bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia-inducible factor 2 regulates alveolar regeneration after repetitive injury in three-dimensional cellular and in vivo models
Authors: McCall A. Scott , Gutor Sergey , Tanjore Hari , Burman Ankita , Sherrill Taylor , Chapman Micah , Calvi Carla L. , Han David , Camarata Jane , Hunt Raphael P. , Nichols David , Banovich Nicholas E. , Lawson William E. , Gokey Jason J. , Kropski Jonathan A. , Blackwell Timothy S.
Published: January 2025

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease in which repetitive epithelial injury and incomplete alveolar repair result in accumulation of profibrotic intermediate/transitional “aberrant” epithelial cell states. The mechanisms leading to the emergence and persistence of aberrant epithelial populations in the distal lung remain incompletely understood. By interrogating single-cell RNA sequencing (scRNA-seq) data from patients with IPF and a mouse model of repeated lung epithelial injury, we identified persistent activation of hypoxia-inducible factor (HIF) signaling in these aberrant epithelial cells. Using mouse genetic lineage-tracing strategies together with scRNA-seq, we found that these disease-emergent aberrant epithelial cells predominantly arose from airway-derived (
Scgb1a1-CreER
–traced) progenitors and exhibited transcriptional programs of
Hif2a
activation. In mice treated with repetitive intratracheal bleomycin, deletion of
Epas1
(Hif2a) but not
Hif1a
, from airway-derived progenitors, or administration of the small-molecule HIF2 inhibitor PT-2385, using both prevention and rescue approaches, attenuated experimental lung fibrosis, reduced the appearance of aberrant epithelial cells, and promoted alveolar repair. In mouse alveolar organoids, genetic or pharmacologic inhibition of Hif2 promoted alveolar differentiation of airway-derived epithelial progenitors. In addition, treatment of human distal lung organoids with PT-2385 increased colony-forming efficiency, enhanced protein and transcriptional markers of alveolar type 2 epithelial cell maturation, and prevented the emergence of aberrant epithelial cells. Together, these studies showed that HIF2 activation drives the emergence of aberrant epithelial populations after repetitive injury and that targeted HIF2 inhibition may represent an effective therapeutic strategy to promote functional alveolar repair in IPF and other interstitial lung diseases.
Transforming the chemotherapy of human African trypanosomiasis
Authors: Barrett Michael P.
Published: January 2025

Prior to 2019, when the orally available drug fexinidazole began its clinical use, the treatment of human African trypanosomiasis (HAT) was complex and unsatisfactory for many reasons. Two sub-species of the
Trypanosoma brucei
parasite are responsible for HAT, namely the rhodesiense form found in East and Southern Africa and the gambiense form found in Central and West Africa. Diseases caused by both forms manifest in two stages: stage 1 before and stage 2 after central nervous system involvement. Prior to 2019, different drugs were required for each of the two parasite sub-species at each stage. Gambiense disease required pentamidine or nifurtimox-eflornithine combination therapy, while for rhodesiense disease, suramin or melarsoprol was given for stages 1 and 2, respectively. These drugs all suffered complications including protracted administration regimens involving multiple injections with drug-induced adverse effects common. Today, a single drug, fexinidazole, can be given orally in most cases for both diseases at either stage. Another compound, acoziborole, effective in both stages 1 and 2 gambiense disease with a single dosing is anticipated to become available within a few years. Moreover, the recent engagement of multilateral organizations in seeking other compounds that could be used in HAT therapy has also been successful, and a rich vein of new trypanocides has been discovered. Here, the clinical use, modes of action, and resistance risks for drugs used against HAT are discussed.
Platelet factor 4-derived C15 peptide broadly inhibits enteroviruses by disrupting viral attachment
Authors: Lv Shuai , Li Congyi , Pei Zhichao , Hu Ziwei , Du Yining , Zheng Baisong , Zhang Wenyan
Published: January 2025

Platelet factor 4 (PF4) has been shown to regulate several viral infections. Our previous study demonstrated that PF4 inhibits the entry of enterovirus A 71 (EV71) and coxsackievirus A16 (CA16), which cause hand, foot, and mouth disease (HFMD). In this study, we report that PF4 also inhibits the circulating HFMD pathogen coxsackievirus A6 (CA6) and the re-emerging enterovirus D68 (EVD68). A 15-amino acid peptide, C15, at the C-terminus of PF4 confers anti-viral activity against multiple enteroviruses (EVs) besides CA6 and EVD68, including EV71 and CA16. Mechanistic studies revealed that wild-type C15 with a net-positive charge (+3), but not its mutants C15M and C15A (both −1), specifically binds to the VP3 capsid protein of CA6 and EVD68, thereby disrupting their attachment to the host cell surface. In addition, VP3 of EVs contains a conserved domain (residues 155–170) crucial for binding to C15. An aspartic acid residue at position 156 imparts a net-negative charge to this domain, which, when substituted with a neutrally charged amino acid, reduces the binding affinity of VP3 for C15. Additionally, C15 protects neonatal mice from lethal challenge upon a CA6 infection. These results suggest that C15 is a promising broad-spectrum anti-viral candidate against multiple EVs.

IMPORTANCE

EVs, which pose a significant public health threat, can be classified into 15 species, with EV-A, -B, -C, and -D infecting humans and causing a wide range of diseases, from mild illnesses, such as HFMD, to more severe conditions, such as acute flaccid paralysis. The emergence of new and alternative strains highlights the urgent need for broad-spectrum anti-viral agents. In this study, we identified that the C15 of PF4 exhibits potent anti-viral activity against multiple EVs by binding to their surface and blocking their entry into host cells. Furthermore, C15 provides significant protection in vivo. These findings highlight the potential of C15 as a broad-spectrum anti-viral candidate. Our study opens a new avenue for developing treatments to combat the diverse and evolving threats posed by EVs.
Genetic and biochemical characterization of a radical SAM enzyme required for post-translational glutamine methylation of methyl-coenzyme M reductase
Authors: Rodriguez Carrero Roy J. , Lloyd Cody T. , Borkar Janhavi , Nath Shounak , Mirica Liviu M. , Nair Satish , Booker Squire J. , Metcalf William
Published: January 2025

Methyl-coenzyme M reductase (MCR), the key catalyst in the anoxic production and consumption of methane, contains an unusual 2-methylglutamine residue within its active site.
In vitro
data show that a B12-dependent radical SAM (rSAM) enzyme, designated MgmA, is responsible for this post-translational modification (PTM). Here, we show that two different MgmA homologs are able to methylate MCR
in vivo
when expressed in
Methanosarcina acetivorans
, an organism that does not normally possess this PTM.
M. acetivorans
strains expressing MgmA showed small, but significant, reductions in growth rates and yields on methylotrophic substrates. Structural characterization of the Ni(II) form of Gln-methylated
M. acetivorans
MCR revealed no significant differences in the protein fold between the modified and unmodified enzyme; however, the purified enzyme contained the heterodisulfide reaction product, as opposed to the free cofactors found in eight prior
M. acetivorans
MCR structures, suggesting that substrate/product binding is altered in the modified enzyme. Structural characterization of MgmA revealed a fold similar to other B12-dependent rSAMs, with a wide active site cleft capable of binding an McrA peptide in an extended, linear conformation.

IMPORTANCE

Methane plays a key role in the global carbon cycle and is an important driver of climate change. Because MCR is responsible for nearly all biological methane production and most anoxic methane consumption, it plays a major role in setting the atmospheric levels of this important greenhouse gas. Thus, a detailed understanding of this enzyme is critical for the development of methane mitigation strategies.
Limnospira
(Cyanobacteria) chemical fingerprint reveals local molecular adaptation
Authors: Roussel Théotime , Hubas Cédric , Halary Sébastien , Chynel Mathias , Duval Charlotte , Cadoret Jean-Paul , Meziane Tarik , Vernès Léa , Yéprémian Claude , Bernard Cécile , Marie Benjamin
Published: January 2025

Limnospira
can colonize a wide variety of environments (e.g., freshwater, brackish, alkaline, or alkaline-saline water) and develop dominant and even permanent blooms that overshadow and limit the diversity of adjacent phototrophs, especially in alkaline and saline environments. Previous phylogenomic analysis of
Limnospira
allowed us to distinguish two major phylogenetic clades (I and II) but failed to clearly segregate strains according to their respective habitats in terms of salinity or biogeography. In the present work, we attempted to determine whether
Limnospira
displays metabolic signatures specific to its different habitats, particularly brackish and alkaline-saline ecosystems. The impact of accessory gene repertoires on respective chemical adaptations was also determined. In complement of our previous phylogenomic investigation of
Limnospira
(Roussel et al., 2023), we develop a specific analysis of the metabolomic diversity of 93 strains of
Limnospira
, grown under standardized lab culture conditions. Overall, this original work showed distinct chemical fingerprints that were correlated with the respective biogeographic origins of the strains. The molecules that most distinguished the different
Limnospira
geographic groups were sugars, lipids, peptides, photosynthetic pigments, and antioxidants. Interestingly, these molecular enrichments might represent consequent adaptations to conditions of salinity, light, and oxidative stress in their respective sampling environments. Although the genes specifically involved in the production of these components remain unknown, we hypothesized that within extreme environments, such as those colonized by
Limnospira
, a large set of flexible genes could support the production of peculiar metabolite sets providing remarkable adaptations to specific local environmental conditions.

IMPORTANCE

Limnospira
are ubiquitous cyanobacteria with remarkable adaptive strategies allowing them to colonize and dominate a wide range of alkaline-saline environments worldwide. Phylogenomic analysis of
Limnospira
revealed two distinct major phylogenetic clades but failed to clearly segregate strains according to their habitats in terms of salinity or biogeography. We hypothesized that the genes found within this variable portion of the genome of these clades could be involved in the adaptation of
Limnospira
to local environmental conditions. In the present paper, we attempted to determine whether
Limnospira
displayed metabolic signatures specific to its different habitats. We also sought to understand the impact of the accessory gene repertoire on respective chemical adaptations.
Devonian–Permian sedimentation in the Central Yunnan basin, SW Yangtze block (South China): Insights into provenance and paleogeography of Li-rich bauxitic claystone
Authors: Yan Zhen , Fu Changlei , Chen Hui , Aitchison Jonathan C. , Xue Chuandong , Zhang Jiahui , Chen Lei , Wang Denghong , Wang Xiaohu , Zhou Renjie
Published: January 2025

Late Paleozoic sedimentary environments and the associated paleogeography of the SW Yangtze block of South China are critical for understanding the formation of bauxite and clay-type Li deposits, which in turn provide insights into the tectonic evolution of East Asia. However, there is a lack of consensus on the sedimentary environments and provenance of these deposits. Analysis of rock assemblages and sedimentary structures shows that Devonian to Permian sediments in the Central Yunnan basin are dominated by siliciclastic and carbonate rocks that are indicative of deposition in coastal tidal environments. Permian bauxite and bauxitic claystone exhibit variable but elevated Li2O contents ranging from 0.35% to 1.62%, with an average Al2O3 content of 60.46%. The lithium (Li) content in these bauxitic claystones is strongly influenced by sedimentary environments, texture, and postdepositional weathering and leaching. Geochemical data suggest that the sediments are highly mature in composition, with sources primarily from felsic igneous rocks and minor contributions from mafic rocks of an uplifted basement within a passive margin setting that underwent significant recycling and intense weathering. Detrital zircon U-Pb age determinations indicate that Devonian and Carboniferous sediments share a primary source, with ages of ca. 832−808 Ma, and minor input from Paleoproterozoic rocks. In contrast, Lower Permian sediments exhibit age distributions similar to those of Ordovician sediments, with key age peaks at ca. 964 Ma, 812 Ma, 624 Ma, and 546 Ma. Regionally, Middle to Upper Devonian coastal−tidal deposits unconformably interfinger with pre-Devonian and Carboniferous shallow-marine sediments. Additionally, Lower Permian tidal lagoon sediments of the Daoshitou Formation unconformably overlie the Carboniferous deposits. These findings suggest that both lithium and aluminum oxides in the Daoshitou Formation originated primarily from the weathering and recycling of ancient sedimentary and felsic primary rocks, and subsequently accumulated in a tidal lagoon environment within an extensional basin. This basin, located in the southwestern Yangtze block, was associated with the late Paleozoic opening of the Paleo-Tethyan Ocean.
Nasal myiasis: an infrequent cause of sinusitis in a critical care patient
Authors: Giglio Jimenez Andres , Dreyse Jorge , Venegas Juan Carlos , Ferre Andres
Published: January 2025

A patient in his 70s, admitted to the cardiac intensive care unit with cardiogenic shock, unexpectedly presented with nasal myiasis during a workup for persistently elevated inflammatory markers. CT scans revealed sinusitis and bronchial secretions, while bronchoscopy identified mucus with positive pathogen testing. Nasal endoscopy was crucial in diagnosing myiasis, and immediate mechanical removal of larvae was performed. Definitive treatment involved surgical debridement, turbinectomy and sinus cleansing, leading to a successful recovery without complications. This case emphasises the importance of considering nasal myiasis as a rare but potential cause of sinusitis in critically ill patients, even in non-endemic regions. Early diagnosis using appropriate imaging and endoscopic techniques, followed by prompt treatment, is essential for preventing severe complications. Increased awareness among healthcare professionals is vital for the timely recognition and management of this condition in critical care settings.
Spontaneous haemorrhage in subdural hygroma in an Alzheimer’s patient on lecanemab
Authors: Watanabe Memi , Okochi Ryotaro , Tezuka Toshiki , Ito Daisuke
Published: January 2025

We report a female patient in her 70s with mild cognitive impairment due to Alzheimer’s disease (AD) who developed a left temporal lobar haemorrhage after the third dose of lecanemab, accompanied by non-traumatic haemorrhage in a pre-existing subdural hygroma, and was diagnosed with amyloid-related imaging abnormalities with haemorrhage. The patient exhibited mild verbal paraphasia and word recall difficulty but had no other major neurological deficits. There was no additional intracranial abnormality during the course of hospitalisation. This case highlights the importance of considering subdural haemorrhage as a part of the amyloid-related imaging abnormality spectrum in AD patients with subdural hygromas undergoing amyloid-targeted therapies.
Factors affecting the quality of postoperative rehabilitation in children with cochlear implants based on the theory of knowledge, attitude and practice
Authors: Lin Ken , Zhang Yiyun , Chi Wenyue , Li Xia , Ma Xiuli , Su Dong , Du Yuling , Ma Jing , Zhang Tiesong
Published: January 2025

Objectives

This study aimed to examine factors that influence postoperative rehabilitation outcomes in children with cochlear implants, using a knowledge–attitude–practice (KAP) framework.

Design

A total of 683 children with cochlear implants participated in this study. Hearing and speech assessments were conducted through face-to-face and/or telephone interviews, while parents’ or guardians’ KAP were assessed following detailed instructions provided beforehand. Responses were recorded meticulously.

Setting

Data were collected through a convenience sampling method at a children’s hospital.

Participants

Out of 840 questionnaires distributed, 683 completed questionnaires were retained for analysis after excluding responses with missing data.

Results

Parents’ average KAP score was 8.03 (SD = 3.13). Household income and education levels directly influenced KAP scores, while certain child characteristics were significantly associated with higher scores on the Infant–Toddler Meaningful Auditory Integration Scale (IT-MAIS). Children who were outgoing (32.29 points), had used a cochlear implant for more than 3 years (32.78 points), and had surgery funded by state support (32.14 points) demonstrated higher MAIS scores. Factors such as personality, monthly family income, surgery funding and parents' beliefs significantly affected rehabilitation outcomes among children.

Conclusion

Parental knowledge about deafness, trust in cochlear implant procedures and healthcare providers, and parental behaviours during the treatment and rehabilitation process have a direct impact on children’s health outcomes. Enhancing parents’ KAP levels is critical to improve rehabilitation outcomes for children with cochlear implants.
Gastric cancer liver metastases in China: a real-world, multicentre, prospective, observational cohort study protocol
Authors: Lu Tingting , Gao Yunhe , Zhang Gan , Zhang Haiya , Chen Zhida , Liu Yi , Chen Lin , Xi Hongqing
Published: January 2025

Introduction

Gastric cancer liver metastases (GCLM) is a highly heterogeneous disease with a poor prognosis. The multidisciplinary diagnosis and treatment model is applied throughout the entire treatment process. In addition to the previous RECORD study, which was based on the C-GCLM classification system developed by our team, there is a lack of recent data on patient baseline characteristics, clinical treatment and efficacy evaluation. A large-scale prospective observational study is necessary to determine the current situation of GCLM treatment in China. The findings of this study may inform the development of relevant healthcare policies, clinical pathways and treatment guidelines.

Methods and analysis

This is a prospective, non-interventional, observational, multicentre, real-world study designed to monitor the general condition, treatment pattern and prognosis of patients with GCLM. Patients with GCLM were classified into three distinct categories: type I (resectable type), type II (potentially resectable type) and type III (unresectable type). The patients' general information, medical history, imaging results, laboratory tests, surgical and systemic therapy details will be recorded and subjected to analysis. The 2-year overall survival (OS) will be recorded as the primary endpoint. The different therapeutic modalities employed in the treatment of GCLM, including surgery, chemotherapy and immunotherapy, will be recorded as secondary endpoints. Additionally, the effects of these therapies on prognosis, including OS of type I, II and III; R0 resection and disease-free survival of type I; and successful conversion rate and R0 resection rate and event-free survival of type II will be documented.

Ethics and dissemination

This study involving human participants was reviewed and approved by the Ethics Committee of Chinese PLA General Hospital (no. S2023-724-02) and will be conducted in accordance with the guidelines of the Declaration of Helsinki. Study findings will be disseminated through international peer-reviewed journal articles as well as public, academic presentations at national and international conferences.

Trial registration numbers

NCT06493448; ChiCTR2400083955.
Treatment of e-cigarette use among hospitalised adolescents and young adults: a protocol for intervention development and evaluation of preliminary efficacy and implementation outcomes in a randomised controlled trial
Authors: Wooten Shelbie , Catley Delwyn , Miller Melissa K , Wilson Karen , Richter Kimber P , Masonbrink Abbey
Published: January 2025

Introduction

Hospitalisation represents an opportunity to identify and treat e-cigarette use among adolescents and young adults (AYAs). Knowledge on how to provide this care is lacking. We aim to fill this gap by developing an e-cigarette use intervention and evaluating preliminary efficacy and implementation outcomes among hospitalised AYAs.

Methods and analysis

We will enrol 144 hospitalised AYAs (14–21 years) who report past 30-day e-cigarette use and randomise 2:1 to intervention or control arms. We will develop an evidence-based intervention that includes education, motivational interviewing, quit planning and nicotine replacement therapy prescription offered confidentially in person during the hospital stay and 4 weekly phone booster sessions. Control participants will receive brief advice and quit programme resources. We will assess self-reported demographics, e-cigarette use behaviours, nicotine dependence, motivation and confidence to quit at baseline and postintervention. Our primary outcome is self-reported 30-day point prevalence e-cigarette abstinence at the 3-month follow-up with biochemical salivary cotinine confirmation. Our secondary implementation outcomes are feasibility, acceptability and fidelity. We will assess our primary outcome using a generalised linear model assuming an underlying binomial distribution and logit link function. X2(categorical variables) and Wilcoxon rank-sum (continuous variables) tests will be used to assess differences between groups.

Ethics and dissemination

Careful consideration will be given to ethical recruitment and implementation of all elements of the study. Our study protocol and documents will be reviewed and approved by the institutional review board at the affiliated academic institution. Only approved study team members will access participant data, and all data will be managed in accordance with institutional review board and Health Insurance Portability and Accountability Act (HIPAA) requirements. Study results will be disseminated to our public committee, youth research advisory board, to relevant stakeholders and through publication.

Trial registration number

NCT05936099; registered on 30 June 2023. Study recruitment and enrolment began in August 2023 and is ongoing.
First pass effect in patients with large core infarcts undergoing mechanical thrombectomy: subgroup analysis of the prospective international ASSIST registry
Authors: Hoffman Haydn , Miralbes Salvador , Naravetla Bharath , Spiotta Alejandro M , Loehr Christian , Martínez-Galdámez Mario , McTaggart Ryan A , Defreyne Luc , Vega Pedro , Zaidat Osama O , Price Lori Lyn , Liebeskind David S , Möhlenbruch Markus A , Gupta Rishi , Goyal Nitin
Published: January 2025

Background

Studies have described a first pass effect (FPE) where patients with successful recanalization after one pass experience better outcomes. Few studies have evaluated this in patients with large core infarctions.

Objective

To determine whether patients with large core infarcts undergoing mechanical thrombectomy in which first pass reperfusion is achieved experience improved outcomes compared with those who undergo more than one pass.

Methods

The ASSIST Registry, a prospective, global, multicenter registry of patients with anterior circulation large vessel occlusion (LVO) undergoing mechanical thrombectomy was used. Adults with internal carotid artery/M1/M2 occlusions and preprocedural Alberta Stroke Program Early CT Score (ASPECTS) <6 were included. The variable of interest was number of thrombectomy passes (dichotomized to 1 or >1) performed for the target occlusion. The primary outcome was 90-day good functional outcome defined as modified Rankin Scale (mRS) score 0–3.

Results

150 patients with a mean age of 66 years were included. Most patients had ASPECTS of 4 (33%) or 5 (59%). 77 patients (51%) underwent one pass. Compared with patients with one pass, those with more than one pass had significantly lower odds of good functional outcome (OR=0.44, 95% CI 0.21 to 0.93; P=0.03). More than one pass was not significantly associated with 90-day mRS score 0–2 (OR=0.46, 95% CI 0.15 to 1.43; P=0.17) or mortality (OR=2.03, 95% CI 0.81 to 5.08; P=0.13). FPE (one pass eTICI≥2c) and modified FPE (one pass extended thrombolysis in cerebral infarction ≥2b50) were not significantly associated with 90-day mRS 0–3, mortality, or symptomatic intracranial hemorrhage.

Conclusion

This analysis suggests that use of multiple passes is associated with worse outcomes in patients with large core infarcts.
Efficacy and safety of the PHIL embolic agent in the treatment of intracranial dural arteriovenous fistulas: results of the PHIL-dAVF study
Authors: Marnat Gaultier , Barreau Xavier , Januel Anne-Christine , Spelle Laurent , Piotin Michel , Mounayer Charbel , Borota Ljubisa , González Alejandro , Casasco Alfredo , Keston Peter , Lobotesis Kyriakos , Cronqvist Mats , Holtmannspötter Markus , Guimaraens Leopoldo , Boccardi Edoardo , Valvassori Luca , Espinosa de Rueda Mariano , Cognard Christophe
Published: January 2025

Background and Purpose

Embolization is the first-line treatment for dural arteriovenous fistulas (dAVF). The precipitating hydrophobic injectable liquid (PHIL) embolic agent is a non-adhesive copolymer with specific features and endovascular behavior. This study assessed its safety and efficacy in a prospective real-life cohort.

Methods

The PHIL-dAVF study was a prospective single-arm open-label observational multicenter study conducted between October 2017 and November 2019 in 14 European centers. Patients with a single intracranial dAVF intended for PHIL embolization were included. Previously partially treated or multiple dAVFs were excluded. Additional devices and embolic agents were permitted as complementary techniques or second-line strategies. Primary endpoints were functional outcome changes from baseline and complete cure rate at 3–6 months after the last embolization. Safety was assessed by adverse events (AE) incidence.

Results

A total of 67 patients (77 endovascular procedures; 70.1% men, mean age 61±14 years) were included. Most DAVFs were unruptured (71.6%), located in the transverse/sigmoid sinus (53.7%) and Cognard grade III or IV (56.7%). Sixty patients (89.6%) received one single embolization. Additional devices were used in 31.2% of procedures. Complete angiographic cure rate was 86.9% at the 3–6 month DSA follow-up after the last endovascular treatment. At least one AE was recorded in 37.3% of patients during follow-up, of which 52.9% were related to the procedure. The procedural rates of AE and serious AE were 32.5% and 15.6%, respectively. Five AEs were related to PHIL. Transient functional deterioration occurred in three patients (4.5%), all resolved by the last follow-up.

Conclusion

The PHIL-dAVF study provides evidence about the efficacy and safety of PHIL in the treatment of intracranial dAVFs, with outcomes comparable to existing liquid embolic agents reported in the literature.
Interplay of NF-κB and PPAR-γ transcription factors in patients with juvenile systemic lupus erythematosus
Authors: Durmus Sinem , Sahin Sezgin , Adrovic Amra , Barut Kenan , Gelisgen Remise , Uzun Hafize , Kasapcopur Ozgur
Published: January 2025

Objective

Juvenile SLE (jSLE) is an autoimmune disease characterised by the presence of high levels of autoantibodies, predominantly targeting nuclear antigens, resulting in a breakdown of self-tolerance. However, its pathogenesis is multifactorial and poorly understood. The aim of this study was to evaluate the potential of nuclear factor-kappa B (NF-κB) and peroxisome proliferator-activated receptor-gamma (PPAR-γ) as biomarkers for jSLE.

Methods

In this study, serum NF-κB and PPAR-γ levels were determined by immunoassay in 42 patients with jSLE. In addition, 19 juvenile systemic sclerosis (jSSc) and 25 age-matched healthy children were selected as patient control and healthy control, respectively.

Results

Serum NF-κB levels in patients with jSLE demonstrated a positive trend towards elevation compared with the controls with no significant difference (p=0.030). In addition, serum NF-κB levels in patients with jSSc were significantly higher than that of the healthy controls (p=0.005). Serum PPAR-γ levels were tend to be lower in both patients with jSLE and jSSc compared with the controls, with no significant difference. Specifically, NF-κB levels were significantly higher in patients with jSLE with cumulative damage (PedSDI≥1) compared with those without, at p=0.044. Logistic regression showed that PPAR-γ levels lower than 2.42 ng/mL were associated with the development of jSLE (OR 7.59) and lower than 2.16 ng/mL for jSSc (OR 10.90). The combined high levels of NF-κB with low PPAR-γ increased the risk of developing jSSc by 21.33-fold.

Conclusions

The observed trend of elevated NF-κB levels and decreased PPAR-γ levels in our study suggests their potential as biomarkers associated with increased proinflammatory signalling in jSLE and jSSc. However, our findings must be regarded as hypothesis-generating and confirmed in larger datasets. Moreover, their roles in monitoring the course of a disease and guiding therapeutic strategies in juvenile systemic autoimmune diseases need to be clearly investigated. Further extension of these findings may lead to better management and improvement in the outcomes of such patients.
Central nervous system vasculopathy: inherited or acquired? The DADA2 conundrum
Authors: Saravanan Sowmya , Aghoram Rajeswari , Narayan Sunil K , Saibaba Jayaram , Madhan R
Published: January 2025

Young people with stroke require detailed investigation because uncommon causes are more likely. A 19-year-old woman presented with multiple cortical and subcortical infarcts, arterial aneurysms, anaemia and hypertension. Further evaluation identified a systemic vasculopathy secondary to a deficiency of adenosine deaminase 2, a rare treatable monogenic disorder.
Deciphering risk factors for severe postherpetic neuralgia in patients with herpes zoster: an interpretable machine learning approach
Authors: Park Soo Jung , Han Jinseon , Choi Jong Bum , Min Sang Kee , Park Jungchan , Choi Suein
Published: January 2025

Introduction

Postherpetic neuralgia (PHN) is a common complication of herpes zoster (HZ). This study aimed to use a large real-world electronic medical records database to determine the optimal machine learning model for predicting the progression to severe PHN and to identify the associated risk factors.

Methods

We analyzed the electronic medical records of 23,326 patients diagnosed with HZ from January 2010 to June 2020. PHN was defined as pain persisting for ≥90 days post-HZ, based on diagnostic and prescription codes. Five machine learning algorithms were compared with select the optimal predictive model and a subsequent risk factor analysis was conducted.

Results

Of the 23,326 patients reviewed, 8,878 met the eligibility criteria for the HZ cohort. Among these, 801 patients (9.0%) progressed to severe PHN. Among the various machine learning approaches, XGBoost—an approach that combines multiple decision trees to improve predictive accuracy—performed the best in predicting outcomes (F1 score, 0.351; accuracy, 0.900; area under the receiver operating characteristic curve, 0.787). Using this model, we revealed eight major risk factors: older age, female sex, history of shingles and cancer, use of immunosuppressants and antidepressants, intensive initial pain, and the neutrophil-to-lymphocyte ratio. When patients were categorized into low-risk and high-risk groups based on the predictive model, PHN was seven times more likely to occur in the high-risk group (p<0.001).

Conclusions

Leveraging machine learning analysis, this study identifies an optimal model for predicting severe PHN and highlights key associated risk factors. This model will enable the establishment of more proactive treatments for high-risk patients, potentially mitigating the progression to severe PHN.
Efficacy of long-acting local anesthetics versus their mixture with shorter-acting local anesthetics for peripheral nerve blocks guided by ultrasound: a systematic review with meta-analysis of randomized controlled trials
Authors: Pietroski dos Santos Natanael , Silva Vanessa de Paula , Oliveira Guilherme Stéfano da Silva , Musacchio Victor Cardoso , Carvalho Vanessa Henriques
Published: January 2025

Background/importance

Local anesthetic (LA) mixtures are used in peripheral nerve blocks (PNB) to improve onset, though study results remain conflicting.

Objective

This systematic review and meta-analysis compared the efficacy outcomes of long-acting LA to their mixture with shorter-acting LA in ultrasound-guided PNB. The primary outcome was sensory block onset.

Evidence review

We searched WoS, Scopus, MEDLINE, EMBASE, BVS/LILACS, and Cochrane databases from 1998 to 2024 for randomized controlled trials (RCTs). We conducted a random-effects meta-analysis, evaluated the risk of bias (RoB) with RoB 2.0, performed sensitivity analyses, assessed non-reporting bias with DOI plots and Luis Furuya-Kanamori index, and evaluated strength of evidence with Grading of Recommendations Assessment, Development and Evaluations.

Findings

We included 10 RCTs (516 participants). Mixture of LA may have no effect on sensory block onset (mean difference (MD) −1.62 min, 95% CI: −4.04 to 0.81; I2=81.50%, 95% CI: 62.82% to 90.80%; prediction interval (PI)=−7.78 to 4.55; very low certainty) and motor block onset (MD −5.60 min; 95% CI: −14.54 to 3.33, I2=98.89%, 95% CI: 98.50% to 99.18%; PI=−31.90 to 20.69; very low certainty), while it may reduce the duration of sensory block (MD −2.16 hours, 95% CI: −4.16 to −0.17; I2=90.77%, 95% CI: 84.22% to 94.60%; PI=−7.24 to 2.92; very low certainty).

Conclusions

LA mixtures may not affect sensory and motor block onset in ultrasound-guided PNB but could shorten the duration of sensory blockade.
Field surveys of chickpea plant damage and association with biotic and abiotic factors in Saskatchewan during 2021–2023
Authors: Marchesini Victoria A. , Hubbard Michelle , Sharpe Shaun , Schoenau Jeff , Hossain Zakir , Tenuta Mario , Pereira Fernanda Gouvea , Phelps Sherrilyn , Anderson Sarah , Brown Mike
Published: January 2025

A chickpea health issue was first noted in July 2019 in southwest Saskatchewan, Canada. Surveys of commercial chickpea fields were undertaken in 2021, 2022, and 2023 to investigate the potential roles of herbicides, fungicides, fertilizer, seed treatments, inoculants, nutrients, nematodes, drought stress, and chickpea cultivars on severity of plant damage. Fields to which herbicide containing the active ingredient metribuzin had been applied had more severe symptoms compared to fields to which it had not. Seed treatment with Apron Advance (active ingredients thiabendazole, fludioxinil, and metalaxyl) was associated with more severe symptoms than treatment with Vibrance Maxx (sedaxane, fludioxonil, and metalaxyl). No effects of rhizobial inoculation of chickpea seed was observed. Fields in which lentil or canola preceded chickpea had higher severity of aboveground plant damage compared to fields in which chickpea followed barley or durum. No significant correlation was found between severity of plant damage and concentrations of nitrogen (N), phosphorus (P), and chloride in plant tissues. A significant negative correlation ( P < 0.05) was found between potassium (K) concentration and severity, especially in 2023. There was a significant positive correlation ( P < 0.05) between severity of plant damage and the amount of P fertilizer applied. Plant ectoparasitic nematodes Paratylenchus and Helicotylenchus species were detected. Paratylenchus species abundance was very high in some fields. Although no clear diagnosis of the causal agent(s) of plant damage was made, crop rotation, metribuzin herbicide application, seed treatments, plant K concentrations, P fertilization, and co-occurrence of stressors may exacerbate the plant and foliar symptoms observed.
Effect of zirconium oxide nanoparticles on structure, dielectric, and optical properties of PVDF/zirconia-based nanocomposites
Authors: Vidadi Hajiyeva Flora , Ahmad Ramazanov Mahammadali
Published: January 2025

In this work, the structure, dielectric and optical properties of PVDF/zirconia-based polymer nanocomposites were investigated. The morphology and structure of the nanocomposites were analyzed by XRD, SEM, FT-IR, UV and EDS analyses. It was determined that the forbidden gap for the PVDF/1%ZrO2-based nanocomposite is 4.7[Formula: see text]eV, for PVDF/5%ZrO2-4.5[Formula: see text]eV, and for PVDF/10%ZrO2-4.2[Formula: see text]eV. It is shown that the dielectric permittivity of the nanocomposites increases sharply up to 3% of ZrO2 nanoparticles in the polymer and then decreases slightly with an increase in the concentration of nanoparticles. An increase in the permittivity indicates an increase in polarization processes in nanocomposites at a 3% conentration of ZrO2 nanoparticles in the PVDF matrix. It has been established that the dielectric loss tangent at low frequencies starts to decrease, and at high frequencies, it increases. The increase in the dielectric loss tangent at high frequencies is explained by an increase in relaxation processes and energy dissipation in these systems.
THE MULTI-FACETED IDENTITY OF FEMALE ENTREPRENEURS IN THE MOROCCAN DIRECT SELLING BUSINESS
Authors: YAMANI ZAKIA EL
Published: January 2025

This study explores how the identities of female independent direct sellers (IDS) influence brand performance in Morocco’s direct selling industry and highlights the entrepreneurial opportunities offered by this sector. Direct selling has become a vital pathway for women in Morocco to achieve economic empowerment and entrepreneurial growth. Through in-depth, semi-structured interviews with 21 direct sellers in the Moroccan context, this research explores how various facets of IDS identity (personal, social, professional, entrepreneurial and self-projection) contribute to brand performance. The findings reveal that IDS are integral in co-creating the brand’s identity, and that their personal and professional identities significantly affect brand success. However, challenges such as limited educational backgrounds and inconsistent representation can hinder effective brand communication and trust-building with customers. Despite these challenges, IDS have developed critical entrepreneurial skills, including interpersonal communication, negotiation and self-confidence, which are essential for their success. The study also highlights that although IDS have made strides in personal development, their entrepreneurial vision and long-term self-projection remain underdeveloped. This research underscores the importance of aligning IDS identities with brand strategies and provides actionable insights for brand managers to enhance brand performance through targeted support and identity-driven training for female IDS.
Looking at Data: Crossing Disciplinary Boundaries in Image Research
Authors: O'Reilly Colleen
Published: January 2025

Black hole images provide new opportunities for interdisciplinary inquiry into the relationship between pictures and knowledge.
A Novel Multi-hop Query Answering System Based on a Large Knowledge Graph and Distributed Computing
Authors: Phan Hong Trung , Do Phuc
Published: January 2025

An automated query answering system
(QAS)
is a very useful application in organizations. Therefore, there is a lot of research to build, develop and improve it. In this paper, we present a method to build a multi-hop query answering system
(MQAS)
based on a large knowledge graph
(KG)
,
Bidirectional Encoder Representations from Transformers (BERT)
, and the indexing structure
K-Dimensional Tree (KD-Tree)
. The large KG provides knowledge for MQAS. BERT is used to transform questions into vectors. KD-Tree helps find the right answers quickly. On the other hand, we also propose a solution for distributed indexing of large vector spaces by building a distributed indexing structure called
Distributed KD-Tree (DKD-Tree)
. In addition, we also present experiments and evaluation results to demonstrate the effectiveness of our solution.
CFTR as a therapeutic target for severe lung infection
Authors: Hook Jaime L. , Kuebler Wolfgang M.
Published: January 2025

Lung infection is one of the leading causes of morbidity and mortality worldwide. Even with appropriate antibiotic and antiviral treatment, mortality in hospitalized patients often exceeds 10%, highlighting the need for the development of new therapeutic strategies. Of late, cystic fibrosis transmembrane conductance regulator (CFTR) is—in addition to its well-established roles in the lung airway and extrapulmonary organs—increasingly recognized as a key regulator of alveolar homeostasis and defense. In the alveolar epithelium, CFTR mediates alveolar fluid secretion and liquid homeostasis; in the microvascular endothelium, CFTR maintains vascular barrier function. CFTR also contributes to alveolar immunity. Yet, in lung infection, diverse molecular mechanisms reduce CFTR abundance and otherwise impair its function, promoting alveolar inflammation, edema, and cell death. Preservation or restoration of CFTR function by CFTR modulator drugs thus presents a promising avenue to combat lung infection in a pathogen-independent manner.
Enhanced Structural and Chemical Stability of New Inorganic Halide Perovskite Solar Cell Structures via Nickel Doping and Silicon Dioxide Encapsulation
Authors: Seol Myeong Jin , Hwang Seunghwan , Kim Soo Young
Published: January 2025

Conventional perovskite solar cells (PSCs) have adapted the organic–inorganic hybrid perovskites as the absorption layer due to low processing temperature, superior optoelectronic properties, and simple solution processing. However, hybrid perovskites are more vulnerable to heat compared to inorganic perovskites. For long‐term operation, heat stability is essential for the commercialization of PSCs based on hybrid perovskite. In this study, we synthesized inorganic halide perovskite CsPbBr3 with SiO2 shell to ensure stability against heat. However, due to the lattice mismatch between the SiO2 shell and CsPbBr3, we introduced nickel doping using nickel acetate to reduce this mismatch. The nickel‐doped CsPbBr3–SiO2 core–shell perovskite exhibited superior thermal stability, maintaining the 92% of its initial performance after 12 h at 353 K.
Back to School After COVID‐19: The Views of Psychological Counselors at Schools About the Effects of the Pandemic on Students
Authors: Bozbayindir Fatih , Akalın Tuğçe Çetiner
Published: January 2025

This study aimed to determine the effects of the pandemic on students returning to school after COVID‐19 from the perspective of school psychological counsellors. The research was designed as a qualitative study using a phenomenological design. The study group of the research consists of 11 psychological counselors at schools working in public schools in Türkiye, who were determined by maximum diversity and criterion sampling from purposeful sampling methods at the end of the 2021–2022 academic year. The data were collected using a semistructured interview form created by the researchers. MAXQDA 2020 program was used to analyze the data. As a result of the analysis, themes were obtained regarding the effects of the pandemic on students. These themes include the changes in students’ emotions, thoughts, behaviors, and academic dimensions, the topics that school psychological counsellors included in their programs after the pandemic, and the topics they suggested to be included in the program in the following years. The results of the study reveal that after the pandemic, there is a need for practices on emotion regulation, conscious use of technology, development of social skills, reducing bullying, improving psychological resilience, and increasing school motivation and academic success. It is thought that the research may contribute to the development of practices that can reduce the harmful effects of COVID‐19 on students and positively affect students’ mental health at school.
Supplementary Data 1 from CD33–CD123 IF-THEN Gating Reduces Toxicity while Enhancing the Specificity and Memory Phenotype of AML-Targeting CAR-T Cells
Authors: Jambon Samy , Sun Jianping , Barman Shawn , Muthugounder Sakunthala , Bito Xue Rachel , Shadfar Armita , Kovach Alexandra E. , Wood Brent L. , Thoppey Manoharan Varsha , Morrissy A. Sorana , Bhojwani Deepa , Wayne Alan S. , Pulsipher Michael A. , Kim Yong-Mi , Asgharzadeh Shahab , Parekh Chintan , Moghimi Babak
Published: January 2025

Single cell data of the clusters, gene expresion, biomarker and called annotations
Supplementary Table 2 from Bispecific Antibodies as Bridging to BCMA CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma
Authors: Fandrei David , Seiffert Sabine , Rade Michael , Rieprecht Susanne , Gagelmann Nico , Born Patrick , Wiemers Thomas , Weidner Heike , Kreuz Markus , Schassberger Tamara , Koßmann Jannik , Mangold Marlene , Fürst Daniel , Fischer Luise , Baber Ronny , Heyn Simone , Wang Song Yau , Bach Enrica , Hoffmann Sandra , Metzeler Klaus H. , Herling Marco , Jentzsch Madlen , Franke Georg-Nikolaus , Köhl Ulrike , Friedrich Maik , Boldt Andreas , Reiche Kristin , Platzbecker Uwe , Vucinic Vladan , Merz Maximilian
Published: January 2025

Proportion of CAR-positive cells in T cell cultures from day 7 after CAR-T infusion used for the in vitro cytotoxicity assay.
Data from Bispecific Antibodies as Bridging to BCMA CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma
Authors: Fandrei David , Seiffert Sabine , Rade Michael , Rieprecht Susanne , Gagelmann Nico , Born Patrick , Wiemers Thomas , Weidner Heike , Kreuz Markus , Schassberger Tamara , Koßmann Jannik , Mangold Marlene , Fürst Daniel , Fischer Luise , Baber Ronny , Heyn Simone , Wang Song Yau , Bach Enrica , Hoffmann Sandra , Metzeler Klaus H. , Herling Marco , Jentzsch Madlen , Franke Georg-Nikolaus , Köhl Ulrike , Friedrich Maik , Boldt Andreas , Reiche Kristin , Platzbecker Uwe , Vucinic Vladan , Merz Maximilian
Published: January 2025

Abstract
Establishing a strategy for sequencing of T cell–redirecting therapies for relapsed/refractory multiple myeloma (RRMM) is a pressing clinical need. We longitudinally tracked the clinical and immunologic impact of bispecific T cell–engaging antibodies (BsAb) as bridging therapy (BT) to subsequent B-cell maturation antigen–directed chimeric antigen receptor T (CAR-T) cell therapies in 52 patients with RRMM. BsAbs were a potent and safe option for BT, achieving the highest overall response rate (100%) to BT compared with chemotherapy, anti-CD38, or anti-SLAMF7 antibody–based regimens (46%). We observed early CD4+CAR+ and delayed CD8+CAR+ T-cell expansion in patients receiving BsAbs as BT. In vitro cytotoxicity of CAR-T cells was comparable among BT options. Single-cell analyses revealed increased clonality in the CD4+ and CD8+ T-cell compartments in patients with previous exposure to BsAbs at leukapheresis and on day 30 after CAR-T cell infusion. This study demonstrates the feasibility and efficacy of BT with BsAbs for CAR-T cell therapy in RRMM.

Significance: CAR-T cell therapy and BsAbs have revolutionized treatment of triple-class refractory multiple myeloma; however, optimal sequencing is unknown. We demonstrate that BT with BsAb before B-cell maturation antigen–directed CAR-T cell therapy is safe and effective, which might have implications for other hematologic malignancies as well.

See related commentary by Bal and Costa, p. 10