery of certain pyrazole compounds exhibiting robust biological activities has spurred interest in this field of inquiry. Heterocyclic compounds incorporating nitrogen and its derivatives have historically served as crucial sources of medicinal compounds. Given that the heterocyclic group constitutes a vast reservoir of organic molecules, its significance in both theoretical and applied chemistry has grown significantly. Extensive literature indicates that researchers have employed diverse synthetic strategies in recent years to produce substituted pyrazole derivatives with promising biological potential as anti-HIV, anti-inflammatory, antitumor and antimicrobial agents. Inflammation, a multifaceted biological response essential for the body’s defense mechanisms, can also contribute to various pathological conditions when dysregulated. Understanding the underlying molecular mechanisms offers a foundation for targeted interventions against inflammatory disorders. These insights fuel ongoing endeavors to discover effective and innovative anti-inflammatory agents with potential therapeutic applications. This review delves into the synthesis and characterization of various pyrazole derivatives, emphasizing structural modifications influencing their anti-inflammatory efficacy. The insights provided herein are invaluable for the rational design and synthesis of novel anti-inflammatory agents. Furthermore, the review concludes with a discussion on future perspectives, underscoring the imperative for further research to optimize the therapeutic potential of pyrazole derivatives as anti-inflammatory agents.