bluuebunny/crossref_metadata_2025 huggingface dataset:
Memory Preservation in Cambodian Graphic Narratives
Authors: Hardman Anneliese
Published: February 2024

Since the Cambodian genocide (1975-79), first-and-second generation survivors have developed new ways of processing personal and national trauma, including through the mode of graphic arts. This paper first extrapolates how graphic narratives differ from comics and cartoons. Then the graphic narrative’s role in assisting genocide survivors will be examined. In this section, the works of graphic artists, Ing Phoussera, Aki Rai, and Vath Nath, will be specifically looked at in relation to Franz Stanzel’s idea of ‘reflector narratives’ and Mieke Bal’s definition of ‘focalization.’ The paper will also focus on how graphic narratives have become a mode for second-generation survivors to engage with the past through Bui Long’s ‘refugee repertoire’ and Marianne Hirsch’s concept of ‘postmemory.’ Within this section, Tian Veasna’s Year of the Rabbit’s will be analyzed. Aspects considered include illustration, dialogue, and layered content. Finally, this paper will look at how graphic narratives contribute to the concept of the memory archive and “memory citizenship” within Cambodia. Specific questions that prompt my research include: What is a graphic narrative? Can graphic narratives be sources of memoir and postmemory? How do graphic narratives function as a tool for remembering and working through trauma for artists and readers?
MEDIAÇÃO DA APRENDIZAGEM POR MEIO DE TECNOLOGIAS DE ENSINO: UMA PROPOSTA DE AUTOESTUDO DE PRÉ-CÁLCULO
Authors: Beneti de Oliveira Patricia , Trevisan André Luis , Kirnev Debora Cristiane Barbosa
Published: February 2024

Neste trabalho discutimos sobre metodologias de ensino utilizadas na disciplina Cálculo que em geral apresentam uma abordagem mais complexa e abstrata, vinculadas a uma prática pedagógica tradicional e conteudista, além das defasagens que os estudantes de engenharias apresentam sobre os conceitos matemáticos de pré-cálculo. Com base nisso, temos como objetivo discutir sobre uma proposta de prática pedagógica de autoestudo para estudantes ingressantes de cursos de engenharia, tendo como finalidade dar subsídio a aprendizagem de conceitos iniciais da disciplina de Cálculo a partir da mediação de uma metodologia ativa com apoio das tecnologias de ensino por meio de atividades sobre funções que buscam relacionar a teoria e prática através de situações contextualizadas, além de se estabelecer diferentes formas de representação, dentre elas a algébrica e a gráfica. Posteriormente o desenvolvimento do autoestudo, espera-se que os resultados para o ensino de funções, devidamente contextualizada e organizada com a metodologia ativa, sejam significativas e possibilitem a aplicação desse conceito na resolução de problemas na área de Engenharia. Palavras-chave: Educação Matemática. Metodologias Ativas. Tecnologias de Ensino. Engenharia. Cálculo Diferencial e Integral.
ABSTRACTIn this work we discuss teaching methodologies used in the Calculus Discipline, which generally present a more complex and abstract approach, linked to a traditional and content-based pedagogical practice, in addition to the gaps that engineering students present in pre-calculus mathematical concepts. Based on this, we aim to discuss a proposal for a self-study pedagogical practice for students entering engineering courses, with the aim of supporting the learning of initial concepts of the Calculus discipline through the mediation of an active methodology with the support of technologies teaching through activities on functions that seek to relate theory and practice through contextualized situations, in addition to establishing different forms of representation, including algebraic and graphical. After the development of self-study, it is expected that the results for teaching functions, properly contextualized and organized with the active methodology, will be significant and enable the application of this concept in solving problems in the area of Engineering.Keywords: Mathematics Education. Active Methodologies. Teaching Technologies. Engineering. Differential and integral calculus.
Middle School Students’ Interest in Learning Sprinting Online Running During New Normal
Authors: SUTİSWO Sutiswo , WİDİASTUTİ Widiastuti , FACHREZZY Fahmi , - Samsudin , HAMBALİ Sumbara , AKBARUDDİN Asep
Published: February 2024

The COVID-19 pandemic has changed the school learning system, which was initially done offline; now, it is done online. However, several problems arise related to the learning process carried out. This study wanted to find out about students' interest in online learning. This study aimed to determine how much middle school students are interested in learning sprinting online during the new normal. The study is quantitative descriptive research, and the method used in this study was a survey with a questionnaire data collection technique in the form of a questionnaire. The population in this study were students of middle schools Informatika Bina Generasi Ciomas Bogor in class VIII, totaling five classes of 150 people. The sample in this study was class VIII-B, with 30 students. The data analysis technique used quantitative descriptive analysis as outlined in the form of a percentage. This study's results indicate that the study's results suggest that the interest of middle school students in online-based sprinting learning during the Covid-19 New Normal period is included in the high category. Where out of 30 respondents, in the very high category were five students (17%); in the high category were 17 students (56%); in the medium category were three students (10%); the low category were three students (10%), and the very low category were two students (7%). This study concludes that middle school students' interest in online-based sprinting learning during the COVID-19 New Normal period is more dominant on intrinsic factors.
Pediatric Thoracoscopy: Ten Years Experience in Tertiary Hospital
Authors: Alharbi Wafa , Almatrfi Ameera , Bawazir Osama
Published: February 2024

Purpose: A minimally invasive Thoracoscopic Surgery (TS) offers several options in diagnosis and surgical treatment in pediatric surgery. This study evaluates experience and outcome of thoracoscopic surgery in pediatrics during 10 years period in tertiary hospital. Patients and methods: This retrospective study conducted at King Faisal Hospital and Research Center, Jeddah, Saudi Arabia from 2012 to 2022. Data of 43 patients who underwent TS were enrolled. Data include patient’s demographic characteristics, co-morbidity, diagnosis, type of thoracoscopic procedures, time of intervention, length of hospital stay, post-operative complications. Results: Mean age of patients was 4.99 years. Females were more than males (55.8 vs. 44.2%). Sixteen (37.2%) patients had comorbidities. Thoracoscopic proce- dures were feasible in 43 children and adolescents with chest diseases including lung empyema (20.9%), congenital lobar emphysema (14.0%), interstitial lung disease (14.0%), congenital pulmonary airway malformation (11.6%), mediastinal mass (9.3%), lung metastasis (11.6%), lymphoma (4.7%), chronic inflamma- tions (7.0%), hemothorax (2.3%), bronchogenic cyst (2.3%), pleural effusion (2.3%) and pulmonary sequestration and right diaphragmatic hernia (2.3%). Proce- dures were made mostly for lung biopsy (25.0%), lobectomy (22.7%), decortication (20.9%), mediastinum mass resection (6.8%), lung metastasectomy (6.8%), lymph node biopsy (4.5%), diagnostic (4.6%), cyst excision (4.6%), diaphragmatic hernia repair (2.3%) and thymectomy (2.3%). Duration of hospital stay ranged from 2-180 days. All of the cases had chest drain (100.0%) and some of them required post-operative intubations (30.2%). Conversion rate to open was (4.7%). Complications were pneumothorax (7.0%), bleeding (2.3%) and air leak (2.3%). Conclusions: Thoracoscopic approach is a challenging method for diagnosis and treatment in pediatrics. However, complications were reported as pneumo- thorax, bleeding and air leak. In order to improve results, conversion rates, and the capacity to handle thoracoscopic complications, proper training is crucial.
Fabrication and Electrical Characterization of p/n PbSe Diodes
Authors: Hwangbo Sukho , Lee Jewon
Published: February 2024

Lead selenide (PbSe) diodes were fabricated using a magnetron sputtering process system with a pulsed DC power supply and a 2-inch PbSe target with a purity of 5N. For p-type PbSe thin films, the process variable was the oxygen ratio in the mixed gas of argon and oxygen. The electrical characteristics of the thin films were observed after heat treatment. For the n-type PbSe, nickel (Ni) was used as a doping material. The deposition and doping were performed simultaneously using a co-sputtering method. During co-sputtering, the input power of the Ni sputter gun was adjusted as a process variable. Hall measurement experiments were performed to measure the doping concentration and resistivity of both the p-type and n-type PbSe semiconducting films. The maximum doping concentration was 2.33×1019 cm-3 for p-type PbSe and 7.55×1020 cm-3 for n-type PbSe thin films, respectively. The p-n junction IV curve showed that the lowest forward voltage generation point, Vf, was 1.5 V and the reverse breakdown voltage was -4.3 V. In the photocurrent measurement, the photo sensitivities of the heat-treated samples were higher than that of the non-treated sample, and the maximum value was 5.148. Photo responsivity was also higher in the heat-treated samples. Its maximum was 0.7306 mA / W.
External comparators and estimands
Authors: Rippin Gerd
Published: February 2024

The estimand framework as defined by the ICH E9(R1) addendum aims to clearly define “the treatment effect reflecting the clinical question posed by the trial objective”. It intends to achieve this goal of a clear definition by specifying the 5 estimand attributes: treatment conditions, population, endpoints, handling of intercurrent events (IEs), and population-level summary. However, hybrid clinical/observational research like External Comparators (ECs) leads to new reflections on existing attributes and to considerations for additional ones. Specifically, treatment conditions and exposure may be more difficult to handle in the EC, and especially Standard of Care (SoC) treatment needs detailed attention. The external population typically cannot be based on the classical Intention-to-treat population and constitutes also an approximation only. Endpoints may not be comparable across cohorts, and IEs may be more different than in an RCT setting, such that the hypothetical treatment policy according to the ICH E9(R1) addendum may become of greater interest especially for long-term endpoints. Finally, the necessary assumptions for some population-level summaries (e.g., the proportional hazards assumption) can become more fragile when joining data from different sources due to induced heterogeneity. Finally, it is shown that the baseline definition and the marginal estimator are candidates for additional estimand attributes in case the estimand framework is revised to account for observational study needs.
Can normalized difference vegetation index and climate data be used to estimate soil carbon, nitrogen, and phosphorus and their ratios in the Xizang grasslands?
Authors: Wang Shaohua , Qi Huxiao , Li Tianyu , Qin Yong , Fu Gang , Pan Xu , Zha Xinjie
Published: February 2024

Accurately quantifying the relative effects of climate change and human activities on soil carbon, nitrogen, and phosphorus in alpine grasslands and their feedback is an important aspect of global change, and high-precision models are the key to solving this scientific problem with high quality. Therefore, nine models, the random forest model (RFM), generalized boosted regression model (GBRM), multiple linear regression model (MLRM), support vector machine model (SVMM), recursive regression tree model (RRTM), artificial neural network model (ANNM), generalized linear regression model (GLMR), conditional inference tree model (CITM), and eXtreme gradient boosting model (eXGBM), were used for modeling soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), the ratio of SOC to TN (C:N), the ratio of SOC to TP (C:P), and the ratio of TN to TP (N:P) at depths of 0–10, 10–20, and 20–30 cm under non-grazing and free-grazing scenarios in the Xizang grasslands. Annual radiation (ARad), annual precipitation (AP), and annual temperature (AT) were used as independent variables under non-grazing scenarios, whereas ARad, AP, AT, and growing season maximum normalized difference vegetation index (NDVImax) were used as independent variables under free-grazing scenarios. Overall, the RFM and GBRM were more accurate than the other seven models. However, the tree numbers of the GBRM were much larger than those of the RFM, indicating that the GBRM may have a greater model complexity and lower running speed. Therefore, the RFM had the best performance among the nine models in modeling SOC, TN, TP, C:N, C:P, and N:P in the Xizang grasslands. The RFM established in this study can not only help scientists save time and money on massive sampling and analysis, but can also be used to construct a database of SOC, TN, and TP, and their ratios, and further scientific research related to ecological and environmental issues (e.g., examining whether soil systems intensified global warming over the past few decades by exploring whether climate change and human activities altered soil organic carbon) in the grasslands of Xizang Plateau.
Characterization and spatiotemporal variations of ambient seismic noise in eastern Bangladesh
Authors: Bin Abdul Rahman Syed Idros , Lythgoe Karen , Muktadir Md. Golam , Akhter Syed Humayun , Hubbard Judith
Published: February 2024

This study analyses the ambient noise field recorded by the seismic network, TREMBLE, in Bangladesh, operational since late 2016. Horizontal-vertical spectral ratios confirm the placement of stations on sediment, many situated on thick sedimentary columns, consistent with local geology. Noise across the broadband spectrum is systematically examined. A high amplitude local microseism (0.4–0.8 Hz) is recorded, originating near the coast and modulated by local tides. The secondary microseism (0.15–0.35 Hz) correlates strongly with wave height in the Bay of Bengal and varies with seasons, with greater power and higher horizontal amplitude in the monsoon season when the wave height is highest. The microseism increases in amplitude and decreases in frequency as a tropical depression moves inland. The primary microseism (∼0.07–0.08 Hz) exhibits no seasonal changes in power but display strong horizontal energy which changes with seasons. Low frequency (0.02–0.04 Hz) noise on the horizontal components has a 24-h periodicity, due to instrument tilt caused by atmospheric pressure changes. A station located next to the major Karnaphuli River shows elevated energy at ∼5 Hz correlated to periods of high rainfall. Anthropogenic noise (∼4–14 Hz) is station-dependent, demonstrating changing patterns in human activity, such as during Ramadan, national holidays and the COVID pandemic. Our work holds implications for seismic deployments, earthquake, and imaging studies, while providing insights into the interaction between the atmosphere, ocean, and solid Earth.
U-Shaped relationship of insulin-like growth factor I and incidence of nonalcoholic fatty liver in patients with pituitary neuroendocrine tumors: a cohort study
Authors: Hu Yan , Yuan Chen , Abdulnaimu Muila , Memetmin Jimilanmu , Jie Zhang , Tuhuti Aihemaitijiang , Abudueini Hanikzi , Guo Yanying
Published: February 2024

Context

Although the role of insulin-like growth factor I (IGF-1) in nonalcoholic fatty liver disease (NAFLD) has garnered attention in recent years, few studies have examined both reduced and elevated levels of IGF-1.

Objective

The aim of this study was to examine the potential relationship between IGF-1 levels and the risk of new-onset NAFLD in patients with pituitary neuroendocrine tumors (PitNET).

Methods

We employed multivariable Cox regression models and two-piecewise regression models to assess the association between IGF-1 and new-onset NAFLD. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated to quantify this association. Furthermore, a dose-response correlation between lgIGF-1 and the development of NAFLD was plotted. Additionally, we also performed subgroup analysis and a series sensitivity analysis.

Results

A total of 3,291 PitNET patients were enrolled in the present study, and the median duration of follow-up was 65 months. Patients with either reduced or elevated levels of IGF-1 at baseline were found to be at a higher risk of NAFLD compared to PitNET patients with normal IGF-1(log-rank test, P < 0.001). In the adjusted Cox regression analysis model (model IV), compared with participants with normal IGF-1, the HRs of those with elevated and reduced IGF-1 were 2.33 (95% CI 1.75, 3.11) and 2.2 (95% CI 1.78, 2.7). Furthermore, in non-adjusted or adjusted models, our study revealed a U-shaped relationship between lgIGF-1 and the risk of NAFLD. Moreover, the results from subgroup and sensitivity analyses were consistent with the main results.

Conclusions

There was a U-shaped trend between IGF-1 and new-onset NAFLD in patients with PitNET. Further evaluation of our discoveries is warranted.
New-onset metabolic syndrome is associated with accelerated renal function decline partially through elevated uric acid: an epidemiological cohort study
Authors: Xu Qiuyu , Fan Xiaohong , Chen Gang , Ma Jie , Ye Wenling , Ai Sanxi , Wang Li , Zheng Ke , Qin Yan , Chen Limeng , Li Mingxi , Li Xuemei
Published: February 2024

Background

The burden of metabolic syndrome (MetS) continues to rise globally and is associated with complications of multiple organ systems. We aimed to identify the association between changes in MetS status and accelerated renal function progression through a regional epidemiological survey in China, thus discovering influence factors with treatable potential.

Methods

This study was a population-based survey conducted in 2008 and 2014, assessing a representative sample of 5,225 individuals from rural areas of China. They were divided into four subgroups according to their MetS status in 2008 and 2014 (Never, Previously abnormal, New-onset, and Consistent). Multivariate logistic regression and stratification analysis evaluated the relationship between clinical factors and renal function decline under different MetS statuses. Smooth curve fitting further addressed the role of serum uric acid, illustrating the vital turning point of uric acid levels in the background of renal function deterioration.

Results

Of all groups of MetS states, the new-onset MetS showed the most significant eGFR decline, with a 6.66 ± 8.21 mL/min/1.73 m2 decrease over 6 years. The population with newly-onset MetS showed a considerable risk increase in delta eGFR with a beta coefficient of 1.66 (95%CI=1.09-2.23) after necessary correction. In searching for the drivers, the strength of the association was significantly reduced after additional adjustment for uric acid levels (β=0.91, 95%CI=0.35-1.45). Regarding the turning point, uric acid levels exceeding 426 μmol/L were more significantly associated with the stepped-up deterioration of kidney function for those with new-onset MetS.

Conclusion

Metabolic syndrome demonstrated a solid correlation with the progression of renal function, particularly in those with newly-onset MetS status. In addition to the diagnostic components of MetS, hyperuricemia could be used as a marker to identify the high risk of accelerating eGFR decline early. Furthermore, we suggested a potential renal benefit for the newly-onset MetS population when maintaining their serum uric acid level below the criteria for asymptomatic hyperuricemia.
Positive correlation between the nuclear expression of GPER and pGLI3 in prostate cancer tissues from patients with different Gleason scores
Authors: Rico-Fuentes Cecilia , López-Pulido Edgar Iván , Pérez-Guerrero Edsaúl Emilio , Godínez-Rubí Marisol , Villegas-Pineda Julio César , Villanueva-Pérez Martha Arisbeth , Sierra-Díaz Erick , Zepeda-Nuño José Sergio , Pereira-Suárez Ana Laura , Ramírez-de-Arellano Adrián
Published: February 2024

Prostate cancer (PCa) is the most prevalent cause of death in the male population worldwide. The G Protein-Coupled Estrogen Receptor (GPER) has been gaining relevance in the development of PCa. Hedgehog (Hh) pathway activation is associated with aggressiveness, metastasis, and relapse in PCa patients. To date, no studies have evaluated the crosstalk between the GPER and the Hh pathway along different group grades in PCa. We conducted an analysis of paraffin-embedded tissues derived from patients with different prognostic grade of PCa using immunohistochemistry. Expression and correlation between GPER and glioma associated oncogene homologue (GLI) transcriptional factors in the parenchyma and stroma of PCa tumors were evaluated. Our results indicate that GPER is highly expressed in the nucleus and increases with higher grade groups. Additionally, GPER’s expression correlates with pGLI3 nuclear expression across different grade groups in PCa tissues; however, whether the receptor induces the activation of GLI transcriptional factors, or the latter modulate the expression of GPER is yet to be discovered, as well as the functional consequence of this correlation.
deepPGSegNet: MRI-based pituitary gland segmentation using deep learning
Authors: Choi Uk-Su , Sung Yul-Wan , Ogawa Seiji
Published: February 2024

Introduction

In clinical research on pituitary disorders, pituitary gland (PG) segmentation plays a pivotal role, which impacts the diagnosis and treatment of conditions such as endocrine dysfunctions and visual impairments. Manual segmentation, which is the traditional method, is tedious and susceptible to inter-observer differences. Thus, this study introduces an automated solution, utilizing deep learning, for PG segmentation from magnetic resonance imaging (MRI).

Methods

A total of 153 university students were enrolled, and their MRI images were used to build a training dataset and ground truth data through manual segmentation of the PGs. A model was trained employing data augmentation and a three-dimensional U-Net architecture with a five-fold cross-validation. A predefined field of view was applied to highlight the PG region to optimize memory usage. The model’s performance was tested on an independent dataset. The model’s performance was tested on an independent dataset for evaluating accuracy, precision, recall, and an F1 score.

Results and discussion

The model achieved a training accuracy, precision, recall, and an F1 score of 92.7%, 0.87, 0.91, and 0.89, respectively. Moreover, the study explored the relationship between PG morphology and age using the model. The results indicated a significant association between PG volume and midsagittal area with age. These findings suggest that a precise volumetric PG analysis through an automated segmentation can greatly enhance diagnostic accuracy and surveillance of pituitary disorders.
A novel NLRP3 inhibitor as a therapeutic agent against monosodium urate-induced gout
Authors: Park Kihyoun , Shin Injae , Kim Yoonseon , Kang Hyereen , Oh Soo-Jin , Jang Eunkyeong , Sim Taebo , Youn Jeehee , Lee Myung-Shik
Published: February 2024

Background

Since NEK7 is critical for NLRP3 inflammasome activation, NEK7 inhibitors could be employed as therapeutic agents against gout, a representative disease caused by NLRP3 inflammasome.

Methods

We designed NEK7 inhibitors based on biochemical kinome profiling of 2,7-substituted thieno[3,2-d]pyrimidine derivatives (SLC3031~3035 and SLC3037). Inflammasome activation was assessed by ELISA of IL-1b and immunoblotting of IL-1b maturation after treatment of bone marrow-derived macrophages with LPS+monosodium urate (MSU). NLPR3 binding to NEK7 and oligomerization were examined using immunoprecipitation and Blue Native gel electrophoresis, respectively. In vivo effect was investigated by studying gross and histopathological changes of food pad tissue of MSU-injected mice, together with assays of maturation of IL-1b and ASC speck in the tissue.

Results

SLC3037 inhibited inflammasome by MSU and other inflammasome activators through blockade of NLRP3 binding to NEK7 or oligomerization, and subsequent ASC oligomerization/phosphorylation. SLC3037 significantly reduced foot pad thickness and inflammation by MSU, which was superior to the effects of colchicine. SLC3037 significantly reduced content or maturation of IL-1b and ASC speck in the food pad. The number and height of intestinal villi were decreased by colchicine but not by SLC3037.

Conclusion

SLC3037, a NLRP3 inhibitor blocking NEK7 binding to NLRP3, could be a novel agent against diseases associated with NLRP3 inflammasome activation such as gout, cardiovascular diseases, metabolic syndrome or neurodegenerative diseases.
Varying conjunctival immune response adaptations of house finch populations to a rapidly evolving bacterial pathogen
Authors: Kuttiyarthu Veetil Nithya , Henschen Amberleigh E. , Hawley Dana M. , Melepat Balraj , Dalloul Rami A. , Beneš Vladimír , Adelman James S. , Vinkler Michal
Published: February 2024

Pathogen adaptations during host-pathogen co-evolution can cause the host balance between immunity and immunopathology to rapidly shift. However, little is known in natural disease systems about the immunological pathways optimised through the trade-off between immunity and self-damage. The evolutionary interaction between the conjunctival bacterial infection Mycoplasma gallisepticum (MG) and its avian host, the house finch (Haemorhous mexicanus), can provide insights into such adaptations in immune regulation. Here we use experimental infections to reveal immune variation in conjunctival tissue for house finches captured from four distinct populations differing in the length of their co-evolutionary histories with MG and their disease tolerance (defined as disease severity per pathogen load) in controlled infection studies. To differentiate contributions of host versus pathogen evolution, we compared house finch responses to one of two MG isolates: the original VA1994 isolate and a more evolutionarily derived one, VA2013. To identify differential gene expression involved in initiation of the immune response to MG, we performed 3’-end transcriptomic sequencing (QuantSeq) of samples from the infection site, conjunctiva, collected 3-days post-infection. In response to MG, we observed an increase in general pro-inflammatory signalling, as well as T-cell activation and IL17 pathway differentiation, associated with a decrease in the IL12/IL23 pathway signalling. The immune response was stronger in response to the evolutionarily derived MG isolate compared to the original one, consistent with known increases in MG virulence over time. The host populations differed namely in pre-activation immune gene expression, suggesting population-specific adaptations. Compared to other populations, finches from Virginia, which have the longest co-evolutionary history with MG, showed significantly higher expression of anti-inflammatory genes and Th1 mediators. This may explain the evolution of disease tolerance to MG infection in VA birds. We also show a potential modulating role of BCL10, a positive B- and T-cell regulator activating the NFKB signalling. Our results illuminate potential mechanisms of house finch adaptation to MG-induced immunopathology, contributing to understanding of the host evolutionary responses to pathogen-driven shifts in immunity-immunopathology trade-offs.
The associations between gut microbiota and inflammatory skin diseases: a bi-directional two-sample Mendelian randomization study
Authors: Zhong Yun , Wang Fan , Meng Xin , Zhou Lei
Published: February 2024

Background

Accumulating evidence shows that dysregulation of intestinal flora is associated with inflammatory skin diseases, specifically atopic dermatitis (AD), psoriasis (PSO), and rosacea (ROS). However, the causality is still unclear.

Objectives

To study the underlying causality between gut microbiota (GM) and AD, PSO, and ROS, a bi-directional two-sample Mendelian randomization (2SMR) analysis was conducted.

Methods

Summary statistics of gut microbiota, AD, PSO, and ROS were extracted from large-scale genome-wide association studies (GWASs). In 2SMR analysis, in addition to the inverse variance weighted as the principal method for evaluating causal association, four different methods were also used. Sensitivity analysis and reverse 2SMR study were implemented to evaluate the robustness of 2SMR results or reverse causal relationship, respectively.

Results

A total of 24 specific gut microbiota species related to AD, PSO, and ROS were identified by 2SMR analysis. After using the Bonferroni method for multiple testing correction, family FamilyXIII (ID: 1957) [OR = 1.28 (1.13, 1.45), p = 9.26e−05] and genus Eubacteriumfissicatenagroup (ID: 14373) [OR = 1.20 (1.09, 1.33), p = 1.65e−04] were associated with an increased risk for AD and PSO, respectively. The genus Dialister showed a negative association, suggesting a protective role against both atopic dermatitis and rosacea. Our reverse 2SMR analysis indicated no reverse causality between these inflammatory skin diseases and the identified gut microbiota.

Conclusions

In summary, this study provided evidence for the causality between GM and inflammatory skin diseases. These findings suggested that supplementing specific bacterial taxa may be an effective therapy for AD, PSO, and ROS.
IgLON5 deficiency produces behavioral alterations in a knockout mouse model
Authors: Landa Jon , Serafim Ana Beatriz , Alba Mercedes , Maudes Estibaliz , Molina-Porcel Laura , Garcia-Serra Anna , Mannara Francesco , Dalmau Josep , Graus Francesc , Sabater Lidia
Published: February 2024

Background

Anti-IgLON5 disease is a neurological disorder characterized by autoantibodies against IgLON5 and pathological evidence of neurodegeneration. IgLON5 is a cell adhesion molecule of unknown function that is highly expressed in the brain. Our aim was to investigate the impact of IgLON5 loss-of-function in evaluating brain morphology, social behavior, and the development of symptoms observed in an IgLON5 knockout (IgLON5-KO) mouse model.

Methods

The IgLON5-KO mice were generated using CRISPR-Cas9 technology. Immunohistochemistry on fixed sagittal brain sections and Western blotting brain lysates were used to confirm IgLON5 silencing and to evaluate the presence of other cell surface proteins. Two- month-old IgLON5-KO and wild-type (WT) mice underwent a comprehensive battery of behavioral tests to assess 1) locomotion, 2) memory, 3) anxiety, 4) social interaction, and 5) depressive-like behavior. Brain sections were examined for the presence of anatomical abnormalities and deposits of hyperphosphorylated tau in young adult (2-month-old) and aged (22-month-old) mice.

Results

Mice did not develop neurological symptoms reminiscent of those seen in patients with anti-IgLON5 disease. Behavioral testing revealed that 2-month-old IgLON5-KO mice showed subtle alterations in motor coordination and balance. IgLON5-KO females exhibited hyperactivity during night and day. Males were observed to have depressive-like behavior and excessive nest-building behavior. Neuropathological studies did not reveal brain morphological alterations or hyperphosphorylated tau deposits.

Conclusion

IgLON5-KO mice showed subtle alterations in behavior and deficits in fine motor coordination but did not develop the clinical phenotype of anti-IgLON5 disease.
Quantifying the combined impacts of anthropogenic CO2 emissions and watershed alteration on estuary acidification at biologically-relevant time scales: a case study from Tillamook Bay, OR, USA
Authors: Pacella Stephen R. , Brown Cheryl A. , Kaldy James E. , Labiosa Rochelle G. , Hales Burke , Mochon Collura T Chris , Waldbusser George G.
Published: February 2024

The impacts of ocean acidification (OA) on coastal water quality have been subject to intensive research in the past decade, but how emissions-driven OA combines with human modifications of coastal river inputs to affect estuarine acidification dynamics is less well understood. This study presents a methodology for quantifying the synergistic water quality impacts of OA and riverine acidification on biologically-relevant timescales through a case study from a small, temperate estuary influenced by coastal upwelling and watershed development. We characterized the dynamics and drivers of carbonate chemistry in Tillamook Bay, OR (USA), along with its coastal ocean and riverine end-members, through a series of synoptic samplings and continuous water quality monitoring from July 2017 to July 2018. Synoptic river sampling showed acidification and increased CO2 content in areas with higher proportions of watershed anthropogenic land use. We propagated the impacts of 1). the observed riverine acidification, and 2). modeled OA changes to incoming coastal ocean waters across the full estuarine salinity spectrum and quantified changes in estuarine carbonate chemistry at a 15-minute temporal resolution. The largest magnitude of acidification (-1.4 pHT units) was found in oligo- and mesohaline portions of the estuary due to the poor buffering characteristics of these waters, and was primarily driven by acidified riverine inputs. Despite this, emissions-driven OA is responsible for over 94% of anthropogenic carbon loading to Tillamook Bay and the dominant driver of acidification across most of the estuary due to its large tidal prism and relatively small river discharges. This dominance of ocean-sourced anthropogenic carbon challenges the efficacy of local management actions to ameliorate estuarine acidification impacts. Despite the relatively large acidification effects experienced in Tillamook Bay (-0.16 to -0.23 pHT units) as compared with typical open ocean change (approximately -0.1 pHT units), observations of estuarine pHT would meet existing state standards for pHT. Our analytical framework addresses pressing needs for water quality assessment and coastal resilience strategies to differentiate the impacts of anthropogenic acidification from natural variability in dynamic estuarine systems.
Signature of the anthropogenic impacts on the epipelagic microbiome of the North-Western Adriatic Sea (Mediterranean Sea)
Authors: Trapella Giulia , Scicchitano Daniel , Foresto Lucia , Dell’Acqua Andrea Nicoló , Radaelli Elena , Turroni Silvia , Rampelli Simone , Corinaldesi Cinzia , Palladino Giorgia , Candela Marco
Published: February 2024

Introduction

In our paper, we explored the impact of different anthropogenic stressors, namely, mussel farming, methane extraction platforms, and summer mass tourism, on the epipelagic microbiomes of the North-Western Adriatic Sea.

Methods

By 16S rRNA gene sequencing, we provided the epipelagic microbiome layout from selected sites corresponding to each of the considered impacts. As an unimpacted reference, we used already published 16S rRNA sequencing data.

Results

According to our findings, each one of the anthropogenic stressors resulted in a peculiar increase of specific epipelagic microbial components, including copiotrophic R-strategists and host-restricted bacteria, as well as some pathobiome components, the latter being detected exclusively in impacted sites. Particularly, potentially harmful pathogenic species such as Legionella impletisoli and Staphylococcus epidermidis have been detected in proximity to the mussel farms, and Escherichia coli and Campylobacter ureolyticus were present close to the methane extraction platform and at the summer mass tourism site, respectively. Particularly, C. ureolyticus is an emerging human gastrointestinal pathogen, capable of destroying intestinal microvilli.

Discussion

In addition to providing evidence supporting the existence of recognizable and impact-driven fingerprints on the epipelagic marine microbiome peculiar to the different anthropogenic stressors, our findings also raise concern about the ecological relevance of the observed changes, in terms of possible loss of ecosystem services and also for the potential release of pathogenic microorganisms in the environment.
The unpredictability of scyphozoan jellyfish blooms
Authors: Fernández-Alías Alfredo , Marcos Concepción , Pérez-Ruzafa Angel
Published: February 2024

The study of jellyfish blooms has gained attention in the recent decades because of the importance of forecasting and anticipating them and avoiding their interference with human activities. However, after thirty years of scientific effort (monitoring systems, empirical laboratory and field studies, modeling, etc.), the occurrence of blooms remains unpredictable, and their consequences unavoidable. Climate change, eutrophication, overfishing, coastal construction, and species translocation have been suggested as stressors that increase them, but robust evidence to support these claims is limited. The widespread belief that jellyfish blooms are “increasing in number” has been challenged in recent years. Among the gelatinous zooplankton, the bloom forming species are concentrated in the class Scyphozoa, and the number of species with at least one recorded bloom has increased during the last decade. The analyses of long-term time series show seasonality in the dynamic of each blooming jellyfish species population, but the blooms vary in intensity and there are years of an unexplained absence of jellyfish. In this review, we focus on the current state of knowledge, uncertainties and gaps in the critical points that can strongly influence the intensity of the bloom or even lead to the absence of the medusa population. These points include ephyrae, planulae and scyphistoma natural, predatory or fishing mortality, the molecular pathway of strobilation, benthic population dynamics, planula settlement and ephyra to medusa transition success. Some of these points account for certain empirical laboratory evidence under controlled conditions, and are difficult to be studied on the field, but the different sources of non-typically recorded variability need to be addressed to improve our understanding of jellyfish population dynamics.
Experimental study on wear failure of spindle hook teeth of cotton picker
Authors: Wang Yugang , Li Zhantao , Gu Yanqing , Zhang Hongwen , Zhao Pengda , Wang Yongzheng , Yang Jianning
Published: February 2024

Introduction: The wear failure of spindle will lead to a decrease in cotton harvesting rate of the cotton picker during field operation and serious wastage.

Method: Three types of spindle samples at different installation positions and working areas were obtained through field experiments to explore the wear failure law of spindle hook teeth of cotton picker during field operation. Hardness of hook tooth coating and substrate of spindles were tested, surface and cross-section microstructure of the spindle hook teeth were characterized, and wear area and width of the spindle hook teeth were extracted.

Results: Results showed that the hardness of the hook tooth coating is evidently higher than that of the substrate; the average coating hardness of the No. 3 spindle hook teeth reaches the maximum at 1033.6 HV0.1; defects, such as microcracks and micropores, exist in the coating of the three types of spindle hook teeth; and the thickness of the coating is between 70 and 130 μm. The wear area of spindle hook tooth changes exponentially and the wear width changes linearly with the increase of field operation area at the same installation position. The wear area and width of the spindle hook teeth gradually increase with the decrease of the installation height and the wear change of the hook teeth is negatively correlated with the installation height in the same field operation area.

Discussion: The wear failure of spindle hook tooth is mainly caused by abrasive, fatigue, and oxidation wear. The results of this study can provide a reference for improving the wear resistance of spindle hook teeth.
Utility of bronchoalveolar lavage for COVID-19: a perspective from the Dragon consortium
Authors: Tomassetti Sara , Ciani Luca , Luzzi Valentina , Gori Leonardo , Trigiani Marco , Giuntoli Leonardo , Lavorini Federico , Poletti Venerino , Ravaglia Claudia , Torrego Alfons , Maldonado Fabien , Lentz Robert , Annunziato Francesco , Maggi Laura , Rossolini Gian Maria , Pollini Simona , Para Ombretta , Ciurleo Greta , Casini Alessandro , Rasero Laura , Bartoloni Alessandro , Spinicci Michele , Munavvar Mohammed , Gasparini Stefano , Comin Camilla , Cerinic Marco Matucci , Peired Anna , Henket Monique , Ernst Benoit , Louis Renaud , Corhay Jean-louis , Nardi Cosimo , Guiot Julien
Published: February 2024

Diagnosing COVID-19 and treating its complications remains a challenge. This review reflects the perspective of some of the Dragon (IMI 2-call 21, #101005122) research consortium collaborators on the utility of bronchoalveolar lavage (BAL) in COVID-19. BAL has been proposed as a potentially useful diagnostic tool to increase COVID-19 diagnosis sensitivity. In both critically ill and non-critically ill COVID-19 patients, BAL has a relevant role in detecting other infections or supporting alternative diagnoses and can change management decisions in up to two-thirds of patients. BAL is used to guide steroid and immunosuppressive treatment and to narrow or discontinue antibiotic treatment, reducing the use of unnecessary broad antibiotics. Moreover, cellular analysis and novel multi-omics techniques on BAL are of critical importance for understanding the microenvironment and interaction between epithelial cells and immunity, revealing novel potential prognostic and therapeutic targets. The BAL technique has been described as safe for both patients and healthcare workers in more than a thousand procedures reported to date in the literature. Based on these preliminary studies, we recognize that BAL is a feasible procedure in COVID-19 known or suspected cases, useful to properly guide patient management, and has great potential for research.
Rapid typing of Klebsiella pneumoniae and Pseudomonas aeruginosa by Fourier-transform Infrared spectroscopy informs infection control in veterinary settings
Authors: Zendri Flavia , Schmidt Vanessa , Mauder Norman , Loeffler Anette , Jepson Rosanne Ellen , Isgren Cajsa , Pinchbeck Gina , Haldenby Sam , Timofte Dorina
Published: February 2024

Introduction

The emergence of multi-drug resistant (MDR) pathogens linked to healthcare-associated infections (HCAIs) is an increasing concern in modern veterinary practice. Thus, rapid bacterial typing for real-time tracking of MDR hospital dissemination is still much needed to inform best infection control practices in a clinically relevant timeframe. To this end, the IR Biotyper using Fourier-Transform InfraRed (FTIR) spectroscopy has the potential to provide fast cluster analysis of potentially related organisms with substantial cost and turnaround time benefits.

Materials and methods

A collection of MDR bacterial isolates (n = 199, comprising 92 Klebsiella pneumoniae and 107 Pseudomonas aeruginosa) obtained from companion animal (i.e., dogs, cats and horses) clinical investigations, faecal and environmental screening from four veterinary facilities between 2012 and 2019 was analysed retrospectively by FTIR spectroscopy. Its performance was compared against MLST extracted from whole genomes of a subset of clustering isolates (proportionally to cluster size) for investigation of potential nosocomial transmission between patients and the surrounding hospital environments.

Results

Concordance between the FTIR and MLST types was overall high for K. pneumoniae (Adjusted Rand Index [ARI] of 0.958) and poor for P. aeruginosa (ARI of 0.313). FTIR K. pneumoniae clusters (n = 7) accurately segregated into their respective veterinary facility with evidence of intra-hospital spread of K. pneumoniae between patients and environmental surfaces. Notably, K. pneumoniae ST147 intensely circulated at one Small Animal Hospital ICU. Conversely, Pseudomonas aeruginosa FTIR clusters (n = 18) commonly contained isolates of diversified hospital source and heterogeneous genetic background (as also genetically related isolates spread across different clusters); nonetheless, dissemination of some clones, such as P. aeruginosa ST2644 in the equine hospital, was apparent. Importantly, FTIR clustering of clinical, colonisation and/or environmental isolates sharing genomically similar backgrounds was seen for both MDR organisms, highlighting likely cross-contamination events that led to clonal dissemination within settings.

Conclusion

FTIR spectroscopy has high discriminatory power for hospital epidemiological surveillance of veterinary K. pneumoniae and could provide sufficient information to support early detection of clonal dissemination, facilitating implementation of appropriate infection control measures. Further work and careful optimisation need to be carried out to improve its performance for typing of P. aeruginosa veterinary isolates.
Association between sleep-related phenotypes and gut microbiota: a two-sample bidirectional Mendelian randomization study
Authors: Wang Xiaoqiu , Wang Chi , Liu Kai , Wan Qingyun , Wu Wenzhong , Liu Chengyong
Published: February 2024

Background

An increasing body of evidence suggests a profound interrelation between the microbiome and sleep-related concerns. Nevertheless, current observational studies can merely establish their correlation, leaving causality unexplored.

Study objectives

To ascertain whether specific gut microbiota are causally linked to seven sleep-related characteristics and propose potential strategies for insomnia prevention.

Methods

The study employed an extensive dataset of gut microbiota genetic variations from the MiBioGen alliance, encompassing 18,340 individuals. Taxonomic classification was conducted, identifying 131 genera and 196 bacterial taxa for analysis. Sleep-related phenotype (SRP) data were sourced from the IEU OpenGWAS project, covering traits such as insomnia, chronotype, and snoring. Instrumental variables (IVs) were selected based on specific criteria, including locus-wide significance, linkage disequilibrium calculations, and allele frequency thresholds. Statistical methods were employed to explore causal relationships, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighted Mode. Sensitivity analyses, pleiotropy assessments, and Bonferroni corrections ensured result validity. Reverse causality analysis and adherence to STROBE-MR guidelines were conducted to bolster the study’s rigor.

Results

Bidirectional Mendelian randomization (MR) analysis reveals a causative interplay between selected gut microbiota and sleep-related phenotypes. Notably, outcomes from the rigorously Bonferroni-corrected examination illuminate profound correlations amid precise compositions of the intestinal microbiome and slumber-associated parameters. Elevated abundance within the taxonomic ranks of class Negativicutes and order Selenomonadales was markedly associated with heightened susceptibility to severe insomnia (OR = 1.03, 95% CI: 1.02–1.05, p = 0.0001). Conversely, the augmented representation of the phylum Lentisphaerae stands in concord with protracted sleep duration (OR = 1.02, 95% CI: 1.01–1.04, p = 0.0005). Furthermore, heightened exposure to the genus Senegalimassilia exhibits the potential to ameliorate the manifestation of snoring symptoms (OR = 0.98, 95% CI: 0.96–0.99, p = 0.0001).

Conclusion

This study has unveiled the causal relationship between gut microbiota and SRPs, bestowing significant latent value upon future endeavors in both foundational research and clinical therapy.