bluuebunny/crossref_metadata_2025 huggingface dataset:
Relative risks of adverse effects across different opioid agonist treatments—A systematic review and meta‐analysis
Authors: Meyer Maximilian , Strazdins Eriks , Guessoum Adrian , Westenberg Jean N. , Appenzeller‐Herzog Christian , Cattaneo Marco E. G. V. , Krausz R. Michael , Dürsteler Kenneth M. , Lang Undine E. , Hemkens Lars G. , Vogel Marc
Published: February 2025

Background and Aims

Opioid agonist treatment (OAT) is established for opioid use disorder, but limited data on adverse effects exist. We aimed to review relative risks of adverse effects across opioid agonists.

Methods

Systematic review with pair‐wise meta‐analysis of randomized clinical trials. A search in Embase, Medline, PsycInfo, CENTRAL and the Web of Science Core Collection was performed from inception to 11 April 2024 (PROSPERO: CRD42022322722). Two reviewers independently extracted data and used the Cochrane Risk of Bias Assessment Tool. Certainty of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Primary outcomes were constipation, sedation, pruritus, sweating, nausea and vomiting, headache and any non‐headache pain.

Results

We identified 25 eligible trials, including 4892 participants. Reported agonists were methadone, levomethadone, methadyl acetate, buprenorphine, buprenorphine/naloxone, slow‐release oral morphine (SROM), diacetylmorphine, hydromorphone and opium tincture. Buprenorphine (all formulations combined) was associated with a lower risk of sedation than methadone [risk ratio (RR) = 0.68 (95% confidence interval = 0.56–0.82)]; 1558 participants, 9 studies]. Methadone had a lower risk of sedation compared with SROM [RR = 0.63 (0.58–0.69); 356 participants, 2 studies] and a lower risk of nausea than methadyl acetate [RR = 0.56 (0.37–0.85); 913 participants, 3 studies]. There was high overall risk of bias in 92% of included trials due to limited and non‐systematic outcome assessment. Certainty of evidence was low or very low for all but one comparison with moderate certainty.

Conclusions

There is currently insufficient data to determine whether the rates of adverse effects differ across opioid agonist treatments for most outcomes, with several exceptions. Moreover, the certainty of evidence is currently low or very low due to a lack of rigorous outcome assessment.
Maternal Phenotype, Infant Size and Breast Milk Composition in Women Living With HIV
Authors: Gilfillan Marlene , Wenhold Friedeburg. A. M. , Mulol Helen , Feucht Ute. D.
Published: February 2025

The impact of maternal factors on the size of HIV‐exposed‐uninfected (HEU) infants and breast milk composition is poorly understood. Anthropometry, bio‐electrical impedance, haemoglobin and HIV viral load data of women living with HIV (WLWH) and without HIV (WLWOH) were compared and related to their infants' anthropometric Z‐scores and breast milk macronutrients 6 weeks and 6 months postnatally. At both time points, WLWH (6‐week: n = 83; 6‐month: n = 63) had lower reactance (measure of body cell mass) (6‐week: p = 0.016; 6‐month: p < 0.001), phase angle (PhA) (measure of cell health) (6‐week: p = 0.001; 6‐month: p = 0.002) and haemoglobin (6‐week: p = 0.002; 6‐month: p = 0.004) than WLWOH (6‐week: n = 90; 6‐month: n = 73). HEU infants had lower weight‐for‐age Z‐scores (WAZ) (6‐week: p = 0.010; 6‐month: p = 0.005). Breast milk composition did not differ between groups. At 6 weeks, HEU infants had lower head circumference‐for‐age Z‐scores (HCAZ) (p = 0.014). Bivariate regression demonstrated maternal HIV predicted lower infant WAZ (ß = −0.442; p = 0.011) and HCAZ (ß = −0.445; p = 0.014). Maternal body mass index (BMI) and mid‐upper arm circumference were positively associated with breast milk protein content (ß = 0.018; p = 0.014 and ß = 0.025; p = 0.002, respectively). At 6 months (bivariate regression) maternal HIV predicted lower infant WAZ (ß = −0.609; p = 0.005) and length‐for‐age Z‐scores (ß = −0.741; p = 0.018). Higher maternal BMI and PhA were associated with higher infant WAZ (ß = 0.622; p = 0.015 and ß = 0.055; p = 0.017, respectively). On multivariable analysis, maternal HIV remained a predictor of lower WAZ (ß = −0.568; p = 0.024). In conclusion, maternal HIV infection and phenotype predict the size of infants and breast milk composition up to 6 months postnatally.
Correlation Analysis of Secondary Metabolism and Endophytic Fungal Assembles Provide Insights Into Screening Efficient Taxol‐Related Fungal Elicitors
Authors: Wang Mingshuang , Liang Xueshuang , Ma Ruoyun , Lin Wanting , Fang Zijin , Zhang Lingxiao , Chen Ganlin , He Jiaxu , Bai Enhui , Pi Erxu , Zhang Pengcheng , Wang Huizhong , Shen Chenjia
Published: February 2025

The efficacy of Taxol, a natural anticancer drug, in the treatment of various types of cancers has been certified globally. Fungal elicitors have been reported as an impressive strategy for enhancing Taxol biosynthesis. We have investigated the effect of twig age on Taxol biosynthesis and the communities of endophytic fungi. A negative correlation between Taxol content and the complexity of the endophytic fungal community in twigs was predicted. Endogenous taxoids, similar to balancing valves, might have a specific effect on controlling the microbiota assembly in Taxus twigs. Utilising the special correlation, 11 isolates of twig age‐associated fungi were used to screen new fungal elicitors involved in Taxol biosynthesis. Two efficient fungal elicitors, L01 (Guignardia) and J02 (Diaporthe), were identified, increasing the Taxol contents by 5.91‐ and 4.83‐folds, respectively. It is confirmed that effective fungal elicitors may be negatively correlated with Taxol contents in Taxus tissues. Furthermore, the J02 and L01 fungal elicitors significantly induced the jasmonic acid (JA) content, speculating the involvement of MYC2a‐controlled JA signalling in fungal elicitor‐activated Taxol biosynthesis. Our data revealed the effect of twig age on Taxol biosynthesis of Taxus and provided a novel approach to screen effective fungal elicitors involved in Taxol biosynthesis.
Heat Transfer Enhancement in a Rotating Wedge-Shaped Cooling Channel with Optimized Detached Guiding Pin-Fin
Authors: Chen Jianian , Xu Chao , Rao Yu
Published: February 2025

Experiments and numerical simulations are conducted to investigate the flow and heat transfer characteristics of the guiding pin-fin array in a rotating wedge-shaped channel. The rotating experiments cover Reynolds number ranges from 10,000 to 80,000 and rotation number ranges from 0 to 0.46. The results demonstrate that the guiding pin-fin array can significantly reduce the endwall temperature and pressure loss in the wedge-shaped channel. To further enhance channel heat transfer uniformity, clearances were introduced to the guiding pin fins at the channel root region. The numerical results show that this structural modification effectively improved the endwall heat transfer intensity at the mid-span of the wedge-shaped channel. In cases Re = 50,000 and Ro = 0.075, the leading and trailing endwall Nusselt numbers of the detached guiding pin-fin array were 6.5% and 4.8% higher than those of the guiding pin-fin array. Further comparisons at Ro =0.075 and 0.15 revealed that the leading and trailing endwall heat transfer discrepancy coefficient (d) of the detached guiding pin-fin array was 61.8% and 42.2% lower than that of the circular pin-fin array, respectively. In high temperature cases with solid domain, the detached guiding pin-fin array also can provide superior cooling performance. In the wedge-shaped channel with detached guiding pin-fin, the maximum and average temperature values of the solid domain are about 10% lower than that of the channel with circular pin-fin.
100-Year Analysis of Roll Decay for Surface-Ship Models
Authors: Park Joel T. , McCoy Andrew M.
Published: February 2025

A history is described on roll decay analysis for experiments with surface-ship scale models at the Naval Warfare Center Carderock Division (NSWCCD), a naval hydrodynamic facilities known as David Taylor Model Basin (DTMB). The earliest roll decay analysis for a model test is from a report in 1923 that compares roll decay analysis for bilge keels off and on. A time history plot provides a measurement of roll period. The roll damping is indicated graphically by a curve fit of the peaks. With modern methods, the damping coefficient is computed with a curve fit of exponential damping. An early example of the estimate of roll damping is by log decrement of the ratio of successive roll peak pairs was in 1976. More recently, both damping coefficient and period are computed from a curve fit of exponentially decaying cosine function, which is the solution of a second-order ordinary differential equation with constant coefficients. The largest uncertainty in damping coefficient is by log decrement, and lowest by the exponential cosine with the exponential fit of peaks in between. For the log decrement method, roll period must be computed independently. The roll period is calculated from the time between zero crossings in the time series, time between peaks, or peak in the power spectrum of the roll angle.
Improvements in friction stir welding strength considering design and process parameters by using Aluminum alloy AA7075-T6
Authors: Ahmad Zaheer , Hussain Salman , Jawad Muhammad , Ahmad Wasim , Jahanzaib Mirza
Published: February 2025

In this research work tool rotational speed, tool hardness, shoulder to pin diameter ratio and welding speed/ feed were selected as the parameters to see how we can increase the quality of the weld by varying these parameters. Highlights of this research work are: (a) Efficient tool design regarding material selection for the tool and design of the tool (D/d ratio) (b) Effects of FSW parameters mostly tool rotational speed on mechanical properties related to quality and strength of the weld (c) effect of tool hardness and welding speed on strength of friction stir welding.

Design of experiment software was used to design experiments and tool geometry. Another technique that was used in this research was related to regression analysis to forecast the tensile strength and hardness of friction stir welded joint. The Tensile strength and hardness were the output responses. From the investigation of influence of the parameters it was concluded that welding speed is the most significant parameter while rotational speed, Tool hardness and D/d ratio are least significant parameters however these parameters still affect the quality of weld. An evaluation was made between measured and predicted results by developing a regression model and the values obtained for the response tensile strengths and hardness were compared with measured values. SEM analysis was done on the low medium and high values samples to visualize the grain structure by fractography. Three confirmation tests were carried out in order to validate the regression models.
Novel precursor for the preparation of vanadium sulfide layers with atomic layer deposition
Authors: Baji Zsófia , Fogarassy Zsolt , Sulyok Attila , Horváth Zsolt Endre , Szabó Zoltán
Published: February 2025

The present paper reports on the atomic layer deposition of vanadium sulfide (VS) layers from tetrakis(ethylmethylamino)vanadium and H2S. The deposition of VS layers with these precursors has proven possible between 200 and 300 °C. The prepared layers were amorphous, but a postdeposition annealing in H2S atmosphere yielded crystalline VS layers. The use of this precursor combination has so far not been reported.
β-Lactamase diversity in
Pseudomonas aeruginosa
Authors: Mack Andrew R. , Hujer Andrea M. , Mojica Maria F. , Taracila Magdalena A. , Feldgarden Michael , Haft Daniel H. , Klimke William , Prasad Arjun B. , Bonomo Robert A.
Published: February 2025

Pseudomonas aeruginosa
is a clinically important Gram-negative pathogen responsible for a wide variety of serious nosocomial and community-acquired infections. Antibiotic resistance is a major concern, as this organism has a wide variety of resistance mechanisms, including chromosomal class C (
bla
PDC
) and D (
bla
OXA-50
family) β-lactamases, efflux pumps, porin channels, and the ability to readily acquire additional β-lactamases. Surveillance studies can reveal the diversity and distribution of β-lactamase alleles but are difficult and expensive to conduct. Herein, we apply a novel approach, using publicly available data derived from whole genome sequences, to explore the diversity and distribution of β-lactamase alleles across 30,452
P
.
aeruginosa
isolates. The most common alleles were
bla
PDC-3
,
bla
PDC-5
,
bla
PDC-8
,
bla
OXA-488
,
bla
OXA-50
, and
bla
OXA-486
. Interestingly, only 43.6% of assigned
bla
PDC
alleles were encountered, and the 10 most common
bla
PDC
and intrinsic
bla
OXA
alleles represent approximately 75% of their respective total alleles, while many other assigned alleles were extremely uncommon. As anticipated, differences were observed over time and geography. Surprisingly, more distinct unassigned alleles were encountered than distinct assigned alleles. Understanding the diversity and distribution of β-lactamase alleles helps to prioritize variants for further research, select targets for drug development, and may aid in selecting therapies for a given infection.
An astrobiological perspective on microbial biofilms: their importance for habitability and production of detectable and lasting biosignatures
Authors: Gonzalez-Henao Sarah , Schrenk Matthew O.
Published: February 2025

The search for life elsewhere in the universe has remained one of the main goals of astrobiological exploration. In this quest, extreme environments on Earth have served as analogs to study the potential habitability of Mars and icy moons, which include but are not limited to hydrothermal vent systems, acid lakes, deserts, and polar ice, among others. Within the various forms that life manifests, biofilms constitute one of the most widespread phenotypes and are ubiquitous in extreme environments. Biofilms are structured communities of microorganisms enclosed in a matrix of extracellular polymeric substances (EPS) that protect against unfavorable and dynamic conditions. These concentrated structures and their associated chemistry may serve as unique and persistent signatures of life processes that may aid in their detection. Here we propose biofilms as a model system to understand the habitability of extraterrestrial systems and as sources of recognizable and persistent biosignatures for life detection. By testing these ideas in extreme analog environments on Earth, this approach could be used to guide and focus future exploration of samples encompassing the geologic record of early Earth as well as other planets and moons of our solar system.
Cryptococcal nutrient acquisition and pathogenesis: dining on the host
Authors: Perfect John R. , Kronstad James W.
Published: February 2025

SUMMARY

Pathogens must acquire essential nutrients to successfully colonize and proliferate in host tissue. Additionally, nutrients provide signals that condition pathogen deployment of factors that promote disease. A series of transcriptomics experiments over the last 20 years, primarily with
Cryptococcus neoformans
and to a lesser extent with
Cryptococcus gattii
, provide insights into the nutritional requirements for proliferation in host tissues. Notably, the identified functions include a number of transporters for key nutrients including sugars, amino acids, metals, and phosphate. Here, we first summarize the
in vivo
gene expression studies and then discuss the follow-up analyses that specifically test the relevance of the identified transporters for the ability of the pathogens to cause disease. The conclusion is that predictions based on transcriptional profiling of cryptococcal cells in infected tissue are well supported by subsequent investigations using targeted mutations. Overall, the combination of transcriptomic and genetic approaches provides substantial insights into the nutritional requirements that underpin proliferation in the host.
Variations in salivary microbiome and metabolites are associated with immunotherapy efficacy in patients with advanced NSCLC
Authors: Huang DanHui , Chen YueHua , Li Cui , Yang Shuang , Lin LiShan , Zhang XiaoNan , Su XiaoFang , Liu LaiYu , Zhao Haijin , Luo Tingyue , Cai Shaoxi , Ren QianNan , Dong Hangming
Published: February 2025

Lung cancer is a leading cause of cancer mortality, with non-small cell lung cancer (NSCLC) comprising the majority of cases. Despite the advent of immune checkpoint inhibitors (ICIs), a significant number of patients fail to achieve a durable response, highlighting the need to understand the factors influencing treatment efficacy. Saliva samples and tumor samples were collected from 20 NSCLC patients. The salivary microbiota was profiled using metagenomic next-generation sequencing, and metabolites were analyzed via liquid chromatography-mass spectrometry to identify correlations among bacteria, metabolites, and immunotherapy responses. Immunohistochemistry (IHC) analysis of tissue samples verified the result. Besides,
in vitro
experiments and tumor tissue microarray, including 70 NSCLC patients, were utilized to further explore the potential mechanism linking the oral microbiome and immunotherapy efficacy. The study revealed several differential species and distinct metabolite compositions between responders and non-responders to ICI therapy in NSCLC and explored correlations and mechanisms between microbiota metabolites and immunotherapy resistance. Notably, it was found that several
Neisseria
and
Actinomyces
species were significantly enriched in responders and identified lipids and lipid-like molecules associated with PD-L1 expression levels and treatment outcomes. Importantly, several differential lipid molecules were associated with differential species. Further,
in vitro
experiments and IHC experiments indicated that abnormal fat metabolism linked to dysbiosis is correlated with immunotherapy resistance through regulation of CD8
+
T cell activity/infiltration and PD-L1 expression. Specific saliva microbiome and its associated lipids metabolites are significantly associated with the efficacy of ICI-based therapy in lung cancer. Our findings suggest that oral microbiome modulation and targeting lipid metabolism could improve immunotherapy responses, offering new avenues for personalized treatment strategies.

IMPORTANCE

In non-small cell lung cancer, our study links specific salivary microbiome profiles and related lipid metabolites to the efficacy of immune checkpoint inhibitor (ICI) therapies. Responders showed enrichment of certain
Neisseria
and
Actinomyces
species and distinct lipid compositions. These lipids correlate with PD-L1 expression and CD8
+
T cell activity, affecting treatment outcomes. Our results imply that modulating the oral microbiome and targeting lipid metabolism may enhance ICI effectiveness, suggesting novel personalized therapeutic approaches.
Origin of big garnet amphibolites at Gore Mountain and other localities, Adirondack Mountains, New York State, USA: Whole-rock geochemical constraints
Authors: Hollocher Kurt , Forgeng Hailey Mundell , Stack Kathryn M. , Morgan Elizabeth , Denny Alden , Lott Erica A.
Published: February 2025

The Barton Mine garnet amphibolite orebody on Gore Mountain hosts garnet porphyroblasts routinely 15−30 cm across. The orebody was developed in the southern margin of a metamorphosed olivine gabbro pluton. Cumulate layering within the gabbro continues into the orebody in some places, through a transition zone 1−3 m thick. Though chemically similar for most elements, the orebody and transition zone are irregularly enriched in Li (×4) and depleted in Cs (×0.07) and Th (×0.15) relative to the gabbro. Though rare earth element patterns for elements heavier than Nd are similar, the average Lan/Ndn ratio in gabbro is 1.45, but it gets as low as 0.94 in ore whole rock. Orebody whole-rock δ18O values from previous workers range from ∼6.8‰, typical for Adirondack olivine gabbro, to ∼4.1‰. This indicates that the olivine gabbro south margin was hydrothermally altered and hydrated with meteoric water during emplacement in the upper crust. Ottawan Orogeny (ca. 1090−1040 Ma) granulite-facies metamorphism produced both the dry, fine-grained pyroxene granulite assemblages in the dry gabbro and the damp, coarse garnet amphibolite assemblages in the orebody. The non-ore-grade Warrensburg garnet amphibolite has been poorly studied compared to that at Barton Mine, but it is similar in having garnet porphyroblasts up to ∼10 cm across and probable derivation from an olivine gabbro protolith. Compared to a nearby, compositionally similar olivine gabbro, Warrensburg amphibolite is enriched in Li (×1.4) and Cs (×6, opposite to the trend at Barton Mine) and depleted in Th (×0.6). Lan/Ndn ratios in the amphibolite are also slightly lower than in the gabbro. Though the apparent chemical changes compared to nearby gabbros are different than those at Barton Mine, we infer that they also took place during low-temperature hydrothermal alteration. The geochemistry of the Ruby Mountain garnet deposit is even less well studied than the Warrensburg deposit. It was derived from an anorthositic troctolite precursor, rather than olivine gabbro.
Photon Drag at the Junction Between Metal and 2d Semiconductor
Authors: Svintsov D. , Devizorova Zh.
Published: February 2025

Photon drag represents a mechanism of photocurrent generation wherein the electromagnetic field momentum is transferred directly to the charge carriers. It is believed to be small by the virtue of low photon momentum compared to the typical momenta of the charge carriers. Here, we show that photon drag becomes particularly strong at the junctions between metals and 2d materials, wherein highly non-uniform local electromagnetic fields are generated upon diffraction. To this end, we combine an exact theory of diffraction at “metal-2d material” junctions with microscopic transport theory of photon drag, and derive the functional dependences of the respective photovoltage on the parameters of electromagnetic field and 2d system. The voltage responsivity appears inversely proportional to the electromagnetic frequency ω, the sheet density of charge, and a dimensionless momentum transfer coefficient α which depends only on 2d conductivity in units of light speed η = 2πσ/c and light polarization. For p-polarized incident light, the momentum transfer coefficient appears finite even for vanishingly small 2d conductivity η, which is a consequence of dynamic lightning rod effect. For s-polarized incident light, the momentum transfer coefficient scales as ηlnη–1, which stems from long-range dipole radiation of a linear junction. An extension of the theory is developed for coupled electron-hole systems, which predicts further growth of photon drag at both sides of charge neutrality.
Association between the subclinical level of problematic internet use and habenula volume: a look at mediation effect of neuroticism
Authors: Zakia Halwa , Kyuragi Yusuke , Dai Qi , Oishi Naoya , Ishikawa Yuzuki , Yao Lichang , Aki Morio , Murai Toshiya , Fujiwara Hironobu
Published: February 2025

Background

Ongoing debates question the harm of internet use with the evolving technology, as many individuals transition from regular to problematic internet use (PIU). The habenula (Hb), located between the thalamus and the third ventricle, is implicated in various psychiatric disorders. In addition, personality features have been suggested to play a role in the pathophysiology of PIU.

Aims

This study aimed to investigate Hb volumetry in individuals with subclinical PIU and the mediating effect of personality traits on this relationship.

Methods

110 healthy adults in this cross-sectional study underwent structural magnetic resonance imaging. Hb segmentation was performed using a deep learning technique. The Internet Addiction Test (IAT) and the NEO Five-Factor Inventory were used to assess the PIU level and personality, respectively. Partial Spearman’s correlation analyses were performed to explore the relationships between Hb volumetry, IAT and NEO. Multiple regression analysis was applied to identify personality traits that predict IAT scores. The significant trait was then treated as a mediator between Hb volume and IAT correlation in mediation analysis with a bootstrap value of 5000.

Results

Relative Hb volume was negatively correlated with IAT scores (partial rho=−0.142, p=0.009). The IAT score was positively correlated with neuroticism (partial rho=0.430, p<0.001) and negatively correlated with extraversion, agreeableness and conscientiousness (partial rho=−0.213, p<0.001; partial rho=−0.279, p<0.001; and partial rho=−0.327, p<0.001). There was a significant indirect effect of Hb volume on this model (β=−0.061, p=0.048, boot 95% confidence interval: −0.149 to −0.001).

Conclusions

This study uncovered a crucial link between reduced Hb volume and heightened PIU. Our findings highlight neuroticism as a key risk factor for developing PIU. Moreover, neuroticism was shown to mediate the relationship between Hb volume and PIU tendency, offering valuable insight into the complexities of this interaction.
HYBRID RAY-TRACING MODEL FOR SOLAR ENERGY ASSESSMENT AND ITS OPEN-SOURCE IMPLEMENTATION AS A SERVICE
Authors: ur Rehman Naveed , Uzair Muhammad
Published: February 2025

The existing solar ray-tracing programs for evaluating energy collection are closed-source platform-dependent packages and therefore, their integration into other programs, and adaptability to modern technologies (e.g. cloud storage and computing), are either not possible or are extremely complicated. This paper develops a hybrid ray-tracing-based mathematical model for assessing the solar energy received by geometrical layouts. Then, the design of a “Software as a Service” (SaaS) architecture, accessible through Representational State Transfer Application Programming Interfaces (REST APIs), is presented. It is implemented in an open-source environment, available under a Creative Commons license. Validation is performed by comparing the results for two layouts (with and without obstacles and reflectors) with semi-analytical manual solutions. Finally, an application is demonstrated for optimization of the tilt angle of a booster mounted on the top of façade-integrated solar receiver. The service with its client program and examples from this paper, is available for free download.
Accelerating Nearest Neighbor Search in 3D Point Cloud Registration on GPUs
Authors: Chang Qiong , Wang Weimin , Miyazaki Jun
Published: February 2025

The Iterative Closest Points (ICP) algorithm is the most widely used method for estimating rigid transformation in 3D point cloud registration. However, the ICP relies on repeatedly performing computationally intensive nearest neighbor searches (NNS) within 3D space. This dependency becomes a significant bottleneck when processing large datasets, thereby hindering the practical deployment of point cloud technologies in real-world applications. To address this issue, we propose two approximate nearest neighbor search (ANNS) acceleration strategies for efficient improvement of the processing speed of the NNS. Our strategies first voxelize target cloud points and then fill voxels in the 3D coordinate space around the source point cloud in two different ways, which can convert the global nearest neighbor search to a local search. Both the proposed methods are suited to be parallelized on GPUs with a low computational load. Extensive experiments show that our methods significantly accelerate NNS processing while maintaining high accuracy, outperforming most of the currently known approaches.
Chloride-Dependent Cation Transport via SLC12 Carriers at Atomic Resolution
Authors: Delpire Eric
Published: February 2025

The SLC12 family of genes encodes electroneutral Cl−-dependent cation transporters (i.e., Na-Cl, K-Cl, Na-K-2Cl cotransporters), which play significant roles in maintaining cell and body homeostasis. Recent resolution of their structures at the atomic level provides a new understanding how these transporters operate in health and disease and how they are targeted for therapeutic intervention. Overall, the SLC12 transporter cryo-EM structures confirm some key features established by traditional biochemical and molecular methods, such as the presence of 12 transmembrane domains and the formation of a functional dimer. Study of these structures also uncovers previously unknown features, such as the presence of strategic salt bridges that explain why transporters are stabilized in specific conformations. The cryo-EM structures show similarities with other transport protein structures, especially regarding the position of the cations. The structures also pose challenging questions regarding the number of ions bound and the strict electroneutrality that is conventional understanding.
Alternative splicing of CADM1 is associated with endothelial progenitor cell dysfunction in preeclampsia
Authors: Welz Ricarda , Ramachandran Dhanya , Schröder-Heurich Bianca , Richter Katja , Geffers Robert , von Kaisenberg Constantin Sylvius , Dörk Thilo , von Versen-Höynck Frauke
Published: February 2025

Preeclampsia is a pregnancy specific hypertensive disorder and is associated with an increased postpartum risk of cardiovascular morbidity for both women and their offspring. Previous studies have indicated that cord blood endothelial colony forming cells (ECFCs) are dysfunctional in preeclampsia. The specific mechanisms are not yet fully understood but dysregulation of alternative splicing has been proposed as one of the pathogenic pathways. In order to identify specific targets of alternative splicing in fetal ECFCs, we performed transcriptome-wide differential splicing analyses between cord blood ECFCs from preeclamptic (n=16) and normal pregnancies (n=13). Selected splicing events were validated using fragment length analysis and Sanger sequencing. In silico transcriptome-wide differential splicing analysis identified a significantly increased abundance of the CADM1 isoform ENST00000542447 in the preeclamptic cohort (p=0.002), which was confirmed by wet-lab validation. The deleted exon 8 harbours glycosylation sites known to mediate cell-cell adhesion. To investigate the functional impact of alternative splice variants, we induced an in vitro splice switch using antisense morpholino treatment and followed cellular effects using migration and angiogenesis assays in ECFCs from six normal pregnancies. The CADM1 exon 8 skipping converted the normal ECFCs to a preeclampsia-like state characterised by a decreased migration ability (panova=0.005) and decreased tubule length (panova=0.02). We propose aberrant splicing of CADM1 and the resulting changes in the adherence properties of ECFCs as a potential contributor to cardiovascular sequelae in the offspring of preeclamptic pregnancies.
Vacuole Membrane Protein 1 and Acute Response to Renal Ischemia and Ischemia/Reperfusion
Authors: Singh Vaishali , Adam Ryan J. , Paterson Mark R. , Kriegel Alison J.
Published: February 2025

Ischemia reperfusion (I/R) injury is an important initiating cause of chronic kidney disease and renal failure. Changes in proximal tubule (PT) morphology, including brush border loss, occur rapidly in response to ischemic stress and I/R injury. Vacuole membrane protein 1 (VMP1) is a compelling target for ischemia-associated renal damage, because it is a necessary regulator of autophagy and the genomic location of hypoxia-responsive microRNA miR-21 lies within an intronic region of the Vmp1 gene. Autophagy is reported to have protective and pathological effects on I/R injury. In this study we find that VMP1 is rapidly upregulated in renal cortex tissue in response to 15 and 30-minutes of ischemia. Intravenous delivery of Vmp1-targeting GapmeR or a scrambled GapmeR was performed on adult male Sprague Dawley rats for two days prior to either 30-minutes of renal ischemia, 30-minutes of ischemia followed by 24-hours of reperfusion (I/R), or corresponding control procedures. Autophagy markers and PT morphology were assessed in the renal cortex. Suppression of ischemia-induced upregulation of VMP1 attenuated PT brush border loss following 30-minutes of ischemia and 24-hours post-I/R. Our study reveals a novel and mechanistically important dissociation between VMP1 expression, miR-21-5p expression, autophagy markers, and I/R tubular injury in the renal cortex.
SOCS1 protects acute myeloid leukemia against allogeneic T cell-mediated cytotoxicity
Authors: Tin Enoch , Rutella Sergio , Khatri Ismat , Na Yoosu , Yan Yongran , MacLean Neil , Vadakekolathu Jayakumar , Minden Mark D. , Schimmer Aaron D. , Lee JongBok , Zhang Li
Published: February 2025

Despite the curative potential of allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia (AML), its efficacy is limited by intrinsic resistance of cancer cells to donor-derived T-cell cytotoxicity. Using a genome-wide CRISPR screen, we identified the SOCS1-JAK1-STAT1 pathway as a mediator of AML susceptibility to T cells. SOCS1 knockdown in AML cells sensitized them to killing by allogeneic T cells, whereas SOCS1 overexpression in AML cells induced resistance to T-cell anti-leukemic activity. Mechanistically, SOCS1 protected AML cells from T-cell killing by antagonizing IFNγ-JAK1-induced ICAM-1 expression. Furthermore, primary AML cells with lower SOCS1 expression correlated with better overall survival in patients, especially those with a lower exhausted CD8+ T-cell score. Thus, this study reveals SOCS1 and its downstream mediators as a potential targetable pathway to enhance T cell-based immunotherapy for AML.
Atheroembolic kidney disease and atypical haemolytic uremic syndrome: two sides of the same coin?
Authors: Pisani Antonio , Buonanno Pasquale , Amicone Maria , Riccio Eleonora , Capuano Ivana
Published: February 2025

Introduction. Atheroembolic kidney disease (AEKD) is an under-recognized cause of kidney failure, secondary to the obstruction of the renal artery and/or its branches due to the rupture of an unstable atherosclerotic plaque in patients treated with surgical and invasive cardiovascular procedures. The embolization of cholesterol crystals in the renal artery activates the complement and trigger an inflammatory reaction. Atypical haemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) caused by the hyperactivation of the alternative complement pathway, leading to a prothrombotic and proinflammatory state on the endothelial surface. AEKD and aHUS could share the involvement of the complement in their pathophysiological mechanism and the former could lead to the latter.
Case presentation. A 72-year-old man was referred to our clinic because of a rapid worsening of renal function after nine months from an EndoVascular Aortic Repair (EVAR). After four months from the intervention, his renal function worsened, he developed hypereosinophilia and skin lesions, the renal ultrasound showed increased resistance indexes, strongly suggestive of atheroembolic kidney disease. Successively, we observed thrombocytopenia, anaemia, increased LDH, low plasmatic haptoglobin, schistocytes in blood smear, and normal ADAMTS13. We promptly diagnosed an atypical haemolytic uremic syndrome and started ravulizumab.
Conclusion. To our knowledge this is the first case of aHUS secondary to a subacute AEKD. Further studies are necessary to fill the gap in the knowledge of the precise mechanism leading to aHUS secondary to AEKD and to confirm that they are two sides of the same coin.
Association of hypoalbuminemia with the risk of peritoneal dialysis-associated peritonitis in peritoneal dialysis patients: a meta-analysis
Authors: Zha Danfeng , Yang Xionghao , Xi Huiqin
Published: February 2025

Introduction: The purpose of this meta-analysis was to assess the association between hypoalbuminemia and the risk of peritoneal dialysis-associated peritonitis (PDAP) in patients receiving peritoneal dialysis (PD).
Methods: By the specified deadline of November 13, 2023, a systematic search across various databases was conducted to identify relevant literature. The databases searched included PubMed, Embase, the Cochrane Library, Web of Science, the China National Knowledge Infrastructure (CNKI), WanFang, and VIP. The effect sizes were quantified using odds ratios (OR) or hazard ratios (HR) and were presented with 95% confidence intervals (CI). The analysis was stratified by the type of PD [continuous ambulatory peritoneal dialysis (CAPD), mixed] and the timing of albumin (ALB) level measurements (at baseline, after initiation of PD, or average over time).
Results: A total of 14 studies encompassing 6,448 PD patients were incorporated in this meta-analysis. The findings revealed a significantly elevated risk of peritonitis in patients with hypoalbuminemia compared to those with an ALB level above 3.5g/dL (OR: 2.70, 95% CI: 1.78 to 4.09, P <0.001). Stratification by PD modality showed consistent results within the CAPD group (OR: 5.79, 95% CI: 3.57 to 9.41, P <0.001). For the timing of ALB measurements, the baseline measurement group maintained these findings (OR: 2.53, 95% CI: 1.40 to 4.58, P =0.002), while the group with post-PD measurements did not show statistical significance (OR: 0.76, 95% CI: 0.49 to 1.17, P =0.212). The HR analysis similarly indicated an increased risk of peritonitis in hypoalbuminemia patients compared to those with higher serum ALB levels (HR: 1.62, 95% CI: 1.44 to 1.82, P <0.001).
Conclusion: Our meta-analysis reveals that hypoalbuminemia raises the risk of peritonitis in PD patients, particularly at baseline. This finding underscores the need for close monitoring to detect peritonitis early. Further research is needed to understand the impact of ALB levels post-PD initiation on peritonitis risk.
Hedgehog signaling during gut formation in the freshwater leech, Helobdella austinensis
Authors: Medina-Jiménez Brenda I. , Kwak Hee-Jin , Aryal Yam Prasad , Lee Chan-Jun , Jeong Geon-Hwi , Pyo In-Hyeok , Park Hyeonwoo , Kim Sangjune , Park Soon Cheol , Cho Sung-Jin
Published: February 2025

Introduction: The hedgehog signaling pathway plays a crucial role in inducing segment polarity through cell-cell interactions in various metazoans, including arthropods and annelids. However, its involvement in organogenesis and segmentation among lophotrochozoans remains inconsistent. This study aimed to explore the role of the hedgehog gene during gut development in the freshwater leech, Helobdella austinensis. Methods: Developmental RT-PCR and in situ hybridization were performed to examine the expressions of hedgehog genes. In addition, embryos were treated with Cyclopamine (a hedgehog signaling antagonist) and Purmorphamine (a Smo agonist) to examine the potential interactions between Helobdella orthologs to hedgehog and two NKL genes: Hau-NK2 and Hau-NK4. Results: We examined the expressions of four core pathway members - Hedgehog (Hh), Patched (Ptc), Smoothened (Smo), and the downstream transcription factor Gli - spatiotemporally during the embryonic stages of H. austinensis. All four genes were expressed in the developing gut and proboscis during organogenesis but not during the segmentation stage. Additionally, the treatment of embryos with Cyclopamine and Purmorphamine revealed that NK genes are regulated by hedgehog signaling. Furthermore, NK2 and NK4 were expressed in the developing gut rather than in a segmental stripe pattern. Conclusions: This study confirms that the hedgehog signaling pathway is associated with gut development in the freshwater leech, Helobdella austinensis. The expression patterns of hedgehog pathway genes and their interaction with NK genes suggest a role for hedgehog signaling in regulating gut development rather than segmentation in the freshwater leeches.
Association between periodontitis and carotid atherosclerosis: an updated systematic review and meta-analysis
Authors: Ye Fangfei , Chen Min , Zhou Qun
Published: February 2025

Introduction Current studies on the relationship between periodontitis and carotid atherosclerosis (CAS) remain inconclusive. This updated meta-analysis was conducted to evaluate the relevant observational studies to drive a definite conclusion.
Methods Four major databases were searched for observational studies regarding the relationship between periodontitis and CAS published up to 14 December 2023. Software STATA 14.0 was used to calculate pooled odds ratios (OR) and 95% confidence interval (CI) in random effects model.
Results Twenty-six articles were finally included. Periodontitis was significantly associated with CAS (OR = 1.97, 95% CI = 1.64 – 2.36; p = 0.000)，however, statistical heterogeneity among studies. Sensitivity analysis indicated our results were robust. Although publication bias was observed, odds ratio corrected by the trim-and-fill method was still increased (OR = 1.30, 95% CI = 1.06 – 1.58; p = 0.000).
Conclusion The findings revealed a significant association between periodontitis and CAS. However, long-term randomized controlled trials should be conducted to identify the causality.
Case report and literature review: A 46, XX infant with atypical genitalia diagnosed with primary ovarian insufficiency (POI) caused by HFM1 gene variants
Authors: Yuan Zheng , Cheng Ming , Meng Xi , Cao Bingyan , Gong Chunxiu
Published: February 2025

Introduction: Primary Ovarian Insufficiency (POI) due to single gene variant is classified as a 46,XX difference of sexual development. Variants in the Helicase Family Member 1 (HFM1) gene are associated with POI in females and non-obstructive azoospermia in males.
Case report：We described a case of POI with unique genital characteristics, including clitoromegaly, fusion of the labia majora, an opening of the urethral meatus at the perineum, and the absence of the vaginal opening. Hormonal analysis revealed hypergonadotropic hypogonadism. Genetic testing identified two variants in the HFM1 gene: c.1978-2A>C and c.2681-3T>A. A comprehensive analysis of published cases with HFM1 gene variations was conducted to summarize the range of variants and phenotypes associated with HFM1 gene mutations.
Discussion：This study connects HFM1 gene variants to external genital malformations, expanding the spectrum of phenotypes related to HFM1 mutations. Clinicians should consider the possibility of POI in 46 XX female infants with atypical genitalia and perform genetic testing for HFM1 to avoid leaving out the diagnosis.
Streptococcus mutans GcrR regulates oral biofilm from a cariogenic state to a non-cariogenic state by affecting exopolysaccharides production and biofilm homeostasis
Authors: Zhang Bin , Zhang Anqi , Hou Shihao , Yang Jielin , Hu Tao , Yang Yingming , Lei Lei , Huang Ruizhe
Published: February 2025

Introduction: Dental caries is a non-communicable disease caused by dysbiosis of dental biofilm. S. mutans is considered the major pathogen. The orphan response regulator GcrR negatively regulates exopolysaccharides (EPSs) synthesis in S. mutans. We aimed to investigate the effect of GcrR on the cariogenicity of oral biofilms. A multispecies biofilm model was constructed, including S. mutans, S. sanguinis, and S. gordonii. Methods: The morphology of multispecies biofilms was detected through scanning electron microscopy (SEM), and the structure was observed using confocal laser scanning microscopy (CLSM). The microbial composition was measured by fluorescence in situ hybridization (FISH) and qPCR. The expression of genes was detected by quantitative RT-PCR (qRT-PCR). A specific pathogen-free (SPF) rat model was used to assess the cariogenicity of the multispecies biofilms. Results: The architecture of the biofilm was significantly impaired when gcrR-overexpressed S. mutans incubated with S. sanguinis, and S. gordonii (SmugcrR++S.s+S.g). The biofilm exhibited a decrease in the production of water-insoluble glucans (WIGs) and water-soluble glucans (WSGs), consistent with a decreased expression of EPS synthesis-related genes. The SmugcrR++S.s+S.g biofilm exhibited an increase in non-cariogenic species with lower lactic acid production. Furthermore, SmugcrR++S.s+S.g biofilm exhibited reduced cariogenicity. Conclusion: The biofilm cariogeneicity could be shifted to a less cariogenic state by increased expression of the GcrR regulator.
Valsalva-induced orbital and subcutaneous periorbital emphysema secondary to lamina papyracea dehiscence: case report
Authors: Tanya Stuti Misty , Kulbay Merve , Kherani Femida , Mydlarski Marc B.
Published: February 2025

Introduction: Pneumo-orbit and periorbital subcutaneous emphysema secondary to defects in the sinus wall have been well described in the context of traumatic or surgical sequelae. However, these rarely occur atraumatically in the setting of an idiopathic or congenital sinus wall dehiscence, with a risk for orbital compartment syndrome and irreversible vision loss. We describe a case of idiopathic lamina papyracea dehiscence with resultant pneumo-orbit and elevated intraocular pressure.
Case Presentation: A 28-year-old man experienced a sudden onset of unilateral orbital and subcutaneous periorbital emphysema following Valsalva maneuver. He had unilateral subcutaneous emphysema, crepitus, violaceous discolouration of the lids, and chemosis of the palpebral conjunctiva. Visual acuity was intact and intraocular pressure was mildly elevated. Imaging showed an idiopathic lamina papyracea dehiscence. The patient was advised of sinus precautions with uneventful spontaneous resolution and no visual sequelae.
Conclusion: Lamina papyracea dehiscence predisposes to spontaneous Valsalva-induced orbital or periorbital emphysema with a risk of elevated intraocular pressure, optic neuropathy, and vision loss; prompt recognition and early management can prevent vision-threatening sequelae.
Comprehension of Traffic Signs among Aeta Motorists: From Challenges to Solutions
Authors: Inong Clariza Buay
Published: February 2025

Traffic signs are vital for ensuring motorists safety on the road, but their effectiveness relies on drivers comprehending their meaning and demonstrating the appropriate actions. This study investigated the traffic sign comprehension of 324 Aeta respondents using a three-part questionnaire: a survey on respondents’ agreement with traffic sign meanings and actions, a matching test to identify traffic sign names, both using convenience sampling, and an interview us-ing purposive sampling. The researcher utilized a convergent paral-lel mixed method design, examining quantitative data with descrip-tive statistics and qualitative data with thematic analysis. The key findings indicate that the overall traffic sign comprehension mean score of the respondents was 3.35, interpreted as “Average,” sug-gesting a general understanding of traffic signs with room for im-provement in specific areas. The data also reveals that the most cor-rectly identified signs in the matching test were those reinforced with both verbal and non-verbal elements and those frequently en-countered, such as the informative sign “Slow Vehicles Use Right Lane” (49.4 %), the warning sign “Slippery When Wet” (47.8%), the regulatory sign “Stop Sign” (66.0%) and the road marking “Single Solid Yellow Line” (46.6%). Most Aeta motorists began driving at a young age without formal training, mostly learning through obser-vations and guidance from family and relatives, leading to misun-derstandings of traffic signs. Interviews highlighted that financial difficulties, lack of resources, and illiteracy prevent many Aeta mo-torists from obtaining driver’s licenses and vehicle registrations. Additionally, they often face prejudice and discrimination, being unfairly blamed for motor vehicle accidents. These findings empha-size the importance of specialized educational initiatives and cul-turally appropriate driving instruction to promote traffic sign litera-cy among Aeta motorists. Proposed initiatives include the develop-ment of simple, engaging materials, such as a tri-fold brochure con-taining locally translated traffic sign names, explanations of Kapampangan language, and pictures. Other rec-ommendations include free or subsidized driver education courses and improved traffic signs combining verbal and non-verbal ele-ments to enhance comprehension.