bluuebunny/crossref_metadata_2025 huggingface dataset:
MeerKLASS L-band deep-field intensity maps: entering the H i dominated regime
Authors:   MeerKLASS Collaboration, Barberi-Squarotti Matilde , Bernal José L , Bull Philip , Camera Stefano , Carucci Isabella P , Chen Zhaoting , Cunnington Steven , Engelbrecht Brandon N , Fonseca José , Grainge Keith , Irfan Melis O , Li Yichao , Mazumder Aishrila , Paul Sourabh , Pourtsidou Alkistis , Santos Mario G , Spinelli Marta , Wang Jingying , Witzemann Amadeus , Wolz Laura
Published: February 2025

We present results from MeerKAT single-dish H i intensity maps, the final observations to be performed in L-band in the MeerKAT Large Area Synoptic Survey (MeerKLASS) campaign. The observations represent the deepest single-dish H i intensity maps to date, produced from 41 repeated scans over $236\, \deg ^2$, providing 62 h of observational data for each of the 64 dishes before flagging. By introducing an iterative self-calibration process, the estimated thermal noise of the reconstructed maps is limited to ${\sim }\, 1.21$ mK ($1.2\, \times$ the theoretical noise level). This thermal noise will be subdominant relative to the H i fluctuations on large scales ($k\, {\lesssim }\, 0.15\, h\, \text{Mpc}^{-1}$), which demands upgrades to power spectrum analysis techniques, particularly for covariance estimation. In this work, we present the improved MeerKLASS analysis pipeline, validating it on both a suite of mock simulations and a small sample of overlapping spectroscopic galaxies from the Galaxy And Mass Assembly (GAMA) survey. Despite only overlapping with ${\sim }\, 25~{{\ \rm per\ cent}}$ of the MeerKLASS deep field, and a conservative approach to covariance estimation, we still obtain a ${\gt }\, 4\, \sigma$ detection of the cross-power spectrum between the intensity maps and the 2269 galaxies at the narrow redshift range $0.39\, {\lt }\, z\, {\lt }\, 0.46$. We briefly discuss the H i autopower spectrum from these data, the detection of which will be the focus of follow-up work. For the first time with MeerKAT single-dish intensity maps, we also present evidence of H i emission from stacking the maps onto the positions of the GAMA galaxies.
An examination of large-scale galactic effects on molecular cloud properties in NGC 628: the significant impact of tidal effects from neighbouring material on the evolution of molecular clouds
Authors: Zhou J W , Dib Sami
Published: February 2025

The physical factors that influence the development of molecular cloud’s density contrast are connected to those that affect star formation in the galaxy. For NGC 628 (M74), the proportion of high- and low-density contrast clouds initially increases with the distance to the galactic centre ($R_{G}$) and then keeps relatively stable. Spiral arms, bubbles, and magnetic fields are not responsible for the variations in density contrast observed among molecular clouds. The effects of shear and tides calculated from the galactic rotation curve consistently decrease as $R_{G}$ increases, and the shear effect can be neglected. We further studied the tidal effects of the neighbouring material on each cloud using the tidal tensor analysis and the pixel-by-pixel computation, after combining molecular gas, atomic gas, and stellar mass surface density maps. When $R_{\rm G} \lt $ 4 kpc, the tidal strengths derived from the pixel-by-pixel computation decrease as $R_{\rm G}$ increases, and then remains relatively constant when $R_{\rm G} \gt $ 4 kpc. This aligns well with the dependence of the proportion of high- and low-density contrast clouds on $R_{\rm G}$. Therefore, the tidal effects of neighbouring material have a significant impact on the development of molecular cloud’s density contrast. A key factor contributing to the low star formation rate in the galactic centre is the excessive tidal influences from neighbouring material on molecular clouds, which hinder the gravitational collapse within these clouds, resulting in low density contrasts. The tidal effects from neighbouring material may also be a significant contributing factor to the slowing down of a pure free-fall gravitational collapse for gas structures on galaxy-cloud scales revealed in our previous works by velocity gradient measurements.
Neural infalling cloud equations (NICE): increasing the efficacy of subgrid models and scientific equation discovery using neural ODEs and symbolic regression
Authors: Tan Brent
Published: February 2025

Galactic systems are inherently multiphase, and understanding the roles and interactions of the various phases is key towards a more complete picture of galaxy formation and evolution. For instance, these interactions play a pivotal role in the cycling of baryons which fuels star formation. The transport and dynamics of cold clouds in their surrounding hot environment are governed by complex small-scale processes (such as the interplay of turbulence and radiative cooling) that determine how the phases exchange mass, momentum, and energy. Large-scale models thus require subgrid prescriptions in the form of models validated on small-scale simulations, which often take the form of coupled differential equations. In this work, we explore using neural ordinary differential equations (ODEs) which embed neural networks as terms in the model to capture an uncertain physical process. We then apply symbolic regression to potentially discover new insights into the physics of cloud–environment interactions. We test this on both generated mock data and actual simulation data. We also extend the neural ODE to include a secondary neural term. We show that neural ODEs in tandem with symbolic regression can be used to enhance the accuracy and efficiency of subgrid models, and/or discover the underlying equations to improve generality and scientific understanding. We highlight the potential of this scientific machine learning approach as a natural extension to the traditional modelling paradigm, both for the development of semi-analytical models and for physically interpretable equation discovery in complex non-linear systems.
Antinuclear antibodies staining patterns and titres in juvenile idiopathic arthritis
Authors: Sener Seher , Batu Ezgi Deniz , Aliyev Emil , Basaran Ozge , Saribas Zeynep , Bilginer Yelda , Sener Burcin , Ozen Seza
Published: February 2025

Objectives

In our study, we evaluated the antinuclear antibodies (ANA) staining patterns and titres in juvenile idiopathic arthritis (JIA) patients.

Methods

JIA patients were retrospectively assessed. ANA was identified by using indirect immunofluorescence assay on HEp-2 cells, with a positivity threshold set at a titre of ≥1/100.

Results

Eight hundred-five patients were evaluated [oligoarticular JIA (n = 396), enthesitis-related arthritis (n = 195), polyarticular JIA (n = 132), systemic JIA (n = 53), psoriatic arthritis (n = 20), and unclassified JIA (n = 9)]. The most frequently observed ANA nuclear staining patterns were AC-4/5 (fine or large speckled) in 29.7% of patients and AC-1 (homogeneous) in 25.9%. The most common ANA cytoplasmic staining pattern was AC-19 (dense, fine speckled) (17.6%). Most systemic and unclassified JIA patients were ANA negative. The most frequently detected ANA titre in oligoarticular JIA and enthesitis-related arthritis patients was 1/160 (P = .026 and P = .018, respectively), while in psoriatic arthritis patients, it was 1/320 (P < .001). In addition, uveitis and inflammatory bowel disease were most frequently associated with AC-4/5 & AC-19 patterns and an ANA titre of 1/160 (all P < .001).

Conclusions

Our study showed that many JIA subtypes and JIA-related comorbidities were associated with the AC-4/5, AC-1, and AC-19 ANA patterns. However, multicentre studies in larger cohorts are needed to generalize these results.
Breakthrough herpes zoster following recombinant zoster vaccinations in a rheumatoid arthritis patient receiving a Janus kinase inhibitor: A case report and literature review
Authors: Nagata Shunya , Yokogawa Naoto
Published: February 2025

The recombinant zoster vaccine (RZV) is immunologically and clinically effective in immunosuppressed patients. Though rheumatoid arthritis (RA) and the Janus kinase inhibitor (JAKi) increase the risk of herpes zoster (HZ) infection, breakthrough cases in which a HZ infection followed RZV administration are rare. We report herein a 63-year-old female patient with seropositive RA who experienced a HZ infection despite receiving the RZV. She had been receiving tocilizumab, methotrexate, and low-dose prednisolone until tocilizumab was switched to upadacitinib 4 weeks after two RZV administrations, which resulted in 63 weeks’ remission. Her current admission was for a painful rash consisting of blisters and erythema on the right nasal alar and lips corresponding to the right V2 segment of the trigeminal nerve. HZ was diagnosed and treated for 7 days with intravenous acyclovir, which alleviated the symptoms. JAKi can suppress a range of immunogenic mechanisms which underlie the efficacy of the RZV. The present patient was expected to respond favourably to the RZV because JAKi had not been administered prior to the vaccinations; however, the later start of JAKi therapy caused a breakthrough HZ infection. Immunocompromised patients have a higher risk of severe HZ, including the disseminated form, but breakthrough cases are relatively rare. The RZV is recommended as prophylaxis against HZ as well as means of mitigating its severity when it does occur.
The structure of the MutL-CTD:processivity-clamp complex provides insight regarding strand discrimination in non-methyl-directed DNA mismatch repair
Authors: Nirwal Shivlee , Jha Ritika , Narayanan Naveen , Sharma Minakshi , Kulkarni Dhananjaya S , Sharma Dalchand , Babu Amith S , Suthar Dhiraj K , Rao Desirazu N , Nair Deepak T
Published: February 2025

Many prokaryotes, including members of the Neisseria species, lack MutH and cannot employ methyl-directed DNA mismatch repair (MMR). The nick on the daughter strand is created by the endonuclease activity present in the C-terminal domain (CTD) of the MutL homodimer. MutL-CTD is known to interact with the processivity-clamp. The crystal structure of the homodimeric MutL-CTD from Neisseria (NgoL-CTD) in complex with homodimeric processivity-clamp (Nβ-Clamp) shows that each NgoL-CTD monomer binds to a Nβ-Clamp monomer through the conserved motif III (517QHLLIP522). The structure and allied biochemical studies plus in vivo growth assays conducted with wild-type (wt) plus mutant proteins shows that the endonuclease dimer sits transversely across the C-terminal face of the Nβ-Clamp ring. The comparison of the structure with that of the partial prokaryotic replisome suggests that the relative orientation of DNA, Nβ-Clamp, and NgoL-CTD may direct the daughter strand towards one of the active sites in endonuclease homodimer. Nicking assays conducted with wt and mutant NgoL-CTD in the presence and absence of Nβ-Clamp support this inference. Overall, our studies posit that strand discrimination in non-methyl-directed MMR is achieved through a structural strategy involving the β-Clamp which is distinct from the chemical strategy employed in prokaryotes like Escherichia coli.
Crossovers are regulated by a conserved and disordered synaptonemal complex domain
Authors: Neves Ana Rita Rodrigues , Čavka Ivana , Rausch Tobias , Köhler Simone
Published: February 2025

During meiosis, the number and distribution of crossovers (COs) must be precisely regulated through CO assurance and interference to prevent chromosome missegregation and genomic instability in the progeny. Here we show that this regulation of COs depends on a disordered and conserved domain within the synaptonemal complex (SC). This domain is located at the C-terminus of the central element protein SYP-4 in Caenorhabditis elegans. While not necessary for synapsis, the C-terminus of SYP-4 is crucial for both CO assurance and interference. Although the SYP-4 C-terminus contains many potential phosphorylation sites, we found that phosphorylation is not the primary regulator of CO events. Instead, we discovered that nine conserved phenylalanines are required to recruit a pro-CO factor predicted to be an E3 ligase and regulate the physical properties of the SC. We propose that this conserved and disordered domain plays a crucial role in maintaining the SC in a state that allows transmitting signals to regulate CO formation. While the underlying mechanisms remain to be fully understood, our findings align with existing models suggesting that the SC plays a critical role in determining the number and distribution of COs along chromosomes, thereby safeguarding the genome for future generations.
DNA replication dynamics are associated with genome composition in Plasmodium species
Authors: Totañes Francis Isidore Garcia , Chapman Sarah E , Rai Subash Kumar , Jones Mathew J K , Boemo Michael A , Merrick Catherine J
Published: February 2025

Plasmodium species have variable genome compositions: many have an A/T content >80%, while others are similar in composition to human cells. Here, we made a direct comparison of DNA replication dynamics in two Plasmodium species whose genomes differ by ∼20% A/T content. This yielded fundamental insights into how DNA composition may affect replication. The highly A/T-biased genome of Plasmodium falciparum showed unusual replication dynamics that were not observed in the more balanced Plasmodium knowlesi—which had dynamics more like those of human cell lines. Replication forks moved 50% slower in P. falciparum than in P. knowlesi. In P. falciparum, replication forks slowed down over the course of S-phase, whereas in P. knowlesi, fork speed increased as in human cells. Furthermore, in both P. knowlesi and human cells, replication forks were strikingly slowed by sequences of particularly high A/T bias, but in P. falciparum, although replication forks were inherently slow, they were not particularly slow in such biased sequences. Thus, the replisome of P. falciparum may have evolved alongside its extremely biased genome, making it unusually robust to sequence bias. Since several antimalarial drugs act to stall DNA replication, this study may have implications for the effectiveness of, and development of, antimalarial therapies.
Current state and future prospects of Horizontal Gene Transfer detection
Authors: Wijaya Andre Jatmiko , Anžel Aleksandar , Richard Hugues , Hattab Georges
Published: February 2025

Artificial intelligence (AI) has been shown to be beneficial in a wide range of bioinformatics applications. Horizontal Gene Transfer (HGT) is a driving force of evolutionary changes in prokaryotes. It is widely recognized that it contributes to the emergence of antimicrobial resistance (AMR), which poses a particularly serious threat to public health. Many computational approaches have been developed to study and detect HGT. However, the application of AI in this field has not been investigated. In this work, we conducted a review to provide information on the current trend of existing computational approaches for detecting HGT and to decipher the use of AI in this field. Here, we show a growing interest in HGT detection, characterized by a surge in the number of computational approaches, including AI-based approaches, in recent years. We organize existing computational approaches into a hierarchical structure of computational groups based on their computational methods and show how each computational group evolved. We make recommendations and discuss the challenges of HGT detection in general and the adoption of AI in particular. Moreover, we provide future directions for the field of HGT detection.
Single cobalt atoms with unconventional dynamic coordination mechanism for selective ammonia sensor
Authors: Li Yuejiao , Li Yaguang , Shi Yushu , Gao Jianmei , Lu Jianmin , Wang Chao , Chang Junyu , Wang Zhenming , Yang Yangyue , Yang Bing , Feng Liang , Fu Qiang , Bao Xinhe , Wu Zhong-Shuai
Published: February 2025

Developing gas sensors that can simultaneously achieve high sensitivity and selectivity for the detection of a single-type gas remains a significant challenge. Herein we demonstrate cobalt (Co) single atoms with an unconventional dynamically changing coordination structure that could be used as NH3-sensing material with superior sensitivity and selectivity. According to the steric effect of 2-methylimidazole (2MI) molecules and carbonyl groups on graphene, the Co single atom is evolved into a bidentate coordinated structure (Co-2MI-G). In-situ characterization and theoretical simulation reveal that the sensing mechanism of Co-2MI-G is the specific chemical adsorption between unsaturated coordinated Co single atoms and NH3 molecules, causing a reversible switching of coordination number from 2 to 4, a valence state transfer from Co2+ to Co3+ of Co single atoms, and a band-gap width from 0.14 eV to 0.50 eV. Consequently, the Co-2MI-G-based gas sensor presents a sensing response of 67.598% for 1 ppm NH3 and a limit of detection of 2.67 ppb, at least 1.8 times higher than that of state-of-the-art NH3 sensors, together with robust stability and reproducibility. This work provides an innovative perspective on utilizing single atoms for ultra-selective gas sensing by coordination regulation.
Infectious Causes of Death: An Autopsy-Based Study of 546 Cases
Authors: Eshaghi Soudabeh , Sheybani Fereshte , Hedjazi Aria , Naderi HamidReza , Shirazinia Matin , Morovatdar Negar
Published: February 2025

Background

Diagnostic accuracy in cases of infectious diseases is crucial for appropriate patient management and public health interventions. This retrospective study aimed to evaluate the most common causes of death caused by infectious diseases and the rate of agreement between clinical diagnoses and autopsy findings in individuals diagnosed with infectious diseases in Mashhad, Iran.

Methods

Autopsy reports from March 2009 to February 2018 were analyzed for patients diagnosed with infectious diseases. Demographic data, clinical diagnoses, and autopsy results were collected and compared. Discrepancies between clinical and autopsy diagnoses were assessed, and potential predictors of diagnostic discrepancy were examined.

Results

Among 28 451 autopsied cases, 546 (1.9%) were diagnosed with infectious diseases. Pleuropulmonary infections were the most common cause of death (69.8%) as determined by autopsy, followed by bloodstream infections (14.1%) and intra-abdominal infections (10.0%). Discrepancies between clinical and autopsy diagnoses were identified in 22.4% of cases. Pleuropulmonary infections had the highest frequency of diagnostic discrepancies (29.1%), followed by central nervous system (CNS) infections (15.8%).

Conclusions

This study underscores the importance of autopsy in identifying diagnostic discrepancies and improving clinical practice in cases of infectious diseases. They also highlight the need for ongoing efforts to enhance diagnostic capabilities, particularly in challenging cases such as pleuropulmonary and CNS infections, to reduce the burden of misdiagnosis and improve patient outcomes.
A framework for sharing power in research teams and promoting justice in scientific publication
Authors: Cockle Kristina L , Cuatianquiz Lima Cecilia , Núñez Montellano María Gabriela , Bonaparte Eugenia Bianca , Zaffignani Daniela , Juncosa Polzella Agostina S , Radi Blas , Ferreira-Xavier Hipólito D , da Hora Jéssica S , Di Sallo Facundo G , Soto-Patiño Juliana , López Fernando G , Zulian Viviane , Miño Carolina I , Pérez Moira , Norris Andrea R , Schaufler María Laura ,   grupo ornitologíaS
Published: February 2025

Many ornithologists seek tools to work more equitably with people from historically marginalized and exploited groups. We developed a process to promote collective construction of ornithological knowledge in the Special Feature series "Ecology and conservation of cavity nesters in the Neotropics'' for the journals Ornithology and Ornithological Applications. Colonialism produces systems that consecrate Eurocentric ideas from dominant nations (including Canada, USA, and countries of western Europe) and reinforce hierarchies of power between and within regions. Recognizing these systems, we proposed a Special Feature to support, highlight, and connect teams from Latin America, a region historically exploited by imperial powers. We adopted sociocracy, a governance model that promotes sharing of power, to create the proposal and organize the call for papers and to write a review and this Perspective article. We adopted and developed transparent, consent-based decision-making processes, including a process for determining authorship order. We crafted open invitations, used collective proposals (structured brainstorming), encouraged citation of work from regional journals, tested a system for manuscript submission and review in Spanish, and introduced mechanisms for multi-way feedback. This framework helped reduce some barriers commonly faced by historically marginalized authors, distribute power more equitably, and recognize a broader diversity of contributions to ornithology. Despite these efforts, several challenges remained. For example, the publishing interests of Ornithology, Ornithological Applications, and most high-impact ornithological journals are often poorly aligned with current research priorities in many parts of Latin America (e.g., reproductive biology of endangered species). We encourage scientists at all career stages, technicians, and non-academics to reflect on their citation politics (which sources they cite, and how their citation practice may unintentionally reproduce inequities), and to implement collective workflows that promote equitable sharing of power within research teams. Translated versions of this article are available in Supplementary Material 1 (Spanish) and Supplementary Material 2 (Portuguese).
Role of epigenetics in mangroves: Recent progress and future perspectives
Authors: Meera Suraj Prasannakumari , Kumar Ajay
Published: February 2025

Epigenetic modifications in plants involve heritable changes in gene expression patterns that are not due to changes in gene sequences. Unlike genetic adaptations, which are long-term evolutionary changes, epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNAs, act as adaptive responses and allow plants to better cope with environmental stresses. As mangroves are uniquely located between the land and sea and remain continuously exposed to varying salinity, submergence, and hypoxia stresses, it is expected that certain epigenetic mechanisms might help them withstand the impacts of recurring stress fluctuations. Therefore, understanding the role of epigenetic regulation in mangrove stress adaptations to the intertidal environment is crucial. Despite only few studies to date having investigated epigenetic responses in mangroves, they nonetheless provide important insights into this process on which to base future research. Here, we present an update on recent progress in mangrove epigenetic research and offer perspectives on the potential roles of various epigenetic players in mangrove adaptations to the intertidal environment.
Trends in the Burden of Epilepsy in China from 1990 to 2021 and Its Forecast until 2044: Based on the 2021 Global Burden of Disease Study
Authors: Fang Zhiyong , Wang Feng , Mei Zhen , Huang Xiaofen , Gao Lin , Zheng Lixian , Lin Yuanxiang , Hu Xuequn
Published: February 2025

Background

Epilepsy is one of the most prevalent neurological disorders, but no updated analysis of its burden in China.

Aims

This study provides the most up-to-date, comprehensive analysis of temporal trends and predicts future trends of idiopathic epilepsy in China.

Design

Secondary analysis based on the Global Burden of Disease (GBD).

Methods

GBD 2021 data were analyzed to estimate the incidence, prevalence, mortality, and Disability-Adjusted Life Years (DALYs) of epilepsy in China across different genders, age groups, and years. Joinpoint regression and decomposition analysis assessed temporal changes and the contributions of aging, population growth, and epidemiological changes to disease trends. The Bayesian Age-Period-Cohort (BAPC) model was used to predict age-standardized rates (ASRs) per 100,000 individuals until 2044.

Results

In 2021, the ASRs of incidence, prevalence, deaths, and DALYs for epilepsy in China were 28.2 (95% uncertainty interval [UI]: 19.0–37.9), 214.7 (150.1–278.6), 0.8 (0.7–1.0), and 101.4 (72.5–139.4) per 100,000 population, respectively. The incidence and prevalence rates were 26.1% and 13.4% higher than those in 1990, while deaths and DALYs decreased by 56.6% and 43.2%, respectively, compared to 1990. The highest burden was seen in the youngest and older adults, with men more affected than women. Predictions indicate rising incidence and prevalence rates by 2044, alongside declining mortality and disability rates.

Conclusion

Epilepsy poses a significant health burden in China, with increasing incidence and prevalence from 1990 to 2021, and projections indicating a continued rise through 2044. The disease burden also varies across genders, age groups, and time periods.
RFSoC receiver calibration system for 21-cm global spectrum experiments from space: the CosmoCube case
Authors: Zhu Jiacong , Acedo Eloy de Lera , Artuc Kaan , Chen Xuelei
Published: February 2025

The CosmoCube project plans to deploy a global 21-cm spectrometer with 10–100 MHz observation band in a lunar orbit. The farside part of such an orbit, i.e. the part of orbit behind the Moon, offers an ideal site for accurately measuring the 21-cm signal from the dark ages, cosmic dawn, and epoch of reionization, as the effects of the Earth’s ionosphere, artificial radio frequency interference, and complex terrain and soil are all avoided. Given the limitations of a satellite platform, we propose a receiver calibration system design based on a radio frequency system-on-chip, consisting of a vector network analyser (VNA) subsystem, and a source switching subsystem. We introduce the measurement principle of the VNA, and discuss the effect of quantization error. The accuracy, stability, and trajectory noise of the VNA are tested in laboratory experiments. We also present the design of the source-switching subsystem, generating mock data sets, showing that the imperfect return loss, insertion loss, and isolation of surface-mounted microwave switches have a minimal effect on the sky foreground fitting residuals, which are within $\pm 10$ mK under optimal fitting condition. When all possible measurement errors in reflection coefficients and physical temperatures are taken into account, the foreground fitting residuals for the 50–90 MHz part of the spectrum remain around $\pm 20$ mK.
A systematic review and meta-analysis of group-based trajectory modeling of sleep duration across age groups and in relation to health outcomes
Authors: Wang Wei , Cheung Sing-Hang , Cheung Shu Fai , Sun Rong Wei , Hui C Harry , Ma Ho Yin Derek , Lau Esther Yuet Ying
Published: February 2025

Study Objectives

To shed light on understanding sleep duration trajectories (SDTs) using different classification methods and their outcomes, this study aimed to (1) identify common SDTs among different age groups, (2) investigate the alignment versus differences between SDTs identification by group-based trajectory modeling (GBTM) and clinical standards, and (3) examine the impacts of SDTs on health outcomes.

Methods

A systematic literature search from four databases yielded 34 longitudinal SDT studies with GBTM analyses spanning three or more data waves. Apart from the proportion meta-analysis, a three-level meta-analysis was conducted with 14 of the studies that examined the association between SDT groups and health outcomes. Assessment of study quality was performed using the Guidelines for Reporting on Latent Trajectory Studies checklist.

Results

Qualitative analysis identified four age-related SDT classes based on longitudinal trends: “persistent sleepers,” “increase sleepers,” “decrease sleepers,” and “variable sleepers.” Meta-analysis also showed differential proportions of “GBTM-defined shortest sleepers” across age groups and sample regions, as well as significant discrepancies in the prevalence of short sleep identified by clinical standards (=50% vs. 15% per GBTM). Overall, SDTs predicted emotional and behavioral outcomes, neurocognitive problems, and physical health (OR = 1.538, p < 0.001), in GBTM-defined “short,” “fluctuating,” “long,” and “decreasing” sleepers as compared to the “adequate” group. The effects were stronger in adolescents and in datasets with more waves.

Conclusions

The identification of the GBTM-defined “short,” “fluctuating,” “long,” and “decreasing” SDT groups and their associations with various health outcomes supported longitudinal investigations, as well as the development of interventions focusing on both the length and stability of sleep durations, especially in younger populations. Study registration: PROSPERO registration number CRD42023412201.
Inhibition of proton sensor GPR68 suppresses endothelial dysfunction and acute lung injury caused by Staphylococcus aureus bacterial particles
Authors: Karki Pratap , Ke Yunbo , Zhang Chen‐Ou , Promnares Kamoltip , Li Yue , Williams Charles H. , Hong Charles C. , Birukov Konstantin G. , Birukova Anna A.
Published: February 2025

Lung bacterial infections, including hospital‐acquired pneumonia, remain a serious problem for public health. Endothelial cell (EC) exposure to heat‐killed Staphylococcus aureus (HKSA) represents a clinical scenario of high titers of killed bacterial particles present in the host after antibiotic therapy, which triggers inflammatory cascades, cytokine storms, and EC dysfunction leading to acute lung injury (ALI). GPR68 is a member of the proton‐sensing G protein‐coupled receptor family. Acting as a pH sensor, GPR68 becomes activated upon pH reduction and contributes to pathologic cell responses by activating ER stress and unfolded protein response. This study investigated the role of GPR68 in HKSA‐induced EC dysfunction and HKSA‐induced ALI. HKSA robustly increased GPR68 mRNA levels in human pulmonary EC and directly stimulated GPR68 activity. A selective GPR68 small molecule inhibitor, OGM‐8345, attenuated HKSA‐induced EC permeability and protected cell junction integrity. OGM‐8345 inhibited HKSA‐induced activation of inflammatory genes TNF‐α, IL‐6, IL‐8, IL‐1β, and CXCL5 and decreased cytokine secretion by HKSA‐challenged EC. Co‐treatment with the GPR68 activator Ogerin or medium acidification to pH 6.5 augmented HKSA‐induced EC dysfunction, which was rescued by OGM‐8345. Intratracheal HKSA injection increased vascular leak and lung inflammation in mice which were monitored by lung Evans blue extravasation, increased cell and protein count in bronchoalveolar lavage, and mRNA expression of inflammatory genes. ALI and barrier dysfunction was attenuated by OGM‐8345. We show for the first time the role of GPR68 in mediating HKSA‐induced lung injury and the strong potential for OGM‐8345 as a therapeutic treatment of bacterial pathogen‐induced ALI associated with tissue acidification.
Dual independent mechanisms underlying gut epithelial remodeling upon sugar substitute consumption
Authors: Seo Dong Woo , Hong Kyung Tae , Lee Jung Hoon , Lee Jun‐Seok , Jeong Yong Taek
Published: February 2025

Intestinal epithelial cells (IECs) are dynamically regulated by luminal contents, including dietary ingredients, food additives, and microbiota‐derived metabolites. Although sugar substitutes are commonly used as food additives for their sweet taste and lower calorie content, there is limited experimental evidence regarding their potential to drive gut remodeling. In this study, we designed experimental models for short‐term consumption of erythritol, a natural sugar alcohol widely used as a sugar substitute, and investigated its effects on gut remodeling and the underlying mechanisms. Our findings indicate that erythritol consumption induces hyperplasia in tuft cells (TCs) and goblet cells (GCs), as well as enhances the activity of intestinal stem cells–increases in expression levels of leucine‐rich repeat containing G protein‐coupled receptor 5 (Lgr5), the key intestinal stem cell marker, in the number of proliferating stem cells, and facilitation of their differentiation into villi cells–while maintaining the number of Lgr5+ intestinal stem cells. Notably, the enhanced stem cell activity was observed even in Trpm5 knockout mice, suggesting that it is mechanistically independent of TC hyperplasia. Instead, we demonstrated the functional involvement of the gut microbiota, as antibiotic treatment abolished this effect, and fecal material transfer from erythritol‐consumed mice replicated the enhancement of stem cell activity in recipient mice. Furthermore, we identified acetate as the metabolite responsible for enhancing stem cell activity. These findings suggest the functional decoupling of TC hyperplasia and the enhancement of stem cell activity, providing a potential therapeutic avenue for gut epithelial diseases.
Alpha protein kinase 1 knockout mitigates microglial pyroptosis and cognition deficits in ADP‐heptose‐stimulated mice
Authors: Zou Xiao , Du Ou , Yang Yan‐Rong , Yang Yu‐Xin , Zheng Zi‐Xing , Li Meng‐Yang , Wu An‐Guo , Du Jun‐Rong
Published: February 2025

Microglial activation and pyroptosis are central to neuroinflammation and significantly contribute to cognitive decline associated with neurodegenerative diseases. Alpha protein kinase 1 (ALPK1) is recently identified as a critical mediator of inflammatory responses in response to ADP‐heptose (a pathogen‐associated molecular pattern). However, its specific role in microglial pyroptosis and cognitive dysfunction remains unclear. In this study, we investigated the effects of ALPK1 on cognitive function and pyroptosis in wild‐type (WT) and ALPK1 KO mice by intracerebroventricular administration of ADP‐heptose to induce neuroinflammation. Cognitive performance was evaluated using behavioral tests (the Y‐Maze, Morris Water Maze, and step‐down passive avoidance), while Western blot, immunofluorescence, transmission electron microscopy, and enzyme‐linked immunosorbent assay were used to evaluate the expression of pyroptosis markers such as NLRP3, Caspase‐1, and gasdermin D (GSDMD) in vivo and in vitro. Our results reveal that the absence of ALPK1 significantly attenuated ADP‐heptose‐induced cognitive deficits and neuronal injury, and inhibited the NLRP3/Caspase‐1/GSDMD pathway of pyroptosis and the secretion of pro‐inflammatory cytokines IL‐1β and IL‐18. Notably, ADP‐heptose‐stimulated conditioned media from primary microglial cells of ALPK1 KO mice significantly enhanced neuronal cell viability, suggesting a protective role for ALPK1 deficiency in supporting neuronal health. These findings suggest the pivotal role of ALPK1 in ADP‐heptose‐induced microglial pyroptosis and cognitive impairment, thereby highlighting its potential as a therapeutic target in neuroinflammatory disorders.
Targeted inhibition of menin promotes β‐catenin‐mediated GLP‐1 expression and improves glucose tolerance in high‐fat diet‐induced obese mice
Authors: Cao Xiaoru , Yu Ling , Zhang Qian , Cheng Zhaosi , Meng Haiyue , Wang Chenghao , Guo Zhitao , Guo Yinghao , Xin Guoshun , Wang Yue , Zhou Pingping , Luo Yakun , Sun Bin , Ma Jian
Published: February 2025

Glucagon‐like peptide‐1 (GLP‐1), derived from enteroendocrine cells, is a pivotal hormone crucial for blood glucose regulation. Menin, encoded by the MEN1 gene and known for its tumor suppressor role, is abundantly expressed in the intestine. Previous research has demonstrated that acute Men1 excision reverses preexisting glucose intolerance in high‐fat diet‐fed mice. However, its impact on GLP‐1 expression in enteroendocrine cells has not been investigated. In the present study, both the knockdown of Men1 and the administration of the MI‐463 menin inhibitor increased GLP‐1 expression in glucose‐stimulated STC‐1 cells. Additionally, administering MI‐463 to obese mice significantly elevated GLP‐1 levels in both ileal epithelial cells and serum. Mechanistically, menin inhibition enhanced the nuclear accumulation of β‐catenin, allowing it to bind TCF7L2, thereby increasing glucagon gene (Gcg) transcription. Furthermore, compared with control mice, mice with intestinal epithelial cell‐specific Men1 knockdown exhibited significant improvements in glucose tolerance under fat challenge, which was correlated with elevated GLP‐1 levels. These findings suggest that menin‐mediated regulation of GLP‐1 expression may be an important mechanism through which menin inhibiton alleviates type 2 diabetes.
Diurnal variation in skeletal muscle mitochondrial function dictates time‐of‐day‐dependent exercise capacity
Authors: Khatri Subhash , Das Souparno , Singh Anshit , Ahmad Shabbir , Kashiv Mohit , Laxman Sunil , Kolthur‐Seetharam Ullas
Published: February 2025

Exercise impinges on almost all physiological processes at an organismal level and is a potent intervention to treat various diseases. Exercise performance is well established to display diurnal rhythm, peaking during the late active phase. However, the underlying molecular/metabolic factors and mitochondrial energetics that possibly dictate time‐of‐day exercise capacity remain unknown. Here, we have unraveled the importance of diurnal variation in mitochondrial functions as a determinant of skeletal muscle exercise performance. Our results show that exercise‐induced muscle metabolome and mitochondrial energetics are distinct at ZT3 and ZT15. Importantly, we have elucidated key diurnal differences in mitochondrial functions that are well correlated with disparate time‐of‐day‐dependent exercise capacity. Providing causal mechanistic evidence, we illustrate that loss of Sirtuin4 (SIRT4), a well‐known mitochondrial regulator, abrogates mitochondrial diurnal variation and consequently abolishes time‐of‐day‐dependent muscle output. Therefore, our findings unequivocally demonstrate the pivotal role of baseline skeletal muscle mitochondrial functions in dictating diurnal exercise capacity.
Cerebral palsy
Authors: Smigelski Garrett D.
Published: February 2025

Cerebral palsy (CP) is an encompassing term for a group of permanent neurologic disorders of movement and posture commonly seen in early childhood and caused by abnormal brain development early in life. The cause of CP is unclear in the majority of patients affected and can be multifactorial, occurring in various time frames such as prenatal, intrapartum, and postpartum. Because CP is a clinical diagnosis, clinicians must have a strong understanding of the clinical presentation to ensure early diagnosis and improved outcomes for patients. This article reviews CP and describes advances in diagnosis and management; it also provides an overview of new treatments that are under investigation.
Respiratory and Postoperative Outcomes in Early-onset Scoliosis Patients Treated With Vertical Expandable Prosthetic Titanium Rib: Single-center Experience of 20 Years
Authors: Ramírez Norman , Lugo Elyette , Camacho Lyanne , Ibañéz Mary K. , Ramírez Nicole , Quiñones-Rodríguez Jailene I. , Olivella Gerardo
Published: February 2025

Background:

This study examines the long-term effectiveness and safety of the vertical expandable prosthetic titanium rib (VEPTR) device, developed in 1989 to treat early-onset scoliosis (EOS) and thoracic insufficiency syndrome (TIS). Specifically, it assesses VEPTR outcomes over 20 years in a single center, focusing on spine deformity correction, pulmonary function, weight percentile changes, and complication rates.

Methods:

A retrospective analysis was conducted on 36 patients from the EOS clinic who underwent VEPTR implantation without prior spine surgery, with at least 2 years of follow-up. Data collected included age, sex, weight, height, BMI, weight percentiles, comorbidities, radiographic parameters, pulmonary function tests, and complications. Weight percentile (WP) was calculated as preoperative WP and last follow-up WP. Coronal and sagittal deformities were measured preoperatively, immediately postimplantation, and at the last follow-up. Pulmonary function tests included forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) and were correlated with weight percentile changes. Complications were classified using established criteria.

Results:

The mean age at VEPTR implantation was 86±34 months, with most cases attributed to neuromuscular scoliosis (56%). The initial coronal Cobb angle improved from 59±18 to 32±14 degrees postimplantation but increased to 60±25 at the final follow-up. Sagittal angles showed similar trends. Pulmonary function tests indicated a decline in FVC and FEV1 over time. There was no correlation between weight percentile changes and pulmonary function changes. Complication rates were high, affecting 63% of patients, which included hardware prominence, device migration, and infections as the most common.

Conclusions:

Although VEPTR devices initially corrected spinal deformities, their long-term benefits are limited as the correction becomes less pronounced over time. Expected improvement in pulmonary function is not observed. A different approach to treating EOS and TIS is necessary, as the significant complication rates challenge the implants’ effectiveness.

Level of evidence.

Level III.
Integrating Remote Monitoring Into the Pregnancy Care
Authors: Likitalo Susanna , Pakarinen Anni , Axelin Anna
Published: February 2025

Remote monitoring has been proposed to provide new opportunities to monitor pregnancy in the home environment and reduce the number of follow-up visits to the maternity clinic. Still, the integration of remote monitoring into the pregnancy care process has not been achieved. This descriptive qualitative study aimed to explore pregnant women’s and healthcare professionals’ perceptions of integrating remote monitoring into pregnancy monitoring process. A convenience sample of 10 pregnant women and 11 healthcare professionals participated in the focus group interviews. The data were analyzed with reflexive thematic analysis. The results comprised a four-step pregnancy monitoring process organizing the issues to consider when integrating remote monitoring into these steps. According to pregnant women and healthcare professionals, remote pregnancy monitoring should allow a holistic assessment to ensure the well-being of the pregnant woman and the fetus. Clear criteria for monitoring should guide the adaptation of monitoring to the identified monitoring needs. Ideally, remote monitoring could enable more personalized maternity care, supporting the monitoring-related decision-making of both pregnant women and healthcare professionals and facilitating the early detection of pregnancy complications. However, integration of remote monitoring would require significant restructuring of current pregnancy care processes.
A Game Changer for Resistant Hypertension: The Rise of Aprocitentan
Authors: Eid Ali H.
Published: February 2025

Hypertension is a major risk factor for cardiovascular disease (CVD), and a major contributor to global morbidity and mortality. In particular, resistant hypertension (rHTN), defined as blood pressure that remains elevated despite treatment with at least three antihypertensive agents including a diuretic, continues to be a major pharmacotherapeutic challenge. Traditional antihypertensive drugs often fail in patients with rHTN, underscoring the need for novel therapies. This is a brief mini-review of aprocitentan, a new drug that promises a glimmer of hope for rHTN patients. This drug is a dual endothelin (ET) receptor antagonist that blocks both ETA and ETB receptors. Given that these two receptors are critical players in vasotone regulation, antagonizing them, such as by aprocitentan, would be expected to significantly reduce blood pressure in patients with rHTN. Indeed, the PRECISION clinical trial demonstrated aprocitentan’s superior effectiveness in reducing blood pressure in resistant patients, and the effects were sustained. Aprocitentan has been recently FDA-approved, marking a major milestone in hypertension management, offering hope for patients with difficult-to-treat hypertension.
A Novel Approach to Intermediate Cleft Rhinoplasty Utilizing a Pedicled Fibrofatty Flap
Authors: Lasky Sasha , Moshal Tayla , Jolibois Marah , Roohani Idean , Jimenez Christian , Manasyan Artur , Naidu Priyanka , Nagengast Eric S. , Magee William P.
Published: February 2025

Patients with cleft lip ± palate may experience psychosocial issues related to their secondary cleft nasal deformities. These concerns can be addressed earlier instead of being required to wait until skeletal maturity. A novel early rhinoplasty intervention utilizing a dorsal fibrofatty pedicled flap is performed by the senior author to address nasal aesthetics in patients with secondary nasal deformities. This study aimed to describe this novel intermediate rhinoplasty technique and to evaluate improvement of nasal aesthetics. A retrospective review of patients with unilateral and bilateral cleft lip who underwent open rhinoplasty by a single surgeon at less than 10 years old from 2008 to 2023 was conducted. To evaluate aesthetic improvement, preoperative and postoperative photographs of patients were graded by 2 reviewers utilizing the Asher-McDade Aesthetic Index. Paired t tests compared preoperative and postoperative Asher-McDade Aesthetic Index nasal form and nasal deviation scores. A total of 43 patients underwent early rhinoplasty utilizing this technique at an average age of 5.5 ± 1.1 years. Compared with preoperative photographs, postoperative photographs of patients demonstrated a significant improvement in nasal form (P < 0.001) and nasal deviation (P < 0.001). No intraoperative or postoperative complications were reported. Only 1 (2.3%) patient underwent revisional surgery. Long-term follow-up will assess the finalized revision rate. This technique is a safe and valuable tool in patients who benefit from earlier treatment of secondary cleft nasal deformities due to significant asymmetry and psychosocial concerns.
Monitoring and Management of Infection following Prepectoral Implant-based Breast Reconstruction: Retrospective Analysis of Conservative Treatment Versus Implant Removal
Authors: Walz Solange N. , Martineau Jérôme , Kalbermatten Daniel F. , Oranges Carlo M.
Published: February 2025

Background:

Infection following implant-based breast reconstruction (IBBR) represents a major complication, potentially leading to prosthesis removal. However, no clear protocol for its prevention and management exists. This study aimed to evaluate the efficacy of conservative treatment methods in preventing implant removal and analyze factors responsible for implant loss in the context of prepectoral IBBR.

Methods:

A single-institution retrospective review chart of patients undergoing immediate prepectoral IBBR for breast cancer between October 2020 and January 2024 was performed. The inclusion criteria were the presence of at least one of the following postoperative complications: seromas, cellulitis, clinically suspected prosthesis infection, and confirmed periprosthetic infection. A comparative analysis between patients with successful conservative treatment (ultrasound-guided aspiration and antibiotic therapy) and patients undergoing implant removal was performed.

Results:

A total of 219 immediate prepectoral IBBR cases were identified, 38 of which met inclusion criteria. Implant removal was required in 11 cases, whereas implant retention was achieved in 27 patients with conservative treatment. Implants were invariably removed when bacterial cultures were positive (P < 0.05). Conversely, when pathogens were not identified, the likelihood of implant removal decreased significantly (P < 0.05). Conservative treatment allowed implant salvage in all patients presenting with postoperative seroma alone, without other associated complications (P < 0.05).

Conclusions:

This study suggests that when bacterial cultures are positive, implant removal is unavoidable. Conversely, noninfected seromas correlated with implant salvage. Infections from Bacillus pumilus and Corynebacterium pseudodiphtheriticum are reported for the first time.