bluuebunny/crossref_metadata_2025 huggingface dataset:
Going beyond general competencies in teachers' technological knowledge: describing and assessing pre-service physics teachers' competencies regarding the use of digital data acquisition systems and their relation to general technological knowledge
Authors: Benz Gregor , Ludwig Tobias
Published: June 2023

The use of digital technologies and media in physics classrooms has pedagogical potential. In addition to everyday common technologies (e. g., presenters or computers), highly subject-specific media and technologies (e. g., simulation and digital data acquisition systems) are now available for these purposes. As the diversity of these technologies/media increases, so do the required competencies on the part of the (pre-service) physics teachers who must be able to exploit the given potential. Corresponding competency frameworks and related evaluation instruments exist to describe and assess the corresponding competencies. These frameworks and scales are characterized by their generality and do not reflect the use of highly subject-specific technologies. Thus, it is not clear how relevant they are for describing competencies in highly subject-specific technological situations, such as working with digital data acquisition systems in educational lab work settings. Against this background, two studies are presented. Study 1 identifies empirically 15 subject-specific competencies for handling digital data acquisition systems in lab work settings based on a literary review of lab manuals and thinking aloud. In Study 2, based on the 15 identified competencies, an abbreviated content- and construct-validated self-efficacy scale for handling digital data acquisition systems is provided. We show that general technological-specific self-efficacy is only moderately related to the highly subject-specific self-efficacy of handling digital data acquisition systems. The results suggest that specific competency frameworks and measurement scales are needed to design and evaluate specific teaching and learning situations.
Serum progesterone concentration on pregnancy test day might predict ongoing pregnancy after controlled ovarian stimulation and fresh embryo transfer
Authors: Duport Percier Marie , Brouillet Sophie , Mollevi Caroline , Duraes Martha , Anahory Tal , Ranisavljevic Noemie
Published: June 2023

Progesterone (P4) is essential for pregnancy. A controlled ovarian stimulation (COS) leads to a iatrogenic luteal defect that indicates a luteal phase support (LPS) at least until pregnancy test day. Some clinicians continue the LPS until week 8 or later, when P4 is mainly secreted by syncytiotrophoblast cells.Measuring serum P4 on pregnancy test day after a fresh embryo transfer could help to identify women who might benefit from prolonged LPS. In women with LPS based on P4 administered by the rectal route, P4 concentration on pregnancy test day was significantly higher in patients with ongoing pregnancy than in patients with abnormal pregnancy.This monocentric retrospective study used data on 99 consecutive cycles of COS, triggered with human chorionic gonadotropin, followed by fresh embryo transfer resulting in a positive pregnancy test (>100 IU/L) (from November 2020 to November 2022). Patients undergoing preimplantation genetic screening or with ectopic pregnancy were excluded. All patients received standard luteal phase support (i.e. micronized vaginal progesterone 600 mg per day for 15 days). The primary endpoint was P4 concentration at day 15 after oocyte retrieval (pregnancy test day) in women with ongoing pregnancy for >12 weeks and in patients with miscarriage before week 12 of pregnancy.The median P4 concentration [range] at pregnancy test day was higher in women with ongoing pregnancy than in women with miscarriage (55.9 ng/mL [11.6; 290.6] versus 18.1 ng/mL [8.3; 140.9], p = 0.002). A P4 concentration ≥16.5 ng/mL at pregnancy test day was associated with higher ongoing pregnancy rate (OR = 12.5, 95% CI 3.61 - 43.33, p <0.001). A P4 concentration ≥16.5 ng/mL at pregnancy test day was significantly associated with higher live birth rate (OR = 11.88, 95% CI 3.30–42.71, p <0.001).After COS and fresh embryo transfer, the risk of miscarriage is higher in women who discontinue luteal support after 15 days, as recommended, but with P4 concentration <16.5 ng/mL. The benefit of individualized prolonged luteal phase support should be evaluated.
Update on acquired hypogonadism in men living with HIV: pathogenesis, clinic, and treatment
Authors: De Vincentis Sara , Rochira Vincenzo
Published: June 2023

Hypogonadism is a frequent finding among men living with HIV (MLWH) and it seems to occur earlier in comparison with the general male population. Although the prevalence of hypogonadism in MLWH has significantly lowered thanks to advancements in medical management, it remains high if compared with age-matched HIV-uninfected men, ranging from 13% to 40% in the age group of 20-60 years. Signs and symptoms of low serum testosterone (T) in MLWH are cause of concern since they are non-specific, of mild-to-moderate degree, and often overlapping with those of infectionper se. For these reasons, hypogonadism can be underestimated in the absence of targeted laboratory blood examinations. With regard to the etiological factors involved in the T decrease, emerging evidence has suggested the functional nature of hypogonadism in MLWH, pointing out the mutual relationship between sex steroids, health status, comorbidities, and HIV-related factors. In agreement with this hypothesis, a therapeutic approach aiming at improving or reversing concomitant diseases through lifestyle changes (e.g. physical activity) rather than pharmacological T treatment should be theoretically considered. However, considering both patient’s barriers to lifestyle changes to be maintained overtime and the lack of evidence-based data on the efficacy of lifestyle changes in normalizing serum T in MLWH, T therapy remains an option when other non-pharmacological interventions are ineffective as well as for all other functional forms of hypogonadism. From this perspective, the traditional therapeutic management of male hypogonadism in MLWH, especially the role of T supplementation, should be revised in the light of the probable functional nature of hypogonadism by considering a good balance between benefits and harmful. This narrative review presents an overview of current knowledge on hypogonadism in MLWH, deepening the factors driving and taking part in T decrease, providing advice for the clinical approach, and underlining the importance of individualized treatment aiming at optimizing non-gonadal comorbidities and thus avoiding over-, or even unnecessary, treatment with T.
Microscopic, mesoscopic, and macroscopic structural correlations between the international energy “investment–trade” networks based on network motifs
Authors: Jin Zanyu , Guan Qing , Duan Yueran
Published: June 2023

In recent years, international energy investment and energy trade activities have developed rapidly. Because energy has commodity and financial product attributes, there is often a correlation between international energy trade and investment. This correlation has regional specificity due to the uneven geographical distribution of energy production and consumption. The existing literature mainly studies the correlation between the international energy “investment–trade” systems from a macroscopic or microscopic perspective. However, the relationship between them among countries from a mesoscopic perspective has not been fully demonstrated. With the development of economic globalization, we need to pay attention to whether the energy trade model of countries can reflect their preference for choosing investment partners and whether the energy investment model can reflect energy trade cooperation. In this paper, by taking the frontier approach of network motifs, we analyzed the correlation between international energy trade and investment from more than 200 economies worldwide from the macroscopic perspective, microscopic perspective, and local structure from a mesoscopic perspective. Meanwhile, we compared the results of the study in 2018 with those in 2022 to obtain the impact of international events on the international energy “investment–trade” networks. We found that 1) the structures of energy trade and investment networks are similar from a macroscopic perspective, which is the basis for exploring the correlation between energy trade and investment. 2) Bilateral cooperation and transaction transmission are important local structures of energy trade and energy investment activities. 3) The formation of an equal and close local structure among economies in energy trade is more likely to be preferred for investment cooperation, and forming a representative local structure with statistical significance among economies in energy investment is more likely to obtain energy trade cooperation. This work innovatively adopts motifs to study the correlation between energy investment and trade, which can help energy investors predict the direction of investment and provide guidance to governments in formulating energy trade policies.
Does tourism affect the long term course of COVID-19 pandemic in a country of destination? Evidence from a popular Greek island in 2020 where control measures were implemented
Authors: Bogogiannidou Zacharoula , Koureas Michalis , Mouchtouri Varvara A. , Dadouli Katerina , Kyritsi Maria A. , Vontas Alexandros , Anagnostopoulos Lemonia , Mina Paraskevi , Matziri Alexia , Vachtsioli Evangelia , Papagiannakis Alexandra , Archontakis Zacharias , Leotsinidis Michael , Theodoridou Kalliopi , Manios George , Gikas Achilleas , Speletas Matthaios , Hadjichristodoulou Christos
Published: June 2023

Greece opened its points of entry on July 1, 2020, with specific guidelines for travellers arriving by sea, air or land. The aim of this article is to examine the effect of tourism on the long term course of the Coronavirus Disease 2019 (COVID-19) pandemic during the pre-vaccination era (June to December 2020) on the popular Greek island of Crete. To achieve this, a cross-sectional serosurvey, repeated at monthly intervals, was conducted to compare the seroprevalence in Crete with seroprevalence in the mainland of Greece. Crete welcomed nearly 2,000,000 travellers during the 2020 summer season. Left-over serum samples were collected and obtained from public and private laboratories located in Greece, including the island of Crete. These samples were tested for the presence of anti-SARS-CoV-2 IgG antibodies. A total of 55,938 samples were collected, 3,785 of which originated from Crete. In Crete, the seroprevalence ranged between 0% (June 2020) and 2.58% (December 2020), while the corresponding seroprevalence in Greece was 0.19% and 10.75%, respectively. We identified 4.16 times lower seropositivity in Crete (2.58%) in comparison with the mainland of Greece (10.75%) during December 2020. Moreover, the monthly infection fatality rate (IFR) in Crete was calculated at 0.09%, compared with 0.21% in mainland Greece for December 2020. The island of Crete presented more than four times lower seroprevalence than the mainland of Greece, despite being a highly attractive tourist destination. This evidence supports the idea that tourism may not have affected the long term course of the COVID-19 pandemic in Greece. However, due to contradicting results from previous studies, further investigation is needed.
NAD(P) transhydrogenase isoform distribution provides insight into apicomplexan evolution
Authors: Tremp Annie Z. , Saeed Sadia , Dessens Johannes T.
Published: June 2023

Membrane-located NAD(P) transhydrogenase (NTH) catalyses reversible hydride ion transfer between NAD(H) and NADP(H), simultaneously translocating a proton across the membrane. The enzyme is structurally conserved across prokaryotes and eukaryotes. In heterotrophic bacteria NTH proteins reside in the cytoplasmic membrane, whereas in animals they localise in the mitochondrial inner membrane. Eukaryotic NTH proteins exists in two distinct configurations (isoforms) and have non-mitochondrial functions in unicellular eukaryotes like Plasmodium, the causative agent of malaria. In this study, we carried out a systematic analysis of nth genes across eukaryotic life to determine its prevalence and distribution of isoforms. The results reveal that NTH is found across all major lineages, but that some organisms, notably plants, lack nth genes altogether. Isoform distribution and phylogenetic analysis reveals different nth gene loss scenarios in apicomplexan lineages, which sheds new light on the evolution of the Piroplasmida and Eimeriidae.
Transnational death and technological haunting
Authors: Sánchez-Querubín Natalia
Published: June 2023

The paper proposes “technological haunting” as a concept in migration and transnational death studies. Existing theory and empirical work in media studies explore connections between new media and grieving practices and how affordances of co-presence and portability shape how people maintain bonds with the deceased. The unique considerations that “technological haunting” brings to the study of transnational families and death still need to be addressed by both media scholars and researchers within digital migration studies.
Identification of ACKR4 as an immune checkpoint in pulmonary arterial hypertension
Authors: Jiang Chen-Yu , Wu Li-Wei , Liu Yi-Wei , Feng Bei , Ye Lin-Cai , Huang Xu , He Yang-Yang , Shen Yi , Zhu Yi-Fan , Zhou Xing-Liang , Jiang Dai-Ji , Qi Hai-Kun , Zhang Hao , Yan Yi
Published: June 2023

Objective

Inflammation is recognized as a contributor in the development of pulmonary arterial hypertension (PAH), and the recruitment and functional capacity of immune cells are well-orchestrated by chemokines and their receptors. This study is aimed at identification of critical chemokines in the progression of PAH via transcriptomic analysis.

Methods

Differentially expressed genes (DEGs) from lungs of PAH patients were achieved compared to controls based on Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GSEA) was applied for functional annotation and pathway enrichement. The abundance of immune cells was estimated by the xCell algorithm. Weighted correlation network analysis (WGCNA) was used to construct a gene expression network, based on which a diagnostic model was generated to determine its accuracy to distinguish PAH from control subjects. Target genes were then validated in lung of hypoxia-induce pulmonary hypertension (PH) mouse model.

Results

ACKR4 (atypical chemokine receptor 4) was downregulated in PAH lung tissues in multiple datasets. PAH relevant biological functions and pathways were enriched in patients with low-ACKR4 level according to GSEA enrichment analysis. Immuno-infiltration analysis revealed a negative correlation of activated dendritic cells, Th1 and macrophage infiltration with ACKR4 expression. Three gene modules were associated with PAH via WGCNA analysis, and a model for PAH diagnosis was generated using CXCL12, COL18A1 and TSHZ2, all of which correlated with ACKR4. The ACKR4 expression was also downregulated in lung tissues of our experimental PH mice compared to that of controls.

Conclusions

The reduction of ACKR4 in lung tissues of human PAH based on transcriptomic data is consistent with the alteration observed in our rodent PH. The correlation with immune cell infiltration and functional annotation indicated that ACKR4 might serve as a protective immune checkpoint for PAH.
Advances in genetic manipulation of Chlamydia trachomatis
Authors: Wan Weiqiang , Li Danni , Li Dan , Jiao Jun
Published: June 2023

Chlamydia trachomatis, one species of Chlamydia spp., has the greatest impact on human health and is the main cause of bacterial sexually transmitted diseases and preventable blindness among all Chamydia spp. species. The obligate intracellular parasitism and unique biphasic developmental cycle of C. trachomatis are the main barriers for the development of tools of genetic manipulation. The past decade has witnessed significant gains in genetic manipulation of C. trachomatis, including chemical mutagenesis, group II intron-based targeted gene knockout, fluorescence-reported allelic exchange mutagenesis (FRAEM), CRISPR interference (CRISPRi) and the recently developed transposon mutagenesis. In this review, we discuss the current status of genetic manipulations of C. trachomatis and highlights new challenges in the nascent field of Chlamydia genetics.
Macrophage IL-1β contributes to tumorigenesis through paracrine AIM2 inflammasome activation in the tumor microenvironment
Authors: Chew Zhi Huan , Cui Jianzhou , Sachaphibulkij Karishma , Tan Isabelle , Kar Shreya , Koh Kai Kiat , Singh Kritika , Lim Hong Meng , Lee Soo Chin , Kumar Alan Prem , Gasser Stephan , Lim Lina H. K.
Published: June 2023

Intracellular recognition of self and non-self -nucleic acids can result in the initiation of effective pro-inflammatory and anti-tumorigenic responses. We hypothesized that macrophages can be activated by tumor-derived nucleic acids to induce inflammasome activation in the tumor microenvironment. We show that tumor conditioned media (CM) can induce IL-1β production, indicative of inflammasome activation in primed macrophages. This could be partially dependent on caspase 1/11, AIM2 and NLRP3. IL-1β enhances tumor cell proliferation, migration and invasion while coculture of tumor cells with macrophages enhances the proliferation of tumor cells, which is AIM2 and caspase 1/11 dependent. Furthermore, we have identified that DNA-RNA hybrids could be the nucleic acid form which activates AIM2 inflammasome at a higher sensitivity as compared to dsDNA. Taken together, the tumor-secretome stimulates an innate immune pathway in macrophages which promotes paracrine cancer growth and may be a key tumorigenic pathway in cancer. Broader understanding on the mechanisms of nucleic acid recognition and interaction with innate immune signaling pathway will help us to better appreciate its potential application in diagnostic and therapeutic benefit in cancer.
A residual network with geographical and meteorological attention for multi-year ENSO forecasts
Authors: Song Dan , Ling Yuting , Hao Tong , Li Wenhui , Liu Wen , Ren Tongwei , Wei Zhiqiang , Liu An-an
Published: June 2023

Introduction

As global temperatures continue to rise, extreme weather phenomena such as El Niño and the Southern Oscillation (ENSO) near the equatorial Pacific Ocean are occurring more frequently and leading to tropical cyclones, droughts, and a series of extreme weather disasters. Accurately predicting ENSO in advance can greatly reduce the serious damage to human society, economy, and ecological environment. However, existing methods often neglect the data relation between geographical regions and meteorological factors, hindering the accuracy of ENSO prediction.

Methods

To overcome this problem, we propose a residual network with geographical and meteorological attention to capture important geographical information and explore the spatio-temporal correlation of different meteorological factors. Specifically, we propose two main attention modules: (1) the Geographical Semantic Information Enhancement Module (GSIEM), which selectively attends to important geographical regions and filters out irrelevant noise through a spatial-axis attention map, and (2) the Meteorological Factors Discriminating Enhancement Module (MFDEM), which aims to learn the spatio-temporal dependency of different meteorological factors using a learnable channel-axis weight map. We then integrate our proposed two attention modules into the backbone using residual connection, enhancing the model's prediction ability.

Results

We conducted extensive experimental comparisons and ablation studies to evaluate the performance of our proposed method. The results show that our method outperforms existing state-of-the-art methods in ENSO prediction, with a significant improvement in prediction accuracy.

Discussion

Our proposed method effectively captures geographical and meteorological information, facilitating accurate ENSO prediction. The attention modules we proposed can effectively filter out irrelevant noise and learn the spatio-temporal dependency of different meteorological factors, contributing to the superior performance of our model. Overall, our study provides a novel approach for ENSO prediction and has great potential for practical applications.
Snow crab (Chionoecetes opilio) hemocytes and hepatopancreas transcriptomes: identification, validation, and application of immune-relevant biomarkers of exposure to noise
Authors: Hall Jennifer R. , Lehnert Sarah J. , Gonzalez Emmanuel , Hanlon Jacqueline M. , Kumar Surendra , Morris Corey J. , Rise Matthew L.
Published: June 2023

The snow crab (Chionoecetes opilio) fishery off the east coast of Newfoundland and Labrador, Canada, has been impacted by annual seismic oil and gas surveying in recent decades, and commercial crab harvesters are concerned that it could potentially affect this resource. A laboratory study was performed to investigate the effects of chronic noise exposure on the transcriptomes of snow crab hemocytes and hepatopancreas, which are important in immunity, metabolism and response to environmental stress. Snow crab were held in replicate control or experimental tanks; on alternating days, the experimental tanks were exposed to noise from an underwater speaker which played a recording of a seismic airgun firing every 10 sec in a continuous loop for ~ 22 weeks (chronic noise). RNA sequencing was used to identify candidate noise-responsive molecular biomarkers in both hemocytes and hepatopancreas. The quantified transcripts of individuals (i.e. n=10 from each of the four groups) were compared using DESeq2, identifying over 300 noise-responsive transcripts in each cell/tissue type. Real-time quantitative polymerase chain reaction (qPCR) assays were designed and run for 61 of these transcripts with significant BLASTx hits. One transcript (rgs2) was significantly (p < 0.05) higher expressed in both hemocytes and hepatopancreas in response to noise; five and seven other transcripts were either significant or showed a non-significant trend of differential expression (0.05 < p ≤ 0.1) in hemocytes (e.g. cfb upregulated, sacs and myof downregulated) and hepatopancreas (e.g. gpx3 and atf3 upregulated, sult1c4 downregulated), respectively. To further investigate the performance and utility of these candidate biomarkers in the field, expression levels of 25 selected transcripts were then examined in the hepatopancreas of snow crab that had been subjected to 2D and 3D seismic surveying using both qPCR and multivariate statistical analyses. Overall, few of these biomarkers showed consistent results in field-collected snow crab, highlighting the need to combine lab and field-based studies to fully evaluate the utility of biomarkers. Nonetheless, our study still identified noise-responsive biomarkers in both settings (including stress and immune relevant genes), providing valuable information for understanding the impact of ocean noise on snow crab physiology and health.
A deep learning model for prediction of post hepatectomy liver failure after hemihepatectomy using preoperative contrast-enhanced computed tomography: a retrospective study
Authors: Xu Xiaoqing , Xing Zijian , Xu Zhiyao , Tong Yifan , Wang Shuxin , Liu Xiaoqing , Ren Yiyue , Liang Xiao , Yu Yizhou , Ying Hanning
Published: June 2023

Objective

Post-hepatectomy liver failure (PHLF) remains clinical challenges after major hepatectomy. The aim of this study was to establish and validate a deep learning model to predict PHLF after hemihepatectomy using preoperative contrast-enhancedcomputed tomography with three phases (Non-contrast, arterial phase and venous phase).

Methods

265 patients undergoing hemihepatectomy in Sir Run Run Shaw Hospital were enrolled in this study. The primary endpoint was PHLF, according to the International Study Group of Liver Surgery’s definition. In this study, to evaluate the proposed method, 5-fold cross-validation technique was used. The dataset was split into 5 folds of equal size, and each fold was used as a test set once, while the other folds were temporarily combined to form a training set. Performance metrics on the test set were then calculated and stored. At the end of the 5-fold cross-validation run, the accuracy, precision, sensitivity and specificity for predicting PHLF with the deep learning model and the area under receiver operating characteristic curve (AUC) were calculated.

Results

Of the 265 patients, 170 patients with left liver resection and 95 patients with right liver resection. The diagnosis had 6 types: hepatocellular carcinoma, intrahepatic cholangiocarcinoma, liver metastases, benign tumor, hepatolithiasis, and other liver diseases. Laparoscopic liver resection was performed in 187 patients. The accuracy of prediction was 84.15%. The AUC was 0.7927. In 170 left hemihepatectomy cases, the accuracy was 89.41% (152/170), and the AUC was 82.72%. The accuracy was 77.47% (141/182) with liver mass, 78.33% (47/60) with liver cirrhosis and 80.46% (70/87) with viral hepatitis.

Conclusion

The deep learning model showed excellent performance in prediction of PHLF and could be useful for identifying high-risk patients to modify the treatment planning.
Non-invasive estimation of split renal function from routine 68Ga-SSR-PET/CT scans
Authors: Weissinger Matthias , Seyfried Kyra Celine , Ursprung Stephan , Castaneda-Vega Salvador , Seith Ferdinand , von Beschwitz Sebastian , Vogel Jonas , Ghibes Patrick , Nikolaou Konstantin , la Fougère Christian , Dittmann Helmut
Published: June 2023

Objective

Patients with impaired kidney function are at elevated risk for nephrotoxicity and hematotoxicity from peptide receptor radionuclide therapy (PPRT) for advanced neuroendocrine tumors. Somatostatin receptor (SSR)-PET/CT imaging is the method of choice to identify sufficient SSR expression as a prerequisite for PRRT. Therefore, our study aimed to explore whether split renal function could be evaluated using imaging data from routine SSR-PET/CT prior to PRRT.

Methods

In total, 25 consecutive patients who underwent SSR-PET/CT (Siemens Biograph mCT®) before PRRT between June 2019 and December 2020 were enrolled in this retrospective study. PET acquisition in the caudocranial direction started at 20 ± 0.5 min after an i.v. injection of 173 ± 20 MBq [68Ga]Ga-ha DOTATATE, and the kidneys were scanned at 32 ± 0.5 min p.i. The renal parenchyma was segmented semi-automatically using an SUV-based isocontour (SUV between 5 and 15). Multiple parameters including SUVmean of renal parenchyma and blood pool, as well as parenchyma volume, were extracted, and accumulation index (ACI: renal parenchyma volume/SUVmean) and total kidney accumulation (TKA: SUVmean x renal parenchyma volume) were calculated. All data were correlated with the reference standard tubular extraction rate (TER-MAG) from [99mTc]Tc-MAG3 scintigraphy and glomerular filtration rate (GFRCDK − EPI).

Results

SUVmean of the parenchymal tracer retention showed a negative correlation with TERMAG (r: −0.519, p < 0.001) and GFRCDK − EPI (r: −0.555, p < 0.001) at 32 min p.i. The herein-introduced ACI revealed a significant correlation (p < 0.05) with the total tubular function (r: 0.482), glomerular renal function (r: 0.461), split renal function (r: 0.916), and absolute single-sided renal function (r: 0.549). The mean difference between the split renal function determined by renal scintigraphy and ACI was 1.8 ± 4.2 % points.

Conclusion

This pilot study indicates that static [68Ga]Ga-ha DOTATATE PET-scans at 32 min p.i. may be used to estimate both split renal function and absolute renal function using the herein proposed “Accumulation Index” (ACI).
Abatacept to induce remission of peanut allergy during oral immunotherapy (ATARI): protocol for a phase 2a randomized controlled trial
Authors: Braun Camille , Azzano Pauline , Gingras-Lessard Florence , Roy Émilie , Samaan Kathryn , Graham François , Paradis Louis , Des Roches Anne , Bégin Philippe
Published: June 2023

Context

While oral immunotherapy (OIT) has been shown to promote the remission of mild peanut allergy in young children, there is still an unmet need for a disease-modifying intervention for older patients and those with severe diseases. In mice models, abatacept, a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) immunoglobulin fusion protein, has been shown to promote immune tolerance to food when used as an adjuvant to allergen immunotherapy. The goal of this study is to explore the potential efficacy of abatacept in promoting immune tolerance to food allergens during OIT in humans.

Methods

In this phase 2a proof-of-concept study (NCT04872218), 14 peanut-allergic participants aged from 14 to 55 years will be randomized at a 1:1 ratio to abatacept vs. placebo for the first 24 weeks of a peanut OIT treatment (target maintenance dose of 300 mg peanut protein). The primary outcome will be the suppression of the OIT-induced surge in peanut-specific IgE/total IgE at 24 weeks, relative to the baseline. Sustained unresponsiveness will be assessed as a secondary outcome starting at 36 weeks by observing incremental periods of peanut avoidance followed by oral food challenges.

Discussion

This is the first study assessing the use of abatacept as an adjuvant to allergen immunotherapy in humans. As observed in preclinical studies, the ability of abatacept to modulate the peanut-specific immune response during OIT will serve as a proxy outcome for the development of clinical tolerance, given the small sample size. The study will also test a new patient-oriented approach to sustained tolerance testing in randomized controlled trials.
Perceptions of medical students toward teledermatology as an educational tool: a cross-sectional study
Authors: Ureña-Paniego Clara , Soto-Moreno Alberto , Montero-Vílchez Trinidad , Martínez-López Antonio , Buendía-Eisman Agustín , Arias-Santiago Salvador
Published: June 2023

Introduction

Teledermatology consultations have recently been on the rise, especially due to the SARS-CoV-2 pandemic. The role of teledermatology has been extensively discussed as a mean for the education of dermatology residents. Nevertheless, little has been explored on its use as a pedagogical tool for medical students. The objectives of this study were to assess the level of satisfaction of medical students with teledermatology and to evaluate their opinion about its use as an educational tool.

Methods

A cross-sectional study was carried out at the Dermatology Department, Hospital Universitario Virgen de las Nieves, Granada (Spain). Participants were fourth-year medical students. Every student would spend half of their internship in face-to-face consultations and the other half in teledermatology consultations. Data was collected via self-administered questionnaires.

Results

Eighty one students were finally surveyed, being 66.67% (73/81) female. A majority of students considered a mixed clinical internship model (face-to-face consultations combined with teledermatology) more suitable for obtaining higher marks in the subject of dermatology and in the Medical Intern Resident exam (p = 0.04). Nevertheless, face-to-face practice was considered more useful for their training as general practitioners (p = 0.04).

Conclusion

Despite the fact that students highly value doctor-patient relationship, teledermatology is considered a powerful educational tool.
The host transcriptome change involved in the inhibitory effect of exogenous interferon-γ on Getah virus replication
Authors: Li Jialei , Gao Xintao , Liu Xingjian , Wu Tong , Song Haozhi , Gao Weisong , Jia Hong , Li Yinü , Zhang Zhifang
Published: June 2023

Introduction

Getah virus (GETV) has become a growing potential threat to the global livestock industry and public health. However, little is known about the viral pathogenesis and immune escape mechanisms, leading to ineffective control measures.

Methods

In this study, the antiviral activity of exogenous interferons (IFNs) was assessed by using western blotting (WB), real-time quantitative PCR (RT-qPCR) and indirect immunofluorescence assay (IFA). The comparative transcriptomics among mock- and GETV-infected (MOI = 0.1) ST cells with or without IFN-γ was performed by RNA-seq, and then the transcriptome profiling of GETV-infected ST cells and key pathways and putative factors involved in inhibitory effect of IFN-γ on GETV replication were analyzed by bioinformatics methods and RT-qPCR.

Results

The results showed that treatment with IFN-γ could suppress GETV replication, and the inhibitory effect lasted for at least 48 h, while the exogenous IFN-α/ω and IFN-λ3 treatments failed to inhibit the viral infection and early replication in vitro. Furthermore, the blueprint of virus-host interaction was plotted by RNA-seq and RT-qPCR, showing systemic activation of inflammatory, apoptotic, and antiviral pathways in response to GETV infection, indicating viral hijacking and inhibition of innate host immunity such as IFN-I/III responses. Last and most importantly, activation of the JAK-STAT signaling pathway and complement and coagulation cascades may be a primary driver for IFN-γ-mediated inhibition of GETV replication.

Discussion

These findings revealed that GETV possessed the capability of viral immune escape and indicated that IFN-γ aided in the prevention and control of GETV, implying the potential molecular mechanism of suppression of GETV by IFN-γ, all of which warrant emphasis or further clarification.
Intraocular complement activation is related to retinal vascular and neuronal degeneration in myopic retinopathy
Authors: Zeng Ling , Li Xiaoning , Pan Wei , Tang Yao , Lin Ding , Wang Min , Cai Wang , Zhu Ruiling , Wan Jianbo , Huang Linghua , Xu Heping , Yang Zhikuan
Published: June 2023

Purpose

To investigate the relationship between the intraocular levels of complement proteins and myopia-related retinal neuronal and vascular degeneration.

Methods

Aqueous humour from 147 myopic patients, including 60 low-myopia and 87 high-myopia were collected during Implantable Collamer Lens implantation surgery. All participants received comprehensive ophthalmic examinations, including logMAR best corrected visual acuity, axial length measurement, fundus photography and ocular B-scan ultrasonography. The myopic eyes were further classified into simple myopia (SM, n = 78), myopic posterior staphyloma (PS, n = 39) and PS with myopic chorioretinal atrophy (PS + CA, n = 30). Retinal thickness and vascular density in the macula (6 mm × 6 mm) and optic nerve head (4.5 mm × 4.5 mm) were measured using Optical Coherence Tomography (OCT) and OCT angiography (OCTA). The levels of complement proteins including C1q, C3, C3b/iC3b, C4, CFB, CFH, C2, C4b, C5, C5a, CFD, MBL and CFI in the aqueous humour were measured using the Luminex Multiplexing system. The real-time RT-PCR was conducted to examine the expression of complement genes (C1q, C2, C3, C4, CFI and CFD) in the guinea pig model of long-term form deprivation-induced myopic retinal degeneration.

Results

OCTA showed that retinal neuronal thickness and vascular density in superficial and deep layers of the macular zone as well as vascular density in the optic nerve head were progressively decreased from SM to PS and PS + CA (p < 0.05). The aqueous humour levels of C1q, C3, C3b/iC3b, C4, CFB, CFH, C2, C4b, C5 and CFI were significantly higher in high-myopic eyes compared to those in low-myopic eyes. Further subgroup analysis revealed the highest levels of complement components/fragments in the PS + CA group. The intraocular levels of complement factors particularly C3b/iC3b and C4 were negatively correlated with macular zone deep layer retinal thickness and vascular density and optic nerve head vascular density. The expression of C2, C3 and C4 genes was significantly higher in guinea pig eyes with myopic retinal degeneration compared to control eyes.

Conclusions

The intraocular classical pathway and alternative pathway of the complement system are partially activated in pathological myopia. Their activation is related to the degeneration of retinal neurons and the vasculature in the macula and the vasculature in the optic nerve head.
Cochlear implantation impairs intracochlear microcirculation and counteracts iNOS induction in guinea pigs
Authors: Ernst Benjamin Philipp , Heinrich Ulf-Rüdiger , Fries Mathias , Meuser Regina , Rader Tobias , Eckrich Jonas , Stauber Roland H. , Strieth Sebastian
Published: June 2023

Introduction

Preservation of residual hearing remains a great challenge during cochlear implantation. Cochlear implant (CI) electrode array insertion induces changes in the microvasculature as well as nitric oxide (NO)-dependent vessel dysfunction which have been identified as possible mediators of residual hearing loss after cochlear implantation.

Methods

A total of 24 guinea pigs were randomized to receive either a CI (n = 12) or a sham procedure (sham) by performing a cochleostomy without electrode array insertion (n = 12). The hearing threshold was determined using frequency-specific compound action potentials. To gain visual access to the stria vascularis, a microscopic window was created in the osseous cochlear lateral wall. Cochlear blood flow (CBF) and cochlear microvascular permeability (CMP) were evaluated immediately after treatment, as well as after 1 and 2 h, respectively. Finally, cochleae were resected for subsequent immunohistochemical analysis of the iNOS expression.

Results

The sham control group showed no change in mean CBF after 1 h (104.2 ± 0.7%) and 2 h (100.8 ± 3.6%) compared to baseline. In contrast, cochlear implantation resulted in a significant continuous decrease in CBF after 1 h (78.8 ± 8.1%, p < 0.001) and 2 h (60.6 ± 11.3%, p < 0.001). Additionally, the CI group exhibited a significantly increased CMP (+44.9% compared to baseline, p < 0.0001) and a significant increase in median hearing threshold (20.4 vs. 2.5 dB SPL, p = 0.0009) compared to sham after 2 h. Intriguingly, the CI group showed significantly lower iNOS-expression levels in the organ of Corti (329.5 vs. 54.33 AU, p = 0.0003), stria vascularis (596.7 vs. 48.51 AU, p < 0.0001), interdental cells (564.0 vs. 109.1 AU, p = 0.0003) and limbus fibrocytes (119.4 vs. 18.69 AU, p = 0.0286).

Conclusion

Mechanical and NO-dependent microvascular dysfunction seem to play a pivotal role in residual hearing loss after CI electrode array insertion. This may be facilitated by the implantation associated decrease in iNOS expression. Therefore, stabilization of cochlear microcirculation could be a therapeutic strategy to preserve residual hearing.
Case report: Steroid-responsive acute chorea as first presentation of the coexistence of Moyamoya and Graves' disease
Authors: Wang Wei-Sheng , Wu Shey-Lin , Chan Wei-Chieh , Chen Yen-Chung
Published: June 2023

Background

Chorea is a movement disorder characterized by abrupt, rapid, and uncontrollable, random movements from one part of the body to another with motor impersistence. Sporadic chorea is rarely caused by either thyrotoxicosis or Moyamoya disease (MMD).

Methods and results

In this case report, we describe a female patient with chorea with the rare coexistence of Graves' disease and Moyamoya disease. Tc-99m ethyl cysteinate dimer (ECD) brain perfusion single-photon emission computed tomography (SPECT) showed mild to moderate hypoperfusion in bilateral frontal and left temporal regions. After administering dexamethasone 20 mg for 5 days, her choreic movement symptoms recovered rapidly.

Conclusion

Although uncommon, thyrotoxicosis and Moyamoya disease can co-occur, especially in Asian female adults. Excessive thyroid hormones contribute to the dysregulation of neurotransmitters in basal ganglia-thalamocortical circuits. Moyamoya disease is responsible for ischemic changes affecting the excitatory–inhibitory circuits between the basal ganglia and the neocortex. Under a state of coexistence, thyrotoxicosis exaggerates cerebral metabolism, aggravating the impaired cerebral perfusion induced by Moyamoya disease. Moreover, inflammatory reactions caused by thyroid autoantibodies may also promote the progression of Moyamoya disease. In our experience, treatment with steroids may not only synergize the anti-thyroid effect but may also be a way to modulate the neurotransmitters within the basal ganglia or restore cerebral perfusion. We suggest that evaluation of the thyroid function status in Moyamoya disease is essential.
Home-based exercise training by using a smartphone app in patients with Parkinson’s disease: a feasibility study
Authors: Putzolu Martina , Manzini Virginia , Gambaro Matteo , Cosentino Carola , Bonassi Gaia , Botta Alessandro , Ravizzotti Elisa , Avanzino Laura , Pelosin Elisa , Mezzarobba Susanna
Published: June 2023

Background

Parkinson’s disease (PD) patients experience deterioration in mobility with consequent inactivity and worsened health and social status. Physical activity and physiotherapy can improve motor impairments, but several barriers dishearten PD patients to exercise regularly. Home-based approaches (e.g., via mobile apps) and remote monitoring, could help in facing this issue.

Objective

This study aimed at testing the feasibility, usability and training effects of a home-based exercise program using a customized version of Parkinson Rehab® application.

Methods

Twenty PD subjects participated in a two-month minimally supervised home-based training. Daily session consisted in performing PD-specific exercises plus a walking training. We measured: (i) feasibility (training adherence), usability and satisfaction (via an online survey); (ii) safety; (iii) training effects on PD severity, mobility, cognition, and mood. Evaluations were performed at: baseline, after 1-month of training, at the end of training (T2), and at 1-month follow-up (T3).

Results

Eighteen out of twenty participants completed the study without important adverse events. Participants’ adherence was 91% ± 11.8 for exercise and 105.9% ± 30.6 for walking training. Usability and satisfaction survey scored 70.9 ± 7.7 out of 80. Improvements in PD severity, mobility and cognition were found at T2 and maintained at follow-up.

Conclusion

The home-based training was feasible, safe and seems to positively act on PD-related symptoms, mobility, and cognition in patients with mild to moderate stage of PD disease. Additionally, the results suggest that the use of a mobile app might increase the amount of daily physical activity in our study population. Remote monitoring and tailored exercise programs appear to be key elements for promoting exercise. Future studies in a large cohort of PD participants at different stages of disease are needed to confirm these findings.
Development of a CT image analysis-based scoring system to differentiate gastric schwannomas from gastrointestinal stromal tumors
Authors: Zhang Sheng , Yang Zhiqi , Chen Xiaofeng , Su Shuyan , Huang Ruibin , Huang Liebin , Shen Yanyan , Zhong Sihua , Zhong Zijie , Yang Jiada , Long Wansheng , Zhuang Ruyao , Fang Jingqin , Dai Zhuozhi , Chen Xiangguang
Published: June 2023

Purpose

To develop a point-based scoring system (PSS) based on contrast-enhanced computed tomography (CT) qualitative and quantitative features to differentiate gastric schwannomas (GSs) from gastrointestinal stromal tumors (GISTs).

Methods

This retrospective study included 51 consecutive GS patients and 147 GIST patients. Clinical and CT features of the tumors were collected and compared. Univariate and multivariate logistic regression analyses using the stepwise forward method were used to determine the risk factors for GSs and create a PSS. Area under the receiver operating characteristic curve (AUC) analysis was performed to evaluate the diagnostic efficiency of PSS.

Results

The CT attenuation value of tumors in venous phase images, tumor-to-spleen ratio in venous phase images, tumor location, growth pattern, and tumor surface ulceration were identified as predictors for GSs and were assigned scores based on the PSS. Within the PSS, GS prediction probability ranged from 0.60% to 100% and increased as the total risk scores increased. The AUC of PSS in differentiating GSs from GISTs was 0.915 (95% CI: 0.874–0.957) with a total cutoff score of 3.0, accuracy of 0.848, sensitivity of 0.843, and specificity of 0.850.

Conclusions

The PSS of both qualitative and quantitative CT features can provide an easy tool for radiologists to successfully differentiate GS from GIST prior to surgery.
Therapeutic strategies to overcome EGFR mutations as acquired resistance mechanism in ALK-rearranged non-small-cell lung cancer: Case Reports
Authors: Michaux Lionel , Perrier Alexandre , Mehlman Camille , Alshehhi Hussa , Dubois Antonin , Lacave Roger , Coulet Florence , Cadranel Jacques , Fallet Vincent
Published: June 2023

Introduction

ALK tyrosine kinase inhibitors (ALK TKIs) have improved prognosis in ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC). However, drug resistance mechanisms occur inevitably during the course of treatment leading to disease progression. Activation of epidermal growth factor receptor (EGFR) bypass signaling pathway is an uncommon cause of acquired resistance to ALK TKIs.

Method

We present two patients with EML4-ALK rearranged NSCLC, developing an acquired EGFR resistance mutation after receiving multiple lines of ALK TKIs.

Results

While preclinical models have showed encouraging data, there is a critical need for clinical studies on treatment strategies to overcome this drug resistance. Three real-life therapeutic approaches were used in this report: i) using brigatinib, an inhibitor targeting both ALK and EGFR tyrosine kinases; ii) combining two ALK TKIs together; and iii) delivering doublet platinum chemotherapy. In case 1, time to treatment failure (TTF) was 9.5 months with brigatinib; in case 2, TTF was 10 months with combined TKIs (osimertinib and brigatinib), whereas TTF with chemotherapy was only 2 months. Tolerability profile TKIs combotherapy was acceptable.

Conclusion

These case reports underline the therapeutic complexity of EGFR-acquired resistance mutation in ALK+ NSCLC and offers some leads to solve this real-life clinical challenge.
Extrachromosomal DNA (ecDNA) in cancer: mechanisms, functions, and clinical implications
Authors: Dong Yucheng , He Qi , Chen Xinyu , Yang Fan , He Li , Zheng Yongchang
Published: June 2023

Extrachromosomal DNA (ecDNA) is circular DNA that plays an important role in the development and heterogeneity of cancer. The rapid evolution of methods to detect ecDNA, including microscopic and sequencing approaches, has greatly enhanced our knowledge of the role of ecDNA in cancer development and evolution. Here, we review the molecular characteristics, functions, mechanisms of formation, and detection methods of ecDNA, with a focus on the potential clinical implications of ecDNA in cancer. Specifically, we consider the role of ecDNA in acquired drug resistance, as a diagnostic and prognostic biomarker, and as a therapeutic target in the context of cancer. As the pathological and clinical significance of ecDNA continues to be explored, it is anticipated that ecDNA will have broad applications in the diagnosis, prognosis, and treatment of patients with cancer.