bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of the transcutaneous electrostimulation in treatment dysfunctions of the TMJ associated with occlusion distortions
Authors: Khachatryan Zhanna , Hambartsoumian Tsovinar , Tatintsyan Lyudmila , Burnazyan Seda , Hakobyan Gagik
Published: November 2023

Background

The study evaluation of the effectiveness the method of electrostimulation in treatment TMJ associated with occlusion disorders with the use of a patches by the company “Aganyan’’.

Methods

The study included 54 patients with temporomandibular dysfunction syndrome who had previously undergone endodontic dental treatment. In patients temporomandibular disorders (TMD) determined on the basis of Diagnostic criteria for temporomandibular disorders(DC/TMD).All patients had occlusion disorders due to errors after dental filling restoration. To diagnose the TMJ, a CT scan was used. The complex therapy also included therapy and with the use of a patches by the company “Aganyan’’. The wearable patch includes a flexible substrate, a binder an adhesive layer, with an electrode foil attached to it. Patients applied one patch behind each TMJ. The patches were applied for eight hours every third day for three months. All the patients were given full-fledged endodontic treatment and restoration of the crown part, taking into account anatomical features.

Results

The dynamics of the complex treatment of patients diagnosed with TMJ dysfunction syndrome showed that after treatment, the clinical symptoms gradually decreased and disappeared at the end of treatment. CT scan a year after treatment showed a normal ratio of TMJ elements. Сomplex treatment was effective in 87% of patients, after 3–5 months gradually decreased pain, noise in the joints, restriction of opening and closing of the mouth disappeared. Patients recovered their chewing functions, psycho-emotional state.

Conclusion

The results of the studies revealed a positive effects for the complex treatment dysfunctions syndrome TMJ the using the patches by the company “Aganyan” through electrical stimulation with low intensity.
Persea americana extract protects intestinal tissue from Eimeria papillata-induced murine Infection
Authors: Alajmi Fatemah , Al-Otaibi Tahani , Al-Quraishy Saleh , Al-Shaebi Esam M. , Al-Hoshani Nawal , Dkhil Mohamed A. , Abdel-Gaber Rewaida
Published: November 2023

Coccidiosis is the most prevalent disease-causing widespread economic loss among farm and domestic animals. Currently, several drugs are available for the control of this disease but resistance has been confirmed for all of them. There is an urgent need, therefore, for the identification of new sources as alternative treatments to control coccidiosis. The present work aimed to study the effect of thePersea americanaextract (PAE) as an anti-coccidial, anti-oxidant, and anti-apoptotic modulator during murine intestinalEimeria papillatainfection. A total of 25 male mice were divided into five groups, as follows:Group1: Non-infected-non-treated (negative control),Group2: Non-infected-treated group with PAE (500 mg/kg b.w).Group3: Infected-non-treated (positive control),Group4: Infected-treated group with PAE (500 mg/kg b.w.), andGroup5: Infected-treated group with Amprolium (120 mg/kg b.w.). Groups (3–5) were orally inoculated with 1 × 103sporulatedE. papillataoocysts. After 60 min of infection, groups (4 and 5) were treated for 5 consecutive days with the recommended doses of PAE and amprolium. The fact that PAE has an anti-coccidial efficacy against intestinalE. papillatainfection in mice has been clarified by the reduction of fecal oocyst output on the 5thday post-infection by about 85.41%. Moreover, there is a significant reduction in the size of each parasite stage in the jejunal tissues of the infected-treated group with PAE. PAE counteracted theE. papillata-induced loss of glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (TCA).E. papillatainfection also induced an increase in the apoptotic cells expressed by caspase-3 which modulated after PAE treatment. Moreover, the mRNA expression of the goblet cell response gene, mucin (MUC2), was upregulated from 0.50 to 1.20-fold after treatment with PAE. Based on our results, PAE is a promising medicinal plant with anti-coccidial, anti-oxidant, and anti-apoptotic activities and could be used as a food additive.
RETRACTED ARTICLE: A novel necroptosis signature for predicting survival in lung adenocarcinoma
Authors: Zang Kui , Wang Min , Zhu Xingxing , Yao Bin , Huang Ying
Published: November 2023

Background

To explore the necroptosis-related genes (NRGs) signature and its
predictive values in lung adenocarcinoma (LUAD).

Methods

The training cohort consisted of tumor samples from The Cancer
Genome Atlas, and the validation set comprised data from the Gene Expression
Omnibus. Univariate and multivariate Cox regression analyses were applied to
identify the prognostic NRG signature as an independent molecular indicator.
Correlation analysis was used for the association assessment between the NRG
signature and immune checkpoint molecules.

Results

NRGs involved in necroptosis and immune NOD-like receptor signaling.
The NRG signature based on eight NRGs can divide tumors into high-risk and
low-risk groups, which was significantly associated with worse survival.
Multivariate Cox regression analysis showed that this NRG signature remained an
independent prognostic indicator. Stratification analyses demonstrated that this
NRG signature was still effective for predicting survival in each stratum of
age, gender, and tumor stage. The ROC curve showed a good predictive ability
using the NRG signature in the validation cohort (AUC = 0.81). The
NRG signature was related to immune checkpoint molecules
PD − 1, PD-L1, and PD-L2.

Conclusions

The NRG signature could be a novel predictor of the prognosis and
may become a potential therapeutic target in LUAD.
Deep learning parametric response mapping from inspiratory chest CT scans: a new approach for small airway disease screening
Authors: Chen Bin , Liu Ziyi , Lu Jinjuan , Li Zhihao , Kuang Kaiming , Yang Jiancheng , Wang Zengmao , Sun Yingli , Du Bo , Qi Lin , Li Ming
Published: November 2023

Objectives

Parametric response mapping (PRM) enables the evaluation of small airway disease (SAD) at the voxel level, but requires both inspiratory and expiratory chest CT scans. We hypothesize that deep learning PRM from inspiratory chest CT scans can effectively evaluate SAD in individuals with normal spirometry.

Methods

We included 537 participants with normal spirometry, a history of smoking or secondhand smoke exposure, and divided them into training, tuning, and test sets. A cascaded generative adversarial network generated expiratory CT from inspiratory CT, followed by a UNet-like network predicting PRM using real inspiratory CT and generated expiratory CT. The performance of the prediction is evaluated using SSIM, RMSE and dice coefficients. Pearson correlation evaluated the correlation between predicted and ground truth PRM. ROC curves evaluated predicted PRMfSAD (the volume percentage of functional small airway disease, fSAD) performance in stratifying SAD.

Results

Our method can generate expiratory CT of good quality (SSIM 0.86, RMSE 80.13 HU). The predicted PRM dice coefficients for normal lung, emphysema, and fSAD regions are 0.85, 0.63, and 0.51, respectively. The volume percentages of emphysema and fSAD showed good correlation between predicted and ground truth PRM (|r| were 0.97 and 0.64, respectively, p < 0.05). Predicted PRMfSAD showed good SAD stratification performance with ground truth PRMfSAD at thresholds of 15%, 20% and 25% (AUCs were 0.84, 0.78, and 0.84, respectively, p < 0.001).

Conclusion

Our deep learning method generates high-quality PRM using inspiratory chest CT and effectively stratifies SAD in individuals with normal spirometry.
Effects of dapagliflozin and dapagliflozin-saxagliptin on erythropoiesis, iron and inflammation markers in patients with type 2 diabetes and chronic kidney disease: data from the DELIGHT trial
Authors: Koshino Akihiko , Neuen Brendon L. , Jongs Niels , Pollock Carol , Greasley Peter J. , Andersson Eva-Marie , Hammarstedt Ann , Karlsson Cecilia , Langkilde Anna Maria , Wada Takashi , Heerspink Hiddo J.L.
Published: November 2023

Background

This post-hoc analysis of the DELIGHT trial assessed effects of the SGLT2 inhibitor dapagliflozin on iron metabolism and markers of inflammation.

Methods

Patients with type 2 diabetes and albuminuria were randomized to dapagliflozin, dapagliflozin and saxagliptin, or placebo. We measured hemoglobin, iron markers (serum iron, transferrin saturation, and ferritin), plasma erythropoietin, and inflammatory markers (urinary MCP-1 and urinary/serum IL-6) at baseline and week 24.

Results

360/461 (78.1%) participants had available biosamples. Dapagliflozin and dapagliflozin-saxagliptin, compared to placebo, increased hemoglobin by 5.7 g/L (95%CI 4.0, 7.3; p < 0.001) and 4.4 g/L (2.7, 6.0; p < 0.001) and reduced ferritin by 18.6% (8.7, 27.5; p < 0.001) and 18.4% (8.7, 27.1; p < 0.001), respectively. Dapagliflozin reduced urinary MCP-1/Cr by 29.0% (14.6, 41.0; p < 0.001) and urinary IL-6/Cr by 26.6% (9.1, 40.7; p = 0.005) with no changes in other markers.

Conclusions

Dapagliflozin increased hemoglobin and reduced ferritin and urinary markers of inflammation, suggesting potentially important effects on iron metabolism and inflammation.

Trial registration

ClinicalTrials.gov NCT02547935.
Bystander preference for naloxone products: a field experiment
Authors: Marks Katherine R. , Oyler Douglas R. , Strickland Justin C. , Jaggers Jody , Roberts Monica F. , Miracle Dustin K. , Barnes Chase , Lei Feitong , Smith Amanda , Mackin Eric , Martin Martika C. , Freeman Patricia R.
Published: November 2023

Background

Bystander administration of naloxone is a critical strategy to mitigate opioid overdose mortality. To ensure bystanders’ willingness to carry and administer naloxone in response to a suspected overdose, it is critical to select products for community distribution with the highest likelihood of being utilized. This study examines bystanders’ preference for and willingness to administer three naloxone products approved by the FDA for bystander use and identify product features driving preference.

Methods

The population was a convenience sample of individuals who attended the Kentucky State Fair, August 18–28, 2022, in Louisville, Kentucky. Participants (n = 503) watched a standardized overdose education and naloxone training video, rated their willingness to administer each of three products (i.e., higher-dose nasal spray, lower-dose nasal spray, intramuscular injection), selected a product to take home, and rated factors affecting choice.

Results

After training, 44.4% chose the higher-dose nasal spray, 30.1% chose the intramuscular injection, and 25.5% chose the lower-dose nasal spray. Factors most influencing choice on a 10-point Likert scale were ease of use (9 [7–10]), naloxone dose (8 [5–10]), and product familiarity (5 [5–9]).

Conclusions

Bystanders expressed high willingness to administer all studied formulations of naloxone products. Product choice preference varied as a function of product features. As the number and variety of available products continue to increase, continuous evaluation of formulation acceptability, in addition to including individuals with lived experience who are receiving and administering overdose reversal agents, is critical to support adoption and save lives.
Outcomes of Ponte osteotomy combined with posterior lumbar interbody fusion for reconstruction of coronal and sagittal balance in degenerative scoliosis
Authors: Zhang Haoran , Du You , Zhao Yiwei , Yang Yang , Zhang Jianguo , Wang Shengru
Published: November 2023

Purpose

The purpose of the study was to evaluate the clinical efficacy and safety of using Ponte osteotomy combined with posterior lumbar interbody fusion in the treatment of patients with degenerative scoliosis.

Method

The medical records and imaging data of degenerative scoliosis patients in our department from 2013 to 2022 were retrospectively collected. A total of 47 patients were included, including 16 male patients and 31 female patients. The mean follow-up was 47.8 months. Whole spine X-rays in the standing position were performed on all patients preoperatively, postoperatively, and at the latest follow-up. The length of hospital stay, complications, operative duration, estimated blood loss, instrumented segment, fused segment, clinical scores, and various radiological indicators were recorded.

Results

The coronal vertical axis improved from 3.1 ± 1.9 cm preoperatively to 1.2 ± 1.0 cm postoperatively with an average reduction of 1.9 ± 1.7 cm. The preoperative coronal Cobb angle was 18.1 ± 10.6°, the immediate postoperative Cobb angle was 6.6 ± 3.9°, and the Cobb angle at the last follow-up was 5.8 ± 3.7°. The sagittal vertical axis decreased from 5.6 ± 3.7 cm preoperatively to 2.7 ± 1.9 cm immediately after the operation and was well maintained at the last follow-up (3.1 ± 2.5 cm). Lumbar lordosis increased from 22.2 ± 10.2° preoperatively to 40.4 ± 8.3° postoperatively and 36.0 ± 8.8° at the last follow-up. The ODI score, VAS low back pain score, and VAS leg pain score were also improved to varying degrees.

Conclusion

Ponte osteotomy combined with posterior lumbar interbody fusion can significantly improve coronal and sagittal plane deformities and postoperative functional scores in patients with adult degenerative scoliosis.
Salvianolic acid B promotes angiogenesis and inhibits cardiomyocyte apoptosis by regulating autophagy in myocardial ischemia
Authors: Chen Qi , Xu QingYang , Zhu Huilin , Wang Junyi , Sun Ning , Bian Huimin , Li Yu , Lin Chao
Published: November 2023

Background

Myocardial ischemia (MI) can cause angina, myocardial infarction, and even death. Angiogenesis is beneficial for ensuring oxygen and blood supply to ischemic tissue, promoting tissue repair, and reducing cell damage. In this study, we evaluated the effects of Salvianolic acid B (Sal B) against myocardial ischemia and explored its underlying mechanism on autophagy.

Methods

The anti-apoptosis effect of Sal B was conducted by staining Annexin V-FITC/PI and Hoechst as well as evaluating apoptosis bio-markers at protein level in H9c2 cells at glucose deprivation condition. HUVECs were co-cultured with H9c2, and the tube formation assay was used to monitor Sal B’s impact on angiogenesis. The MI model of mice was induced by intraperitoneal injection of isoproterenol (ISO). The effect of Sal B on MI mice was evaluated by HE, Masson, immunohistochemistry, WB and kits. In addition, Atg5 siRNA was applied to verify whether the protective effect of Sal B was regulated to autophagy.

Results

In H9c2, Sal B reduced the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA) and reactive oxygen species (ROS), improved the levels of superoxide dismutase (SOD) and mitochondrial membrane potential, downregulated the expressions of Bax and cleaved-Caspase3, upregulated the expression of Bcl-2. Therefore, Sal B could significantly inhibit the damage of H9c2 caused by glucose deprivation. In the co-culture system of H9c2 and HUVECs, vascular endothelial growth factor (VEGF) level in the supernatant was dramatically raised by Sal B. Sal B upregulated the expressions of VEGF, platelet derived growth factor (PDGF) and endothelial marker CD31. It implied that Sal B exerted a significant pro-angiogenic effect. Moreover, Sal B increased the expression of LC3, Atg5, and Beclin1, while reducing the level of P62. When the expression of Atg5 was inhibited, the protective effects of Sal B on apoptosis and angiogenesis was reversed.

Conclusions

Sal B inhibited cardiomyocyte apoptosis and promoted angiogenesis by regulating autophagy, thereby improving MI.
Explorative research on glucolipid metabolism and levels of adipokines in pseudohypoparathyroidism type 1 patients
Authors: Yang Yi , Song An , Gong Fengying , Jiang Yan , Li Mei , Xia Weibo , Xing Xiaoping , Wang Ou , Pan Hui
Published: November 2023

Background

Pseudohypoparathyroidism type 1 (PHP1) is a rare disease featuring hypocalcemia and elevated PTH level. Though disturbed calcium and phosphorus metabolism under PTH resistant have been widely studied, glucolipid metabolism abnormalities observed in PHP1 patients have received little attention. The aim of this research is to explore the glucolipid metabolism features in a rather large cohort of PHP1 patient. In the current study, PHP1 patients and primary hyperparathyroidism patients as well as normal control were recruited for the investigation. Glucolipid metabolic indices as well as the level of four adipokines were examined.

Results

A total of 49 PHP1 patients, 64 PHPT patients and 30 healthy volunteers were enrolled. A trend of higher HOMA-β index was found in PHP1 patients than normal controls (median 97.08% vs 68.19%, p = 0.060). Both the PHP1 and PHPT group presented with significantly lower TNFα level compared to normal controls (average 10.74 pg/ml and 12.53 pg/ml vs 15.47 pg/ml, p = 0.002 and 0.041, respectively). FGF21 level was significantly higher in PHPT group than in PHP1 group (median 255.74 pg/ml vs 167.46 pg/ml, p = 0.019). No significant difference in glucolipid metabolic indices and adipokines was found between PHP1A or PHP1B patients and normal controls, while overweight/obese PHP1 patients tended to have higher leptin than normal-BMI cases (p = 0.055). Multiple linear regression analysis showed BMI rather than PTH or HOMA-IR to be an independent variable of leptin in PHP1.

Conclusion

Metabolic stress given upon especially overweight PHP1 patients may resulted in possible β-cell compensation. Elevated TNFα may be related with hyper-PTH level regardless of calcium level.
Transitioning to adult mental health services for young people with ADHD: an Italian-based survey on practices for pediatric and adult services
Authors: Roberti Elisa , Scarpellini Francesca , Campi Rita , Giardino Michele , Clavenna Antonio , Bonati Maurizio ,   the TransiDEA group, Stoppa Patrizia , Martinelli Ottaviano , Morosini Paola , Capovilla Giuseppe , Costantino Maria Antonella , Raviglione Federico , Conti Patrizia , Rossi Giorgio , Giarelli Maria Teresa , Fazzi Elisa Maria , Carpanelli Marialuisa , Canevini Maria Paola , Rinaldi Francesco , Molteni Massimo , Vignoli Aglaia , Borgatti Renato , Farinotti Laura , Arcangeli Donatella , Bona Paola , Giovannoni Franco , Pincherle Maurizio , Canitano Roberto , Gennaro Elena , Caucci Chiara , Bravaccio Carmela , Sotgiu Stefano , Costanza Giancarlo , Briatore Eleonora , Vitiello Benedetto , Zappulla Giuseppe , Colombi Elisa , Ferrario Mariarosa , Franzoi Malida , Martinez Federica , Obino Laure , Carrozzi Marco , Durbano Federico , Grignani Marco , Grignani Marco , Antonucci Alessandro , Rella Angelo , Di Paolo Pietro , Fiore Germano , Piemontese Gianluca , De Nicola Giulio , Conca Andres , Cucciniello Angelo , Rosa Moro Anna , Francobandiera Giorgio , Moraca Maria Carla , Corsini Paola , Antonucci Alessandro , Bondi Emi , Aroasio Luisa , Imperadore Giuseppe , Malagamba Daniela , Callegari Camilla , Toscano Marco , Di Cesare Gialuigi , Cappa Corrado , Gardellin Francesco , Laudani Elio , Raschitelli Nicoletta , Zanetti Michele , Cartabia Massimo , Graziani Vanna , Marchetti Federico , Suprani Tosca , Di Bartolo Paolo , Viganò Ilaria , Costantino Ilaria , Tessarollo Valeria , Ruffoni Giampaolo
Published: November 2023

Background

Supporting young ADHD patients in transition to adult services is essential. Yet, the low percentages of successful referrals and the issues reported by patients and clinicians stress the need for further attention to transitioning practices. The present study assessed the transitioning process of Attention-Deficit/Hyperactivity Disorder (ADHD) patients in Child and Adolescent Mental Health Services (CAMHS) and Adult Mental Health Services (AMHS) in the Italian territory. We asked child and adult psychiatrists to report the current state of services and their observations on limitations and possible future matters that must be addressed.

Method

Seventy-seven centers (42 CAMHS, 35 AMHS) filled in a web-based survey in which they reported the number of ADHD patients, how many transitioning patients they had within the past year, and how they structured transition.

Results

A fragmented picture emerged from the survey. Lack of resources, training, and communication between services hinder the transition process, and many adult patients remain under CAMHS’ care. While some services have a protocol, there is no structured guidance that can help improve integration and continuity of treatment.

Conclusion

The observed situation reflects a need for improvement and standard guidelines to enable a successful transition process, considering clinicians' and patients’ necessities.
Inhibiting NR5A2 targets stemness in pancreatic cancer by disrupting SOX2/MYC signaling and restoring chemosensitivity
Authors: Zheng Quan , Tang Jiajia , Aicher Alexandra , Bou Kheir Tony , Sabanovic Berina , Ananthanarayanan Preeta , Reina Chiara , Chen Minchun , Gu Jian-Min , He Bin , Alcala Sonia , Behrens Diana , Lawlo Rita T. , Scarpa Aldo , Hidalgo Manuel , Sainz Bruno , Sancho Patricia , Heeschen Christopher
Published: November 2023

Background

Pancreatic ductal adenocarcinoma (PDAC) is a profoundly aggressive and fatal cancer. One of the key factors defining its aggressiveness and resilience against chemotherapy is the existence of cancer stem cells (CSCs). The important task of discovering upstream regulators of stemness that are amenable for targeting in PDAC is essential for the advancement of more potent therapeutic approaches. In this study, we sought to elucidate the function of the nuclear receptor subfamily 5, group A, member 2 (NR5A2) in the context of pancreatic CSCs.

Methods

We modeled human PDAC using primary PDAC cells and CSC-enriched sphere cultures. NR5A2 was genetically silenced or inhibited with Cpd3. Assays included RNA-seq, sphere/colony formation, cell viability/toxicity, real-time PCR, western blot, immunofluorescence, ChIP, CUT&Tag, XF Analysis, lactate production, and in vivo tumorigenicity assays. PDAC models from 18 patients were treated with Cpd3-loaded nanocarriers.

Results

Our findings demonstrate that NR5A2 plays a dual role in PDAC. In differentiated cancer cells, NR5A2 promotes cell proliferation by inhibiting CDKN1A. On the other hand, in the CSC population, NR5A2 enhances stemness by upregulating SOX2 through direct binding to its promotor/enhancer region. Additionally, NR5A2 suppresses MYC, leading to the activation of the mitochondrial biogenesis factor PPARGC1A and a shift in metabolism towards oxidative phosphorylation, which is a crucial feature of stemness in PDAC. Importantly, our study shows that the specific NR5A2 inhibitor, Cpd3, sensitizes a significant fraction of PDAC models derived from 18 patients to standard chemotherapy. This treatment approach results in durable remissions and long-term survival. Furthermore, we demonstrate that the expression levels of NR5A2/SOX2 can predict the response to treatment.

Conclusions

The findings of our study highlight the cell context-dependent effects of NR5A2 in PDAC. We have identified a novel pharmacological strategy to modulate SOX2 and MYC levels, which disrupts stemness and prevents relapse in this deadly disease. These insights provide valuable information for the development of targeted therapies for PDAC, offering new hope for improved patient outcomes.

Graphical Abstract

A Schematic illustration of the role of NR5A2 in cancer stem cells versus differentiated cancer cells, along with the action of the NR5A2 inhibitor Cpd3. B Overall survival of tumor-bearing mice following allocated treatment. A total of 18 PDX models were treated using a 2 x 1 x 1 approach (two animals per model per treatment); n=36 per group (illustration created with biorender.com).
Ginseng-derived nanoparticles reprogram macrophages to regulate arginase-1 release for ameliorating T cell exhaustion in tumor microenvironment
Authors: Lv Yan , Li Mengyuan , Weng Ling , Huang Haoying , Mao Yujie , Yang Danchen Aaron , Wei Qingyun , Zhao Mengmeng , Wei Qin , Rui Ke , Han Xuan , Fan Weiwei , Cai Xueting , Cao Peng , Cao Meng
Published: November 2023

Background

Lines of evidence indicated that, immune checkpoints (ICs) inhibitors enhanced T cell immune response to exert anti-tumor effects. However, T cell exhaustion has been so far a major obstacle to antitumor immunotherapy in colorectal cancer patients. Our previous studies showed that ginseng-derived nanoparticles (GDNPs) inhibited the growth of various tumors by reprograming tumor-associated macrophages (TAMs) and downregulated the ICs expression on T cells in tumor microenvironment (TME), but the underlying effector mechanisms remained unclear.

Methods

The correlation between arginase-1 (ARG1) and T cells was computed based on the colorectal cancer patients in TCGA database. In vitro, we observed that GDNPs reprogrammed TAMs inhibited ARG1 release and ultimately ameliorated T cell exhaustion according to several techniques including WB, PCR, ELISA and flow cytometry. We also used an in vivo MC38 tumor-bearing model and administered GDNPs to assess their anti-tumor effects through multiple indices. The mechanism that GDNPs improved T cell exhaustion was further clarified using the bioinformatics tools and flow cytometry.

Results

GDNPs reprogramed TAMs via reducing ARG1 production. Moreover, normalized arginine metabolism ameliorated T cell exhaustion through mTOR-T-bet axis, resulting in reduced ICs expression and enhanced CD8+ T cells expansion.

Conclusions

By regulating the mTOR-T-bet axis, GDNPs reprogramed macrophages to regulate ARG1 release, which further ameliorated T cell exhaustion in TME. These findings provided new insights into comprehending the mechanisms underlying the mitigation of T cell exhaustion, which may facilitate the development of innovative therapeutic strategies in the field of cancer treatment.
BRCA1 and BRCA2 deficient tumour models generate distinct ovarian tumour microenvironments and differential responses to therapy
Authors: Farokhi Boroujeni Salar , Rodriguez Galaxia , Galpin Kristianne , Yakubovich Edward , Murshed Humaira , Ibrahim Dalia , Asif Sara , Vanderhyden Barbara C.
Published: November 2023

Clinical trials are currently exploring combinations of PARP inhibitors and immunotherapies for the treatment of ovarian cancer, but their effects on the ovarian tumour microenvironment (TME) remain unclear. Here, we investigate how olaparib, PD-L1 monoclonal antibodies, and their combination can influence TME composition and survival of tumour-bearing mice. We further explored how BRCA deficiencies can influence the response to therapy. Olaparib and combination therapies similarly improved the median survival of Brca1- and Brca2-deficient tumour-bearing mice. Anti-PD-L1 monotherapy improved the survival of mice with Brca1-null tumours, but not Brca2-null tumours. A detailed analysis of the TME revealed that olaparib monotherapy resulted in a large number of immunosuppressive and immunomodulatory effects in the more inflamed Brca1-deficient TME but not Brca2-deficient tumours. Anti-PD-L1 treatment was mostly immunosuppressive, resulting in a systemic reduction of cytokines and a compensatory increase in PD-L1 expression. The results of the combination therapy generally resembled the effects of one or both of the monotherapies, along with unique changes observed in certain immune populations. In-silico analysis of RNA-seq data also revealed numerous differences between Brca-deficient tumour models, such as the expression of genes involved in inflammation, angiogenesis and PD-L1 expression. In summary, these findings shed light on the influence of novel therapeutics and BRCA mutations on the ovarian TME.
The implication of a translational triage tool in mass casualty incidents: part three: a multinational study, using validated patient cards
Authors: Khorram-Manesh Amir , Carlström Eric , Burkle Frederick M. , Goniewicz Krzysztof , Gray Lesley , Ratnayake Amila , Faccincani Roberto , Bagaria Dinesh , Phattharapornjaroen Phatthranit , Sultan Mohammed A. S. , Montán Carl , Nordling Johan , Gupta Shailly , Magnusson Carl
Published: November 2023

Background

Mass casualty incidents (MCI) pose significant challenges to existing resources, entailing multiagency collaboration. Triage is a critical component in the management of MCIs, but the lack of a universally accepted triage system can hinder collaboration and lead to preventable loss of life. This multinational study uses validated patient cards (cases) based on real MCIs to evaluate the feasibility and effectiveness of a novel Translational Triage Tool (TTT) in primary triage assessment of mass casualty victims.

Methods

Using established triage systems versus TTT, 163 participants (1575 times) triaged five patient cases. The outcomes were statistically compared.

Results

TTT demonstrated similar sensitivity to the Sieve primary triage method and higher sensitivity than the START primary triage system. However, the TTT algorithm had a lower specificity compared to Sieve and higher over-triage rates. Nevertheless, the TTT algorithm demonstrated several advantages due to its straightforward design, such as rapid assessment, without the need for additional instrumental interventions, enabling the engagement of non-medical personnel.

Conclusions

The TTT algorithm is a promising and feasible primary triage tool for MCIs. The high number of over-triages potentially impacts resource allocation, but the absence of under-triages eliminates preventable deaths and enables the use of other personal resources. Further research involving larger participant samples, time efficiency assessments, and real-world scenarios is needed to fully assess the TTT algorithm's practicality and effectiveness in diverse multiagency and multinational contexts.
The effects of Olmesartan/amlodipine administered in the Morning or At Night on nocturnal blood pressure reduction in Chinese patients with mild-moderate essential hypertension (OMAN Trial): study protocol for a prospective, multicenter, randomized, open-label clinical trial {1}
Authors: Xu Mengzhuo , Zhang Xin , Ye Runyu , Liu Xueting , Sun Lirong , Jia Shanshan , Zhang Zhipeng , Li Xinran , Wang Ziqiong , Liao Hang , Shi Rufeng , Liu Kai , Wang Si , Meng Qingtao , Chen Xiaoping
Published: November 2023

Introduction

Hypertension increases the risk of cardiovascular disease. Uncontrolled nocturnal blood pressure is prevalent in patients taking antihypertensive medication, with an incidence rate of 30–60%. Although chronotherapy with antihypertensive agents may provide a new direction for effective control of nocturnal blood pressure, the clinical evidence base remains controversial. This research is presently underway to compare the effects of morning and bedtime administration of antihypertensive medication on nocturnal reduction and circadian rhythm of blood pressure in patients with hypertension.

Methods and analysis

This study is being performed as a randomized, multicenter, open-label, parallel-group, clinical trial in which 720 participants are to undergo 24-h ambulatory blood pressure measurement (ABPM) and office blood pressure measurement (OBPM) at baseline before being randomly assigned to a morning (6–10 am) or a bedtime (6–10 pm) administration group. Each participant receives one 20/5-mg tablet of olmesartan/amlodipine (OA) daily for 4 weeks and is then followed up at 4-week intervals for a total of 12 weeks. During follow-up, the OA dosage is adjusted according to the ABPM and OBPM results. Patients with uncontrolled hypertension at the first follow-up visit will receive an increase in OA dosage to 1.5 tablets/day. For patients with blood pressure that is still uncontrolled after a further 4 weeks, the dosage of OA can be increased to 2 tablets/day. The primary objective is the reduction in mean nocturnal systolic blood pressure between baseline and week 12. The secondary objectives are the reduction in ambulatory blood pressure at weeks 4 and 12 and the blood pressure control rate at weeks 4, 8, and 12.

Discussion

Antihypertensive chronotherapy remains controversial. A superiority test hypothesis design has been adopted for this trial, in which all participants will be taking the same antihypertensive medication. We anticipate that our findings will determine if nocturnal blood pressure control in Chinese patients with essential hypertension varies according to whether antihypertensive medication is taken in the morning or at bedtime. This study may provide scientific evidence for the application of chronotherapy in clinical practice.

Trial registration

ChiCTR2200059719. Registered on 10 May 2022

(http://www.chictr.org.cn/edit.aspx?pid=169782&htm=4) {2a,2b}
Hearing intervention for decreasing risk of developing dementia in elders with mild cognitive impairment: study protocol of a multicenter randomized controlled trial for Chinese Hearing Solution for Improvement of Cognition in Elders (CHOICE)
Authors: Chen Ying , Guan Lei , Chen Jie , Han Kun , Yu Qiongfei , Zhou Jin , Wang Xue , Ma Yunqian , Ji Xiangyu , Zhao Zhonglu , Shen Qiyue , Wang Anxian , Wang Mengping , Li Jin , Yu Jiali , Zhang Yiwen , Xu Sijia , Liu Jie , Lu Wen , Ye Bin , Fang Yuan , Hu Haixia , Shi Haibo , Xiang Mingliang , Li Xia , Li Yun , Wu Hao
Published: November 2023

Background

Age-related hearing loss (ARHL) signifies the bilateral, symmetrical, sensorineural hearing loss that commonly occurs in elderly individuals. Several studies have suggested a higher risk of dementia among patients diagnosed with ARHL. Although the precise causal association between ARHL and cognitive decline remains unclear, ARHL has been recognized as one of the most significant factors that can be modified to reduce the risk of developing dementia potentially. Mild cognitive impairment (MCI) typically serves as the initial stage in the transition from normal cognitive function to dementia. Consequently, the objective of our randomized controlled trial (RCT) is to further investigate whether the use of hearing aids can enhance cognitive function in older adults diagnosed with ARHL and MCI.

Methods and design

This study is a parallel-arm, randomized controlled trial conducted at multiple centers in Shanghai, China. We aim to enlist a total of 688 older adults (age ≥ 60) diagnosed with moderate-to-severe ARHL and MCI from our four research centers. Participants will be assigned randomly to either the hearing aid fitting group or the health education group using block randomization with varying block sizes. Audiometry, cognitive function assessments, and other relevant data will be collected at baseline, as well as at 6, 12, and 24 months post-intervention by audiologists and trained researchers. The primary outcome of our study is the rate of progression to dementia among the two groups of participants. Additionally, various evaluations will be conducted to measure hearing improvement and changes in cognitive function. Apart from the final study results, we also plan to conduct an interim analysis using data from 12-month follow-up.

Discussion

In recent years, there has been a notable lack of randomized controlled trials (RCTs) investigating the possible causal relationship between hearing fitting and the improvement of cognitive function. Our findings may demonstrate that hearing rehabilitation can be a valuable tool in managing ARHL and preventing cognitive decline, which will contribute to the development of a comprehensive framework for the prevention and control of cognitive decline.

Trial registration

Chinese Clinical Trial Registry chictr.org.cn ChiCTR2000036139. Registered on 21 August 2020.
Interaction of sulfasalazine with outer surface of boron-nitride nanotube as a drug carrier in aqueous solution: insights from quantum mechanics and Monte Carlo simulation
Authors: Ketabi Sepideh , Shalmashi Saba , Hallajian Sara
Published: November 2023

The improvement of the solubility of sulfasalazine in physiological media was the major aim of this study. Accordingly, BNNT inspected as a notable candidate for the carriage of this drug in aqueous media. For this purpose, four possible interactions of two tautomer of sulfasalazine with (9,0) boron-nitride nanotube were considered in aqueous media. The compounds were optimized in gas phase using density functional calculations. Solvation free energies and association free energies of the optimized structures were then studied by Monte Carlo simulation and perturbation method in water environment. Outcomes of quantum mechanical calculations presented that interaction of keto form of sulfasalazine produce the most stable complexes with boron-nitride nanotube in gas phase. Simulation results revealed that electrostatic interactions play a vital role in the intermolecular interaction energies after binding of drug and nanotube in aqueous solution. Results of association free energy calculations indicated that complexes of both two sulfasalazine tautomers (keto and enol) and nanotube were stable in solution. Computed solvation free energies in water showed that the interaction with boron-nitride nanotube significantly improved the solubility of sulfasalazine, which could improve its in vivo bioavailability.
Determination of cut-off points for the Move4 accelerometer in children aged 8–13 years
Authors: Beck Franziska , Marzi Isabel , Eisenreich Alina , Seemüller Selina , Tristram Clara , Reimers Anne K.
Published: November 2023

Background

To assess physical activity (PA) there is a need of objective, valid and reliable measurement methods like accelerometers. Before these devices can be used for research, they need to be calibrated and validated for specific age groups as the locomotion differs between children and adults, for instance. Therefore, the aim of the present study was the calibration and validation of the Move4 accelerometer for children aged 8–13 years.

Methods

53 normal weighted children (52% boys, 48%girls) aged 8–13 years (mean age = 10.69 ± 1.46, mean BMI = 17.93 kg/m− 2, 60th percentile), wore the Move4 sensor at four different body positions (thigh, hip, wrist and the Move4ecg including heart rate measurement at the chest). They completed nine activities that considered the four activity levels (sedentary behavior (SB), light PA (LPA), moderate PA (MPA) and vigorous PA (VPA)) within a test-retest design. Intensity values were determined using the mean amplitude deviation (MAD) as well as the movement acceleration intensity (MAI) metrics. Determination of activities and energy expenditure was validated using heart rate. After that, cut-off points were determined in Matlab by using the Classification and Regression Trees (CART) method. The agreement for the cut-off points between T1 and T2 was analyzed.

Results

MAD and MAI accelerometer values were lowest when children were lying on the floor and highest when running or doing jumping jacks. The mean correlation coefficient between acceleration values and heart rate was 0.595 (p = 0.01) for MAD metric and 0.611 (p = 0.01) for MAI metric, indicating strong correlations. Further, the MAD cut-off points for SB-LPA are 52.9 mg (hip), 62.4 mg (thigh), 86.4 mg (wrist) and 45.9 mg (chest), for LPA-MPA they are 173.3 mg (hip), 260.7 mg (thigh), 194.4 mg (wrist) and 155.7 mg (chest) and for MPA-VPA the cut-off points are 543.6 mg (hip), 674.5 mg (thigh), 623.4 mg (wrist) and 545.5 mg (chest). Test-retest comparison indicated good values (mean differences = 9.8%).

Conclusion

This is the first study investigating cut-off points for children for four different sensor positions using raw accelerometer metrics (MAD/MAI). Sensitivity and specificity revealed good values for all positions. Nevertheless, depending on the sensor position, metric values differ according to the different involvement of the body in various activities. Thus, the sensor position should be carefully chosen depending on the research question of the study.
How healthy participants value additional diagnostic testing with amyloid-PET in patients diagnosed with mild cognitive impairment — a bidding game experiment
Authors: van Maurik I. S. , Bakker E. D. , van Unnik A. A. J. M. , Broulikova H. M. , Zwan M. D. , van de Giessen E. , Berkhof J. , Bouwman F. H. , Bosmans J. E. , van der Flier W. M.
Published: November 2023

Background

To estimate the perceived value of additional testing with amyloid-PET in Euros in healthy participants acting as analogue patients with mild cognitive impairment (MCI).

Methods

One thousand four hundred thirty-one healthy participants acting as analogue MCI patients (mean age 65 ± 8, 929 (75%) female) were recruited via the Dutch Brain Research Registry. Participants were asked to identify with a presented case (video vignette) of an MCI patient and asked whether they would prefer additional diagnostic testing with amyloid PET in this situation. If yes, respondents were asked how much they would be willing to pay for additional diagnostic testing. Monetary value was elicited via a bidding game in which participants were randomized over three conditions: (A) additional testing results in better patient management, (B) Same as condition A and a delay in institutionalization of 3 months, and (C) same as A and a delay in institutionalization of 6 months. Participants who were not willing to take a test were compared with participants who were willing to take a test using logit models. The highest monetary value per condition was analyzed using random-parameter mixed models.

Results

The vast majority of participants acting as analogue MCI patients (87% (n = 1238)) preferred additional testing with amyloid PET. Participants who were not interested were more often female (OR = 1.61 95% CI [1.09–2.40]) and expressed fewer worries to get AD (OR = 0.64 [0.47–0.87]). The median “a priori” (i.e., before randomization) monetary value of additional diagnostic testing was €1500 (IQR 500–1500). If an additional amyloid PET resulted in better patient management (not further specified; condition A), participants were willing to pay a median price of €2000 (IQR = 1000–3500). Participants were willing to pay significantly more than condition A (better patient management) if amyloid-PET testing additionally resulted in a delay in institutionalization of 3 months (€530 [255–805] on top of €2000, condition B) or 6 months (€596 [187–1005] on top of €2000, condition C).

Conclusions

Members of the general population acting as MCI patients are willing to pay a substantial amount of money for amyloid-PET and this increases when diagnostic testing leads to better patient management and the prospect to live longer at home.
Comparative study of the sensitivity of ultra-high-resolution CT and high-resolution CT in the diagnosis of isolated fenestral otosclerosis
Authors: Xu Ning , Ding Heyu , Tang Ruowei , Li Xiaoshuai , Zhang Zhengyu , Lv Han , Dai Chihang , Qiu Xiaoyu , Huang Yan , Han Xu , Wang Guo-Peng , Liu Yuhe , Gong Shusheng , Yang Zhenghan , Wang Zhenchang , Zhao Pengfei
Published: November 2023

Purpose

To compare the diagnostic sensitivity of ultra-high-resolution computed tomography (U-HRCT) and HRCT in isolated fenestral otosclerosis (IFO).

Methods

A retrospective analysis was conducted on 85 patients (85 ears) diagnosed with IFO between October 2020 and November 2022. U-HRCT (0.1 mm thickness) was performed for 20 ears, HRCT (0.67 mm thickness) for 45 ears, and both for 20 ears. The images were evaluated by general radiologists and neuroradiologists who were blinded to the diagnosis and surgical information. The diagnostic sensitivity of U-HRCT and HRCT for detecting IFO was compared between the two groups.

Results

Excellent inter-observer agreement existed between the two neuroradiologists (Cohen’s κ coefficient 0.806, 95% CI 0.692–0.920), with good agreement between the general radiologists (Cohen’s κ coefficient 0.680, 95% CI 0.417–0.943). U-HRCT had a sensitivity of 100% (40/40 ears) for neuroradiologists and 87.5% (35/40 ears) for general radiologists, significantly higher than HRCT (89.2% [58/65 ears] for neuroradiologists; 41.5% [27/65 ears] for general radiologists) (p = 0.042, p′ < 0.000). General radiologists’ sensitivity with HRCT was significantly lower compared to neuroradiologists (p < 0.000), but no significant difference was observed when general radiologists switched to U-HRCT (p = 0.152). Among the 20 ears that underwent both examinations, U-HRCT detected lesions smaller than 1 mm in 5 ears, whereas HRCT’s sensitivity for neuroradiologists was 40% (2/5 ears), significantly lower than for lesions larger than 1 mm (93.3%, 14/15 ears, p = 0.032).

Conclusion

U-HRCT exhibits higher sensitivity than HRCT in diagnosing IFO, suggesting its potential as a screening tool for suspected otosclerosis patients.

Critical relevance statement

Ultra-high-resolution computed tomography has the potential to become a screening tool in patients with suspected otosclerosis and to bridge the diagnostic accuracy gap between general radiologists and neuroradiologists.

Key points

• U-HRCT exhibits higher sensitivity than HRCT in the diagnosis of IFO.

• U-HRCT has a significant advantage in the detection of less than 1 mm IFO.

• U-HRCT has the potential to be used for screening of patients with suspected otosclerosis.

Graphical Abstract
Evaluation of preventive tract embolization with standardized gelatin sponge slurry on chest tube placement rate after CT-guided lung biopsy: a propensity score analysis
Authors: Grange Rémi , Di Bisceglie Mathieu , Habert Paul , Resseguier Noémie , Sarkissian Robin , Ferre Marjorie , Dassa Michael , Grange Sylvain , Izaaryene Jean , Piana Gilles
Published: November 2023

Background

To evaluate the effect of tract embolization (TE) with gelatin sponge slurries during a percutaneous lung biopsy on chest tube placement and to evaluate the predictive factors of chest tube placement.

Methods

Percutaneous CT-guided lung biopsies performed with (TE) or without (non-TE) tract embolization or between June 2012 and December 2021 at three referral tertiary centers were retrospectively analyzed. The exclusion criteria were mediastinal biopsies, pleural tumors, and tumors adjacent to the pleura without pleural crossing. Variables related to patients, tumors, and procedures were collected. Univariable and multivariable analyses were performed to determine risk factors for chest tube placement. Furthermore, the propensity score matching analysis was adopted to yield a matched cohort.

Results

A total of 1157 procedures in 1157 patients were analyzed, among which 560 (48.4%) were with TE (mean age 66.5 ± 9.2, 584 men). The rates of pneumothorax (44.9% vs. 26.1%, respectively; p < 0.001) and chest tube placement (4.8% vs. 2.3%, respectively; p < 0.001) were significantly higher in the non-TE group than in the TE group. No non-targeted embolization or systemic air embolism occurred. In the whole population, two protective factors for chest tube placement were found in univariate analysis: TE (OR 0.465 [0.239–0.904], p < 0.05) and prone position (OR 0.212 [0.094–0.482], p < 0.001). These data were confirmed in multivariate analysis (p < 0.001 and p < 0.0001 respectively). In the propensity matched cohort, TE reduces significatively the risk of chest tube insertion (OR = 0.44 [0.21–0.87], p < 0.05).

Conclusions

The TE technique using standardized gelatin sponge slurry reduces the need for chest tube placement after percutaneous CT-guided lung biopsy.

Critical relevance statement

The tract embolization technique using standardized gelatin sponge slurry reduces the need for chest tube placement after percutaneous CT-guided lung biopsy.

Key points

1. Use of tract embolization with gelatine sponge slurry during percutaneous lung biopsy is safe.

2. Use of tract embolization significantly reduces the risk of chest tube insertion.

3. This is the first multicenter study to show the protective effect of tract embolization on chest tube insertion.

Graphical Abstract