bluuebunny/crossref_metadata_2025 huggingface dataset:
Manipulating perovskite structural asymmetry for high-performing self-powered full-stokes polarimetry
Authors: Chen Quanlin , Ge Mingwei , Geng Cong , Zhang Jia , Gao Linyue , Huang Zhuanzhuan , Wang Saike , Feng Yanxing , Yue Xinxin , Qaid Saif M. H. , Fu Xuewen , Wang Mei , Jiang Yuanzhi , Yuan Mingjian
Published: February 2025

Developing direct full-stokes imaging polarimetry is essential for various applications but remains challenging. Perovskites have superior optoelectronic properties and structural diversity, making them ideal candidates for high-performing direct full-stokes polarimetry. However, perovskite suffers low chiroptical activity due to inefficient chiral transfer, which greatly limits its circular-polarization-vector discrimination. These issues urgently require remedy. Here, we demonstrate that perovskites’ chiroptical activity is highly related to their structural chiral-distortion extent. We propose using halide mixing to construct asymmetric chiral transfer to heighten its structural chiral-distortion extent. Accordingly, we report a 16-fold increment in the optical chiroptical activity. Further ab initio calculations verify that the enhancement is due to the strengthened magnetic transition dipole in mixed-halide structures. We herein report a self-powered, direct full-Stokes polarimetry with a high detectivity up to 1.2 × 10
12
Jones and low detection errors (Δ
S
1–3
≤ 5.0%). We further showcase their application in full-stokes imaging polarimetry with the lowest detection errors yet.
Norovirus co-opts NINJ1 for selective protein secretion
Authors: Song Jaewon , Zhang Li , Moon Seokoh , Fang Ariana , Wang Guoxun , Gheshm Newsha , Loeb Skylar A. , Cao Paul , Wallace Joselynn R. , Alfajaro Mia Madel , Strine Madison S. , Beatty Wandy L. , Jamieson Amanda M. , Orchard Robert C. , Robinson Bridget A. , Nice Timothy J. , Wilen Craig B. , Orvedahl Anthony , Reese Tiffany A. , Lee Sanghyun
Published: February 2025

Plasma membrane rupture by Ninjurin-1 (NINJ1) executes programmed cell death, releasing large cellular damage-associated molecular patterns (DAMPs). However, the regulation and selectivity of NINJ1-mediated DAMP release remain unexplored. Here, we uncover that murine norovirus (MNoV) strategically co-opts NINJ1 to selectively release the intracellular viral protein NS1, while NINJ1-mediated plasma membrane rupture simultaneously bulk-releases various cellular DAMPs. Host caspase-3 cleaves the precursor NS1/2, leading to NS1 secretion via an unconventional pathway. An unbiased CRISPR screen identifies NINJ1 as an essential factor for NS1 secretion. During infection, NINJ1 is recruited to the viral replication site, where it oligomerizes and forms speckled bodies, directly interacting with NS1. Subsequent mutagenesis studies identify critical amino acid residues of NS1 necessary for its interaction with NINJ1 and selective secretion. Genetic ablation or pharmaceutical inhibition of caspase-3 inhibits oral MNoV infection in mice. This study underscores the co-option of NINJ1 for controlled release of an intracellular viral protein.
Antiretrovirus Activity of a Novel Class of Acyclic Pyrimidine Nucleoside Phosphonates
Authors: Balzarini J. , Pannecouque C. , De Clercq E. , Aquaro S. , Perno C.-F. , Egberink H. , Holý A.
Published: July 2002

A novel class of acyclic nucleoside phosphonates has been discovered in which the base consists of a pyrimidine preferably containing an amino group at C-2 and C-4 and a 2-(phosphonomethoxy)ethoxy (PMEO) or a 2-(phosphonomethoxy)propoxy (PMPO) group at C-6. The 6-PMEO 2,4-diaminopyrimidine (compound 1) and 6-PMPO 2,4-diaminopyrimidine (compound 11) derivatives showed potent activity against human immunodeficiency virus (HIV) in the laboratory (i.e., CEM and MT-4 cells) and in primary (i.e., peripheral blood lymphocyte and monocyte/macrophage) cell cultures and pronounced activity against Moloney murine sarcoma virus in newborn NMRI mice. Their in vitro and in vivo antiretroviral activity was comparable to that of reference compounds 9-[(2-phosphonomethoxy)ethyl]adenine (adefovir) and (
R
)-9-[(2-phosphonomethoxy)-propyl]adenine (tenofovir), and the enantiospecificity of (
R
)- and (
S
)-PMPO pyrimidine derivatives as regards their antiretroviral activity was identical to that of the classical (
R
)- and (
S
)-9-(2-phosphonomethoxy)propyl purine derivatives. The prototype PMEO and PMPO pyrimidine analogues were relatively nontoxic in cell culture and did not markedly interfere with host cell macromolecular (i.e., DNA, RNA, or protein) synthesis. Compounds 1 and 11 should be considered attractive novel pyrimidine nucleotide phosphonate analogues to be further pursued for their potential as antiretroviral agents in the clinical setting.
Functional modulation of the human gut microbiome by bacteria vehicled by cheese
Authors: Milani Christian , Longhi Giulia , Alessandri Giulia , Fontana Federico , Viglioli Martina , Tarracchini Chiara , Mancabelli Leonardo , Lugli Gabriele Andrea , Petraro Silvia , Argentini Chiara , Anzalone Rosaria , Viappiani Alice , Carli Elisa , Vacondio Federica , van Sinderen Douwe , Turroni Francesca , Mor Marco , Ventura Marco
Published: February 2025

Since cheese is one of the most commonly and globally consumed fermented foods, scientific investigations in recent decades have focused on determining the impact of this dairy product on human health and well-being. However, the modulatory effect exerted by the autochthonous cheese microbial community on the taxonomic composition and associated functional potential of the gut microbiota of human is still far from being fully dissected or understood. Here, through the use of an
in vitro
human gut-simulating cultivation model in combination with multi-omics approaches, we have shown that minor rather than dominant bacterial players of the cheese microbiota are responsible for gut microbiota modulation of cheese consumers. These include taxa from the genera
Enterococcus
,
Bacillus
,
Clostridium,
and
Hafnia
. Indeed, they contribute to expand the functional potential of the intestinal microbial ecosystem by introducing genes responsible for the production of metabolites with relevant biological activity, including genes involved in the synthesis of vitamins, short-chain fatty acids, and amino acids. Furthermore, tracing of cheese microbiota-associated bacterial strains in fecal samples from cheese consumers provided evidence of horizontal transmission events, enabling the detection of particular bacterial strains transferred from cheese to humans. Moreover, transcriptomic and metabolomic analyses of a horizontally transmitted (cheese-to-consumer) bacterial strain, i.e.,
Hafnia paralvei
T10, cultivated in a human gut environment-simulating medium, confirmed the concept that cheese-derived bacteria may expand the functional arsenal of the consumer’s gut microbiota. This highlights the functional and biologically relevant contributions of food microbes acquired through cheese consumption on the human health.

IMPORTANCE

Diet is universally recognized as the primary factor influencing and modulating the human intestinal microbiota both taxonomically and functionally. In this context, cheese, being a fermented food with its own microbiota, serves not only as a source of nourishment for humans, but also as a source of nutrients for the consumer’s gut microbiota. Additionally, it may act as a vehicle for autochthonous food-associated microorganisms which undergo transfer from cheese to the consumer, potentially influencing host gut health. The current study highlights not only that cheese microbiota-associated bacteria can be traced in the human gut microbiota, but also that they may expand the functional repertoire of the human gut microbiota, with potentially significant implications for human health.
CARPDM: cost-effective antibiotic resistome profiling of metagenomic samples using targeted enrichment
Authors: Hackenberger Dirk , Imtiaz Hamna , Raphenya Amogelang R. , Alcock Brian P. , Poinar Hendrik N. , Wright Gerard D. , McArthur Andrew G.
Published: February 2025

Better interrogation of antimicrobial resistance requires new approaches to detect the associated genes in metagenomic samples. Targeted enrichment is an ideal method for their sequencing and characterization. However, no open-source, up-to-date hybridization probe set targeting antimicrobial resistance genes exists. Here, we describe the Comprehensive Antibiotic Resistance Probe Design Machine (CARPDM), a probe design software package made to run alongside all future Comprehensive Antibiotic Resistance Database releases. To test its efficacy, we have created and tested two separate probe sets: allCARD, which enriches all genes encoded in the Comprehensive Antibiotic Resistance Database’s protein homolog models (
n
= 4,661), and clinicalCARD, which focuses on a clinically relevant subset of resistance genes (
n
= 323). We demonstrate that allCARD increases the number of reads mapping to resistance genes by up to 594-fold. clinicalCARD performs similarly when clinically relevant genes are present, increasing the number of resistance-gene mapping reads by up to 598-fold. In parallel with this development, we have established a protocol to synthesize any probe set in-house, saving up to 350 dollars per reaction. Together, these probe sets, their associated design program CARPDM, and the protocol for in-house synthesis will democratize metagenomic resistome analyses, allowing researchers access to a cost-effective and efficient means to explore the antibiotic resistome.

IMPORTANCE

Antimicrobial resistance threatens to undermine all modern medicine and is driven by the spread of antimicrobial resistance genes among pathogens, environments, patients, and animals. DNA sequencing of complex samples, such as wastewater, shows considerable promise for tracking these genes and making risk assessments. However, these methods suffer from high costs and low detection limits, plus a requirement for frequent redesign due to the constantly evolving diversity of resistance genes. Building upon our Comprehensive Antibiotic Resistance Database, our research provides software for on-demand renewal, based on the latest knowledge of resistance gene diversity, of our novel bait-capture hybridization platform that simultaneously reduces cost and increases detection levels for DNA sequencing of complex samples. The significance of our research is in the development of new software tools, reagent synthesis protocols, and hybridization enrichment protocols to provide affordable, high-resolution metagenomics DNA sequencing, which we test using environmental and wastewater samples.
Effect of fecal microbiota transplantation on diabetic wound healing through the IL-17A–mTOR–HIF1α signaling axis
Authors: Peng Chenmei , Lei Pan , Qi Hongying , Zhu Qianjun , Huang Chushun , Fu Ju , Zhao Chengyu
Published: February 2025

Diabetes is the third most common chronic disorder worldwide. Diabetic wounds are a severe complication that is costly and often results in non-traumatic lower limb amputation. Recent investigations have demonstrated that the gut microbiota as a “virtual organ” can regulate metabolic diseases like diabetes. Fecal microbiota transplantation (FMT) is an innovative therapeutic approach for promoting wound healing, but its function remains incompletely defined. A diabetes model was established by supplying mice with a high-fat diet and performing an intraperitoneal injection of streptozotocin. Diabetic wounds were then created, followed by bacterial transplantation. The relevant indexes of wound healing were evaluated to verify the promoting effect of FMT on the diabetic wounds. Human skin keratinocytes were also cultured, and cell scratch experiments were conducted to further investigate the underlying mechanism. The FMT regulated the levels of specific bacteria in the diabetic mice and helped restore the balance of intestinal microbes. This transplantation also enhanced wound healing in the diabetic mice by augmenting the closure rate, accelerating re-epithelialization, and boosting collagen deposition in skin wounds. Furthermore, FMT promoted the production of IL-17A, which significantly enhanced the growth and movement of human keratinocytes. Inhibiting molecules related to the IL-17A–mTOR–HIF1α signaling axis were shown to hinder wound re-epithelialization.This study clarifies the function of the IL-17A–mTOR–HIF1α signaling axis in the utilization of FMT in diabetic wound healing, providing a new therapeutic method and target for promoting the healing of diabetic wounds.

IMPORTANCE

The Intestinal microbiota, as the organ with the largest number of microorganisms in the body, plays a crucial role in the physiological functions of the human body. Normal microbiota can be involved in various functions such as energy absorption, metabolism, and immunity of the body, and microbiota imbalance is related to many diseases such as obesity and diabetes. Diabetes, as one of the world’s three major chronic diseases, is a significant health issue that troubles more than a billion people globally. Diabetic wounds are a problem that all diabetic patients must confront when undergoing surgery, and it is an important cause of non-traumatic amputations. Exploring the role of intestinal microorganisms in the wound-healing process of diabetic mice can offer the possibility of using microorganisms as a therapeutic means to intervene in clinically related diseases.
LeishmaniaPromastigotes Release a Granulocyte Chemotactic Factor and Induce Interleukin-8 Release but Inhibit Gamma Interferon-Inducible Protein 10 Production by Neutrophil Granulocytes
Authors: van Zandbergen G. , Hermann N. , Laufs H. , Solbach W. , Laskay T.
Published: July 2002

Recent data from our laboratory suggest that neutrophil granulocytes (polymorphonuclear leukocytes [PMN]) can serve as host cells forLeishmania majorin the early phase of infection. In line with these findings, an early influx of PMN to the infected tissues was shown by others to be associated with susceptibility to infection withL. major. The mechanisms underlying the initial PMN recruitment to the site of infection is poorly understood. In the present study we investigated whetherLeishmaniacan influence PMN migration. Supernatants ofLeishmaniapromastigotes were tested for their chemotactic activity using an in vitro chemotaxis assay. AllLeishmaniaspecies tested (L. major,L. aethiopica, andL. donovani) displayed a marked chemotactic effect on human PMN. However, no effect on the migration of macrophages and NK cells was observed. Checkerboard analysis revealed that the observed PMN migration was due to chemotaxis rather than chemokinesis. Most of the chemotactic activity was found in fractions containing molecules with sizes between 10 and 50 kDa. Pretreatment of PMN withN-formyl-methionyl-leucyl-phenylalanine blocked the chemotactic activity ofLeishmaniasupernatants up to 75%. In addition, we found that leishmanial contact induced the release of interleukin-8 (IL-8) and inhibited the production of gamma interferon-inducible protein 10 (IP-10) by PMN. These data suggest that infection withLeishmaniapromastigotes leads to PMN accumulation via the production of a chemotactic factor by the parasites, and this effect is amplified by the induction of IL-8 production in PMN. On the other hand, the inhibition of IP-10 production can lead to prevention of NK cell activation.
A single residue in domain II of envelope protein of yellow fever virus is critical for neutralization sensitivity
Authors: Lou Ya-Nan , Sun Meng-Xu , Li Kai , Xiong Xiao-Chuan , Zhou Chao , Cao Tian-Shu , Li Xiao-Feng , Qin Cheng-Feng
Published: February 2025

The live-attenuated yellow fever (YF) vaccine strain 17D (referred to as YF-17D) is the only commercially available vaccine against YF. Recent yellow fever virus (YFV) isolates of South American genotype I (SAI) showed reduced sensitivity to sera from individuals vaccinated with YF-17D. However, the underlying mechanisms remain inadequately elucidated. Here we conducted a screening of a panel of amino acid changes prevalent in domain II of the envelope protein (EDII) of SAI YFV isolates. Each mutation was introduced into the infectious clone of YF-17D utilizing standard reverse genetics. Subsequent neutralization assays demonstrated that the A83E mutant was more sensitive to sera from YF-17D-vaccinated mice and individuals than YF-17D did. Additionally, the A83E mutant displayed neurovirulence and viscerotropic characteristics comparable to those of the parental YF-17D in murine models. Notably, administration of a single dose of the A83E mutant resulted in an enhanced neutralization response against this variant compared to YF-17D and provided complete protection against lethal YFV challenge in mice. Collectively, these findings not only identify a crucial amino acid residue that influences the neutralization sensitivity of YFV but also provide a promising candidate for the development of an updated YF vaccine.

IMPORTANCE

The YF-17D vaccine has been used to prevent YF disease. However, recent strains belonging to the SAI displayed reduced sensitivity to the antibodies produced by vaccination, raising concerns about potential future outbreaks. To identify potential amino acid residues responsible for the decreased neutralizing activity of YF-17D-vaccinated sera, we conducted a screening and generated recombinant viruses with amino acid changes specific to the SAI in EDII using the YF-17D genome as a genetic backbone. We found the A83E mutation played a key role in reducing neutralizing sensitivity to YF-17D-vaccinated mouse sera. Importantly, the A83E mutant maintained a comparable attenuation phenotype to YF-17D but elicited enhanced neutralization activity and conferred protection in mice. Together, we identify a key amino acid residue responsible for the neutralization escape of SAI YFV isolates. We propose that this substitution could act as a target for developing an updated YF-17D vaccine.
Walleye Dermal Sarcoma Virus Cyclin Interacts with Components of the Mediator Complex and the RNA Polymerase II Holoenzyme
Authors: Rovnak Joel , Quackenbush Sandra L.
Published: July 2002

Walleye dermal sarcoma virus (WDSV) encodes an accessory protein, OrfA, with sequence homology to cyclins (retrovirus cyclin). In cells transfected with an expression construct, OrfA was localized to the nucleus and was concentrated in interchromatin granule clusters (IGCs), sites where splicing factors are concentrated. Other proteins identified in IGCs include transcription factors, the large subunit of RNA polymerase II (Pol II), and cyclin-dependent kinase 8 (cdk8). cdk8 is the kinase partner of cyclin C and a component of the mediator complex, associated with the Pol II holoenzyme. cdk8 and cyclin C can regulate transcription via phosphorylation of cyclin H and the carboxy-terminal domain of Pol II. OrfA in transfected HeLa cells was found to colocalize and copurify with hyperphosphorylated forms of Pol II (Pol IIO) in IGCs, and OrfA was coimmunoprecipitated from lysates of transfected cells with an antibody against Pol IIO. Likewise, Pol IIO could be coprecipitated with an antibody against OrfA. A survey with antibodies against several different cdks resulted in coimmunoprecipitation of OrfA with anti-cdk8, and antiserum against OrfA was able to coprecipitate cdk8 from lysates of cells that express OrfA. Coprecipitation of OrfA with anti-cyclin C demonstrated that it was included in complexes with OrfA and cdk8. OrfA has sequence and structural similarities to cyclin C, and, functionally, OrfA appears to have the capacity to both enhance and inhibit the activity of promoters in a cell-specific manner, similar to functions of the mediator complex. These data suggest that WDSV OrfA functions through its interactions with these large, transcription complexes. Further investigations will clarify the role of the retrovirus cyclin in control of virus expression and transformation.
Brucella suis
S2 strain inhibits IRE1/caspase-12/caspase-3 pathway-mediated apoptosis of microglia HMC3 by affecting the ubiquitination of CALR
Authors: Wang Zhao , Wang Yanbai , Yang Shulong , Wang Zhenhai , Yang Qian
Published: February 2025

Neurobrucellosis represents a severe complication of brucellosis, posing a considerable risk to human health and quality of life. This condition arises from an increased susceptibility to chronic
Brucella
infection, a significant clinical challenge. One key factor contributing to chronic neurobrucellosis is the regulation of microglial apoptosis by
Brucella
; however, the exact molecular mechanisms remain largely unresolved. In this study, human microglial clone 3 (HMC3) cells were infected with
Brucella suis
vaccine strain S2 (
B. suis
S2) at varying multiplicity of infection (MOI) and durations to assess its effects on the IRE1/caspase-12/caspase-3 signaling pathway. Following the suppression of this pathway by
B. suis
S2, calreticulin (CALR) was identified through ubiquitin-modified proteomics (data accessible via ProteomeXchange, identifier PXD056006). To further investigate, CALR-overexpression and knockdown HMC3 cell lines were infected with
B. suis
S2 to elucidate the mechanism by which
B. suis
S2 inhibits apoptosis in HMC3 cells. In conclusion, our findings demonstrate that
B. suis
S2 suppresses HMC3 cell apoptosis via the IRE1/caspase-12/caspase-3 pathway by modulating CALR ubiquitination. This study provides a theoretical basis for exploring the mechanisms of neurobrucellosis and offers insights into its clinical treatment.

IMPORTANCE

Neurobrucellosis is a severe complication impacting the central nervous system (CNS) due to neurological deficits caused by
Brucella
, with primary clinical features including meningitis, encephalitis, brain abscesses, and demyelinating lesions. These nonspecific symptoms often lead to misdiagnosis or delayed diagnosis, increasing the risk of recurrent or chronic neurobrucellosis infections. Consequently, persistent infection and relapse are critical challenges in the clinical management of neurobrucellosis, which are closely linked to
Brucella
’s survival and replication within microglia. Interestingly,
Brucella
may inhibit microglia apoptosis by mitigating endoplasmic reticulum (ER) stress, though the precise molecular mechanisms remain largely unexplored. Thus, this study will elucidate the specific mechanisms by which
Brucella
suppresses microglial apoptosis and provide deeper insights into the molecular pathogenesis and clinical treatment of neurobrucellosis.
Bridging assessment and treatment for repeat suicidality in prisons: development and validation of a risk model
Authors: Fazel Seena , Heathcote Leanne , Farouki Leen , Senior Jane , Perry Amanda , Fanshawe Thomas R , Shaw Jenny
Published: February 2025

Background

Suicidal thoughts and behaviours are common in people in prison and associated with poor health outcomes, including suicide, injury and repeat self-harm.

Objective

To develop and validate a model to stratify risk of repeat suicidality up to 3 months in people in prison.

Methods

In seven English prisons, we identified 754 people aged over 17 who had been placed on a suicide risk management plan after a self-harm episode or elevated risk. We developed a multivariable model to stratify risk of repeat suicidality at 3 months using routinely collected sociodemographic, clinical and prison-related factors, which were tested using Cox proportional HR models. In a prospective validation sample of 390 people from 13 prisons, we tested this model to assess risk of repeat suicidality at 3 months across a range of performance measures.

Findings

Of the overall sample of 1144 people in prison (n=966 men or 84%, mean age 33 years), 22% had the outcome of repeat suicidality over 3 months. The final risk model consisted of nine factors, including sex, calendar age and features of recent suicidal behaviour. Calibration and discrimination were similar in both development and validation samples, with O:E ratio=1.09 (95% CI 0.88 to 1.35) and c-statistic=0.66 (95% CI 0.60 to 0.72) in external validation. At a 25% cut-off, sensitivity was 58% (50 to 66) and specificity was 72% (68 to 75) in external validation. The tool (Risk Assessment for people in Prison at risk of Self-harm and Suicide, RAPSS) is available as an online risk calculator athttps://oxrisk.com/rapsstrial/.

Interpretation

A novel assessment approach for repeat suicidality can provide an evidence-based approach to stratify risk and better allocate resources.
Sleep disorders and the association with frailty among community-dwelling older adults in Northwest China: a cross-sectional study
Authors: Yu Xingfeng , Wang Dan , Yao Lipei , Shi Zhengyan , Liu Xiaomei , Wu Hongjuan , Jiang Jia , Zhang Yulian , He Qianfeng
Published: February 2025

Objectives

To investigate the status of sleep disorders and their association with comprehensive frailty in the community-dwelling older adults.

Design

A cross-sectional study.

Setting

Six community healthcare centres in Xi’an City, Northwest China.

Participants

A total of 2647 community-dwelling older adults completed the study.

Primary and secondary outcome measures

The primary outcomes included frailty and sleep disorders, measured with the Comprehensive Frailty Assessment Instrument and Pittsburgh Sleep Quality Index (PSQI), respectively. The secondary outcomes were potential factors associated with frailty.

Results

The participants averaged 5.23±2.94 in the total score of the PSQI, with a poor sleep quality prevalence of 19.9%. Individuals with poor sleep quality are more likely to have mild and high frailty, with an OR of 1.64 and 2.81, respectively. Both shortened (<5 hours) and prolonged (>8 hours) sleep duration are associated with higher level of frailty. Poor overall sleep, poor subjective sleep quality, extended sleep latency, sleep disturbances, use of sleeping medication and daytime dysfunction were associated with higher level of frailty (with a correlational coefficient of 0.237, 0.201, 0.223, 0.197, 0.087 and 0.378, respectively).

Conclusion

Sleep disorders are common problems among community-dwelling older adults, the severity of which rises with the increase in frailty level. Poor overall sleep quality, poor subjective sleep quality, extended sleep latency, sleep disturbances, daytime dysfunction and abnormal sleep duration are associated with frailty.
Frizzled-7-targeting antibody-derived bifunctional protein retargets NK cells against triple-negative breast cancer cells via MICA-NKG2D axis
Authors: Wang Chenyue , Wu Lisha , Li Xingxing , Mao Shuyang , Wang Zitong , Xie Haiyan , Xu Jing , Li Danfang , Yang Hao , Wang Tong , Huang Qingqing , Yang Lin , Zhang Xiaofei , Liu Yuxia , Wang Jin , Huang Gang , Xie Wei
Published: February 2025

Background

Hypoxia is associated with the evasion of triple-negative breast cancer (TNBC) from immune surveillance. Hypoxia increases the subpopulation of putative TNBC stem-like cells (TNBCSCs) through activating Wnt/β-Catenin signaling. The shedding of MHC class I-related chain A (MICA) is particularly noteworthy in cancer stem cells (CSCs), promoting the resistance of CSCs to natural killer (NK) cell cytotoxicity. To reestablish MICA/NKG2D-mediated immunosurveillance, we proposed the design of a fusion protein (SHH002-hu1-MICA) which consists of Frizzled-7 (Fzd7)-targeting antibody and MICA, serving as an engager retargeting NK cells against TNBCs, especially TNBCSCs.

Methods

Opal multicolor immunohistochemistry staining was used to validate the expression of membrane MICA (mMICA) and existence of NK cells in TNBC tumors; flow cytometry (FCM) assay was used to detect the expression of Fzd7/mMICA on TNBCs. Biolayer interferometry (BLI) and surface plasmon resonance (SPR) assays were executed to assess the affinity of SHH002-hu1-MICA towards rhFzd7/rhNKG2D; near-infrared imaging assay was used to evaluate the targeting capability. A cytotoxicity assay was conducted to assess the effects of SHH002-hu1-MICA on NK cell-mediated killing of TNBCs, and FCM assay to analyze the effects of SHH002-hu1-MICA on the degranulation of NK cells. Finally, TNBC cell-line-derived xenografts were established to evaluate the anti-tumor activities of SHH002-hu1-MICA in vivo.

Results

The expression of mMICA is significantly downregulated in hypoxic TNBCs and TNBCSCs, leading to the evasion of immune surveillance exerted by NK cells. The expression of Fzd7 is significantly upregulated in TNBCSCs and exhibits a negative correlation with the expression of mMICA and infiltration level of NK cells. On accurate assembly, SHH002-hu1-MICA shows a strong affinity for rhFzd7/rhNKG2D, specifically targets TNBC tumor tissues, and disrupts Wnt/β-Catenin signaling. SHH002-hu1-MICA significantly enhances the cytotoxicity of NK cells against hypoxic TNBCs and TNBCSCs by inducing the degranulation of NK cells and promotes the infiltration of NK cells in CD44highregions within TNBC xenograft tumors, exhibiting superior anti-tumor activities than SHH002-hu1.

Conclusions

SHH002-hu1-MICA maintains the targeting property of SHH002-hu1, successfully activates and retargets NK cells against TNBCs, especially TNBCSCs, exhibiting superior antitumor activities than SHH002-hu1. SHH002-hu1-MICA represents a promising new engager for NK cell-based immunotherapy for TNBC.
Impact of iron deficiency on congestion and postdischarge survival in patients recently hospitalised for decompensated heart failure: a multicentre, prospective, observational analysis of the FERIC-RO study
Authors: Margineanu Cornelia , Antohi Laura , Ambrosy Andrew , Bartos Daniela , Collins Sean , Sinescu Crina , Tatu Chitoiu Gabriel , Lighezan Daniel , Vinereanu Dragos , Pop Dana , Pang PS , Butler Javed , Chioncel Ovidiu
Published: February 2025

Background

Iron deficiency (ID) is a highly prevalent comorbidity in patients with chronic and acute heart failure and is associated with worse clinical outcomes. We aimed to evaluate the prevalence and clinical characteristics of ID and its association with in-hospital congestion and postdischarge outcomes.

Methods

FiER deficit in Insuficienta Cardiaca in Romania was a prospective, multicentric study, enrolling 163 patients hospitalised for worsening chronic heart failure (WCHF) irrespective of left ventricular ejection fraction. ID was evaluated at discharge and defined as ferritin<100 ng/mL or ferritin 100–299 ng/mL with transferrin saturation<20%. Patients were classified based on ID status. In-hospital changes of clinical signs of congestion and natriuretic peptides (NT-proBNP) were reported and correlated with ID status. Additionally, survival analysis at 30 and 90 days was performed and compared between patients with ID+ and ID−.

Results

The prevalence of ID was 54.6% (N=89) among 163 eligible patients. Patients with ID+ had more clinical signs of congestion and advanced New York Heart Association functional class at discharge (classes III and IV 58.4% vs 31.1%; p 0.002). NT-proBNP values at admission were higher in ID+ (9288 pg/dL vs 4414 pg/dL, p<0.001), with lower NT-proBNP decrease during hospitalisation (−45.7% vs −63.3%, p 0.003). Additionally, there was no difference in ID prevalence between discharge and 30 days after (54.6% vs 51.3%, p 0.782). Postdischarge all-cause mortality did not differ between ID+ and ID− at 30 days (5.6%% vs 2.7%, p 0.361), but at 90 days, it was higher in ID+ group (30.9% ID+ vs 9.6% ID−, p 0.005).

Conclusions

Patients hospitalised for WCHF and ID had more residual congestion, higher absolute values and significantly lower in-hospital change of NT-proBNP. A significant difference in survival between the two ID groups emerged within 90 days of hospital discharge.
EducAR: implementing a multicomponent strategy to improve therapeutic adherence in rheumatoid arthritis
Authors: Ahijón Lana María , Sivera Mascaró Francisca , Fernández-Nebro Antonio , Muntadas Castelló Sara , Pérez Marina , Otón Teresa , García de Yébenes María Jesús , Carmona Loreto
Published: February 2025

Introduction

The EULAR points to consider (PtC) for reducing non-adherence need implementation.

Objectives

To design, implement and evaluate a strategy based on the PtC to improve treatment adherence in rheumatoid arthritis (RA).

Methods

A multidisciplinary panel cocreated an intervention that was subsequently tested in a cluster trial, where centres were randomised to access the developed intervention or follow the standard of care (SOC). 6-month initiation and implementation adherence were measured in consecutive patients with <2 years of RA. The results were discussed among the centres assigned to the intervention to explore barriers and facilitators to implementation.

Results

The intervention was a two-sided website. The items on the patient site mainly addressed disease and treatment education, self-management and peer support. The healthcare professional site has tutorials on communication to improve trust and adherence, plus shared decision-making aids. It was tested in 141 RA patients (67 control and 74 intervention). Both groups increased adherence at 6 months, mainly in the control group (48% to 67% vs 42% to 47% in the intervention group). Implementation had been very low in relation to barriers identified as lack of time, inadequate focus (exclusively for nurses) and consideration of the current SOC as adequate.

Conclusion

Despite designing an intervention based on the best evidence, the results were inconclusive; the lack of a detected effect could be explained by the limited implementation, which was insufficient for the complexity of the changes required (change of culture).

Trial register number

ClinicalTrials.gov IDNCT05425485.
Root structure of western hemlock and western redcedar in single- and mixed-species stands
Authors: Wang X L , Klinka K , Chen H Y.H , Montigny L de
Published: July 2002

Root structure of western hemlock (Tsuga heterophylla (Raf.) Sarg.) and western redcedar (Thuja plicata Donn. ex D. Don) was studied in single- and mixed-species stands of hemlock and western redcedar in Capilano River watershed, University of British Columbia Malcolm Knapp Research Forest, and Mission, southern coastal British Columbia. We sampled roots using a tree-to-tree trench excavation method. In each stand, roots were collected from three randomly located trenches using a 20 × 20 × 10 cm template along (i) a soil depth gradient: forest floor (FF), 0- to 10-cm (MS1), and 10- to 20-cm mineral soil layers (MS2) and (ii) a lateral soil gradient (tree-to-tree trenches). Hemlockredcedar mixtures had the greatest root density, followed by pure hemlock and redcedar stands. In both pure hemlock stands and hemlock-redcedar mixtures, root density of all size classes (fine, medium, and coarse roots) decreased with increasing soil depth, whereas that of pure redcedar stands peaked at the MS1 layer. Density of roots along the lateral gradient varied among stand types and root size classes. Density of coarse roots was higher towards tree stems, while that of fine and medium roots was more evenly distributed. In the forest floor of the hemlockredcedar mixtures, root density of all sizes except that of redcedar coarse roots was not related to the distance to stems, but fine root density of hemlock was greater than that of redcedar. The highest root density in the hemlockredcedar mixtures may indicate the presence of overlapping and intermingling roots and intense competition for available soil resources.
Elk population dynamics in areas with and without predation by recolonizing wolves in Banff National Park, Alberta
Authors: Hebblewhite Mark , Pletscher Daniel H , Paquet Paul C
Published: July 2002

Gray wolves (Canis lupus) recolonized the Bow Valley of Banff National Park in the mid-1980s after a 30-year absence. Wolves recolonized one zone of the Bow Valley in 1985 and another in 1991, but human activity excluded wolves from a third zone throughout the study. Elk (Cervus elaphus) are the primary prey of wolves in Banff National Park. We studied the effects of wolf predation, snow depth, elk density, and human-caused mortality on the elk population growth rate in the three different wolf recolonization treatments from 1985 to 2000. We constructed a set of generalized linear models of factors affecting population growth, and used Akaike Information Criteria to guide model selection and inference. In the low wolf predation zone, elk population growth was density-dependent and limited by human-caused mortality. In the zone that wolves recolonized in 1991, elk population growth was limited by the combined effects of snow depth and wolf predation after wolf recolonization, in addition to preexisting mortality caused by humans and other predators. Our correlative approach failed to yield insights into population dynamics in the zone where wolves were present throughout the study. However, by comparing zones we demonstrate important differences in ungulate population dynamics in the presence and absence of wolf predation.
α-decay half-lives calculations with Killingbeck potential
Authors: Ndzono V. P. , Ema’a Ema’a J. M. , Zarma A. , Ahmadou K. , Ben-Bolie G. H.
Published: February 2025

In this paper, we propose a new analytical solution of the [Formula: see text]-decay process for the Killingbeck potential with the spherical Coulomb potential and determine the half-lives of some [Formula: see text]-emitters with atomic number [Formula: see text] located in the region [Formula: see text] using the Wentzel–Kramers–Brillouin (WKB) approximation. The Killingbeck potential, with its complex form including harmonic and linear confinement terms, offers a greater richness of interaction and nuclear shape. We provide a solution to the problem of multiple turning points by showing that they can be reduced to two nonsymmetric points. Results obtained show relationships between the paramater of the nuclear potential and experimental data. Those results are compared with experimental data and other theoretical results from the literature. We find that our results are in very good agreement with the experimental data.
Optical, physical and structural study of cadmium sodium bismuth borate glasses system
Authors: Maan Deepika , Nain Deepika , Sonia  , Pilania Ravita , Rao A. S. , Meenakshi
Published: February 2025

The classic melt-quench method was used to make unique transparent cadmium sodium bismuth borate glasses with a composition of [Formula: see text] (18[Formula: see text] Na2[Formula: see text]Bi2O[Formula: see text]B2O3; for ([Formula: see text], 6, 8, 10, 12). Different analytical equipment such as XRD, UV-Vis-NIR, Raman, DSC, and FTIR were employed to characterize and analyze the manufactured glass samples. The density and oxygen packing density of produced glass samples increased linearly with CdO addition, whereas the molar volume decreased. The X-ray diffraction method was employed to anticipate the amorphous nature of the prepared glass samples. The structural alterations of the generated glasses were investigated using FTIR and RAMAN spectra. DSC was employed to assess the thermal characteristics related to the crystallization temperature ([Formula: see text] and glass transition temperature ([Formula: see text]. DSC demonstrates the result that CdO content contributes most to enhancing the thermal stability of glasses. The ([Formula: see text] values increased while ([Formula: see text] values decreased as CdO substitution increased. Infrared and Raman spectroscopy were used to conduct a thorough examination of structure, which revealed that these glasses were comprised of both symmetric and asymmetric stretched vibrations of bonds. The absorption spectra in the ultraviolet-visible range of the samples indicated a reduction in the optical bandgap as CdO content increased. All the findings indicate that the CdO level in glass samples acts as a network modulator, while BO4 does not.
Large Language Model-Aware In-Context Learning for Code Generation
Authors: Li Jia , Tao Chongyang , Li Jia , Li Ge , Jin Zhi , Zhang Huangzhao , Fang Zheng , Liu Fang
Published: February 2025

Large Language Models (LLMs) have shown impressive In-Context Learning (ICL) ability in code generation. LLMs take a prompt context consisting of a few demonstration examples and a new requirement as input, and output new programs without any parameter update. Existing studies have found that the performance of ICL-based code generation heavily depends on the quality of demonstration examples and thus arises research on selecting demonstration examples: given a new requirement, a few demonstration examples are selected from a candidate pool, where LLMs are expected to learn the pattern hidden in these selected demonstration examples. Existing approaches are mostly based on heuristics or randomly selecting examples. However, the distribution of randomly selected examples usually varies greatly, making the performance of LLMs less robust. The heuristics retrieve examples by only considering textual similarities of requirements, leading to sub-optimal performance.

To fill this gap, we propose a
L
arge language model-
A
ware selection approach for
I
n-context-
L
earning-based code generation named LAIL. LAIL uses LLMs themselves to select examples. It requires LLMs themselves to label a candidate example as a positive example or a negative example for a requirement. Positive examples are helpful for LLMs to generate correct programs, while negative examples are trivial and should be ignored. Based on the labeled positive and negative data, LAIL trains a model-aware retriever to learn the preference of LLMs and select demonstration examples that LLMs need. During the inference, given a new requirement, LAIL uses the trained retriever to select a few examples and feed them into LLMs to generate desired programs. We apply LAIL to four widely used LLMs and evaluate it on five code generation datasets. Extensive experiments demonstrate that LAIL outperforms the state-of-the-art (SOTA) baselines by 11.58%, 3.33%, and 5.07% on CodeGen-Multi-16B, 1.32%, 2.29%, and 1.20% on CodeLlama-34B, and achieves 4.38%, 2.85%, and 2.74% improvements on Text-davinci-003 in terms of Pass@1 at MBJP, MBPP, and MBCPP, respectively. In addition to function-level code generation, LAIL improves the performance of LLMs on DevEval, a repository-level code generation dataset, which achieves 10.04%, 8.12%, and 4.63% improvements compared to the SOTA baselines at Pass@1, 3, and 5 on CodeLlama-7B. Human evaluation further verifies that the generated programs of LAIL are superior in correctness, code quality, and maintainability. Besides, LAIL has satisfactory transferability across different LLMs and datasets, where the retriever learned on one LLM (dataset) can be transferred to other LLMs (datasets).
Revisiting GPS Spoofing in Phasor Measurement: Real-World Exploitation and Practical Detection in Power Grids
Authors: Kim Chunghyo , Noh Juhwan , Ghahremani Esmaeil , Kim Yongdae
Published: February 2025

Phasor Measurement Units (PMUs) are critical devices in modern power grids, providing precise voltage and current phasor measurements (synchrophasors) for real-time monitoring, fault detection, and stability assessment. While previous research suggested that arbitrary time manipulation through GPS spoofing could disrupt grid operations, our study reveals that successful attacks require specific conditions, contrary to earlier assumptions.

Through careful analysis of the synchrophasor data specification (IEEE Standard C37.118.x), we demonstrate that arbitrary time manipulation
does not
directly lead to phase manipulation. Instead, arbitrary manipulations can cause GPS holdover (loss of lock), alert operators with erroneous timing, and ultimately invalidate the received synchrophasors. An experiment with a commercial PMU confirms our specification analysis. We identify the time spoofing conditions to avoid GPS holdover and discover that nanosecond-scale signal alignment (approximately 375 ns error) and gradual time manipulation (around 50 ns/s error) are required.

Experiments on a commercial Wide Area Monitoring System (WAMS) testbed demonstrate that GPS spoofing meeting the identified criteria results in a 500-microsecond time error (10.8-degree phase error) after 12 hours without triggering alarms. Given that a 60-degree phase variation is considered a fault, triggering protection mechanisms, this GPS spoofing technique could potentially induce false faults within 70 hours.

To counter this threat, we propose a practical method to distinguish GPS spoofing-induced false faults from actual faults caused by events like lightning strikes or ground shorts. Analysis of 10 real-world incidents from the past six months demonstrates that genuine faults consistently exhibit instantaneous phase variations within three electrical cycles, providing a basis for differentiation.
Burst tries
Authors: Heinz Steffen , Zobel Justin , Williams Hugh E.
Published: July 2002

Many applications depend on efficient management of large sets of distinct strings in memory. For example, during index construction for text databases a record is held for each distinct word in the text, containing the word itself and information such as counters. We propose a new data structure, the burst trie, that has significant advantages over existing options for such applications: it uses about the same memory as a binary search tree; it is as fast as a trie; and, while not as fast as a hash table, a burst trie maintains the strings in sorted or near-sorted order. In this paper we describe burst tries and explore the parameters that govern their performance. We experimentally determine good choices of parameters, and compare burst tries to other structures used for the same task, with a variety of data sets. These experiments show that the burst trie is particularly effective for the skewed frequency distributions common in text collections, and dramatically outperforms all other data structures for the task of managing strings while maintaining sort order.
CPU Sim 3.1
Authors: Skrien Dale
Published: July 2002

CPU Sim 3.1 is an educational software package written in Java for
use in CS3 courses. CPU Sim provides students an active learning
environment in which they can design, modify, and compare various
computer architectures at the register-transfer level and higher.
They can run assembly language or machine language programs for
those architectures through simulation. CPU Sim is a complete
development environment, including dialog boxes for designing the
CPU architecture, a text editor for editing assembly language
programs, an assembler, several display windows for viewing the
registers and RAMs during the execution of programs, and many
debugging features such as the ability to step forward or backward
during execution, inspecting and optionally changing the values in
the registers and RAMs after each step. These features and
suggested uses of CPU Sim in CS3 classes are discussed.
REVERSIBLE POLYMERIZATIONS AND AGGREGATIONS
Authors: Greer Sandra C.
Published: July 2002

▪ Abstract  The aggregation of monomers into polymers, whether by covalent or noncovalent interactions, is often reversible and frequently occurs with the entropy and enthalpy of the aggregation sharing the same sign. In such a case, the aggregation goes forward or reverses, depending on such variables as temperature and composition, rather like a phase transition. We explore the physical chemistry of three such systems: an organic monomer (α-methylstyrene), an inorganic monomer (sulfur), and a biopolymer (actin). We compare the available theories and experiments and list issues still open.