bluuebunny/crossref_metadata_2025 huggingface dataset:
UV photo-sensing performance of NiSnO3 thin films deposited by pulsed spray pyrolysis technique
Authors: El Desouky Fawzy G. , Moussa I. , Obaida M.
Published: March 2024

Pure nanostructured thin films of nickel stannite (NiSnO3; NSO) semiconducting oxide are synthesized by a simple pulsed spray pyrolysis technique on glass substrates at different deposition temperatures and spray times. XRD recorded patterns exhibit a polycrystalline nature for the deposited films. The Raman spectra provide confirmation of the presence of Sn–O and Ni–O bands. FESEM demonstrates a membrane-like structure with hexagonal pores’ formation and different diameter sizes. The NSO energy bandgap is calculated to be 3.72 eV using the absorption spectrum fitting method. The photoluminescence intensities of NSO films were found to fluctuate with the influence of deposited substrate temperature and spray time. The photo-sensing performance was examined by calculating the change in the resistance of the deposited films corresponding to the UV light exposure at room temperature. NSO samples prepared at high substrate temperatures, and long spray times perform the best dynamic photo-response for the UV illumination.

Graphical abstract
A novel Swin transformer approach utilizing residual multi-layer perceptron for diagnosing brain tumors in MRI images
Authors: Pacal Ishak
Published: March 2024

Serious consequences due to brain tumors necessitate a timely and accurate diagnosis. However, obstacles such as suboptimal imaging quality, issues with data integrity, varying tumor types and stages, and potential errors in interpretation hinder the achievement of precise and prompt diagnoses. The rapid identification of brain tumors plays a pivotal role in ensuring patient safety. Deep learning-based systems hold promise in aiding radiologists to make diagnoses swiftly and accurately. In this study, we present an advanced deep learning approach based on the Swin Transformer. The proposed method introduces a novel Hybrid Shifted Windows Multi-Head Self-Attention module (HSW-MSA) along with a rescaled model. This enhancement aims to improve classification accuracy, reduce memory usage, and simplify training complexity. The Residual-based MLP (ResMLP) replaces the traditional MLP in the Swin Transformer, thereby improving accuracy, training speed, and parameter efficiency. We evaluate the Proposed-Swin model on a publicly available brain MRI dataset with four classes, using only test data. Model performance is enhanced through the application of transfer learning and data augmentation techniques for efficient and robust training. The Proposed-Swin model achieves a remarkable accuracy of 99.92%, surpassing previous research and deep learning models. This underscores the effectiveness of the Swin Transformer with HSW-MSA and ResMLP improvements in brain tumor diagnosis. This method introduces an innovative diagnostic approach using HSW-MSA and ResMLP in the Swin Transformer, offering potential support to radiologists in timely and accurate brain tumor diagnosis, ultimately improving patient outcomes and reducing risks.
Aftereffects, High-Levelism and Gestalt Properties
Authors: Başoğlu Yavuz Recep
Published: March 2024

According to high-levelism, one can perceptually be aware of high-level properties such as natural kind properties. Against high-levelism, the Gestalt proposal suggests that instead of high-level properties, one can have a perceptual experience as of Gestalt properties, i.e., determinables of determinate low-level properties. When one looks at a bird, the high-levelist argues that one can perceive the property of being a bird, and the proponent of the Gestalt proposal argues that one first perceives the property of having the bird Gestalt (shared by all and only birds) and only post-perceptually recognizes that it is a bird. In the present study, to resolve the dispute between high-levelism and the Gestalt proposal, I aim to test their abilities to explain the attribution of multiple perceptible properties to the same object by making use of various empirical studies on high-level aftereffects. I conclude that the Gestalt proposal fails the test and hence shall not be a viable alternative to high-levelism.
The practice of historical ecology: What, when, where, how and what for
Authors: Santana-Cordero Aarón Moisés , Szabó Péter , Bürgi Matthias , Armstrong Chelsey Geralda
Published: March 2024

In recent decades, there has been a growing number of studies exploring the historical dimensions of the interconnectedness of human societies and the environment. A core approach in this field is historical ecology. We analyzed 544 historical-ecological papers to assess patterns and trends in the field. We found a high degree of interdisciplinarity with a focus on local case studies, of periods of fewer than 500 years, analyzing archival sources through quantitative approaches. The proportion of papers containing management recommendations has increased over time. To make historical ecology globally relevant, more effort should be made to utilize studies across languages, borders and worldviews. We call for high standards regarding the use of social scientific methodologies. Lastly, we argue that fostering longer-term studies and assessing the real-life impact of policy recommendations emerging from historical ecology can help the discipline better contribute solutions to the challenges facing humanity in an uncertain future.
Acceleration-Based Switching Surfaces for Impulsive Trajectory Design Between Cislunar Libration Point Orbits
Authors: Saloglu Keziban , Taheri Ehsan
Published: March 2024

A method is proposed to generate an initial guess for impulsive trajectory design in the circular restricted three-body problem. The method uses acceleration-based switching surfaces to obtain near-impulsive solutions. A numerical continuation is performed on the maximum acceleration value to find near-impulsive solutions. A nonlinear programming problem is formulated by providing primer vector based analytical gradients. The solution space is narrowed down to aid the optimizer with the use of the near-impulsive solutions. The proposed method is used for the trajectory design of four different maneuvers between L1 and L2 Halo orbits in the Earth–Moon system. The results demonstrate the utility of the proposed method in generating extremal impulsive trajectories.
Ælfrician Homilies and Varia
Authors: Kleist Aaron J. , Upchurch Robert K.
Published: March 2024

This is the first modern edition and translation of the homilies of one of the most important religious figures of his time.
Patterson–Sullivan theory for groups with a strongly contracting element
Authors: COULON RÉMI
Published: March 2024

Using Patterson–Sullivan measures, we investigate growth problems for groups acting on a metric space with a strongly contracting element.
A comprehensive diagnostic system of ultra-thin liquid sheet targets
Authors: Peng Ziyang , Cao Zhengxuan , Liu Xuan , Shou Yinren , Zhao Jiarui , Chen Shiyou , Gao Ying , Wang Pengjie , Mei Zhusong , Pan Zhuo , Kong Defeng , Xu Shirui , Liu Zhipeng , Liang Yulan , Xu Tianqi , Song Tan , Chen Xun , Wu Qingfan , Zhang Yujia , Zhang Zihao , Yan Xueqin , Ma Wenjun
Published: March 2024

To meet the demands of laser-ion acceleration at a high repetition rate, we have developed a comprehensive diagnostic system for real-time and in situ monitoring of liquid sheet targets (LSTs). The spatially resolved rapid characterizations of an LST’s thickness, flatness, tilt angle and position are fulfilled by different subsystems with high accuracy. With the help of the diagnostic system, we reveal the dependence of thickness distribution on collision parameters and report the 238-nm liquid sheet generated by the collision of two liquid jets. Control methods for the flatness and tilt angle of LSTs have also been provided, which are essential for applications of laser-driven ion acceleration and others.
Exploring slip effects of ferrofluid film flow over a slanted rough surface
Authors: Bhandari Anupam , Parmar K.P.S.
Published: March 2024

We examined the influences of slip parameters on the velocity and thermal characteristics of a ferrofluid film of fixed thickness. The flow is generated on a rough and inclined whirling surface that is positioned in an external magnetic (dipole) field. The similarity transformation reduces the model equations (continuity, momentum, energy and concentration), and the solution of the normalized coupled ordinary differential equations is carried out through the finite element process. The influences of slip effects, Brownian motion, thermophoresis and a heat source on the velocity (radial, tangential and axial), gravity (drainage, induced), temperature profile and concentration profile are determined. The tangential flow and temperature are both decreased by an increase in the velocity slip parameter, whereas drainage, induced, radial and axial flows are increased. Enlarging the thermal slip parameter decreases the temperature. Improving slip parameters (velocity and thermal) also improves the concentration profile. Both Nusselt and Sherwood numbers are found to improve on improving the velocity slip parameter, while they decrease on decreasing the thermal slip parameter. The results and insights from this work could be applied to a wide range of medicinal fields, such as targeted medication therapy and delivery, tissue engineering, etc. as well as different industrial processes including coating, lubrication, heat transfer, etc.
New records and range extension of two deep-sea skate genera,AmblyrajaandNotoraja(Elasmobranchii: Rajiformes), in the southeastern Pacific Ocean
Authors: Zavalaga Fabiola , Contreras Ignacio , Campos-León Sarita , Moreno-Méndez Andrey , Saldarriaga Maritza
Published: March 2024

Two species of deep-sea skates,Amblyraja frerichsiandNotoraja martinezi, are reported for the first time in Peruvian waters, representing the first record of their respective genera from the country. Earlier,A.frerichsiwas known from both the southwestern Atlantic (off Brazil, Uruguay, and Argentina) and southeastern Pacific (off Chile), whileN.martineziwas known from Costa Rica to Ecuador in the eastern-central and southeastern Pacific. This study contributes to the limited knowledge of deep-sea fish diversity along the South American west coast, and stresses the need of further taxonomic research in the region, particularly in light of the ecological importance of this group of fishes in marine ecosystems and its conservation state worldwide.
HTA community perspectives on the use of patient preference information: lessons learned from a survey with members of HTA bodies
Authors: Hiligsmann Mickael , Liden Barry , Beaudart Charlotte , Germeni Evi , Hanna Alissa , Joshi Maya , Koola Catherine P. , Stein Barry , Tonkinson Mandy , Marshall Deborah , Fifer Simon
Published: March 2024

This research sought to assess whether and how patient preference (PP) data are currently used within health technology assessment (HTA) bodies and affiliated organizations involved in technology/drug appraisals and assessments. An exploratory survey was developed by the PP Project Subcommittee of the HTA International Patient and Citizen Involvement Interest Group to gain insight into the use, impact, and role of PP data in HTA, as well as the perceived barriers to its incorporation. Forty members of HTA bodies and affiliated organizations from twelve countries completed the online survey. PP data were reported to be formally considered as part of the HTA evidence review process by 82.5 percent of the respondents, while 39.4 percent reported that most of the appraisals and assessments within their organization in the past year had submitted PP data. The leading reason for why PP data were not submitted in most assessments was time/resource constraints followed by lack of clarity on PP data impact. Participants reported that PP data had a moderate level of influence on the deliberative process and outcome of the decision, but a higher level of influence on the decision’s quality. Most (81.8 percent) felt patient advocacy groups should be primarily responsible for generating and submitting this type of evidence. Insights from the survey confirm the use of PP data in HTA but reveal barriers to its broader and more meaningful integration. Encouragingly, participants believe obstacles can be overcome, paving the way for a second phase of research involving in-depth collaborative workshops with HTA representatives.
Trait anxiety predicting the developmental trajectories of depression symptoms in children: The mediating role of attentional control
Authors: Zhang Qiaochu
Published: March 2024

Trait anxiety and attentional control are important factors related to depression symptoms. The study investigated how trait anxiety and attentional control predicted the trajectories of depression symptoms during the transition into early adolescence. The mediating effect of attentional control on the relationship of trait anxiety to the trajectories of depression symptoms was also examined. Children of 9 to 10 years were recruited at Time 1. Trait anxiety, attentional control, and depression symptoms were assessed at Time 1. Depression symptoms were measured at three follow-up assessments across 18 months. Latent class growth modeling revealed high (14.4%) and low (85.6%) trajectories of depression symptoms. Higher trait anxiety and lower attentional control predicted a higher likelihood of showing the trajectory of high depressive symptoms. Attentional control mediated the relationship of trait anxiety to the trajectory membership of depression symptoms. The findings had important implications for the association of trait anxiety with the trajectory membership of depression symptoms and highlighted the importance of attentional control in the development of depression symptoms for children with high trait anxiety.
Accounting for Carbon Pricing in Third Countries Under the EU Carbon Border Adjustment Mechanism
Authors: Boute Anatole
Published: March 2024

To avoid penalizing exporters that already paid carbon prices, the EU Carbon Border Adjustment Mechanism credits carbon taxes and Emissions Trading Schemes in third countries. By excluding instruments of traditional regulation (e.g. emission standards) and indirect carbon prices (e.g. fuel excise taxes) from this crediting mechanism, the EU is criticized for discriminating against countries that do not follow its climate model, in breach of international trade and climate law. This article seeks to nuance this criticism by arguing that the calculation of actual emissions (instead of default values) under the EU CBAM allows exporters to reflect compliance with foreign emission standards, and thus respects states' right to pursue emission reductions through traditional regulation. However, amendments of the CBAM Regulation are necessary to recognize the positive and negative impact of indirect carbon prices on decarbonization, and the role of carbon-crediting mechanisms in equalizing carbon costs in a more flexible and equitable way.
Using an intersectionality-based approach to evaluate mental health services use among gay, bisexual and other men who have sex with men in Montreal, Toronto and Vancouver
Authors: Marbaniang Ivan , Moodie Erica E. M. , Latimer Eric , Skakoon-Sparling Shayna , Hart Trevor A. , Grace Daniel , Moore David M. , Lachowsky Nathan J. , Jollimore Jody , Lambert Gilles , Zhang Terri , Dvorakova Milada , Cox Joseph ,   Engage Team Members
Published: March 2024

Aims

To cope with homonegativity-generated stress, gay, bisexual and other men who have sex with men (GBM) use more mental health services (MHS) compared with heterosexual men. Most previous research on MHS among GBM uses data from largely white HIV-negative samples. Using an intersectionality-based approach, we evaluated the concomitant impact of racialization and HIV stigma on MHS use among GBM, through the mediating role of perceived discrimination (PD).

Methods

We used baseline data from 2371 GBM enrolled in the Engage cohort study, collected between 2017 and 2019, in Montreal, Toronto and Vancouver, using respondent-driven sampling. The exposure was GBM groups:Group 1(n= 1376): white HIV-negative;Group 2(n= 327): white living with HIV;Group 3(n= 577): racialized as non-white HIV-negative;Group 4(n= 91): racialized as non-white living with HIV. The mediator was interpersonal PD scores measured using the Everyday Discrimination Scale (5-item version). The outcome was MHS use (yes/no) in the prior 6 months. We fit a three-way decomposition of causal mediation effects utilizing the imputation method for natural effect models. We obtained odds ratios (ORs) for pure direct effect (PDE, unmediated effect), pure indirect effect (PIE, mediated effect), mediated interaction effect (MIE, effect due to interaction between the exposure and mediator) and total effect (TE, overall effect). Analyses controlled for age, chronic mental health condition, Canadian citizenship, being cisgender and city of enrolment.

Results

Mean PD scores were highest for racialized HIV-negative GBM (10.3, SD: 5.0) and lowest for white HIV-negative GBM (8.4, SD: 3.9). MHS use was highest in white GBM living with HIV (GBMHIV) (40.4%) and lowest in racialized HIV-negative GBM (26.9%). Compared with white HIV-negative GBM, white GBMHIV had higher TE (OR: 1.71; 95% CI: 1.27, 2.29) and PDE (OR: 1.68; 95% CI: 1.27, 2.24), and racialized HIV-negative GBM had higher PIE (OR: 1.09; 95% CI: 1.02, 1.17). Effects for racialized GBMHIV did not significantly differ from those of white HIV-negative GBM. MIEs across all groups were comparable.

Conclusions

Higher MHS use was observed among white GBMHIV compared with white HIV-negative GBM. PD positively mediated MHS use only among racialized HIV-negative GBM. MHS may need to take into account the intersecting impact of homonegativity, racism and HIV stigma on the mental health of GBM.
Vocabulary acquisition in the language classroom: what it is, how it works, which strategies and approaches are suitable for Latin instruction
Authors: Aguilar García María Luisa
Published: March 2024

This paper aims to guide the training of all Latin instructors and learners who want to optimise the process of acquiring the language by applying the results of research carried out in the field of Second Language Acquisition (SLA), specifically here those related to the acquisition of vocabulary. Consequently, some theoretical considerations on the psycholinguistic operations that govern vocabulary learning are first offered, in order to build a better understanding of language acquisition and to make instructors and learners more knowledgeable about the vocabulary learning process, from the noticing of an unknown word and its integration into the subject's competence to the expansion and development of knowledge about the acquired words. The theoretical aspects of vocabulary learning will be illustrated at all times with practical examples taken from methods and books for learning Latin, as well as, in the fourth section, with a wide catalogue of practical advice – must-do items for the class – that can be easily implemented by Latin instructors.
Dehumanization and the Association With Nonsuicidal Self-Injury and Suicidal Ideation in an Incarcerated Population
Authors: Robison Morgan , Abderhalden Frances P. , Joiner Thomas E.
Published: March 2024

Abstract: Background: Self-injurious and suicidal thoughts create critical concerns for incarcerated populations, yet relatively little is known about how they are formed and perpetuated within US jails. Dehumanization has been presented as a potentially novel risk factor toward aspects of self-harm; thus, this study assessed the perception of dehumanization from officers by those currently incarcerated. Methods: Across two jail settings ( n = 410), self-report surveys were administered asking questions relating to perception of officer dehumanization alongside aspects of nonsuicidal self-injury (NSSI) and suicidal ideation. Results: The findings indicate that perceived officer dehumanization is associated with NSSI thoughts, actively seeking NSSI, and suicidal ideation in jail, but not with NSSI in jail. Limitations: These data are cross-sectional, thus future work should examine the temporal order of these relationships. Conclusions: Perceptions of officer dehumanization appear to be clinically relevant in jail settings; therefore, future research should longitudinally determine how dehumanization imparts suicide risk.
A Theory of Maximum Entropy Production and Its Application to Microwave Remote Sensing—Simultaneous Retrieval of Soil Moisture and Vegetation Water Content
Authors: Wang J. , Cho K. , Negron‐Juarez R. I. , Colliander A. , Caravasi E. C. , Revilla N. S.
Published: March 2024

A theory of maximum entropy production (MEP) for electromagnetic wave propagation in dielectric materials is proposed and applied to simultaneously retrieving soil moisture (SM) and vegetation water content (VWC) from L‐band microwave brightness temperature (TB). One representation of the MEP principle states that a non‐equilibrium system corresponds to such a configuration of energy fluxes that minimizes a dissipation function under the constraint of energy conservation. The dissipation function for radiative transfer is formulated as an analogy of that for heat transfer. A new physical parameter, radiative inertia as an analogy of thermal inertia, is introduced to characterize radiative attenuation in dielectric media. The radiative inertia is parameterized in terms of the penetration depth of electromagnetic waves as a function of the complex dielectric constant. The MEP based retrieval algorithm predicts SM and VWC by minimizing the dissipation function under the constraint of the conservation of radiative energy. The retrievals of SM and VWC based on the MEP theory were validated against field observations in tropical and temperate forested regions of the Amazon and North America. The proof‐of‐concept analysis demonstrates the capability of the MEP algorithm for simultaneous retrievals of SM and VWC even for dense canopy (e.g., VWC > 5 kg m−2). The MEP method is a new theoretical framework for developing innovative remote sensing algorithms of the Earth system not limited to microwave observations.
Variability of Eddy Kinetic Energy in the Eurasian Basin of the Arctic Ocean Inferred From a Model Simulation at 1‐km Resolution
Authors: Müller Vasco , Wang Qiang , Koldunov Nikolay , Danilov Sergey , Sidorenko Dmitry , Jung Thomas
Published: March 2024

Mesoscale eddies play an important role in driving the dynamics of the Arctic Ocean. Understanding their behavior is crucial for comprehending the ongoing changes in the region. In this study, by using a novel decade‐long simulation at 1 km resolution with the unstructured‐mesh Finite volumE Sea ice‐Ocean Model, we evaluate the spatial and temporal variability of eddy kinetic energy in the Eurasian Basin. We find that monthly, annual, and interannual variability of EKE near the surface is predominantly influenced by changes in sea ice cover, while the eddy activity at deeper depth, being shielded from the surface by ocean stratification, is more strongly influenced by local baroclinic energy conversion. Moreover, our research demonstrates that eddies in the Eurasian Basin can transport ocean heat from the Atlantic Water layer toward sea ice and cause local basal melting in the order of about 20 cm per month even in wintertime. Our study suggests that eddy activity in the Arctic Ocean will strengthen along with future sea ice decline, and that the impact of ocean heat of the Atlantic Water layer on sea ice retreat may become prominent.
Tectonic Evolution of the Eastern Southern Alps (Italy): A Reappraisal From New Structural Data and Geochronological Constraints
Authors: Curzi Manuel , Viola Giulio , Zuccari Costantino , Aldega Luca , Billi Andrea , van der Lelij Roelant , Kylander‐Clark Andrew , Vignaroli Gianluca
Published: March 2024

The Eastern Southern Alps fold‐and‐thrust belt (ESA) is part of the seismically active S‐verging retro‐wedge of the European Alps. Its temporal tectonic evolution during continental shortening has so far been constrained by few and low‐resolution indirect time constraints. Aiming at better elucidating the ESA spatiotemporal evolution, we gathered new structural and geochronological data from two regional thrust systems: the innermost south verging Valsugana Thrust (VT) and the more external Belluno Thrust System (BTS). Field work allowed us to constrain the geometry and kinematics of those thrusts and related folds and informed our sampling strategy to carry out fault gouge K‐Ar and tectonic carbonate U‐Pb dating from representative samples structurally associated with the VT and BTS. Our results suggest that the VT was active already in the Late Cretaceous (between ∼78 and 76 Ma) in response to far‐field stresses, with repeated reactivation continuing to the Late Miocene (∼6 Ma). The BTS recorded two distinct deformation events during the Oligocene (∼30 Ma) and at the Oligocene‐Miocene boundary (∼23 Ma). The VT was active for ∼72 Myr and partly acted during out‐of‐sequence thrusting. Based on regional correlations, we propose that the ESA share a similar spatiotemporal deformation history with the central Southern Alps farther to the west. We suggest a conceptual regional tectonic model wherein multiple, broadly coeval deformation events occurred in the entire Southern Alps during their long‐lived orogenic deformation in response to generally continuous NW‐SE shortening.
Rebuilding the microenvironment of primary tumors in humans: a focus on stroma
Authors: Mun Siwon , Lee Hyun Jin , Kim Pilnam
Published: March 2024

Conventional tumor models have critical shortcomings in that they lack the complexity of the human stroma. The heterogeneous stroma is a central compartment of the tumor microenvironment (TME) that must be addressed in cancer research and precision medicine. To fully model the human tumor stroma, the deconstruction and reconstruction of tumor tissues have been suggested as new approaches for in vitro tumor modeling. In this review, we summarize the heterogeneity of tumor-associated stromal cells and general deconstruction approaches used to isolate patient-specific stromal cells from tumor tissue; we also address the effect of the deconstruction procedure on the characteristics of primary cells. Finally, perspectives on the future of reconstructed tumor models are discussed, with an emphasis on the essential prerequisites for developing authentic humanized tumor models.
The Mst1/2-BNIP3 axis is required for mitophagy induction and neuronal viability under mitochondrial stress
Authors: Jeong Dae Jin , Um Jee-Hyun , Kim Young Yeon , Shin Dong Jin , Im Sangwoo , Lee Kang-Min , Lee Yun-Hee , Lim Dae-sik , Kim Donghoon , Yun Jeanho
Published: March 2024

Mitophagy induction upon mitochondrial stress is critical for maintaining mitochondrial homeostasis and cellular function. Here, we found that Mst1/2 (Stk3/4), key regulators of the Hippo pathway, are required for the induction of mitophagy under various mitochondrial stress conditions. Knockdown of Mst1/2 or pharmacological inhibition by XMU-MP-1 treatment led to impaired mitophagy induction upon CCCP and DFP treatment. Mechanistically, Mst1/2 induces mitophagy independently of the PINK1-Parkin pathway and the canonical Hippo pathway. Moreover, our results suggest the essential involvement of BNIP3 in Mst1/2-mediated mitophagy induction upon mitochondrial stress. Notably, Mst1/2 knockdown diminishes mitophagy induction, exacerbates mitochondrial dysfunction, and reduces cellular survival upon neurotoxic stress in both SH-SY5Y cells and Drosophila models. Conversely, Mst1 and Mst2 expression enhances mitophagy induction and cell survival. In addition, AAV-mediated Mst1 expression reduced the loss of TH-positive neurons, ameliorated behavioral deficits, and improved mitochondrial function in an MPTP-induced Parkinson’s disease mouse model. Our findings reveal the Mst1/2-BNIP3 regulatory axis as a novel mediator of mitophagy induction under conditions of mitochondrial stress and suggest that Mst1/2 play a pivotal role in maintaining mitochondrial function and neuronal viability in response to neurotoxic treatment.
Teclistamab in relapsed refractory multiple myeloma: multi-institutional real-world study
Authors: Mohan Meera , Monge Jorge , Shah Nishi , Luan Danny , Forsberg Mark , Bhatlapenumarthi Vineel , Balev Metodi , Patwari Anannya , Cheruvalath Heloise , Bhutani Divaya , Thanendrarajan Sharmilan , Dhakal Binod , Zangari Maurizio , Al-Hadidi Samer , Cooper Dennis , Lentzsch Suzanne , van Rhee Frits , D’Souza Anita , Szabo Aniko , Schinke Carolina , Chakraborty Rajshekhar
Published: March 2024

The objective of our study was to report real-world data on the safety and efficacy of standard-of-care teclistamab in patients with relapsed/refractory multiple myeloma (MM). This is a multi-institutional retrospective cohort study and included all consecutive patients that received at least one dose of teclistamab up until August 2023. One hundred and ten patients were included, of whom, 86% had triple-class refractory disease, 76% penta-refractory disease, and 35% had prior exposure to B-cell maturation antigen (BCMA)-targeting therapies. The overall response rate (ORR) in our cohort was 62%, with a ≥ very good partial remission (VGPR) rate of 51%. The ORR in patients with and without prior BCMA-targeted therapies was 54% vs 67%, respectively (p = 0.23). At a median follow-up of 3.5 months (range, 0.39–10.92), the estimated 3 month and 6 month progression free survival (PFS) was 57% (95% CI, 48%, 68%) and 52% (95% CI, 42%, 64%) respectively. The incidence of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) was 56% and 11% respectively, with grade ≥3 CRS and ICANS noted in 3.5% and 4.6% of patients respectively. 78 unique infections were diagnosed in 44 patients, with the incidence of all-grade and grade ≥3 infections being 40% vs 26% respectively. Primary prophylaxis with intravenous immunoglobulin (IVIG) was associated with a significantly lower infection risk on multivariate analysis (Hazard ratio [HR] 0.33; 95% CI 0.17, 0.64; p = 0.001).
Harmonizing definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism in allogeneic hematopoietic cell transplantation: a report on behalf of the EBMT, ASTCT, CIBMTR, and APBMT
Authors: Sureda Anna , Carpenter Paul A. , Bacigalupo Andrea , Bhatt Vijaya Raj , de la Fuente Josu , Ho Aloysius , Kean Leslie , Lee Jong Wook , Sánchez-Ortega Isabel , Savani Bipin N. , Schetelig Johannes , Stadtmauer Edward A. , Takahashi Yoshiyuki , Atsuta Yoshiko , Koreth John , Kröger Nicolaus , Ljungman Per , Okamoto Shinichiro , Popat Uday , Soiffer Robert , Stefanski Heather E. , Kharfan-Dabaja Mohamed A.
Published: March 2024

Despite emergence of novel therapies to treat hematologic malignancies, allogeneic hematopoietic cell transplantation (allo-HCT) remains an essential treatment modality capable of curing these diseases. Allo-HCT has been also shown to be curative in benign hematologic disorders such as aplastic anemia, sickle cell disease, and thalassemia, among others. Recently, the American Society for Transplantation and Cellular Therapy (ASTCT) published standardized definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism. To attempt broader international consensus, a panel of adult and pediatric physician transplant experts was assembled from European Society for Blood and Marrow Transplantation (EBMT), ASTCT, the Center for International Blood and Marrow Transplant Research (CIBMTR), and Asia-Pacific Blood and Marrow Transplantation (APBMT). Consensus was defined as ≥70% of voting members strongly agreeing or somewhat agreeing with a definition. With few exceptions, there was a consensus to endorse the prior ASTCT definitions. Importantly, we revised existing EBMT and CIBMTR data collection forms to align with these harmonized definitions that will facilitate research and international collaboration among transplant researchers and across transplant registries.
Environmental sustainability: the attitudes and experiences of UK students in the oral health care profession
Authors: Durnall Olivia , Martin Nicolas , Mulligan Steven , Dixon Jonathan
Published: March 2024

Objective This study aims to provide insight into the attitudes and perspectives of undergraduate dental students from UK dental schools regarding environmental sustainability in dentistry (ESD) and the manner and extent in which ESD is included in the current undergraduate oral health care curricula.

Methods This study is a multi-centre, nationally representive study involving a cross-sectional online survey of undergraduate Bachelor of Dental Surgery and dental hygiene and therapy students in UK-based dental schools. Data analysis was conducted through descriptive statistics and thematic analysis.

Results In total, 263 students from 13 UK schools completed the survey, resulting in a national school response rate of 68.4%. Key findings are: 97.3% of students believe that the dental profession should be more actively engaged in environmental sustainability but students currently have very little exposure to ESD at an undergraduate level; and 76.8% of students expressed that they are concerned about the impact that oral health care provision has on the environment, but only 23% of students have independently researched ESD.

Conclusions Students identify that oral health care professionals should become more engaged in efforts to mitigate the negative impacts from our activities on the environment, principally via education at all levels. The data from this study provide insight into the current level of awareness and concerns for the environmental impacts of oral health care provision, and are a powerful driver for the inclusion of ESD into the undergraduate curriculum in UK based dental schools.
Development of NK cell-based cancer immunotherapies through receptor engineering
Authors: Page Audrey , Chuvin Nicolas , Valladeau-Guilemond Jenny , Depil Stéphane
Published: March 2024

Natural killer (NK) cell-based immunotherapies are attracting increasing interest in the field of cancer treatment. Early clinical trials have shown promising outcomes, alongside satisfactory product efficacy and safety. Recent developments have greatly increased the therapeutic potential of NK cells by endowing them with enhanced recognition and cytotoxic capacities. This review focuses on surface receptor engineering in NK cell therapy and discusses its impact, challenges, and future directions.

Most approaches are based on engineering with chimeric antigen receptors to allow NK cells to target specific tumor antigens independent of human leukocyte antigen restriction. This approach has increased the precision and potency of NK-mediated recognition and elimination of cancer cells. In addition, engineering NK cells with T-cell receptors also mediates the recognition of intracellular epitopes, which broadens the range of target peptides. Indirect tumor peptide recognition by NK cells has also been improved by optimizing immunoglobulin constant fragment receptor expression and signaling. Indeed, engineered NK cells have an improved ability to recognize and destroy target cells coated with specific antibodies, thereby increasing their antibody-dependent cellular cytotoxicity. The ability of NK cell receptor engineering to promote the expansion, persistence, and infiltration of transferred cells in the tumor microenvironment has also been explored. Receptor-based strategies for sustained NK cell functionality within the tumor environment have also been discussed, and these strategies providing perspectives to counteract tumor-induced immunosuppression.

Overall, receptor engineering has led to significant advances in NK cell-based cancer immunotherapies. As technical challenges are addressed, these innovative treatments will likely reshape cancer immunotherapy.
Himplant® subcutaneous penile implant improves penile appearance and erectile dysfunction after radical prostatectomy: a case series
Authors: Valenzuela Robert J. , Elist James J. , Moon Daniel , Cvijanovic Luka , Wilson Steven K.
Published: March 2024

Erectile dysfunction is a major postoperative complication following radical prostatectomy. Various treatments for post- radical prostatectomy erectile dysfunction including nonsurgical phosphodiesterase-5 inhibitors, intraurethral alprostadil, intracavernosal injections and penile implant prosthesis, often yield suboptimal results. In this prospective single-center case series, we examine the efficacy and outcomes of Himplant®, a subcutaneous silicone penile implant, placement in four patients with post-radical prostatectomy erectile dysfunction who experienced limited benefits with phosphodiesterase-5 inhibitors. Patient data including demographics, prostate cancer diagnoses, erectile dysfunction characteristics, previous treatments, and outcomes were collected. Himplant® placement was performed in a standardized manner through a high scrotal incision in all cases. Follow-up evaluations were conducted to assess the effectiveness of the procedure and any associated complications. Patients were contacted and asked 15 questions regarding satisfaction and erectile function with the responses recorded. This study presents findings of high patient satisfaction, increases in flaccid penile length and girth, no incidence of adverse events, and improved erectile function following Himplant® placement post-radical prostatectomy. Accordingly, we suggest Himplant® placement in patients who are frustrated by their penile appearance and suffering from erectile dysfunction after radical prostatectomy. Further multicenter studies are warranted to validate these findings and assess long-term outcomes and patient-reported satisfaction.
Janus microparticles-based targeted and spatially-controlled piezoelectric neural stimulation via low-intensity focused ultrasound
Authors: Han Mertcan , Yildiz Erdost , Bozuyuk Ugur , Aydin Asli , Yu Yan , Bhargava Aarushi , Karaz Selcan , Sitti Metin
Published: March 2024

Electrical stimulation is a fundamental tool in studying neural circuits, treating neurological diseases, and advancing regenerative medicine. Injectable, free-standing piezoelectric particle systems have emerged as non-genetic and wireless alternatives for electrode-based tethered stimulation systems. However, achieving cell-specific and high-frequency piezoelectric neural stimulation remains challenging due to high-intensity thresholds, non-specific diffusion, and internalization of particles. Here, we develop cell-sized 20 μm-diameter silica-based piezoelectric magnetic Janus microparticles (PEMPs), enabling clinically-relevant high-frequency neural stimulation of primary neurons under low-intensity focused ultrasound. Owing to its functionally anisotropic design, half of the PEMP acts as a piezoelectric electrode via conjugated barium titanate nanoparticles to induce electrical stimulation, while the nickel-gold nanofilm-coated magnetic half provides spatial and orientational control on neural stimulation via external uniform rotating magnetic fields. Furthermore, surface functionalization with targeting antibodies enables cell-specific binding/targeting and stimulation of dopaminergic neurons. Taking advantage of such functionalities, the PEMP design offers unique features towards wireless neural stimulation for minimally invasive treatment of neurological diseases.
ALKBH5-mediated m6A modification of IL-11 drives macrophage-to-myofibroblast transition and pathological cardiac fibrosis in mice
Authors: Zhuang Tao , Chen Mei-Hua , Wu Ruo-Xi , Wang Jing , Hu Xi-De , Meng Ting , Wu Ai-Hua , Li Yan , Yang Yong-Feng , Lei Yu , Hu Dong-Hua , Li Yan-Xiu , Zhang Li , Sun Ai-Jun , Lu Wei , Zhang Guan-Nan , Zuo Jun-Li , Ruan Cheng-Chao
Published: March 2024

Cardiac macrophage contributes to the development of cardiac fibrosis, but factors that regulate cardiac macrophages transition and activation during this process remains elusive. Here we show, by single-cell transcriptomics, lineage tracing and parabiosis, that cardiac macrophages from circulating monocytes preferentially commit to macrophage-to-myofibroblast transition (MMT) under angiotensin II (Ang II)-induced hypertension, with accompanying increased expression of the RNA N6-methyladenosine demethylases, ALKBH5. Meanwhile, macrophage-specific knockout of ALKBH5 inhibits Ang II-induced MMT, and subsequently ameliorates cardiac fibrosis and dysfunction. Mechanistically, RNA immunoprecipitation sequencing identifies interlukin-11 (IL-11) mRNA as a target for ALKBH5-mediated m6A demethylation, leading to increased IL-11 mRNA stability and protein levels. By contrast, overexpression of IL11 in circulating macrophages reverses the phenotype in ALKBH5-deficient mice and macrophage. Lastly, targeted delivery of ALKBH5 or IL-11 receptor α (IL11RA1) siRNA to monocytes/macrophages attenuates MMT and cardiac fibrosis under hypertensive stress. Our results thus suggest that the ALKBH5/IL-11/IL11RA1/MMT axis alters cardiac macrophage and contributes to hypertensive cardiac fibrosis and dysfunction in mice, and thereby identify potential targets for cardiac fibrosis therapy in patients.
Distinct pathways drive anterior hypoblast specification in the implanting human embryo
Authors: Weatherbee Bailey A. T. , Weberling Antonia , Gantner Carlos W. , Iwamoto-Stohl Lisa K. , Barnikel Zoe , Barrie Amy , Campbell Alison , Cunningham Paula , Drezet Cath , Efstathiou Panagiota , Fishel Simon , Vindel Sandra Gutiérrez , Lockwood Megan , Oakley Rebecca , Pretty Catherine , Chowdhury Nabiha , Richardson Lucy , Mania Anastasia , Weavers Lauren , Christie Leila , Elder Kay , Snell Phillip , Zernicka-Goetz Magdalena
Published: March 2024

Development requires coordinated interactions between the epiblast, which generates the embryo proper; the trophectoderm, which generates the placenta; and the hypoblast, which forms both the anterior signalling centre and the yolk sac. These interactions remain poorly understood in human embryogenesis because mechanistic studies have only recently become possible. Here we examine signalling interactions post-implantation using human embryos and stem cell models of the epiblast and hypoblast. We find anterior hypoblast specification is NODAL dependent, as in the mouse. However, while BMP inhibits anterior signalling centre specification in the mouse, it is essential for its maintenance in human. We also find contrasting requirements for BMP in the naive pre-implantation epiblast of mouse and human embryos. Finally, we show that NOTCH signalling is important for human epiblast survival. Our findings of conserved and species-specific factors that drive these early stages of embryonic development highlight the strengths of comparative species studies.
Social perception of robots is shaped by beliefs about their minds
Authors: Momen Ali , Hugenberg Kurt , Wiese Eva
Published: March 2024

Roboticists often imbue robots with human-like physical features to increase the likelihood that they are afforded benefits known to be associated with anthropomorphism. Similarly, deepfakes often employ computer-generated human faces to attempt to create convincing simulacra of actual humans. In the present work, we investigate whether perceivers’ higher-order beliefs about faces (i.e., whether they represent actual people or android robots) modulate the extent to which perceivers deploy face-typical processing for social stimuli. Past work has shown that perceivers’ recognition performance is more impacted by the inversion of faces than objects, thus highlighting that faces are processed holistically (i.e., as Gestalt), whereas objects engage feature-based processing. Here, we use an inversion task to examine whether face-typical processing is attenuated when actual human faces are labeled as non-human (i.e., android robot). This allows us to employ a task shown to be differentially sensitive to social (i.e., faces) and non-social (i.e., objects) stimuli while also randomly assigning face stimuli to seem real or fake. The results show smaller inversion effects when face stimuli were believed to represent android robots compared to when they were believed to represent humans. This suggests that robots strongly resembling humans may still fail to be perceived as “social” due pre-existing beliefs about their mechanistic nature. Theoretical and practical implications of this research are discussed.
Investigating the mechanisms underlying resistance to chemotherapy and to CRISPR-Cas9 in cancer cell lines
Authors: Tomasi Francesca , Pozzi Matteo , Lauria Mario
Published: March 2024

Cancer is one of the major causes of death worldwide and the development of multidrug resistance (MDR) in cancer cells is the principal cause of chemotherapy failure. To gain insights into the specific mechanisms of MDR in cancer cell lines, we developed a novel method for the combined analysis of recently published datasets on drug sensitivity and CRISPR loss-of-function screens for the same set of cancer cell lines. For our analysis, we first selected cell lines that consistently exhibit drug resistance across several classes of compounds. We then identified putative resistance genes for each class of compound and used inferred gene regulatory networks (GRNs) to study possible mechanisms underlying the development of MDR in the identified cancer cell lines. We show that the same method of analysis can also be used to identify cell lines that consistently exhibit resistance to the gene knockout effect of the CRISPR-Cas9 technique and to study the possible underlying mechanisms. In the GRN associated to the drug resistant cell lines, we identify genes previously associated with resistance (UHMK1, RALYL, MGST3, USP9X, and ESRG), genes for which an indirect association can be identified (SPINK13, LINC00664, MRPL38, and EMILIN3), and genes that are found to be overexpressed in non-resistant cancer cell lines (MRPL38, EMILIN3 and RALYL). In the GRNs associated to the CRISPR-Cas9 resistance mechanism, none of the identified genes has been previously reported in the admittedly sparse literature on the subject. However, some of these genes have a common role: APBB2, RUNX1T1, ZBTB7C, and ISX regulate transcription, while APBB2, BTG3, ZBTB7C, SZRD1 and LEF1 have a function in regulating proliferation, suggesting a role for these two pathways. While our results are specific for the lung cancer cell lines we selected for this work, our method of analysis can be applied to cell lines from other tissues and for which the required data is available.
Machine learning and XAI approaches highlight the strong connection between $$O_3$$ and $$NO_2$$ pollutants and Alzheimer’s disease
Authors: Fania Alessandro , Monaco Alfonso , Amoroso Nicola , Bellantuono Loredana , Cazzolla Gatti Roberto , Firza Najada , Lacalamita Antonio , Pantaleo Ester , Tangaro Sabina , Velichevskaya Alena , Bellotti Roberto
Published: March 2024

Alzheimer’s disease (AD) is the most common type of dementia with millions of affected patients worldwide. Currently, there is still no cure and AD is often diagnosed long time after onset because there is no clear diagnosis. Thus, it is essential to study the physiology and pathogenesis of AD, investigating the risk factors that could be strongly connected to the disease onset. Despite AD, like other complex diseases, is the result of the combination of several factors, there is emerging agreement that environmental pollution should play a pivotal role in the causes of disease. In this work, we implemented an Artificial Intelligence model to predict AD mortality, expressed as Standardized Mortality Ratio, at Italian provincial level over 5 years. We employed a set of publicly available variables concerning pollution, health, society and economy to feed a Random Forest algorithm. Using methods based on eXplainable Artificial Intelligence (XAI) we found that air pollution (mainly $$O_3$$

O
3

and $$NO_2$$

N

O
2

) contribute the most to AD mortality prediction. These results could help to shed light on the etiology of Alzheimer’s disease and to confirm the urgent need to further investigate the relationship between the environment and the disease.