bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Rgg quorum-sensing machinery to create an innovative recombinant protein expression system in Streptococcus thermophilus
Authors: Gardan Rozenn , Honvo-Houeto Edith , Mézange Christine , Maillot Nathanael Jean , Balvay Aurélie , Rabot Sylvie , Bermúdez-Humarán Luis G. , Langella Philippe , Monnet Véronique , Juillard Vincent
Published: September 2024

Streptococcus thermophilus holds promise as a chassis for producing and secreting heterologous proteins. Used for thousands of years to ferment milk, this species has generally recognized as safe (GRAS) status in the USA and qualified presumption of safety (QPS) status in Europe. In addition, it can be easily genetically modified thanks to its natural competence, and it secretes very few endogenous proteins, which means less downstream processing is needed to purify target proteins, reducing costs. Extracellular degradation of heterologous proteins can be eliminated by introducing mutations that inactivate the genes encoding the bacterium’s three major surface proteases. Here, we constructed an inducible expression system that utilizes a peptide pheromone (SHP1358) and a transcriptional regulator (Rgg1358) involved in quorum-sensing regulation. We explored the functionality of a complete version of the system, in which the inducer is produced by the bacterium itself, by synthesizing a luciferase reporter protein. This complete version was assessed with bacteria grown in a chemically defined medium but also in vivo, in the faeces of germ-free mice. We also tested an incomplete version, in which the inducer had to be added to the culture medium, by synthesizing luciferase and a secreted form of elafin, a human protein with therapeutic properties. Our results show that, in our system, protein production can be modulated by employing different concentrations of the SHP1358 inducer or other SHPs with closed amino acid sequences. We also constructed a genetic background in which all system leakiness was eliminated. In conclusion, with this new inducible expression system, we have added to the set of tools currently used to produce secreted proteins in S. thermophilus, whose myriad applications include the delivery of therapeutic peptides or proteins.
Decoding Cytokine Networks in Ulcerative Colitis to Identify Pathogenic Mechanisms and Therapeutic Targets
Authors: Olbei Marton , Hautefort Isabelle , Thomas John P. , Csabai Luca , Bohar Balazs , Ibraheim Hajir , Saifuddin Aamir , Modos Dezso , Powell Nick , Korcsmaros Tamas
Published: September 2024

Ulcerative colitis (UC) is a chronic inflammatory disorder of the gastrointestinal tract characterised by dysregulated cytokine signalling. Despite the advent of advanced therapies targeting cytokine signalling, treatment outcomes for UC patients remain suboptimal. Hence, there is a pressing need to better understand the complexity of cytokine regulation in UC by comprehensively mapping the interconnected cytokine signalling networks that are perturbed in UC patients. To address this, we undertook systems immunology modelling of single-cell transcriptomics data from colonic biopsies of treatment-naive and treatment-exposed UC patients to build complex cytokine signalling networks underpinned by putative cytokine–cytokine interactions. The generated cytokine networks effectively captured known physiologically relevant cytokine–cytokine interactions which we recapitulated in vitro in UC patient-derived colonic epithelial organoids. These networks revealed new aspects of UC pathogenesis, including a cytokine subnetwork that is unique to treatment-naive UC patients, the identification of highly rewired cytokines across UC disease states (IL22, TL1A, IL23A, and OSM), JAK paralogue-specific cytokine-cytokine interactions, and the positioning of TL1A as an important upstream regulator of TNF and IL23A as well as an attractive therapeutic target. Overall, these findings open up several avenues for guiding future cytokine-targeting therapeutic approaches in UC, and the presented methodology can be readily applied to gain similar insights into other immune-mediated inflammatory diseases (IMIDs).

One Sentence Summary

A systems immunology map of cytokine interaction networks in ulcerative colitis reveals novel insights into disease pathogenesis, with potential to guide future cytokine-targeting therapeutic strategies.
Elucidating early intestinal stem cell response to bacterial infection
Authors: Lebon S. , Davidzohn N. , Habshush Menachem A. , Katz A. , Wigoda N. , Rotkopf R. , Dadosh T. , Levin-Zaidman S. , Dezorella N. , Blumberger N. , Hoffman D. , Hofree M. , Biton M.
Published: September 2024

Intestinal stem cells (ISCs) are the regenerative force of the gut epithelium. Lgr5+-ISC have been shown to respond to changes in their microenvironment by coping with different metabolites, adapting to caloric changes, and recovering from injury and inflammation. However, how pathogenic bacteria affect adult stem cell regeneration and, as a consequence, the overall tissue adaption to infection has yet to be explored in depth. Here, we interrogated early Lgr5+ ISC responses to an enteric intracellular pathogen by profiling individual IECs from the mouse small intestine. Utilizing GFP-labeledSalmonella enterica,we isolated intracellular invaded cells to elucidate invasion programs of epithelial cell subsets. In particular, we identified aSalmonella-specific infection signature comprised of antimicrobial peptide (AMP) genes, including the Defensin gene family. Our findings demonstrate thatSalmonella entericatargets differentiated Paneth, enterocytes, and stem/progenitor cells at these early stages of infection. In response, a rapid Lg5+ ISC-driven cellular remodeling to enterocyte and Paneth lineages expressing AMP genes is initiated to combat the intruders. Importantly, we uncovered an ISC differentiation program via inflammasome activation to protect the crypt environment, while eliminating infected stem cells from the overall stem cell pool. This novel Lgr5+ stem cell defense mechanism not only protects the gut epithelium from persistent bacterial infection but also promotes tissue regeneration. We propose epithelial remodeling to AMP-secreting cells as a novel innate immune response to handle different gut stresses mediated by Lgr5+ ISCs to maintain organizational principles of gut homeostasis and physiology.
Network-driven identification of indisulam neo-substrates for targeted protein degradation
Authors: Jarnuczak Andrew F. , Andres Angelo , Yogev Orli , Ashenden Stephanie K. , Ye Cheng , Pachl Fiona , Zhang Andrew , Cuomo Maria Emanuela , Jin Meizhong
Published: September 2024

Indisulam, a DCAF15-based molecular glue degrader, induces widespread proteome changes with implications for cell division and chromosome segregation. While RBM39 and RBM23 are two well-characterized indisulam neo-substrates, additional targets likely exist. To identify those degradation targets, we applied a network-based approach to prioritize novel neo-substrates from large-scale omics data. Our approach integrates proteome-wide expression measurements with information from publicly accessible databases into a multiplex heterogeneous network. Utilizing a Random Walk with Restart algorithm, we identified a preliminary list of 30 neo-substrates. These proteins are likely interactors with DCAF15 in the presence of indisulam and are subject to subsequent degradation. Experimental validation of RBM5, one of the shortlisted candidates, confirmed its degradation in a proteasome-dependent manner, supporting its identification as a novel indisulam neo-substrate. Our work employs established network resources and analytical methods to effectively identify direct targets of indisulam molecular glue degrader. This approach is readily adaptable for exploring novel targets across other molecular glue systems, enhancing its applicability and value to the drug discovery community.

Molecular glue neo-substrate identification via network analysis and proteomics profiling
PTPN11Mutation Clonal Hierarchy in Acute Myeloid Leukemia
Authors: Fobare Sydney , Sharpe Chia , Quinn Kate , Bryant Kinsey , Miles Linde A. , Bowman Robert L. , Cheney Carolyn , Furby Casie , Long Marissa , Fyock Kaytlynn , Wronowski Ben , Lerma James R. , Mullaney Allison , Mrózek Krzysztof , Nicolet Deedra , Sesterhenn Tom , Johnstone Megan E. , Rai Shesh N. , Pasare Chandrashekhar , Zimmermann Nives , Carroll Andrew J. , Stone Richard M. , Wang Eunice S. , Kolitz Jonathan E. , Powell Bayard L. , Perentesis John P. , Eisfeld Ann-Kathrin , Hertlein Erin , Byrd John C.
Published: September 2024

Mutations in protein tyrosine phosphatase non-receptor type 11 (PTPN11) have been considered late acquired mutations in acute myeloid leukemia (AML) development. To interrogate the ontogeny ofPTPN11mutations, we utilized single-cell DNA sequencing and identified thatPTPN11mutations can occur as initiating events in some AML patients when accompanied by strong oncogenic drivers, commonlyNPM1mutations. The co-driver role ofPTPN11mutations was confirmed in a novel murine model that exhibits an AML phenotype with early expansion of a diverse set of variably differentiated myeloid cells that engrafted into immunodeficient and immunocompetent mice. This immune diversity was reconstituted from early precursor cells when engrafted into immunodeficient mice. Moreover, immune diversity was also observed in the blast component of patient samples withNPM1andPTPN11mutations, providing novel antigen targets for immune based approaches in this subset of AML that is resistant to multiple targeted therapies.
Photoproduction of
ηc,b
near threshold
Authors: Liu Wei-Yang , Zahed Ismail
Published: September 2024

We analyze the photoproduction of ηc,b off a proton in the threshold region, in terms of C-odd gluonic correlations in the off-forward proton matrix element. Near threshold, the skewness is large, leading to a production amplitude that is dominated by four C-odd twist-3 gluon GPDs. We use the QCD instanton vacuum to estimate these C-odd contributions in the proton. The results are used to estimate the differential cross sections for coherent photoproduction of ηc,b in the threshold region, at current electron facilities.

Published by the American Physical Society
2024
Chiral-odd GPDs in the bag model
Authors: Tezgin Kemal , Maynard Brean , Schweitzer Peter
Published: September 2024

A study of chiral-odd generalized parton distributions (GPDs) of the nucleon is presented in the bag model demonstrating that in this model all four chiral-odd GPDs are nonzero contrary to other claims in literature. The bag model results for the GPDs HTq(x,ξ,t), ETq(x,ξ,t), H˜Tq(x,ξ,t) agree with other models within a typical quark model accuracy. We present one of the few quark model calculations where polynomiality is satisfied and the sum rule ∫dxE˜Tq(x,ξ,t)=0 holds. We confront our results with predictions from the large-Nc limit, and with lattice QCD calculations. We conclude that the bag model successfully catches the main features of chiral-odd GPDs.

Published by the American Physical Society
2024
Supersymmetric Virasoro minimal strings
Authors: Johnson Clifford V.
Published: September 2024

A random matrix model definition of a family of N=1 supersymmetric extensions of the Virasoro minimal string of Collier, Eberhardt, Mühlmann, and Rodriguez is presented. An analysis of the defining string equations shows that the models all naturally have unambiguous nonperturbative completions, which are explicitly supplied by the double-scaled orthogonal polynomial techniques employed. Perturbatively, the multiloop correlation functions of the model define a special supersymmetric class of “quantum volumes,” generalizing the prototype case, some of which are computed.

Published by the American Physical Society
2024
Safeguarding economic stability: the interplay of fiscal dominance and monetary policy in South Africa
Authors: Buthelezi Eugene Msizi
Published: September 2024

Purpose

The purpose of this study is to investigate the interplay between fiscal dominance and monetary policy in South Africa from 1960 to 2023.

Design/methodology/approach

The study employs a structural vector autoregression (SVAR) medel to analyze the relationship between fiscal dominance and monetary policy. Short-term and long-term shocks of government borrowing and deficits are examined to understand their impact on inflation dynamics.

Findings

Fiscal dominance has a significant effect both in the short and long run. There is evidence that government debt and deficits increase inflation, overriding the effects of monetary policy aimed at maintaining price stability. On the other hand, the study reveals that money supply shocks have a greater effect in reducing fiscal dominance compared to interest rate shocks. The variance movement on inflation is significantly explained by government debt and deficits. This emphasizes the persistence of inflationary pressures associated with fiscal dominance, highlighting the importance of effective policy interventions to mitigate inflationary risks.

Originality/value

This study contributes to the existing literature by providing insights into the dynamics of fiscal dominance in South Africa. Moreover, this study extends the theoretical framework of the fiscal theory of the price level (FTPL) and the government budget constraint. This study contributes valuable insights into the dynamics of fiscal dominance in South Africa and offers guidance for policymakers in formulating strategies to safeguard economic stability.
A systematic review of stakeholder’s interest towards achieving net zero carbon building
Authors: Falana Justina , Osei-Kyei Robert , Tam Vivian W.Y.
Published: September 2024

Purpose

Stakeholder interests are complex, sensitive and highly uncertain and may influence the development of net zero carbon building (NZCB). However, this study aims to conduct a systematic literature review to explore the stakeholder interests towards achieving NZCB.

Design/methodology/approach

A total of 62 articles were identified from the Scopus database and thoroughly reviewed to extract relevant information on stakeholders' interest towards achieving NZCB.

Findings

A total of 28 stakeholder interests influencing the development of NZCB were identified from the literature and were classified into six major groups according to their uniqueness (economic, social, environmental, technological, political, regulatory and legal).

Research limitations/implications

The findings of this study provide insight into the specific stakeholder interests towards achieving NZCB. Thus, the findings of this study could serve as a guide for future research, policy formulation and implementation to expedite the practice of building towards net zero carbon (NZC). Empirical studies are suggested in future studies to test and consolidate the theoretical claims of this study.

Originality/value

This paper undertakes a comprehensive systematic review of studies on stakeholder interests towards achieving NZCB, which is the least investigated in the literature.
The determinants of participation in online business forums: exploring the interplay of need factors and reciprocity
Authors: Gharib Rebwar Kamal
Published: September 2024

Purpose

The purpose of this study is to enhance the understanding of the drivers of participation in online business forums (OBFs). Specifically, it examines how reciprocity and three distinct types of needs (functional, psychological and hedonic) shape the participation behaviour of members in OBFs.

Design/methodology/approach

This study employs a multilevel analysis, integrating Social Exchange Theory and Uses and Gratification Theory to develop and validate a research framework. Data were collected via online questionnaires (N = 596) from 48 business forums on LinkedIn. The data analysis was carried out using PLS-SEM in stages. A confirmatory factor analysis was carried out to assess the measurement model, including validating the reliability and validity of the measurement items. The direct hypotheses were tested, followed by a post ad-hoc analysis to test the mediation and moderation hypotheses.

Findings

This study shows the impact of three need factors – functional, psychological and hedonic – and reciprocity on community members' participation behaviour in OBFs. The findings indicate that fulfiling functional, psychological and hedonic needs are key determinants driving active participation. The study further highlights the coexistence of two types of reciprocity: direct and indirect. However, the data analysis results show that only indirect reciprocity motivates participation in OBFs. Furthermore, the study reveals that indirect reciprocity not only precedes participation but also acts as a pivotal factor interacting with the interrelationship between the need factors and participation levels in OBFs.

Originality/value

This research advances theoretical understanding of participation in OBFs by offering novel insights into its complex, multi-faceted nature. Unlike some previous simplistic models, this study employs innovative multilevel analysis, uniquely demonstrating the synergistic impact of need factors and reciprocity on participation. It offers a nuanced perspective previously unexplored by addressing reciprocity’s paradoxical role and uncovering interconnections between various factors. This approach provides groundbreaking insights into OBF dynamics, advancing theoretical understanding while offering actionable strategies for enhancing member engagement and community development.
Harran earthen houses as a precedent for environmental comfort
Authors: Gülmüş Serhat , Alaçam Sema , Güzelci Orkan Zeynel
Published: September 2024

Purpose

This study aims to conduct environmental comfort analyses of vernacular architecture to establish design principles for a more sustainable design domain. In the scope of this research, 47 individual Harran earthen houses, comprising 32 different types and six typologies are examined.

Design/methodology/approach

Environmental comfort is selected as an umbrella term for the analysis of thermal comfort, visual comfort, and natural ventilation performance criteria. The performance simulations are conducted utilizing ClimateStudio and SolidWorks software. These simulations yield values for thermal comfort, glare, daylight, solar radiation, airflow, and pressure, which are used to compare different Harran earthen house typologies.

Findings

The study’s results indicate that various environmental comfort standards are met by Harran earthen houses through passive systems, without the need for technology or mechanical equipment. In terms of thermal comfort, visual comfort, and natural ventilation performance criteria, a typology that has advantages in one criterion may have disadvantages in the others. Factors such as orientation, material selection, opening arrangement, and architectural form are found to have an impact on environmental comfort.

Originality/value

This study differs from previous Harran earthen house and environmental comfort studies by focusing on multiple performance criteria and conducting a typology-based comparison based on performance analysis. The results of the study are expected to provide valuable insights into the environmental comfort studies of Harran earthen houses, emphasizing their relevance and applicability in contemporary architectural and urban design.
Authoritarian cue effect of state repression
Authors: Zhu Jiangnan , Bai Steve , Kang Siqin , Wang Juan , Liu Kaixiao
Published: September 2024

State repression in autocracies has long been assumed to elicit explicit or implicit disapproval from citizens. Recent studies suggest that authoritarian governments can garner support for repressive policies through active information manipulation or exploiting social cleavages. However, is it possible for citizens to support repression even without government manipulation? We propose the “authoritarian cue effect,” arguing that citizens’ attitudes toward state repression can be endogenously shaped by instances of state repression, which may be interpreted as cueing messages signaling the regime's disapproval of the punished behaviors. Using a novel belief correction survey experiment, we empirically demonstrate that state repression can induce the public to pick up on cues and automatically adopt the state's stance, perceiving repressed behavior as having more negative externalities and supporting state repression more. This cue effect suggests that authoritarian state repression can self‐legitimize and evade public opinion backlash in a less costly manner than previously presumed.
Utility of exome sequencing in primary spermatogenic disorders: From research to diagnostics
Authors: Riera‐Escamilla Antoni , Nagirnaja Liina
Published: September 2024

Background

Primary spermatogenic disorders represent a severe form of male infertility whereby sperm production is impaired due to testicular dysfunction, leading to reduced quality or quantity of spermatozoa. Gene‐centered research has certainly demonstrated the importance of the genetic factor in the etiology of both poor sperm morphology or motility and reduced sperm count. In the last decade, next‐generation sequencing has expanded the research to whole exome which has transformed our understanding of male infertility genetics, but uncertainty persists in its diagnostic yield, especially in large unrelated populations.

Objective

To evaluate the utility of exome sequencing in detecting genetic factors contributing to various traits of primary spermatogenic disorders, which is a crucial step before interpreting the diagnostic yield of the platform.

Materials and Methods

We manually curated 415 manuscripts and included 19 research studies that predominantly performed whole exome sequencing in cohorts of unrelated cases with primary spermatogenic defects.

Results

The detection rate, defined as the fraction of cases with an identifiable genetic cause, typically remained below 25% for quantitative defects of spermatozoa, whereas improved rates were observed for traits of abnormal sperm morphology/motility and in populations enriched with consanguineous families. Unlike the quantitative defects, the genetic architecture of the qualitative issues of spermatozoa featured a small number of recurrent genes describing a large fraction of studied cases. These observations were also in line with the lower biological complexity of the pathways affected by the reported genes.

Discussion and Conclusions

This review demonstrates the variability in detection rates of exome sequencing across semen phenotypes, which may have an impact on the expectations of the diagnostic yield in the clinical setting.
From spermatogonia to spermatozoa: Filling gaps in andrology at the 16th Network of Young Researchers in Andrology meeting
Authors: Delgouffe Emily , Paturlanne Juan Manuel , Kovacevic Andjela , Keselj Isidora , Ammar Omar , Gaikwad Avinash S. , Saritas Gülizar , Egeberg Dorte , Marcu Daniel , de la Iglesia Alberto
Published: September 2024

The 16th Network of Young Researchers in Andrology meeting, hosted at the Sleepwell Hostel in Brussels, Belgium, was the first Network of Young Researchers in Andrology meeting as the young arm of the European Academy of Andrology. Over three days, this vibrant event provided a valuable platform for early‐career researchers in andrology to present and discuss their research. With 41 attendees from 12 different countries, the meeting featured a diverse scientific program including keynote lectures from six world‐leading experts, covering a broad range of topics in andrology. The 16th Network of Young Researchers in Andrology meeting showcased advancements in fertility preservation, single‐cell applications, in vitro testis modeling, and epigenetics. Networking opportunities were a key highlight, featuring a scientific speed‐dating session and a networking dinner designed to foster meaningful connections and collaborations among participants. The meeting concluded with a workshop on the science of sleep, offering attendees practical strategies to enhance their rest and well‐being. Overall, the 16th Network of Young Researchers in Andrology meeting significantly advanced the audience's knowledge, strengthened the network of young researchers, and underlined Network of Young Researchers in Andrology's commitment to supporting and collaborating with emerging scientists in the andrology community.
Antimicrobial susceptibility testing of bone and joint pathogens using isothermal microcalorimetry
Authors: Christensen Mads H. , Jakobsen Tim H. , Lichtenberg Mads , Hertz Frederik B. , Dahl Benny , Bjarnsholt Thomas
Published: September 2024

The rise in osteomyelitis and periprosthetic joint infections, in combination with increasing life expectancy and the prevalence of diabetes, underscores the urgent need for rapid and accurate diagnostic tools. Conventional culture‐based methods are often time‐consuming and prone to false‐negatives, leading to prolonged and inappropriate antibiotic treatments. This study aims to improve osteomyelitis diagnostics by decreasing the time to detection and the time to an antibiotic susceptibility result to enable a targeted treatment using isothermal microcalorimetry (IMC). IMC measures heat flow in real‐time, providing insights into bacterial metabolism without the need for labeling. Using clinical isolates from bone infections, assessing their response to antibiotics through IMC, we demonstrated that IMC could detect bacteria within 4 h and determine antimicrobial susceptibility profiles within 2–22 h (median 4.85, range 1.28–21.78). This is significantly faster than traditional methods. A decision tree, based on antibiotic susceptibility, accurately categorized pathogens, achieving high accuracy (74–100%), sensitivity (100%), and specificity (65–100%). These findings suggest that IMC could redefine diagnostics of bone and joint infections and potentially infections in general, offering timely and precise treatment guidance, thereby improving patient outcomes and reducing health care burdens. Further optimization and clinical validation are needed to fully integrate IMC into routine diagnostics.
How Social Media Social Comparison Influences Chinese Adolescents' Flourishing: The Mediation Effects of Identity Processing Styles
Authors: Guo Sijia , Lei Junan , Zhang Fan
Published: September 2024

The pervasive use of social media among adolescents has been linked to various aspects of their development, encompassing both beneficial and detrimental effects. However, the precise mechanisms through which social media influences adolescent development remain underexplored. This study seeks to elucidate the associations between social media use and the flourishing of Chinese adolescents, employing a strength‐based perspective that integrates social comparison theory and identity theory. In this research, 786 Chinese adolescents aged 11–19 years participated by completing self‐report questionnaires. Findings suggest that (1) neither social comparisons of ability nor opinions on social media exhibit any significant correlation with the flourishing of Chinese adolescents; (2) a diffuse‐avoidant identity processing style is inversely related to adolescent flourishing, whereas normative and informational identity processing styles are predictive of Chinese adolescents' flourishing; and (3) informational identity processing style positively mediates the relationship between social comparisons of opinion on social media and the flourishing of Chinese adolescents. These results underscore the importance of factors such as social comparison tendencies and personal identity processing styles in influencing adolescent well‐being in the context of social media use. Furthermore, the discussion delves into the implications of these findings for fostering adolescent flourishing.
Intraoperative Mean Arterial Pressure and Postoperative Delayed Graft Function in Kidney Transplantation: Evaluating Three Commonly Used Thresholds
Authors: Pongpruksa Chinnarat , Khampitak Nutchanok , Chang Drew , Bunnapradist Suphamai , Gritsch Hans , Xia Victor W.
Published: September 2024

Background

Delayed graft function (DGF) is a common early complication after kidney transplantation (KT) and is associated with various long‐term adverse outcomes. Despite numerous studies on hemodynamic management, the optimal hemodynamic goals during KT remain unclear. In this retrospective study, we aimed to investigate if three mean artery pressure (MAP) thresholds (≤75, 80, and 85 mmHg) that were commonly used in clinical practice were associated with DGF in adult patients undergoing KT.

Methods

We extracted de‐identified data on adult patients who underwent deceased donor KT from our Discovery Data Repository. DGF was defined as the requirement for dialysis within the first 7 days after transplantation. Three MAP thresholds (≤75, 80, and 85 mmHg) and the duration of pressure below the three thresholds were recorded. Multivariable logistic analysis was used to identify risk factors for DGF.

Results

We included 2301 adult KT patients. The mean age was 52.5±12.9 years and 59% were male. DGF occurred in 1066 patients (46.3%). Patients frequently experienced MAP ≤75, 80, and 85 mmHg (approximately 70%, 80%, and 90% of patients experienced 10 min of MAP ≤75, 80, and 85 mmHg, respectively). Patients with DGF spent significantly longer durations below the three MAP thresholds during surgery compared with those without DGF. Further analysis revealed that the minimal time spent on MAP ≤75, 80, and 85 mmHg that were significantly associated with DGF were 6, 23, and 37 min, respectively. After adjusting for non‐hemodynamic risk factors (age, basiliximab administration, and urine output), prolonged exposure to the three MAP thresholds remained significant predictors for DGF (for MAP ≤75 mmHg, OR 1.257, 95% CI 1.017–1.554, p = 0.034; MAP ≤80 mmHg, OR 1.220, 95% CI 1.018–1.463, p = 0.031; MAP ≤85 mmHg, OR 1.253, 95% CI 1.048–1.498, p = 0.013).

Conclusion

Prolonged exposure to the three common MAP thresholds (≤75, 80, and 85 mmHg) occurred frequently during adult deceased donor KT and was associated with DGF.
Impact of putatively beneficial genomic loci on gene expression in little brown bats (Myotis lucifugus, Le Conte, 1831) affected by white‐nose syndrome
Authors: Kwait Robert , Pinsky Malin L. , Gignoux‐Wolfsohn Sarah , Eskew Evan A. , Kerwin Kathleen , Maslo Brooke
Published: September 2024

Genome‐wide scans for selection have become a popular tool for investigating evolutionary responses in wildlife to emerging diseases. However, genome scans are susceptible to false positives and do little to demonstrate specific mechanisms by which loci impact survival. Linking putatively resistant genotypes to observable phenotypes increases confidence in genome scan results and provides evidence of survival mechanisms that can guide conservation and management efforts. Here we used an expression quantitative trait loci (eQTL) analysis to uncover relationships between gene expression and alleles associated with the survival of little brown bats (Myotis lucifugus) despite infection with the causative agent of white‐nose syndrome. We found that 25 of the 63 single‐nucleotide polymorphisms (SNPs) associated with survival were related to gene expression in wing tissue. The differentially expressed genes have functional annotations associated with the innate immune system, metabolism, circadian rhythms, and the cellular response to stress. In addition, we observed differential expression of multiple genes with survival implications related to loci in linkage disequilibrium with focal SNPs. Together, these findings support the selective function of these loci and suggest that part of the mechanism driving survival may be the alteration of immune and other responses in epithelial tissue.
Nonconforming Preferences: Jumbo Mortgage Lending and Large Bank Stress Tests
Authors: HAUGHWOUT ANDREW , MORGAN DONALD , NEUBAUER MICHAEL , PINKOVSKIY MAXIM , KLAAUW WILBERT VAN DER
Published: September 2024

We document a substantial shift toward nonconforming (“jumbo”) mortgage lending by banks subject to Comprehensive Capital Analysis and Review (CCAR) stress tests. Using two measures of this jumbo shift and difference‐in‐difference analysis, we show that jumbos as a share of all mortgage originations by CCAR banks rose and that their originations were less “bunched” just below the conforming loan limit. We explore several potential mechanisms that might explain CCAR banks' increased preference for jumbo with varying degrees of support. Our evidence is most consistent with the hypothesis that CCAR banks were attracted to the relatively lower credit risk of jumbo mortgages.
Melatonin Attenuates Diabetic Retinopathy by Regulating EndMT of Retinal Vascular Endothelial Cells via Inhibiting the HDAC7/FOXO1/ZEB1 Axis
Authors: Ning Jiayi , Pan Minghong , Yang Hanyi , Wang Zhaoyang , Wang Xiaolan , Guo Kai , Feng Yingtong , Xie Tingke , Chen Yixuan , Chen Chengming , Liu Sida , Zhang Yimeng , Wang Yuanyong , Yan Xiaolong , Han Jing
Published: September 2024

Diabetic retinopathy (DR) is characterized as a microvascular disease. Nonproliferative diabetic retinopathy (NPDR) presents with alterations in retinal blood flow and vascular permeability, thickening of the basement membrane, loss of pericytes, and formation of acellular capillaries. Endothelial–mesenchymal transition (EndMT) of retinal microvessels may play a critical role in advancing NPDR. Melatonin, a hormone primarily secreted by the pineal gland, is a promising therapeutic for DR. This study explored the EndMT in retinal microvessels of NPDR and its related mechanisms. The effect of melatonin on the retina of diabetic rats was evaluated by electroretinogram (ERG) and histopathologic slide staining. Furthermore, the effect of melatonin on human retinal microvascular endothelial cells (HRMECs) was detected by EdU incorporation assay, scratch assay, transwell assay, and tube formation test. Techniques such as RNA‐sequencing, overexpression or knockdown of target genes, extraction of cytoplasmic and nuclear protein, co‐immunoprecipitation (co‐IP), and multiplex immunofluorescence facilitated the exploration of the mechanisms involved. Our findings reveal, for the first time, that melatonin attenuates diabetic retinopathy by regulating EndMT of retinal vascular endothelial cells via inhibiting the HDAC7/FOXO1/ZEB1 axis. Collectively, these results suggest that melatonin holds potential as a therapeutic strategy to reduce retinal vascular damage and protect vision in NPDR.
Sleep characteristics and self‐reported sleep quality in the oldest‐old: Results from a prospective longitudinal cohort study
Authors: Saner Hugo , Möri Kevin , Schütz Narayan , Buluschek Philipp , Nef Tobias
Published: September 2024

Little is known about the correlation between subjective perception and objective measures of sleep quality in particular in the oldest‐old. The aim of this study was to perform longitudinal home sleep monitoring in this age group, and to correlate results with self‐reported sleep quality. This is a prospective longitudinal home sleep‐monitoring study in 12 oldest‐old persons (age 83–100 years, mean 93 years, 10 females) without serious sleep disorders over 1 month using a contactless piezoelectric bed sensor (EMFIT QS). Participants provided daily information about perceived sleep. Duration in bed: 264–639 min (M = 476 min, SD = 94 min); sleep duration: 239–561 min (M = 418 min, SD = 91 min); sleep efficiency: 83.9%–90.7% (M = 87.4%, SD = 5.0%); rapid eye movement sleep: 21.1%–29.0% (M = 24.9%, SD = 5.5%); deep sleep: 13.3%–19.6% (M = 16.8%, SD = 4.5%). All but one participant showed a weak (r = 0.2–0.39) or very weak (r = 0–0.19) positive or negative correlation between self‐rated sleep quality and the sleep score. In conclusion, longitudinal sleep monitoring in the home of elderly people by a contactless piezoelectric sensor system is feasible and well accepted. Subjective perception of sleep quality does not correlate well with objective measures in our study. Our findings may help to develop new approaches to sleep problems in the oldest‐old including home monitoring. Further studies are needed to explore the full potential of this approach.
Pharmacokinetics, Tissue Residues, and Withdrawal Times of Florfenicol in Chukar Partridges (Alectoris chukar)
Authors: Yardimci Sara Busra , Sakin Fatih , Corum Orhan
Published: September 2024

The aim of this study was to determine pharmacokinetics of florfenicol and its metabolite florfenicol amine after a single (30 mg/kg) intravenous (IV) and oral administration of florfenicol in chukar partridges. It also aimed to investigate tissue residue and withdrawal time of florfenicol after multiple‐dose (30 mg/kg, every 24 h for 5 days) oral administration. The research was carried out in two stages: pharmacokinetics and residue. Plasma and tissue concentrations of florfenicol and florfenicol amine were determined by HPLC. The elimination half‐life of florfenicol was 5.25 h for IV and 5.44 h for oral. The volume of distribution at a steady state and total body clearance of florfenicol were 0.38 L/kg and 0.07 L/h/kg, respectively, after IV administration. The peak plasma concentration and bioavailability for oral administration were 45.26 ± 4.06 and 51.55%, respectively. After multiple‐dose oral administration, the highest concentration was detected in the liver (9.21 μg/g) for florfenicol and in the kidney (0.67 μg/g) for florfeniol amine. The calculated withdrawal period of florfenicol was determined as 6, 3, 4, and 5 days for muscle, liver, kidney, and skin + fat, respectively. These data indicate that a 6‐day WT after multiple‐dose administration of florfenicol in chukar partridges can be considered safe for human consumption.
Response inhibition deficits in math‐anxious individuals
Authors: Núñez‐Peña María Isabel , Campos‐Rodríguez Carlos
Published: September 2024

We examined whether math anxiety is related to a response inhibition deficit and, if so, whether it is a domain‐specific inhibition deficit in numerical tasks or a general inhibition deficit. Behavioral performance and electroencephalogram activity were recorded while 28 highly math–anxious (HMA) and 28 low math–anxious (LMA) individuals performed both a numerical and a non‐numerical Go/Nogo task. In the numerical task, single‐digit numbers were presented, and participants were asked to press a button if the number was even. In the non‐numerical task, letters were presented, and the button had to be pressed if the letter was a vowel. Nogo trials were answered less accurately and elicited larger Nogo‐N2 and Nogo‐P3 than Go trials in both tasks and both groups. Importantly, behavioral and brain response differences between tasks were only found in the HMA group. First, they were more error‐prone in numerical Nogo than in non‐numerical Nogo trials; and second, their Nogo‐N2 and N2d (Nogo–Go difference) were smaller in the numerical task than in the non‐numerical task. No differences were found in the LMA group. These results suggest that HMA individuals’ response inhibition is impaired specifically when dealing with numbers, which could contribute to their low achievement in math tasks.
Mechanisms of pacemaking in mammalian neurons
Authors: Bean Bruce P.
Published: September 2024

Many neurons in the mammalian brain show pacemaking activity: rhythmic generation of action potentials in the absence of sensory or synaptic input. Slow pacemaking of neurons releasing modulatory transmitters is easy to rationalize. More surprisingly, many neurons in the motor system also show pacemaking activity, often rapid, including cerebellar Purkinje neurons that fire spontaneously at 20–100 Hz, as well as key neurons in the basal ganglia, including subthalamic nucleus neurons and globus pallidus neurons. Although the spontaneous rhythmic firing of pacemaking neurons is phenomenologically similar to cardiac pacemaking, the underlying ionic mechanism in most neurons is quite different than for cardiac pacemaking. Few spontaneously active neurons rely on HCN ‘pacemaker’ channels for their activity. Most commonly, a central element is ‘persistent’ sodium current, steady‐state subthreshold current carried by the same voltage‐dependent sodium channels that underlie fast action potentials. Persistent sodium current is a steeply voltage‐dependent current with a midpoint near −60 mV, which results in regenerative spontaneous depolarization once it produces a net inward current when summed with all other background currents, often at voltages as negative as −70 mV. This ‘engine’ of pacemaking is present in almost all neurons and must be held in check in non‐pacemaking neurons by sufficiently large competing outward currents from background potassium channels. The intrinsic propensity of neurons to fire spontaneously underlies key normal functions such as respiration and generates the complex background oscillatory circuits revealed in EEGs, but can also produce out‐of‐control oscillations of overall brain function in epilepsy, ataxia and tremor.

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An Experimental and Modeling Study on Device- and System-Level Two-Phase Cooling for High-Heat-Flux Application
Authors: Feng Zhaozan , Song Guomeng , Xia Fan , Liu Bin , Yang Jinfeng , He Kai
Published: September 2024

A multi-microchannel two-phase cold plate made of copper is tested for temperature rise and flow resistance to verify its feasibility for heat dissipation in high-heat-flux devices such as GPU, as well as programmed with EES (Engineering Equation Solver) to predict its temperature profile and pressure drop across the device. The microchannel cold plate has a channel height of 3mm, a channel width of 0.3mm, a fin thickness of 0.2mm, a total width of 50mm, and a total length of 60mm. The 3D model of the cold plate and heat source was imported into COMSOL to complete the three dimensional heat conduction analysis based on the convective flux boundary conditions calculated with EES. Through correlation-based EES coding for thermal and hydraulic behaviors in the cold plate, the heat transfer and flow resistance have been predicted very well. Among the components of the overall pressure drop across the cold plate, the local two phase flow resistances, especially the abrupt bend and restriction of the outlet, play an extremely vital role. Moreover, the adiabatic pressure drop between the micro-channel cold plate and condenser is proved to be a key factor that affects the working pressure or saturation fluid temperature in the cold plate, which in turn determines the temperature rise of the cold plate over the atmosphere. This study provides not only a feasibility analysis for the high-heat-flux cooling solution, but also a reliable and easy-to-use tool for predicting multi-microchannel cooling device and system.
Numerical and Experimental Study on Fluid-Structure Interactions in the Oscillating Flow in a Microfluidic Device
Authors: Hou Tuo , Wang Jing , Ren Yong
Published: September 2024

Microcapsules, sized 1–1000 μm, offer a core-shell structure for encapsulating diverse substances, crucial in drug delivery and various applications. This work explores microcapsule deformation in microchannels with oscillating walls, utilizing a front-tracking-based 2D membrane model for Poiseuille flow. The microcapsules are created using a needle-based device, and the shell is made of a high-precision PLA bio-based resin, encapsulating the liquid core. The microcapsules are subjected to parallel plate compression experiments to assess their mechanical properties. Numerical simulations of the compression experiment are conducted, showing stress distribution within the capsule shell. A front-tracking-based 2D membrane model was applied to investigate the deformation of the microcapsule with a thin membrane shell and a liquid core in the Poiseuille flow. The microcapsules are further tested in an oscillating microchannel under different frequencies.
An Enhanced Volume of Fluid Based Numerical Modelling Approach for Sub-Micron Scale Boiling Heat Transfer
Authors: Chakraborty Bhaskar , Gallo Mirko , Marengo Marco , Coninck Joel De , Casciola Carlo Massimo , Miche Nicholas , Georgoulas Anastasios
Published: September 2024

To explore the complicated physics of boiling heat transfer, researchers are increasingly using numerical simulation methods like the Volume of Fluid (VOF) and the Diffuse Interface (DI) approaches. The VOF method, popular for macro-scale simulations (μm to mm), effectively tracks the bubble growth and detachment. On the other hand, the DI method, which represents the interface as a continuous phase field, is mainly used for mesoscale simulations (nm to μm). The DI method is precise in resolving microscopic interfacial phenomena, but is computationally expensive for larger domains. Based on the pros and cons of the VOF and DI methods, a multi-scale modeling approach that combines the strengths of both can be utilised in the future. To pursue the goal, an initial attempt is taken to check the scaling capability of VOF in lower spatial and temporal limits. Therefore, an enhanced customised VOF methodology that has been developed within the OpenFOAM tool-box is employed here for various bubble growth scenarios exploring its applicability at progressively lower temporal and spatial scales, scaling down traditional application scales with a factor of 10 and 100, aiming to identify the resulting accuracy. It is shown for the first time, that the enhanced VOF model can accurately and effectively simulate phase-change and boiling behaviour at sub-micron scales that have not been explored in the past.
Study on Heat Transfer Characteristics of Successive Droplet Trains Impacting on Silicon Surface
Authors: Li Yuhang , Gao Xu , Deng Wenhao , Xia Yakang , Li Haiwang , Gao Xuan
Published: September 2024

With the development of electronic devices towards multifunctionality and miniaturization, spray cooling is still a highly effective cooling method in high heat flux thermal management. Important parameters of spray such as droplet diameter, quantity and velocity etc. are unpredictable due to the considerable variation in manufacturing standards and working conditions. To achieve a predictable spray, a droplet generator was self-designed and fabricated. It can produce a large number of predictable monodisperse controlled droplets depending on the setting frequency fG. The experiments used deionized water as the cooling fluid. The droplets generated by the droplet generator is captured by a high-speed camera, which ensures that the droplets are uniformly broken up according to the Plateau-Rayleigh instability. The heating element is based on a silicon base, deposited with chromium and platinum by physical vapor deposition (PVD), and then combined through gold wire bonding. In the cooling area, the temperature field was investigated by IR thermal imaging techniques through a reflective path.

Heat transfer characteristics of controllable droplet trains were experimentally conducted from single-phase to two-phase. The number of droplet trains is from 5*5 square-arrayed droplet train to 14*14 square-arrayed droplet trains, corresponding to droplet flux range is from N = 140750 1/cm2s to N = 2044280 1/cm2s. There are two factors affecting heat transfer performance, one is volumetric flow flux, and the other is the droplet flux. Compared to relatively low droplet flux, heat transfer studies revealed that more dense spray has significantly higher heat transfer coefficients and uniformity. This study is based on the thermodynamic analysis of controllable successive droplet trains, which is beneficial for the further application of controlled spray.