bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Novel Method to Fabricate Highly Functional Human Purkinje Networks
Authors: Ji Pengfei , Heinle Jeffrey S. , Birla Ravi K.
Published: October 2024

BACKGROUND

In this study, we present a method to bioengineer functional Purkinje networks using recent advances in laser-based bioprinting.

METHODS

A custom bioink as formulated using optimized concentrations of polyethylene glycol diacrylate (PEGDA), gelatin methacryloyl (GELMA), lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), and tartrazine. A standard triangle language (STL) model of Purkinje networks was developed based on the mammalian Purkinje network mapped out using India ink staining. A commercial bioprinter, the Lumen X, from CellInk, was used to bioprint Purkinje networks. The biocompatibility of the bioprinted Purkinje networks was tested using iPSCs from healthy donors. Negative molds of the Purkinje networks were designed to simulate interaction between Purkinje cells and adjacent cardiomyocytes using different degrees of overlap between the two cell types. The negative molds were also shown to be biocompatible, based on the culture of iPSCs derived from healthy donors.

RESULTS

We were able to successfully bioprint over 100 Purkinje networks and demonstrate biocompatibility with iPSCs for up to 7 days. Three different configurations of the negative molds were designed and fabricated and all three shown to be biocompatible with iPSCs for up to 7 days. A co-culture system was developed by placing the Purkinje networks in proximity to the negative molds for all three configurations designed.

CONCLUSION

Our results demonstrate the ability to bioprint Purkinje networks and molds and provide an in vitro system to study the functional interaction between Purkinje cells and adjacent cardiomyocytes.
Proton channel inactivation results in loss of chloroplast NDH complex activity
Authors: Strand Deserah D. , Ruf Stephanie , Sandoval-Ibáñez Omar A. , Bock Ralph
Published: October 2024

The plastidal photosynthetic complex I (formerly NAD(P)H dehydrogenase-like complex, NDH) remains enigmatic in its function within the electron transport chain of higher plants. While the NDH complex shares high homology with complex I, a key component of the respiratory electron transport chain, electron transport rates through the NDH complex in thylakoids are relatively low. In this study, we took a structure-function approach and mutated the plastid genome-encodedndhFgene to abolish the NdhF proton channel of the NDH complex. These mutations led to loss of plastoquinone reductase activity, indicating tight coupling between the proton and electron transfer reactions within NDH. Additionally, loss of the transverse helix of NdhF led to loss of the NDH complex, suggesting that this region of the NdhF subunit is required for complex stability. In agreement with previous studies usingndhknockout mutants, loss of NDH complex activity did not result in measurable changes in rates of steady-state cyclic electron flow. However, all mutants displayed a shift in the sensitivity of pH-dependent feedback regulation of the photosystem II antennae to total protonmotive force (pmf), indicating a defect in either stromal redox state orpmfdistribution into ΔpH and Δψ.
Interrogating the plasma proteome of repetitive head impact exposure and chronic traumatic encephalopathy
Authors: Saloner Rowan , Casaletto Kaitlin B. , Rayaprolu Sruti , Chakrabarty Paramita , Abisambra Jose F. , Spina Salvatore , Grinberg Lea T. , Seeley William W. , Miller Bruce L. , Kramer Joel H. , Rabinovici Gil D. , Asken Breton M.
Published: October 2024

Background

Exposure to repetitive head impacts (RHI) is associated with increased risk for chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy, and other neuropathological changes. Biological drivers of RHI-related neurodegeneration are not well understood. We interrogated the plasma proteome in aging adults with prior RHI compared to healthy controls (CTL) and individuals with Alzheimer’s disease (AD), including a subset characterized neuropathologically at autopsy.

Methods

Proximity extension assay (Olink Explore®) quantified 2,779 plasma proteins in 22 RHI patients (all AD-biomarker negative), 39 biomarker-confirmed AD, and 44 CTL. A subset of participants went to autopsy (N=16) allowing for comparisons of the antemortem plasma proteome between autopsy-confirmed CTE+ (N=7) and CTE-(N=9). Differential abundance and co-expression network analyses identified plasma proteomic signatures of RHI, which were functionally annotated using gene ontology and cell type enrichment analysis. Nonparametric correlations examined plasma proteomic associations with orthogonally-measured plasma biomarkers, global cognitive function, and semi-quantitative ratings of neuropathology burden at autopsy.

Results

Differential abundance analysis revealed 434 increased (vs. 6 decreased) proteins in RHI vs. CTL and 193 increased (vs. 14 decreased) in RHI vs. AD. Network analysis identified 9 protein co-expression modules (M1-M9), of which 7 were elevated in RHI compared to AD or CTL. Modules with increased abundance in RHI were enriched for mitochondrial/metabolic, cell division, and immunovascular (e.g., cell adhesion, TNF-signaling) processes. RHI-related modules exhibited strong and selective correlations with immunoassay-based plasma IL-6 in RHI cases, including the M2 TNF-signaling/cell adhesion module which harbored proteins that strongly tracked with cognitive function. RHI-related plasma protein signatures were similar in the subset of participants with autopsy-confirmed CTE, including immune and metabolic modules that positively correlated with medial temporal lobe tau and TDP-43 burden.

Conclusions

Molecular pathways in plasma most consistently implicated in RHI were tied to immune response, mitochondrial function, and cell metabolism. RHI-related proteomic signatures tracked with antemortem cognitive severity and postmortem neuropathological burden, providing converging evidence for their role in disease progression. Differentially abundant proteins and co-expression modules in RHI may inform mechanisms linking RHI to increased dementia risk, thus guiding diagnostic biomarker and therapeutic development for at-risk populations.
Late-life short-term dietary restriction ameliorates intestinal stem cell function and impacts intestinal stem cell DNA methylation
Authors: Kurup Kavitha , Chan Michael , Moore Eric , Ranjo-Bishop Michelle , Pham Kevin , Stanford David R , Freeman Willard M , Unnikrishnan Archana
Published: October 2024

Aging reduces the function of intestinal stem cells (ISCs) and dietary restriction (DR) has been shown to improve ISC function in young mice. However, there are no studies to-date that has evaluated the effect of short-term DR (stDR) implemented late-in-life on ISC function. Data from our laboratory shows for thefirst timethatstDR can ameliorate the age-related decline in ISC function by in-vitroenteroid forming assay. Transcriptomic analysis of the Lgr5+ISCs identified genes not commonly known for ISC function but showed a robust change with age which were reversed by stDR. Evaluation of the methylation status of selected genes (Slc28a3, Ly9, Cd2, Platr4) showed association between changes in 5mCG levels in the cis-acting regions of the genes and their expression. Our data suggest a potential role for DNA methylation in stDR’s effect on ISC function.
Rapid two-step target capture ensures efficient CRISPR-Cas9-guided genome editing
Authors: Shi Honglue , Al-Sayyad Noor , Wasko Kevin M. , Trinidad Marena I. , Doherty Erin E. , Vohra Kamakshi , Boger Ron S. , Colognori David , Cofsky Joshua C. , Skopintsev Petr , Bryant Zev , Doudna Jennifer A.
Published: October 2024

RNA-guided CRISPR-Cas enzymes initiate programmable genome editing by recognizing a 20-base-pair DNA sequence adjacent to a short protospacer-adjacent motif (PAM). To uncover the molecular determinants of high-efficiency editing, we conducted biochemical, biophysical and cell-based assays onS. pyogenesCas9 (SpyCas9) variants with wide-ranging genome editing efficiencies that differ in PAM binding specificity. Our results show that reduced PAM specificity causes persistent non-selective DNA binding and recurrent failures to engage the target sequence through stable guide RNA hybridization, leading to reduced genome editing efficiency in cells. These findings reveal a fundamental trade-off between broad PAM recognition and genome editing effectiveness. We propose that high-efficiency RNA-guided genome editing relies on an optimized two-step target capture process, where selective but low-affinity PAM binding precedes rapid DNA unwinding. This model provides a foundation for engineering more effective CRISPR-Cas and related RNA-guided genome editors.
Group B streptococci lyse endothelial cells to infect the brain in a zebrafish meningitis model
Authors: Ravishankar Sumedha , Tuohey Samantha M. , Ramos Nicole O. , Uchiyama Satoshi , Hayes Megan I. , Nizet Victor , Madigan Cressida A.
Published: October 2024

To cause meningitis, bacteria move from the bloodstream to the brain, crossing the endothelial cells of the blood-brain barrier. Most studies on how bacteria cross the blood-brain barrier have been performedin vitrousing cultured endothelial cells, due to a paucity of animal models. Group BStreptococcus(GBS) is the leading cause of bacterial meningitis in neonates and is primarily thought to cross the blood-brain barrier by transcytosis through endothelial cells. To test this hypothesisin vivo, we used optically transparent zebrafish larvae. Timelapse confocal microscopy revealed that GBS forms extracellular microcolonies in brain blood vessels and causes perforation and lysis of blood-brain barrier endothelial cells, which promotes bacterial entry into the brain. Vessels infected with GBS microcolonies were distorted and contained thrombi. Inhibition of clotting worsened brain invasion, suggesting a host-protective role for thrombi. The GBS lysincylE, implicated in brain invasionin vitro,was found dispensablein vivo. Instead, pro-inflammatory mediators associated with endothelial cell damage and blood-brain barrier breakdown were specifically upregulated in the zebrafish head upon GBS entry into the brain. Therefore, GBS crosses the blood-brain barrierin vivonot by transcytosis, but by endothelial cell lysis and death. Given that we observe the same invasion route for a meningitis-associated strain ofStreptococcus pneumoniae,our findings suggest that streptococcal infection of brain blood vessels triggers endothelial cell inflammation and lysis, thereby facilitating brain invasion.
Understanding TCR T cell knockout behavior using interpretable machine learning
Authors: Blennemann Marcus , Verma Archit , Bachl Stefanie , Carnevale Julia , Engelhardt Barbara E.
Published: October 2024

Genetic perturbation of T cell receptor (TCR) T cells is a promising method to un-lock better TCR T cell performance to create more powerful cancer immunotherapies, but understanding the changes to T cell behavior induced by genetic perturbations remains a challenge. Prior studies have evaluated the effect of different genetic modifications with cytokine production and metabolic activity assays. Live-cell imaging is an inexpensive and robust approach to capture TCR T cell responses to cancer. Most methods to quantify T cell responses in live-cell imaging data use simple approaches to count T cells and cancer cells across time, effectively quantifying how much space in the 2D well each cell type covers, leaving actionable information unexplored. In this study, we characterize changes in TCR T cell’s interactions with cancer cells from live-cell imaging data using explainable artificial intelligence (AI). We train convolutional neural networks to distinguish behaviors in TCR T cell with CRISPR knock outs of CUL5, RASA2, and a safe harbor control knockout. We use explainable AI to identify specific interaction types that define different knock-out conditions. We find that T cell and cancer cell coverage is a strong marker of TCR T cell modification when comparing similar experimental time points, but differences in cell aggregation characterize CUL5KO and RASA2KO behavior across all time points. Our pipeline for discovery in live-cell imaging data can be used for characterizing complex behaviors in arbitrary live-cell imaging datasets, and we describe best practices for this goal.
Characterization of vaginal microbiomes in clinician-collected bacterial vaginosis diagnosed samples
Authors: Brochu Hayden N , Zhang Qimin , Song Kuncheng , Wang Ling , Deare Emily A , Williams Jonathan D , Icenhour Crystal R , Iyer Lakshmanan K
Published: October 2024

Bacterial vaginosis (BV) is a type of vaginal inflammation caused by bacterial overgrowth, upsetting the healthy microbiome of the vagina. Existing clinical testing for BV is primarily based upon physical and microscopic examination of vaginal secretions, while more modern PCR-based clinical tests target panels of BV-associated microbes, such as the Labcorp NuSwab test. Remnant clinician-collected NuSwab vaginal swabs underwent DNA extraction and 16S V3-V4 rRNA gene sequencing to profile microbes in addition to those included in the Labcorp NuSwab test. Community State Types (CSTs) were determined using the most abundant taxon detected in each sample. PCR results for NuSwab panel microbial targets were compared against the corresponding microbiome profiles. Metabolic pathway abundances were characterized via metagenomic prediction from amplicon sequence variants (ASVs). Sequencing of 75 remnant vaginal swabs yielded 492 unique 16S V3-V4 ASVs, identifying 83 unique genera. NuSwab assay microbe quantification was strongly concordant with quantification by sequencing (p << 0.01). Samples in CST-I (18 of 18, 100%), CST-II (3 of 3, 100%), CST-III (15 of 17, 88%), and CST-V (1 of 1, 100%) were largely categorized as BV-negative via the NuSwab panel, while most CST-IV samples (28 of 36, 78%) were BV-positive or BV-indeterminate. BV-associated microbial and predicted metabolic signatures were shared across multiple CSTs. These findings show that 16S V3-V4 rRNA gene sequencing robustly reproduces PCR-based BV diagnostic testing results, accurately discriminates vaginal microbiome CSTs dominated by distinct Lactobacilli, and further elucidates BV-associated bacterial and metabolic signatures.
The Role of Interoception in Lifestyle Factors: A Systematic Review
Authors: Mulder Jesper , Boelens Mirte , van der Velde Laura A. , Brust Michelle , Kiefte-de Jong Jessica C.
Published: October 2024

Background

Interoception, the perception of the internal state of the body, offers an underrepresented and intriguing potential avenue for altering lifestyle-related behaviors. Interoception is intrinsically related to maintaining homeostasis and the flexible allostatic regulation of complex demands. Internal bodily states may also be influenced by lifestyle factors and related problems. This systematic review aimed to provide insight into the current state of evidence about the role of interoception in lifestyle factors.

Methods

Studies from three databases (PubMed, Embase, and Web of Science) were screened for eligibility based on two inclusion criteria: 1) at least one measure of interoception (e.g., interoceptive accuracy, attention, or awareness), and 2) at least one measure of a lifestyle factor (i.e., alcohol consumption, cognitive leisure and relaxation activities, eating behavior, exercise, sleep, or smoking). Risk of bias was assessed using an adjusted quality score checklist, consisting of five items related to study design, population size, exposure measurement, outcome measurement, and adjustment for confounders.

Results

The review included 73 studies. Out of the included studies, 51 measured interoceptive accuracy and 36 measured interoceptive attention. Six studies quantified interoceptive awareness. In terms of lifestyle factors, 26 studies on cognitive leisure and relaxation activities, 19 studies on eating behavior, 12 studies focused on alcohol consumption, 10 studies on exercise, five studies on smoking, and four studies on sleep were identified. Findings show positive relations between interoception and cognitive leisure and relaxation activities, eating behavior, and exercise.

Conversely, the consumption of alcohol is negatively related to interoception. Studies in the smoking and sleep lifestyle factors were sparse and of varying methodological quality.

Discussion

The findings of this review show that interoceptive domains are associated with various lifestyle factors, but the quality of the evidence is limited. Future longitudinal studies with more objective measures of interoception are needed in order to better understand the interrelations between interoception and lifestyle factors.

Highlights

Strong support for importance of mindfulness in interoception

Less strong positive relations between interoception, eating behavior, and exercise

Less strong negative relation between interoception and alcohol consumption

Results show lack of articles using objective interoceptive attention measures

Results show lack of quantification of interoceptive awareness
Nanopore strand-specific mismatch enables de novo detection of bacterial DNA modifications
Authors: Liu Xudong , Ni Ying , Ye Lianwei , Guo Zhihao , Tan Lu , Li Jun , Yang Mengsu , Chen Sheng , Li Runsheng
Published: October 2024

DNA modifications in bacteria present diverse types and distributions, playing crucial functional roles. Current methods for detecting bacterial DNA modifications via nanopore sequencing typically involve comparing raw current signals to a methylation-free control. In this study, we found that bacterial DNA modification induces errors in nanopore reads. And these errors are found only in one strand but not the other, showing a strand-specific bias. Leveraging this discovery, we developed Hammerhead, a pioneering pipeline designed for de novo methylation discovery that circumvents the necessity of raw signal inference and a methylation-free control. The majority (14 out of 16) of the identified motifs can be validated by raw signal comparison methods or by identifying corresponding methyltransferases in bacteria. Additionally, we included a novel polishing strategy employing duplex reads to correct modification-induced errors in bacterial genome assemblies, achieving a reduction of over 85% in such errors. In summary, Hammerhead enables users to effectively locate bacterial DNA methylation sites from nanopore FASTQ/FASTA reads, thus holds promise as a routine pipeline for a wide range of nanopore sequencing applications, such as genome assembly, metagenomic binning, decontaminating eukaryotic genome assemblies, and functional analysis for DNA modifications.
Identifying crystal structures beyond known prototypes from x-ray powder diffraction spectra
Authors: Parackal Abhijith S. , Goodall Rhys E. A. , Faber Felix A. , Armiento Rickard
Published: October 2024

The large amount of powder diffraction data for which the corresponding crystal structures have not yet been identified suggests the existence of numerous undiscovered, physically relevant crystal structure prototypes. In this paper, we present a scheme to resolve powder diffraction data into crystal structures with precise atomic coordinates by screening the space of all possible atomic arrangements, i.e., structural prototypes, including those not previously observed, using a pre-trained machine learning (ML) model. This involves (i) enumerating all possible symmetry-confined ways in which a given composition can be accommodated in a given space group, (ii) ranking the element-assigned prototype representations using energies predicted using the Wyckoff representation regression  ML model [Goodall , ], (iii) assigning and perturbing atoms along the degree of freedom allowed by the Wyckoff positions to match the experimental diffraction data, and (iv) validating the thermodynamic stability of the material using density-functional theory. An advantage of the presented method is that it does not rely on a database of previously observed prototypes and is, therefore capable of finding crystal structures with entirely new symmetric arrangements of atoms. We demonstrate the workflow on unidentified x-ray diffraction spectra from the ICDD database and identify a number of stable structures, where a majority turns out to be derivable from known prototypes. However, at least two are found not to be part of our prior structural data sets.

Published by the American Physical Society
2024
Quantum Rabin oblivious transfer using two pure states
Authors: Stroh Lara , Peat James T. , Kroneberg Mats , Puthoor Ittoop V. , Andersson Erika
Published: October 2024

Oblivious transfer between two untrusting parties is an important primitive in cryptography. There are different variants of oblivious transfer. In Rabin oblivious transfer, the sender Alice holds a bit, and the receiver Bob either obtains the bit, or obtains no information with probability p?. Alice should not know whether or not Bob obtained the bit. We examine a quantum Rabin oblivious transfer (OT) protocol that uses two pure states. Investigating different cheating scenarios for the sender and for the receiver, we determine optimal cheating probabilities in each case. Comparing the quantum Rabin oblivious transfer protocol to classical Rabin oblivious transfer protocols, we show that the quantum protocol outperforms classical protocols, which do not use a third party, for some values of p?. We find that quantum Rabin OT protocols that use mixed states can outperform quantum Rabin OT protocols that use pure states for some values of p?.

Published by the American Physical Society
2024
Real-space perspective on dephasing in solid-state high harmonic generation
Authors: Brown Graham G. , Jiménez-Galán Álvaro , Silva Rui E. F. , Ivanov Misha
Published: October 2024

We develop and demonstrate a fully real-space perspective on high harmonic generation (HHG) in crystals. Due to the Wannier-Stark localization induced on subcycle timescales in the presence of a strong field, real-space descriptions are natural for strongly driven solids. Our approach allows us to address the origin of the extremely short dephasing times, which appear necessary for agreement between experimental HHG measurements and theoretical calculations generally performed in reciprocal space. We develop a physically transparent model of real-space dephasing which relates its rate to the distance between different sites in a laser-driven lattice. Our approach leads to well-structured high harmonic spectra at the microscopic level, reproduces the results of macroscopic propagation, and demonstrates that the requirement for ultrafast dephasing times stems from the need for suppressing recombination events with large electron-hole separations during radiative recombination.

Published by the American Physical Society
2024
Phase diagram of the three-dimensional subsystem toric code
Authors: Li Yaodong , von Keyserlingk C. W. , Zhu Guanyu , Jochym-O'Connor Tomas
Published: October 2024

Subsystem quantum error-correcting codes typically involve measuring a sequence of noncommuting parity check operators. They can sometimes exhibit greater fault tolerance than conventional codes, which use commuting checks. However, unlike subspace codes, it is unclear if subsystem codes—in particular their advantages—can be understood in terms of ground-state properties of a physical Hamiltonian. In this paper, we address this question for the three-dimensional subsystem toric code (3D STC), as recently constructed by Kubica and Vasmer [], which exhibits single-shot error correction. Motivated by a conjectured relation between single-shot properties and thermal stability, we study the zero- and finite-temperature phases of an associated noncommuting Hamiltonian. By mapping the Hamiltonian model to a pair of 3D Z2 gauge theories coupled by a kinetic constraint, we find various phases at zero temperature, all separated by first-order transitions: There are 3D toric code-like phases with deconfined point-like excitations in the bulk, and there are phases with a confined bulk supporting a 2D toric code on the surface when appropriate boundary conditions are chosen. The latter is similar to the surface topological order present in 3D STC. However, the similarities between the single-shot correction in 3D STC and the confined phases are only partial: they share the same sets of degrees of freedom, but they are governed by different dynamical rules. Instead, we argue that the process of single-shot error correction can more suitably be associated with a path (rather than a point) in the zero-temperature phase diagram, a perspective, which inspires alternative measurement sequences enabling single-shot error correction. Moreover, since none of the above-mentioned phases survives at nonzero temperature, the single-shot error-correction property of the code does not imply thermal stability of the associated Hamiltonian phase.

Published by the American Physical Society
2024
Flowering plant communities mediate the effects of habitat composition and configuration on wild pollinator communities
Authors: Gillespie Mark A. K. , Baude Mathilde , Biesmeijer Jacobus , Boatman Nigel , Budge Giles E. , Crowe Andrew , Davies Nancy , Evans Rebecca , Memmott Jane , Morton R. Daniel , Moss Ellen , Potts Simon G. , Roberts Stuart P. M. , Rowland Clare , Senapathi Deepa , Smart Simon M. , Wood Claire , Kunin William E.
Published: October 2024

There is strong evidence that landscape‐scale factors such as habitat diversity, composition and configuration are important drivers of declines in pollinators and pollination services. However, context and species‐specific responses make it challenging to draw general conclusions about the most important components of landscapes that support diverse and abundant pollinator communities.

In this study, we took a functional‐traits approach to community assembly and tested the hypothesis that landscape properties act most strongly on pollinators indirectly, through their influence on flowering plant communities. Using plant and pollinator data from 96 landscapes in Britain, we tested the associations between plant and pollinator communities and local environmental factors, such as habitat cover and configuration, using path analysis based on Mantel and partial Mantel statistics.

When all pollinators were considered, we found that the environmental factors had stronger links to the composition of flowering plant communities than to the composition of pollinator communities. Further, the flowering plant community was strongly linked to the pollinator community suggesting a mediating role between land use and pollinators. When separating the pollinator community into taxonomic groups, we found the same result for hoverflies, but wild bees were linked to both environmental factors and flowering plants.

We further explored these links with structural equation models using the response‐effect trait framework as a guiding principle. We found strong evidence that land‐use composition and configuration influence the trait distribution and functional diversity of the pollinator community via plant community composition.

These findings suggest that the indirect effect of land use on pollinators via flowering plants should be considered in informing the design of pollinator friendly landscapes and in future research of the effects of land use and management on wild pollinators.

Read the free Plain Language Summary for this article on the Journal blog.
Developing an initial explanatory theory for Partnering for Change using realist evaluation
Authors: VanderKaay Sandra , Missiuna Cheryl , Bennett Sheila , Whalen Sandra Sahagian , Dix Leah , Camden Chantal , Kennedy Jennifer , Campbell Wenonah
Published: October 2024

Introduction

Partnering for Change (P4C) is an innovative practice model for school‐based occupational therapy developed in Canada and informed by a program of research spanning nearly two decades. National and international interest in P4C necessitated development of an explanatory theory to guide implementation in varied contexts. The purpose of this study is to document the process of theory development and to provide an overview of the initial P4C explanatory theory.

Methods

Realist evaluation was used to construct an initial explanatory theory of P4C drawing on P4C developers' conceptualisations of the model, document analysis, and analysis of transcripts from interviews and focus groups.

Consumer and community involvement

No consumers were involved in the study design or analysis.

Findings

Four sets of premises expressed as context‐mechanism‐outcome configurations (CMOCs) comprise the initial explanatory theory of P4C. An abstracted summary of these four sets along with contexts, mechanisms, and outcomes central to the P4C initial explanatory theory is presented. An exemplar CMOC is shared to illustrate how theoretical premises are developed and expressed using realist evaluation.

Conclusion

This study advances knowledge regarding the hypothesised core elements of P4C and provides an example of using realist evaluation to advance knowledge in occupational therapy. Preliminary implications for clinical practice are discussed.

PLAIN LANGUAGE SUMMARY

Partnering for Change (P4C) is a way of providing occupational therapy services in schools that helps all children to learn and participate successfully. P4C was created in Ontario, Canada, and has been researched for almost 20 years. People in different parts of Canada and other countries are interested in trying P4C. As the researchers who created P4C, we think there is a need to explain how it works so it can be used in different places. This study explains how we created a theory to describe P4C. To develop this theory, we used a method called realist evaluation that would help us explain how, why, and in what situations P4C works best. To do this, we analysed documents and transcripts of interviews and focus groups. Our findings are organised into four main ideas, each explained in terms of contexts (the situations), mechanisms (how and why P4C works), and outcomes (the impacts of P4C). One detailed example is given to show how these ideas were formed and work together. In conclusion, our study helps us understand the key parts of P4C and shows how realist evaluation can be used to improve knowledge in occupational therapy. The study also suggests some early ideas on how P4C can be used in practice.
Examination of the impact of using lactose or permeate for protein standardisation of skimmed milk on viscosity characteristics during evaporation
Authors: Long Tom , Finnegan Eoin W , Girivasan Amrutha , Tarapata Justyna , McCarthy Noel A , O'Mahony James A , O'Callaghan Tom F
Published: October 2024

The effect of permeate and lactose for protein standardisation of skim milk concentrate, was investigated during evaporation. Analysis of the viscosity–total solids (TS) profiles of each treatment demonstrated that the unstandardised protein sample had the greatest increase in viscosity, followed by permeate and finally lactose‐standardised samples. Heat stability and acid buffering capacity of the permeate standardised skim milk samples were higher when compared to the lactose‐standardised samples. This work identifies how standardisation media can impact the viscosity of concentrated skim milk, enabling higher TS at the evaporator outlet in some circumstances which could have the potential to improve overall process efficiency. Furthermore this work demonstrates that, evaporating to a target viscosity rather than target TS would offer greater control and consistency during processing.
Comparison of flavour of ghee from different pastoral areas based on electronic nose and GC–MS
Authors: Su Axi , Dai Anna , Yan Liqi , Zhang Zhechuan , Ding Bo , Bai Jialin , Gao Dandan , Yang Jutian , Zhang Hao , Liu Hongna
Published: October 2024

To compare the physicochemical properties and flavour differences of ghee in different pastoral areas, the moisture, fat, protein and volatile components of ghee were analysed. The results showed that yak ghee's moisture content was lower than cow ghee's moisture content, but the protein and fat content was higher than cow ghee's moisture content. Electronic nose (E‐nose) analysis showed that the flavour characteristics of ghee from different pastoral areas were similar, but the flavours of cow ghee and yak ghee were different. A total of 50 volatile components were identified by gas chromatography–mass spectrometry (GC–MS), mainly acids, aldehydes and alcohols. In addition, there were 13, 9, 4 and 13 characteristic volatile components in ghee from Gansu, Qinghai, Tibet and Xinjiang pastoral areas, respectively. This study distinguished the flavour differences of ghee in different pastoral areas and provided a theoretical basis for the traceability of ghee origin.
The role of large language models in interdisciplinary research: Opportunities, challenges and ways forward
Authors: Mammides Christos , Papadopoulos Harris
Published: October 2024

Large language models (LLMs) are gaining importance in research as they offer many benefits. One often overlooked benefit is their potential to facilitate and support interdisciplinary research, which is key to addressing current global challenges, such as the twin crises of biodiversity loss and climate change.

LLMs can help reduce the costs associated with knowledge transfer and bridge gaps between different fields of study. They can also be especially useful in helping ecologists understand and adopt powerful techniques common in other fields.

However, using LLMs in research, especially for complex tasks, carries important risks, including the possibility of generating inaccurate information, which can lead to false conclusions.

We recommend that researchers adhere to best practices when using LLMs for research by providing appropriate prompts and dividing complex tasks into smaller, more manageable tasks that facilitate learning and testing. Moreover, journals should implement policies to ensure that information and code generated using LLMs are properly validated. Academic programs should incorporate formal training in LLMs, equipping students and researchers with the necessary skills to use these tools more effectively and responsibly, including for interdisciplinary research.
Laparoscopic colectomy for patients with poor American Society of Anesthesiology classifications
Authors: Noda Keisuke , Nonaka Takashi , Tominaga Tetsuro , Takamura Yuma , Oishi Kaido , Hashimoto Shintaro , Shiraishi Toshio , Ono Rika , Ishii Mitsutoshi , Hisanaga Makoto , Takeshita Hiroaki , Fukuoka Hidetoshi , Oyama Shosaburo , Ishimaru Kazuhide , Kunizaki Masaki , Sawai Terumitsu , Matsumoto Keitaro
Published: October 2024

Introduction

The American Society of Anesthesiologists (ASA) classification is used to assess the fitness of a patient for surgery. Whether laparoscopic surgery is appropriate for colorectal cancer patients with poor ASA performance status (PS) remains unclear.

Methods

Among 4585 patients who underwent colorectal surgery between 2016 and 2023, this study retrospectively reviewed all 458 patients with ASA‐PS ≥3. Patients were divided into two groups: patients treated by open surgery (O group, n = 80); and patients treated by laparoscopic surgery (L group, n = 378). We investigated the impact of surgical approach on postoperative complications in patients with colorectal cancer and ASA‐PS ≥3.

Results

Operation time was longer (170 min vs. 233 min, p < .001), blood loss was less (156 mL vs. 23 mL, p < .001), postoperative complications were less frequent (40.0% vs. 25.1%, p = .008), and hospital stay was shorter (23 days vs. 14 days, p < .001) in L group. Univariate analysis revealed rectal cancer, open surgery, longer operation time, and blood loss as factors significantly associated with postoperative complications. Multivariate analysis revealed open surgery (odds ratio [OR] 2.100, 95% confidence interval [CI] 1.164–3.788; p = .013) and longer operation time (OR 1.747, 95% CI 1.098–2.778; p = .018) as independent predictors of postoperative complications.

Conclusion

Laparoscopic surgery provides favorable outcomes for colorectal cancer patients with poor ASA‐PS.
When products speak differently: Designing new languages for established products
Authors: Artusi Federico , Bellis Paola , Verganti Roberto
Published: October 2024

Innovating product language has been proven to be an effective measure to change what products mean to customers and create new product categories. However, how to embed a new language into a product characterized by an established design has not been addressed in the past. Thus, we discuss a single case study of Videndum, a company producing premium branded tools and accessories for content creation (i.e., photography supports and accessories) that is redefining their product language and seeking to incorporate new narratives into their existing line‐up of products. Our case study is based on 18 interviews across all levels of the organization, analysis of archival data and observations to explore the actions the company is taking to change product language for their established products. Our findings show that designers can work at the level of the design principles to inform how new meanings can be embedded into signs at the product level, to build a new coherent product language. We identify two layers of design principles, value‐principles and solution‐principles, and show their different impact on product language. By doing so, we contribute to understand how companies design new product languages for established products in practice, providing managers with practical knowledge on how to perform the translation from abstract values to product features.
Genetic Analysis of Neurite Outgrowth Inhibitor‐Associated Genes in Parkinson's Disease: A Cross‐Sectional Cohort Study
Authors: Huang Xiurong , Wang Yige , Xiang Yaqin , Zhao Yuwen , Pan Hongxu , Liu Zhenhua , Xu Qian , Sun Qiying , Tan Jieqiong , Yan Xinxiang , Li Jinchen , Tang Beisha , Guo Jifeng
Published: October 2024

Background

Parkinson's disease (PD) is a neurodegenerative disease caused by a combination of aging, environmental, and genetic factors. Previous research has implicated both causative and susceptibility genes in PD development. Nogo‐A, a neurite outgrowth inhibitor, has been shown to impact axon growth through ligand‐receptor interactions negatively, thereby involved in the deterioration of dopaminergic neurons. However, rare genetic studies have identified the relationship between neurite outgrowth inhibitor (Nogo)‐associated genes and PD from a signaling pathway perspective.

Methods

We enrolled 3959 PD patients and 2931 healthy controls, categorized into two cohorts based on their family history and age at onset: sporadic early Parkinson's disease & familial Parkinson's disease (sEOPD & FPD) cohort and sporadic late Parkinson's disease (sLOPD) cohort. We selected 17 Nogo‐associated genes and stratified them into three groups via their function, respectively, ligand, receptors, and signaling pathway groups. Additionally, we conducted the burden analysis in rare variants, the logistic regression analysis in common variants, and the genotype–phenotype association analysis. Last, bioinformatics analysis and functional experiments were conducted to identify the role of the MTOR gene in PD.

Results

Our findings demonstrated that the missense variants in the MTOR gene might increase PD risk, while the deleterious variants in the receptor subtype of Nogo‐associated genes might mitigate PD risk. However, common variants of Nogo‐associated genes showed no association with PD development in two cohorts. Furthermore, genotype–phenotype association analysis suggested that PD patients with MTOR gene variants exhibited relatively milder motor symptoms but were more susceptible developing dyskinesia. Additionally, bioinformatics analysis results showed MTOR gene was significantly decreased in PD, indicating a potential negative role of the mTOR in PD pathogenesis. Experimental data further demonstrated that MHY1485, a mTOR agonist, could rescue MPP+‐induced axon inhibition, further implicating the involvement of mTOR protein in PD by regulating cell growth and axon growth.

Conclusions

Our preliminary investigation highlights the association of Nogo‐associated genes with PD onset in the Chinese mainland population and hints at the potential role of the MTOR gene in PD. Further research is warranted to elucidate the mechanistic pathways underlying these associations and their therapeutic implications.
Institutional Investors and the Fight Against Climate Change
Authors: Kolasa Thea , Sautner Zacharias
Published: October 2024

Research Question/Issue

This article examines the role of institutional investors in the fight against climate change. We explain the institutional context, provide evidence highlighting institutional investors' bright and dark sides in this fight, and develop multiple ideas for future research.

Research Findings/Insights

We show that climate change has a significant impact on institutional investors. Simultaneously, we demonstrate that institutional investors can have a significant positive impact on fighting climate change, particularly if they actively engage with portfolio firms to reduce carbon emissions. For risk management reasons, this is in their own interest, and it is also in the interests of society.

Theoretical/Academic Implications

We highlight possible future research avenues on the link between institutional investors and climate change, emphasizing issues related to environmental, social, and governance (ESG) rating agencies, greenwashing, and the risk of a loss of trust in ESG products. Climate change constitutes one of the grand challenges of our time, and substantially more research on the role of finance is required.

Practitioner/Policy Implications

Climate change imposes financial risks on institutional investors' portfolio firms, which must be actively addressed in the investment process. Nascent evidence indicates that markets have begun pricing these risks. Institutional investors can positively influence climate change by engaging portfolio firms on their emissions and simultaneously reducing climate transition risks.
Is there a possibility that P‐glycoprotein reduces reproductive toxicity in males but breast cancer resistance protein does not?
Authors: Yu Zhiheng , Liu Wei , Wang Ziyu , Chen Yidong , Yan Jie , Benet Leslie Z. , Zhai Suodi
Published: October 2024

In traditional understanding, P‐glycoprotein (P‐gp) and Breast Cancer Resistance Protein (BCRP) are regarded as efflux transporters that can decrease the concentration of their substrates in the testis, thereby reducing reproductive toxicity in males (RTM) and protecting spermatogenesis. However, there is currently no direct pharmacological evidence demonstrating that P‐gp and BCRP can reduce the occurrence of drug‐induced RTM. In this study, we chose small molecule targeted anti‐tumor agents as model drugs and systematically retrieved and collected information on the transporters and RTM for these drugs, followed by correlation analysis. The results showed a lower incidence of RTM for P‐gp substrate drugs, which aligns with previous knowledge. Surprisingly, BCRP substrate drugs exhibited higher rates of RTM in various dimensions, contradicting previous notions. This discrepancy may be attributed to the differential distribution and transport directions of P‐gp and BCRP on the blood–testis barrier (BTB). For the first time, this study may provide clues that BCRP may facilitate the passage of exogenous compounds across the BTB, increasing the occurrence of RTM, rather than protecting spermatogenesis as traditionally believed. Furthermore, this study provides the first direct verification of the role of P‐gp in reducing RTM and protecting spermatogenesis.
The Prognostic Significance of Tumoral Melanosis
Authors: Potter Alison J. , Ferguson Peter M. , Lo Serigne N. , Ahmed Tasnia , Rawson Robert V. , Thompson John F. , Long Georgina V. , Scolyer Richard A.
Published: October 2024

Background

Tumoral melanosis (TM) is a histological term to describe a nodular aggregation of macrophages containing melanin pigment (melanophages) that is devoid of viable melanocytes. It is most often identified in skin, where it may be appreciated clinically as a pigmented lesion; however, it can also be found in other organs such as lymph nodes. The presence of TM is usually thought to signify the presence of a regressed melanoma or other pigmented tumor. Until recently, it was a relatively uncommon finding; however, with the use of effective systemic therapies against melanoma, its occurrence in histological specimens is more frequent.

Methods

We identified and reviewed all histopathological diagnoses of TM at any organ site reported at a single institution from 2006 to 2018. TM cases were paired with non‐TM cases of cutaneous melanoma through propensity score matching at a 1:2 ratio, and their survival outcomes were compared. The clinical outcomes examined included recurrence‐free survival (RFS), distant disease‐free survival (DDFS), melanoma‐specific survival (MSS), and overall survival (OS).

Results

TM was reported in 79 patients. Their median age was 65 years (range 22–88), with a 2:1 male predominance (51 out of 79, 65%). The most common organ involved was the skin (67%), with a third of all cases localized to a lower limb (36%). TM had a strong association with the presence of melanoma (91%) and regression at other sites of melanoma (54%), suggesting that it is part of a systemic immune response against melanoma. Most patients with TM either previously or subsequently developed histologically confirmed melanoma in the same anatomical region as the TM (89%). Thirty‐five TM patients were matched with 70 non‐TM cases. Patients with melanoma who developed TM without prior regional or systemic therapy showed improved MSS (p = 0.03), whereas no statistically significant differences were observed in terms of RFS, DDFS, and OS.

Conclusions

TM usually occurs in the context of a previous or subsequent cutaneous melanoma and is associated with improved MSS. It is important that TM is recognized by pathologists and documented in pathology reports.
A root mucilage analogue from chia seeds reduces soil gas diffusivity
Authors: Haupenthal Adrian , Duddek Patrick , Benard Pascal , Knott Mathilde , Carminati Andrea , Jungkunst Hermann F. , Kroener Eva , Brüggemann Nicolas
Published: October 2024

Gas exchange in the soil is determined by the size and connectivity of air‐filled pores. Root mucilage reduces air‐filled pore connectivity and thus gas diffusivity. It is unclear to what extent mucilage affects soil pore connectivity and tortuosity. The aim of this study was to gain a better understanding of gas diffusion processes in the rhizosphere by explaining the geometric alterations of the soil pore space induced by mucilage. We quantified the effect of a root mucilage analogue collected from chia seeds without intrinsic respiratory activity on oxygen diffusion at different water contents during drying–rewetting cycles in a diffusion chamber experiment. Quantification of oxygen diffusion showed that mucilage decreased the gas diffusion coefficient in dry soil without affecting air‐filled porosity. Without mucilage, a hysteresis in gas diffusion coefficient during a drying–rewetting cycle was observed. The effect depended on particle size and diminished with increasing mucilage content. X‐ray computed tomography imaging indicated a hysteresis in the connectivity of the gas phase during a drying–rewetting cycle for samples without mucilage. This effect was attenuated with increasing mucilage content. Furthermore, electron microscopy showed that mucilage structures formed in drying soil increase with mucilage content, thereby progressively reducing the connectivity of the gas phase. In conclusion, the effect of mucilage on soil gas diffusion highly depends on soil texture and mucilage content. The diminishing hysteresis with the addition of mucilage suggests that plant roots secrete mucilage to balance oxygen availability and water content, even under fluctuating moisture conditions.