bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergies and Trade-offs Between Cultural and Natural Values of Sacred Sites – a Case Study of Ancient Burial Mounds in Central Europe
Authors: Deák Balázs , Bede Ádám , Süveges Kristóf , Dózsai József , Ormsby Alison A. , Dixon Anna R. , Valkó Orsolya
Published: August 2024

In the Eurasian steppes, ancient burial mounds called ‘kurgans’ are among the most widespread manmade structures. These sacred sites hold cultural values and often provide safe havens for grassland-related plant species. We established links between kurgans' cultural and natural values through a comprehensive multi-layered evaluation of human and landscape history, cultural attributes, and botanical composition on selected mounds in Hungary, Romania, and Serbia. We evaluated factors that can support or endanger the grasslands on kurgans and assessed whether there are synergies or trade-offs between the presence of cultural and natural values. We found that kurgans act as cultural hotspots in transformed landscapes, and we found the following evidence for the synergies between cultural and natural values: i) Extensive land use and management connected to the cultural functions could considerably contribute to the preservation of grassland specialist plants on the mounds. ii) Over the past three centuries, most grasslands we studied were converted to cropland, but the cultural importance of the kurgans could hinder their destruction through ploughing or construction works. However, we also found that built cultural objects decreased the grassland cover area and supported the establishment and spread of several weedy and invasive species. Consequently, to preserve the valuable biocultural systems, it is essential to focus efforts on the maintenance of the already existing traditional cultural functions and not the establishment of new objects.
Antecedents, Characteristics, and Dynamics of IPV in the Israeli Jewish Ultra-Orthodox Community: A Cultural Exploration
Authors: Lipinsky Aiala Szyfer , Goldner Limor
Published: August 2024

Purpose

This qualitative study explored Intimate Partner Violence (IPV) in the Israeli Jewish Ultra-Orthodox (JUO) community to better understand the cultural and religious risk factors and features underlying IPV in this under-researched sector.

Method

Semi-structured interviews implementing the Clinical Ethnographic Narrative Interviews approach were conducted with 15 JUO women currently living with or separated/divorced from their abusive partners who were victims of IPV. The interviews were analyzed using the Interpretive Phenomenological approach.

Results

Two key themes emerged from the analysis. The first theme involves the normalization and exacerbation of violence due to specific religious and societal norms that perpetuate silence and stigma. Factors such as early marriage, religious beliefs about the sanctity of marriage, disadvantaged childhood experiences, and distorted religious justifications contributed to the victims’ vulnerability and hindered their ability to seek help.

The second theme is related to the specific features of the abuse. It covers a range of tactics employed by husbands, including financial oppression, social isolation, physical violence, and manipulation during pregnancy, all based on and justified by distorted religious concepts.

Conclusions

Though aspects of intergenerational abuse and control tactics to aggravate violence are common universal strategies in IPV, the findings here underscore the interplay between religious practices and societal expectations within the JUO community that contribute to the perpetration and perpetuation of IPV. These findings contribute to a better understanding of IPV in religious and traditional contexts and highlight the importance of tailoring interventions to address the needs of specific collectivistic and religious-based societies.
Time Reverse Modeling of Acoustic Waves for Enhanced Mapping of Cracking Sound Events in Textile Reinforced Concrete
Authors: Kocur Georg Karl , Markert Bernd
Published: August 2024

Time reverse modeling (TRM) is successfully applied to acoustic signals from a circular microphone array, for mapping of sudden cracking sound events. Numerical feasibility using synthetic acoustic sources followed by an experimental study with steel pendulum impacts on a steel plate is carried out. The mapping results from the numerical and experimental data are compared and verified using a delay-and-sum beamforming technique. Based on the feasibility and experimental study, a mapping error is estimated. In the main experimental study, cracking sound events obtained during a tensile test on a textile-reinforced concrete specimen are mapped with the TRM. The enhanced capability of the TRM to map simultaneously occurring cracking sound events along crack paths is demonstrated.
A New Look at Job Demands, Resources, and Volunteers’ Intentions to Leave: The Role of Work–Home Interference and Burnout
Authors: Magrone Monica , Montani Francesco , Emili Silvia , Bakker Arnold B. , Sommovigo Valentina
Published: August 2024

Volunteers’ intention to leave is a relevant issue for organizations. Thus, it is critical to advance knowledge on its determinants. This study proposes that burnout symptoms mediate the relationship of work–home interference with leaving intentions. In addition, we hypothesize that job resources, namely organizational appreciation and organizational task support, buffer the positive indirect relationship of work–home interference with volunteers’ leaving intentions through burnout symptoms. To this end, we rely on the job demands–resources theory, a theoretical framework first conceived for the paid work context that has been widely applied in volunteering settings. Consistent with our predictions, (moderated) mediation analyses on a sample of 220 Italian volunteers showed that only cynicism, and not emotional exhaustion, significantly mediated the positive relationship between work–home interference and leaving intentions and that organizational appreciation and task support weakened this indirect relationship. We discuss how these findings contribute to theory and practice for the volunteering sector.
Skin Boats in Scandinavia? Evaluating the Maritime Technologies of the Neolithic Pitted Ware Culture
Authors: Fauvelle Mikael , Horn Christian , Alvå Jacob , Artursson Magnus
Published: August 2024

The Early and Middle Neolithic (3500–2300 [Before Current Era] BCE) Pitted Ware Culture (PWC) was a critical component of the historical trajectory of Scandinavia’s maritime history. The hunter-gatherer societies of the PWC were highly adapted to maritime environments, and they fished, hunted, travelled, and traded across great distances over water. Exactly what boat types they used, however, is still an open question. Understanding the maritime technologies used by the PWC is a critical research area as they had an important impact on subsequent maritime adaptations in Scandinavian prehistory. Unfortunately, finding intact boats from Neolithic contexts is extremely difficult. Here, we present indirect evidence for the use of skin boats by PWC people as a first step towards building a dialog on the types of boats that would have been used during this period. We argue that multiple lines of evidence suggest that skin boats were widely used for every-day activities and long-distance voyages by PWC peoples and will discuss the implications of possible complex boat use by Neolithic peoples for our understanding of early Scandinavian maritime societies.
The Impact of Strategic Orientations on the Born Globals’ Export Performance: An Ambidexterity Approach
Authors: Presutti Manuela , Fratocchi Luciano , Odorici Vincenza
Published: August 2024

According to international entrepreneurship scholars, the success of Born Globals (BGs) depends on their capacity to develop an organizational ambidexterity perspective, i.e. a dual function of simultaneous knowledge exploration and exploitation. In this respect, it has been pointed out that ambidexterity can be associated with the ability to balance the development of different strategic orientations (SOs), namely, entrepreneurial orientation (EO), market orientation (MO), and learning orientation (LO). While several authors have investigated the impact of MO, EO and LO on BGs’ performance, the results of such research are often inconsistent. Based on the resource orchestration view, we assume that the combined – rather than the single – contribution of resources and capabilities provided by EO, MO, and LO, ultimately result in a superior export performance. Such an indicator is typically adopted to evaluate international performance, especially for micro and small companies. More specifically, the study aims to verify the significance of dyadic (namely, MO*EO, EO*LO, and MO*LO) and triadic (MO*EO* LO) interactions of the SO typologies on BGs’ export performance. Moreover, the paper aspires to verify if some of these interactions are more relevant than others. We test our hypotheses on a sample of 100 Italian hi-tech BGs located inside a technological cluster near Rome through a longitudinal analysis. Our findings show that all the investigated interactions positively and significantly impact on the BGs’ export performances, independently of the adopted measurement variable. However, a certain type of hierarchy emerges among the different impacts of the investigated interactions among the three SO typologies.
Medical Mistrust Among Black Patients with Serious Illness: A Mixed Methods Study
Authors: Cueva Kristine L. , Marshall Arisa R. , Snyder Cyndy R. , Young Bessie A. , Brown Crystal E.
Published: August 2024

Background

Medical mistrust among Black patients has been used to explain the existence of well-documented racial inequities at the end of life that negatively impact this group. However, there are few studies that describe patient perspectives around the impact of racism and discriminatory experiences on mistrust within the context of serious illness.

Objective

To better characterize experiences of racism and discrimination among patients with serious illness and its association with medical mistrust.

Participants

Seventy-two Black participants with serious illness hospitalized at an academic county hospital.

Approach

This is a convergent mixed methods study using data from participant-completed surveys and existing semi-structured interviews eliciting participants’ perspectives around their experiences with medical racism, communication, and decision-making.

Main Measures

The experience of medical racism and its association with Group-Based Medical Mistrust (GBMM) scale scores, a validated measure of medical mistrust.

Key Results

Of the 72 Black participants, 35% participated in interviews. Participants were mostly men who had significant socioeconomic disadvantage, including low levels of wealth, income, and educational attainment. There were reported high levels of race-based mistrust in the overall GBMM scale score (mean [SD], 36.6 [9.9]), as well as high scores within the suspicion (14.2 [5.0]), group disparities in healthcare (9.9 [2.8]), and lack of support (9.1 [2.7]) subscales. Three qualitative themes aligned with the GBMM subscales. Participants expressed skepticism of healthcare workers (HCWs) and modern medicine, recounted personal experiences of discrimination in the medical setting, and were frustrated with poor communication from HCWs.

Conclusions

This study found high levels of mistrust among Black patients with serious illness. Suspicion of HCWs, disparities in healthcare by race, and a lack of support from HCWs were overarching themes that influenced medical mistrust. Critical, race-conscious approaches are needed to create strategies and frameworks to improve the trustworthiness of healthcare institutions and workers.

Graphical abstract
Evaluation of neutrophil activation marker in patients with vitiligo
Authors: El-Sadek Hala M. , Elmadbouly Asmaa A. , Risha Basma E. M.
Published: August 2024

Background

Vitiligo is an inflammatory, autoimmune disorder. Its pathogenesis is unclear. A neutrophil activation marker (calprotectin) is a protein complex present in many different types of cells and may be used as an indicator of inflammation.

Aims

This study is to assess calprotectin levels in non-segmental vitiligo patients and compare them to the severity of the illness to identify potential associations.

Methods

The present inquiry was conducted on thirty non-segmental vitiligo patients and thirty healthy volunteers matched in terms of age and gender. The Vitiligo Area Scoring Index was used to assess the vitiligo severity. Calprotectin levels were measured in serum samples obtained from all participants by Enzyme Linked Immunosorbent Assay.

Results

Compared to controls, non-segmental vitiligo patients had considerably elevated serum calprotectin levels. Additionally, calprotectin levels were shown to have a significant positive association with disease severity (r = 0.833, P = 0.000).

Conclusions

Elevated levels of serum calprotectin in non-segmental vitiligo patients relative to healthy individuals with high sensitivity indicated that it may have a role in the vitiligo pathophysiology and can act as a marker for disease monitoring.
Optimal $$L^{2}$$-growth of the generalized Rosenau equation
Authors: Li Xiaoyan , Ikehata Ryo
Published: August 2024

We report that the quantity measured in the $$L^2$$

L
2

norm of the solution itself of the generalized Rosenau equation, which was completely unknown in this equation, grows in the proper order at time infinity. It is also immediately apparent that this growth aspect does not occur in three or more spatial dimensions, so we will apply the results obtained in this study to provide another proof that Hardy-type inequalities do not hold in the case of one or two spatial dimensions.
Gewalt junger Menschen mit Migrationshintergrund im Amateurfußball
Authors: Kaya Fatih , Uslucan Hacɪ-Halil
Published: August 2024

Die mediale Berichterstattung über den deutschen Amateurfußball wird oft von Spielunterbrechungen aufgrund eskalierender Gewalt begleitet, an der häufig junge Menschen mit Migrationshintergrund beteiligt sind. Dabei werden zum Teil ethnische Stigmatisierungen vorgenommen, gleichwohl die Ursachen dafür komplexer und vielschichtiger sind. Um einen Einblick in die Ursachen zu bekommen, werden in dem folgenden Beitrag individuelle und gesellschaftliche Prozesse erörtert und die Frage aufgeworfen, wie diese auf die Betroffenen wirken. In diesem Kontext wird zudem diskutiert, welche möglichen Präventionsmaßnahmen hier eingeführt werden können.
Enterprise Foundations and Faithful Agency as Drivers of Sustainable Long-Termism in Philanthropy
Authors: Ørberg Mark
Published: August 2024

The literature on enterprise foundations – foundations that own companies – is booming. As something new, this article compares the (civil law) public good enterprise foundation with the (common law) perpetual purpose trust. While the article is focused on Danish and US law, the analysis and discussions are designed to be useful for anyone interested in enterprise foundation law. The article offers insights on enterprise foundations as ownerless special-purpose institutions with legal personhood becoming majority owners of an otherwise traditional enterprise. The article bridges existing comparative law scholarship on civil law foundations and common law trusts in the light of recent developments within enterprise foundations and similar hybrids in Europe and the US. The US Patagonia perpetual purpose trust and the Danish Novo Nordisk enterprise foundation are used as examples of the different approaches in common law and civil law. Although trusts and foundations may functionally appear remarkably similar, significant differences exist. The article discusses a broad range of policy arguments regarding public good variants of the Danish enterprise foundation model. It argues that enterprise foundations may function as drivers of sustainable long-termism in US business and philanthropy, and explains how and why. Particularly, the article highlights that the ‘purpose lock’ and ‘asset lock’ combined with strong supervision powers may deliver a non-profit entity which includes public good distributions as well as responsible and active ownership, taking the hard edges off capitalism. Arguably, the public good enterprise foundation is one of the ‘queens’ of non-profit succession planning.
How Affective Science Can Inform Behavioral Public Policy
Authors: Västfjäll Daniel , Asutay Erkin , Tinghög Gustav
Published: August 2024

In this commentary, we expand on the special issue themes of applied affective science, ecologically valid data and application, and the need for transdisciplinary collaboration by discussing and exemplifying how affective science can inform behavioral public policy.
The associated risk factors for type 2 diabetes mellitus among adults: a cross-sectional study using electronic medical records in the Primary Health Care Corporation, Qatar
Authors: Elshaikh Usra , Elashie Sana , Alhussaini Nour Waleed Zuhair , Yaseen Manar , Mohamed Hafiz Ahmed , Syed Mohamed Ahmed , Zainel Abduljaleel Abdullatif
Published: August 2024

Background

Type 2 diabetes mellitus (T2DM) has a high prevalence in Qatar, necessitating a thorough understanding of its risk factors. This study explored the associations between specific risk factors and T2DM among adults attending Primary Health Care Corporation (PHCC) centers in Qatar.

Methods

Employing a cross-sectional study design, data were extracted from the electronic medical records of individuals aged 18 years and older who visited the PHCC health centers during the year 2017. Data analysis was performed using univariate and multiple regression models.

Results

The study included 127,941 participants, 33% of whom were diagnosed with T2DM. Age was the most significant risk factor, with individuals aged 60 years and older having an adjusted odds ratio (aOR) of 7.53, and those aged 40–59 years having an aOR of 3.55. Sex was also found to influence T2DM risk, as males had an aOR of 1.47. Nationality also played a role, as individuals of southern Asian descent exhibited an increased risk of T2DM, with an aOR of 2.40, while Qataris had an aOR of 1.55. Having high blood pressure was associated with more than doubling the risk of developing T2DM.

Conclusion

This study provides essential epidemiological insights that can inform decision-making related to T2DM in Qatar. Our findings highlight that males over the age of 40, particularly those of South Asian descent with high blood pressure are at increased risk of T2DM. Identifying the major risk factors is  essential for the prevention and management of T2DM.
Controls on Upper Ocean Salinity Variability in the Eastern Subpolar North Atlantic During 1992–2017
Authors: Siddiqui Ali H. , Haine Thomas W. N. , Nguyen An T. , Buckley Martha W.
Published: August 2024

The upper ocean salinity in the eastern subpolar North Atlantic undergoes decadal fluctuations. A large fresh anomaly event occurred during 2012–2016. Using the ECCOv4r4 state estimate, we diagnose and compare mechanisms of this low salinity event with those of the 1990s fresh anomaly event. To avoid issues related to the choice of reference salinity values in the freshwater budget, we perform a salt mass content budget analysis of the eastern subpolar North Atlantic. It shows that the recent low salt content anomaly occurs due to the circulation of anomalous salinity by mean currents entering the eastern subpolar basin from its western boundary via the North Atlantic Current. This is in contrast to the early 1990s, when the dominant mechanism governing the low salt content anomaly was the transport of the mean salinity field by anomalous currents.
Fracture Characterization Via AI‐Assisted Analysis of Temperature Logs
Authors: Yang Xiaoyu , Horne Roland N. , Tartakovsky Daniel M.
Published: August 2024

Fractures control fluid flow, mass transport, and heat transfer in a geothermal reservoir. This makes accurate characterization of fracture networks a prerequisite for optimal design and control of a reservoir's exploitation. We develop a deep‐learning procedure to identify fracture locations via interpretation of temporally and spatially continuous downhole temperature measurements. A long short‐term memory fully convolutional network (LSTM‐FCN) is used both to capture long‐term dependencies in sequential temperature data and to distill local features around fractures. A wellbore and fractured‐reservoir thermal model is established to generate temperature data for network training. The trained LSTM‐FCN exhibits a unique ability to detect multiple fractures intersecting a borehole. We use the LSTM‐FCN algorithm to evaluate the effectiveness of different‐stage wellbore temperature measurements on fracture detection in a complex fractured system. Our experiments reveal that the use of various‐stage temperature information as an input feature set improves the robustness of fracture detection to noise interference. This study indicates the practical feasibility of obtaining accurate fracture‐network reconstructions from temperature signals, at reasonable computational cost.
A multidimensional analysis reveals distinct immune phenotypes and the composition of immune aggregates in pediatric acute myeloid leukemia
Authors: Koedijk Joost B. , van der Werf Inge , Penter Livius , Vermeulen Marijn A. , Barneh Farnaz , Perzolli Alicia , Meesters-Ensing Joyce I. , Metselaar Dennis S. , Margaritis Thanasis , Fiocco Marta , de Groot-Kruseman Hester A. , Moeniralam Rubina , Bang Christensen Kristina , Porter Billie , Pfaff Kathleen , Garcia Jacqueline S. , Rodig Scott J. , Wu Catherine J. , Hasle Henrik , Nierkens Stefan , Belderbos Mirjam E. , Zwaan C. Michel , Heidenreich Olaf
Published: August 2024

Because of the low mutational burden and consequently, fewer potential neoantigens, children with acute myeloid leukemia (AML) are thought to have a T cell-depleted or ‘cold’ tumor microenvironment and may have a low likelihood of response to T cell-directed immunotherapies. Understanding the composition, phenotype, and spatial organization of T cells and other microenvironmental populations in the pediatric AML bone marrow (BM) is essential for informing future immunotherapeutic trials about targetable immune-evasion mechanisms specific to pediatric AML. Here, we conducted a multidimensional analysis of the tumor immune microenvironment in pediatric AML and non-leukemic controls. We demonstrated that nearly one-third of pediatric AML cases has an immune-infiltrated BM, which is characterized by a decreased ratio of M2- to M1-like macrophages. Furthermore, we detected the presence of large T cell networks, both with and without colocalizing B cells, in the BM and dissected the cellular composition of T- and B cell-rich aggregates using spatial transcriptomics. These analyses revealed that these aggregates are hotspots of CD8+ T cells, memory B cells, plasma cells and/or plasmablasts, and M1-like macrophages. Collectively, our study provides a multidimensional characterization of the BM immune microenvironment in pediatric AML and indicates starting points for further investigations into immunomodulatory mechanisms in this devastating disease.
Stearoyl-CoA desaturase inhibition is toxic to acute myeloid leukemia displaying high levels of the de novo fatty acid biosynthesis and desaturation
Authors: Dembitz Vilma , Lawson Hannah , Burt Richard , Natani Sirisha , Philippe Céline , James Sophie C. , Atkinson Samantha , Durko Jozef , Wang Lydia M. , Campos Joana , Magee Aoife M. S. , Woodley Keith , Austin Michael J. , Rio-Machin Ana , Casado Pedro , Bewicke-Copley Findlay , Rodriguez Blanco Giovanny , Pereira-Martins Diego , Oudejans Lieve , Boet Emeline , von Kriegsheim Alex , Schwaller Juerg , Finch Andrew J. , Patel Bela , Sarry Jean-Emmanuel , Tamburini Jerome , Schuringa Jan Jacob , Hazlehurst Lori , Copland III John A. , Yuneva Mariia , Peck Barrie , Cutillas Pedro , Fitzgibbon Jude , Rouault-Pierre Kevin , Kranc Kamil , Gallipoli Paolo
Published: August 2024

Identification of specific and therapeutically actionable vulnerabilities, ideally present across multiple mutational backgrounds, is needed to improve acute myeloid leukemia (AML) patients’ outcomes. We identify stearoyl-CoA desaturase (SCD), the key enzyme in fatty acid (FA) desaturation, as prognostic of patients' outcomes and, using the clinical-grade inhibitor SSI-4, show that SCD inhibition (SCDi) is a therapeutic vulnerability across multiple AML models in vitro and in vivo. Multiomic analysis demonstrates that SCDi causes lipotoxicity, which induces AML cell death via pleiotropic effects. Sensitivity to SCDi correlates with AML dependency on FA desaturation regardless of mutational profile and is modulated by FA biosynthesis activity. Finally, we show that lipotoxicity increases chemotherapy-induced DNA damage and standard chemotherapy further sensitizes AML cells to SCDi. Our work supports developing FA desaturase inhibitors in AML while stressing the importance of identifying predictive biomarkers of response and biologically validated combination therapies to realize their full therapeutic potential.
Microfluidic QCM enables ultrahigh Q-factor: a new paradigm for in-liquid gravimetric sensing
Authors: Zhao Yicheng , Parlak Zehra , Yu Wenjun , French Daniel , Aquino Wilkins , Zauscher Stefan
Published: August 2024

Acoustic gravimetric biosensors attract attention due to their simplicity, robustness, and low cost. However, a prevailing challenge in these sensors is dissipation which manifests in a low quality factor (Q-factor), which limits their sensitivity and accuracy. To mitigate dissipation of acoustic sensors in liquid environments we introduce an innovative approach in which we combine microfluidic channels with gravimetric sensors. To implement this novel paradigm we chose the quartz crystal microbalance (QCM) as our model system, owing to its wide applicability in biosensing and the relevance of its operating principles to other types of acoustic sensors. We postulate that the crucial determinant for enhancing performance lies in the ratio between the width of the microfluidic channels and the wavelength of the pressure wave generated by the oscillating channel side walls driven by the QCM. Our hypothesis is supported by finite element analysis (FEA) and dimensional studies, which revealed two key factors that affect device performance: (1) the ratio of the channel width to the pressure wavelength ($$W/{\lambda }_{{\rm {p}}}$$

W
/

λ

p

) and (2) the ratio of the channel height to the shear evanescent wavelength ($$H/{\lambda }_{{\rm {s}}}$$

H
/

λ

s

). To validate our hypothesis, we fabricated a microfluidic QCM (µ-QCM) and demonstrated a remarkable 10-fold improvement in its dissipation when compared to conventional QCM. The novel microfluidic approach offers several additional advantages, such as direct data interpretation, reduced volume requirement for sample liquids, and simplified temperature control, augmenting the sensor’s overall performance. By fostering increased sensitivity, accuracy, and ease of operation, our novel paradigm unlocks new possibilities for advancing gravimetric technologies, potentially for biosensing applications.
Predicting gastric cancer response to anti-HER2 therapy or anti-HER2 combined immunotherapy based on multi-modal data
Authors: Chen Zifan , Chen Yang , Sun Yu , Tang Lei , Zhang Li , Hu Yajie , He Meng , Li Zhiwei , Cheng Siyuan , Yuan Jiajia , Wang Zhenghang , Wang Yakun , Zhao Jie , Gong Jifang , Zhao Liying , Cao Baoshan , Li Guoxin , Zhang Xiaotian , Dong Bin , Shen Lin
Published: August 2024

The sole use of single modality data often fails to capture the complex heterogeneity among patients, including the variability in resistance to anti-HER2 therapy and outcomes of combined treatment regimens, for the treatment of HER2-positive gastric cancer (GC). This modality deficit has not been fully considered in many studies. Furthermore, the application of artificial intelligence in predicting the treatment response, particularly in complex diseases such as GC, is still in its infancy. Therefore, this study aimed to use a comprehensive analytic approach to accurately predict treatment responses to anti-HER2 therapy or anti-HER2 combined immunotherapy in patients with HER2-positive GC. We collected multi-modal data, comprising radiology, pathology, and clinical information from a cohort of 429 patients: 310 treated with anti-HER2 therapy and 119 treated with a combination of anti-HER2 and anti-PD-1/PD-L1 inhibitors immunotherapy. We introduced a deep learning model, called the Multi-Modal model (MuMo), that integrates these data to make precise treatment response predictions. MuMo achieved an area under the curve score of 0.821 for anti-HER2 therapy and 0.914 for combined immunotherapy. Moreover, patients classified as low-risk by MuMo exhibited significantly prolonged progression-free survival and overall survival (log-rank test, P < 0.05). These findings not only highlight the significance of multi-modal data analysis in enhancing treatment evaluation and personalized medicine for HER2-positive gastric cancer, but also the potential and clinical value of our model.
Tert promotes cardiac regenerative repair after MI through alleviating ROS-induced DNA damage response in cardiomyocyte
Authors: Wei Xiaomin , Zhou Yilin , Shao Enge , Shi Xiaoran , Han Yuan , Zhang Yeshen , Wei Guoquan , Zheng Hao , Huang Senlin , Chen Yanmei , Sun Jie , Liao Yulin , Liao Wangjun , Wang Yanbing , Bin Jianping , Li Xinzhong
Published: August 2024

Telomerase reverse transcriptase (Tert) has been found to have a protective effect on telomeric DNA, but whether it could improve the repair of reactive oxygen species (ROS)-induced DNA damage and promote myocardial regenerative repair after myocardial infarction (MI) by protecting telomeric DNA is unclear. The immunofluorescence staining with TEL-CY3 and the TeloTAGGG Telomerase PCR ELISA kit were used to show the telomere length and telomerase activity. The heart-specific Tert-deletion homozygotes were generated by using commercial Cre tool mice and flox heterozygous mice for mating. We measured the telomere length and telomerase activity of mouse cardiomyocytes (CMs) at different days of age, and the results showed that they were negatively correlated with age. Overexpressed Tert could enhance telomerase activity and lengthen telomeres, thereby repairing the DNA damage induced by ROS and promoting CM proliferation in vitro. The in vivo results indicated that enhanced Tert could significantly improve cardiac function and prognosis by alleviating CM DNA damage and promoting angiogenesis post-MI. In terms of mechanism, DNA pulldown assay was used to identify that nuclear ribonucleoprotein A2B1 (hnRNPA2B1) could be an upstream regulator of Tert in CMs. Overexpressed Tert could activate the NF-κB signaling pathway in CMs and bind to the VEGF promoter in the endothelium to increase the VEGF level. Further immunoblotting showed that Tert protected DNA from ROS-induced damage by inhibiting ATM phosphorylation and blocking the Chk1/p53/p21 pathway activation. HnRNPA2B1-activated Tert could repair the ROS-induced telomeric DNA damage to induce the cell cycle re-entry in CMs and enhance the interaction between CMs and endothelium, thus achieving cardiac regenerative repair after MI.
Single-cell transcriptomics reveal transcriptional programs underlying male and female cell fate during Plasmodium falciparum gametocytogenesis
Authors: Mohammed Mubasher , Dziedziech Alexis , Macedo Diego , Huppertz Frederik , Veith Ylva , Postel Zoé , Christ Elena , Scheytt Richard , Slotte Tanja , Henriksson Johan , Ankarklev Johan
Published: August 2024

The Plasmodium falciparum life cycle includes obligate transition between a human and mosquito host. Gametocytes are responsible for transmission from the human to the mosquito vector where gamete fusion followed by meiosis occurs. To elucidate how male and female gametocytes differentiate in the absence of sex chromosomes, we perform FACS-based cell enrichment of a P. falciparum gametocyte reporter line followed by single-cell RNA-seq. In our analyses we define the transcriptional programs and predict candidate driver genes underlying male and female development, including genes from the ApiAP2 family of transcription factors. A motif-driven, gene regulatory network analysis indicates that AP2-G5 specifically modulates male development. Additionally, genes linked to the inner membrane complex, involved in morphological changes, are uniquely expressed in the female lineage. The transcriptional programs of male and female development detailed herein allow for further exploration of the evolution of sex in eukaryotes and provide targets for future development of transmission blocking therapies.
Conformational flexibility of HIV-1 envelope glycoproteins modulates transmitted/founder sensitivity to broadly neutralizing antibodies
Authors: Parthasarathy Durgadevi , Pothula Karunakar Reddy , Ratnapriya Sneha , Cervera Benet Héctor , Parsons Ruth , Huang Xiao , Sammour Salam , Janowska Katarzyna , Harris Miranda , Sodroski Joseph , Acharya Priyamvada , Herschhorn Alon
Published: August 2024

HIV-1 envelope glycoproteins (Envs) of most primary HIV-1 strains exist in closed conformation and infrequently sample open states, limiting access to internal epitopes. Thus, immunogen design aims to mimic the closed Env conformation as preferred target for eliciting broadly neutralizing antibodies (bnAbs). Here we identify incompletely closed Env conformations of 6 out of 13 transmitted/founder (T/F) strains that are sensitive to antibodies that recognize internal epitopes typically exposed on open Envs. A 3.6 Å cryo-electron microscopy structure of unliganded, incompletely closed T/F Envs (1059-SOSIP) reveals protomer motion that increased sampling of states with incompletely closed trimer apex. We reconstruct de novo the post-transmission evolutionary pathway of a second T/F. Evolved viruses exhibit increased Env resistance to cold, soluble CD4 and 19b, all of which correlate with closing of the adapted Env trimer. Lastly, we show that the ultra-broad N6 bnAb efficiently recognizes different Env conformations and exhibits improved antiviral breadth against VRC01-resistant Envs isolated during the first-in-humans antibody-mediated-prevention trial.
Trophic evolution in ornithopod dinosaurs revealed by dental wear
Authors: Ősi Attila , Barrett Paul M. , Nagy András Lajos , Szenti Imre , Vásárhelyi Lívia , Magyar János , Segesdi Martin , Csiki-Sava Zoltán , Botfalvai Gábor , Jó Viviána
Published: August 2024

Ornithopod dinosaurs evolved numerous craniodental innovations related to herbivory. Nonetheless, the relationship between occlusion, tooth wear rate, and tooth replacement rate has been neglected. Here, we reconstruct tooth wear rates by measuring tooth replacement rates and tooth wear volumes, and document their dental microwear. We demonstrate that total tooth volume and rates of tooth wear increased steadily during ornithopod evolution, with deeply-nested taxa wearing up to 3360 mm3 of tooth volume/day. Increased wear resulted in asymmetric tooth crown formation with uneven von Ebner line increment width by the Late Jurassic, and in faster tooth replacement rates in multiple lineages by the mid-Cretaceous. Microwear displays a contrasting pattern, with decreasing complexity and pit percentages in deeply-nested and later-occurring taxa. We hypothesize that early ornithopods were browsers and/or frugivores but deeply nested iguanodontians were bulk-feeders, eating tougher, less nutritious plants; these trends correlate with increasing body mass and longer gut passage times.
Transparent and high-porosity aluminum alkoxide network-forming glasses
Authors: Zhang Zihui , Zhao Yingbo
Published: August 2024

Metal-organic network-forming glasses are an emerging type of material capable of combining the modular design and high porosity of metal-organic frameworks and the high processability and optical transparency of glasses. However, a generalizable strategy for achieving both high porosity and high glass-forming ability in modularly designed metal-organic networks has yet to be developed. Herein, we develop a series of aluminum alkoxide glasses and monoliths by linking aluminum-oxo clusters with alcohol linkers. A bulky monodentate alcohol modulator is introduced during synthesis and act as both network plasticizer and pore template, which can be removed by the subsequent solvent exchange to give gas accessible pores. Glasses synthesized with the modulator template exhibit well-defined glass transitions in their as-synthesized form and high surface areas up to 500 m2/g after activation, making them among the most porous glassy materials. The aluminum alkoxide glasses also have optical transparency and fluorescent properties, and their structures are elucidated by pair-distribution functions, spectroscopic and compositional analysis. These findings could significantly expand the library of microporous metal-organic network-forming glasses and enable their future applications.
A novel stacking ensemble learner for predicting residual strength of corroded pipelines
Authors: Wang Qiankun , Lu Hongfang
Published: August 2024

Accurately assessing the residual strength of corroded oil and gas pipelines is crucial for ensuring their safe and stable operation. Machine learning techniques have shown promise in addressing this challenge due to their ability to handle complex, non-linear relationships in data. Unlike previous studies that primarily focused on enhancing prediction accuracy through the optimization of single models, this work shifts the emphasis to a different approach: stacking ensemble learning. This study applies a stacking model composed of seven base learners and three meta-learners to predict the residual strength of pipelines using a dataset of 453 instances. Automated hyperparameter tuning libraries are utilized to search for optimal hyperparameters. By evaluating various combinations of base learners and meta-learners, the optimal stacking configuration was determined. The results demonstrate that the stacking model, using k-nearest neighbors as the meta-learner alongside seven base learners, delivers the best predictive performance, with a coefficient of determination of 0.959. Compared to individual models, the stacking model also significantly improves generalization performance. However, the stacking model’s effectiveness on low-strength pipelines is limited due to the small sample size. Furthermore, incorporating original features into the second-layer model did not significantly enhance performance, likely because the first-layer model had already extracted most of the critical features. Given the marginal contribution of model optimization to prediction accuracy, this work offers a novel perspective for improving model performance. The findings have important practical implications for the integrity assessment of corroded pipelines.
The genetic architecture of repeated local adaptation to climate in distantly related plants
Authors: Whiting James R. , Booker Tom R. , Rougeux Clément , Lind Brandon M. , Singh Pooja , Lu Mengmeng , Huang Kaichi , Whitlock Michael C. , Aitken Sally N. , Andrew Rose L. , Borevitz Justin O. , Bruhl Jeremy J. , Collins Timothy L. , Fischer Martin C. , Hodgins Kathryn A. , Holliday Jason A. , Ingvarsson Pär K. , Janes Jasmine K. , Khandaker Momena , Koenig Daniel , Kreiner Julia M. , Kremer Antoine , Lascoux Martin , Leroy Thibault , Milesi Pascal , Murray Kevin D. , Pyhäjärvi Tanja , Rellstab Christian , Rieseberg Loren H. , Roux Fabrice , Stinchcombe John R. , Telford Ian R. H. , Todesco Marco , Tyrmi Jaakko S. , Wang Baosheng , Weigel Detlef , Willi Yvonne , Wright Stephen I. , Zhou Lecong , Yeaman Sam
Published: August 2024

Closely related species often use the same genes to adapt to similar environments. However, we know little about why such genes possess increased adaptive potential and whether this is conserved across deeper evolutionary lineages. Adaptation to climate presents a natural laboratory to test these ideas, as even distantly related species must contend with similar stresses. Here, we re-analyse genomic data from thousands of individuals from 25 plant species as diverged as lodgepole pine and Arabidopsis (~300 Myr). We test for genetic repeatability based on within-species associations between allele frequencies in genes and variation in 21 climate variables. Our results demonstrate significant statistical evidence for genetic repeatability across deep time that is not expected under randomness, identifying a suite of 108 gene families (orthogroups) and gene functions that repeatedly drive local adaptation to climate. This set includes many orthogroups with well-known functions in abiotic stress response. Using gene co-expression networks to quantify pleiotropy, we find that orthogroups with stronger evidence for repeatability exhibit greater network centrality and broader expression across tissues (higher pleiotropy), contrary to the ‘cost of complexity’ theory. These gene families may be important in helping wild and crop species cope with future climate change, representing important candidates for future study.
A 27-country test of communicating the scientific consensus on climate change
Authors: Većkalov Bojana , Geiger Sandra J. , Bartoš František , White Mathew P. , Rutjens Bastiaan T. , van Harreveld Frenk , Stablum Federica , Akın Berkan , Aldoh Alaa , Bai Jinhao , Berglund Frida , Bratina Zimic Aleša , Broyles Margaret , Catania Andrea , Chen Airu , Chorzępa Magdalena , Farahat Eman , Götz Jakob , Hoter-Ishay Bat , Jordan Gesine , Joustra Siri , Klingebiel Jonas , Krajnc Živa , Krug Antonia , Andersen Thomas Lind , Löloff Johanna , Natarajan Divya , Newman-Oktan Sasha , Niehoff Elena , Paerels Celeste , Papirmeister Rachel , Peregrina Steven , Pohl Felicia , Remsö Amanda , Roh Abigail , Rusyidi Binahayati , Schmidt Justus , Shavgulidze Mariam , Vellinho Nardin Valentina , Wang Ruixiang , Warner Kelly , Wattier Miranda , Wong Chloe Y. , Younssi Mariem , Ruggeri Kai , van der Linden Sander
Published: August 2024

Communicating the scientific consensus that human-caused climate change is real increases climate change beliefs, worry and support for public action in the United States. In this preregistered experiment, we tested two scientific consensus messages, a classic message on the reality of human-caused climate change and an updated message additionally emphasizing scientific agreement that climate change is a crisis. Across online convenience samples from 27 countries (n = 10,527), the classic message substantially reduces misperceptions (d = 0.47, 95% CI (0.41, 0.52)) and slightly increases climate change beliefs (from d = 0.06, 95% CI (0.01, 0.11) to d = 0.10, 95% CI (0.04, 0.15)) and worry (d = 0.05, 95% CI (−0.01, 0.10)) but not support for public action directly. The updated message is equally effective but provides no added value. Both messages are more effective for audiences with lower message familiarity and higher misperceptions, including those with lower trust in climate scientists and right-leaning ideologies. Overall, scientific consensus messaging is an effective, non-polarizing tool for changing misperceptions, beliefs and worry across different audiences.
Continuous spectral and coupling-strength encoding with dual-gradient metasurfaces
Authors: Aigner Andreas , Weber Thomas , Wester Alwin , Maier Stefan A. , Tittl Andreas
Published: August 2024

To control and enhance light–matter interactions at the nanoscale, two parameters are central: the spectral overlap between an optical cavity mode and the material’s spectral features (for example, excitonic or molecular absorption lines), and the quality factor of the cavity. Controlling both parameters simultaneously would enable the investigation of systems with complex spectral features, such as multicomponent molecular mixtures or heterogeneous solid-state materials. So far, it has been possible only to sample a limited set of data points within this two-dimensional parameter space. Here we introduce a nanophotonic approach that can simultaneously and continuously encode the spectral and quality-factor parameter space within a compact spatial area. We use a dual-gradient metasurface design composed of a two-dimensional array of smoothly varying subwavelength nanoresonators, each supporting a unique mode based on symmetry-protected bound states in the continuum. This results in 27,500 distinct modes and a mode density approaching the theoretical upper limit for metasurfaces. By applying our platform to surface-enhanced molecular spectroscopy, we find that the optimal quality factor for maximum sensitivity depends on the amount of analyte, enabling effective molecular detection regardless of analyte concentration within a single dual-gradient metasurface. Our design provides a method to analyse the complete spectral and coupling-strength parameter space of complex material systems for applications such as photocatalysis, chemical sensing and entangled photon generation.
Inferring pattern-driving intercellular flows from single-cell and spatial transcriptomics
Authors: Almet Axel A. , Tsai Yuan-Chen , Watanabe Momoko , Nie Qing
Published: August 2024

From single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (ST), one can extract high-dimensional gene expression patterns that can be described by intercellular communication networks or decoupled gene modules. These two descriptions of information flow are often assumed to occur independently. However, intercellular communication drives directed flows of information that are mediated by intracellular gene modules, in turn triggering outflows of other signals. Methodologies to describe such intercellular flows are lacking. We present FlowSig, a method that infers communication-driven intercellular flows from scRNA-seq or ST data using graphical causal modeling and conditional independence. We benchmark FlowSig using newly generated experimental cortical organoid data and synthetic data generated from mathematical modeling. We demonstrate FlowSig’s utility by applying it to various studies, showing that FlowSig can capture stimulation-induced changes to paracrine signaling in pancreatic islets, demonstrate shifts in intercellular flows due to increasing COVID-19 severity and reconstruct morphogen-driven activator–inhibitor patterns in mouse embryogenesis.