bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interplay between the cyclophilin homology domain of RANBP2 and MX2 regulates HIV-1 capsid dependencies on nucleoporins
Authors: Flick Haley , Venbakkam Ananya , Singh Parmit K. , Layish Bailey , Huang Szu-Wei , Radhakrishnan Rajalingam , Kvaratskhelia Mamuka , Engelman Alan N. , Kane Melissa 
Published: January 2025

ABSTRACT

Interlinked interactions between the viral capsid (CA), nucleoporins (Nups), and the antiviral protein myxovirus resistance 2 (MX2/MXB) influence human immunodeficiency virus 1 (HIV-1) nuclear entry and the outcome of infection. Although RANBP2/NUP358 has been repeatedly identified as a critical player in HIV-1 nuclear import and MX2 activity, the mechanism by which RANBP2 facilitates HIV-1 infection is not well understood. To explore the interactions between MX2, the viral CA, and RANBP2, we utilized CRISPR-Cas9 to generate cell lines expressing RANBP2 from its endogenous locus but lacking the C-terminal cyclophilin (Cyp) homology domain and found that both HIV-1 and HIV-2 infections were reduced significantly in RANBP2
ΔCyp
cells. Importantly, although MX2 still localized to the nuclear pore complex in RANBP2
ΔCyp
cells, antiviral activity against HIV-1 was decreased. By generating cells expressing specific point mutations in the RANBP2-Cyp domain, we determined that the effect of the RANBP2-Cyp domain on MX2 anti-HIV-1 activity is due to direct interactions between RANBP2 and CA. We further determined that CypA and RANBP2-Cyp have similar effects on HIV-1 integration targeting. Finally, we found that the Nup requirements for HIV infection and MX2 activity were altered in cells lacking the RANBP2-Cyp domain. These findings demonstrate that the RANBP2-Cyp domain affects viral infection and MX2 sensitivity by altering CA-specific interactions with cellular factors that affect nuclear import and integration targeting.

IMPORTANCE
Human immunodeficiency virus 1 (HIV-1) entry into the nucleus is an essential step in viral replication that involves complex interactions between the viral capsid (CA) and multiple cellular proteins, including nucleoporins (Nups) such as RANBP2. Nups also mediate the function of the antiviral protein myxovirus resistance 2 (MX2); however, determining the precise role of Nups in HIV infection has proved challenging due to the complex nature of the nuclear pore complex (NPC) and significant pleiotropic effects elicited by Nup depletion. We have used precise gene editing to assess the role of the cyclophilin domain of RANBP2 in HIV-1 infection and MX2 activity. We find that this domain affects viral infection, nucleoporin requirements, MX2 sensitivity, and integration targeting in a CA-specific manner, providing detailed insights into how RANBP2 contributes to HIV-1 infection.
Signal peptidase SpsB coordinates staphylococcal cell cycle, surface protein septal trafficking, and LTA synthesis
Authors: Zhang Ran , Jia Yaosheng , Scaffidi Salvatore J. , Madsen Jesper J. , Yu Wenqi 
Published: January 2025

ABSTRACT

Cell wall-anchored surface proteins of Gram-positive bacteria, harboring a highly conserved YSIRK/G-S signal peptide (SP
YSIRK+
), are deposited at cell division septum and anchored to septal peptidoglycan. The mechanisms supporting YSIRK protein septal trafficking remain elusive. Previously, we identified that LtaS-mediated lipoteichoic acid (LTA) synthesis restricts septal trafficking of YSIRK+ proteins in
Staphylococcus aureus
. Interestingly, both LtaS and SP
YSIRK+
are cleaved by the signal peptidase SpsB, but the biological implications remain unclear. Here, we show that SpsB is required for cleaving SP
SpA(YSIRK+)
of staphylococcal surface protein A (SpA). Depletion of
spsB
not only diminished SP
SpA
processing but also abolished SpA septal localization. The mis-localization is attributed to the cleavage activity of SpsB, as an A37P mutation of SP
SpA
that disrupted SpsB cleavage abrogated SpA septal localization. Strikingly, depletion of
spsB
led to aberrant cell morphology, cell cycle arrest, and daughter cell separation defects. Localization studies showed that SpsB was enriched at the septum of dividing staphylococcal cells. Finally, we show that SpsB spatially regulates LtaS as
spsB
depletion enriched LtaS at the septum. Collectively, the data suggest a new dual-mechanism model mediated by SpsB: the abundant YSIRK+ proteins are efficiently processed by septal localized SpsB; SpsB cleaves LtaS at the septum, which spatially regulates LtaS activity contributing to YSIRK+ proteins septal trafficking. The study identifies SpsB as a novel and key regulator orchestrating protein secretion, cell cycle, and cell envelope biogenesis.

IMPORTANCE
Surface proteins containing a YSIRK/G-S-positive signal peptide are widely distributed in Gram-positive bacteria and play essential roles in bacterial pathogenesis. They are highly expressed proteins that are enriched at the septum during cell division. The biogenesis of these proteins is coordinated with cell cycle and LTA synthesis. The current study identified the staphylococcal signal peptidase SpsB as a key determinant in regulating surface protein septal trafficking. Furthermore, this study highlights the novel functions of SpsB in coordinating LtaS-mediated LTA production and regulating staphylococcal cell cycle. As SpsB, YSIRK+ proteins, and LTA synthesis are widely distributed and conserved, the mechanisms identified here may be shared across Gram-positive bacteria.
Supplemental Material: Apatite Lu–Hf dating of late Archean banded iron formations
Authors: Lan Zhongwu , al. et 
Published: January 2025

<p>Supplemental text; Figures S1 and S2; Table S1 (apatite LA-ICP-MS U–Pb data); Table S2 (apatite LA-ICP-MS Lu–Hf data); Table S3 (apatite EPMA major element data); and Table S4 (apatite LA-ICP-MS trace element data). </p>
How climate change is shaping young people’s health: a participatory, youth co-led study from Bangladesh, Guatemala and Nigeria
Authors: Pinchoff Jessie , Etetim Eno-Obong , Babatunde Damilola , Blomstrom Eleanor , Ainul Sigma , Akomolafe Toyin Olamide , Medina Carranza Brian , Del Valle Angel , Austrian Karen 
Published: January 2025

IntroductionClimate change is shaping adolescent and young people’s (AYP) transitions to adulthood with significant and often compounding effects on their physical and mental health. The climate crisis is an intergenerational inequity, with the current generation of young people exposed to more climate events over their lifetime than any previous one. Despite this injustice, research and policy to date lacks AYP’s perspectives and active engagement.MethodsParticipatory, youth co-led qualitative focus group discussions were held in Bangladesh, Guatemala and Nigeria in mid-2023. A total of 196 AYP ages 12–25 years participated. Open-ended questions elicited responses regarding AYP knowledge, experiences and perceptions of climate change. Using NVivo software, translated transcripts were coded to explore and synthesise key thematic areas.ResultsRespondents discussed varied climate exposures and associated health risks, for example, how flooding events were impeding access to sexual and reproductive health commodities. Acute climate events like flooding and cyclones increased perceived risk of early marriage and gender-based violence in Bangladesh and Guatemala. In Nigeria, respondents discussed health effects of extreme heat, and how droughts were shifting women into more traditionally male roles in agriculture and income-generating activities, increasing the perceived risk of household tensions and gender-based violence. Commonly reported themes included perceived climate impacts on sexual and reproductive health including early marriage or gender-based violence. Another common theme was anxiety about climate change, its effects on economic and food insecurity in communities and feeling hopeless, lacking agency and not feeling supported by local institutions, all linked with worse mental health.ConclusionOur results summarise how AYP perceive climate change is affecting their physical and mental health, finding similarities and differences across these three settings. Our results can inform the development of policies and programmes that directly address AYP needs in a way that is inclusive and responsive.
Fingolimod and risk of skin cancer among individuals with multiple sclerosis: a population-based cohort study protocol
Authors: Jia Analisa , Kuramoto Lisa , Khakban Amir , Sio Weng Sut , Traboulsee Anthony , De Vera M A , Oh Jiwon , Loree Jonathan , Tam Roger , Lynd Larry D , Cragg Jacquelyn J 
Published: January 2025

Introduction
Long-term population-based safety studies, applying advanced causal inference techniques, including an active comparator with new-user design, are needed to investigate skin cancer outcomes among individuals with multiple sclerosis (MS) treated with fingolimod. This study aims to describe a protocol for investigating the relationship between fingolimod use and the incidence of skin cancer among individuals with MS.

Methods and analysis
We will use population-based administrative health data from two Canadian provinces (British Columbia and Alberta) to conduct an observational cohort ‘trial emulation’ study with an active comparator and new-user design. Individuals with MS aged ≥18 years will be identified using a validated algorithm. Incident users of fingolimod and active comparators (natalizumab, alemtuzumab, dimethyl fumarate, teriflunomide) will then be identified. The outcome of interest will be skin cancer (melanoma and non-melanoma skin cancers). Survival analysis will be used to estimate HRs and corresponding 95% CIs, adjusted for potential confounders.

Ethics and dissemination
Ethics approval for this study was obtained from the University of British Columbia Clinical Research Ethics Board (H24-03199). No personal identifying information will be made available as part of this study. Findings will be disseminated through presentations and peer-reviewed publications.

Trial registration number

NCT06705608
.
Optimising investigative pathways in military medicine: operational impact of a military cardiopulmonary exercise testing clinic
Authors: Holland Jennifer Louise , Cowie P , Gardner L , Mulae J , Richards S , Holdsworth DA 
Published: January 2025

IntroductionAbnormal cardiorespiratory symptoms and investigative findings in service personnel typically result in prolonged investigation and occupational restriction. This analysis aimed to assess the impact of theOxfordMilitary CardiopulmonaryExercise TestingClinic (OMEC), which investigates such symptoms and findings, on occupational recommendations.MethodsA service evaluation was conducted on all OMEC attendances over a 5-year period. Referral indication and occupational grading, demographics, exercise testing parameters, clinical diagnosis and occupational recommendation were recorded.Results141 individuals were reviewed. Mean age was 36 (±11.3) years, and 91% were male. Median waiting time for an appointment was 14.4 weeks (cf NHS 17.4 weeks).Individuals were referred for dyspnoea (22.1%), syncope (11.4%), chest pain (8.1%) (referred to as ‘higher risk’ symptom group), and pre-syncope (8.1%), palpitations (8.1%), and fatigue and/or exercise intolerance (6.0%) (referred to as ‘lower risk’ symptom group). 34% were asymptomatic with incidental findings on cardiac screening investigations. Reduced exercise capacity was rare, affecting only 11% of individuals, which was borderline/mild at worst.Median peak VO2(as a percentage of the predicted peak) was lower in the higher-risk symptom group than in the lower-risk symptom group (97.8% vs 121%; p<0.001). This was also seen for median workload as %PP (82.6% vs 98.0%; p<0.001). 80.5% of patients were given an immediate occupational recommendation; 78% of which were favourable outcomes (ie, a recommended occupational upgrade (72%) or to remain fully deployable (6%)).ConclusionOMEC is tailored to the unique needs of the military population, providing outcomes that support operational requirements. Despite geographical distribution and operational commitments, OMEC waiting time is equivalent to the NHS, with the great majority of patients upgraded after attendance. These findings establish OMEC as a benchmark for military-specific clinical services based in public (NHS) hospitals, highlighting its role in facilitating rapid and effective occupational management.
Nonextensive black hole thermodynamics from generalized Euclidean path integral and Wick’s rotation
Authors: Barzi F. , El Moumni H. , Masmar K. 
Published: January 2025

Abstract
This paper extends the Euclidean path integral formalism to account for nonextensive thermodynamics. Concretely, we introduce a generalized Wick’s rotation from real time t to imaginary time

$$\tau $$

τ

such that,

$$t\rightarrow -i f_\alpha (\tau )$$

t
→
-
i

f
α

(
τ
)

, where

$$f_\alpha $$

f
α

a differentiable function and

$$\alpha $$

α

is a parameter related to nonextensivity. The standard extensive formalism is recovered in the limit

$$\alpha \rightarrow 0$$

α
→
0

and

$$f_0(\tau )=\tau $$

f
0

(
τ
)

=
τ

. Furthermore, we apply this generalized Euclidean path integral to black hole thermodynamics and derive the generalized Wick’s rotations given the nonextensive statistics. The proposed formulation enables the treatment of nonextensive statistics on the same footing as extensive Boltzmann–Gibbs statistics. Moreover, we define a universal measure,

$$\eta $$

η

, for the nonextensivity character of statistics. Lastly, based on the present formalism, we strengthen the equivalence between the AdS-Schwarzschild black hole in Boltzmann–Gibbs statistics and the flat-Schwarzschild black hole within Rényi statistics and suggest a potential reformulation of the

$$AdS_5$$

A
d

S
5

/

$$CFT_4$$

C
F

T
4

duality.
RACEME: Embedded Intelligence for Correlation-driven Predictive Energy-harvesting Management in LoRa Networks
Authors: Jewsakul Sukanya , Ngai Edith Cheuk Han 
Published: January 2025

The prolonged lifetime of energy-harvesting (EH) LoRa networks requires that all EH LoRa sensors utilize available harvested energy in an energy-neutral manner to avoid power failures. This requirement is challenging to fulfill due to the unpredictability of ambient energy sources and the spatio-temporal heterogeneity of sensors’ harvesting abilities. We present RACEME, a novel predictive EH-management framework by exploiting the embedded intelligence capability of energy-harvesting LoRa devices. It empowers energy-neutral operation in EH LoRa networks by leveraging the spatio-temporal correlation between EH LoRa sensors to optimize the harvested energy utilization. RACEME is an integrated system that consists of embedded machine learning (ML) for predictive EH management on the sensors and online cluster-based data reduction and recovery on the server. To maximize the accuracy of EH predictions, RACEME allows each sensor to implement an ML pipeline locally. Coupled with the cluster-based data-reduction feedback from the server, RACEME enables the sensors with higher harvested-energy availability and communication quality to transmit critical data more frequently in a probabilistic manner without sacrificing data quality. Compared with the state of the art, the experimental results reveal that RACEME improves EH prediction accuracy, network lifetime, and transmission overhead by up to 1.7, 2, and 8 times, respectively.
TagRecon: Fine-Grained 3D Reconstruction of Multiple Tagged Packages via RFID Systems
Authors: Wang Ziang , Duan Chunhui , Xue Jiawei , Li Fan , Feng Qihua , Zhu Yinan , Zhou Ziyang 
Published: January 2025

To meet the new requirements of Industry 4.0, the logistics field has introduced 3D reconstruction technology. Computer vision-based solutions face challenges like bad lighting conditions and line-of-sight constraints. Meanwhile, the widespread adoption of RFID tags in supply chains offers an opportunity to enhance current reconstruction methods.
In this paper, we propose TagRecon, a fine-grained multi-object 3D reconstruction scheme utilizing well-deployed RFIDs. Specifically, TagRecon transforms the task of reconstruction into a problem of estimating 3D bounding boxes for tagged packages. By placing dual anchor tags on each target package, TagRecon enables accurate inference of the package’s translation and rotation using RFID-based localization and orientation sensing. Our scheme introduces a novel method to estimate rotations and translations for tagged packages, utilizing the known geometric relationship of anchor tags. Besides, to achieve simultaneous reconstruction of multiple packages, we manage to match tags from various packages through the correlation between anchor tag pairs. As far as we know, this is the first RFID-based solution that can simultaneously realize 3D translation and rotation estimation of multiple objects to a fine granularity. Experiments validate TagRecon achieves a 28.0 cm translation error and 6.8°, 6.0°, and 7.5° rotation errors for roll, pitch, and yaw angles on average.
Cow’s Milk Protein May Induce Allergy and Inflammation in Intestinal Epithelial Cells Through Regulating HOTAIR Expression and NF‐κB Signaling Pathway
Authors: Mao Kangwei , Liu Jiangyan , Li Dalei , Gu Siyu , Zhang Chenxi , Li Mengmeng , Sun Jun , Wang Juan 
Published: January 2025

Background: Cow’s milk protein allergy (CMPA) is associated with activation of proinflammatory signaling pathways and overexpression of inflammatory mediators. Long noncoding RNA (LncRNA) HOX transcript antisense intergenic RNA (HOTAIR) is a LncRNA, which is involved in the occurrence and development of many biological processes and diseases. HOTAIR can prevent necrotizing enterocolitis. This study aims to explore the effect of milk protein on NCM‐460 cells and its mechanism of action with HOTAIR.Methods: NCM‐460 cells were induced by cow’s milk protein to establish in vitro cell models. CCK‐8 and EdU staining were used for evaluating the effects of cow’s milk protein on the viability and proliferation. ELISA was used for comparing the levels of inflammatory cytokines. TUNEL staining was conducted for evaluating the apoptosis. Expression levels of HOTAIR were detected by RT‐qPCR. The expression of NF‐κB signaling pathway–related molecules in cells was explored to evaluate the mechanism of HOTAIR in improving ALI.Results: Cow’s milk protein decreased the viability NCM‐460 cells and also decreased the expression of HOTAIR. Moreover, it can induce the antiproliferative and proapoptotic effects on NCM‐460 cells, and overexpression of LncRNA HOTAIR can partially reverse the effects of cow’s milk protein. In addition, overexpression of LncRNA HOTAIR reversed the effects of cow’s milk protein on NF‐κB signaling.Conclusions: Cow’s milk protein may induce the allergy and inflammation in intestinal epithelial cells through regulating HOTAIR expression and NF‐κB signaling pathways.
Accumulation of CD38 in Hybrid Epithelial/Mesenchymal Cells Promotes Immune Remodeling and Metastasis in Breast Cancer
Authors: Visal Tanvi H. , Bayraktar Recep , den Hollander Petra , Attathikhun Michael A. , Zhou Tieling , Wang Jing , Shen Li , Minciuna Corina-Elena , Chen Meng , Barrientos-Toro Elizve , Batra Harsh , Raso Maria Gabriela , Yang Fei , Parra Edwin R. , Sahin Aysegul A. , Calin George A. , Mani Sendurai A. 
Published: January 2025

Abstract
Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer. The epithelial-to-mesenchymal transition is a nonbinary process in the metastatic cascade that generates tumor cells with both epithelial and mesenchymal traits known as hybrid EM cells. Recent studies have elucidated the enhanced metastatic potential of cancers featuring the hybrid EM phenotype, highlighting the need to uncover molecular drivers and targetable vulnerabilities of the hybrid EM state. Here, we discovered that hybrid EM breast tumors are enriched in CD38, an immunosuppressive molecule associated with worse clinical outcomes in liquid malignancies. Altering CD38 expression in tumor cell impacted migratory, invasive, and metastatic capabilities of hybrid EM cells. Abrogation of CD38 expression stimulated an antitumor immune response, thereby preventing the generation of an immunosuppressive microenvironment in hybrid EM tumors. CD38 levels positively correlated with PD-L1 expression in samples from patients with TNBC. Moreover, targeting CD38 potentiated the activity of anti–PD-L1, eliciting strong antitumor immunity, with reduced tumor growth in hybrid EM models. Overall, this research exposes upregulation of CD38 as a specific survival strategy utilized by hybrid EM breast tumors to suppress immune cell activity and sustain metastasis, with strong implications in other carcinomas that have hybrid EM properties.
Significance: Hybrid cells co-featuring epithelial and mesenchymal traits in triple-negative breast cancer express elevated levels of CD38 to induce immunosuppression and metastasis, indicating CD38 inhibition as potential strategy for treating breast cancer.
Follow-up Analysis Enhances Understanding of Molecular Residual Disease in Localized Non–Small Cell Lung Cancer
Authors: Zhang Jia-Tao , Liu Si-Yang , Gao Xuan , Liu Si-Yang Maggie , Yan Bingfa , Huang Chen , Jiao Zicong , Yan Hong-Hong , Pan Yi , Dong Song , Gao Wei , Gong Yuhua , Tu Hai-Yan , Xia Xue-Feng , Zhou Qing , Zhong Wen-Zhao , Yang Xue-Ning , Yi Xin , Wu Yi-Long 
Published: January 2025

Abstract

Purpose:
The prognostic value of molecular residual disease (MRD) in non–small cell lung cancer (NSCLC) is well established, with treatment-guiding results anticipated. Here, we present updated analyses from our previously published cohort study of 261 patients with NSCLC undergoing complete resection.

Experimental Design:
A total of 261 patients with stage I to III lung cancer who underwent radical surgery were enrolled. Enrolled patients underwent follow-up blood draws according to the predefined time points after surgery. As of December 31, 2023, with a median follow-up of 43.4 months, 948 postoperative blood samples were collected.

Results:
Landmark and longitudinal MRD exhibited positive predictive values of 91.3% and 92.8%, respectively, with a median lead time of 5.2 months. Negative predictive values were 76.5% and 93.2%, respectively. Patients with landmark undetectable MRD could not benefit from adjuvant therapy through the updated follow-up (P = 0.529). Among the 13 patients with recurrent NSCLC and longitudinal undetectable MRD, seven (53.8%) had brain-only metastases, and four (30.8%) had no updated blood samples for over 6 months prior to recurrence. Besides, for those with longitudinal detectable MRD, higher maximum variant allele frequency (&gt;0.55%) and ctDNA level (&gt;13 hGE/mL) were associated with a high risk of short-term recurrence. Additionally, updated follow-up data further support that the peak time for detectable MRD was 18 months after landmark detection.

Conclusions:
These findings suggest the significant potential of MRD in guiding personalized treatment for NSCLC. Postoperative longitudinal undetectable MRD can indicate a cured population.