bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulating the field‐induced AFE‐FE transition in NaNbO3 from the perspective of powder surface energy
Authors: Wang L. G. , Guan Z. H. , Zhang Q. , Wang M. S. , Zhu C. M. , Yu G. B. , Wang R. , Cui H. , Jiang X. L. , Su X. F.
Published: February 2025

Sodium niobate (NaNbO3, NN) has drawn growing attention for its wide application in engineering fields due to the room‐temperature antiferroelectric phase with an orthorhombic Pbcm space group, which is generally known as the P phase. However, a ferroelectric Q phase is commonly induced out of P phase under the applied electric field leading to a coexistence of these two phases. Accordingly, this irreversible transition reported in previous literature causes the unobservable double polarization hysteresis loops of NN at ambient conditions. Thus, it has significant implications in investigating the formation of ferroelectric or antiferroelectric phase and the corresponding field‐induced transition. Herein, the content ratio of P/Q phase in polycrystalline NN ceramics is effectively regulated from the perspective of powder surface energy, through adjusting the ball‐milling time during solid‐state reaction process. Moreover, the physical mechanism of field‐induced transition is explored based on analyzing the room‐temperature ferroelectric properties and the in situ Raman spectra with varying electric field. This work provides feasible strategy of modulating the inversion between ferroelectric and antiferroelectric phases in NN. The analysis of theoretical results can facilitate further design of NN‐based materials for actual application in technologies.
The Vulnerability of AI‐Based Scoring Systems to Gaming Strategies: A Case Study
Authors: Baldwin Peter , Yaneva Victoria , North Kai , Ha Le An , Zhou Yiyun , Mechaber Alex J. , Clauser Brian E.
Published: February 2025

Recent developments in the use of large‐language models have led to substantial improvements in the accuracy of content‐based automated scoring of free‐text responses. The reported accuracy levels suggest that automated systems could have widespread applicability in assessment. However, before they are used in operational testing, other aspects of their performance warrant examination. In this study, we explore the potential for examinees to inflate their scores by gaming the ACTA automated scoring system. We explore a range of strategies including responding with words selected from the item stem and responding with multiple answers. These responses would be easily identified as incorrect by a human rater but may result in false‐positive classifications from an automated system. Our results show that the rate at which these strategies produce responses that are scored as correct varied across items and across strategies but that several vulnerabilities exist.
Treatment of Submucous Alveolar Cleft With Hard‐ and Soft‐Tissue Reconstruction in the Aesthetic Zone: A Case Report
Authors: Niu Li , Wang Yujia , Zu Cancan , Zhao Junjie , Ouyang Yuanyuan , Zhong Shengwei , Lei Lang , Li Houxuan
Published: February 2025

Objective

This case report offers information on accurate diagnostic and soft‐ and hard‐tissue reconstruction periodontal surgery deal with “black triangles” in the aesthetic zone of anterior teeth caused by submucous alveolar cleft, which is rare and easily overlooked.

Clinical Considerations

Vertical and horizontal bone augmentation was conducted via guided tissue regeneration and alveolar bone grafting (ABG) at the cleft site where favorable bone grafting conditions were absent. A customized, vascularized interpositional periosteal‐connective tissue (VIP‐CT) flap was applied as the barrier membrane to maintain the stability of bone replacement graft and provide soft‐tissue foundation for gingival papilla growth. Adjustment on the contact point position of the anterior teeth and the shapes of crowns induced growth of the gingival papillae with resin restoration. The radiological and clinical parameters, and smiling photographs demonstrated a satisfactory treatment outcome.

Conclusions

When the inflammation and local alveolar bone destruction in the anterior area are disproportionate, submucous alveolar cleft should be considered a potential etiology. Surgical treatment combined with resin restoration substantially improved the affected area.

Clinical Significance

The hard‐ and soft‐tissue defects can be improved through ABG and VIP‐CT flap in a single surgery.
Morphology and Molecular Phylogeny of Endosymbiotic Ciliates (Peritrichia, Mobilida) of Marine Invertebrates with Descriptions of Two Novel Species Urceolaria clepsydra n. sp. and Urceolaria bratalia n. sp.
Authors: Martinez Gabrielle , Leander Brian S. , Park Eunji
Published: February 2025

Mobilid ciliates are a morphologically distinct group of protists that form a wide range of symbiotic relationships with aquatic animals and includes three subgroups: Trichodinidae, Urceolariidae, and Polycyclidae. Trichodinids are best known for infecting fishes, whereas urceolariids infect diverse marine invertebrates. Polycyclidae was established for mobilid ciliates infecting sea cucumbers; however, molecular data have been unavailable for this group. In this study, we discovered and characterized two novel mobilid species, one infecting two species of sea cucumbers (Eupentacta quinquesemita and Cucumaria miniata) and one infecting brachiopods or lamp shells (Terebratalia transversa) collected from the Northeast Pacific Ocean. These new mobilid species were characterized at the morphological level using light microscopy (LM) and scanning electron microscopy (SEM). We also inferred the molecular phylogenetic positions of these species using small subunit (SSU) rDNA sequences. Based on combined morphological and molecular data, we demonstrate that the two new species belong to Urceolaria, U. clepsydra n. sp. and U. bratalia n. sp., and support synonymization of Polycycla with Urceolaria. By providing the first molecular data from new species of mobilids infecting sea cucumbers and brachiopods, we expand the host range and improve our knowledge of this diverse but poorly understood group of symbionts.
Efficacy and Safety of Once‐Daily Roflumilast Cream 0.05% in Pediatric Patients Aged 2–5 Years With Mild‐to‐Moderate Atopic Dermatitis (INTEGUMENT‐PED): A Phase 3 Randomized Controlled Trial
Authors: Eichenfield Lawrence F. , Serrao Rocco , Prajapati Vimal H. , Browning John C. , Swanson Lisa , Funk Tracy , Gonzalez Mercedes E. , Hebert Adelaide A. , Lee Mark , Boguniewicz Mark , Simpson Eric L. , Seal Melissa S. , Krupa David , Hanna Diane , Snyder Scott , Burnett Patrick , Chu David H. , Almaraz Erin , Higham Robert C. , Berk David R.
Published: February 2025

Background/Objectives

Efficacy and safety of roflumilast cream 0.15% were demonstrated in patients aged ≥ 6 years with atopic dermatitis (AD) in two Phase 3 trials. This Phase 3 parallel‐group, double‐blind trial (INTEGUMENT‐PED; NCT04845620) compared the efficacy and safety of roflumilast cream 0.05% and a vehicle in patients aged 2–5 years with AD.

Methods

Patients aged 2–5 years with mild‐to‐moderate AD were treated with once‐daily roflumilast cream 0.05% or vehicle for 4 weeks. The primary efficacy endpoint was Validated Investigator Global Assessment for AD (vIGA‐AD) Success (0 [Clear] or 1 [Almost Clear] plus ≥ 2‐grade improvement from baseline) at Week 4. Other endpoints included ≥ 75% improvement in Eczema Area and Severity Index (EASI‐75) and Worst Itch‐Numeric Rating Score (WI‐NRS) Success (≥ 4‐point improvement in patients with baseline ≥ 4). Safety and tolerability were also assessed.

Results

Among 437 and 215 patients treated with roflumilast and vehicle, respectively, significantly greater proportions of the roflumilast group achieved Week‐4 vIGA‐AD Success (25.4% vs. 10.7%; p < 0.0001), EASI‐75 (39.4% vs. 20.6%; p < 0.0001), and WI‐NRS Success (35.3% vs. 18.0%; nominal p = 0.0002). Improvement in pruritus was observed within 24 h after the first application (nominal p = 0.0014). Treatment‐emergent adverse event (TEAE) rates were low in both groups, and 98.9% were mild or moderate. At all timepoints, stinging/burning that caused definite discomfort was reported by ≤ 0.7% of caregivers of patients in the roflumilast group.

Conclusions

In this Phase 3 trial, once‐daily roflumilast cream 0.05% improved AD signs/symptoms in patients aged 2–5 years, with early pruritus improvement, low AE rates, and local tolerability comparable with vehicle.

Trial Registration: ClinicalTrials.gov: NCT04845620
Effectiveness of Psychosocial Interventions in Alcohol and Substance Use Disorders: A Meta‐Analysis Study
Authors: Helvacı Çelik Fatma Gül , Bayrak Nurten Gülsüm , Uzun Sevda
Published: February 2025

Alcohol and substance use disorders (ASUD), are increasing worldwide, and these psychiatric disorders are difficult to treat. The search for new treatments for these disorders continues. Psychosocial interventions (PI) are among them, and it is important to evaluate their effectiveness. This study aimed to assess the effectiveness of PI applied to individuals with ASUD. This meta‐analysis was conducted by searching PubMed, Web of Science, EBSCOhost, Google Scholar, and YOK Thesis Center databases without year restrictions between October and December 2023. After reviewing the studies, 18 research articles were included in the analysis. The meta‐analysis revealed that PI applied to individuals with ASUD were effective in reducing depression (SMD: −0.753, 95% CI: −1.215 to −2.91; I2 = 94.515; p < 0.05) and enhancing self‐efficacy (SMD: 0.709, 95% CI: 0.096–1.321; I2 = 93.34; p < 0.05). However, these interventions were not found to be effective in improving self‐esteem (SMD: 0.655, 95% CI: −1.641 to 0.331)
Significance of land management practices under haskap orchards to mitigate the degradations of soil organic carbon stocks and soil health because of land use changes from forest and grassland
Authors: Brahma Biplab , Hammermeister Andrew , Lynch Derek , Smith Peter , Nath Arun Jyoti
Published: February 2025

Managing the impact of land use change (LUC) in soil organic carbon (SOC) and soil health is imperative while climate change (CC) and food security are in concern. Land management practices in major land uses play a vital role in maintaining SOC concentrations and soil health. Haskap is one of the fastest growing berry orchards in Canada, covering around 0.1 Mha. Therefore, the present study has been conducted in two different haskap orchards established after replacing forest and grassland, respectively. The shallow (S) and furrow (F) tilling as tillage management and control (Cn) and compost + fertilizer (CF) as nutrient management have been incorporated in the present study to explore the effect of different land use management practices on soil properties. The estimated loss of SOC stocks because of LUC from forest to haskap for 0–10 and 10–30 cm soil depth is around 40% and 50%, respectively. However, around a 20% increase in SOC stocks has been estimated while the grassland was replaced by the haskap orchard. Moreover, under Cn nutrient management, the F tillage showed a 50% gain in SOC stocks over S tillage, but under CF nutrient management, the S tillage showed at least 25% higher SOC stocks over F tillage management. The CF nutrient management showed a significant effect on AC stocks estimated to be 31% higher than that under Cn management. The C:N ratio for 0–10 and 10–30 cm soil depths is significantly influenced by the LUC. However, the management induced in the present study does not have any significant influences on the C:N ratio. The present study suggests that the conversion of grassland soils into haskap orchards could play a significant role in SOC stocks management. Moreover, S tillage and F tillage with nutrient management under haskap orchards could be viable management options to improve soil carbon sequestration in upper and lower soil depths, respectively, by maintaining the N content in the soil.
Reduction in Length of Hospital Stays for Allogeneic Hematopoietic Stem‐Cell Transplantation in the Letermovir Era
Authors: Hosoi Hiroki , Tane Misato , Okamura Tadashi , Tabata Shotaro , Wan Ke , Murata Shogo , Mushino Toshiki , Nishikawa Akinori , Sonoki Takashi
Published: February 2025

Background

In recent years, letermovir has been routinely used for cytomegalovirus (CMV) infection prophylaxis in patients receiving allogeneic hematopoietic stem‐cell transplantation (HSCT). The reduction effect of letermovir on CMV infection rates and the impact on survival have been studied, but other potential benefits of letermovir remain underexplored.

Methods

This retrospective study included patients who underwent first‐time allogeneic HSCT between October 2013 and August 2023. We compared the length of hospital stay between eras before and after the introduction of letermovir (“nonletermovir group” and “letermovir group,” respectively). Secondary outcomes included clinically significant CMV infection rates and hospitalization costs.

Results

A total of 59 patients were analyzed in the nonletermovir group and 65 patients in the letermovir group. The median length of hospital stay was 51 days in the nonletermovir group and 42 days in the letermovir group (p < 0.001). Among standard‐risk disease patients, the letermovir group also had significantly shorter hospital stays (p = 0.0048). Additionally, the cumulative incidence of clinically significant CMV infection and grade II–IV acute graft‐versus‐host disease were both lower in the letermovir group. Hospitalization costs were not significantly different between the two groups.

Conclusion

The length of hospital stays after HSCT was observed to be shorter following the introduction of letermovir in this study. This reduction in hospital stays did not decrease hospitalization costs in relation to allogeneic HSCT, but it may alleviate the burden on both patients and healthcare providers.
DNA methylation dynamics in gymnosperm duplicate genes: implications for genome evolution and stress adaptation
Authors: Huang Kai‐Yuan , Feng Yuan‐Yuan , Du Hong , Ma Chang‐Wang , Xie Dan , Wan Tao , Feng Xiu‐Yan , Dai Xiao‐Gang , Yin Tong‐Ming , Wang Xiao‐Quan , Ran Jin‐Hua
Published: February 2025

Duplicate genes are pivotal in driving evolutionary innovation, often exhibiting expression divergence that offers a system to investigate the role of DNA methylation in transcriptional regulation. However, previous studies have predominantly focused on angiosperms, leaving the methylation patterns in major lineages of land plants still unclear. This study explores DNA methylation evolution in duplicate genes across representative gymnosperm species with large genomes, spanning over 300 million years, using genomic, transcriptomic, and high‐depth DNA methylomic data. We observed variations in DNA methylation levels along gene bodies, flanking regions, and methylation statuses of coding regions across different duplication types. Biased divergences in DNA methylation and gene expression frequently occurred between duplicate copies. Specifically, methylation divergences in the 2‐kb downstream regions negatively correlated with gene expression. Both CG and CHG DNA methylation in gene bodies were positively correlated with gene length, suggesting these methylation types may function as an epigenomic buffer to mitigate the adverse impact of gene length on expression. Duplicate genes exhibiting both methylation and expression divergences were notably enriched in adaptation‐related biological processes, suggesting that DNA methylation may aid adaptive evolution in gymnosperms by regulating stress response genes. Changes in expression levels correlated with switches in methylation status within coding regions of transposed duplicates. Specifically, depletion for CG methylation or enrichment for non‐CG methylation significantly reduced the expression of translocated copies. This correlation suggests that DNA methylation may reduce genetic redundancy by silencing translocated copies. Our study highlights the significance of DNA methylation in plant genome evolution and stress adaptation.
Victimización en las relaciones de noviazgo y exposición a conflictos familiares
Authors: Gutiérrez Prieto Beatriz , Bringas Molleda Carolina , Tornavacas Amado Rocío
Published: February 2025

La violencia en las relaciones interpersonales de pareja se ha demostrado, depende de diferentes factores personales y situacionales. El objetivo de este estudio es analizar la victimización sufrida por adolescentes y jóvenes en sus relaciones de pareja, teniendo en cuenta algunas variables personales y del contexto familiar. Los participantes son 450 jóvenes de ambos sexos, de entre 15 y 28 años y estudiantes de diferentes niveles educativos. Se analizan los factores de maltrato en función de la edad, sexo, nivel educativo y la presencia de conflictos en el ámbito familiar. Los datos nos muestran algunas diferencias significativas en la experiencia de maltrato en función del sexo, nivel educativo y de la existencia de conflictos entre los progenitores. Asimismo, la presencia de problemas entre los padres va a incrementar la probabilidad de victimización por parte de los jóvenes.
Sound field estimation for source-included region based on Gaussian process using prior source information
Authors: Matsuda Ryo , Otani Makoto
Published: February 2025

Estimating a sound field in a region that includes sources (i.e., an inhomogeneous sound field) is challenging. This paper proposes the Gaussian process (GP) for estimating an inhomogeneous sound field in the case of anechoic condition. A kernel function is formulated as a weighted spatial correlation of free-field transfer functions in the modal domain. The weights for the kernel function are derived by introducing the probability distribution of source positions in spherical regions containing the sound sources. Here, a weight obtained by analytically solving the spherical integral with the probability distribution as Gaussian is proposed. Schemes of order truncation and hyperparameter optimization for the kernel function are also proposed. Compared with conventional methods, numerical experiments reveal that the proposed method achieves higher sound field estimation accuracy. In addition, Gaussian process regression, using the kernel function with the proposed weight, achieves higher estimation accuracy with lower computational cost than those using the kernel functions with other weights. Moreover, the advantages of the proposed method, which are obtained by treating the sound source as a distribution rather than a point source, are revealed.
“Slayyyed Head to Toe”: Social Media Discourses of Blackness, Queerness, Gender, and the Women’s National Basketball Association Draft
Authors: Hindman Lauren C. , Keaton Ajhanai C.I. , Walker Nefertiti A.
Published: February 2025

As potential draftees walked the “orange carpet” at the 2022 Women’s National Basketball Association (WNBA) Draft, social media commentary dissected the fashion choices of the women athletes, many of whom were Black, and/or queer, and whose appearances spanned the gender spectrum. Through a critical discourse analysis of 447 tweets using the #WNBADraft hashtag, this study analyzes how social media discourse produced meanings related to gender, race, sexuality, and women athletes. Applying a Black Queer Feminism framework, findings show that WNBA consumers produced discourse that constructed the gaze at WNBA athletes, produced meanings of (Black and queer) womanhood, and established the WNBA as a site of cultural relevance. Study implications include an understanding of the queer gaze toward women athletes, the impact of consumer discourse in women’s sports, and a call for a “love ethic” in sport management scholarship.
Draft genome sequences of
Salmonella
recovered from organic and conventional retail chickens in Maryland, USA
Authors: Punchihewage-Don Anuradha J. , Chen Zhao , Meng Jianghong , Parveen Salina
Published: February 2025

We report the draft genome sequences of 94 multidrug-resistant
Salmonella
isolates (
S
. Infantis, Enteritidis, and Typhimurium) from organic and conventional retail chickens in Maryland, USA (average genome size = 4.97 Mb; guanine–cytosine content = 52.12%). These isolates harbored diverse antimicrobial resistance and virulence genes,
Salmonella
pathogenicity islands, and plasmids, highlighting potential public health risks.
Toxoplasma gondii
PROP1 is critical for autophagy and parasite viability during chronic infection
Authors: Thaprawat Pariyamon , Wang Fengrong , Chalasani Shreya , Schultz Tracey L. , Di Cristina Manlio , Carruthers Vern B.
Published: February 2025

Macroautophagy is an important cellular process involving lysosomal degradation of cytoplasmic components, facilitated by autophagy-related proteins. In the protozoan parasite
Toxoplasma gondii
, autophagy has been demonstrated to play a key role in adapting to stress and the persistence of chronic infection. Despite limited knowledge about the core autophagy machinery in
T. gondii
, two PROPPIN family proteins (TgPROP1 and TgPROP2) have been identified with homology to Atg18/WIPI. Prior research in acute-stage tachyzoites suggests that TgPROP2 is predominantly involved in a non-autophagic function, specifically apicoplast biogenesis, while TgPROP1 may be involved in canonical autophagy. Here, we investigated the distinct roles of TgPROP1 and TgPROP2 in chronic stage
T. gondii
bradyzoites, revealing a critical role for TgPROP1, but not TgPROP2, in bradyzoite autophagy. Conditional knockdown of TgPROP2 did not impair bradyzoite autophagy. In contrast, TgPROP1 KO parasites had impaired autolysosome formation, reduced cyst burdens in chronically infected mice, and decreased viability. Together, our findings clarify the indispensable role of TgPROP1 to
T. gondii
autophagy and chronic infection.

IMPORTANCE

It is estimated that up to a third of the human population is chronically infected with
Toxoplasma gondii
; however, little is known about how this parasite persists long term within its hosts. Autophagy is a self-eating pathway that has recently been shown to play a key role in parasite persistence, yet few proteins that carry out this process during
T. gondii
chronic infection are known. Here, we provide evidence for a non-redundant role of TgPROP1, a protein important in the early steps of the autophagy pathway. Genetic disruption of TgPROP1 resulted in impaired autophagy and chronic infection of mice. Our results reveal a critical role for TgPROP1 in autophagy and underscore the importance of this pathway in parasite persistence.
Gut microbiota development in very preterm infants following fortification of human milk
Authors: Yang Lin , Hui Yan , Sangild Per Torp , Kot Witold Piotr , Aunsholt Lise , Zachariassen Gitte , Jiang Ping-Ping , Nielsen Dennis Sandris
Published: February 2025

Very preterm infants (VPIs) are born with an immature gut and predisposed to gut microbiota dysbiosis-related diseases, for example, necrotizing enterocolitis. Although fortification of human milk is required for these infants, the optimal fortifier remains uncertain. Bovine colostrum (BC), rich in protein and bioactive components, could serve as an alternative to conventional fortifiers (CF). The gut microbiota (GM) of 225 VPIs fed human milk fortified with either BC or CF (FortiColos study, NCT03537365) was profiled by 16S rRNA gene amplicon sequencing of fecal samples collected before, and after 1 and 2 weeks of fortification. Birth mode exhibited transient effects on the microbial community structure shortly after birth, with cesarean section-born VPIs dominated by
Firmicutes
, whereas vaginally born VPIs were dominated by
Proteobacteria
. This birth mode-derived difference diminished with age and disappeared around 1 month after birth. Fortifier type affected the microbial community structure to a modest extent, but no specific taxa significantly differed between the BC and CF groups. Fecal pH, increased by BC, was positively correlated with
Staphylococcus
and
Corynebacterium
and negatively with
Bifidobacterium
abundance. Change in the relative abundance of
Staphylococcus
was negatively correlated with body weight gain. Collectively, fortification of human milk with BC or CF does influence the GM of VPIs but only to a modest extent during early life. Birth mode appears to have a significant, but temporary influence on the GM during this period.

IMPORTANCE

Early life is a key period for gut microbiota (GM) establishment, where enteral feeding plays a significant role. This is also the case for infants born preterm, who, due to their immature gut, are at a high risk of developing GM dysbiosis-related diseases. Human milk is the optimal feed for preterm infants, but it requires fortification to reach adequate levels of especially protein. Only a few studies have investigated the impact of fortifiers on GM development in preterm infants. Here, we demonstrate that two different bovine milk-based fortifiers, bovine colostrum and a conventional fortifier based on mature bovine milk, exhibit limited effects on the microbial community structure of very preterm infants. These findings suggest that although great care in terms of optimally maturing the preterm infant GM should be taken, the choice of fortifier only has limited impact. In clinical practice, the choice of fortifier can thus be fully focussed on optimizing preterm infant nutrition.

CLINICAL TRIALS

This study is registered with ClinicalTrials.gov as
NCT03537365
.
Targeting efflux pumps prevents the multi-step evolution of high-level resistance to fluoroquinolone in
Pseudomonas aeruginosa
Authors: Yu Xiao-Quan , Yang Hao , Feng Han-Zhong , Hou Jun , Tian Jun-Qiang , Niu Shao-Min , You Chong-Ge , Tao Xuan-Yu , Zhang Si-Ping , Wang Zhi-Ping , He Yong-Xing
Published: February 2025

Antibiotic resistance is emerging as a significant global health crisis, necessitating the urgent development of novel antibiotics or alternative therapies. Although it is recognized that bacteria require multiple mutations to develop resistance levels exceeding the mutant prevention concentration, the specific mutation combinations conferring high resistance have been largely undefined. Here, we investigated the multi-step evolution of fluoroquinolone resistance in
Pseudomonas aeruginosa
through experimental evolution and whole-genome sequencing coupled with proteomic approaches. We discovered that in low-dose and high-dose experimental evolution scenarios, combinations of mutations in the negative regulators of efflux pumps (
nfxB/mexR
) and DNA gyrases (
gyrA/gyrB
) contributed to the high-level resistance and some of these combinations were also prevalent in clinical isolates of
P. aeruginosa
. Notably, the selected
nfxB
mutation, which resulted in the overexpression of the MexCD-OprJ efflux pump, also exhibited collateral sensitivity to aminoglycosides and enhanced antibiotic tolerance. It was further revealed that the efflux pump inhibitor phenylalanine-arginine β-naphthylamide (PAβN) could effectively prevent evolution to high-level resistance for both laboratory and clinical
P. aeruginosa
strains. Our work highlights the critical role of efflux pump repressor-related mutations in the evolution of high-level antibiotic resistance and demonstrates the potential of targeting these mutations to impede the evolution toward high-level resistance.

IMPORTANCE

In this study, we examined the stepwise evolution of fluoroquinolone resistance in
Pseudomonas aeruginosa
using experimental evolution, whole-genome sequencing, and proteomic analyses. Our findings revealed that under both low-dose and high-dose conditions, mutations in efflux pump regulators (
nfxB
/
mexR
) and DNA gyrase genes (
gyrA
/
gyrB
) synergistically contributed to high-level resistance. These mutation combinations were not only observed in experimental settings but also detected in clinical isolates of
P. aeruginosa
. This work underscores the pivotal role of efflux pump repressor-related mutations in the progression to high-level antibiotic resistance. It also highlights the promise of targeting efflux pumps as a strategy to prevent the multi-step evolution of resistance in
P. aeruginosa
.
Nonlinear Optical Properties of Ge7Se93 Chalcogenide Glass as a Low-Melting Immersion Medium for Femtosecond Laser Marking of Diamonds in the Near-Infrared Range
Authors: Pakholchuk P. P. , Smirnov N. A. , Busleev N. I. , Pomazkin D. A. , Vins V. G. , Kudryashov S. I. , Shiryaev V. S.
Published: February 2025

The possibility of the femtosecond laser structural micromodification (microlabeling) of diamond through a solid immersion layer made of Ge7Se93 chalcogenide glass at a wavelength of 1.55 μm has been investigated. The two-photon absorption coefficient of Ge7Se93 has been measured to be β2 = (0.09 ± 0.01) cm/GW, which allows the propagation of intense femtosecond laser radiation in this spectral range through realistically thin (<0.1–1 mm) immersion layers. Despite the nonlinear absorption and optical damage in the immersion volume, photoluminescent microlabels have been observed in the test writing modes in the volume of diamond, which become more uniform with decreasing exposure time and pulse energy.
Demographic disparity in Wikipedia coverage: a global perspective
Authors: Yu Yulin , Li Xianglong , Li Tianyi , Dhillon Paramveer S. , Romero Daniel M.
Published: February 2025

Despite decades-long efforts to increase diversity, underrepresented social groups remain small minorities in many fields. Here, we ask whether disparities in global recognition exist for traditionally underrepresented demographic groups. We investigate whether a notable person’s demographic attributes are associated with their global recognition, considering both the global availability of public information about the person’s life and the consistency of such information. To track bibliographical information about notable people, we study Wikipedia, one of the most accessible knowledge bases on the Web. Using more than 1 million biographical articles from Wikipedia over ten years across the 12 largest language editions of Wikipedia, we study global gender and citizenship disparities in Wikipedia coverage. We measure global coverage in several ways, including the number of languages in which a person appears, the length of a person’s articles, and the global consensus about the person, which measures content similarity in the person’s articles across languages. We find that while females are broadly well-represented in terms of coverage in multiple languages starting from 2015, the quantity of the content of their articles and global consensus disparities persist consistently over time from 2010 to 2020. Additionally, some traditionally underrepresented nationalities are still covered less than their majority counterparts. Also, we observe an improvement on average in coverage while finding a persistent gender disparity in a specific domain, the global appearance of Olympic medal winners.
Graphene Oxide/CuO/ZnO Nanocomposite Combined Carbon Fibers as a Sensor for the Determination of Antibiotic Chloramphenicol
Authors: Shruthi S.M.G , KP Latha , Kumar Mohan , Revansiddappa Raghavendra R B , Reddy Sathish
Published: February 2025

A nano-composition of graphene oxide (GO), copper oxide (CuO), and zinc oxide (ZnO) was synthesized by utilizing the co-precipitation method and characterized by various methods. The synthesized GO/CuO/ZnO nanocomposite was utilized as a modifier combined with carbon fiber (CF) on the glassy carbon electrode (GO/CuO/ZnO@CF/GCE). The modified electrode was utilized to determine the antibiotic chloramphenicol (CAP), which risks public and environmental health by arising as residue, especially in food samples. Cyclic voltammetry and differential voltammetric techniques were used to investigate the electrochemical performance of CAP on the GO/CuO/ZnO@CF/GCE, and it established excellent electrocatalytic activity compared to bare glassy carbon electrode (BGCE). The electroactive surface area of BGCE and GO/CuO/ZnO@CF/GCE were found to be 0.03605 cm2 and 0.05215 cm2 respectively. Scan-rate studies reveal the diffusion-controlled electrode process at GO/CuO/ZnO@CF/GCE. The modified electrode showed a high sensitivity of 1.45 µA/µM cm2 with a low detection limit (13.3 µM). The prepared modified electrochemical sensor had well repeatability and reproducibility, adequate stability, and good selectivity toward the determination of CAP. Moreover, prepared (GO/CuO/ZnO@CF/GCE) was utilized to measure CAP in real samples such as milk and honey.
Activity and function of the endothelial sodium channel is regulated by the effector domain of MARCKS like protein 1 in mouse aortic endothelial cells
Authors: Yu Ling , Bala Niharika , Nguyen Van-Anh L. , Kessler Leah , LaDisa John F. , Alli Abdel A.
Published: February 2025

Enhanced endothelial sodium channel (EnNaC) functioning causes an increase in vessel stiffness. Here, we investigated the regulation of EnNaC in mouse aortic endothelial cells (mAoEC) by the actin cytoskeleton and lipid raft association protein myristoylated alanine-rich C-kinase substrate like protein 1 (MLP1). We hypothesized that mutation of specific amino acid residues within the effector domain of MLP1 or loss of association between MLP1 and the anionic phospholipid phosphate PIP2 would significantly alter membrane association and EnNaC activity in mAoEC. mAoEC transiently transfected with a mutant MLP1 construct (three serine residues in the effector domain replaced with aspartate residues) showed a significant decrease in EnNaC activity compared to cells transfected with wildtype MLP1. Compared to vehicle treatment, mAoEC treated with the PIP2 synthesis blocker wortmannin showed less colocalization of EnNaC and MLP1. In other experiments, Western blot and densitometric analysis showed a significant decrease in MLP1 and caveloin-1 protein expression in mAoEC treated with wortmannin compared to vehicle. Finally, wortmannin treatment decreased sphingomyelin content and increased membrane fluidity in mAoEC. Taken together, these results suggest that constitutive phosphorylation of MLP1 attenuates the function of EnNaC in aortic endothelial cells by a mechanism involving a decrease in association with MLP1 and EnNaC at the membrane, while deletion of PIP2 decreases MLP1 expression and overall membrane fluidity.
Inhibition of PIM kinase in tumor-associated macrophages suppresses inflammasome activation and sensitizes prostate cancer to immunotherapy
Authors: Clements Amber N. , Casillas Andrea L. , Flores Caitlyn E. , Liou Hope , Toth Rachel K. , Chauhan Shailender S. , Sutterby Kai , Deshmukh Sachin Kumar , Wu Sharon , Xiu Joanne , Farrell Alex , Radovich Milan , Nabhan Chadi , Heath Elisabeth I. , McKay Rana R. , Subah Noor , Centuori Sara , Wheeler Travis J. , Cress Anne E. , Rogers Gregory C. , Wilson Justin E. , Recio-Boiles Alejandro , Warfel Noel A.
Published: February 2025

Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm for many cancers but have not shown benefit in prostate cancer (PCa). Chronic inflammation contributes to the immunosuppressive prostate tumor microenvironment (TME) and is associated with poor response to ICIs. The primary source of inflammatory cytokine production is the inflammasome. Here, we identify PIM kinases as regulators of inflammasome activation in tumor-associated macrophages (TAMs). Analysis of clinical data from a cohort of treatment naïve, hormone-responsive PCa patients revealed that tumors from patients with high PIM1/2/3 displayed an immunosuppressive TME characterized by high inflammation and a high density of repressive immune cells, most notably TAMs. Macrophage-specific knockout of PIM reduced tumor growth in syngeneic models of PCa. Transcriptional analyses indicated that eliminating PIM from macrophages enhanced the adaptive immune response and increased cytotoxic immune cells. Combined treatment with PIM inhibitors and ICIs synergistically reduced tumor growth. Immune profiling revealed that PIM inhibitors sensitized PCa tumors to ICIs by increasing tumor suppressive TAMs and increasing the activation of cytotoxic T cells. Our data implicate macrophage PIM as a driver of inflammation that limits ICI potency and provide preclinical evidence that PIM inhibitors are an effective strategy to improve the ICI efficacy in PCa.
Table 2 from A Phase 2 Study of Sotigalimab, a CD40 Agonist Antibody, plus Concurrent Chemoradiation as Neoadjuvant Therapy for Esophageal and Gastroesophageal Junction Cancers
Authors: Ko Andrew H. , Chao Joseph , Noel Marcus S. , Shankaran Veena , Sohal Davendra , Crow Mary , Oberstein Paul E. , Scott Aaron J. , McRee Autumn J. , Rocha Lima Caio Max Sao Pedro , Fong Lawrence , Keenan Bridget P. , Soto Maira , Filbert Erin L. , Hsu Frank J. , Yang Xiaodong
Published: February 2025

Most common TEAEs (occurring in ≥10% of subjects; n = 33)
Nutrition for Optimal Lactation
Authors: Perichart-Perera Otilia
Published: February 2025

Background:: Breastfeeding is the ideal method of feeding for all newborns and is associated with multiple positive health outcomes. Human milk provides all essential nutrients and bioactive molecules needed for optimal infant health and development. Maternal nutrition during lactation plays an important role in supporting breastfeeding and in preventing nutrition and metabolic imbalances. The aim of this narrative review was to describe the most prevalent nutrition issues in lactating women and provide a summary of current diet recommendations as well as controversies on supplementation, in order to facilitate the information for clinicians and health professionals. Summary:: Breastfeeding is a nutritionally demanding stage and adequate nutrition is key to avoid alterations in maternal nutritional status, to produce an adequate quantity of milk with good quality, and to avoid nutrition programming of diseases. Anemia and vitamin D, A, iodine, and iron deficiencies are common, while obesity and metabolic diseases keep rising. Inadequate maternal intake of many nutrients is also frequent in this stage.
Inflammatory Bowel Disease in a Patient Returning from Colombia: Association with Dipeptidyl Peptidase 4 Inhibitor?
Authors: Bayoumy Ahmed B. , Masclee Gwen M.C. , de Boer Nanne K.H. , Neefjes-Borst Andra , Stenvers Dirk Jan
Published: February 2025

Introduction: Recent-onset colitis poses a diagnostic challenge, necessitating a thorough evaluation to identify potential infectious and non-infectious etiologies. We considered inflammatory bowel disease (IBD) secondary to dipeptidyl peptidase 4 (DPP-4) inhibitor-induced colitis. Case Presentation: This case report details the presentation and management of a patient with persistent dysentery, refractory to conventional treatments, ultimately attributed to IBD possibly secondary to long-term DPP-4 inhibitor use. Following an episode of suspected amebiasis, the patient experienced prolonged bloody diarrhea with an endoscopic image compatible with ulcerative colitis. Extensive infectious diagnostics were negative. Ultimately, the cessation of sitagliptin therapy resulted in rapid symptom resolution and normalization of eosinophilia, as well as endoscopic improvement. However, after a few weeks, the patient was readmitted with diarrhea after continued cessation of sitagliptin. Conclusion: This case underscores the importance of considering IBD secondary to DPP-4 inhibitor use in the evaluation of patients with recent-onset IBD. Further research is needed to elucidate the pathophysiological mechanisms underlying the relationship between DPP-4 inhibitors and IBD.
Endoscopic and Clinicopathological Features of a Colorectal Mucin-Rich Variant of Traditional Serrated Adenoma
Authors: Kamba Eiji , Murakami Takashi , Tsugawa Naoki , Otsuki Yudai , Nomura Kei , Kadomatsu Yuichiro , Fukushima Hirofumi , Saito Tsuyoshi , Shibuya Tomoyoshi , Yao Takashi , Nagahara Akihito
Published: February 2025

Introduction: The mucin-rich variant of traditional serrated adenoma (MR-TSA), pathologically defined by the presence of goblet cells comprising over 50% of the lesion compared to the absorptive epithelial eosinophilic cytoplasm, was recently introduced as one morphological variants of traditional serrated adenoma (TSA). This study aimed to characterize the endoscopic and clinicopathological characteristics of MR-TSAs. Methods: Lesions pathologically diagnosed as TSAs at our hospital between 2011 and 2023 were reviewed. We analyzed the endoscopic and clinicopathological features of 49 MR-TSAs and 236 conventional TSAs (C-TSAs). Furthermore, immunohistochemical and genetic analyses were performed to ensure that there were no discrepancies with our previous study. Results: MR-TSAs, like C-TSAs, were often located in the sigmoid colon and rectum, with no significant difference in lesion size. Macroscopically, MR-TSAs frequently appeared as type 0-Is with a weak reddish color and had a mucous cap, less often exhibiting a pinecone-like or coral-shaped appearance compared to C-TSAs (p < 0.001). Magnifying endoscopy showed expanded crypt openings in 80% of MR-TSAs (p < 0.001). Both groups had similar IIIH and IVH pit patterns. Immunohistochemical analysis revealed that MUC5AC was expressed more frequently in MR-TSAs than in C-TSAs. Additionally, genetic analysis showed that MR-TSAs more frequently harbored the BRAF mutation than C-TSAs (p < 0.001), whereas MR-TSAs less frequently harbored the KRAS mutation than C-TSAs (p = 0.047). Conclusion: MR-TSAs, frequently harboring the BRAF but not KRAS mutation, exhibited several distinct endoscopic findings, including a sessile morphology, lack of pinecone-like or coral-like appearance, weak reddish color, and mucous cap.
Familial Non-autoimmune Hyperthyroidism Caused by an Extracellular Domain Variant (p.Leu267Phe) of the TSH Receptor.
Authors: Shimura Kazuhiro , Ichihashi Yosuke , Abe Kiyomi , Ishii Tomohiro , Hasegawa Tomonobu , Narumi Satoshi
Published: February 2025

Introduction: Non-autoimmune hyperthyroidism (NAH) is a rare genetic disorder caused by germline activating variants in the TSH receptor (TSHR) gene. While most NAH-related TSHR variants are located in the seven-transmembrane domain (7TMD), three variants (p.Leu267Phe, p.Ser281Asn, and p.Asn406Ser) have been identified in the extracellular domain (ECD), with p.Leu267Phe previously not showing constitutively active in vitro.
Methods: We searched for TSHR variants in a Japanese family with NAH using PCR-based direct sequencing. We created three ECD variants (p.Leu267Phe, p.Ser281Asn, and p.Asn406Ser) and a series of variants in which Leu267 was mutated to 18 amino acids other than Leu and Phe. Based on the cryo-electron microscopic structures, we evaluated the structure-function relationship of TSHR. We compared their cAMP-producing capacities to WT-TSHR in the luciferase activity assay using HEK293 cells. Western blot and fluorescence immunostaining were performed using HA-tagged TSHR vectors to compare Leu267Phe-TSHR with WT-TSHR.
Results: A heterozygous TSHR variant (p.Leu267Phe) was identified. Comparison of the cryo-electron microscopy structures of the activated and inactivated TSHRs revealed a significant change in the ECD structure around Leu267. The ligand-independent cAMP-producing capacities compared to WT-TSHR were 238 ± 20% (mean ± SEM) for Leu267Phe. Of all 19 possible variants created through systematic mutagenesis, only Leu267Phe-TSHR and Leu267Tyr-TSHR exhibited significantly higher ligand-independent cAMP-producing capacities. Immunoblotting and fluorescence immunostaining showed that the Leu267Phe variant did not affect protein expression levels and intracellular localization of TSHR..
Discussion/Conclusion: Leu267Phe-TSHR causes NAH. Substituting Leu267 to aromatic amino acids may shift the equilibrium of the TSHR state toward activation.
Modinha e seus paradigmas através de Word painting: Viola de Lereno, modinha oitocentista e modinha de Catulo da Paixão Cearense
Authors: Vaccari Pedro Razzante
Published: February 2025

Trata do gênero modinha e seus paradigmas por meio dos séculos, a saber: os espécimes publicados em Viola de Lereno, de Caldas Barbosa, que denotam a modinha do século XVIII, em forma simples, binária ou tripartida, em compasso binário e acompanhada de cordas dedilhadas. Com a chegada da Corte portuguesa em 1808, as modinhas lusitanas são importadas para o Brasil, ocorrendo o processo inverso – absorvidas pela produção da colônia, passam para o acompanhamento de teclado, como as modinhas do padre José Maurício Nunes Garcia. Derivadas fortemente da ópera italiana, mantém a estrutura melismática da modinha setecentista, porém incorporam o baixo de Alberti do classicismo no acompanhamento do piano doméstico e de salão, principalmente a partir de meados do século XIX, com o advento da impressão no Brasil. Por essa época viveu no país a soprano italiana Augusta Candiani, responsável por disseminar e firmar a modinha como gênero preferido nos salões cariocas, mostrando como eram as modinhas da época praticamente árias de ópera. A repopularização se daria gradualmente, passando por Chiquinha Gonzaga, após a abolição da escravidão, e a implosão de novas necessidades socioculturais advindas da estruturação de novas classes sociais urbanas consumidoras. Surge, então, o momento paradigmático que irá nortear a modinha de violão, mais uma vez, popular e com versos arrojados, principalmente nas composições de Catulo da Paixão Cearense. O fio condutor de todo esse repertório pode ser a técnica de utilizar um método renascentista europeu, chamado Word painting, em que clichês musicais são traduzidos dos elementos da poesia de forma literal.
Right-Wing Populists and the Politics of Renegotiating International Environmental Agreements
Authors: Huynh Nguyen Khoi
Published: February 2025

The rise of right-wing populist (RWP) parties across democracies who disparage and seek to dismantle international (environmental) agreements poses a grave threat to the liberal international order. Yet we know surprisingly little about how RWP parties influence the design of international agreements, including international environmental agreements (IEAs). This article addresses this lacuna by exploring the link between RWP parties and a key outcome in the design of IEAs—flexibility provisions used by democracies to reduce their obligations to curb environmental pollution. The theoretical framework first posits that RWP parties allege that IEAs hurt ordinary people to garner support from domestic constituents adversely affected by IEA environmental mandates. When a RWP party holds a majority of seats in its country’s legislature, it employs its legislative leverage in the international arena to negotiate and obtain maximum flexibility provisions from other member states to safeguard their constituents. Statistical results provide robust support for my theoretical predictions.
Evaluation of multimode capabilities and overall performance of RRR-type legged mobile lander
Authors: Mahmood Azhar , Guo Weizhong , Zhu Gaohan , Sohaib Muhammad
Published: February 2025

This paper introduces an inverted modeling method that simplifies the kinematic analysis and enables efficient estimation of overall performance capability of legged mobile lander, rather than focusing solely on performance of single leg. The modeling is transformed and measured in the body frame. The orientation of plane passing through all the footpads is taken into consideration rather than body of robot. This approach allows the method to be universally applicable to various legged robotic systems. Several performance measurements using Inverted Modeling are presented and used in performance evaluation. The method is applied to the multimode overall performance evaluation of an RRR type legged mobile lander. Then an experimental study assesses impact forces across different operational modes, providing valuable insights into the LML’s behavior under various conditions. Ultimately, this research presents an innovative approach for simplifying lander’s overall performance evaluation while validating the potential of LMLs to enhance extraterrestrial exploration.