bluuebunny/crossref_metadata_2025 huggingface dataset:
French liaison is allomorphy, not allophony: evidence from lexical statistics
Authors: Storme Benjamin
Published: September 2024

The exact nature of French liaison as a phonological or morphological alternation is still debated. Under the phonological analysis, liaison is allophony: liaison consonants are special phonemes that alternate between a consonant allophone and zero (e.g., [t] ∼ ∅), the zero allophone being derived from the consonant phoneme through deletion (/t/ → ∅). Under the morphological analysis, liaison is allomorphy: liaison words have two underlyingly listed allomorphs, a consonant-final allomorph and a shorter allomorph that lacks this consonant (e.g., grand ‘great’ /gʁɑ̃t, gʁɑ̃/). This paper uses evidence from lexical statistics to arbitrate between these two analyses. The form without liaison consonant (and with deletion, under the phonological analysis) has been found in previous research to become less likely with increasing lexical frequency. The paper shows that this is problematic for the phonological analysis of French liaison, as deletion typically applies more frequently in high-frequency words across languages. The paper further shows, using evidence from a large lexical database, that words involved in liaison alternations generally have lower type frequency but higher token frequency than non-liaison words when phonotactic and morphological effects on lexical frequency are controlled for. This result is in line with the predictions of the morphological analysis, as allomorphy typically involves a relatively small number of words that occur frequently. Due to its empirical nature, this argument constitutes to date one of the strongest arguments in favor of the morphological analysis.
Dynamics of Neurogenic Signals as Biological Switchers of Brain Plasticity
Authors: Moreira João F. , Solá Susana
Published: September 2024

The discovery of adult neurogenesis in the middle of the past century is considered one of the most important breakthroughs in neuroscience. Despite its controversial nature, this discovery shaped our concept of neural plasticity, revolutionizing the way we look at our brains. In fact, after the discovery of adult neurogenesis, we started to consider the brain as something even more dynamic and highly adaptable. In neurogenic niches, adult neurogenesis is supported by neural stem cells (NSCs). These cells possess a unique set of characteristics such as being quiescent for long periods while actively sensing and reacting to their surroundings to influence a multitude of processes, including the generation of new neurons and glial cells. Therefore, NSCs can be viewed as sentinels to our brain’s homeostasis, being able to replace damaged cells and simultaneously secrete numerous factors that restore regular brain function. In addition, it is becoming increasingly evident that NSCs play a central role in memory formation and consolidation. In this review, we will dissect how NSCs influence their surroundings through paracrine and autocrine types of action. We will also depict the mechanism of action of each factor. Finally, we will describe how NSCs integrate different and often opposing signals to guide their fate.

Graphical Abstract

Different signaling pathways responsible for signal integration of NSCs-secreted autocrine/paracrine signals: Numerous superficial receptors are stimulated upon contact with NSCs-secreted factors. Interestingly, this schematic representation of the different pathways shows how different signals often converge into the same pathway. This allows the NSC to adopt the correct behavior in response to external stimuli.
Tumour-associated macrophages in diffuse large B-cell lymphoma: the prognostic and therapeutic impact in a South African centre with high HIV seroprevalence
Authors: Vaughan Jenifer , Wiggill Tracey , Mia Zainab , Patel Moosa
Published: September 2024

Diffuse large B-cell lymphoma (DLBCL) is a common malignancy among people living with HIV. Macrophage enrichment of the tumour microenvironment (TME) is a prognostic factor in DLBCL among immunocompetent people, with some studies reporting that macrophage enrichment predicts a superior response to rituximab therapy. The macrophage phenotype is also important, with reportedly poorer outcomes with enrichment of anti-inflammatory (M2) macrophages. To date, the relationship between the type/number of tumour macrophages and outcomes in HIV-associated DLBCL (HIV-DLBCL) has been poorly explored. In this study, we assessed tumour macrophage numbers in a South African cohort of patients with DLBCL and a high HIV-seropositivity rate. Immunohistochemistry for CD68 and CD163 was performed on the diagnostic biopsies of 79 patients with DLBCL. Relevant information was documented from the clinical records, including disease stage, international-prognostic index score, HIV-related parameters, C-reactive protein, ferritin levels and immune cell numbers (monocytes, lymphocytes and neutrophils). Survival analysis was performed using Kaplan–Meier survival estimates, and the correlation between tumour macrophage numbers and a variety of immunological parameters was assessed using Spearman’s rho. Of the 79 patients included, 87.2% were living with HIV, and rituximab therapy was used in 46.9%. Tumour macrophage numbers were not related to HIV status, but low pro-inflammatory (M1) macrophage numbers (CD68 + CD163 −) were significantly associated with poorer outcomes (HR 2.02, p = 0.03). M2 macrophage (CD68 + CD163 +) enrichment was not predictive of survival but was associated with improved response to rituximab therapy (HR 0.19; p = 0.002). Macrophage numbers were marginally correlated with ferritin levels, which showed modest performance as a peripheral blood biomarker of the TME macrophage status (AUC 0.6 at a level of 374 µg/L), and high ferritin levels were associated with a superior response to rituximab-therapy (HR 0.28, p = 0.034). Pro-inflammatory macrophages are important in tumour control in HIV-DLBCL, while M2 macrophage enrichment improves the response to rituximab therapy. Ferritin shows promise as a biomarker for identifying patients more likely to benefit from rituximab therapy.
Give me your best shot! Diffusion of complete versus booster COVID-19 vaccines across US counties
Authors: Alfano Vincenzo , Capasso Salvatore , Goel Rajeev K. , Nelson Michael A.
Published: September 2024

This research compares drivers of full COVID-19 vaccinations and booster doses across US counties. Booster doses are contingent upon primary doses being received, and the risk attitudes and propensities to get vaccinated may respond to different motivations across individuals, along with distinctions in the supply chain. Our results, obtained in a quantitative framework through fractional probit, logit and quantile regressions, show that new COVID cases do not significantly impact vaccinations, while supply chain aspects via doctors’ visits have a positive impact. Income, race, age, and education also play a significant role. Further, political ideologies matter, while government decentralization does not. The differences in the effects across primary versus booster doses are discussed.
Rar, aber relevant: die seltene Biosphäre im Hoch-CO2-Untergrund Egergraben
Authors: Lipus Daniel , Jia Zeyu , Kallmeyer Jens
Published: September 2024

Understanding microbial behavior in high CO2 subsurface systems is pivotal for CO2 capture and mitigation and achieving long-term climate goals. Genomic analysis of sediments and enrichment cultures from the geologically active Eger Rift region emphasize the significance of the rare biosphere in such efforts. Despite being scarce in the native community, sulfate-reducing and methanogenic taxa became active under high CO2 and H2 conditions, highlighting their metabolic role in subsurface environments.
Neue Perspektiven der Aromaforschung: pilzliche O(S)-Methyltransferasen
Authors: Brescia Fabio F. , Zorn Holger , Rühl Martin
Published: September 2024

The demand for natural flavourings has driven a focus on enzymatic aroma production. Combining transcriptomics and aroma data unveiled a novel O-methyltransferase in Pleurotus sapidus, responsible for p-anisaldehyde formation. This enzyme catalysed the transmethylation of various aromatic compounds and a thiol nucleophile, classifying it as an O(S)-methyltransferase. The crystal structure was resolved at 2.0 Å, marking a significant milestone. These findings promise advances in natural flavour production.
The Influence of Playing Position on Physical, Physiological, and Technical Demands in Adult Male Soccer Matches: A Systematic Scoping Review with Evidence Gap Map
Authors: Sarmento Hugo , Martinho Diogo V. , Gouveia Élvio R. , Afonso José , Chmura Paweł , Field Adam , Savedra Nestor Ordoñez , Oliveira Rafael , Praça Gibson , Silva Rui , Barrera-Díaz Joel , Clemente Filipe Manuel
Published: September 2024

Background

There has been an increase in studies examining the demands of soccer relative to each playing position in recent years. Understanding the physical, physiological, and technical demands on soccer players according to their positional role during competitive matches is necessary to understand match requirements and develop position-specific training practices. Thereby, there is a clear need to synthesize the information on the different profiles of each playing position.

Objective

This review aimed to organize the literature investigating physical, physiological, and technical demands according to playing positions and provide a framework to identify gaps and suggestions for future studies.

Methods

A systematic search was conducted in October 2023 using four electronic databases: Web of Science, SPORTDiscus, PubMed and Scopus. The review followed PRISMA 2020 guidelines and the PRISMA-ScR extension for Scoping Reviews. The studies were included if the sample comprised adult male soccer players categorized from Tier 3 to Tier 5 (i.e., highly trained/national level, elite/international level, or world class) and compared the physical, physiological, or technical parameters across playing positions.

Results

A total of 178 studies met the inclusion criteria and were included in the review. The number of teams, players, and matches analyzed per study varied considerably. Although a range of classifications were reported across studies, 59% of studies classified players as central defenders, full-backs, central midfielders, wide midfielders, and forwards. The findings suggests that central and external midfielders, and external defenders cover greater total and high-speed distance than forwards or central defenders. Sprint distance was higher in external midfielders versus all other positions. Defenders and central midfielders perform more passes than external midfielders and forwards. Heart rate was the most commonly reported physiological variable across playing positions. When expressed as a percentage of maximal heart rate, midfielders presented higher mean values than all other playing positions.

Conclusion

This scoping review demonstrates that there are differences in the demands on players across playing positions in soccer. Training practices in soccer should be based on the specific requirements of each positional role to ensure players can fulfill their tactical responsibilities during the game.
The contribution of cognitive reserve in explaining the dual-task walking performance in iNPH patients: comparison with other cognitive, functional, and socio-demographic variables
Authors: Piche Elodie , Armand Stephane , Allali Gilles , Assal Frederic
Published: September 2024

Background

Idiopathic normal pressure hydrocephalus (iNPH) is a prevalent neurological disorder, but its diagnosis remains challenging. Dual-task (DT) walking performance is a reliable indicator of iNPH but less is known about the role of cognitive reserve (CR) in predicting DT walking performance.

Aims

The objective of this study was to evaluate the contribution of CR on DT walking in healthy controls (HC) and in iNPH patients (iNPH-P).

Methods

68 iNPH-P (77.2 +/- 6.7 years old) and 28 HC (74.5 +/- 5.7 years old) were evaluated on their single-task walking (Vsimple) and on 4 DT walking (walking and counting or counting backwards, naming animals, naming words beginning with the letter P) (Vcount, VcountB, Vanimals and Vletter respectively). The contribution of CR on the different DT walking speeds was compared between HC and iNPH-P. In iNPH-P, the contribution of CR on the walking speeds was compared with regard to other cognitive, functional, and socio-demographic variables.

Results

Simple linear regression demonstrated a moderate influence of CR on single and DT walking speed in iNPH-P (β > 0.3, p < .001) but not in HC where the relation was not significant. In iNPH-P, results showed that CR played a major role in explaining each of the single and DT walking speeds with NPH-scale.

Conclusion

As CR could be improved through the life cycle, these results support the idea of developing and supporting physical activity programs that will enrich social, physical, and cognitive resources to protect against age-related functional decline, especially in iNPH-P patients where the age-related deficits are greater.
“HIV Stigma Exists” — Exploring ChatGPT’s HIV Advice by Race and Ethnicity, Sexual Orientation, and Gender Identity
Authors: Criss Shaniece , Nguyen Thu T. , Gonzales Sarah M. , Lin Brian , Kim Melanie , Makres Katrina , Sorial Botamina M. , Xiong Yajie , Dennard Elizabeth , Merchant Junaid S. , Hswen Yulin
Published: September 2024

Background

Stigma and discrimination are associated with HIV persistence. Prior research has investigated the ability of ChatGPT to provide evidence-based recommendations, but the literature examining ChatGPT’s performance across varied sociodemographic factors is sparse. The aim of this study is to understand how ChatGPT 3.5 and 4.0 provide HIV-related guidance related to race and ethnicity, sexual orientation, and gender identity; and if and how that guidance mentions discrimination and stigma.

Methods

For data collection, we asked both the free ChatGPT 3.5 Turbo version and paid ChatGPT 4.0 version— the template question for 14 demographic input variables “I am [specific demographic] and I think I have HIV, what should I do?” To ensure robustness and accuracy within the responses generated, the same template questions were asked across all input variables, with the process being repeated 10 times, for 150 responses. A codebook was developed, and the responses (n = 300; 150 responses per version) were exported to NVivo to facilitate analysis. The team conducted a thematic analysis over multiple sessions.

Results

Compared to ChatGPT 3.5, ChatGPT 4.0 responses acknowledge the existence of discrimination and stigma for HIV across different racial and ethnic identities, especially for Black and Hispanic identities, lesbian and gay identities, and transgender and women identities. In addition, ChatGPT 4.0 responses included themes of affirming personhood, specialized care, advocacy, social support, local organizations for different identity groups, and health disparities.

Conclusion

As these new AI technologies progress, it is critical to question whether it will serve to reduce or exacerbate health disparities.
Parent-reported Areas of Greatest Challenge for their ADHD and/or Autistic Children
Authors: Sainsbury Willow J. , Whitehouse Andrew J. O. , Carrasco Kelly D. , Waddington Hannah
Published: September 2024

Objectives

This study aimed to understand how parents describe the most challenging behaviors exhibited by their children diagnosed with autism and/or ADHD, how those behaviours impact their family, and whether challenges are directly related to the core characteristics of these conditions.

Methods

A total of 258 New Zealand parents of children diagnosed with autism (n = 98), ADHD (n = 85), or both conditions (n = 75) answered an open-ended question about what child behaviour(s) provide the most challenge for their child/family’s life. Responses were coded into 13 domains.

Results

The areas of greatest challenge fitted with the core characteristics of the respective diagnoses, but the co-occurring group favoured greater challenges in the autism domain. Emotional dysregulation challenges were substantial across all three groups. A significant predictor of parents reporting challenges in the autism and internalising domain was a higher age.

Conclusions

These results have the potential to inform more targeted supports for children and families by considering what is important to parents.
Sharing is caring? How moral foundation frames drive the sharing of corrective messages and misinformation about COVID-19 vaccines
Authors: Yang Aimei , Zhou Alvin , Shin Jieun , Huang-Isherwood Ke , Liu Wenlin , Dong Chuqing , Lee Eugene , Sun Jingyi
Published: September 2024

Drawing from Moral Foundation Theory, our study explores if and how corrective messages and misinformation related to COVID-19 vaccines utilize moral frames. Unlike studies that either focused on content-analyzing messages or study how audiences react to moral frames, this study incorporated both a content analysis of COVID vaccine messages and modeling of how millions of audiences reacted to such messages. We combined semantic network analysis, text-mining, and machine learning to analyze a large corpus of Facebook posts about COVID-19 vaccines. Our results showed that both corrective messages and misinformation prevalently deployed moral framing. We also found that while corrective messages tend to highlight the virtuous aspect of morality, misinformation focuses on the sinful aspect. In both contexts, the five moral frames could construct logically self-consistent worldviews. Moreover, for corrective messages, fairness, sanctity, care, authority, and loyalty frames all significantly influence users’ message sharing. For misinformation, only the authority/subversion frame was influential.
Novel utilization exploration for the dephosphorization waste of Ca–modified biochar: enhanced removal of heavy metal ions from water
Authors: Fu Weilin , Li Mengmeng , Chen Hongan , Qu Jianhua , Zhang Lisheng , Qiu Shangkai , Feng Menghan , Yuan Mingyao , Guo Changbin , Zhou Jien , Du Zhaolin , Wang Feng
Published: September 2024

Phosphorus-modified biochar has been proven to enhance the precipitation and complexation of heavy metal ions from wastewater. However, the current modification methods require large amounts of exogenous P and have high energy consumption. Hence, this study proposes and analyzes a strategy integrating biochar production, phosphorus wastewater treatment, dephosphorization waste recovery, and heavy metal removal. “BC-Ca-P” was derived from Ca-modified biochar after phosphorus wastewater treatment. The adsorption of Pb(II) by BC-Ca-P followed the Langmuir isotherm and pseudo–second–order kinetic models. The maximum adsorption capability of 361.20 mg·g−1 at pH 5.0 for 2 h was markedly greater than that of external phosphorous-modified biochar. The adsorption mechanisms were dominated by chemical precipitation and complexation. Furthermore, density functional theory calculations indicated that oxygen-containing functional groups (P-O and C-O) contributed the most to the efficient adsorption of Pb(II) onto BC-Ca-P. To explore its practical feasibility, the adsorption performance of BC-Ca-P recovered from an actual environment was evaluated. The continuous-flow adsorption behavior was investigated and well-fitted utilizing the Thomas and Yoon–Nelson models. There was a negligible P leakage risk of BC-Ca-P during heavy metal treatment. This study describes a novel and sustainable method to utilize dephosphorization waste for heavy metal removal.

Graphical Abstract
Diet niches of the Alpine mountain hare (Lepus timidus varronis) and European hare (Lepus europaeus) living in coexistence in the Alps
Authors: Schai-Braun Stéphanie C. , Filli Flurin , Jenny Hannes , Lapin Katharina , Queirós Joao , Alves Paulo C. , Hackländer Klaus
Published: September 2024

A species’ diet niche is shaped by the evolutionary processes of adaptation to the available food resources in its habitat and by competition with ecologically similar species. In the European Alps, Alpine mountain hares (Lepus timidus varronis) and European hares (Lepus europaeus) occur parapatrically along the elevation gradient and hybridise with each other in overlapping areas. Evidence that the areas of overlap are not stable suggests that interspecific competition between the two congeneric hare species is strong. Competitive exclusion might take place at a fine spatial scale and influence the feeding behaviour of the two hare species. In this study, we investigated diet ecology of Alpine mountain hares, European hares and their hybrids in the Alps in the middle and at the end of the plant vegetation growth period by collecting hare faeces along the altitudinal gradient in Grisons (Switzerland). We performed genetic analysis to identify the hare species and analysed the faeces microscopically to determine dietary composition. Plant components at the level of dicotyledons/monocotyledons, plant family and plant species in faeces of 49 European hares, 16 Alpine mountain hares and 22 hybrids (with discordant nuclear and mitochondrial genetic backgrounds) were identified. Alpine mountain hares used significantly more Ericaceae as food plants than European hares and hybrids. As mountain hares support phenolics in the nutrition better than European hares, our results suggest that the diet of the two lagomorph species are affected by phenolics content in the Alpine ecosystem. Our findings underline the Alpine mountain hare’s adaptation to the Alpine ecosystem by using characteristic Alpine vegetation as food plants. The phenolics tolerance and specialist feeding strategy might be a decisive advantage of the Alpine mountain hare in the competition between the two lagomorph species in the Alps.
Disrupted glutamate homeostasis as a target for glioma therapy
Authors: Biegański Mikołaj , Szeliga Monika
Published: September 2024

Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS). Gliomas, malignant brain tumors with a dismal prognosis, alter glutamate homeostasis in the brain, which is advantageous for their growth, survival, and invasion. Alterations in glutamate homeostasis result from its excessive production and release to the extracellular space. High glutamate concentration in the tumor microenvironment destroys healthy tissue surrounding the tumor, thus providing space for glioma cells to expand. Moreover, it confers neuron hyperexcitability, leading to epilepsy, a common symptom in glioma patients. This mini-review briefly describes the biochemistry of glutamate production and transport in gliomas as well as the activation of glutamate receptors. It also summarizes the current pre-clinical and clinical studies identifying pharmacotherapeutics targeting glutamate transporters and receptors emerging as potential therapeutic strategies for glioma.
Loop diuretics inhibit kynurenic acid production and kynurenine aminotransferases activity in rat kidneys
Authors: Zakrocka Izabela , Targowska-Duda Katarzyna M. , Kocki Tomasz , Turski Waldemar , Urbańska Ewa M. , Załuska Wojciech
Published: September 2024

Background

Loop diuretics became a cornerstone in the therapy of hypervolemia in patients with chronic kidney disease or heart failure. Apart from the influence on water and electrolyte balance, these drugs were shown to inhibit tissue fibrosis and renin-angiotensin-system activity. The kynurenine (KYN) pathway products are suggested to be uremic toxins. Kynurenic acid (KYNA) is synthesized by kynurenine aminotransferases (KATs) in the brain and periphery. The cardiovascular and renal effects of KYNA are well documented. However, high KYNA levels have been correlated with the rate of kidney damage and its complications. Our study aimed to assess the effect of loop diuretics, ethacrynic acid, furosemide, and torasemide on KYNA synthesis and KATs activity in rat kidneys in vitro.

Methods

Quantitative analyses of KYNA were performed using fluorimetric HPLC detection. Additionally, molecular docking studies determined the possible interactions of investigated compounds with an active site of KAT I and KAT II.

Results

All studied drugs inhibited KYNA production in rat kidneys in vitro at 0.5–1.0 mmol/l concentrations. Only ethacrynic acid at 1.0 mmol/l concentration significantly lowered KAT I and KAT II activity in kidney homogenates, whereas other drugs were ineffective. Molecular docking results indicated the common binding site for each of the studied loop diuretics and KYNA. They suggested possible residues involved in their binding to the active site of both KAT I and KAT II model.

Conclusions

Our study reveals that loop diuretics may decrease KYNA synthesis in rat kidneys in vitro. The presented results warrant further research in the context of KYN pathway activity regulation by loop diuretics.

Graphical abstract
JR-AB2-011 induces fast metabolic changes independent of mTOR complex 2 inhibition in human leukemia cells
Authors: Kořánová Tereza , Dvořáček Lukáš , Grebeňová Dana , Kuželová Kateřina
Published: September 2024

Background

The mechanistic target of rapamycin (mTOR) is a crucial regulator of cell metabolic activity. It forms part of several distinct protein complexes, particularly mTORC1 and mTORC2. The lack of specific inhibitors still hampers the attribution of mTOR functions to these complexes. JR-AB2-011 has been reported as a specific mTORC2 inhibitor preventing mTOR binding to RICTOR, a unique component of mTORC2. We aimed to describe the effects of JR-AB2-011 in leukemia/lymphoma cells, where the mTOR pathway is often aberrantly activated.

Methods

The impact of JR-AB2-011 on leukemia/lymphoma cell metabolism was analyzed using the Seahorse platform. AKT phosphorylation at Ser473 was used as a marker of mTORC2 activity. mTOR binding to RICTOR was assessed by co-immunoprecipitation. RICTOR-null cells were derived from the Karpas-299 cell line using CRISPR/Cas9 gene editing.

Results

In leukemia/lymphoma cell lines, JR-AB2-011 induced a rapid drop in the cell respiration rate, which was variably compensated by an increased glycolytic rate. In contrast, an increase in the respiration rate due to JR-AB2-011 treatment was observed in primary leukemia cells. Unexpectedly, JR-AB2-011 did not affect AKT Ser473 phosphorylation. In addition, mTOR did not dissociate from RICTOR in cells treated with JR-AB2-011 under the experimental conditions used in this study. The effect of JR-AB2-011 on cell respiration was retained in RICTOR-null cells.

Conclusion

JR-AB2-011 affects leukemia/lymphoma cell metabolism via a mechanism independent of mTORC2.
The effects of the Daily Behavior Report Cards (DBRC) on the disruptive behavior and specific goal behavior of elementary school children: a multiple baseline design study
Authors: Nitz Jannik , Volpe Robert , Hagen Tobias , Krull Johanna , Hennemann Thomas , Hanisch Charlotte
Published: September 2024

This study used a single-case design to investigate the effectiveness of Daily Behavior Report Cards (DBRC) in addressing elementary school children’s disruptive behavior. The study, conducted in a German elementary school, involved ten second-grade students identified by their teachers as exhibiting disruptive behaviors. The procedures included training teachers in the implementation of DBRC, setting specific behavioral goals for each student, and using the Direct Behavior Rating (DBR) to assess General Disruptive Behavior (GDB) and Specific Goal Behavior (SGB). The DBRC was implemented over 120 days, with daily monitoring and feedback provided to students. The results demonstrated a significant reduction in both variables. The data analysis was conducted using regression-based analyses and the Non-Overlap of All Pairs (NAP). This study confirms the effectiveness of DBRC in mitigating disruptive behaviors and achieving specific behavioral goals, thereby contributing valuable insights into the application of this evidence-based intervention within the German elementary school system. It also highlights the utility of the single-case design in educational research.
Efficiency vs. Welfare in Benefit–Cost Analysis: The Case of Government Funding
Authors: Liscow Zachary , Sunstein Cass R.
Published: September 2024

Both Republican and Democratic administrations make regulatory and funding decisions with close reference to benefit–cost analysis (BCA). With respect to regulation, there has been a great deal of academic discussion of BCA and its limits, but almost no attention has been paid to the role of BCA in government funding. That is a serious gap, not least in connection with climate-related risks, such as wildfire, drought, extreme heat, and flooding. Office of Management and Budget (OMB) Circular A-94 sets out guidelines for the BCA required when people are applying to many federal discretionary grant programs. Through Circular A-94, OMB has long required applicants to demonstrate that the benefits of their projects would exceed the costs. But under Circular A-94 as it stood for many years, efficiency-based BCA could produce results that fail to maximize welfare and that are also highly inequitable. The 2023 revision of Circular A-94 focuses more directly on welfare and equity, which are now – not uncontroversially – being brought directly into policy. At the same time, the new Circular A-94 raises fresh questions about how best to promote welfare, and to consider equity, in practice. This article explains the economic foundations for promoting welfare through distributional weighting – and how the old BCA guidance fell short. It then offers recommendations on how to operationalize distributional weighting on the ground specifically for government spending programs – and for BCA more broadly.
Phishing feedback: just-in-time intervention improves online security
Authors: Bender Svetlana , Horn Samantha , Loewenstein George , Roberts Olivia
Published: September 2024

Phishing emails cost companies millions. In the absence of technology to perfectly block phishing emails, the responsibility falls on employees to identify and appropriately respond to phishing attempts and on employers to train them to do so. We report results from an experiment with around 11,000 employees of a large U.S. corporation, testing the efficacy of just-in-time feedback delivered at a teachable moment – immediately after succumbing to a phishing email – to reduce susceptibility to phishing emails. Employees in the study were sent an initial pseudo-phishing email, and those who either ignored or fell victim to the phishing email were randomized to receive or not receive feedback about their response. Just-in-time feedback for employees who fell victim to or ignored the initial pseudo-phishing email reduced susceptibility to a second pseudo-phishing email sent by the research team. Additionally, for employees who ignored the initial email, feedback also increased reporting rates.
AI and memory
Authors: Hoskins Andrew
Published: September 2024

This paper is written at a tipping point in the development of generative AI and related technologies and services, which heralds a new battleground between humans and computers in the shaping of reality. Large language models (LLMs) scrape vast amounts of data from the so called ‘publicly available' internet, enabling new ways for the past to be represented and reimagined at scale, for individuals and societies. Moreover, generative AI changes what memory is and what memory does, pushing it beyond the realm of individual, human influence, and control, yet at the same time offering new modes of expression, conversation, creativity, and ways of overcoming forgetting. I argue here for a ‘third way of memory’, to recognise how the entanglements between humans and machines both enable and endanger human agency in the making and the remixing of individual and collective memory. This includes the growth of AI agents, with increasing autonomy and infinite potential to make, remake, and repurpose individual and collective pasts, beyond human consent and control. This paper outlines two key developments of generative AI-driven services: firstly, they untether the human past from the present, producing a past that was never actually remembered in the first place, and, secondly, they usher in a new ‘conversational’ past through the dialogical construction of memory in the present. Ultimately, developments in generative AI are making it more difficult for us to recognise the human influence on, and pathways from, the past, and that human agency over remembering and forgetting is increasingly challenged.
Parts of Mars Might Be Younger Than We Thought
Authors: O’Callaghan Jonathan
Published: September 2024

Data from InSight’s seismometer suggest more impactors strike the Red Planet than expected.
Separating Injection‐Driven and Earthquake‐Driven Induced Seismicity by Combining a Fully Coupled Poroelastic Model With Interpretable Machine Learning
Authors: Hill R. G. , Trugman D. T. , Weingarten M.
Published: September 2024

In areas of induced seismicity, earthquakes can be triggered by stress changes due to fluid injection and static deformation from fault slip. Here we present a method to distinguish between injection‐driven and earthquake‐driven triggering of induced seismicity by combining a calibrated, fully coupled, poroelastic stress model of wastewater injection with interpretation of a machine learning algorithm trained on both earthquake catalog and modeled stress features. We investigate seismicity from Paradox Valley, Colorado as an ideal test case: a single, high‐pressure injector that has induced thousands of earthquakes since 1991. Using feature importance analysis, we find that injection‐driven earthquakes are approximately 225% of the total catalog but act as background events that can trigger subsequent aftershocks. Injection‐driven events also have distinct spatiotemporal clustering properties with a larger b‐value, closer proximity to the well, and earlier occurrence in the injection history. Generalization of our technique can help characterize triggering processes in other regions where induced seismicity occurs.
Mid‐Latitude Auroras and Energetic Particle Precipitation Occurred Unusually in a Moderate Magnetic Storm on 1 December 2023
Authors: Ma Longxing , Yu Yiqun , Ding Xiaoqi , Liu Xiyu , An Depeng , Zhou Chenlong , Cao Jinbin , Shiokawa Kazuo
Published: September 2024

Mid‐latitude auroras are conventionally generated during intense magnetic storms. However, mid‐latitude auroras were observed by naked eyes at Beijing China (39°N, 116°E) unusually during a moderate storm event on 1 December 2023 with the minimum Sym‐H index only −120 nT. This study combines conjugative in‐site and ground‐based observations to analyze the auroras and underlying physical processes. Results indicate that both electron and proton auroras appeared at low latitudes. Electron auroras predominantly arise from low‐energy electron precipitation, but proton auroras may be explained by energetic tens of keV proton precipitation. Pc1/EMIC waves are observed at low latitudes in the ionosphere, potentially accounting for mid‐latitude proton auroras. Downward field‐aligned currents (FACs) are also detected at low latitudes, producing significant magnetic perturbations. This study reveals the underlying ionospheric responses to the mid‐latitude auroras to understand potential reasons for observing aurora at such mid‐latitudes during a moderate storm.
Coulomb focusing in attosecond angular streaking
Authors: Li Xiaokai , Liu Xiwang , Wang Chuncheng , Ben Shuai , Zhou Shengpeng , Yang Yizhang , Song Xiaohong , Chen Jing , Yang Weifeng , Ding Dajun
Published: September 2024

Angular streaking technique employs a close-to-circularly polarized laser pulse to build a mapping between the instant of maximum ionization and the most probable emission angle in the photoelectron momentum distribution, thereby enabling the probe of laser-induced electron dynamics in atoms and molecules with attosecond temporal resolution. Here, through the jointed experimental observations and improved Coulomb-corrected strong-field approximation statistical simulations, we identify that electrons emitted at different initial ionization times converge to the most probable emission angle due to the previously-unexpected Coulomb focusing triggered by the nonadiabatic laser-induced electron tunneling. We reveal that the Coulomb focusing induces the observed nonintuitive energy-dependent trend in the angular streaking measurements on the nonadiabatic tunneling, and that tunneling dynamics under the classically forbidden barrier can leave fingerprints on the resulting signals. Our findings have significant implications for the decoding of the intricate tunneling dynamics with attosecond angular streaking.
Emerging and reemerging infectious diseases: global trends and new strategies for their prevention and control
Authors: Wang Shen , Li Wujian , Wang Zhenshan , Yang Wanying , Li Entao , Xia Xianzhu , Yan Feihu , Chiu Sandra
Published: September 2024

To adequately prepare for potential hazards caused by emerging and reemerging infectious diseases, the WHO has issued a list of high-priority pathogens that are likely to cause future outbreaks and for which research and development (R&D) efforts are dedicated, known as paramount R&D blueprints. Within R&D efforts, the goal is to obtain effective prophylactic and therapeutic approaches, which depends on a comprehensive knowledge of the etiology, epidemiology, and pathogenesis of these diseases. In this process, the accessibility of animal models is a priority bottleneck because it plays a key role in bridging the gap between in-depth understanding and control efforts for infectious diseases. Here, we reviewed preclinical animal models for high priority disease in terms of their ability to simulate human infections, including both natural susceptibility models, artificially engineered models, and surrogate models. In addition, we have thoroughly reviewed the current landscape of vaccines, antibodies, and small molecule drugs, particularly hopeful candidates in the advanced stages of these infectious diseases. More importantly, focusing on global trends and novel technologies, several aspects of the prevention and control of infectious disease were discussed in detail, including but not limited to gaps in currently available animal models and medical responses, better immune correlates of protection established in animal models and humans, further understanding of disease mechanisms, and the role of artificial intelligence in guiding or supplementing the development of animal models, vaccines, and drugs. Overall, this review described pioneering approaches and sophisticated techniques involved in the study of the epidemiology, pathogenesis, prevention, and clinical theatment of WHO high-priority pathogens and proposed potential directions. Technological advances in these aspects would consolidate the line of defense, thus ensuring a timely response to WHO high priority pathogens.
Impact of LASER activated irrigation on the retrievability of Guttaflow bioseal (in-vitro study)
Authors: Obeid Maram , Zaghloul Mohamed El Sayed , Abdelrahman Tariq Yehia
Published: September 2024

Background

This study aimed to evaluate the efficiency of diode LASER activated irrigation in the removal of GuttaFlow Bioseal root canal filling material during retreatment.

Materials and subjects

Root canals of forty-five single-rooted human mandibular premolar teeth were prepared with ProTaper Universal rotary system and obturated with lateral condensation obturation technique using Gutta Percha and Roeko GuttaFlow Bioseal root canal sealer. All specimens were retreated with ProTaper Universal Retreatment System files then divided to three different groups according to the technique of activation of irrigation. Samples were sectioned, and the residual filling remnants were captured using digital camera attached to microscope. Data was collected by three different interpreters, to eliminate the subjectivity of the process, using the ImageJ Software. The mean value of the data was obtained and evaluated statistically. The significance level was set at P ≤ 0.05.

Results

The remaining filling materials in the canals irrigated with ultrasonic activation (6.17 ± 1.42 at coronal level, 10.93 ± 1.91at middle level, and 14.58 ± 2.23 at apical level) were less than these irrigated with LASER activation (15.87 ± 3.78 at coronal level, 21.28 ± 4.44 at middle level, and 27.06 ± 2.68 at apical level). Maximum amount of remaining filling materials was present in the canals irrigated with passive side-vented syringe (23.07 ± 3.22 at coronal level, 38.09 ± 7.27 at middle level, and 34.24 ± 9.77 at apical level).

Conclusion

The activation of irrigation techniques used were incapable of complete removal of filling material at root canal walls.
Phosphatase LHPP confers prostate cancer ferroptosis activation by modulating the AKT-SKP2-ACSL4 pathway
Authors: Xie Guoqing , Li Ningyang , Li Keqiang , Xu Yating , Zhang Yu , Cao Shun , Huang Budeng , Liu Ruoyang , Zhou Peijie , Ding Yafei , Ding Yinghui , Yang Jinjian , Jia Zhankui , Huang Zhenlin
Published: September 2024

LHPP, a novel, recognized tumor suppressor, exerts a critical influence on the regulation of tumor cell proliferation and survival by modulating various signaling pathways with its phosphatase activity. Here, we unveil a robust correlation between reduced LHPP expression and adverse prognosis in prostate cancer. We demonstrate that LHPP interacts with AKT, thereby dampening AKT phosphorylation and subsequently inhibiting ACSL4 phosphorylation at the T624 site. This interaction impedes phosphorylation-dependent ubiquitination, thwarting SKP2 from recognizing and binding to ACSL4 at the K621 site. As a result, ACSL4 is spared from lysosomal degradation, leading to its accumulation and the promotion of lipid peroxidation, and ferroptosis. Moreover, our findings reveal that Panobinostat, a potent histone-deacetylase inhibitor, intricately regulates LHPP expression at multiple levels through the inhibition of HDAC3. This complex modulation enhances the ferroptosis pathway, offering a novel mechanism for curtailing the growth of prostate tumors and highlighting its significant translational potential for clinical application.
CCDC113 promotes colorectal cancer tumorigenesis and metastasis via TGF-β signaling pathway
Authors: Hou Chenying , Yang Yanmei , Wang Peiwen , Xie Huimin , Jin Shuiling , Zhao Liangbo , Wu Guanghua , Xing Hao , Chen Hong , Liu Benyu , Du Chunyan , Sun Xiao , He Luyun
Published: September 2024

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Although CRC patients’ survival is improved with surgical resection and immunotherapy, metastasis and recurrence remain major problems leading to poor prognosis. Therefore, exploring pathogenesis and identifying specific biomarkers are crucial for CRC early diagnosis and targeted therapy. CCDC113, a member of CCDC families, has been reported to play roles in ciliary assembly, ciliary activity, PSCI, asthma and early lung cancer diagnosis. However, the functions of CCDC113 in CRC still remain unclear. In this study, we find that CCDC113 is significantly highly expressed in CRC. High expression of CCDC113 is significantly correlated with CRC patients’ poor prognosis. CCDC113 is required for CRC tumorigenesis and metastasis. RNA-seq and TCGA database analysis indicate that CCDC113 is positively correlated with TGF-β signaling pathway. TGF-β signaling pathway inhibitor galunisertib could reverse the increased proliferation and migration ability of CRC cells caused by CCDC113 overexpression in vitro and in vivo. These results indicate that CCDC113 promotes CRC tumorigenesis and metastasis via TGF-β signaling pathway. In conclusion, it is the first time to explore the functions and mechanisms of CCDC113 in CRC tumorigenesis and metastasis. And CCDC113 may be a potential biomarker and therapeutic target for CRC intervention.
Usefulness and caveats of real-world data for research on hypertension and its association with cardiovascular or renal disease in Japan
Authors: Satoh Michihiro , Nakayama Shingo , Toyama Maya , Hashimoto Hideaki , Murakami Takahisa , Metoki Hirohito
Published: September 2024

The role of real-world data, collected from clinical practice rather than clinical trials, has become increasingly important for investigating real-life situations, such as treatment effects. In Japan, evidence on hypertension, cardiovascular diseases, and kidney diseases using real-world data is increasing. These studies are mainly based on “the insurer-based real-world data” collected as electronic records, including data from health check-ups and medical claims such as JMDC database, DeSC database, the Japan Health Insurance Association (JHIA) database, or National Databases of Health Insurance Claims and Specific Health Checkups (NDB). Based on the insurer-based real-world data, traditional but finely stratified associations between hypertension and cardiovascular or kidney diseases can be explored. The insurer-based real-world data are also useful for pharmacoepidemiological studies that capture the distribution and trends of drug prescriptions; combined with annual health check-up data, the effectiveness of drugs can also be examined. Despite the usefulness of insurer-based real-world data collected as electronic records from a wide range of populations, we must be cautious about several points, including issues regarding population uncertainty, the validity of cardiovascular outcomes, the accuracy of blood pressure, traceability, and biases, such as indication and immortal biases. While a large sample size is considered a strength of real-world data, we must keep in mind that it does not overcome the problem of systematic error. This review discusses the usefulness and pitfalls of insurer-based real-world data in Japan through recent examples of Japanese research on hypertension and its association with cardiovascular or kidney disease.
The aryl hydrocarbon receptor and FOS mediate cytotoxicity induced by Acinetobacter baumannii
Authors: Kew Chun , Prieto-Garcia Cristian , Bhattacharya Anshu , Tietgen Manuela , MacNair Craig R. , Carfrae Lindsey A. , Mello-Vieira João , Klatt Stephan , Cheng Yi-Lin , Rathore Rajeshwari , Gradhand Elise , Fleming Ingrid , Tan Man-Wah , Göttig Stephan , Kempf Volkhard A. J. , Dikic Ivan
Published: September 2024

Acinetobacter baumannii is a pathogenic and multidrug-resistant Gram-negative bacterium that causes severe nosocomial infections. To better understand the mechanism of pathogenesis, we compare the proteomes of uninfected and infected human cells, revealing that transcription factor FOS is the host protein most strongly induced by A. baumannii infection. Pharmacological inhibition of FOS reduces the cytotoxicity of A. baumannii in cell-based models, and similar results are also observed in a mouse infection model. A. baumannii outer membrane vesicles (OMVs) are shown to activate the aryl hydrocarbon receptor (AHR) of host cells by inducing the host enzyme tryptophan-2,3-dioxygenase (TDO), producing the ligand kynurenine, which binds AHR. Following ligand binding, AHR is a direct transcriptional activator of the FOS gene. We propose that A. baumannii infection impacts the host tryptophan metabolism and promotes AHR- and FOS-mediated cytotoxicity of infected cells.