bluuebunny/crossref_metadata_2025 huggingface dataset:
Validity of inferences and validity of demonstrations
Authors: Sundholm Göran
Published: September 2024

The lecture spells out the difference between the validity of inference (‐figure)s and validity applied to demonstrations (‘proof acts’). The latter notion is not an ordinary characterizing one; in Brentano's terminology it is a modifying one. A demonstration lacking validity is not a real demonstration, just as a false friend is no true friend. Throughout, the treatment makes crucial use of an epistemological perspective that is cast in the first person. Furthermore, the difference between (logical) consequence among propositions and the validity of inference from judgement to judgement is explained. Particular attention is paid to alleged issues of circularity in the definition of the validity of inference, and to the ‘explosion’ validity of inference from contradictory premisses. Drawing upon a version of the dialogical framework of Per Martin‐Löf, namely, ‘When I say Therefore, I give others my permission to assert the conclusion’, while stressing also the importance of the first person perspective, both difficulties can be neutralized.
Do tax incentives for innovation attract high‐technology investment from emerging markets? Evidence from China's outward foreign direct investment
Authors: Ma Shuzhong , Liu Kai , Wu Peng
Published: September 2024

We examine whether the innovation box regime (IBR), a tax incentive with lower tax rates on intellectual property (IP)‐related income, attracts high‐technology investment from emerging markets. Using the staggered difference‐in‐differences (DID) method, we find that China's high‐technology investment in IBR countries, relative to non‐IBR countries, increases significantly after the implementation of IBR. This finding is robust to a battery of sensitivity tests. The mechanism analysis suggests that the attraction of the IBR for high‐technology investment is realised through the encouragement of innovation, and this finding is also verified in the heterogeneity analysis. We also find that the IBR has a positive effect on high‐technology investment only if the tax incentives apply to pre‐existing IP before the regime implementation, and the ease with which enterprises can directly use the latest technologies in the host country does not have an impact on the effectiveness of the IBR. Moreover, the effect of IBR on M&A is larger than that on greenfield investment. Our study contributes to the literature and policy assessment on IBR.
Content Feature of Medical Crowdfunding Information in Social Media—A Content and Effectiveness Analysis of Medical Crowdfunding Posts on Sina Weibo in China
Authors: Cai Yingying , Kamarudin Syafila , Nujaimi Saiful , Jiang Xiaoyu , Zhang Xin
Published: September 2024

Attracting donations is challenging but imperative for fundraisers to secure donations. Solicitation narratives serve as a key strategy for attracting both acquaintances and strangers, thereby influencing donation behavior. To optimize medical crowdfunding messaging on social media, this study explores prevalent content features of medical crowdfunding messages on Sina Weibo and determines whether these features impact message effectiveness. A retrospective content analysis was conducted on medical crowdfunding posts on Sina Weibo in China throughout 2023. The posts were systematically coded for the author’s gender, author type, target audience, key themes, human imagery, message sentiments, and message strategies, with their effectiveness analyzed using SPSS. Out of the 394 posts analyzed, private authors emerged as the dominant voices, directing their appeals predominantly toward the general public and often expressing neutral to negative sentiments. The overarching theme across these posts centered on the dire need for medical assistance. Including human imagery and informative message strategies was pivotal in determining post-effectiveness, eliciting heightened audience engagement in terms of likes and shares. Negative sentiment posts influenced comment effectiveness. These findings underscore the potential of social media campaigns in promoting altruistic health behaviors while emphasizing the critical role of strategic message design through the use of human imagery, informative message strategies, and negative sentiment to improve audience engagement.
On a Galois property of fields generated by the torsion of an abelian variety
Authors: Checcoli S. , Dill G. A.
Published: September 2024

In this article, we study a certain Galois property of subextensions of , the minimal field of definition of all torsion points of an abelian variety defined over a number field . Concretely, we show that each subfield of that is Galois over (of possibly infinite degree) and whose Galois group has finite exponent is contained in an abelian extension of some finite extension of . As an immediate corollary of this result and a theorem of Bombieri and Zannier, we deduce that each such field has the Northcott property, that is, does not contain any infinite set of algebraic numbers of bounded height.
THE ROLE OF PERICYTES IN BONE TISSUE REGENERATION AND THERAPEUTIC APPLICATIONS
Authors: Mukhlis S. , Issabekova A. , Kudaibergen G. , Mukhambetova A. , Nurkina A. , Altayeva N. , Ashikbayeva M. , Temirzhan A. , Baidarbekov M. , Ogay V.
Published: September 2024

The regeneration of massive bone defects poses a significant challenge in traumatology and orthopedics, often requiring bone grafting procedures following tumor resection, surgery, or severe injury. Current treatment methods include autologous and allogeneic bone grafts, as well as bone substitutes. While autologous transplantation is considered the standard, it is limited by donor site morbidity and availability. Allogeneic transplantation presents risks such as graft rejection and disease transmission. Bone substitutes may not fully restore bone defects. Tissue-engineered biomaterials offer promise for effective regeneration, utilizing stem cells, growth factors, and scaffolds. Adipose tissue, rich in mesenchymal stem cells and perivascular stem cells (pericytes), is a promising cell source for tissue engineering. This thesis explores the therapeutic potential of pericytes combined with various biological carriers and stimulating factors to enhance bone tissue regeneration.
Pericytes, contractile cells surrounding small blood vessels, are crucial for vessel integrity and blood flow regulation. They express markers like α-SMA and PDGFR-β and participate in angiogenesis, immune function, and tissue repair. Interactions with endothelial cells via signaling pathways involving molecules like VEGF and TGF-β are vital for vessel formation and stability. With their multipotent nature, pericytes show promise for regenerative medicine. Ongoing research is essential to address challenges in pericyte biology, including identification and understanding their roles in tissue regeneration. Studies highlight the potential of adipose tissue-derived pericytes in bone regeneration, particularly CD146+ pericytes, showing efficacy in spinal fusion and nonunion fracture treatment when combined with DBM. Preclinical studies confirm their effectiveness, especially when incorporated into various scaffold materials. Clinical studies using adipose-derived stem cells and autologous microfragmented adipose tissue have shown promise, with pericyte-enriched fractions holding potential for improved outcomes. Future research into pericyte application, combined with growth factors and scaffolds, could significantly advance bone tissue regeneration and regenerative medicine.
Human pericytes show promise for bone tissue regeneration due to their mesenchymal stem cell properties and role in vascular stabilization. Injectable hydrogels are crucial for bone tissue engineering, with various biomaterials developed for this purpose. Studies using injectable hydrogels with pericytes have demonstrated their efficacy in accelerating bone regeneration in different models. Further advancements in injectable hydrogel technology incorporating stem cells and osteoinductive factors are needed for more efficient bone tissue restoration.
DATA DRIVEN AND CELL SPECIFIC DETERMINATION OF NUCLEI-ASSOCIATED ACTIN STRUCTURE
Authors: Nikitina N.N , Bursa N. , Satici A. , Uzer G.
Published: September 2024

In the specialized field of cellular mechanosignaling, the intricate relationship between the cytoskeleton and nucleus is crucial for determining the behavior and fate of mesenchymal stem cells (MSCs). Existing analytical methods for filamentous actin fibers (F-actin) suffer from issues of accuracy and reproducibility. To address this, our research introduces a significant advancement in image analysis by utilizing two deep-learning segmentation Convolutional Neural Networks (CNNs) based on U-Net architecture. This algorithm precisely quantifies F-actin and offers reproducible data from 3D confocal microscopy images. Our CNNs automatically extract the 3D shape of both the nucleus and individual actin fibers, thereby enabling the geometric reconstruction of these critical cellular components. We applied this methodology to MSCs exposed to low-intensity vibration, and hypothesized that mechanical stimuli will induce perinuclear actin remodeling.
Confocal Z-stack images of MSCs were captured using a 40x oil lens and a Zeiss LSM 900 microscope. Nucleus and F-actin structures were stained with Hoechst 33342 and Phalloidin, respectively. Nucleus-based images were employed to mask and isolate actin fibers within the nuclear vicinity.
A specialized deep-learning segmentation model was engineered within the PyTorch framework. For model training, a selective 2% of nuclei and F-actin images were annotated. Specifically, three layers from each of six representative nuclei, among approximately 500 cross-sectional layers, were meticulously selected; a similar approach was employed for actin. The model underwent 200 epochs of training. Post-training, the deep-learning model was employed to process all collected cross-sectional images of F-actin and nuclei. A subsequent analytical step involved the scrutiny of intersecting segmented fibers between consecutive layers for geometrically accurate actin fiber reconstruction.
We analyzed 102 control and 110 vibration-treated mesenchymal stem cells (MSCs) by utilizing our deep-learning-based reconstruction algorithm on confocal Z-stack images. Our data revealed an 8% decrease in nuclear height from 5.73 µm to 5.28 µm (p < 0.001) upon application of low-intensity vibration. In contrast, the two groups observed no significant difference in nuclear volume.  Accompanying these changes at the nuclear level, the following changes in the F-actin cytoskeleton were observed upon LIV application. The total number of actin filaments per cell increased from 117 to 150. The average volume of individual actin fibers rose from 0.40 µm³ to 0.43 µm³. Notably, the volume of fibers at the apical nuclear surface increased from 0.35 µm³ to 0.46 µm³.
While the average length of actin fibers in the apical nuclear surface remained largely unchanged due to the addition of smaller fibers in LIV groups, the LIV group had a larger number of fibers that were larger than 15µm.
АНАЛИЗ ИНДУЦИРОВАНИЯ АНТИТЕЛ С ИСПОЛЬЗОВАНИЕМ МЫШИНЫХ МАКРОФАГОВ, ОБРАБОТАННЫХ EX VIVO РЕКОМБИНАНТНЫМИ ЧЕЛОВЕЧЕСКИМИ БЕЛКАМИ
Authors: Нуртлеу М.
Published: September 2024

Макрофаги представляют собой важный клеточный компонент, содержащийся в различных тканях организма. Они модулируют имунный ответ против патогенов, поддерживая гомеостаз тканей в организме. Особый интерес в изучении макрофагов связан с их прогностической способностью к индуцированию противоракового иммунитета и осуществлнеию фагоцитоза раковых клеток. Это определяет важность ex vivo обработки макрофагов рекомбинантными человеческими белками PD-L1 (rPD-L1), CTLA-4 (rCTLA-4) и PD-1 (rPD-1) для создания персонализированного иммунитета против цитотоксического лимфоцита 4 типа (CTLA-4), лиганда рецептора программируемой клеточной гибели 1 (PD-L1) и белка запрограммированной клеточной смерти 1 (PD-1).      
            Исследование развития гуморального иммунитета против CTLA-4, PD-L1 и PD-1 проводилось посредством введения мышам макрофагов, обработанных ex vivo соответствующими белками. Для иммунизации и получения макрофагов использовались инбредные самки мышей линии BALB в возрасте 6–8 недель. Положительную сыворотку получали путем внутрибрюшинного введения рекомбинантных белков. Наличие антител детектировали с использованием иммуноферментного анализа (ИФА). Результаты оценивали с использованием статистической обработки. Перитонеальные макрофаги мышей BALB/c культивировались в среде, содержащей рекомбинантные человеческие белки CTLA-4, PD-L1 и PD-1. Макрофаги, обработанные рекомбинантными белками анализировали посредством иммунофлуоресцентного окрашивания с использованием антител против CTLA-4, PD-L1 и PD-1. Обработанные макрофаги вводили мышам внутрибрюшинно для индукции антител против CTLA-4, анти-PD-L1 и анти-PD-1. Титр антител у вакцинированных мышей определяли методом иммуноферментного анализа с последующей статистической обработкой результатов. Специфичность антител определяли иммунофлуоресцентным окрашиванием клеток MCF7.
            Способность макрофагов активировать клеточный и гуморальный иммунитет стала основой их использования в терапии онкологических и инфекционных заболеваний. Успех лечения макрофагами связан с их способностью активировать иммунитет независимо от условий загрузки клеток антигенами. Макрофаги, загруженные ex vivo rCTLA-4, rPD-L1 и rPD-1, индуцировали достаточно высокие титры антител у вакцинированных мышей. Кроме того, иммунофлуоресцентное окрашивание показало, что антитела против rCTLA-4 и rPD-L1 специфически реагируют с клетками MCF7. Дальнейшие исследования макрофагов и ДК, презентирующих rCTLA-4, rPD-L1 и rPD-1, могут привести к новым подходам в иммунизации против онкологических и инфекционных заболеваний. Обработка макрофагов ex vivo rCTLA-4, rPD-L1 и rPD-1 может помочь индуцировать гуморальный иммунитет и разработать инновационные методы в иммунотерапии рака.
Hip Fracture in the Sportive Adult: Case Report of Complete Functional Recovery After Removal of Hardware
Authors: Lormans Pieter , Loos Pieter-Jan , Vanbrabant Stefanie , Quetin Philippe , Huybrechts Xavier , Ghekiere Olivier
Published: September 2024

Context: Pertrochanteric hip fractures in sportive young adults are mainly caused by a high-energy trauma and treated in the same way as in the older population, using an osteosynthesis immediately followed by a rehabilitation program for several months. The current standard is not to remove osteosynthesis material, similar to the case of older patients. Case Presentation: A 45-year-old male cyclist experienced a right pertrochanteric femoral fracture, treated with cephalomedullary nails. After 9 months of adequate rehabilitation, weakness of the quadriceps musculature and functional complaints persisted, objectified through an isokinetic strength test and a significantly reduced score on the Hip Disability and Osteoarthritis Outcome Score questionnaire. The patient was unable to return to his previous level of cycling performance. Management and Outcome: After exclusion of structural bone complications, nerve injury, and central sensitization, the functional complaints and strength deficiency were hypothesized to be related to the osteosynthesis material. Therefore, the hardware was removed 9 months after the first surgery, and the rehabilitation was continued for another 20 weeks. Very soon after the removal of the hardware, the functional complaints disappeared with a remarkable improvement of the Hip Disability and Osteoarthritis Outcome Score. The isokinetic strength test showed complete recovery of muscle strength 20 weeks after osteosynthesis removal, and preinjury cycling performance values were obtained 9 months posthardware removal. Conclusion: Despite an adequate rehabilitation following a hip fracture, sporty young adults may fail to reach their previous level of functioning. Osteosynthesis removal may be indicated in this sportive population to reach complete muscle strength and functional recovery. The management of hip fractures in the sportive young adult and the identification of patients who may benefit from removal of the hardware require more research.
From Fear to Resilience: A Scoping Review of Psychological Components in Anterior Cruciate Ligament Rehabilitation
Authors: Al Ta’ani Zaid , Al Ta’ani Omar , Gabr Ahmad , Tanashat Mohammad , Lin Lee Justin , Al-Bitar Farah , Lee Jessica Lin , Al-Ajlouni Yazan A.
Published: September 2024

Context: Anterior cruciate ligament (ACL) injuries, prevalent in athletic contexts have profound physical and psychological impacts. Despite extensive research on the physiological aspects of ACL recovery, the psychological dimensions of this process have gained increased attention. This scoping review delves into the intricate landscape of psychological factors influencing ACL rehabilitation. Design: Scoping review. Methods: A literature search across multiple databases was conducted to identify relevant published studies that provide insight into the psychological aspects of ACL recovery. This search spanned various study designs, enabling a nuanced understanding of the psychological intricacies surrounding ACL recovery. Overall, a total of 1830 unique articles were screened, of which 66 were included in this review. Our findings are further contextualized through alignment with insights from prior reviews on similar themes. Through a comprehensive analysis of diverse literature, we explore 3 key themes: psychological challenges, current rehabilitation programs, and the integration of psychological support. Results: Psychological challenges emerged as a pervasive aspect of ACL rehabilitation, encompassing fear, anxiety, motivation, and depression. The nuanced emotional responses, particularly the fear of reinjury, impact treatment adherence and overall well-being. Contemporary rehabilitation programs revealed inconsistencies in incorporating psychological support, emphasizing the need for standardized, multidisciplinary approaches. The alignment with prior reviews in the literature reinforced the importance of psychological traits, such as knee self-efficacy, in predicting positive outcomes. Conclusion: This scoping review provides a comprehensive overview of psychological factors within ACL rehabilitation, highlighting the importance of tailored interventions and standardized approaches. The integration of multidisciplinary expertise emerges as crucial for optimizing patient outcomes. Our findings not only contribute to a nuanced understanding of psychological nuances in ACL rehabilitation but also offer valuable implications for clinical practice and policy development.
A brain microbiome in salmonids at homeostasis
Authors: Mani Amir , Henn Cory , Couch Claire , Patel Sonal , Lieke Thora , Chan Justin T.H. , Korytar Tomas , Salinas Irene
Published: September 2024

Ectotherms have peculiar relationships with microorganisms. For instance, bacteria are recovered from the blood and internal organs of healthy teleosts. However, the presence of microbial communities in the healthy teleost brain has not been proposed. Here, we report a living bacterial community in the brain of healthy salmonids with bacterial loads comparable to those of the spleen and 1000-fold lower than in the gut. Brain bacterial communities share >50% of their diversity with gut and blood bacterial communities. Using culturomics, we obtained 54 bacterial isolates from the brains of healthy trout. Comparative genomics suggests that brain bacteria may have adaptations for niche colonization and polyamine biosynthesis. In a natural system, Chinook salmon brain microbiomes shift from juveniles to reproductively mature adults. Our study redefines the physiological relationships between the brain and bacteria in teleosts. This symbiosis may endow salmonids with a direct mechanism to sense and respond to environmental microbes.
Identification of immunogenic HLA class I and II neoantigens using surrogate immunopeptidomes
Authors: Tokita Serina , Fusagawa Minami , Matsumoto Satoru , Mariya Tasuku , Umemoto Mina , Hirohashi Yoshihiko , Hata Fumitake , Saito Tsuyoshi , Kanaseki Takayuki , Torigoe Toshihiko
Published: September 2024

Neoantigens arising from somatic mutations are tumor specific and induce antitumor host T cell responses. However, their sequences are individual specific and need to be identified for each patient for therapeutic applications. Here, we present a proteogenomic approach for neoantigen identification, named Neoantigen Selection using a Surrogate Immunopeptidome (NESSIE). This approach uses an autologous wild-type immunopeptidome as a surrogate for the tumor immunopeptidome and allows human leukocyte antigen (HLA)–agnostic identification of both HLA class I (HLA-I) and HLA class II (HLA-II) neoantigens. We demonstrate the direct identification of highly immunogenic HLA-I and HLA-II neoantigens using NESSIE in patients with colorectal cancer and endometrial cancer. Fresh or frozen tumor samples are not required for analysis, making it applicable to many patients in clinical settings. We also demonstrate tumor prevention by vaccination with selected neoantigens in a preclinical mouse model. This approach may benefit personalized T cell–mediated immunotherapies.
Adapting magnetoresistive memory devices for accurate and on-chip-training-free in-memory computing
Authors: Xiao Zhihua , Naik Vinayak Bharat , Lim Jia Hao , Hou Yaoru , Wang Zhongrui , Shao Qiming
Published: September 2024

Memristors have emerged as promising devices for enabling efficient multiply-accumulate (MAC) operations in crossbar arrays, crucial for analog in-memory computing (AiMC). However, variations in memristors and associated circuits can affect the accuracy of analog computing. Typically, this is mitigated by on-chip training, which is challenging for memristors with limited endurance. We present a hardware-software codesign using magnetic tunnel junction (MTJ)–based AiMC off-chip calibration that achieves software accuracy without costly on-chip training. Hardware-wise, MTJ devices exhibit ultralow cycle-to-cycle variations, as experimentally evaluated over 1 million mass-produced devices. Software-wise, leveraging this, we propose an off-chip training method to adjust deep neural network parameters, achieving accurate AiMC inference. We validate this approach with MAC operations, showing improved transfer curve linearity and reduced errors. By emulating large-scale neural network models, our codesigned MTJ-based AiMC closely matches software baseline accuracy and outperforms existing off-chip training methods, highlighting MTJ’s potential in AI tasks.
NF-κB and TET2 promote macrophage reprogramming in hypoxia that overrides the immunosuppressive effects of the tumor microenvironment
Authors: de la Calle-Fabregat Carlos , Calafell-Segura Josep , Gardet Margaux , Dunsmore Garett , Mulder Kevin , Ciudad Laura , Silvin Aymeric , Moreno-Càceres Joaquim , Corbí Ángel L. , Muñoz-Pinedo Cristina , Michels Judith , Gouy Sébastien , Dutertre Charles-Antoine , Rodríguez-Ubreva Javier , Ginhoux Florent , Ballestar Esteban
Published: September 2024

Macrophages orchestrate tissue homeostasis and immunity. In the tumor microenvironment (TME), macrophage presence is largely associated with poor prognosis because of their reprogramming into immunosuppressive cells. We investigated the effects of hypoxia, a TME-associated feature, on the functional, epigenetic, and transcriptional reprogramming of macrophages and found that hypoxia boosts their immunogenicity. Hypoxic inflammatory macrophages are characterized by a cluster of proinflammatory genes undergoing ten-eleven translocation–mediated DNA demethylation and overexpression. These genes are regulated by NF-κB, while HIF1α dominates the transcriptional reprogramming, demonstrated through ChIP-seq and pharmacological inhibition. In bladder and ovarian carcinomas, hypoxic inflammatory macrophages are enriched in immune-infiltrated tumors, correlating with better patient prognoses. Coculture assays and cell-cell communication analyses support that hypoxic-activated macrophages enhance T cell–mediated responses. The NF-κB–associated hypomethylation signature is displayed by a subset of hypoxic inflammatory macrophages, isolated from ovarian tumors. Our results challenge paradigms regarding the effects of hypoxia on macrophages and highlight actionable target cells to modulate anticancer immune responses.
Reduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection by blocking the epidermal growth factor receptor (EGFR) pathway
Authors: Han Yeonju , Kim Seunghwan , Park Taehyun , Hwang Hyemin , Park Sanghee , Kim Jimin , Pyun Jae-chul , Lee Misu
Published: September 2024

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants presents challenges in global efforts to transition from the pandemic to an endemic stage. The spike protein of the SARS-CoV-2 virus, which is pivotal for cell entry, exhibits significant mutations in its variants, potentially affecting infectivity and therapeutic efficacy. Recent findings indicate upregulation of the epidermal growth factor receptor (EGFR) pathway, a key target in cancer therapy, by the spike protein of SARS-CoV-2. This study aimed to investigate the activity of the EGFR pathway against SARS-CoV-2 variants and to assess the inhibitory effects of EGFR inhibitors using SARS-CoV variant pseudoviral particles to guide future therapeutic strategies. Omicron variant SARS-CoV pseudoviral particles exhibited heightened infectivity in human angiotensin-converting enzyme 2 (hACE2)-expressing HEK293 and A549 lung cancer cells accompanied by increased EGFR pathway activation in infected cells. Using the EGFR tyrosine kinase inhibitor, osimertinib, we observed a reduction in viral infection rates in hACE2-HEK293 and A549 cells infected with the SARS-CoV-2 variant pseudoviral particles. We conducted further experiments to confirm that the reduction in infection efficacy with osimertinib treatment was not associated to a decrease in cell viability. Furthermore, this inhibitory effect of osimertinib in cell lines was corroborated in a spheroid cell culture model derived from hACE2-A549 cells. These findings suggest the potential application of EGFR-targeted antiviral therapy against highly infectious SARS-CoV-2 variants.

IMPORTANCE

The emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is concerning as vaccines designed for one variant need not essentially protect against other novel variants. Therefore, there is an urgent need to identify therapies that can act against multiple novel variants that have heightened virulence compared with the wild type. It has been reported that the spike protein of the SARS-CoV-2 virus elicits an increased expression of the epidermal growth factor receptor (EGFR) pathway. We used this information and examined whether treatment with an EGFR inhibitor, osimertinib, which is already approved for clinical use in cancer therapy, can reduce the infection caused by SARS-CoV-2, wild type, and Omicron and Delta variants, in two cell lines and one spheroid model. The results showed that osimertinib treatment successfully reduced infection efficacy, particularly in variants, and that this effect was not related to a reduction in cell viability, making this a promising strategy for treating SARS-CoV-2 infections.
Supplemental Material: Crustal thickening and multipoint delamination for the ca. 90 Ma high-Sr/Y intrusions and the associated porphyry-skarn Cu-Au-Mo mineralization in the western central Lhasa terrane, Tibetan Plateau
Authors: Wang Liqiang , al. et
Published: September 2024

Supplemental Text S1–S3, Figures S1–S7, and Table S1–S7.
Supplemental Material: Exhumation history of the Shanxi Rift, Central Asia, derived from low-temperature thermochronology
Authors: Wang Hongtao , al. et
Published: September 2024

QTQt inverse modeling methodology, comparison of the QTQt and GLIDE modeling results, Figures S1–S5, and Tables S1–S3. 
Virtual clinical simulation as a paedagogical strategy in healthcare learning: Evidence and Gap Map protocol
Authors: Engler Jamille Costa , Castro Luiza Sheyla Evenni Porfírio Will , Guesser Joice Cristina , da Silva Flôr Janaína , De Luca Canto Graziela , Zimmermann Glaucia Santos , Lino Monica Motta
Published: September 2024

Introduction

Virtual clinical simulation involves creating and applying scenarios using technology like computers or virtual reality. This method provides a secure experiential learning environment, encouraging active student participation and stimulating clinical, critical and reflective thinking. This article outlines the development of the Evidence and Gap Map, which aims to identify, quantify and visually and interactively classify existing systematic reviews on the effectiveness of virtual clinical simulations in health professional training.

Methods and analysis

The Evidence and Gap Map will adhere to the Campbell Collaboration Guidelines. Bibliographic searches in six databases will follow inclusion criteria determined by the Population, Intervention, Comparison, Outcome and Study design strategy. After the initial calibration, two reviewers will independently apply the inclusion and exclusion criteria to the title and abstract of each identified study, with subsequent full reading of the selected articles. The methodological quality of the included systematic reviews will be assessed with the AMSTAR 2 tool. The map will be developed using the EPPI-Mapper software.

Ethics and dissemination

There is no requirement for ethical approval for this systematic review. On completion, it will be published in a peer-reviewed academic journal and presented at a conference. This review protocol was registered on the Open Science Framework platform (OSF Associated Project Registration: osf.io/r6wdc and received the following DOI: 10.17605/OSF.IO/R6WDC).
Cross-sectional analysis of healthcare worker mental health and utilisation of a digital mental health platform from 2020 to 2023
Authors: Agarwal Anish K , Southwick Lauren , Pelullo Arthur , McCalpin Haley J , Gonzales Rachel E , Asch David A , Livesey Cecilia , Bellini Lisa , Kishton Rachel , Beck Sarah , Merchant Raina M
Published: September 2024

Background

Healthcare worker (HCW) anxiety and depression worsened during the pandemic, prompting the expansion of digital mental health platforms as potential solutions offering online assessments, access to resources and counselling. The use of these digital engagement tools may reflect tendencies and trends for the mental health needs of HCWs.

Objectives

This retrospective, cross-sectional study investigated the association between the use of an online mental health platform within a large academic health system and measures of that system’s COVID-19 burden during the first 3 years of the pandemic.

Methods

The study investigated the use of Cobalt, an online mental health platform, comprising deidentified mental health assessments and utilisation metrics. Cobalt, serves as an online mental health resource broadly available to health system employees, offering online evidence-based tools, coaching, therapy options and asynchronous content (podcasts, articles, videos and more). The analyses use validated mental health assessments (Generalised Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9) and post-traumatic stress disorder (PTSD)) alongside publicly available COVID-19 data. Statistical analyses employed univariate linear regression with Stata SE Statistical Software.

Results

Between March 2020 and March 2023, 43 308 independent user sessions were created on Cobalt, a majority being anonymous sessions (72%, n=31 151). Mental health assessments, including PHQ-4, PHQ-9, GAD-7 and primary care-PTSD, totalled 9462 over the time period. Risk for self-harm was noted in 17.1% of PHQ-9 assessments. Additionally, 4418 appointments were scheduled with mental health counsellors and clinicians. No significant associations were identified between COVID-19 case burden and Cobalt utilisation or assessment scores.

Conclusion

Cobalt emerged as an important access point for assessing the collective mental health of the workforce, witnessing increased engagement over time. Notably, the study indicates the nuanced nature of HCW assessments of anxiety, depression and PTSD, with mental health scores reflecting moderate decreases in depression and anxiety but signalling potential increases in PTSD. Tailored resources are imperative, acknowledging varied mental health needs within the healthcare workforce. Ultimately, this investigation lays the groundwork for continued exploration of the impact and effectiveness of digital platforms in supporting HCW mental health.
The new progress in injector and positron source of STCF
Authors: Luo Q. , Xu X. , Yuan Y. J. , Gu D. , Pei G. X. , Huang P. W. , Peng H. P. , Zhang A. L.
Published: September 2024

A proposal has been made for the construction of a new generation of high-luminosity electron-positron colliders known as the Super Tau-Charm Facility (STCF) in China. The STCF aims to achieve a luminosity exceeding [Formula: see text][Formula: see text]cm[Formula: see text][Formula: see text]s[Formula: see text] and will operate within a center-of-mass energy range of 2 to 7[Formula: see text]GeV. Given the design challenges of the STCF collider ring, swap-out injection has been proposed as an alternative method for achieving the desired luminosity. Consequently, the STCF injector will explore both off-axis injection and swap-out injection methods concurrently. This paper will detail the ongoing research progress on these two injection techniques.
Transient Dynamics in Fast–Slow Predator–Prey Model with Monod–Haldane Functional Response and Asymptotic Behaviors
Authors: Zhang Wenjing
Published: September 2024

This paper studies the transient dynamics in a fast–slow ecological model with a Monod–Haldane functional response. Geometric singular perturbation theory is utilized to examine the transient dynamics generated by intrinsic multiple time scales. An asymptotic series solution is derived for the normally hyperbolic sub-manifold in the slow flow. The paper proves the existence of relaxation oscillations near fold points and the existence of a smooth family of canard cycles arising from folded singularities. Furthermore, it investigates the resulting canard explosion and transient dynamics numerically. By incorporating the Monod–Haldane functional response, which represents the inhibitory effect on predation at high prey population levels, this study illustrates the occurrence of transient dynamics under this mechanism.
Entropic Regression Dynamic Mode Decomposition (ERDMD) Discovers Informative Sparse and Nonuniformly Time Delayed Models
Authors: Curtis Christopher W. , Bollt Erik , Alford-Lago Daniel Jay
Published: September 2024

In this work, we present a method that determines optimal multistep Dynamic Mode Decomposition (DMD) models via Entropic Regression (ER), which is a nonlinear information flow detection algorithm. Motivated by the Higher-Order DMD (HODMD) method of [ Le Clainche & Vega ,  2017 ], and the ER technique for network detection and model construction found in [ Sun et al. ,  2015 ;  AlMomani et al. ,  2020 ], we develop a method that we call ERDMD, which produces high fidelity time-delay DMD models that allow for nonuniformity in the delays. This optimal choice of delays is discovered by maximizing informativity as measured through ER. These models are shown to be highly efficient and robust. We test our method over several data sets generated by chaotic attractors and show that we are able to build excellent reconstructions using relatively minimal models. We likewise are able to better identify multiscale features via our models which enhances the utility of DMD.
Nonintegrability of 3 DoF Hamiltonian Resonant Systems
Authors: Verhulst Ferdinand , Bakri Taoufik
Published: September 2024

We review a number of methods to prove nonintegrability of Hamiltonian systems and focus on 3 Degrees-of-Freedom (DoF) systems listing the known results for the prominent resonances. Associated with the Hamiltonian systems are the averaged-normal forms that provide us with geometric insight, approximations of orbits and measures of chaos. Symmetries do change the qualitative and quantitative pictures; we illustrate this for the 1:2:1 resonance with discrete symmetry in the 1st and 3rd DoF. In this case, the averaged-normal form is still nonintegrable, but it becomes integrable when adding discrete symmetry in all DoF. Apart from the short-periodic solutions obtained by averaging, we find many periodic solutions. There is numerical evidence of the presence of Šilnikov bifurcation which clarifies the presence of nonintegrability phenomena qualitatively and quantitatively.
Cellular and Molecular Mechanisms Regulating Retinal Synapse Development
Authors: Stevens-Sostre Whitney A. , Hoon Mrinalini
Published: September 2024

Synapse formation within the retinal circuit ensures that distinct neuronal types can communicate efficiently to process visual signals. Synapses thus form the core of the visual computations performed by the retinal circuit. Retinal synapses are diverse but can be broadly categorized into multipartner ribbon synapses and 1:1 conventional synapses. In this article, we review our current understanding of the cellular and molecular mechanisms that regulate the functional establishment of mammalian retinal synapses, including the role of adhesion proteins, synaptic proteins, extracellular matrix and cytoskeletal-associated proteins, and activity-dependent cues. We outline future directions and areas of research that will expand our knowledge of these mechanisms. Understanding the regulators moderating synapse formation and function not only reveals the integrated developmental processes that establish retinal circuits, but also divulges the identity of mechanisms that could be engaged during disease and degeneration.
Impact of Glaucomatous Ganglion Cell Damage on Central Visual Function
Authors: Kwon MiYoung
Published: September 2024

Glaucoma, a leading cause of irreversible blindness, is characterized by the progressive loss of retinal ganglion cells (RGCs) and subsequent visual field defects. RGCs, as the final output neurons of the retina, perform key computations underpinning human pattern vision, such as contrast coding. Conventionally, glaucoma has been associated with peripheral vision loss, and thus, relatively little attention has been paid to deficits in central vision. However, recent advancements in retinal imaging techniques have significantly bolstered research into glaucomatous damage of the macula, revealing that it is prevalent even in the early stages of glaucoma. Thus, it is an opportune time to explore how glaucomatous damage undermines the perceptual processes associated with central visual function. This review showcases recent studies addressing central dysfunction in the early and moderate stages of glaucoma. It further emphasizes the need to characterize glaucomatous damage in both central and peripheral vision, as they jointly affect an individual's everyday activities.
Assessing the Performance of Models from the 2022 RSNA Cervical Spine Fracture Detection Competition at a Level I Trauma Center
Authors: Hu Zixuan , Patel Markand , Ball Robyn L. , Lin Hui Ming , Prevedello Luciano M. , Naseri Mitra , Mathur Shobhit , Moreland Robert , Wilson Jefferson , Witiw Christopher , Yeom Kristen W. , Ha Qishen , Hanley Darragh , Seferbekov Selim , Chen Hao , Singer Philipp , Henkel Christof , Pfeiffer Pascal , Pan Ian , Sheoran Harshit , Li Wuqi , Flanders Adam E. , Kitamura Felipe C. , Richards Tyler , Talbott Jason , Sejdić Ervin , Colak Errol
Published: September 2024

Winning machine learning models from the RSNA 2022 Cervical Spine Fracture Detection competition demonstrated high performance on a large clinical test set of emergency department cervical spine CT scans from a level I trauma center.
Assessment on the Personal Exposure Risk Associated With Real‐Time Indoor PM2.5 in Different Microenvironments
Authors: Dai Shuiping , He Yuhang , Zeng Ni , Wang Zhenglu
Published: September 2024

The cytotoxicity of PM2.5 (fine particulate) derived from varying fuels burning in different microenvironments remains unclear. In this study, the toxicity of PM2.5 collected from northern China in the winter on human cervical carcinoma (HeLa) cells was determined. The PM2.5 from chunk coal (CC) combustion caused greater apoptosis (22.47%) than firewood (FW) burning (5.32%), while the effects on cell viability showed contrary patterns between FW (stimulation: 132.38%) and CC (inhibition: 87.05%). Furthermore, all the samples induced significant oxidative stress and inflammatory responses in cells. Intriguingly, PM2.5 samples collected from FW burning upregulated the expression genes involved in pathways in cancer, whereas those from CC burning downregulated the levels. Accordingly, the health risks of different samples were assessed through a probabilistic model. The risk level of samples of CC burning from the living room (CC/L) was 0.752, followed by CC from the bedroom (CC/B, 0.736), and then CC from the kitchen (CC/K, 0.562), FW without a chimney (FW‐C, 0.451), and FW with a chimney (FW+C, 0.446). Meanwhile, the survival curves established by gene expression indicated that PM2.5 from FW might be positively correlated with cancer progression. This pilot investigation demonstrated that CC combustion in the living room posed the highest health risk, and improved cookstoves (with a chimney) markedly reduced the risk. This pilot study presents a novel model for assessing health risks associated with air pollution using the toxicology method and real‐time PM2.5 quantification.
Residential Building Duration Prediction Based on Mean Clustering and Neural Network
Authors: Ji Fanrong , Nan Yunquan , Wei Aifang , Fan Peiyan , Luo Zhaoyuan , Song Xiaoqing
Published: September 2024

The duration of a residential building project will directly influence its successful implementation; hence, it is essential to estimate a reasonable timeframe. In this study, a genetic algorithm (GA) was employed to optimize and refine the weights and thresholds of a back propagation (BP) neural network, thereby creating a GA‐BP neural network model. A dataset comprising 111 instances of residential building durations was gathered, segmented into 90 training sets and 21 test sets. The model was validated and assessed through root mean square error (RMSE), correlation coefficient (R), and average error rate, demonstrating that the GA‐BP neural network model is effective in predicting the duration of residential buildings. To enhance the predictive accuracy of the GA‐BP neural network model, this research utilized an artificial bee colony (ABC)‐improved K‐means clustering algorithm to categorize 111 experimental datasets and 33 new datasets. The results indicated that the ABC‐K‐means‐GA‐BP model exhibited robust generalization capabilities and high predictive accuracy, with the fitness function showing optimal performance after 10, 15, and 35 generations, and the best validation performances recorded as 0.0019156, 0.00035905, and 0.0036914. This validates that the proposed ABC‐K‐means‐GA‐BP neural network model significantly aids in forecasting the construction period of residential buildings, which holds substantial practical value for enhancing construction efficiency.
Synovial Matrix Remodeling and Inflammatory Profile in Disc Displacement of the Temporomandibular Joint: An Observational Case‐Control Study
Authors: Khattar Pallavi , Ulmner Mattias , Häbel Henrike , Lund Bodil , Sugars Rachael V.
Published: September 2024

Background: Pain‐related temporomandibular joint disorders (TMJD) are a major public health problem, including the diagnoses of disc displacement (DD) with and without reduction (DDwR/DDwoR).

Objectives: The study aimed to examine the matrix remodeling and the inflammatory profile in synovial tissues of patients with TMJ‐DD, with a view to understand the pathophysiology, and to contribute to the development of tissue‐based diagnostic criteria.

Methods: This laboratory‐based observational case‐control study included 30 synovial tissue samples obtained from 30 patients, diagnosed with delayed (DO) or sudden (SO) onset of DDwoR, which were compared against the reference patient material, DDwR (n = 10/diagnosis group). Tissue samples were investigated histologically and via quantitative immunohistochemistry for a panel of antibodies targeted against extracellular matrix proteins and inflammatory markers. The data were analyzed using a generalized linear model with a gamma family distribution (p < 0.05).

Results: Quantification of immunostaining revealed significant differences in the distribution of collagen type III (DO, p < 0.001), lumican (DO, p < 0.05), matrix metalloproteinase‐2 (DO, p < 0.05), CD4 T‐helper cells (DO, p < 0.01; SO, p < 0.001), and CD68 monocytic immune cells (both SO and DO, p < 0.001) in DDwoR groups compared to the reference patient material, DDwR.

Conclusions: The observations confirmed differences in matrix remodeling and an increase in local inflammatory activity in the DDwoR diagnosis compared to the reference patient material, DDwR. The study highlighted the importance of synovial tissue characterization to unite micropathology and clinical findings, leading to more reliable diagnostic tools.
The Efficacy of Methazolamide Combined With Ibuprofen for Treating Acute Mountain Sickness
Authors: Zhao Wenqi , Gao Zhiqi , Zhang Erlong , Xu Gang , Sun Binda , Liu Bao , Wu Gang , Wang Shouxian , Gao Yuqi , Chen Jian
Published: September 2024

Aims: When entering a mountain plateau, people are at risk of developing acute mountain sickness (AMS), for which there are limited prophylactic medicines available. This study aimed at exploring the effectiveness of ibuprofen, acetazolamide, and methazolamide in preventing AMS and at providing valuable insights for the future development of related drugs.

Methods: A total of 137 mountaineers were recruited for this study and divided into six groups: a control group, an ibuprofen group, an acetazolamide group, a methazolamide group, an ibuprofen/methazolamide combination group, and a high‐dose ibuprofen/methazolamide combination group. After the assigned drug was taken for three days at a lower elevation (300 m), the participants ascended to a plateau environment at 5050 m. The Lake Louise AMS Score (LLS) system was used to diagnose and evaluate the AMS rates of the mountaineers in each group, and the results were compared through statistical analysis.

Results: The results show that all the medications tested herein were effective in preventing AMS, but their level of effectiveness varied. The prevalence of AMS was 50.00% in the control group, 14.29% in the ibuprofen group, 5.56% in the acetazolamide group, 27.27% in the methazolamide group, 44.8% in the ibuprofen and methazolamide group, and 22.50% in the high‐dose ibuprofen and methazolamide group. Acetazolamide demonstrated a significant prophylactic effect on symptoms related to AMS diagnosis, and ibuprofen showed the best efficacy for preventing headache.

Conclusion: Acetazolamide remains an effective medicine for preventing AMS. Ibuprofen combined with methazolamide is less effective than ibuprofen alone to prevent AMS.

Trial Registration: ClinicalTrials.gov identifier: ChiCTR-TRC-12002219