bluuebunny/crossref_metadata_2025 huggingface dataset:
“It's Very Cisnormatively Structured”: An Interpretive Description of Undergraduate Nursing Students' Experiences of Gender Inclusive and Affirming Practices
Authors: Crawford Jess , Kramer Marnie , Ristock Janice , Schultz Annette S. H.
Published: February 2025

This study explores the experiences of undergraduate nursing students learning about transgender and gender diverse (TGD) health. We discuss nursing education's perpetuation of discrimination and erasure of TGD people and upholding of gender norms (cisnorms) is not sufficiently preparing students to care for TGD patients. Further, this rampant cisnormativity harms TGD nursing students. This interpretive description drew on queer theory and Hafferty's three levels of curriculum and engaged 18 undergraduate nursing students in initial and 13 in follow‐up focus groups or interviews. Three key themes included (1) cisnormativity is perpetuated in nursing education through pervasive power and norms across the three levels of curriculum; (2) “The Trans Problem”: Transgender and gender diverse people are othered in nursing education; and (3) Welcoming the other: Individual educators who welcome and affirm TGD people are crucial. Critical recommendations from students to advance gender inclusive and affirming practices are provided, including normalizing gender diversity in formal nursing education, the importance of accountability and representation in schools of nursing, and the need for nursing governing bodies to disrupt cisnormativity.
The relation between clutter and visual fatigue in children with cerebral visual impairment
Authors: Van Hove C. , Damiano C. , Ben Itzhak N.
Published: February 2025

Purpose

Cerebral visual impairment (CVI) is a brain‐based condition which can be exacerbated by clutter. This study aimed to explore the relation between clutter and visual fatigue in children with CVI and evaluate the effectiveness of clutter algorithm metrics in assessing visual clutter in photographs of children's play areas and the relation to visual fatigue.

Methods

Visual clutter was measured using algorithmic metrics, subjective observations by a clinical researcher (who also observed visual fatigue) and a Qualtrics survey.

Results

Seventy‐two children (mean performance age = 7 years 4 months) were included. Visual fatigue was present in over 90% of children. Results revealed a relation between clutter and visual fatigue observations (rs = 0.29; p = 0.01) and between visual clutter observations from researchers and Qualtrics participants (rs = 0.32; p = 0.02). Certain metrics were correlated with visual clutter observations (rs ranging from −0.30 to 0.51, p‐values ranging from <0.001 to 0.03), but not with visual fatigue.

Conclusions

Children with CVI presented with visual fatigue, particularly in cluttered environments. Therefore, parents, caregivers, teachers and clinicians should be attentive to visual fatigue signs, as early recognition and intervention can help address the child's needs more effectively. Algorithms that effectively quantify visual clutter are valuable tools that can be integrated to enhance the assessment of clutter and its relation with visual fatigue to advance CVI research methodology. However, a clinician is required to assess visual fatigue and to obtain detailed information on environmental clutter, which algorithms alone may not fully capture. Finally, we recognise that visual fatigue and the impact of clutter should be integrated into psychoeducation and the comprehensive assessment of individuals with CVI.
The Healthcare Needs of Children With Down Syndrome in the First Year of Life: An Analysis of the EUROlinkCAT Data Linkage Study
Authors: Seaton Sarah E. , Rankin Judith , Cavero‐Carbonell Clara , Garne Ester , Gissler Mika , Loane Maria , Neville Amanda J. , Santoro Michele , Tan Joachim , Tucker David , Morris Joan K.
Published: February 2025

Background

Globally, Down syndrome is the most common chromosomal anomaly, often co‐occurring with cardiac or gastrointestinal anomalies. There is a lack of robust data on specific healthcare needs of children with Down syndrome compared to children with other major congenital anomalies.

Objectives

To quantify the healthcare needs of children with Down syndrome in the first year of life compared to children with major congenital anomalies in a large population‐based cohort across Europe.

Methods

The EUROlinkCAT study was a multicentre data linkage study between congenital anomaly registries in Europe and hospital and mortality databases. Children born between 1st January 1997 and 31st December 2014 were included. Summary statistics were used to compare differences between children (those with Down syndrome compared to all major anomalies) and regions. Random‐effects meta‐analysis was used to pool results related to survival, need for intensive care and ventilation support.

Results

A total of 3554 children were born with Down syndrome out of 89,081 children with major congenital anomalies. The pooled 1‐year survival was 95.4%. In every region, > 80% of children with Down syndrome had a hospital admission excluding the birth admission. Hospital length of stay in the first year was higher for children with Down syndrome compared to those with all anomalies (median: 14 versus 7 days). Despite having similar need for ventilation support (9.7% vs. 8.4%), children with Down syndrome had higher rates of intensive care admission than all children with anomalies (24.8% vs. 13.0%).

Conclusions

There is a high need for hospital care for children born with Down syndrome in the first year of life. Future work should continue to explore the long‐term prognosis for children with Down syndrome to ensure their care needs are met.
Blue and green light‐induced release of swarmers in Petalonia fascia (Ectocarpales, Phaeophyceae)
Authors: Hiyama Tsunami , Yoshikawa Shiya
Published: February 2025

Understanding the environmental factors that influence the release of eggs and swarmers, including gametes, zoospores and unsexual swimming cells, is essential for deciphering the survival strategies of brown algae. In the present study, we investigated the mechanisms underlying the light‐induced release of swarmers in Petalonia fascia. We found that swarmer release was triggered by light, especially blue and green light, with red light having a significantly smaller effect. Swarmer release was not directly affected by photosynthesis. In addition, the duration of light exposure was crucial: even when the total number of photons was low, a longer exposure time resulted in a higher release rate of swarmers. This result suggests that a minimum light exposure time is necessary for swarmer release. We also investigated the influence of a circadian rhythm on swarmer release. Under continuous light conditions, swarmers were released at subjective dawn, thus indicating a circadian rhythm influence. By contrast, no release occurred at subjective dawn in continuous darkness. This result suggests that light is necessary to trigger release, even when circadian rhythms are involved. Our findings, which demonstrate that light quality, exposure time and circadian regulation are critical factors for swarmer release in P. fascia, provide new insights into how environmental cues influence reproductive processes in brown algae.
Basel III Regulations and Financing Decisions of Nonfinancial Firms: The South African Evidence
Authors: Lemma Tesfaye T. , Machokoto Michael , Gwatidzo Tendai
Published: February 2025

This study examines the impact of the Basel III regulatory framework on financing decisions within South Africa's real sector. Using a sample of 2045 firm‐year observations spanning the years 2011–2015 and employing the difference‐in‐differences approach, we find a significant decrease in debt financing and debt maturity for firms deemed ‘constrained’ relative to ‘unconstrained’ firms in the post‐Basel III implementation period. Further analyses suggest that the Basel III regulatory framework has a persistent effect on financing decisions in the real sector. Our findings indicate that the Basel III regulatory framework reduces leverage and debt maturity, especially for constrained firms.
SDG8 and HUB2 depositing euchromatin histone marks play important roles in meiosis and crossing‐over regulation
Authors: Singh Amit Kumar , Chowdary K.V.S.K. Arjun , Shen Wen‐Hui
Published: February 2025

Histone modifications play critical roles in plant growth and development. Crossing‐over (CO) during meiosis, which constitutes a fundamental process ensuring sexual transmission of genetic material to the next generation and, meanwhile, generating diversity within species by creating new chromosome/allele combinations, occurs predominantly in euchromatin, which is enriched in active histone marks such as H3K4me3, H3K36me3, and H2Bub1. In plants, it is known that CO hotspots are correlated with H3K4me3 but the role of H3K36me3 and H2Bub1 during meiosis remains elusive so far. Here, we studied the Arabidopsis (Arabidopsis thaliana) sdg8‐1 and hub2‐2 mutants impeded in depositing H3K36me3 and H2Bub1, respectively. Chromosome spreading using 4′,6‐diamidino‐2‐phenylindole (DAPI) staining indicated that male meiotic stages are defective in the sdg8‐1 mutant, and the defect increases synergistically in the sdg8‐1hub2‐2 double mutant. Defects in meiosis, seed formation, and silique length were also observed by RNAi‐knockdown of SDG8 using the meiosis‐specific gene DMC1 promoter. This corroborates to support a bona fide role of active histone marks during meiosis and plant reproduction. Using the tetrad‐based visual reporter lines and immunostaining with antibodies against HEI10 and ZYP1, it was found that synapsis and pairing of homologous chromosomes are abnormal and CO rate increases in sdg8 mutants, pointing to a repressive role of SDG8 in Arabidopsis male meiotic homologous recombination.
The chloroplast‐located HKT transporter plays an important role in fertilization and development in Physcomitrium patens
Authors: Yanez‐Dominguez Carolina , Macedo‐Osorio Karla , Lagunas‐Gomez Daniel , Torres‐Cifuentes Diana , Castillo‐Gonzalez Juan , Zavala Guadalupe , Pantoja Omar
Published: February 2025

Cell survival depends on the maintenance of cell homeostasis that involves all the biochemical, genomic and transport processes that take place in all the organelles within a eukaryote cell. In particular, ion homeostasis is required to regulate the membrane potential and solute transport across all membranes, any alteration in these parameters will reflect in the malfunctioning of any organelle, and consequently, in the development of the organism. In plant cells, sodium transporters play a central role in keeping the concentrations of this cation across all membranes under physiological conditions to prevent its toxic effects. HKT transporters are a family of membrane proteins exclusively present in plants, with some homologs present in prokaryotes. HKT transporters have been associated to salt tolerance in plants, retrieving any leak of the cation into the xylem, or removing it from aerial parts, including the flowers, to be transported to the roots along the phloem. This function has been assigned as most of the HKT transporters are located at the plasma membrane. Here, we report the localization of the HKT from Physcomitrium patens to the thylakoid membrane, reminiscent of the prokaryote origin of these family of transporters. Mutation of PpHKT leads to several alterations in the phenotype of the organism, including the lack of sporophyte formation, and changes in expression of many genes. These alterations suggest that the breakdown in chloroplast ion homeostasis triggers a signalling cascade to the nucleus to communicate its status, being important for the moss to complete its life cycle.
Short‐term complications of internal versus external fixation of closed diaphyseal tibial fractures in 95 skeletally immature dogs
Authors: Chitty Jake W. , Sharp Callum A. T. , Low Daniel , Chapman Thomas , Singleton David , Murdoch Andrew , Aldridge Paul
Published: February 2025

Objective

To determine the influence of fixation method (internal vs. external) on short‐term postoperative complications of closed diaphyseal tibial fractures in skeletally immature dogs.

Study design

Retrospective observational multicenter study.

Animal population

Skeletally immature dogs stabilized with internal fixation (IF) via plate osteosynthesis (n = 59) and external skeletal fixation (ESF) (n = 36).

Methods

Medical records from skeletally immature dogs with closed tibial diaphyseal fractures were reviewed. Data collected included signalment, fracture morphology, etiology, fixation technique, surgeon status, complications, time to discharge and time to final discharge.

Results

The total complication rate for IF was lower at 20.3% (p < .001, CI: 11.0–32.8) compared to ESF at 55.6% (CI: 38.1–72.1). A total of 95% of complications were considered major for external fixation versus 75% for internal fixation. Multivariable analysis revealed decreased odds of a postoperative short‐term complication when a closed tibial diaphyseal fracture was stabilized with IF compared to ESF (p = .004, OR: 0.2, CI: 0.09–0.63). The median time to final discharge for ESF was 4 weeks (range: 2–13) and for IF was 6 weeks (range: 4–32) (p = .01).

Conclusion

ESF had a higher rate of short‐term complications than IF, primarily due to pin‐tract morbidity. The complication rate was 35.3% higher for ESF than for IF.

Clinical significance

Surgeons should consider the use of IF over ESF for skeletally immature dogs to reduce the risk of major complications.
Impact of resistance and endurance exercise training on femoral artery function: sex differences in humans
Authors: Green Daniel J. , Thomas Hannah J. , Marsh Channa E. , Lester Leanne , Naylor Louise H. , Haynes Andrew
Published: February 2025

Exercise has direct and indirect anti‐atherogenic impacts on arterial function and health in humans. Few studies have directly compared the impacts of different commonly adopted exercise approaches on femoral artery function. We hypothesized that, owing to its direct impact via sustained increases in shear stress, endurance (END) training would have larger impacts on arterial diameter and function than resistance (RES) training. Thirty‐nine young, healthy participants (age 26.9 ± 6.2 years, 22♀) completed 12 weeks of both RES and END training in random order, separated by a 12 week washout. Resting femoral artery diameter and flow‐mediated dilatation (FMD) were collected before and after each exercise intervention. END training was associated with an increase in both FMD (Δ1.61 ± 3.09%, P = 0.005) and resting diameter (Δ0.15 ± 0.29 mm, P = 0.004). Neither resting diameter nor FMD increased following RES. However, sex difference analysis revealed that males increased FMD following RES (Δ2.21 ± 3.76%, P = 0.015), whereas no RES change was evident for females. Following END, both males and females increased FMD (♂, Δ1.11 ± 1.65%; ♀, Δ1.88 ± 3.67%; both P = 0.025), with males also showing an increase in resting arterial diameter following END (Δ0.23 ± 0.2 mm, P < 0.001). Group data revealed that END has greater impacts than RES on femoral artery diameter and flow‐mediated functional responses, which are endothelium mediated and nitric oxide dependent. Males exhibit beneficial impacts in response to both END and RES, whereas females respond predominantly to END. Our findings suggest that arterial adaptation to exercise might be influenced by exercise modality and sex.

image

Key points

Exercise has anti‐atherogenic effects and lowers the risk of cardiovascular diseases. This is mediated, in part, by the direct haemodynamic impacts of exercise on arterial function, structure and health. Different modalities of exercise have distinct effects on arterial haemodynamics, but few studies have directly compared, within subjects and using a cross‐over design of trial, the relative impacts of distinct forms of exercise training on arterial adaptation.

In this study, endurance training increased baseline femoral artery diameter and flow‐mediated dilatation, which is endothelium dependent and mediated by nitric oxide. Resistance training had a beneficial but lesser impact.

Females and males were responsive to endurance training, but only males responded positively to resistance training in this study.

These results show that changing the training mode modifies training‐induced arterial adaptation; this has implications for the optimization of exercise prescription for individual benefit.
Sensitivity Analysis Based on the Fisher Information Matrix Applied to Systems With Random Design Inputs
Authors: Andrade Luis , Langley Robin , Yang Jiannan
Published: February 2025

Uncertainties in the parameters adopted during the design process make it challenging to design against the reliability of an engineering system. The identification of parameters that are more sensitive to uncertainties is carried out by a sensitivity analysis of the distribution of the output variables. In this context, we have explored the relation between the Fisher information matrix (FIM) and the design entropy, to develop a framework to analyze the degree of change of the probability of failure and entropy as a result of the variation of input parameters. It is found that the changes in the entropy and probability of failure, associated to the variation of the parameters of the distribution of the input variables, are linear combinations of the eigenvalues of the FIM and the projections of the eigenvectors onto the sensitivity vectors, respectively. As an application, the FIM-based sensitivity analysis is performed from Monte Carlo simulations in a physical dynamic structure subjected to random design parameters drawn from Gaussian and Gamma distributions.
Error Propagation Analysis of Kinematic Quantities for Robots and Mechanisms
Authors: Cantún-Avila K. B. , Peón-Escalante R. , Montoya J. A. , Peñuñuri F.
Published: February 2025

We introduce a comprehensive methodology for calculating the propagation of errors in kinematic quantities up to the jerk for robotic systems and mechanical linkages. Our study utilizes two distinct computational approaches: a deterministic method that relies on derivative calculations, and a stochastic method that utilizes Monte Carlo simulations. Kinematic quantities are computed using dual numbers while the variation in the parameters is computed using the complex step approximation method, as well as with the use of dual numbers to include the general case of a function of complex variables. Although the deterministic approach is generally more efficient, the stochastic method stands out for its simplicity and ease of implementation. The efficacy of our methodology is demonstrated through practical applications. We perform error propagation analyses up to the jerk for planar and spherical four-bar (4R) mechanisms and a revolute–cylindrical–revolute (RCR) robot manipulator, highlighting its versatility across different mechanical systems.
Improved Multi-Objective Coati Optimization Algorithm for Optimizing Energy Efficiency and Thermal Comfort in Chilled Water Systems
Authors: Feng Zengxi , Liu Xuefeng , Zhang Xian , Lu Shuai , Wang Bo , Liu Li , Quan Wei , An Jianhu , Wang Chang , Kang Limin
Published: February 2025

As the main energy consumption part of the central air-conditioning systems, the energy saving of the chilled water system is particularly crucial. This system realizes heat exchange with indoor air by delivering chilled water to air-conditioning units, effectively regulating indoor temperature and humidity to ensure thermal comfort. In this article, an improved multi-objective coati optimization algorithm (IMOCOA) is used to optimize the operating parameters and thermal comfort environment parameters of chilled water systems to improve thermal comfort and reduce energy consumption. The algorithm introduces chaotic mapping to enhance search diversity, balances global and local search capabilities through Levy flight and Gauss variation strategies, and uses location greedy choices to help coatis jump out of local optima. To verify the optimization effect of IMOCOA, a multi-objective optimization model was established, combining the energy consumption model of the chilled water system and the simplified thermal comfort model. Key parameters, including chilled water supply temperature, pump speed ratio, indoor temperature, and relative humidity, are optimized. The simulation results from the experiments show that the average energy-saving rate of the chilled water system using IMOCOA is 7.8% and thermal comfort is improved by 19.6%. Compared to other optimization algorithms, this method demonstrates a better optimization effect.
Time Domain Analysis for Motions of Ships With the Effects of Steady Flow Using a Rankine Panel Method
Authors: Zhou Bo , Wu Zhifei , Wang Yu , Han Xiaoshuang , Zhang Teng , Zhang Guiyong
Published: February 2025

A novel numerical approach, leveraging the 3D time domain Rankine panel method, has been introduced to simulate ship motions while accounting for the effects of ship wave. This method treats ship wave as steady flow, enabling a more accurate representation of physical phenomena. The underlying numerical formulation used to solve the ship wave potential is comprehensively derived, establishing the unsteady disturbance potential's boundary value problem and incorporating the effects of steady motion. Wave forces and motion responses of various ship forms were computed and compared with experimental data and results from other numerical techniques. The findings reveal that calculations based on uniform stream exhibit significantly larger errors than those considering double body flow or ship wave. For the Wigley I and S175 models, the discrepancies between double body flow and ship wave predictions are relatively minor, with ship wave calculations demonstrating slightly higher accuracy. In contrast, for the intricate KRISO Container Ship (KCS) model, where ship wave is more pronounced, the error margin for ship wave calculations relative to experimental results remains within 21.9%, while errors for double body flow calculations can reach up to 50.2%. This highlights the superior accuracy of ship wave-based calculations for the KCS model. Overall, the proposed method effectively captures the influence of steady flow and demonstrates significant advantages in computing pronounced ship wave generated during realistic ship motion.
Viability of HFO-1234ze(E) (trans-1,3,3,3-tetrafluoropropene) as a low global warming potential silicon dioxide etch gas
Authors: Windsor Aaron J. , Clark Jeremy C. , McMurdy George , Joseph Eric A. , Syvret Robert G. , Olson Ronald J. , Cha Judy J.
Published: February 2025

The American Innovation and Manufacturing Act, enacted by Congress in 2020, grants the U.S. Environmental Protection Agency the authority to phase down the production and consumption of hydrofluorocarbons (HFCs), thereby reducing carbon emissions and addressing the negative environmental impact of HFCs. To comply, the semiconductor industry, which uses a variety of processing gases that contain HFCs, must transition to alternative gases in chip manufacturing, particularly in etching processes. Many of the HFC etch gases in current use have high global warming potentials (GWPs). One potential alternative to the high-GWP gases are hydrofluoroolefins (HFOs), which were developed by the refrigerant industry as fourth generation, low-GWP alternatives to legacy refrigerants and foam expansion agents. The present work will investigate the viability of the environmentally friendly HFO, trans-1,3,3,3-tetrafluoropropene [C3H2F4 or HFO-1234ze(E)], as a replacement gas for reactive ion etching of silicon dioxide (SiO2). Initial etch tests demonstrated that HFO-1234ze(E) has higher etch rates and better selectivity than the saturated alkane legacy gases trifluoromethane (CHF3) and difluoromethane (CH2F2). Repeated SiO2 etching with HFO-1234ze(E) appears to not affect the etch chamber or future etch processes. Thus, the present work suggests that the low-GWP HFO-1234ze(E) could be an effective etch gas for the semiconductor industry as an alternative to HFC gases.
Broadband noise modulation of multirotor aircraft
Authors: Gan Ze Feng (Ted) , Tumelero Valente Vitor , Brentner Kenneth S. , Greenwood Eric
Published: February 2025

Rotor broadband noise is typically analyzed over time scales encompassing multiple rotor periods. However, modulation of broadband noise levels with the blade passage frequency has been shown to be significant for human perception of wind turbine and helicopter noise. In contrast, broadband noise modulation has not been extensively studied for aircraft with many rotors, such as unmanned aerial vehicles (UAVs) or advanced air mobility aircraft. In this work, significant broadband noise modulation was measured in flight tests and anechoic chamber experiments of hexacopter UAVs. The amplitude of this modulation depended on the azimuthal phase offsets between rotors, demonstrating the potential for synchrophasing control to reduce broadband noise modulation, analogous to synchrophasing control of tonal noise. If rotors are not synchronized, as in typical flight, the azimuthal phase offsets between rotors vary with time. This variation was found to follow a uniform random distribution, resulting in modulation depth also varying randomly with time. The probability distribution of modulation depth was computed using offset copies of the modulation of a single rotor. These results contribute understanding to how the broadband noise modulation of rotors sum together, and showed that this modulation is likely to be significant in flight.
Single-stranded DNA binding to the transcription factor PafBC triggers the mycobacterial DNA damage response
Authors: Schilling Charlotte M. , Zdanowicz Rafal , Rabl Julius , Müller Andreas U. , Boehringer Daniel , Glockshuber Rudi , Weber-Ban Eilika
Published: February 2025

The DNA damage response in mycobacteria is controlled by the heterodimeric transcription factor PafBC, a member of the WYL domain–containing protein family. It has been shown that PafBC induces transcription of its regulon by reprogramming the housekeeping RNA polymerase holoenzyme to recognize PafBC-dependent promoters through sigma adaptation. However, the mechanism by which DNA damage is sensed and translated into PafBC activation has remained unclear. Here, we demonstrate that the binding of single-stranded DNA (ssDNA) to the WYL domains of PafBC activates the transcription factor. Our cryo–electron microscopy structure of full-length PafBC in its active conformation, bound to the transcription initiation complex, reveals a previously unknown mode of interaction between the ssDNA and the WYL domains. Using biochemical experiments, we show that short ssDNA fragments bind to PafBC dynamically, resulting in deactivation as ssDNA levels decrease postrepair. Our findings shed light on the mechanism linking DNA damage to PafBC activation and expand our understanding of WYL domain–containing proteins.
Evolution of entanglement entropy at SU(
N
) deconfined quantum critical points
Authors: Song Menghan , Zhao Jiarui , Cheng Meng , Xu Cenke , Scherer Michael , Janssen Lukas , Meng Zi Yang
Published: February 2025

Over past two decades, the enigma of the deconfined quantum critical point (DQCP) has attracted broad attention across physics communities, as it offers a new paradigm beyond the Landau-Ginzburg-Wilson framework. However, the nature of DQCP has been controversial based on conflicting numeric results. In our work, we demonstrate that an anomalous logarithmic behavior in the entanglement entropy (EE) persists in a class of models analogous to the DQCP. On the basis of quantum Monte Carlo computation of the EE on SU(
N
) DQCP spin models, we show that for a series of
N
smaller than a critical value, the anomalous logarithmic behavior always exists, which implies that previously determined DQCPs in these models do not belong to conformal fixed points. In contrast, when

N
≥

N
c

with an

N
c

we evaluate to lie between 7 and 8, DQCPs are consistent with conformal fixed points that can be understood within the Abelian Higgs field theory.
Pioneer factor GATA6 promotes colorectal cancer through 3D genome regulation
Authors: Lyu Huijue , Chen Xintong , Cheng Yang , Zhang Te , Wang Ping , Wong Josiah Hiu-yuen , Wang Juan , Stasiak Lena , Sun Leyu , Yang Guangyu , Wang Lu , Yue Feng
Published: February 2025

Colorectal cancer (CRC) is one of the most lethal and prevalent malignancies. While the overexpression of pioneer factor GATA6 in CRC has been linked with metastasis, its role in genome-wide gene expression dysregulation remains unclear. Through studies of primary human CRC tissues and analysis of the TCGA data, we found that GATA6 preferentially binds at CRC-specific active enhancers, with enrichment at enhancer-promoter loop anchors. GATA6 protein also physically interacts with CTCF, suggesting its critical role in 3D genome organization. The ablation of GATA6 through AID and CRISPR systems severely impaired cancer cell clonogenicity and proliferation. Mechanistically, GATA6 knockout induced global loss of CRC-specific open chromatins and extensive alterations of critical enhancer-promoter interactions for CRC oncogenes. Last, we showed that GATA6 knockout greatly reduced tumor growth and improved survival in mice. Together, we revealed a previously unidentified mechanism by which GATA6 contributes to the pathogenesis of colorectal cancer.
Interactions between human immunodeficiency virus and human endogenous retroviruses
Authors: Li Mengying , Yu Fengting , Zhu Baoli , Xiao Jiang , Yan Chang , Yang Xiaojie , Liang Xuelei , Wang Fang , Zhang Hanxi , Zhang Fujie
Published: February 2025

Human immunodeficiency virus (HIV), a retrovirus of the Lentivirus genus, targets CD4
+
T cells, causing immune dysfunction and AIDS. Approximately 8% of the human genome consists of human endogenous retroviruses (HERVs), ancient retroviral remnants that may interact with HIV. Despite antiretroviral therapy, challenges such as drug resistance, poor immune reconstitution (PIR), and reservoirs remain. This GEM discusses the impact of HIV on HERVs, the potential roles of HERVs in PIR and reservoirs, and provides insights into future research directions.
Bayesian phylogeographic analysis infers cross-border transmission dynamics of drug-resistant
Salmonella
Enteritidis
Authors: Woh Pei Yee , Chen Yehao , Kwok Kevin Wing Hin , Quiroga Jose
Published: February 2025

Salmonella
Enteritidis (
S
. Enteritidis) stands as a leading cause of human salmonellosis worldwide with a tendency to spread through contaminated foodstuffs and animals. In Hong Kong, a significant proportion of food products are imported, and many cases are often caused by the consumption of contaminated food, hence making the geographical surveillance of drug-resistant
S
. Enteritidis important for strong public health and food safety measures. We analyzed the whole genomes of 207
S
. Enteritidis from Hong Kong, Australia, Canada, mainland China, the United States of America, South Africa, Taiwan, and the United Kingdom to examine associated antimicrobial resistance and the transmission dynamics between continents. Phylogenetic cluster inferences and Bayesian phylogeographical analysis were performed. Overall, sequence type ST11 strains were dominant (92.8%, 192/207). Five phylogenomic clusters A to E were identified, where most isolates from mainland China and Hong Kong were in Cluster E. Among the 22 plasmid types identified, IncX1 was dominant in the Asian isolates. Most of the virulence genes were distributed in
Salmonella
pathogenicity islands −1 and −2, with two universal virulence operons responsible for the effector delivery system and bacterial cell adhesion. The phylogeographic inference analysis showed a statistically significant link between mainland China and Hong Kong with the highest relative migration rate (relativeGeoRates mean ± standard error = 2.93 ± .07, Bayes Factor [BF] = 1285.5], with some traceable to Canada (0.61 ± 0.03, BF = 6.9) and Australia (1.02 ± 0.04, BF = 4.2). Our analysis suggests hypothetical transmission of
S
. Enteritidis and its associated antimicrobial resistance across borders.

IMPORTANCE

Antimicrobial resistance and disease severity in nontyphoidal
Salmonella
have constituted a serious public health challenge worldwide. Drug-resistant
Salmonella
Enteritidis is a leading pathogen that causes human infections primarily through the consumption of contaminated food products. Previous research focuses on the whole-genome analysis of antimicrobial resistance and virulence factors in
S
. Enteritidis; however, details on how this bacterium localized, expanded, and diversified from location to location remain unknown. Our study for the first time addresses this gap by investigating the phylogeographic transmission to estimate the frequency and location of cross-border spread. By evidence-based inferred transmission, we aim to uncover novel insights into the dynamic spread of
S
. Enteritidis, revealing the route of emergence and migration. This research is crucial for enhancing our understanding of the control strategies to safeguard human health.
Blocking the shikimate pathway amplifies the impact of carvacrol on biofilm formation in
Candida albicans
Authors: Molaeitabari Ali , Dahms Tanya E. S.
Published: February 2025

Candida albicans
typically thrives in a commensal relationship with humans but is also an opportunistic fungal pathogen. As an opportunistic pathogen,
C. albicans
relies heavily on its ability to assimilate nutrients, for which it must compete with the host and other microorganisms. Amino acid biosynthesis, sensing, and uptake play pivotal roles in
C. albicans
growth and pathogenicity.
C. albicans
biosynthesizes aromatic amino acids and co-enzyme Q
de novo
through the shikimate pathway, including the Aro1, Aro2, and Aro7 enzymes, but also has amino acid transporters for uptake from the environment. Thus, antifungal approaches targeting aromatic amino acid biosynthesis must simultaneously inhibit amino acid biosynthesis and uptake. Herein, we investigate the plant-based antifungal, carvacrol, in conjunction with aromatic amino acid biosynthetic mutants, as a potential anti-candidal strategy. Growth of the WT,
ARO2
, and
ARO7
strains were inhibited by 150 µg/mL carvacrol, whereas the
ARO1
mutant was slightly more sensitive (with MIC 125 µg/mL). All repressed mutants exposed to carvacrol are partially rescued in the presence of para-aminobenzoic acid (PABA) (CoQ precursor), indicating that blocking the shikimate pathway impacts both aromatic amino acid and CoQ biosynthesis. Moreover, carvacrol at sublethal concentrations significantly inhibits
ARO1
adhesion and hyphal formation, along with pre-attached and pre-formed hyphae, ultimately impacting biofilm metabolic activity and biomass accumulation and significantly reducing biofilm growth. In summary, carvacrol increases the sensitivity of
C. albicans
to
ARO1
repression, with attenuated adhesion, hyphal formation, mycelial growth and biofilm formation, likely by blocking aromatic amino acid uptake.

IMPORTANCE

The opportunistic pathogen
Candida albicans
remains the leading cause of candidemia and invasive candidiasis (IC), causing significant morbidity and mortality in immunocompromised patients. Our current arsenal of effective antifungal drugs is limited in number, mechanistic diversity, and efficacy, are cytotoxic and associated with antifungal resistance, necessitating the development of novel antifungals and combination therapies. Here, we show how simultaneously blocking the shikimate pathway, through
ARO1
repression, and disrupting aromatic amino acid uptake by carvacrol prevent
C. albicans
biofilm formation. Thus, inhibitors of the Aro1 enzyme in combination with carvacrol are expected to shut down
C. albicans
biofilm formation and virulence.
A qualitative study of community perceptions and practices relating to blood donation in Cameroon
Authors: Asahngwa Constantine T , Dongho Ghyslaine Bruna Djeunang , Ngwa Wilfred , Sinsai Regina , Dabou Solange , Kepgang Evrard , Kibu Odette D , Ngo Ngo Valery , Gobina Ronald Mbua , Foretia Denis Alemka
Published: February 2025

Introduction

Blood and blood products are essential for patients in need of transfusion therapy, especially those undergoing surgical procedures, childbirth and other injuries. In Cameroon, there is an annual deficit of over 270 000 pints of blood, with a coverage rate of only 17%. This qualitative study investigates the barriers and motivators to blood donation among Cameroonian adults, with the aim of better understanding community perceptions and practices.

Methods

This ethnographic study was performed using a purposive sampling strategy. Focus group discussions and in-depth interviews were conducted with community members to understand perceptions and practices that serve as motivators and deterrents to blood donation in Yaoundé, Cameroon. Data were transcribed verbatim and analysed thematically to identify emerging themes.

Results

A total of 25 Cameroonian adults were interviewed. Some participants believed that donating blood is: (1) a humanitarian and life-saving gesture, (2) an act of social and religious responsibility and (3) a means for donors to access health services. Some people do not want to donate blood due to: (1) fear of needles, donor-site pain or possible ritualistic use of donated blood, (2) certain religious beliefs, such as those held by Jehovah’s Witnesses, (3) local and cultural beliefs, (4) the perception that blood donation is a commercial activity for many health personnel and (5) lack of transparency from health personnel. The practice of free and voluntary donation, as well as donations specifically to family and friends, was common. Occasionally, requests for financial remuneration prior to blood donation also emerged.

Conclusions

Community members displayed both favourable and unfavourable perceptions as well as both safe and risky practices related to blood donation. The positive aspects highlighted the potential for creating a supportive environment for blood donation, while the negative aspects presented the significant challenges facing the development of high-quality blood donation and transfusion services. Efforts to reduce apathy toward blood donation and expand the pool of regular, repeat donors must carefully address the diverse perceptions and practices identified in this study.
Economic development, alcohol consumption and life expectancy in low- and lower-middle-income countries in the Western Pacific Region: a structural equation modelling study
Authors: Rehm Jürgen , Jiang Huan , Hassan Ahmed S , Rovira Pol , Shield Kevin D
Published: February 2025

Introduction

Economic transition has historically been shown to be associated with longer life expectancy in current high-income countries. We examined the role of alcohol consumption in this transition process for lower- and middle-income countries.

Methods

We tested three hypotheses on the interrelationship between economic growth, level of alcohol consumption and life expectancy in all six countries in the WHO Western Pacific Region, which transitioned from low- to lower-middle-income countries over the past 20 years. Structural equation modelling, corrected for autoregressive effects, was used to test the association between economic development and life expectancy, adult per capita consumption of alcohol, the prevalence of past-year drinkers and alcohol-attributable mortality. The direct impact of alcohol per capita consumption (APC) on life expectancy was also estimated.

Results

Overall, economic development was strongly positively associated with both life expectancy and alcohol consumption, and a higher level of alcohol consumption resulted in a lowered life expectancy, when directly measured. Thus, changes in gross domestic product per capita at purchasing power parity of $ 1000 Int. were linked to changes in the same direction in life expectancy of 0.94% (95% CI 0.66%, 1.21%) and with an increase in APC of 76.8% (55.38%, 98.3%). Average loss in life expectancy due to alcohol consumption was 1.76 (0.81, 2.72) years for males and 0.59 (0.12, 1.07) for females. There was heterogeneity found between countries.

Conclusion

Alcohol consumption is expected to increase in an economic transition from a low- to lower-middle-income country and to have a negative impact on life expectancy. Alcohol control policies should be enacted to reap the full health benefits of economic growth.
Factors associated with early childhood development: results from the Brazilian National Survey on Child Nutrition (ENANI-2019)
Authors: Freitas-Costa Nathalia Cristina , Farias Dayana Rodrigues , Alves-Santos Nadya Helena , Scincaglia Raquel , Normando Paula , Rugani Inês , de Aquino Lacerda Elisa Maria , Crispim Sandra , Brentani Alexandra Valeria Maria , Alves Claudia Regina Lindgren , Kac Gilberto
Published: February 2025

Introduction

The full achievement of early childhood development (ECD) is a human right and adhering to the nurturing care framework may facilitate it.

Objective

To evaluate the association between distal and proximal variables and developmental quotient (DQ).

Methods

Data from 14 159 children <5 years were evaluated in the Brazilian National Survey on Child Nutrition. The Survey of Well-being of Young Children—Brazilian version milestones questionnaire was used to evaluate ECD. The developmental age was estimated using the graded response models. DQ was calculated by dividing developmental age by chronological age. The expected age milestones are attained when DQ=1. DQ predictors were defined considering distal and proximal levels/variables using a multiple linear regression model and a hierarchical approach.

Results

The DQ mean was significantly lower among children aged 36–59 months (0.91 (0.88 to 0.93)), boys (1.03 (1.01 to 1.06)) and those from the North region (0.98 (0.93 to 1.04)) compared with children aged 1–35 months (1.18 (1.15 to 1.22)), girls (1.11 (1.08 to 1.13)) and from the Southeast region (1.11 (1.07 to 1.16)). For children aged 1–35 months, DQ was inversely associated with emergency C-section (β=−0.08; p<0.01), consumption of ultra-processed food (β=−0.33; p<0.01), and positively associated with attendance at daycare/school (private: β=0.09; p=0.02 and No: β=0.12; p<0.01). For children aged 36–59 months, attendance to private daycare/school (β=0.08; p<0.01) was positively associated with DQ, and small for gestational age at birth (β=−0.05; p=0.01) and access to public health services (no-primary care) (β=−0.07; p<0.01) were inversely associated with DQ.

Conclusions

Adverse health, nutrition and learning factors predicted the ECD, demonstrating an inequitable environment for Brazilian children. These findings indicate a need for public policies to ensure social and health equity in early childhood.
Acne due to JAK inhibitors in inflammatory bowel disease
Authors: Awad Andrew , Christensen Britt , Segal Jonathan P , Ross Gayle
Published: February 2025

Janus kinase inhibitors (JAKi) are a class of medications that mediate immune signalling and are commonly used in inflammatory bowel disease. In multiple clinical trials, they have been shown to cause acne vulgaris in a dose-dependent manner. In our review, the incidence of acne was more prevalent in women, non-white patients and in a younger demographic. Acne pathogenesis involves four main factors; sebum alteration, follicular hyperkeratinisation,Cutibacterium acnesproliferation and inflammation. The mechanism of how JAKi may be causing an increased incidence of acne includes: increasing follicle hyperkeratinisation, altering the skin microbiome and sebum lipid composition and through androgen modulation. We suggest a treatment guideline that includes dose reduction, topical and systemic agents for mild-to-moderate acne and isotretinoin for severe acne.
Phase I study of efineptakin alfa (NT-I7) for the treatment of Kaposi sarcoma
Authors: Ramaswami Ramya , Kask Angela Shaulov , D’Amico Leonard , Menon Manoj P , Lurain Kathryn , Yarchoan Robert , Ekwede Irene , Couey Paul , Burnham Eli , Angeldekao Allysson , Ha Lee Byung , Kaiser Judith C , Cheever Martin , Uldrick Thomas S , Kwok Li-Lian , Wright Anna , Fling Steven P , Wang Chia-Ching Jackie
Published: February 2025

Background

CD4+T-cell lymphocytopenia and immune dysfunction are factors that drive the onset and persistence of Kaposi sarcoma (KS) in people with (PWH) and without HIV. Standard chemotherapy agents for KS can contribute to increasing CD4+T cell lymphocytopenia. IL-7 is a cytokine that is essential in T-cell development, proliferation and homeostasis. In PWH, IL-7 administration leads to increased numbers of circulating central memory and naïve T-cell phenotypes.

Methods

In this multicenter phase I study with a 3+3 dose escalation design, participants with KS with or without HIV received up to four intramuscular injections of IL-7 (NT-I7) every 9 weeks. The primary endpoint of the study was to evaluate safety over three escalating dose levels (DL) of NT-I7 (DL1:480 µg/kg, DL2: 960 µg/kg and DL3: 1200 µg/kg) and identify a maximum tolerated dose. Secondary endpoints included evaluation of antitumor activity per the modified AIDS Clinical Trials Group Criteria and assessment of the effect of NT-I7 on the kinetics of CD4+and CD8+T-cells.

Results

Eight cisgender male participants (five with HIV infection) were enrolled. Six participants were treated at DL1, and two were treated at DL2. The study was closed to accrual after enrolment of the second participant on DL2 due to termination of study funding. Four of the eight participants (three in DL1 and one in DL2) completed all four doses of the NT-I7. With regard to treatment-emergent adverse events (AEs), all participants had <grade 2 AEs, which included injection site reaction and alanine aminotransferase increase. Injection site reaction was a dose-limiting toxicity in one participant at DL1. The overall KS objective response rate to NT-I7 was 42.9% (95% CI 9.9%, 81.6%) and all three responders were PWH. Absolute lymphocyte counts, CD4+and CD8+T-cell counts increased among all participants following administration of NT-I7. Participants who experienced a response had HIV and lower CD4/CD8 ratio at baseline and throughout the study as compared with those who did not have KS response to NT-I7.

Conclusions

Preliminary data demonstrate safety and activity of IL-7 in patients with KS and activity specifically among individuals HIV-associated KS.

Trial registration number

NCT04893018.
A review of the common causes of acute coronary syndrome (ACS) in females, and the role of estrogen on its pathologies and risk factors
Authors: Namkoong Jenny Youn , Minhas Kunal
Published: February 2025

As our understanding of acute coronary syndromes (ACS) has increased, we have been able to better delineate the unique pathologies that cause ACS. This review article on the common causes of ACS in females explores the atherosclerotic pathologies of plaque rupture and plaque erosion, and non-atherosclerotic pathologies of SCAD, MINOCA and Takotsubo cardiomyopathy. It reviews the literature on the link between estrogen and its protection against both atherosclerotic risk factors and induction of plaque vulnerability.
The mechanistic plausibility of estrogen causing higher risk in SCAD, MINOCA and Takotsubo cardiomyopathy, the female-predominant non-atherosclerotic ACS presentations are also summarised. Whilst there is still much to be researched about these pathologies, an analysis of the biological impact of sex hormones at the molecular level has helped identify links between mechanisms suggesting a possible unifying pathology between plaque erosion, MINOCA and microvascular spasm. In this way, a new paradigm for ACS as an equilibrium between thrombus-stabilisation and thrombus-dissolution states is also explored in this article.
What has become evident is that the attempt to understand the common causes of ACS in females has resulted also in a deeper understanding of atherosclerotic ACS in males, and highlighted areas of exciting further discovery.