bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attention-deficit/hyperactivity disorder symptoms and subsequent cardiometabolic disorders in adults: investigating underlying mechanisms using a longitudinal twin study
Authors: Dobrosavljevic Maja , Kuja-Halkola Ralf , Li Lin , Chang Zheng , Larsson Henrik , Du Rietz Ebba 
Published: November 2023

Abstract
Background
Emerging research suggests that attention-deficit/hyperactivity disorder (ADHD) increases the risk for cardiovascular (CVDs) and metabolic disorders (i.e., cardiometabolic disorders) in adulthood. Yet, available studies are scarce and have mainly been focused on individuals receiving clinical ADHD diagnoses. We aimed to investigate the prospective associations of ADHD symptoms in young and mid-adulthood with subsequent cardiometabolic disorders and the underlying mechanisms.

Methods
We studied 10,394 twins from the Swedish Twin Registry (STR), born between 1958 and 1985 without previous medical history of cardiometabolic disorders. They provided self-assessment of ADHD symptoms (score range 0–36) via a validated, DSM-IV-based scale in a web-based questionnaire/telephone interview within the Study of Twin Adults: Genes and Environment (STAGE), in 2005–2006 (aged 19–47 years), and were followed until the end of 2018 (33–59 years) to identify incident clinical diagnoses/medication prescriptions for cardiometabolic disorders acquired from Swedish national registers. We used Cox regression models to investigate the associations between ADHD symptoms score and cardiometabolic outcomes, with and without adjustment for relevant covariates, and a co-twin control design to study familial confounding.

Results
A one-unit increase in the level of ADHD symptoms was associated with a 2% increase in the rate of CVDs (hazard ratio [HR] = 1.02, 95% confidence interval 1.01–1.04) and a 3% increase in the rate of metabolic disorders (HR = 1.03, 1.02–1.05), after adjusting for birth year and sex. The associations were no longer significant after adjusting for educational attainment, lifestyle factors, and comorbid psychiatric disorders. The associations remained significant after adjusting for familial factors shared by dizygotic twin pairs but became nonsignificant after adjusting for factors shared by monozygotic twin pairs. However, the strength of the associations attenuated significantly in monozygotic twins compared to dizygotic twins for CVDs only, suggesting genetic confounding.

Conclusions
ADHD symptom score is associated with a higher risk for cardiometabolic disorders, which may be explained by lower educational attainment, adverse lifestyle factors, and psychiatric comorbidities. Moreover, the associations appear to be partly confounded by shared genetic factors, especially for CVDs. Further research is needed to investigate the identified associations at the level of individual cardiometabolic disorders and to follow-up participants until a more advanced older age.
P2X7 receptor activation leads to NLRP3-independent IL-1β release by human macrophages
Authors: Bockstiegel Judith , Engelhardt Jonas , Weindl Günther 
Published: November 2023

Abstract
Background
The purinergic receptor P2X7 plays a crucial role in infection, inflammation, and cell death. It is thought that P2X7 receptor stimulation triggers processing and release of the pro-inflammatory cytokine interleukin (IL)-1β by activation of the NLRP3 inflammasome; however, the underlying mechanisms remain poorly understood.

Methods
Modulation of IL-1β secretion was studied in THP-1 macrophages. Adenosine 5’-triphosphate (ATP), BzATP, nigericin and pharmacological inhibitors of P2X receptors, inflammatory caspases and the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome were used to characterize signaling.

Results
In primed macrophages, IL-1β release was increased after P2X7 receptor activation by ATP and 2,3-O-(4-benzoylbenzoyl)-ATP (BzATP). Pharmacological inhibition or genetic knockout of NLRP3 does not completely inhibit IL-1β release in TLR2/1-primed macrophages. Increase in extracellular K+ as well as inhibition of caspase-1 or serine proteases maintained IL-1β release in macrophages stimulated with P2X7 receptor agonists at 50%.

Conclusions
Our findings suggest a previously unrecognized mechanism of P2X7 receptor mediated IL-1β release and highlight the existence of an NLRP3-independent pathway in human macrophages.
Improving the therapeutic efficacy of oncolytic viruses for cancer: targeting macrophages
Authors: Shen Zhen , Liu Xiyu , Fan Guixiang , Na Jintong , Liu Qiaoqiao , Lin Faquan , Zhang Zhikun , Zhong Liping 
Published: November 2023

AbstractOncolytic viruses (OVs) for cancer treatment are in a rapid stage of development, and the direct tumor lysis and activation of a comprehensive host immune response are irreplaceable advantages of cancer immunotherapy. However, excessive antiviral immune responses also restrict the spread of OVs in vivo and the infection of tumor cells. Macrophages are functionally diverse innate immune cells that phagocytose tumor cells and present antigens to activate the immune response, while also limiting the delivery of OVs to tumors. Studies have shown that the functional propensity of macrophages between OVs and tumor cells affects the overall therapeutic effect of oncolytic virotherapy. How to effectively avoid the restrictive effect of macrophages on OVs and reshape the function of tumor-associated macrophages in oncolytic virotherapy is an important challenge we are now facing. Here, we review and summarize the complex dual role of macrophages in oncolytic virotherapy, highlighting how the functional characteristics of macrophage plasticity can be utilized to cooperate with OVs to enhance anti-tumor effects, as well as highlighting the importance of designing and optimizing delivery modalities for OVs in the future.
Talniflumate abrogates mucin immune suppressive barrier improving efficacy of gemcitabine and nab-paclitaxel treatment in pancreatic cancer
Authors: Agostini Antonio , Guerriero Ilaria , Piro Geny , Quero Giuseppe , Roberto Luca , Esposito Annachiara , Caggiano Alessia , Priori Lorenzo , Scaglione Giulia , De Sanctis Francesco , Sistigu Antonella , Musella Martina , Larghi Alberto , Rizzatti Gianenrico , Lucchetti Donatella , Alfieri Sergio , Sgambato Alessandro , Bria Emilio , Bizzozero Laura , Arena Sabrina , Ugel Stefano , Corbo Vincenzo , Tortora Giampaolo , Carbone Carmine 
Published: November 2023

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. This is due to its aggressive course, late diagnosis and its intrinsic drugs resistance. The complexity of the tumor, in terms of cell components and heterogeneity, has led to the approval of few therapies with limited efficacy. The study of the early stages of carcinogenesis provides the opportunity for the identification of actionable pathways that underpin therapeutic resistance.

Methods
We analyzed 43 Intraductal papillary mucinous neoplasms (IPMN) (12 Low-grade and 31 High-grade) by Spatial Transcriptomics. Mouse and human pancreatic cancer organoids and T cells interaction platforms were established to test the role of mucins expression on T cells activity. Syngeneic mouse model of PDAC was used to explore the impact of mucins downregulation on standard therapy efficacy.

Results
Spatial transcriptomics showed that mucin O-glycosylation pathway is increased in the progression from low-grade to high-grade IPMN. We identified GCNT3, a master regulator of mucins expression, as an actionable target of this pathway by talniflumate. We showed that talniflumate impaired mucins expression increasing T cell activation and recognition using both mouse and human organoid interaction platforms. In vivo experiments showed that talniflumate was able to increase the efficacy of the chemotherapy by boosting immune infiltration.

Conclusions
Finally, we demonstrated that combination of talniflumate, an anti-inflammatory drug, with chemotherapy effectively improves anti-tumor effect in PDAC.
Optimizing percutaneous vertebroplasty: extra-facet puncture for osteoporotic vertebral compression fractures
Authors: Zheng Huo-Liang , Li Bo , Jiang Qin-Yu , Jiang Lei-Sheng , Zheng Xin-Feng , Jiang Sheng-Dan 
Published: November 2023

Abstract
Purpose
To assess the safety and efficacy of the extra-facet puncture technique applied in unilateral percutaneous vertebroplasty (PVP) for treating osteoporotic vertebral compression fractures.

Methods
Demographics (age, gender, body mass index and underlying diseases) were recorded for analyzing. Visual analog scale (VAS) and Oswestry Disability Index (ODI) scores as well as their corresponding minimal clinically important difference (MCID) were used to evaluate clinical outcomes. The segmental kyphotic angle, the vertebral compression ratio and bone cement distribution pattern were evaluated by the plain radiographs. The facet joint violation (FJV) was defined by the postoperative computed tomography scan. Binary logistic regression analysis was performed to investigate relationships between multiple risk factors and residual back pain.

Results
VAS and ODI scores in both traditional puncture group and extra-facet puncture group were significantly decreased after PVP surgery (p < 0.05). However, no significant difference was observed between the two groups according to VAS and ODI scores. The proportion of patients achieving MCID of VAS and ODI scores was higher in extra-facet puncture group as compared to traditional puncture group within a month (p < 0.05). Finally, multivariate logistic regression analysis showed that FJV (odds ratio 16.38, p < 0.001) and unilateral bone cement distribution (OR 5.576, p = 0.020) were significant predictors of residual back pain after PVP surgery.

Conclusions
Extra-facet puncture percutaneous vertebroplasty can decrease the risk of FJV and it also has the advantage of more satisfied bone cement distribution.
CSPG4 CAR-redirected Cytokine Induced Killer lymphocytes (CIK) as effective cellular immunotherapy for HLA class I defective melanoma
Authors: Giraudo Lidia , Cattaneo Giulia , Gammaitoni Loretta , Iaia Ilenia , Donini Chiara , Massa Annamaria , Centomo Maria Laura , Basiricò Marco , Vigna Elisa , Pisacane Alberto , Picciotto Franco , Berrino Enrico , Marchiò Caterina , Merlini Alessandra , Paruzzo Luca , Poletto Stefano , Caravelli Daniela , Biolato Andrea Michela , Bortolot Valentina , Landoni Elisa , Ventin Marco , Ferrone Cristina R. , Aglietta Massimo , Dotti Gianpietro , Leuci Valeria , Carnevale-Schianca Fabrizio , Sangiolo Dario 
Published: November 2023

Abstract
Background
Even acknowledging the game-changing results achieved in the treatment of metastatic melanoma with the use of immune checkpoint inhibitors (ICI), a large proportion of patients (40–60%) still fail to respond or relapse due to the development of resistance. Alterations in the expression of Human Leukocyte Antigen class I (HLA-I) molecules are considered to play a major role in clinical resistance to ICI. Cellular immunotherapy with HLA-independent CAR-redirected lymphocytes is a promising alternative in this challenging setting and dedicated translational models are needed.

Methods
In this study, we propose an HLA-independent therapeutic strategy with Cytokine Induced Killer lymphocytes (CIK) genetically engineered with a Chimeric Antigen Receptor (CAR) targeting the tumor antigen CSPG4 as effector mechanism. We investigated the preclinical antitumor activity of CSPG4-CAR.CIK in vitro and in a xenograft murine model focusing on patient-derived melanoma cell lines (Mel) with defective expression of HLA-I molecules.

Results
We successfully generated CSPG4-CAR.CIK from patients with metastatic melanoma and reported their intense activity in vitro against a panel of CSPG4-expressing patient-derived Mel. The melanoma killing activity was intense, even at very low effector to target ratios, and not influenced by the expression level (high, low, defective) of HLA-I molecules on target cells. Furthermore, CAR.CIK conditioned medium was capable of upregulating the expression of HLA-I molecules on melanoma cells. A comparable immunomodulatory effect was replicated by treatment of Mel cells with exogenous IFN-γ and IFN-α. The antimelanoma activity of CSPG4-CAR.CIK was successfully confirmed in vivo, obtaining a significant tumor growth inhibition of an HLA-defective Mel xenograft in immunodeficient mice.

Conclusions
In this study we reported the intense preclinical activity of CSPG4-CAR.CIK against melanoma, including those with low or defective HLA-I expression. Our findings support CSPG4 as a valuable CAR target in melanoma and provide translational rationale for clinical studies exploring CAR-CIK cellular immunotherapies within the challenging setting of patients not responsive or relapsing to immune checkpoint inhibitors.
Effects of SARS-CoV-2 infection on embryological outcomes in assisted reproductive technology during the Omicron epidemic
Authors: Mao Yuling , Yao Yachao , Du Hongzi , Wang Zheng , Zhou Xueliang , Zeng Ming , Wang Chunyan , Liu Hanyan , Luo Yang , Hong Honghai , Liu Jianqiao , Li Lei 
Published: November 2023

Abstract
Background
The influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on assisted reproductive technology (ART) has received increasing attention. It has been reported that the SARS-CoV-2 RiboNucleic Acid (RNA) cannot be detected in follicular fluid and granulosa cells. However, the detection rate of SARS-CoV-2 RNA in immature oocytes and blastocysts has still unknown. Moreover, the effect of SARS-CoV-2 infection on embryological outcomes in ART during the Omicron epidemic is limited.

Methods
A prospective study was performed to explore the detection rate of viral RNA in biological specimens from patients who tested positive for SARS-CoV-2 RNA and the effects of SARS-CoV-2 infection on embryological outcomes. A total of 211 patients underwent transvaginal oocyte retrieval at the Third Affiliated Hospital of Guangzhou Medical University between December 13, 2022 and December 30, 2022. Prior to transvaginal oocyte retrieval, 61 individuals tested positive for SARS-CoV-2 RNA within 24 h. Follicular fluid was preserved during oocyte retrieval. Granular cells were collected after degranulation (Intracytoplasmic sperm injection only). Immature oocytes were collected at the end of the ICSI. Unavailable blastocysts were collected on day 6 (D6). The TIANLONG SARS-CoV-2 RT-PCR-Kit was used to detect SARS-CoV-2 RNA in all samples. The COVID-19 and Non COVID-19 groups were contrasted in the following areas: fertilization rate, 2PN rate, Day 3 (D3) available embryos rate, D3 good-quality embryos rate, blastocyst formation rate, good-quality blastocyst formation rate.

Results
All samples were negative except for an immature oocytes sample that was positive for SARS-CoV-2 viral RNA with a detection rate of 6.67%. Whether in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), the rate of fertilization, 2PN, D3 available embryos, D3 good-quality embryos, blastocyst formation, good-quality blastocyst formation was not significantly negative different between the COVID-19 and the Non COVID-19 groups. Our findings were validated by an overview of the embryological outcome from the cycles before SARS- Cov-2 infection from the same patient.

Conclusions
Except for immature oocytes, none of the follicular fluid, granulosa cells, or blastocysts samples contained viral RNA. In addition, SARS-CoV-2 infection had no detrimental effects on the embryological outcomes of ART.
Erythropoietic protoporphyria: case reports for clinical and therapeutic hints
Authors: Tumminelli Cristina , Burlo Francesca , Pastore Serena , Severini Giovanni Maria , Berti Irene , Marchini Stefano , Zanon Davide , De Martino Eleonora , Tommasini Alberto 
Published: November 2023

Abstract
Background
Erythropoietic protoporphyria is a rare disorder which represents an important health problem in children, causing painful photosensitivity. Little is known on the correlation between genetic profile and clinical manifestations. The standard of care for Erythropoietic protoporphyria is based on avoiding sun and using sun protections, but recent literature has suggested that cimetidine may have a role in improving sun sensitivity. Herein we report our case series describing the successful use of cimetidine and analyzing potential phenotype-genotype correlations.

Case presentation
This case series describes five patients presented to our Rheumatology Service complaining sun sensitivity. Blood exams and genetic analysis were consistent with the diagnosis of erythropoietic protoporphyria. Four of 5 patients received cimetidine in addition to standard therapies and the effect of treatment was evaluated by Erythropoietic Protoporphyria - Quality of Life questionnaire.

Conclusions
Erythropoietic protoporphyria usually manifests in early childhood after a short sun exposure. Skin manifestations are the main reason for investigations, although sometimes they can be more subtle, leading to a significant diagnostic delay. Skin diseases in children can have profound effects on their family and social relationships. A treatment with cimetidine appears to be an excellent therapeutic option in children with Erythropoietic protoporphyria.
Effect of wearing peripheral focus-out glasses on emmetropization in Chinese children aged 6–8 years: study protocol for a 2-year randomized controlled intervention trial
Authors: Shen Li , He Wennan , Yang Weiming , Yan Weili , Yang Chenhao 
Published: November 2023

Abstract
Background
Myopia is one of the most common eye diseases causing visual impairment and blindness, and the high prevalence in adolescents remains a major public health concern. Based on clinical studies using optical defocus to regulate ocular growth and refractive changes through visual feedback, we hypothesize that early wearing of peripheral myopic defocusing spectacles in children with high risk of myopia may slow the process of emmetropization and even prevent the onset of myopia by inducing more peripheral myopic defocus. The aim of this study is to investigate whether the wearing of peripheral focus-out glasses can be effective in delaying emmetropization in non-myopic children aged 6–8 years.

Methods
The study is a 2-year randomized controlled trial. A total of 160 subjects will be randomized into the experimental group or the control group. The experimental group will be fitted with direct emmetropia with focus-out glasses (DEFOG) to guide the emmetropization process. The control group will not receive any treatment and will serve as a blank control group. The primary aim is to determine whether non-myopic children wearing DEFOG lenses are superior to those who do not receive any intervention on the progression of cycloplegic objective refraction over 2 years.

Discussion
This is the first randomized controlled trial aiming at myopic prevention by non-invasive intervention in non-myopic children. This study aims to initially investigate whether wearing peripheral focus-out glasses can effectively delay the process of emmetropization in children aged 6–8 years with high risk of myopia, which might give potential clues for further exploration on early prevention of myopia.

Trial registration
ClinicalTrials.gov NCT05689567. Registered on 10 January 2023.
Impact of carbonization conditions and adsorbate nature on the performance of activated carbon in water treatment
Authors: Karume Ibrahim , Bbumba Simon , Tewolde Simon , Mukasa Is’harq Z. T. , Ntale Muhammad 
Published: November 2023

AbstractThe physical and chemical structure of activated carbon (AC) varies with the carbonization temperature, activation process and time. The texture and toughness of the starting raw material also determine the morphology of AC produced. The Brunauer-Emmet-Teller surface area (SBET) is small for AC produced at low temperatures but increases from 500 to 700 °C, and generally drops in activated carbons synthesized > 700 °C. Mild chemical activators and low activator concentrations tend to generate AC with high SBET compared to strong and concentrated oxidizing chemicals, acids and bases. Activated carbon from soft starting materials such as cereals and mushrooms have larger SBET approximately twice that of tough materials such as stem berks, shells and bones. The residual functional groups observed in AC vary widely with the starting material and tend to reduce under extreme carbonization temperatures and the use of highly concentrated chemical activators. Further, the adsorption capacity of AC shows dependency on the size of the adsorbate where large organic molecules such as methylene blue are highly adsorbed compared to relatively small adsorbates such as phenol and metal ions. Adsorption also varies with adsorbate concentration, temperature and other matrix parameters.
Understanding factors associated with the trajectory of subjective cognitive complaints in groups with similar objective cognitive trajectories
Authors: Cacciamani Federica , Bercu Ariane , Bouteloup Vincent , Grasset Leslie , Planche Vincent , Chêne Geneviève , Dufouil Carole ,   for the MEMENTO Cohort Study Group
Published: November 2023

Abstract
Background
Cognitive complaints are often regarded as an early sign of Alzheimer’s disease (AD) but may also occur in several other conditions and contexts. This study examines the correlates of cognitive complaint trajectories over a 5-year period in individuals who shared similar objective cognitive trajectories.

Methods
We analyzed a subsample (n = 1748) of the MEMENTO cohort, consisting of individuals with subjective cognitive decline or mild cognitive impairment at baseline. Participants were stratified based on their latent MMSE trajectory over a 5-year period: “high and increasing,” “subtle decline,” and “steep decline.” Within each of the three strata, we used a latent-class longitudinal approach to identify distinct trajectories of cognitive complaints. We then used multiple logistic regressions to examine the association between these complaint trajectories and several factors, including AD biomarkers (blood pTau/Aβ42 ratio, cortical thickness, APOE genotype), anxiety, depression, social relationships, a comorbidity-polypharmacy score, and demographic characteristics.

Results
Among participants with high and increasing MMSE scores, greater baseline comorbidity-polypharmacy scores (odds ratio (OR) = 1.30, adjusted p = 0.03) were associated with higher odds of moderate and increasing cognitive complaints (as opposed to mild and decreasing complaints). Baseline depression and social relationships also showed significant associations with the complaint pattern but did not survive correction for multiple comparisons. Among participants with subtle decline in MMSE scores, greater baseline depression (OR = 1.76, adjusted p = 0.02) was associated with higher odds of moderate and increasing cognitive complaints (versus mild and decreasing). Similarly, baseline comorbidity-polypharmacy scores and pTau/Aβ42 ratio exhibited significant associations, but they did not survive correction. Among participants with a steep decline in MMSE scores, greater baseline comorbidity-polypharmacy scores increased the odds of moderate complaints (versus mild, OR = 1.38, unadjusted p = 0.03, adjusted p = 0.32), but this effect did not survive correction for multiple comparisons.

Conclusions
Despite similar objective cognitive trajectory, there is heterogeneity in the subjective perception of these cognitive changes. This perception was explained by both AD-related and, more robustly, non-AD-related factors. These findings deepen our understanding of the multifaceted nature of subjective cognitive complaints in individuals at risk for dementia and underscore the importance of considering a range of factors when interpreting cognitive complaints.