bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthcare in an unstable climate: the case for health climate change resilience
Authors: Cummins Paul J
Published: February 2025

As a response to the well-documented projects for how anthropogenic climate change (ACC) will negatively impact human health, health and bioethics scholars have argued for the urgency of mitigating ecological damage healthcare systems cause. Mitigation is not the only focus because ACC is already affecting health. Under current plans to reduce emissions, the sixth Intergovernmental Panel on Climate Change (IPCC) predicts warming to exceed safe levels. Climate health scholars have begun to advocate for climate change adaptation (CCA) as it is essential to anticipate and prepare for how extreme ACC will affect health. CCA strategies that emphasize continuity of operation in the face of extreme weather events dominate. These plan project the future climate to be much like the present one, just worse, and assume an unwarranted future of climate stability. Recent scientific evidence indicate ACC is accelerating faster than climate models predicted. We may be moving from an era of climate stability to an era of instability. The dominance of CCA in preparing for ACC will, at best, preserve the status quo for population health at the expense of envisioning initiatives to help all people live healthier lives in a radically changed world. To prepare for an unstable climate future, healthcare should adopt a stance of climate change resilience (CCR) that prioritizes public health initiatives to secure healthier lives among a broader population segment.
Prospects for offshore hydrogen production in the Netherlands
Authors: van Stralen Joost , Janssen Gaby , Koornneef Joris , Scheepers Martin , Sipma Jeffrey , van der Zwaan Bob
Published: February 2025

Using a technology-rich optimization model for the Netherlands, we analyse the potential role of offshore energy options for system integration purposes. Our focus is on offshore hydrogen production produced by wind power in the Dutch Exclusive Economic Zone of the North Sea. We conclude that large-scale offshore green hydrogen development is a robust outcome of our scenarios. We also find that offshore green hydrogen production dominates over onshore hydrogen generation with green electricity delivered to shore through power lines in the North Sea. The main reason is the avoidance of elevated costs associated with a high voltage electricity grid at sea. We observe a large range of possible offshore hydrogen production levels, from 40 to 250 TWh/yr in 2050, depending e.g. on the level of total hydrogen demand, the availability of competing emission abatement options, and the offshore wind energy potential. After 2040 it becomes optimal to transport most energy from newly installed offshore wind capacity to shore in the form of hydrogen. Because of the long lead times involved in infrastructure planning, offshore hydrogen production and transportation should be put high on political and industrial agendas.
Transforming abandoned mines into solar farms: a pathway to renewable energy development and sustainable land use
Authors: Mariotti Erin , Engström Johanna
Published: February 2025

The demand for renewable energy is becoming increasingly apparent, but a significant challenge lies in the limited availability of land. To limit environmental impacts associated with new development in previously undisturbed lands, this study investigates the potential to convert abandoned mines in Florida and Pennsylvania into solar farms, aligning with state-level clean energy goals and climate objectives. Thirteen abandoned mines in Florida and five in Pennsylvania were identified as suitable sites for solar farm development. These solar installations have the potential to generate up to 22% of Florida's and 0.017% of Pennsylvania's annual electricity needs. Employing various criteria such as acreage, slope, aspect, proximity to infrastructure, and insolation, the research assesses the feasibility of this conversion using advanced modeling techniques. The study was conducted in two phases: first, an in-depth spatial suitability assessment utilizing GIS tools (ArcGIS Pro) to evaluate potential mine sites based on specified criteria. Second, solar power potential and carbon emission reduction are estimated based on the use of two different types of solar panels. This study underscores the importance of interdisciplinary approaches in addressing environmental and energy challenges by advancing our understanding of sustainable land use practices and contributing to the collective pursuit of clean energy objectives.
Tips and Traps When Conducting Network Analysis in Practice
Authors: Petit Nicolas
Published: February 2025

An organizational network analysis project has the potential to generate very rich and useful relational data. In many organizations, this kind of data has never been seen before. It can offer exciting new insights about how the organization functions and is also very sensitive. It reveals how people interact with each other, including how they are bonded (or not) to one another, which, for some people, touches the very heart of who they are or would like to be. For an organizational network analysis project to succeed, it must be carefully prepared and scoped, with strong buy-in secured, and be executed flawlessly with only one purpose: to generate value for the organization and its people while respecting their integrity and privacy. Ticking all those boxes is not easy. This chapter provides tips and calls out traps to avoid.
Strategically Building Network Connections Across Geographic Markets to Improve Sales Agility and Enhance Organizational Growth
Authors: Bilgen Victor , Gideon Chris , Shah Neha Parikh
Published: February 2025

As market forces generate continuous change, organizations pursuing a competitive advantage must coordinate constant collaboration across geographies to meet customer needs, operate efficiently, and remain agile. However, spanning across local markets often proves difficult because of organizational structures that support long-standing patterns of regional autonomy and decision-making. In the case study presented in this chapter, a global sales organization faced challenges in achieving its strategic growth goals, despite the commitment and efforts of the chief executive officer and top management team. Critically, through organizational network analysis, collaboration barriers were diagnosed and systemic interventions were defined to enhance connectivity and agility, measuring progress over time. This chapter describes how the intentional mapping, reshaping, and mobilization of collaboration networks can drive large-scale change and unlock long-term business value.
The Role of Networks in Leadership Effectiveness
Authors: Weinberger Caton , Bauer Laura , Carter Dorothy
Published: February 2025

A growing body of literature examines leadership through a social network lens. According to the social network approach, leadership is a process that occurs in the relationships between people. As such, leadership effectiveness partially depends on the structure of relationships in a group. Despite widespread acknowledgment of the utility of the social network approach to leadership, there is relatively little work communicating the implications of network-based leadership research for managerial practice. The purpose of this chapter is to summarize the networks and leadership research in a way that is useful in practice. The chapter discusses the processes by which managers reveal, develop, and leverage their own networks and the networks of the groups they lead. It concludes with suggestions for productive avenues of research about leadership and social networks going forward.
Personalization and Privatization of Politics
Authors: Atia Renana , Balmas Meital
Published: February 2025

In the fields of political science and political communication, considerable research attention has been devoted to political personalization, a phenomenon whereby politicians become the main anchor in interpreting and evaluating the political process. While the personalization of politics has indeed become a hallmark of contemporary democracies, the phenomenon itself is by no means new. Historically, political power has long been identified with individuals, as is elaborated in the 1957 classic work The King’s Two Bodies by Ernst Kantorowicz. In his studies of the historical development of social and political orders, Max Weber identifies, as one of the three main forms of political legitimacy, what he termed “charismatic authority,” which is based on a leader’s personal charisma. Similarly, studies of the early phases of representative democracies have emphasized that, during that time, political representation largely centered on personal factors rather than on nationally identifiable collective interests and loyalties. This personalization process has gained momentum in Western liberal democracies as of the second half of the 20th century, and the 21st century is expected to see a continuation of that trend.

Three basic types of political personalization are institutional, media, and behavioral. The first pertains to the shifting focus from collective bodies, such as parties and other political entities, to individual politicians within governments. The second entails a growing concentration of media attention on individual politicians as opposed to parties, institutions, or policy issues, while the latter is anchored in politicians’ conduct and voters’ electoral behavior.

An important distinction that has been increasingly developed in the literature is between personalization and privatization; the latter, sometimes termed intimization, is considered a subcategory of the former. Personalization refers to focus on a public figure’s political activities, whereas privatization refers to focus on their personal life. In the context of political campaigns, privatization involves strategies that emphasize candidates’ personal attributes over their and their parties’ political suitability, achievements, and goals.

Personalization influences not only voters and politicians but also international perceptions, and they can enhance engagement and trust by humanizing politics. However, it also risks simplifying complex issues, fostering polarization and undermining trust in political institutions over time. Thus, the study of political personalization is essential for understanding its significant impact in various forms and spheres.
Nonprofits and Interest Groups in Crisis Management
Authors: McKeague Lauren K. , Bies Angela L.
Published: February 2025

Nonprofit organizations and interest groups play a significant role in supplementing, complementing, and carrying out crisis management activities worldwide. Prior to a crisis event, nonprofits and interest groups are valuable in disaster planning as they may have expertise in certain specialized areas, such as a diversity of substantive expertise, familiarity with local communities and their unique needs, the ability to represent and advocate for vulnerable populations, or the ability to compile resources needed to mitigate or prevent the most devastating consequences from crises. Once a crisis occurs, these groups are also valuable during acute responses because they may already be on site, may be more flexible and expeditious in mobilizing resources than public or private organizations, have the trust of the local community, and have the ability to draw from multiple sources of funding, including serving as intermediaries between survivors, volunteers, and other groups, catalyzing cross-sector collaboration. Finally, nonprofit organizations and interest groups play vital roles in crisis recovery processes, including coordinating services, providing case management, assisting with rebuilding and reconstruction, providing mental health support, and financial counseling.

Their participation, however, is dependent upon a series of variables including organizational characteristics like size, structure, and capacity; areas of substantive expertise or mission focus; geographic jurisdiction; and the unique demands of the crisis. Despite their increasing involvement, it has been argued that nonprofit organizations and interest groups remain underutilized in crisis management as they often face barriers to effectively engaging and integrating in preparedness and response phases, achieving interorganizational coordination and collaboration, and creating trust, equity, and accountability in disaster recovery. Increasingly, crisis management is moving toward an “all-of-society” approach that includes community-based groups and individuals in planning for, responding to, and recovering from disaster events. More rigorous, comprehensive, and generalizable research is needed to build evidence-based practices to help overcome these known challenges to fully incorporating nonprofits and interest groups in crisis management to reduce disaster vulnerability and build community resiliency.
Anti-Carceral Social Work
Authors: Murray Bethany
Published: February 2025

There is a growing movement within social work known as anti-carceral social work, an adjunct term to abolitionist social work. Drawing from anti-carceral feminism, anti-carceral social work critiques carceral approaches within social work, advocating for practices that resist rather than reinforce carceral systems. This approach emphasizes community-based, non-punitive interventions aligned with social justice principles.

Social work scholars, practitioners, and activists are rethinking interventions beyond law enforcement in four primary emerging practices: transformative justice, school-based diversion, anti-carceral advocacy, and harm reduction.

Transformative justice is a comprehensive approach that seeks to address interpersonal violence by fostering community accountability and healing, rather than relying on punitive measures. Organizations like Generation 5 utilize community-based strategies such as pods to support survivors and hold aggressors accountable within their communities. Community resource hubs like Creative Interventions provide toolkits and accountability frameworks to help guide communities in creating safer communities without reliance on carceral systems.

School-based diversion initiatives aim to counter the criminalization of students, particularly Black students, by advocating for alternative disciplinary measures and reallocating funds from school police to student well-being programs. The Police-Free LAUSD coalition’s successful campaign serves as a notable example, redirecting funds to the Black Student Achievement Plan.

Anti-carceral advocacy within social work involves movements like the National Association of Abolitionist Social Workers and the upEND movement, which challenge the role of social workers in the family policing system (child welfare) and advocate for community empowerment and support structures as alternatives.

Harm reduction, rooted in activism from the 1970s, emphasizes client self-determination and aims to minimize risks associated with behaviors like substance use through non-punitive approaches. Examples include low-barrier shelter models that prioritize safety and support over strict behavioral regulations, as seen in programs like Safe Harbor in San Francisco.

These innovative approaches face challenges and limitations, however. Funding dependencies on government and nonprofit sectors can co-opt anti-carceral practices, potentially compromising their radical intentions. Moreover, regulatory constraints like mandated reporting requirements present barriers to fully implementing anti-carceral approaches in social work practice, particularly in contexts involving substance use or past harms.

A deeper interrogation of social work’s entanglement with carceral systems is needed, along with advancing anti-carceral praxis to align with social work’s ethical imperatives of social justice, dignity, and self-determination. Practitioners and scholars must continue innovating and advocating for transformative change within the profession.
CoDNet: Controlled Diffusion Network for Structure Based Drug Design
Authors: Kazi Md Fahmi , Haque Shahil Yasar , Jahan Eashrat , Chakma Latin , Shermin Tamanna , Uddin Ahmed Asif , Islam Salekul , Shatabda Swakkhar , Azim Riasat
Published: February 2025

Motivation

Structure-based drug design (SBDD) holds promising potential to design ligands with high binding affinity and rationalize their interaction with targets. By utilizing geometric knowledge of the three-dimensional structures of target binding sites, SBDD enhances the efficacy and selectivity of therapeutic agents by optimizing binding interactions at the molecular level. Here we present CoDNet, a novel approach that combines the conditioning capabilities of ControlNet with the potency of the Diffusion model to create generative frameworks for molecular compound design. This proposed method pioneers the application of ControlNet in diffusion model-based drug development. Its ability to generate drug-like compounds from 3D conformations is prominent due to its capability to bypass Open Babel post-processing and integrate bond details and molecular information.

Results

For the gold standard QM9 dataset, CoDNet outperforms existing state-of-the-art methods with a validity rate of 99.02%. This competitive performance underscores the precision and efficacy of CoDNet's drug design, establishing it as a significant advancement with great potential for enhancing drug development initiatives.

Availability and implementation

https://github.com/CoDNet1/EDM_Custom
Diffuse nuclear Overhauser effect MRI contrast changes detected in multiple sclerosis subjects at 7T
Authors: Jacobs Paul S , Swain Anshuman , Wilson Neil , Liu Fang , Benyard Blake , Spangler Bailey , Seitz Madeleine , Fu Allen , Nanga Ravi Prakash Reddy , Elliott Mark A , Bar-Or Amit , Detre John , Murphy Jennifer Orthmann , Schindler Matthew K , Reddy Ravinder
Published: February 2025

Multiple sclerosis is an inflammatory demyelinating condition of the central nervous system affecting approximately 1 million people in the USA. Although standard structural MRI techniques are now the main imaging modality for multiple sclerosis diagnosis and management, they are yet to provide information regarding the metabolic profile of the disease. Ultra-high field 7T MRI systems have provided gains in signal-to-noise ratio (SNR) and spatial resolution for structural MRI as well as larger chemical shifts leading to improvements in specialized imaging sequences, such as nuclear Overhauser effect (NOE) imaging, that can evaluate macromolecular metabolite composition. In this work, NOE images were acquired on a cohort of multiple sclerosis and healthy control subjects to spatially map differences in their lipid metabolites as a result of NOE effects. NOE image data were acquired on a total of 25 subjects {15 multiple sclerosis subjects [10 females, 5 males (21–70 years)] and 10 healthy controls [5 females, 5 males (23–71 years)]} on a 7T MRI system with a frequency offset range of −5 to 5 ppm. A five-pool Lorentzian line fitting model was utilized to fit and quantitatively compare direct saturation (DS), magnetization transfer (MT), amide proton transfer (APT), amine, and relayed NOE (rNOE) and used as a comparison to conventional T1 maps. Grey and white matter tissues were segmented using the T1 maps, while the lesion tissue was segmented manually. Correlations between disease duration and lesion load were performed to investigate any existing relationship to image contrast. The primary findings of this work include statistically significant decreases in the rNOE pool for the normal-appearing white matter (NAWM) (11.4% decrease) and normal-appearing grey matter (NAGM) (10.6% decrease) in multiple sclerosis subjects compared to healthy controls. Additionally, a significant decrease in the amine pool was also observed for NAWM (15.3% decrease) in multiple sclerosis subjects compared to healthy controls. Changes in multiple sclerosis lesion contrast were also observed for several pools (DS, amine, and rNOE). Decreases in both the rNOE and amine pools suggest that in multiple sclerosis, there are diffuse decreases in mobile lipids, such as those found in neuronal cell bodies, as well as a decrease in proteins with amine groups. Furthermore, these measurable contrast changes were not detected in the corresponding T1 maps. NOE imaging can provide complementary metabolic information to conventional MRI methods. Future studies will focus on utilizing this technique for longitudinal tracking of disease progression and investigating similar demyelinating diseases.
Neural correlates of uncertainty processing in psychosis spectrum disorder
Authors: Fromm Sophie Pauline , Wieland Lara , Deneault Alix , Heinz Andreas , Katthagen Teresa , Schlagenhauf Florian
Published: February 2025

Psychotic beliefs are typically held with high certainty. Altered computation of uncertainty about a belief and about environmental dynamics may be an underlying mechanism of psychotic symptoms. We set out to shed light on behavioral and neural correlates of uncertainty processing and how it drives belief updating in psychosis.

This cross-sectional study included 19 participants with psychosis spectrum disorder (5 female 14 male) and 40 healthy control participants (21 female, 19 male) between 18-65 years of age. Participants performed a predictive inference task that required belief updating of a noisy outcome in a suddenly changing environment during functional magnetic resonance imaging. Behavioral and imaging data was analyzed with a computational model that approximates an ideal Bayesian observer. The model expects beliefs to be updated based on the relative belief uncertainty and environmental change point probability. Task performance, model parameters and associated neural activation were compared between groups and associated with self-reported delusional ideation and cognitive functioning.

While the belief updating speed overall did not differ between groups, the psychosis group showed lower task performance. Lower performance was associated with higher self-reported delusional ideation, even when controlling for cognitive functioning. Persons with psychosis spectrum disorder tended to persevere on beliefs after large prediction errors that signal environmental changes. They informed belief updates less by the probability of environmental change points, although this capacity seemed to depend on general cognitive functioning. The psychosis group also encoded the change point probability less in the superior occipital and fusiform gyrus, as well as a cluster comprising precentral to middle frontal gyrus. Activity in these clusters was associated with lower self-reported delusional ideation across the whole sample and lower general and negative symptoms in the clinical sample.

Persons with psychosis spectrum disorder did not seem to overestimate environmental volatility in general. Instead, they showed altered processing of information that occurred after environmental change points, whose probability was less well represented in brain regions encoding visual surprise and motor responses. Possibly, persons with psychosis spectrum disorder inadequately integrated visual surprise signals, leading to ineffective transmission to motor regions that eventually guide behavior. Summarizing, our study suggests that delusions could result from a tendency to stick to old beliefs even in the light of contrary evidence, due to a failure to integrate uncertainty information based on inferred environmental dynamics.
Ascending aorta over-angulation is a risk factor for acute type A aortic dissection: evidence from advanced finite element simulations
Authors: Ianniruberto Ione , Lo Presti Federica , Bifulco Olimpia , Tondi Davide , Saitta Simone , Astori Davide , Galgano Viviana L , De Feo Marisa , Redaelli Alberto , Di Eusanio Marco , Votta Emiliano , Della Corte Alessandro
Published: February 2025

OBJECTIVES

To assess whether ascending aorta over-angulation, a morphological feature recently found to be associated with acute type A aortic dissection, precedes dissection and how it affects wall stress distribution.

METHODS

A baseline finite element model, previously created by a neural network tool from end-diastolic CTA measurements in 124 healthy subjects, was modified to simulate the over-angulation accompanying aortic elongation, obtaining paradigmatic models with different ascending angulations (ascending-arch angle 145°-110°). The models were discretized and embedded in a deformable continuum representing surrounding tissues, aortic wall anisotropy and nonlinearity were accounted for, pre-tensioning at diastolic pressures was applied and peak systolic stresses were computed. Then, from 15 patients’ pre-dissection geometries, patient-specific finite element models of pre-dissection aorta were created through the same framework. The sites of maximum longitudinal stress were compared with the respective sites of dissection entry tear in post-dissection imaging.

RESULTS

Paradigmatic models showed that progressive narrowing of the ascending-arch angle was associated with increasing longitudinal stress (becoming significant for angles <130°), whereas the impact on circumferential stress was less consistent. In pre-dissection patient-specific models, the ascending-arch angle was narrowed (113°±11°) and the region of peak longitudinal stresses corresponded to the entry tear location in the respective post-dissection CTA.

CONCLUSIONS

This study strongly supports the hypothesis that the ascending-arch angle, as quantifier of aorta over-angulation, can be a good predictor of aortic dissection, since its narrowing below 130° increases longitudinal wall stress, and the dissection entry tears develop in the aortic wall in areas of highest longitudinal stress.
Assessing the environmental impact of coronary artery bypass grafting to decrease its footprint
Authors: Van Bree Egid M , Stobernack Tim , Boom Tadzjo , Geene Klaske , Kooistra Emma J , Li Wilson , Brakema Evelyn A , Golsteijn Laura , Hemelaar Pleun , Mcalister Scott , Mcgain Forbes , Van Zelm Rosalie , Touw Hugo R W
Published: February 2025

OBJECTIVES

An urgent transition to environmentally sustainable healthcare is required. The purpose of this study was to identified key areas for environmental impact mitigation for a coronary artery bypass grafting trajectory.

METHODS

An ISO14040/44-standardised life cycle assessment was conducted for the functional unit of an individual patient trajectory of elective coronary artery bypass grafting surgery, from operating room admission until intensive care unit discharge. Data were collected for products, processes, and services required for care delivery in a Dutch academic hospital for 12 patients. The environmental impact was calculated using the ReCiPe 2016 method.

RESULTS

A single patient trajectory caused 414 [IQR 383–461] kg CO2 equivalents of global warming, equal to 2,753km of driving an average Dutch petrol-fuelled car. Other notable environmental impacts were fine particulate matter, (non-)carcinogenic toxicity, land use, and terrestrial acidification. Operating room disposable products (162 kgCO2eq), energy use (48 kgCO2eq), and employee commute (36 kgCO2eq) contributed most to global warming. The extracorporeal circulation set, surgical drapes, intraoperative salvage set, surgical gowns, and cotton gauzes caused most of the disposables’ environmental impact. Most energy use occurred in the operating room via heating, ventilation, and air conditioning.

CONCLUSIONS

A coronary artery bypass grafting trajectory’s environmental impact primarily contributed to global warming. Most impact mitigation could be achieved by avoiding/reducing disposable product use when possible, or replacing these with reusables. Optimising operating room energy systems, switching to renewable energy, and encouraging low-emission employee commute can further reduce the environmental impact.
Classic hemiarch versus hemiarch and hybrid noncovered open stenting for acute DeBakey Type I dissection—a propensity score-matched analysis
Authors: Pitts Leonard , Montagner Matteo , Kofler Markus , Seeber Fabian , Heck Roland , Sündermann Simon , Buz Semih , Starck Christoph , Falk Volkmar , Kempfert Jörg
Published: February 2025

OBJECTIVES

This study investigates early and midterm outcomes after surgery for acute DeBakey type I dissection between classic hemiarch replacement or additional open noncovered stenting of the aortic arch.

METHODS

Patients who underwent surgery for acute DeBakey type I dissection receiving solely hemiarch replacement (2015–2022) or additional open noncovered stenting of the aortic arch (2018–2022) using the “Ascyrus Medical Dissection Stent” (AMDS) were included. After propensity score matching, the groups were compared in terms of clinical and radiological outcomes.

RESULTS

A total of 261 patients (155 hemiarch, 106 AMDS) were included. After matching, the cohort comprised two balanced groups with 108 patients (54 each group): thirty-day mortality was 19% in the hemiarch group vs 15% in the AMDS group (p = 0.61, OR = 0.77 (CI 0.27–2.12)). New postoperative stroke (p = 0.99, OR = 0.98 (CI 0.11–8.43)) and revision for malperfusion did not differ (p = 0.38, OR = 1.70 (CI 0.53–5.99)). The incidence of new distal anastomotic entries was significantly lower in the AMDS group with 17% vs 45% in the hemiarch group (p = 0.028, OR = 0.35 (CI 0.13–0.87)). True lumen expansion was significantly improved in the aortic arch (p = 0.006, OR = 3.15 (CI 1.41–7.34)) and stented portion of the descending aorta (p < 0.001, OR = 8.51 (CI 3.65–21.24)) as well as false lumen thrombosis in the aortic arch (p = 0.048, OR = 2.24 (CI 1.02–5.07)). Two-year survival did not differ (p = 0.170).

CONCLUSIONS

Additional AMDS implantation shows similar clinical outcomes, reduces the risk for new distal anastomotic entries and may be associated with superior positive aortic remodelling in the aortic arch and stented portion of the descending aorta. Long-term results regarding aortic remodelling and reintervention rate are highly needed.
Impact of a lambda-cyhalothrin formulation residues on larval Apis mellifera: Examining midgut and fat body morphological response to insecticide chronic exposure
Authors: Nere Pedro Henrique Ambrosio , Kern Rebecca Rey-Chai , Carneiro Lenise Silva , Lima Bárbara Soares Amoroso , Souza Diego dos Santos , Serrão José Eduardo
Published: February 2025

Pollination by honey bees (Apis mellifera) is crucial for maintaining biodiversity and crop yields. However, the widespread use of pesticides may threaten bees' survival by contaminating their resources. Lambda-cyhalothrin, a neurotoxic insecticide commonly used in agricultural pest control, poses particular risks. In insects, the midgut and fat body serve as primary barriers against xenobiotics, and exposure to these chemicals during larval development can impact adult bees. This study aimed to assess whether the residual concentration of lambda-cyhalothrin in pollen grains affects the midgut and fat body of larval A. mellifera workers after chronic exposure. The midgut epithelium of larvae exposed to a lambda-cyhalothrin-based insecticide exhibited autophagic vacuoles, apical cell protrusions, apocrine secretion, nuclear pyknosis, and high levels of polysaccharides and glycoconjugates in the cytoplasm, with smaller amounts in the brush border. Histochemical analysis revealed areas of vacuolation and damage to cell integrity in the midgut. In fat body cells, the insecticide increased polysaccharide storage and decreased lipid droplet diameter. Despite the histopathological damages, no effects were found in the larval development and adult emergence. These findings suggest the occurrence of apoptosis and autophagy in midgut cells and alterations in nutrient storage in the fat body of A. mellifera larvae exposed to the lambda-cyhalothrin-based insecticide, potentially impacting the physiology and development of this pollinator with possible effects on adult workers.
The Histone Chaperone Spn1 Preserves Chromatin Protections at Promoters and Nucleosome Positioning in Open Reading Frames
Authors: Tonsager Andrew J , Zukowski Alexis , Radebaugh Catherine A , Weirich Abigail , Stargell Laurie A , Ramachandran Srinivas
Published: February 2025

Spn1 is a multifunctional histone chaperone that associates with RNA polymerase II during elongation and is essential for life in eukaryotes. While previous work has elucidated regions of the protein important for its many interactions, it is unknown how these domains contribute to the maintenance of chromatin structure. Here, we employ digestion by micrococcal nuclease followed by single-stranded library preparation and sequencing (MNase-SSP) to characterize chromatin structure in Saccharomyces cerevisiae expressing wild-type or mutants of Spn1 (spn1K192N or spn1141-305). We mapped protections of all sizes genome-wide. Surprisingly, we observed a widespread loss of short fragments over nucleosome-depleted regions (NDRs) at promoters in the spn1K192N-containing strain, indicating critical functions of Spn1 in maintaining normal chromatin architecture outside open reading frames. Additionally, there are shifts in DNA protections in both Spn1 mutant expressing strains over open reading frames, which indicate changes in nucleosome and subnucleosome positioning. This was observed in markedly different Spn1 mutant strains, demonstrating that multiple functions of Spn1 are required to maintain proper chromatin structure in open reading frames. Changes in chromatin structure correlate positively with changes in gene expression as shown by RNA-seq analysis in the Spn1 mutant strains. Taken together, our results reveal a previously unknown role of Spn1 in the maintenance of NDR architecture and deepen our understanding of Spn1-dependent chromatin maintenance over transcribed regions.
It is One Big Puzzle
Authors: Hall Jon G
Published: February 2025

In a break from tradition, Jon G. Hall presents a cryptic crossword designed to tax the brains of even the most ardent computing professional. Good luck!
Validation of an automated method for the isolation and purification of fat-soluble vitamins and cholesterol for chromatographic analysis
Authors: van Aardt Marleen , Komarek Andrew R , Roche Michael , Ivarsen Elise
Published: February 2025

Background

The isolation and purification of vitamins A, E, D and cholesterol from food and feed test materials, for quantitation, is currently a time consuming and labor-intensive process. It includes separate steps for saponification, extraction, purification, and solvent evaporation. A new instrument (FLEX) was developed which improves and automates all steps involved, and which uses solid phase extraction (SPE). This study validates the FLEX automated method.

Objectives

The objective of this study was to validate the automated method by recovery of standards, analysis of reference materials, comparison against proficiency test materials, and comparison against manual reference methods.

Methods

The FLEX instrument automatically adds reagents, mixes and heats to saponify test materials, filters the digestate, extracts with SPE, and evaporates solvent.

Results

The accuracy of the automated FLEX Instrument method was confirmed by the agreement with NIST reference materials for retinol, α-tocopherol, cholecalciferol, ergocalciferol, and cholesterol. Accuracy also was compared against manual reference methods on 11 different food types that ranged from 4–100% fat, 0–75% protein, and 0–85% carbohydrates. The automated and manual methods were highly correlated with no bias or distortion over the range of test materials. Precision was similar to the manual methods for retinol recovery but improved for α-tocopherol and cholecalciferol analysis. The accuracy of the automated method also was confirmed for feed analysis. Eleven different animal feeds were analyzed in the FLEX and results were highly correlated with Association of American Feed Control Officials proficiency test results.

Conclusions

The automated method accurately and efficiently performed the multiple analytical steps necessary for the isolation and purification of the analytes in preparation for chromatographic analysis.

Highlights

The automated method was compared against industry standard methods and yielded equivalent results and improved precision. SPE technology was optimized to efficiently elute non-polar analytes, while retaining protein and other medium-polar analytes.
Involvement of a NIMA-related kinase in cell division in a liverwort Marchantia polymorpha
Authors: Mase Hikari , Sumiura Aoi , Yoshitake Yoshihiro , Kohchi Takayuki , Takahashi Taku , Motose Hiroyasu
Published: February 2025

NIMA-related kinases (NEKs) regulate a series of mitotic events in fungi and animals, whereas plant NEKs have been shown to control the growth direction of cells and organs. Plant NEKs are highly expressed in the meristem, but whether they regulate meristematic activity remains unknown. The liverwort Marchantia polymorpha has a single functional MpNEK1 gene, and its knockout results in twisted rhizoid growth. For a gain-of-function approach, we generated lines for the inducible expression of MpNEK1 using an estrogen receptor mediated system. Estradiol treatment effectively induced the accumulation of MpNEK1 mRNA and MpNEK1-Citrine fusion protein throughout the plant. MpNEK1 overexpression severely suppressed rhizoid and thallus growth, ultimately leading to the lethality of juvenile plants. This severe effect was observed even at the nanomolar level of estradiol. EdU staining and microtubule imaging clearly indicated suppression of cell division by estradiol-induced MpNEK1. MpNEK1 induction also reduced cortical microtubule density and dynamics, but not severely affected cell growth and morphology in thalli. Overexpression of kinase-deficient MpNEK1 also suppressed thallus and rhizoid growth, although to a slightly lesser extent than wild-type MpNEK1, indicating a phosphorylation-independent mechanism of growth suppression. Furthermore, Mpnek1 mutants exhibited growth suppression in their reproductive organs, the gametangiophores. This supports the role of MpNEK1 in cell division, as observed in both fungi and animals.
Sitting Together and Reaching to Play (START-Play) Physical Therapy Affects Dyadic Emotional Availability in Children and with Neuromotor Delay and their Families
Authors: Molinini Rebecca , Stuyvenburg Corri , Koziol Natalie A , Harbourne Regina T , Hsu Lin-Ya , Lobo Michele A , Willett Sandra L , Bovaird James A , Chu Virginia W , Price Sarah K , Shall Mary S , Dusing Stacey C
Published: February 2025

Objective

Emotional availability (EA) describes caregiver-child emotional attunement and is critical to fostering adaptive development. Although early physical therapist interventions adopt a family-centered approach, the impact of interventions on families is often not quantified. This study compares EA in dyads receiving usual care–early intervention (UC-EI) versus sitting together and reaching to play (START-Play) in addition to UC-EI.

Methods

Data were drawn from 106 children with neuromotor delay who were 7 to 16 months old at baseline (mean = 10.5 months) and from their caregiver (91% were mothers). The Emotional Availability Scale, Fourth Edition, was scored from 5-minute videotaped interactions collected at baseline and at 3, 6, and 12 months after baseline. Piecewise multilevel modeling controlling for baseline age and motor delay estimated short- and long-term effects between treatment groups. Additionally, within-group change over time was analyzed to understand if groups differed in direction of EA trajectories. Analyses were run aggregated across all participants and stratified by baseline severity of motor delay or caregiver-reported education.

Results

When comparing EA between groups, there were significant positive short- and long-term effects of START-Play on adult EA (gs > 0.38), sensitivity (gs > 0.26), structuring (gs > 0.43), and nonintrusiveness (gs > 0.36). For dyads with mild or significant motor delay or whose parent reported less than a bachelor’s degree at baseline, positive effects of START-Play were observed.

Conclusion

Results support important clinical implications for the positive effect of START-Play on EA. Similar child-level treatment effects highlight that the key difference between START-Play and UC-EI may lie in the way intervention affects caregivers. START-Play may be more beneficial to dyads with higher versus lower risks to EA.

Impact

Early physical therapist interventions can have a significant impact on parents, children, and the parent–child relationship. Measuring the effect of these interventions on the relationship is critical to optimizing the delivery of family-centered care.
Toward Procedural Judicial Review of Constitutional Law-Making Process in Israel
Authors: Ilan Gonen , Rosilio Gal
Published: February 2025

As part of Israel’s 2023 judicial overhaul, the Knesset enacted Amendment No. 3 to the Basic Law: The Judiciary on 24 July 2023. This amendment barred courts from reviewing the reasonableness of decisions made by the government, prime minister, or ministers. In response, numerous petitions were filed with the Israeli High Court of Justice. Given its importance, the High Court of Justice convened all 15 justices for the hearing, and in an 800-plus page ruling, it annulled the amendment citing abuses of the Knesset’s constituent power. This article examines the rulings of former Chief Justice Esther Hayut (acting Chief Justice during the ruling) and her successor Chief Justice Uzi Vogelman, focusing on alleged procedural flaws. After reviewing their rulings, we will propose an analysis of the impact of their judgments on procedural judicial review of the constitutional law-making process. Based on this, we will suggest refining and updating the Doctrine of the Principle of Participation—a doctrine developed in case law as a tool for procedural-constitutional review—to align with the stricter judicial standards of the constitutional process.
Mechanisms of ARA290 in counteracting cadmium-triggered neurotoxicity in PC12 cells
Authors: Motafeghi Farzaneh , Fakhri B Maryam S , Ghassemi Barghi Nasrin
Published: February 2025

Erythropoietin (EPO) is known for its role in hematopoiesis and also exhibits anti-inflammatory, anti-apoptotic, antioxidant, and cytoprotective properties. However, its clinical application is limited by hematopoietic side effects. ARA290, a non-hematopoietic derivative of EPO, selectively activates the innate repair receptor (IRR) and replicates these protective effects without the associated hematopoietic complications. Cadmium (Cd), a prevalent environmental toxin, causes neurotoxic damage through mechanisms such as oxidative stress, genotoxicity, apoptosis, and inflammation. This study explored ARA290’s neuroprotective effects against cadmium-induced toxicity in PC12 cells, an in vitro model for neuronal health. PC12 cells pretreated with ARA290 showed significantly improved cell viability in the MTT assay, indicating reduced cytotoxicity. The comet assay revealed decreased DNA damage, suggesting reduced genotoxicity. ARA290 also alleviated oxidative stress, as evidenced by reduced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), alongside increased glutathione (GSH), total antioxidant capacity (TAC), and superoxide dismutase (SOD) activities. A marker of apoptosis, TUNEL-positive cells, was significantly reduced. Additionally, ARA290 decreased inflammatory markers such as TNF alpha, IL1ß and IL 6. These findings demonstrate that ARA290, via IRR activation, provides robust neuroprotection against cadmium-induced toxicity, suggesting a multi-faceted protective mechanism. This highlights ARA290’s potential therapeutic role in managing heavy metal-induced neurotoxicity and supports further research into its long-term effects and applications in other neurodegenerative diseases or conditions involving environmental toxins.

Highlights
NUP98‐p65 complex regulates DNA repair to maintain glioblastoma stem cells
Authors: Li Feifei , Zhang Ying , Li Jiahui , Jiang Ranran , Ci Shusheng
Published: February 2025

The nuclear pore complex (NPC) is an evolutionarily conserved structure that maintains the traffic between the nucleus and cytoplasm. Here, we profiled the expression of nucleoporins (NUPs) in glioblastoma stem cells (GSCs) and found that NUP98 promoted GSC maintenance and therapeutic resistance. GSCs preferentially expressed NUP98, which is essential for GSC tumorigenesis in vitro and in vivo. RNA sequencing demonstrated that NUP98 regulated the expression of key DNA damage and repair pathways. NUP98 formed a complex with transcription factor p65 to directly activate genes involved in homologous repair. Attenuation of NUP98 or p65 expression induced unrepaired intrinsic DNA damage and sensitized GSC to ionizing radiation. Clinically, overexpression of NUP98 informs poor clinical outcome among glioblastoma (GBM) patients. Collectively, our results demonstrate that NUP98‐p65 represents a novel node in the regulation of DNA repair, suggesting a therapeutic strategy with potential clinical benefits for GBM patients.
A “Totally Different Beast”: The Effect of Time Variability on Clinical Competency Committee Decision-Making
Authors: Kinnear Benjamin , Santen Sally A. , DeCoursey Bailey , Ferris Sarah , Schumacher Daniel J.
Published: February 2025

Purpose

Competency-based, time-variable training (CBTVT) uses educational outcomes rather than time to determine learner readiness to progress through training. Clinical competency committees (CCCs) are critical components of CBTVT because they ultimately render time-variable promotion decisions. However, the effect of time variability on CCC member decision-making remains unclear. In this study, the authors explored the effect of time variability on the decision-making of CCC members at an internal medicine residency program.

Method

The authors used an evaluative case study approach to study the University of Cincinnati internal medicine residency program’s CBTVT pilot, called Transitioning in Internal Medicine Education Leveraging Entrustment Scores Synthesis (TIMELESS), with 2 to 3 residents per postgraduate year participating longitudinally between October 2020 and March 2022. Taking a constructionist worldview, the authors used semistructured interviews with members of the TIMELESS CCC to explore how time variability affected their decision-making about resident promotion. Interviews and observations were completed between February 2021 and January 2022.

Results

In total, the authors completed 16 interviews with 11 unique CCC members. Participants reported that time variability significantly affected their decision-making process. The authors developed 3 related themes. First, time variability created a sense of increased stakes of promotion decisions. Second, the increased perceived stakes of decisions led to more deliberate decision-making. Third, time in training and clinical experience still influenced time-variable promotion decisions.

Conclusions

Time variability changed CCC member perception of the decision-making (more risk, higher stakes), with subsequent change in their behaviors (in-depth review, active decision-making). Although many time-based programs make entrustment determinations that are not linked to tangible consequences (i.e., Would I trust?), TIMELESS asked CCC members to make entrustment decisions that were consequential (i.e., Will I trust?).