bluuebunny/crossref_metadata_2025 huggingface dataset:
The glycosylation deficiency of flavivirus NS1 attenuates virus replication through interfering with the formation of viral replication compartments
Authors: Huang Shuhan , Shi Pan-Deng , Fan Xiao-Xuan , Yang Yang , Qin Cheng-Feng , Zhao Hui , Shi Lei , Ci Yali
Published: June 2024

Background

Flavivirus is a challenge all over the world. The replication of flavivirus takes place within membranous replication compartments (RCs) derived from endoplasmic reticulum (ER). Flavivirus NS1 proteins have been proven essential for the formation of viral RCs by remodeling the ER. The glycosylation of flavivirus NS1 proteins is important for viral replication, yet the underlying mechanism remains unclear.

Methods

HeLa cells were used to visualize the ER remodeling effects induced by NS1 expression. ZIKV replicon luciferase assay was performed with BHK-21 cells. rZIKV was generated from BHK-21 cells and the plaque assay was done with Vero Cells. Liposome co-floating assay was performed with purified NS1 proteins from 293T cells.

Results

We found that the glycosylation of flavivirus NS1 contributes to its ER remodeling activity. Glycosylation deficiency of NS1, either through N-glycosylation sites mutations or tunicamycin treatment, compromises its ER remodeling activity and interferes with viral RCs formation. Disruption of NS1 glycosylation results in abnormal aggregation of NS1, rather than reducing its membrane-binding activity. Consequently, deficiency in NS1 glycosylation impairs virus replication.

Conclusions

In summary, our results highlight the significance of NS1 glycosylation in flavivirus replication and elucidate the underlying mechanism. This provides a new strategy for combating flavivirus infections.
Development and validation of a nomogram for predicting cancer-specific survival in small-bowel adenocarcinoma patients using the SEER database
Authors: Xu Duogang , He Yulei , Liao Changkang , Tan Jing
Published: June 2024

Background

Small bowel adenocarcinoma (SBA) is a rare gastrointestinal malignancy forwhich survival is hampered by late diagnosis, complex responses to treatment, and poor prognosis. Accurate prognostic tools are crucial for optimizing treatment strategies and improving patient outcomes. This study aimed to develop and validate a nomogram based on the Surveillance, Epidemiology, and End Results (SEER) database to predict cancer-specific survival (CSS) in patients with SBA and compare it to traditional American Joint Committee on Cancer (AJCC) staging.

Methods

We analyzed data from 2,064 patients diagnosed with SBA between 2010 and 2020 from the SEER database. Patients were randomly assigned to training and validation cohorts (7:3 ratio). Kaplan‒Meier survival analysis, Cox multivariate regression, and nomograms were constructed for analysis of 3-year and 5-year CSS. The performance of the nomograms was evaluated using Harrell’s concordance index (C-index), the area under the receiver operating characteristic (ROC) curve, calibration curves, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

Results

Multivariate Cox regression identified sex, age at diagnosis, marital status, tumor site, pathological grade, T stage, N stage, M stage, surgery, retrieval of regional lymph nodes (RORLN), and chemotherapy as independent covariates associated with CSS. In both the training and validation cohorts, the developed nomograms demonstrated superior performance to that of the AJCC staging system, with C-indices of 0.764 and 0.759, respectively. The area under the curve (AUC) values obtained by ROC analysis for 3-year and 5-year CSS prediction significantly surpassed those of the AJCC model. The nomograms were validated using calibration and decision curves, confirming their clinical utility and superior predictive accuracy. The NRI and IDI indicated the enhanced predictive capability of the nomogram model.

Conclusion

The SEER-based nomogram offers a significantly superior ability to predict CSS in SBA patients, supporting its potential application in clinical decision-making and personalized approaches to managing SBA to improve survival outcomes.
Altered glia-neuron communication in Alzheimer’s Disease affects WNT, p53, and NFkB Signaling determined by snRNA-seq
Authors: Soelter Tabea M. , Howton Timothy C. , Clark Amanda D. , Oza Vishal H. , Lasseigne Brittany N.
Published: June 2024

Background

Alzheimer’s disease is the most common cause of dementia and is characterized by amyloid-β plaques, tau neurofibrillary tangles, and neuronal loss. Although neuronal loss is a primary hallmark of Alzheimer’s disease, it is known that non-neuronal cell populations are ultimately responsible for maintaining brain homeostasis and neuronal health through neuron-glia and glial cell crosstalk. Many signaling pathways have been proposed to be dysregulated in Alzheimer’s disease, including WNT, TGFβ, p53, mTOR, NFkB, and Pi3k/Akt signaling. Here, we predict altered cell-cell communication between glia and neurons.

Methods

Using public snRNA-sequencing data generated from postmortem human prefrontal cortex, we predicted altered cell-cell communication between glia (astrocytes, microglia, oligodendrocytes, and oligodendrocyte progenitor cells) and neurons (excitatory and inhibitory). We confirmed interactions in a second and third independent orthogonal dataset. We determined cell-type-specificity using Jaccard Similarity Index and investigated the downstream effects of altered interactions in inhibitory neurons through gene expression and transcription factor activity analyses of signaling mediators. Finally, we determined changes in pathway activity in inhibitory neurons.

Results

Cell-cell communication between glia and neurons is altered in Alzheimer’s disease in a cell-type-specific manner. As expected, ligands are more cell-type-specific than receptors and targets. We identified ligand-receptor pairs in three independent datasets and found involvement of the Alzheimer’s disease risk genes APP and APOE across datasets. Most of the signaling mediators of these interactions were not significantly differentially expressed, however, the mediators that are also transcription factors had differential activity between AD and control. Namely, MYC and TP53, which are associated with WNT and p53 signaling, respectively, had decreased TF activity in Alzheimer’s disease, along with decreased WNT and p53 pathway activity in inhibitory neurons. Additionally, inhibitory neurons had both increased NFkB signaling pathway activity and increased TF activity of NFIL3, an NFkB signaling-associated transcription factor.

Conclusions

Cell-cell communication between glia and neurons in Alzheimer’s disease is altered in a cell-type-specific manner involving Alzheimer’s disease risk genes. Signaling mediators had altered transcription factor activity suggesting altered glia-neuron interactions may dysregulate signaling pathways including WNT, p53, and NFkB in inhibitory neurons.
Homotherapy for heteropathy: therapeutic effect of Butein in NLRP3-driven diseases
Authors: Liao Wenhao , Li Yuchen , Liu Jingwen , Mou Yu , Zhao Mei , Liu Juan , Zhang Tianxin , Sun Qin , Tang Jianyuan , Wang Zhilei
Published: June 2024

Background

Aberrant inflammatory responses drive the initiation and progression of various diseases, and hyperactivation of NLRP3 inflammasome is a key pathogenetic mechanism. Pharmacological inhibitors of NLRP3 represent a potential therapy for treating these diseases but are not yet clinically available. The natural product butein has excellent anti-inflammatory activity, but its potential mechanisms remain to be investigated. In this study, we aimed to evaluate the ability of butein to block NLRP3 inflammasome activation and the ameliorative effects of butein on NLRP3-driven diseases.

Methods

Lipopolysaccharide (LPS)-primed bone-marrow-derived macrophages were pretreated with butein and various inflammasome stimuli. Intracellular potassium levels, ASC oligomerization and reactive oxygen species production were also detected to evaluate the regulatory mechanisms of butein. Moreover, mouse models of LPS-induced peritonitis, dextran sodium sulfate-induced colitis, and high-fat diet-induced non-alcoholic steatohepatitis were used to test whether butein has protective effects on these NLRP3-driven diseases.

Results

Butein blocks NLRP3 inflammasome activation in mouse macrophages by inhibiting ASC oligomerization, suppressing reactive oxygen species production, and upregulating the expression of the antioxidant pathway nuclear factor erythroid 2-related factor 2 (Nrf2). Importantly, in vivo experiments demonstrated that butein administration has a significant protective effect on the mouse models of LPS-induced peritonitis, dextran sodium sulfate-induced colitis, and high-fat diet-induced non-alcoholic steatohepatitis.

Conclusion

Our study illustrates the connotation of homotherapy for heteropathy, i.e., the application of butein to broaden therapeutic approaches and treat multiple inflammatory diseases driven by NLRP3.
Progression of monoclonal gammopathy of undetermined significance to multiple myeloma is associated with enhanced translational quality control and overall loss of surface antigens
Authors: Ravn Berg Sigrid , Dikic Aida , Sharma Animesh , Hagen Lars , Vågbø Cathrine Broberg , Zatula Alexey , Misund Kristine , Waage Anders , Slupphaug Geir
Published: June 2024

Background

Despite significant advancements in treatment strategies, multiple myeloma remains incurable. Additionally, there is a distinct lack of reliable biomarkers that can guide initial treatment decisions and help determine suitable replacement or adjuvant therapies when relapse ensues due to acquired drug resistance.

Methods

To define specific proteins and pathways involved in the progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM), we have applied super-SILAC quantitative proteomic analysis to CD138 + plasma cells from 9 individuals with MGUS and 37 with MM.

Results

Unsupervised hierarchical clustering defined three groups: MGUS, MM, and MM with an MGUS-like proteome profile (ML) that may represent a group that has recently transformed to MM. Statistical analysis identified 866 differentially expressed proteins between MM and MGUS, and 189 between MM and ML, 177 of which were common between MGUS and ML. Progression from MGUS to MM is accompanied by upregulated EIF2 signaling, DNA repair, and proteins involved in translational quality control, whereas integrin- and actin cytoskeletal signaling and cell surface markers are downregulated.

Conclusion

Compared to the premalignant plasma cells in MGUS, malignant MM cells apparently have mobilized several pathways that collectively contribute to ensure translational fidelity and to avoid proteotoxic stress, especially in the ER. The overall reduced expression of immunoglobulins and surface antigens contribute to this and may additionally mediate evasion from recognition by the immune apparatus. Our analyses identified a range of novel biomarkers with potential prognostic and therapeutic value, which will undergo further evaluation to determine their clinical significance.
Spatiotemporal heterogeneity of LMOD1 expression summarizes two modes of cell communication in colorectal cancer
Authors: Li Jie-pin , Liu Yuan-jie , Li Yang , Yin Yi , Ye Qian-wen , Lu Zhi-hua , Dong Yu-wei , Zhou Jin-yong , Zou Xi , Chen Yu-gen
Published: June 2024

Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknown. Here, we investigated the spatiotemporal heterogeneity of CC molecular expression during malignant transformation. It was found that although both tight junctions (TJs) and gap junctions (GJs) were involved in maintaining the tumor microenvironment (TME), they exhibited opposite characteristics. Mechanistically, for epithelial cells (parenchymal component), the expression of TJ molecules consistently decreased during normal-cancer transformation and is a potential oncogenic factor. For fibroblasts (mesenchymal component), the expression of GJs consistently increased during normal-cancer transformation and is a potential oncogenic factor. In addition, the molecular profiles of TJs and GJs were used to stratify colorectal cancer (CRC) patients, where subtypes characterized by high GJ levels and low TJ levels exhibited enhanced mesenchymal signals. Importantly, we propose that leiomodin 1 (LMOD1) is biphasic, with features of both TJs and GJs. LMOD1 not only promotes the activation of cancer-associated fibroblasts (CAFs) but also inhibits the Epithelial–mesenchymal transition (EMT) program in cancer cells. In conclusion, these findings demonstrate the molecular heterogeneity of CC and provide new insights into further understanding of TME heterogeneity.

Graphical Abstract
Developing a comprehensive abortion prevention program for couples based on I-change model: study protocol for a mixed method research
Authors: Dolatabadi Zari , Moridi Maryam , Farnam Farnaz , Damghanian Maryam
Published: June 2024

Background

In countries where abortion laws are stringent, induced abortions are prevalent. The limited availability of abortion services within these regions amplifies the likelihood of maternal complications and mortality. Induced abortions represent a significant public health concern in Iran and are characterized by a multitude of intricate factors that remain largely unexplored. Gaps in knowledge persist pertaining to the influences driving induced abortion within the Iranian context. To adequately address the issue of induced abortion, it is imperative to discern the determinants that shape the decision-making process. The primary objective of this study was to design an intervention program focused on mitigating the occurrence of induced abortion within couples, with an emphasis on identifying the key factors that contribute to this phenomenon.

Methods

This study comprises three phases. In the first phase, a qualitative approach based on the I-change model will be employed to identify the factors influencing induced abortion. The second phase involves a systematic review to identify the determinants of induced abortion and strategies to prevent induced abortion. In the third phase, the outcomes of the qualitative approach and systematic review will be shared with experts and specialists using the Delphi method to categorize and prioritize strategies. Subsequently, based on the final consensus, a comprehensive program will be developed to prevent induced abortion.

Discussion

This study introduces an I-change model-based program for the prevention of induced abortion. The prevention of induced abortion holds great significance in mitigating maternal morbidity and mortality, curtailing healthcare expenses, and fostering population growth rates. The research findings will be disseminated via reputable peer-reviewed journals and communicated to the academic and medical communities. This dissemination aims to provide valuable insights that can contribute to the advancement of induced abortion and abortion prevention programs.
Hypoxia-mediated repression of pyruvate carboxylase drives immunosuppression
Authors: Coleman Michael F. , Cotul Eylem Kulkoyluoglu , Pfeil Alexander J. , Devericks Emily N. , Safdar Muhammad H. , Monteiro Marvis , Chen Hao , Ho Alyssa N. , Attaar Numair , Malian Hannah M. , Kiesel Violet A. , Ramos Alexis , Smith Matthew , Panchal Heena , Mailloux Adam , Teegarden Dorothy , Hursting Stephen D. , Wendt Michael K.
Published: June 2024

Background

Metabolic plasticity mediates breast cancer survival, growth, and immune evasion during metastasis. However, how tumor cell metabolism is influenced by and feeds back to regulate breast cancer progression are not fully understood. We identify hypoxia-mediated suppression of pyruvate carboxylase (PC), and subsequent induction of lactate production, as a metabolic regulator of immunosuppression.

Methods

We used qPCR, immunoblot, and reporter assays to characterize repression of PC in hypoxic primary tumors. Steady state metabolomics were used to identify changes in metabolite pools upon PC depletion. In vivo tumor growth and metastasis assays were used to evaluate the impact of PC manipulation and pharmacologic inhibition of lactate transporters. Immunohistochemistry, flow cytometry, and global gene expression analyzes of tumor tissue were employed to characterize the impact of PC depletion on tumor immunity.

Results

PC is essential for metastatic colonization of the lungs. In contrast, depletion of PC in tumor cells promotes primary tumor growth. This effect was only observed in immune competent animals, supporting the hypothesis that repression of PC can suppress anti-tumor immunity. Exploring key differences between the pulmonary and mammary environments, we demonstrate that hypoxia potently downregulated PC. In the absence of PC, tumor cells produce more lactate and undergo less oxidative phosphorylation. Inhibition of lactate metabolism was sufficient to restore T cell populations to PC-depleted mammary tumors.

Conclusions

We present a dimorphic role for PC in primary mammary tumors vs. pulmonary metastases. These findings highlight a key contextual role for PC-directed lactate production as a metabolic nexus connecting hypoxia and antitumor immunity.

Graphical abstract
Multi-dimensional cell-free DNA-based liquid biopsy for sensitive early detection of gastric cancer
Authors: Yu Pengfei , Chen Ping , Wu Min , Ding Guangyu , Bao Hua , Du Yian , Xu Zhiyuan , Yang Litao , Fang Jingquan , Huang Xingmao , Lai Qian , Wei Jia , Yan Junrong , Yang Shanshan , He Peng , Wu Xue , Shao Yang , Su Dan , Cheng Xiangdong
Published: June 2024

Background

Gastric cancer is the fifth most common cancer type. Most patients are diagnosed at advanced stages with poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing associated mortality.

Methods

We collected a prospective study cohort of 110 stage I–II gastric cancer patients and 139 non-cancer individuals. We performed whole-genome sequencing with plasma samples and profiled four types of cell-free DNA (cfDNA) characteristics, fragment size pattern, copy number variation, nucleosome coverage pattern, and single nucleotide substitution. With these differential profiles, we developed an ensemble model to detect gastric cancer signals. Further, we validated the assay in an in-house first validation cohort of 73 gastric cancer patients and 94 non-cancer individuals and an independent second validation cohort of 47 gastric cancer patients and 49 non-cancer individuals. Additionally, we evaluated the assay in a hypothetical 100,000 screening population by Monte Carlo simulation.

Results

Our cfDNA-based assay could distinguish early-stage gastric cancer from non-cancer at an AUROC of 0.962 (95% CI: 0.942–0.982) in the study cohort, 0.972 (95% CI: 0.953–0.992) in the first validation cohort and 0.937 (95% CI: 0.890–0.983) in the second validation cohort. The model reached a specificity of 92.1% (128/139) and a sensitivity of 88.2% (97/110) in the study cohort. In the first validation cohort, 91.5% (86/94) of non-cancer individuals and 91.8% (67/73) of gastric cancer patients were correctly identified. In the second validation cohort, 89.8% (44/49) of non-cancer individuals and 87.2% (41/47) of gastric cancer patients were accurately classified.

Conclusions

We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify early-stage gastric cancer from non-cancerous conditions. As a cost-effective non-invasive approach, it may provide population-wide benefits for the early detection of gastric cancer.

Trial registration

This study was registered on ClinicalTrials.gov under the identifier NCT05269056 on March 7, 2022.
In vitro phenotypic characterisation of two genotype I African swine fever viruses with genomic deletion isolated from Sardinian wild boars
Authors: Franzoni Giulia , Fiori Mariangela S. , Mura Lorena , Carta Tania , Di Nardo Antonello , Floris Matteo , Ferretti Luca , Zinellu Susanna , Angioi Pier Paolo , Sechi Anna Maria , Carusillo Francesca , Brundu Diego , Fadda Manlio , Bazzardi Riccardo , Giammarioli Monica , Cappai Stefano , Dei Giudici Silvia , Oggiano Annalisa
Published: June 2024

African swine fever virus (ASFV) causes a devastating disease affecting domestic and wild pigs. ASF was first introduced in Sardinia in 1978 and until 2019 only genotype I isolates were identified. A remarkable genetic stability of Sardinian ASFV isolates was described, nevertheless in 2019 two wild boar isolates with a sustained genomic deletion (4342 base pairs) were identified (7303WB/19, 7212WB/19). In this study, we therefore performed in vitro experiments with monocyte-derived macrophages (moMФ) to unravel the phenotypic characteristics of these deleted viruses. Both 7303WB/19 and 7212WB/19 presented a lower growth kinetic in moMФ compared to virulent Sardinian 26544/OG10, using either a high (1) or a low (0.01) multiplicity of infection (MOI). In addition, flow cytometric analysis showed that both 7303WB/19 and 7212WB/19 presented lower intracellular levels of both early and late ASFV proteins. We subsequently investigated whether deleted virus variants were previously circulating in wild boars in Sardinia. In the four years preceding the last genotype I isolation (February 2015–January 2019), other eight wild boar isolates were collected, all belonging to p72 genotype I, B602L subgroup X, but none of them presented a sustained genomic deletion. Overall, we observed the deleted virus isolates in Sardinia only in 2019, at the end of a strong eradication campaign, and our data suggest that it might possess an attenuated phenotype in vivo. A better understanding of ASFV evolution in endemic territories might contribute to development of effective control measures against ASF.
Performance analysis of partial NOMA-based layered D2D communications
Authors: Ju Jinjuan , Sun Qiang
Published: June 2024

Conventionally, non-orthogonal multiple access (NOMA) has traditionally been implemented separately from orthogonal multiple access (OMA), aiming to improve the capacity of multi-user systems. However, a recent study has ventured beyond this conventional approach by integrating OMA and NOMA proportionally within the same system. In spite of these advancements, the consideration towards optimizing multi-user systems remains incomplete especially when user service requirements vary significantly. Therefore, this paper explores a novel layered device-to-device (D2D) partial NOMA (P-NOMA) scheme, which introduces a hybrid power-domain access method into multi-user systems. The analysis primarily focuses on evaluating both the system performance and the impact of various parameters on it. In contrast to conventional fully overlapped NOMA signals, P-NOMA signals are partially overlapped with an overlap rate that can be determined based on quality-of-service (QoS) requirements. Simulation results demonstrate that judicious utilization of P-NOMA can effectively enhance overall system performance, particularly in terms of sum rate (SR) metrics, while also flexibly accommodating diverse QoS requirements for multiple users.
Navigating intersectoral collaboration in nutrition programming: implementors’ perspectives from Assam, India
Authors: Aivalli Praveenkumar , Gilmore Brynne , Srinivas Prashanth Nuggehalli , De Brún Aoife
Published: June 2024

Background

There is a growing interest in the use of intersectoral collaborative (ISC) approaches to address complex health-related issues. However, relatively little empirical research exists on the challenges of implementing, fostering and sustaining these approaches. Our study explores the perceptions and experiences of programme implementers regarding the implementation of an ISC approach, focusing on a case study of nutrition programming in Assam, India.

Methods

We conducted qualitative semi-structured face-to-face in-depth interviews with eleven programme implementers from two selected districts of Assam, India. These participants were purposefully sampled to provide a comprehensive understanding of the experiences of implementing intersectoral collaboration. Following the interviews, an inductive thematic analysis was performed on the collected data.

Results

The study identified three main themes: operationalisation of ISC in daily practice, facilitators of ISC, and barriers to effective ISC. These were further broken down into six subthemes: defined sectoral mandates, leadership dynamics, interpersonal relationships and engagement, collective vision and oversight, resource allocation, and power dynamics. These findings highlight the complexity of ISC, focusing on the important structural and relational aspects at the macro, meso, and micro levels. Interpersonal relationships and power dynamics among stakeholders substantially influenced ISC formation in both the districts.

Conclusion

Despite challenges, there is ongoing interest in establishing ISC in nutrition programming, supported by political development agendas. Success relies on clarifying sectoral roles, addressing power dynamics, and engaging stakeholders systematically. Actionable plans with measurable targets are crucial for promoting and sustaining ISC, ensuring positive programme outcomes. The insights from our study provide valuable guidance for global health practitioners and policymakers dealing with similar challenges, emphasising the urgent need for comprehensive research given the lack of universally recognised policies in the realm of ISC in global health practice.
The protective role of cognitive reserve: an empirical study in mild cognitive impairment
Authors: Marselli Giulia , Favieri Francesca , Forte Giuseppe , Corbo Ilaria , Agostini Francesca , Guarino Angela , Casagrande Maria
Published: June 2024

Background

Mild cognitive impairment (MCI) describes an aging profile characterized by a cognitive decline that is worse than expected in normal aging but less pervasive and critical than full-blown dementia. In the absence of an effective treatment strategy, it is important to identify factors that can protect against progression to dementia. In this field, it is hypothesized that one aspect that may be a protective factor against the neurotypical outcome of dementia is cognitive reserve (CR). Cognitive reserve is the ability to maintain cognitive functionality despite accumulating brain pathology.

Objectives

The present study aimed to identify and analyze the differences in CR between healthy adults and patients with MCI. Specifically, it is hypothesized that (i) healthy older adult people have higher CR than older adult people diagnosed with MCI, and (II) CR could predict the classification of subjects into people with or without MCI.

Methods

Two hundred forty-three adults (mean age = 60.4, SD = 7.4) participated in the present study and were classified into three groups based on Petersen’s MCI criteria: healthy controls (HC), amnestic MCI (aMCI), and non-amnestic MCI (naMCI). The Cognitive Reserve Index questionnaire (CRIq) was administered to assess the level of CR,

Findings

Results showed that HC had significantly higher CR scores than participants diagnosed with aMCI and naMCI. Moreover, a binomial logistic regression suggested that low CR was a significant risk factor for the MCI diagnosis.

Conclusions

The clinical picture that emerged from the results showed that lower CR could be considered a characteristic of pathological aging, such as MCI.Public significance statement, Since the brain attempts to cope with life-related changes or pathologies, it is fundamental for both clinicians and researchers to investigate further the factors that contribute to brain resilience. As an indirect expression of brain reserve, cognitive reserve may be both a marker and a predictor of adaptive aging.
Predicting suitable habitats for foraging and migration in Eastern Indian Ocean pygmy blue whales from satellite tracking data
Authors: Ferreira Luciana C. , Jenner Curt , Jenner Micheline , Udyawer Vinay , Radford Ben , Davenport Andrew , Moller Luciana , Andrews-Goff Virginia , Double Mike , Thums Michele
Published: June 2024

Background

Accurate predictions of animal occurrence in time and space are crucial for informing and implementing science-based management strategies for threatened species.

Methods

We compiled known, available satellite tracking data for pygmy blue whales in the Eastern Indian Ocean (n = 38), applied movement models to define low (foraging and reproduction) and high (migratory) move persistence underlying location estimates and matched these with environmental data. We then used machine learning models to identify the relationship between whale occurrence and environment, and predict foraging and migration habitat suitability in Australia and Southeast Asia.

Results

Our model predictions were validated by producing spatially varying accuracy metrics. We identified the shelf off the Bonney Coast, Great Australian Bight, and southern Western Australia as well as the slope off the Western Australian coast as suitable habitat for migration, with predicted foraging/reproduction suitable habitat in Southeast Asia region occurring on slope and in deep ocean waters. Suitable foraging habitat occurred primarily on slope and shelf break throughout most of Australia, with use of the continental shelf also occurring, predominanly in South West and Southern Australia. Depth of the water column (bathymetry) was consistently a top predictor of suitable habitat for most regions, however, dynamic environmental variables (sea surface temperature, surface height anomaly) influenced the probability of whale occurrence.

Conclusions

Our results indicate suitable habitat is related to dynamic, localised oceanic processes that may occur at fine temporal scales or seasonally. An increase in the sample size of tagged whales is required to move towards developing more dynamic distribution models at seasonal and monthly temporal scales. Our validation metrics also indicated areas where further data collection is needed to improve model accuracy. This is of particular importance for pygmy blue whale management, since threats (e.g., shipping, underwater noise and artificial structures) from the offshore energy and shipping industries will persist or may increase with the onset of an offshore renewable energy sector in Australia.
Biomarker-Driven Oncology Trial Design and Subgroup Characterization: Challenges and Potential Solutions
Authors: Wang Jian , Yu Binbing , Dou Yannan Nancy , Mascaro Jacques
Published: June 2024

In oncology drug development, using biomarkers to select a study population more likely to benefit from a therapeutic effect is critical to increase the efficiency of a clinical trial in demonstrating effectiveness. This perspective delves into therapeutic product approvals that were tested in pivotal trials with all-comers populations, but ultimately received US Food and Drug Administration approval for use within specific patient subgroups identified by biomarkers. Despite initial designs for efficacy and safety assessments in overall populations, a favorable benefit-risk assessment was primarily established in biomarker-positive subgroups. Analyzing these cases, we summarize key considerations pivotal to totality of evidence for regulatory benefit-risk assessments for biomarker-defined subgroup versus all-comers approvals, including biological and clinical rationales, biomarker prevalence, safety data, overall trial design, and subgroup efficacy characterization. Furthermore, a decision tree is proposed to guide optimal clinical trial design, delineating between patient enrichment and stratification, accounting for key factors including biological and clinical rationale, marker type (discreate or continuous), prevalence, assay readiness, and turnaround times for marker assessment. Finally, a recommended approach for subgroup characterization involves prespecifying magnitude of improvement that would be considered clinically meaningful in the biomarker-negative subgroup, which can be supplemented with methodologies such as Bayesian to incorporate evidence from similar studies when available. In summary, this perspective underscores the importance of clinical trial innovations, statistical methodologies and regulatory considerations, to optimize biomarker-driven drug development for patients with cancer.
Toward an Oceanic “Becoming With”
Authors: Parkin Justine
Published: June 2024

It is hard not to consider sea-level rise as reflective of an imminent crisis. Drawing together insights from Black feminism and Indigenous thought from the Island Pacific, this article counters a discourse of crisis without uncritically accepting the “oceanifying” of the planet. It moves between analyses of poetic, visual, and plant cultivation practices to show that there is a rubric for living and thinking with the ocean that emphasizes how human and nonhuman life can “become-with” each other in response to ecological degradation while still grappling with the lived legacies of colonial pasts. These oceanic coordinations are ways of knowing that destabilize human exceptionalism from the outset while not excluding the human entirely. Rather, these frameworks incorporate human-nonhuman relations to expand our frame of reference, challenging dominant anthropocentric narratives of crisis and helping imagine and live within oceanic futures.
A β-catenin chromobody-based probe highlights endothelial maturation during vascular morphogenesis in vivo
Authors: Gauvrit Sébastien , Zhao Shengnan , Rothbauer Ulrich , Stainier Didier Y. R.
Published: June 2024

Visualization of protein dynamics is a crucial step in understanding cellular processes. Chromobodies, fluorescently labelled single-domain antibodies, have emerged as versatile probes for live cell imaging of endogenous proteins. However, how these chromobodies behave in vivo and how accurately they monitor tissue changes remain poorly explored. Here, we generated an endothelial-specific β-catenin chromobody-derived probe and analyzed its expression pattern during cardiovascular development in zebrafish. Using high-resolution confocal imaging, we show that the chromobody signal correlates with the localization of β-catenin in the nucleus and at cell-cell junctions, and thereby can be used to assess endothelial maturation. Loss of Cadherin 5 strongly affects the localization of the chromobody at the cell membrane, confirming the cadherin-based adherens junction role of β-catenin. Furthermore, using a genetic model to block blood flow, we observed that cell junctions are compromised in most endothelial cells but not in the endocardium, highlighting the heterogeneous response of the endothelium to the lack of blood flow. Overall, our data further expand the use of chromobodies for in vivo applications and illustrate their potential to monitor tissue morphogenesis at high resolution.
Ritual: Violence and Non-violence
Authors: Thite Ganesh U.
Published: June 2024

Current paper looks at the vicissitudes of thought on violence and non-violence in India, from Vedic period to the present. The early Vedic people lived a nomadic life and practiced customary animal sacrifice. Gradually, however, they started using euphemisms in connection with ritualistic violence and switched subsequently to non-violent rituals. Possibly, because there was a lot of opposition to ritualistic violence, mainly from the Buddhist and the Jaina thinkers, even the later Hinduism ultimately accepted the principle of ahiṃsā (non-violence). Although at present most followers of Vedic rituals do not practice violence when performing Vedic rituals, some others still partly accept it and act accordingly. Also, there is some ritualistic violence outside the Vedic ritual, but there is definitely a change in outlook.
Cursing the daēvas as an Example of Verbal Aggression in the Zoroastrian “Declaration of Faith”?
Authors: Paraskiewicz Kinga
Published: June 2024

This article examines the notion of verbal aggression evident in Zoroastrian prayers. Although one may be surprised that a declaration of Zoroastrian faith, called Fravarānē (Yasna 12), begins with the words “I hate / abhor / am disgusted” instead of “I believe,” cursing (nifrīn kunišn) the demons is a pious religious act.
Atividade física e fatores associados durante a pandemia de COVID-19 em universitários brasileiros: revisão de escopo
Authors: Goveia Jean Carlos de , Vargas Thaiane Moleta , Cantorani José Roberto Herrera , Pedroso Bruno , Vargas Leandro Martinez
Published: June 2024

Neste estudo objetivou-se mapear as publicações nacionais que abordam a variável atividade física e fatores associados entre estudantes universitários brasileiros durante a pandemia de COVID-19. Trata-se de uma revisão de escopo a partir de estudos originais, desenvolvidos no Brasil, publicados entre 2020 e 2023, realizados no cenário clínico da pandemia de COVID-19 e indexados nas bases de dados: Web of Science, PubMed, Scopus, LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde) e Google Scholar. Ao constatar-se diferentes abordagens e fatores associados a problemática, a síntese descritiva foi explorada em subtópicos “nível de atividade física e comportamento sedentário” “saúde mental” e “sono”. Dos 1.180 artigos iniciais, 11 artigos compuseram a síntese, abrangendo distintos padrões amostrais, variando de 68 a 5.720 estudantes, conduzidos em diferentes estados brasileiros. Apesar dessa variedade regional, observou-se uma escassez de estudos nas regiões Norte e Centro-Oeste. A prevalência de inatividade física entre os estudantes variou de 40,0% a 49,3%. O isolamento social e as restrições contribuíram para essa tendência. A saúde mental também foi acometida, com sintomas de ansiedade e depressão mais comuns entre os inativos. Por outro lado, os estudantes ativos relataram melhor saúde mental. A relação entre atividade física e sono não foi clara, mas a pandemia intensificou os problemas de sono em geral. Em suma, futuras pesquisas são relevantes para explorar causas, efeitos e influências regionais. A combinação de métodos qualitativos e quantitativos podem oferecer perspectivas mais abrangentes das experiências dos estudantes em relação à atividade física durante crises de saúde pública.
The unexpected politics of ILGA-Europe’s rainbow maps: (de)constructing queer utopias/dystopias
Authors: Ammaturo Francesca Romana , Slootmaeckers Koen
Published: June 2024

Recently, we have seen a proliferation of maps visualising the global state of lesbian, gay, bisexual, transgender, queer, intersex, plus (LGBTQI+) rights. While they represent a productive advocacy tool for activists, we critically examine the politics embedded and reinforced by the way maps and indices are constructed and represented. By exploring the discrepancies between ILGA-Europe’s rainbow maps and the lived experiences of LGBTQI+ people within Europe, we argue that these maps reproduce hierarchies often mediated by Eurocentric understandings of linear progress while discounting the importance that an interpenetration of legal and social aspects has in evaluating national contexts in which LGBTQI+ persons live. The emphasis on legislative frameworks, thus, in part displaces lived experiences of LGBTQI+ people in Europe, projecting both queer utopias and dystopias onto different geographical localities and feeding into existing homonationalist discourses. With such findings, we argue against the fetishisation of legislation within LGBTQI+ activism and academia.
Improvement of beam quality of high-power edge-emitting lasers using inhomogeneous waveguides
Authors: Wu Cheng-Kun , Xue Xiao-E , Tian Si-Cong , Miah Md. Jarez , Strittmatter André , Bimberg Dieter
Published: June 2024

Inhomogeneous waveguides with corrugations have the potential to increase the fundamental mode brightness of edge-emitting lasers as compared to straight waveguides. The corrugations partly suppress the high-order lateral modes of the lasers. The impact of the shape and size of rectangular and triangular types of corrugations on the lasing performance is compared for the first time, and an optimized design is presented. This concept of introducing corrugations is investigated for conventional edge-emitting lasers, as well as high-brightness vertical broad-area edge-emitting (HiBBEE) lasers. The corrugated HiBBEE lasers provide an almost two times larger brightness than the reference lasers.
Optical frequency dissemination via 103-km urban fiber link with remote passive phase stabilization
Authors: Zhang Xiang , Zhou Qian , Zang Qi , Liu Jie , Liu Tao , Dong Ruifang , Zhang Shougang
Published: June 2024

In this paper, we propose a technique for a fiber-based optical frequency dissemination system with remote passive phase noise cancellation. At the remote site, a 1×2 fiber pigtailed acousto-optic modulator (AOM) with two diffraction order outputs (0 and −1 order) is employed as the phase-compensated device, the undesired phase noise of fiber link introduced by environmental perturbations are passively canceled at remote sites. Different from other existing schemes, the proposed technique harnesses the benefits of remote radio frequency (RF) independence and low-temperature sensitivity in this noise-suppression configuration. Consequently, the system noise floor of the proposed optical frequency dissemination system achieves 9.44 × 10−21 without requiring a precise remote RF reference, and the phase-temperature coefficient is reduced to about 2 fs/K. A real-world experiment is conducted over a noisy round-trip 103 km urban fiber link. After being passively compensated, we demonstrate a fractional frequency instability of 1.57 × 10−14 at the integration time of 1 s and scales down to 3.96 × 10−20 at 10,000 s in terms of modified Allan deviation. The frequency uncertainty of the retrieved light after transferring through this noise-compensated fiber link relative to that of the input light achieves 1.80 × 10−18. This work demonstrates the system’s capability to disseminate the ultra-stable optical frequency standards and is a significant step towards realizing multi-node dissemination of the state-of-the-art optical clock signal with remote noise compensation via a tree-like topology fiber network.
High-brightness green CdSe/ZnS quantum dots stimulated by solar-blind deep-ultraviolet light in optical wireless communications
Authors: Xiao Hua , Zhang Kuokuo , Xu Bing , Shen Huaibin , Wang Lei , Sun Caiming
Published: June 2024

Ultraviolet-based optical wireless communication (OWC) is emerging as a significant technology for the next-generation secure communication, particularly within the solar-blind spectra. In this study, we have synthesized two types of green-emitting II–VI family colloidal quantum dots (QDs), specifically ZnCdSe/ZnS and CdSe/CdZnS/ZnS QDs, which are stimulated by ultraviolet (UV) and solar-blind deep-ultraviolet (DUV) light, respectively. With a transmission distance of 1.5 m, the maximum data rate of ZnCdSe/ZnS QDs reaches 40 Mb/s, which is below the forward-error-correction (FEC) limit (3.8 × 10−3) when excited by 385-nm UV light. However, both brightness and bit error rate are significantly deteriorated when excited by 280-nm DUV light. Conversely, 28 and 24 Mb/s were attained using CdSe/CdZnS/ZnS QDs under UV and DUV excitation, respectively. Our studies on light-conversion and communication capabilities of green QDs within the DUV OWC system may provide valuable insights for subsequent research in the field.
Phase-locked and phase-unlocked multicolor solitons in a fiber laser
Authors: Widjaja Justin , Thuy Hoang Van , Martijn de Sterke C. , Runge Antoine F. J.
Published: June 2024

Multicolor solitons are nonlinear pulses composed of two or more solitons centered at different frequencies, propagating with the same group velocity. In the time domain, multicolor solitons consist of an envelope multiplying a more rapidly varying fringe pattern that results from the interference of these frequency components. Here, we report the observation in a fiber laser of a novel, to the best of our knowledge, type of dynamics in which different frequency components still have the same group velocity but have different propagation constants. This causes the relative phases between the constituent spectral components to change upon propagation, corresponding to the fringes moving under the envelope. This leads to small periodic energy variations that we directly measure. Our experimental results are in good agreement with realistic numerical simulations based on an iterative cavity map.
Sub-ppt level detection of carbon monoxide and nitrous oxide enabled by mid-infrared doubly resonant photoacoustic spectroscopy
Authors: Nie Qinxue , Wang Zhen , Duan Kun , Hu Mai , Du Mengran , Ren Wei
Published: June 2024

We report highly sensitive detection of carbon monoxide (CO) and nitrous oxide (N2O) using doubly resonant photoacoustic spectroscopy paired with a quantum cascade laser (QCL) at 4.57 μm. The butterfly-packaged QCL is used to exploit the CO absorption line at 2190.02 cm−1 and the N2O absorption line at 2191.42 cm−1 by scanning the injection current. Leveraging the simultaneous acoustic and optical resonances and adopting a lower photoacoustic detection frequency, we achieve a minimum detection limit of 0.85 part-per-trillion (ppt) for CO over the 500 s averaging time, and 0.7 ppt for N2O over the 200 s averaging time. Our approach demonstrates record sensitivity for CO and N2O detection compared to state-of-the-art optical gas sensors.
Die vier Phasen von Citizen Development-Initiativen: Treiber, Herausforderungen und Handlungsempfehlungen
Authors: Binzer Björn , Winkler Till J.
Published: June 2024

Moderne Low-Code/No-Code-Plattformen transformieren die Art und Weise, wie Unternehmen digitale Lösungen entwickeln und Innovationen voranbringen. Durch den Fortschritt in Technologien wie Cloud-Computing, künstlicher Intelligenz und maschinellem Lernen ermöglichen diese Plattformen Fachbereichsmitarbeitern ohne umfassende IT-Kenntnisse – den sogenannten Citizen Developern – das Entwerfen und Implementieren eigener leichtgewichtiger digitaler Lösungen. Dieser Trend motiviert immer mehr Unternehmen, Citizen Development-Initiativen ins Leben zu rufen und somit einen kulturellen Wandel hin zu einer demokratisierten Entwicklung digitaler Innovationen zu fördern. Trotz des erkennbaren Potenzials stehen viele Unternehmen jedoch vor der Frage, wie sie ihre Citizen Development-Initiativen effektiv starten und unternehmensweit skalieren können. Dieser Artikel beleuchtet diese Fragestellung basierend auf Interviews mit 21 Verantwortlichen für Citizen Development aus 16 verschiedenen Unternehmen, die früh in Low-Code/No-Code investiert haben. Wir identifizieren vier Phasen, die Unternehmen im Rahmen von Citizen Development durchlaufen, und die spezifischen Herausforderungen, die in jeder Phase bewältigt werden müssen. Unsere Forschungsergebnisse eröffnen Unternehmen Einblicke in aktuelle Praktiken und Zielzustände, um die Herausforderungen einer erfolgreichen Implementierung von Citizen Development zu meistern. Unternehmen sollen befähigt werden, ihre Ressourcen effizienter zu nutzen und Citizen Development nahtlos in ihre Digitalstrategie zu integrieren.