bluuebunny/crossref_metadata_2025 huggingface dataset:
Engagement of Peer Educators from India’s National Adolescent Health Programme for the COVID-19 response activities: Qualitative findings from i-Saathiya study
Authors: Bassi Shalini , Bahl Deepika , Maity Heeya , Dringus Stefanie , Rizvi Zoya Ali , Kumar Deepak , Raina Agrima , Arora Monika
Published: August 2024

Background

The COVID-19 pandemic strained India’s healthcare system and health workers unprecedentedly.

Purpose

The extent of the contribution by peer educators (PEs) from India’s National Adolescent Health Programme-Rashtriya Kishor Swasthya Karyakram (RKSK) to COVID-19 response activities remains uncertain necessitating an imperative investigation. Within the overarching objective of the ‘i-Saathiya’ study (‘i’ signifies implementation science and Saathiya represents PEs in Madhya Pradesh), a key focus was to understand the role of PEs recruited under RKSK during COVID-19 in two Indian states, namely Madhya Pradesh and Maharashtra. The study states differ in sociodemographic characteristics and peer education implementation models.

Methods

In-depth interviews (IDIs) were conducted with stakeholders (n=110, Maharashtra: 57; Madhya Pradesh: 53) engaged in the implementation of RKSK’s peer education programme at state, district, block and village levels. Focus group discussions (FGDs) (n=16 adolescents, Maharashtra: 8; Madhya Pradesh: 8) were conducted with adolescents, part of the peer group of PEs (n=120 adolescents, Maharashtra: 66; Madhya Pradesh: 54). IDIs and FGDs were audio-recorded, translated, transcribed verbatim and analysed thematically. Adopting inductive and deductive approaches, a data-driven open coding framework was developed for thematic analysis.

Results

The PE recruited under RKSK took a central role that extended beyond their predefined responsibilities within the RKSK. They provided crucial support to healthcare workers in curbing the spread of COVID-19. Their diverse contributions, including COVID-19 pandemic response support, addressing community and adolescent needs, role in COVID-19 vaccination efforts, navigating access to the health system and facilitating health workers in the implementation of various national health programmes and campaigns during COVID-19.

Conclusion

The findings underscore the potential of PEs in bolstering the health system. Despite their unpreparedness for the context (COVID-19), PEs demonstrated tenacity and adaptability, extending their roles beyond their predefined responsibilities. Recognising PEs through awards and incentives, skill courses and additional grades, can enhance their visibility, sustaining impactful work within RKSK and beyond.
Epidemiology and health care of hyperhidrosis in Germany: claims data analysis
Authors: Hagenström Kristina , Müller Katharina , Ohm Frenz , Augustin Matthias
Published: August 2024

Background and objectives

Data on the population-based epidemiology of hyperhidrosis (HH) are scarce. This study investigated the epidemiology and healthcare of HH in Germany.

Design and setting

Claims data of adult persons insured by a German statutory health insurance (DAK-Gesundheit) between 2016 and 2020 were analysed. Included were persons aged 18 years and older with a diagnosis of HH (confirmed inpatient or outpatient diagnosis in the observation year) who were continuously insured. Following outcomes were measured: prevalence and incidence rates, severity of hyperhidrosis and inpatient and outpatient care by a group of specialists.

Results

In 2020, 0.70% of insured adults were confirmed to have HH (mean age 59.5 years, SD 18.9, 61.6% female), with 9.24% having a ‘localised’ form, 8.65% a ‘generalised’ form and 84.80% an ‘unspecified’ form. 0.04% of the total population had a severe form. The incidence was 0.35%. Localised HH was more common in younger age groups (18 to <30 years), while older age groups (70 to <80 years) were significantly more likely to suffer from generalised HH. Systemic anticholinergics were used in 4.55%, and botulinum toxin injection therapy in 0.81%. General practitioners were most frequently involved in care. Inpatient stays due to HH were very rare, with 0.14% in 2019 and 0.04% in 2020.

Conclusion

Multisource data analysis connecting primary and secondary data will be needed for a complete picture of the healthcare and epidemiology of HH.
Gene panel predicts neoadjuvant chemoimmunotherapy response and benefit from immunotherapy in HER2-negative breast cancer
Authors: Lu Xunxi , Gou Zongchao , Chen Hong , Li Li , Chen Fei , Bao Chunjuan , Bu Hong
Published: August 2024

Background

It is encountering the dilemma of lacking precise biomarkers to predict the response to neoadjuvant chemoimmunotherapy (NACI) and determine whether patients should use immune checkpoint inhibitors (ICIs) in early breast cancer (BC). We aimed to develop a gene signature to predict NACI response for BC patients and identify individuals suitable for adding ICIs.

Patients and methods

Two I-SPY2 cohorts and one West China Hospital cohort of patients treated with NACI were included. Machine learning algorithms were used to identify key genes. Principal component analysis was used to calculate the ImPredict (IP) score. The interaction effects between biomarkers and treatment regimens were examined based on the logistic regression analysis. The relationship between the IP score and immune microenvironment was investigated through immunohistochemistry (IHC) and multiplex IHC.

Results

The area under the curves of the IP score were 0.935, 0.865, and 0.841 in the discovery cohort, validation cohort 1, and in-house cohort. Marker-treatment interaction tests indicated that the benefits from immunotherapy significantly varied between patients with high and low IP scores (p for interaction <0.001), and patients with high IP scores were more suitable for immunotherapy addition.

Conclusions

Our IP model shows favorable performance in predicting NACI response and is an effective tool for identifying BC patients who will benefit from ICIs. It may help clinicians optimize treatment strategies and guide clinical decision-making.
Sex-specific association of cardiovascular drug doses with adverse outcomes in atrial fibrillation
Authors: Moor Jeanne , Kuhne Michael , Moschovitis Giorgio , Kobza Richard , Netzer Seraina , Auricchio Angelo , Beer Juerg H , Bonati Leo , Reichlin Tobias , Conen David , Osswald Stefan , Rodondi Nicolas , Clair Carole , Baumgartner Christine , Aubert Carole Elodie
Published: August 2024

Objectives

Sex differences occur in atrial fibrillation (AF), including age at first manifestation, pathophysiology, treatment allocation, complication rates and quality of life. However, optimal doses of cardiovascular pharmacotherapy used in women with AF with or without heart failure (HF) are unclear. We investigated sex-specific associations of beta-blocker and renin–angiotensin system (RAS) inhibitor doses with cardiovascular outcomes in patients with AF or AF with concomitant HF.

Methods

We used data from the prospective Basel Atrial Fibrillation and Swiss Atrial Fibrillation cohorts on patients with AF. The outcome was major adverse cardiovascular events (MACEs), including death, myocardial infarction, stroke, systemic embolisation and HF-related hospitalisation. Predictors of interest were spline (primary analysis) or quartiles (secondary analysis) of beta-blocker or RAS inhibitor dose in per cent of the maximum dose (reference), in interaction with sex. Cox models were adjusted for demographics, comorbidities and comedication.

Results

Among 3961 patients (28% women), MACEs occurred in 1113 (28%) patients over a 5-year median follow-up. Distributions of RAS inhibitor and beta-blocker doses were similar in women and men. Cox models revealed no association between beta-blocker dose or RAS inhibitor dose and MACE. In a subgroup of patients with AF and HF, the lowest hazard of MACE was observed in women prescribed 100% of the RAS inhibitor dose. However, there was no association between RAS dose quartiles and MACE.

Conclusions

In this study of patients with AF, doses of beta-blockers and RAS inhibitors did not differ by sex and were not associated with MACE overall.
SIMUnet: an open-source tool for simultaneous global fits of EFT Wilson coefficients and PDFs
Authors:   PBSP Collaboration, Costantini Mark N. , Hammou Elie , Kassabov Zahari , Madigan Maeve , Mantani Luca , Morales-Alvarado Manuel , Moore James M. , Ubiali Maria
Published: August 2024

We present the open-source code, designed to fit Standard Model Effective Field Theory (SMEFT) Wilson coefficient alongside Parton Distribution Functions (PDFs) of the proton. can perform SMEFT global fits, as well as simultaneous fits of the PDFs and of an arbitrarily large number of SMEFT degrees of freedom, by including both PDF-dependent and PDF-independent observables. can also be used to determine whether the effects of any New Physics models can be fitted away in a global fit of PDFs. is built upon the open-source code and is released together with documentation, and tutorials. To illustrate the functionalities of the new tool, we present a new global analysis of the SMEFT Wilson coefficients accounting for their interplay with the PDFs. We increment our previous analysis of the LHC Run II top quark data with both (i) the Higgs production and decay rates data from the LHC, and (ii) the precision electroweak and diboson measurements from LEP and the LHC.
Neutrino masses from new seesaw models: low-scale variants and phenomenological implications
Authors: Giarnetti Alessio , Herrero-García Juan , Marciano Simone , Meloni Davide , Vatsyayan Drona
Published: August 2024

With just the Standard Model Higgs doublet, there are only three types of seesaw models that generate light Majorana neutrino masses at tree level after electroweak spontaneous symmetry breaking. However, if there exist additional TeV scalars acquiring vacuum expectation values, coupled with heavier fermionic multiplets, several new seesaw models become possible. These new seesaws are the primary focus of this study and correspond to the tree-level ultraviolet completions of the effective operators studied in a companion publication. We are interested in the genuine cases, in which the standard seesaw contributions are absent. In addition to the tree-level generation of neutrino masses, we also consider the one-loop contributions. Furthermore, we construct low-energy versions that exhibit a very rich phenomenology. Specifically, we scrutinise the generation of dimension-6 operators and explore their implications, including non-unitarity of the leptonic mixing matrix, non-universal $$Z-$$

Z
-

boson interactions, and lepton flavor violation. Finally, we provide (Generalised) Scotogenic-like variants that incorporate viable dark matter candidates.
Echoes of Veltman criteria on the next-two-Higgs-doublet model
Authors: Arhrib Abdesslam , Benbrik Rachid , Rahili Larbi , Semlali Souad , Taki Bassim
Published: August 2024

We investigate how the Next-Two-Higgs Doublet Model extension (N2HDM) should look if we are to address the naturalness problem using dimensional regularization. In such a model, new Higgs states are predicted, namely: three CP-even $$h_{1,2,3}$$

h

1
,
2
,
3

, one CP-odd A, and a pair of charged Higgs boson $$H^\pm $$

H
±

. Our calculations of the overall quadratic divergences have been performed with full consistency with the latest data from the Large Hadron Collider (LHC) concerning the observed 125 GeV Higgs boson, alongside precision electroweak data tests and lower mass limits on charged Higgs boson. It is shown that the quadratically divergent quantum corrections $$\delta _i$$

δ
i

(i=1,2,3) for the three CP-even Higgs bosons are controllably small, though hidden fine-tuning might still be required. This reveals a significant impact on the model parameter space, Higgs spectrum mass and notably the singlet-doublet admixture.
Hardening Active Directory Graphs via Evolutionary Diversity Optimization based Policies
Authors: Goel Diksha , Ward Max , Neumann Aneta , Neumann Frank , Nguyen Hung , Guo Mingyu
Published: August 2024

Active Directory (AD) is the default security management system for Windows domain networks. An AD environment can be described as a cyber-attack graph, with nodes representing computers, accounts, etc., and edges indicating existing accesses or known exploits that enable attackers to move from one node to another. This paper explores a Stackelberg game model between one attacker and one defender on an AD attack graph. The attacker’s goal is to maximize their chances of successfully reaching the destination before getting detected. The defender’s aim is to block a constant number of edges to minimize the attacker’s chance of success. The paper shows that the problem is #P-hard and, therefore, intractable to solve exactly. To defend the AD graph from cyber attackers, this paper proposes two defensive approaches. In the first approach, we convert the attacker’s problem to an exponential sized Dynamic Program that is approximated by a Neural Network (NN). Once trained, the NN serves as an efficient fitness function for defender’s Evolutionary Diversity Optimization based defensive policy. The diversity emphasis on the defender’s solution provides a diverse set of training samples, improving the training accuracy of our NN for modeling the attacker. In the second approach, we propose a RL based policy to solve the attacker’s problem and Critic network assisted Evolutionary Diversity Optimization based defensive policy to solve defender’s problem. Experimental results on synthetic AD graphs show that the proposed defensive policies are scalable, highly effective, approximate attacker’s problem accurately, and generate good defensive plans.
Exploring the Enhanced Oxidation Potential through Green Synthesis of Ofloxacin–Silver Complex: Investigating Silver and Ofloxacin Interaction at Varied Concentrations
Authors: Elaslani K. , Loudiki A. , Chhaibi B. , Laghrib F. , El Houssame S. , Bakasse M. , Lahrich S. , Farahi A. , El Mhammedi M. A.
Published: August 2024

The purpose for this work is to synthesize ofloxacin–Silver(I) complex with the highest oxidation potential in liquid state with green methodology. Initially, we investigated the complexation of the OFL ligand with silver ions using UV-visible spectrophotometry, differential pulse wave voltammetry, and electrochemical impedance spectroscopy. The UV-visible results indicated the interaction between OFL and Ag+ through a complexation reaction. Notably, the peak corresponding to OFL oxidation at 0.98 V showed a significant increase in the presence of silver, leading to an oxidation potential shift towards positive values attributed to the bond formation between the OFL and Ag+. In terms of structural characterization, various spectroscopic analyses were employed, including Fourier transform infrared spectroscopy (FTIR), X-ray diffraction, and scanning electron microscopy. The OFL–Ag+ complex formation was confirmed by the appearance of two distinct sharp bands at 547 and 950 cm−1 in the FTIR spectra. The average particle diameter of the OFL–Ag+ complex was determined to be 187.5 nm. This complex, synthesized as a brown solid powder soluble in water, exhibited the highest oxidation potential of 1.32 V. Hence, it holds promise for potential application in antibacterial activity.
Characterization of Goji Quality at Different Harvest Stages in Qaidam Basin Based on Transcriptome and Widely Targeted Metabolome
Authors: Cui Mingming , Xiao Ming , Zhang Defang , Xie Zhanling
Published: August 2024

Goji, a renowned traditional Chinese medicine and food source, is characterized by a long fruiting period. This study was conducted to investigate the variations in nutritional quality of goji berries across different harvest stages by utilizing widely targeted metabolome and transcriptome. The results showed that goji berries of the first harvest stage had advantages in terms of size and metabolic levels, and there was little difference in sugars and organic acids levels. Within significantly enriched phenylpropanoid and flavonoid pathways, chlorogenic acid, and its positional isomers (neochlorogenic acid and cryptochlorogenic acid) increased significantly along with P‐coumaroyl quinic acid as the harvest stages progressed, while the other bioactive DEMs including scopoletin, scopolin, naringenin, and pruning exhibited a decreasing trend. The key DEGs encoding PAL, HCT, 4CL, C4H, TOGT1, and C12RT1 were suggested to regulate the variations of these DEMs. Furthermore, six oxidative metabolites enriched in alpha‐linolenic acid and linoleic acid metabolism pathways all peaked at the second harvest stage. Climate or plant weakening is suggested as potential factors influencing the metabolic and transcriptomic changes in goji berries. This study provides a fresh perspective on understanding the accumulation of metabolites and their molecular mechanisms in goji at different harvest stages in the Qaidam Basin and can be used to guide goji production and processing.
Contrastive Learning with Edge‐Wise Augmentation for Rumor Detection
Authors: Liu Nan , Zhang Fengli , Gao Qiang , Chen Xueqin
Published: August 2024

Exploring and modeling the spreading process of rumors have shown great potential in improving rumor detection performance. However, existing propagation‐based rumor detection models often overlook the uncertainty of the underlying propagation structure and typically require a large amount of labeled data for training. To address these challenges, we propose a novel rumor detection framework, namely, the Uncertainty‐Inference Contrastive Learning (UICL) model. Specifically, UICL innovatively incorporates an edge‐wise augmentation strategy into the general contrastive learning framework, including an edge‐inference augmentation component and an EdgeDrop augmentation component, which primarily aim to capture the edge uncertainty of the propagation structure and alleviate the sparsity problem of the original dataset. A new negative sampling strategy is also introduced to enhance contrastive learning on rumor propagation graphs. Furthermore, we use labeled data to fine‐tune the detection module. Our experiments, conducted on three real‐world datasets, demonstrate that UICL can not only significantly improve detection accuracy but also reduce the dependency on labeled data compared to state‐of‐the‐art baselines.
Immobilisation and Epidural Anaesthesia in a Eurasian Lynx (Lynx lynx) Undergoing Pelvic Limb Orthopaedic Surgery
Authors: Campos Sonia , Picavet Pierre , Bertrand Olivier , Sandersen Charlotte , Tutunaru Alexandru
Published: August 2024

Immobilisation and anaesthesia of wild felids may be complex and potentially dangerous events, making it difficult to implement more advanced anaesthetic techniques such as neuraxial anaesthesia. A Eurasian lynx was referred for femur fracture repair after it was seen with lameness of the left pelvic limb sustained in its natural environment. The animal was remotely darted using a combination of ketamine (5 mg/kg) and xylazine (5 mg/kg) intramuscularly. Once immobilised, the lynx was transported to the veterinary hospital in a restraining cage. After induction and endotracheal intubation, pelvic limb radiographs confirmed a closed, comminuted fracture of the left femur that required open reduction and internal stabilisation. A sacrococcygeal epidural was performed before surgery using lidocaine (2 mg/kg) and morphine (0.1 mg/kg) to complement the ketamine–xylazine–isoflurane anaesthesia, which allows a low‐end‐tidal isoflurane concentration. Clinical signs were continuously monitored and remained stable during the entire procedure, with the exception of a temperature that decreased to 35.8°C. No intraoperative analgesic rescues were necessary. Recovery was smooth and uneventful. The lynx showed no signs of motor weakness after surgery or other side effects related to the anaesthetic procedure. The successful management of this surgical case suggests that the described anaesthetic protocol could be recommended in orthopaedic procedures of the pelvic limbs in wild Felidae.
Construction and Evaluation of a Predictive Model for Liver Injury Associated with Heatstroke: A Multicenter Retrospective Study
Authors: Gao Hongguang , Tang Guo , Yang Sha , Yang Ying , Sheng Jie , Yao Rong
Published: August 2024

Background. Liver injury related to heatstroke plays a pivotal role in secondary multiorgan damage and is a direct cause of mortality in affected patients of heatstroke. This study was designed to identify independent risk factors associated with liver injury in heatstroke and to construct a clinically applicable predictive model. Methods. We conducted a retrospective analysis of 188 patients diagnosed with heatstroke, treated in the emergency departments of eight medical institutions from July 1, 2022, to September 30, 2023. Patients were categorized into a liver injury group (n = 80) and a nonliver injury group (n = 108), based on liver function indices recorded during hospitalization. Lasso regression was employed for variable refinement, while multifactorial logistic regression was utilized to identify independent risk factors for liver injury in heatstroke and to construct a nomogram model. The model’s efficacy was evaluated using the C‐index, calibration curves, and decision curve analysis, examining its discriminative ability, calibration, and clinical utility. Results. The nomogram included predictive factors such as the Glasgow score, absolute lymphocyte count, lactate dehydrogenase levels, and creatine kinase isoenzyme. The model showed high accuracy and discriminative capability. The C‐index was 0.852 (95% CI 0.80–0.905) with a calibration index of 0.843. Decision curve analysis revealed significant clinical applicability for this nomogram. Conclusion. The study identified four key independent risk factors for liver injury in heatstroke patients. The constructed nomogram, based on the four clinical indicators, demonstrated robust predictive accuracy, discriminative power, and clinical relevance.
The CCR6–CCL20 Axis Promotes Regulatory T-cell Glycolysis and Immunosuppression in Tumors
Authors: Pant Ayush , Jain Aanchal , Chen Yiyun , Patel Kisha , Saleh Laura , Tzeng Stephany , Nitta Ryan T. , Zhao Liang , Wu Caren Yu-Ju , Bederson Maria , Wang William Lee , Bergsneider Brandon Hwa-Lin , Choi John , Medikonda Ravi , Verma Rohit , Cho Kwang Bog , Kim Lily H. , Kim Jennifer E. , Yazigi Eli , Lee Si Yeon , Rajendran Sakthi , Rajappa Prajwal , Mackall Crystal L. , Li Gordon , Tyler Betty , Brem Henry , Pardoll Drew M. , Lim Michael , Jackson Christopher M.
Published: August 2024

Regulatory T cells (Treg) are important players in the tumor microenvironment. However, the mechanisms behind their immunosuppressive effects are poorly understood. We found that CCR6–CCL20 activity in tumor-infiltrating Tregs is associated with greater glycolytic activity and ablation of Ccr6 reduced glycolysis and lactic acid production while increasing compensatory glutamine metabolism. Immunosuppressive activity toward CD8+ T cells was abrogated in Ccr6−/− Tregs due to reduction in activation-induced glycolysis. Furthermore, Ccr6−/− mice exhibited improved survival across multiple tumor models compared to wild-type mice and Treg and CD8+ T-cell depletion abrogated the improvement. In addition, Ccr6 ablation further promoted the efficacy of anti-PD-1 therapy in a preclinical glioma model. Follow-up knockdown of Ccl20 with siRNA also demonstrated improvement in antitumor efficacy. Our results unveil CCR6 as a marker and regulator of Treg-induced immunosuppression and identify approaches to target the metabolic determinants of Treg immunosuppressive activity.
Table S4 from p53R172H and p53R245W Hotspot Mutations Drive Distinct Transcriptomes in Mouse Mammary Tumors Through a Convergent Transcriptional Mediator
Authors: McDaniel Joy M. , Morrissey Rhiannon L. , Dibra Denada , Patel Lalit R. , Xiong Shunbin , Zhang Yun , Chau Gilda P. , Su Xiaoping , Qi Yuan , El-Naggar Adel K. , Lozano Guillermina
Published: August 2024

Summary of Hallmarks enriched in MaP-/- mammary tumors compared ompared to MaPR172H/- mammary tumors.
Figure 5 from Tumor Vessel Normalization via PFKFB3 Inhibition Alleviates Hypoxia and Increases Tumor Necrosis in Rectal Cancer upon Radiotherapy
Authors: Edelmann Marcus , Fan Shuang , De Oliveira Tiago , Goldhardt Tina , Sartorius Dorothée , Midelashvili Teona , Conrads Karly , Paul Niels B. , Beißbarth Tim , Fleischer Johannes R. , Blume Moritz L. , Bohnenberger Hanibal , Josipovic Natasa , Papantonis Argyris , Linnebacher Michael , Dröge Leif H. , Ghadimi Michael , Rieken Stefan , Conradi Lena-Christin
Published: August 2024

3PO administration in combination with radiotherapy increases tumor necrosis and DNA damage in RC cells in vivo. A, Relative body weight curves of mice in different therapy groups. B, Relative growth curve of rectal PDX tumors upon treatment with vehicle (control; n = 5), 3PO (25 mg/kg; 3×/week; n = 4), RT (1.8 Gy single dose; 5×/week; n = 4), and dual therapy 3PO + RT (25 mg/kg; 3×/week; 1.8 Gy single dose; 5×/week; n = 5). Arrows indicate administration of 3PO and RT. Data are displayed as means ± SEM, ∗, P < 0.05; one-way ANOVA. ∗, P value refers to RT or RT + 3PO compared with control. C, PDX tumor weight. Data are displayed as means ± SD. ∗, P < 0.05; one-way ANOVA. D, Representative H&E staining images of PDX tumors upon treatment with vehicle (control), 3PO, RT, and 3PO + RT. Scale bars, 500 and 100 µm. Arrow heads: representative necrotic areas; asterisks: viable tumor areas. E, Viable tumor area quantification (% of total tumor area). Data are displayed as means SD. ∗, P < 0.05; ∗∗∗∗, P < 0.0001; Student t test. F, Quantification of apoptosis by cleaved caspase-3 staining. Data are displayed as means SD. ∗∗∗, P < 0.001; ∗∗∗∗, P < 0.0001; one-way ANOVA. G, Quantification of DNA fragmentation using TUNEL staining. Data are displayed as means SD. ∗, P < 0.05; ∗∗, P < 0.01; ∗∗∗∗, P < 0.0001; one-way ANOVA. H, Representative images from TUNEL staining in PDX tumors upon treatment with vehicle (control), 3PO, RT, and 3PO + RT. Scale bars, 25 µm. I, Quantification of proliferation using bromodeoxyuridine (BrdU) staining. Data are displayed as means ± SD. ∗, P < 0.05; ∗∗∗∗, P < 0.0001; one-way ANOVA. J, Quantification of PFKFB3 expression in tumor tissue. Data are displayed as means SD. ∗∗∗, P < 0.001; ∗∗∗∗, P < 0.0001; one-way ANOVA. K, Representative images from PFKFB3 staining in PDX tumors upon treatment with vehicle (control), 3PO, RT, and 3PO + RT. Scale bars, 200 µm.
Figure 1 from Tumor Vessel Normalization via PFKFB3 Inhibition Alleviates Hypoxia and Increases Tumor Necrosis in Rectal Cancer upon Radiotherapy
Authors: Edelmann Marcus , Fan Shuang , De Oliveira Tiago , Goldhardt Tina , Sartorius Dorothée , Midelashvili Teona , Conrads Karly , Paul Niels B. , Beißbarth Tim , Fleischer Johannes R. , Blume Moritz L. , Bohnenberger Hanibal , Josipovic Natasa , Papantonis Argyris , Linnebacher Michael , Dröge Leif H. , Ghadimi Michael , Rieken Stefan , Conradi Lena-Christin
Published: August 2024

3PO affects normal epithelial and colorectal cancer cell proliferation and viability in a concentration-dependent manner. A, xCELLigence assay performed with HCT-116, HT-29, SW-1463, SW-837, HUVECs, and RPE-1 cells. Real-time cell analysis following treatment with different concentrations of 3PO over a period of 96 hours. Dotted lines indicate the fitted saturation curve in logarithm, n = 3 independent experiments. B and C, CellTiter-Blue assay performed with HCT-116, HT-29, SW-1463, SW-837, HUVECs, and RPE cells treated with different concentrations of 3PO for 24 and 48 hours. D and E, LDH assay performed with HCT-116, HT-29, SW-1463, SW-837, HUVECs, and RPE cells treated with different concentrations of 3PO for 24 and 48 hours. B–E, Data are displayed as means SD, ∗, P < 0.05; ∗∗, P < 0.01; ∗∗∗, P < 0.001; ∗∗∗∗, P < 0.0001. One-way ANOVA was used to calculate statistical significance, n = 3 independent experiments.
High Expression of Cancer-Derived Sialylated Immunoglobulin G: A Novel Biomarker for Poor Prognosis in Laryngeal Squamous Cell Carcinoma
Authors: Xu Meng , Zhang Shenghua , Zhang Ye , Qiu Xiaoyan , Wang Xiaolei
Published: August 2024

Introduction: Laryngeal squamous cell carcinoma (LSCC) is the most common type of laryngeal cancer, with around 60% of patients being diagnosed at an advanced stage. Recently, cancer-derived sialylated immunoglobulin G (SIA-IgG) has been suggested to play a role in the progression of various epithelial tumors, but its significance in LSCC remains unknown. This study aimed to investigate the clinical significance of SIA-IgG as a novel biomarker in relation to the initiation, progression, and prognostication of LSCC. Methods: Immunohistochemistry (IHC) was utilized to assess SIA-IgG expression in tumor samples from 75 LSCC patients, aiming to investigate its correlation with clinical prognosis. In vitro functional experiments were conducted to explore the impact of SIA-IgG expression on the proliferative and migratory abilities of laryngocarcinoma cells. Results: High expression of SIA-IgG was associated with pT stage, pN stage, TNM stage, and recurrence during follow-up and was correlated with poor disease-free survival (DFS) and overall survival (OS). Multivariate Cox analysis demonstrated that SIA-IgG served as an independent risk factor for OS and DFS. Knocking down SIA-IgG significantly weakened laryngocarcinoma cells’ proliferation, clonogenesis, and migration abilities. Conclusions: The frequent expression of SIA-IgG in LSCC is significantly associated with poor prognosis. High levels of SIA-IgG can enhance proliferation and migration in laryngocarcinoma cells. These findings suggest that SIA-IgG has potential as a novel biomarker for LSCC.
Rates and Impact of Serious Adverse Events after Endovascular Thrombectomy among Large Vessel Occlusion Stroke Patients
Authors: Lei Bo , Yang Shuang , Tian Ling , Zhou Simin , Nguyen Thanh N. , Abdalkader Mohamad K. , Liu Xing , Sun Yingbin , Zhao Ning , Han Qin , Mao An , Tao Zhaojun , Wang Yan , Cao Wenfeng , Yang Shiquan , Zhang Jun , Guo Fuqiang , Wen Hongbin , Zhang Jinhua , Yue Chengsong , Yang Jie , Sang Hongfei , Qiu Zhongming , Jin Ying , Luo Weidong
Published: August 2024

Objective: Complications or serious adverse events (SAEs) are common in the treatment of patients with large vessel occlusion stroke. There has been limited study of the impact of SAEs for patients after endovascular thrombectomy (EVT). The goal of this study was to characterize the rates and clinical impact of SAEs following EVT. Methods: A post hoc analysis was performed using pooled databases of the “DEVT” and “RESCUE BT” trials. SAEs were designated as symptomatic intracranial hemorrhage, brain herniation or craniectomy, respiratory failure, circulatory failure, pneumonia, deep venous thrombosis, and systemic bleeding. The primary endpoint was functional independence (modified Rankin scale score 0–2 within 90 days). Logistic regression analysis was used to determine the predictors and associations between SAEs and outcomes. Results: Of 1,182 enrolled patients, 402 (34%) had a procedural complication and 745 (63%) had 1,404 SAE occurrences with 4.65% in-hospital mortality. The three most frequent SAEs were pneumonia (620, 52.5%), systemic bleeding (174, 14.7%), and respiratory failure (173, 14.6%). Pneumonia, systemic bleeding, or deep venous thrombosis was less life-threatening. Patients with advanced age (adjusted odds ratio, 1.28 [95% confidence interval, 1.14–1.43]), higher NIHSS (1.09 [1.06–1.11]), occlusion site (middle cerebral artery-M1 vs. internal carotid artery [ICA]: 0.75 [0.53–1.04]; M2 vs. ICA: 1.30 [0.80–2.12]), longer procedure time (1.01 [1.00–1.01]), and unsuccessful vessel recanalization (1.79 [1.06–2.94]) were more likely to experience SAEs. Compared with no SAE, patients with SAEs had lower odds of functional independence (0.46 [0.40–0.54]). Conclusions: Overall, SAEs diagnosed following thrombectomy in patients with stroke were common (more than 60%) and associated with functional dependence. Patients with advanced age, higher NIHSS, longer procedure time, and failed recanalization were more likely to experience SAEs. There was no statistical difference in the risk of SAEs among patients with M1 and M2 occluded compared with those ICA occluded. An understanding of the prevalence and predictors of SAEs could alert clinicians to the estimated risk of an SAE for a patient after EVT.
Coagulation Risk Predicting in Anticoagulant-Free Continuous Renal Replacement Therapy
Authors: Liu Liang , Liu Dashuang , He Ting , Liang Bo , Zhao Jinghong
Published: August 2024

Introduction: Continuous renal replacement therapy (CRRT) is a prolonged continuous extracorporeal blood purification therapy to replace impaired renal function. Typically, CRRT therapy requires routine anticoagulation, but for patients at risk of bleeding and with contraindications to sodium citrate, anticoagulant-free dialysis therapy is necessary. However, this approach increases the risk of CRRT circuit coagulation, leading to treatment interruption and increased resource consumption. In this study, we utilized artificial intelligence machine learning methods to predict the risk of CRRT circuit coagulation based on pre-CRRT treatment metrics. Methods: We retrospectively analyzed 212 patients who underwent anticoagulant-free CRRT from October 2022 to October 2023. Patients were categorized into high-risk and low-risk groups based on CRRT circuit coagulation within 24 h. We employed eight machine learning methods to predict the risk of circuit coagulation. The performance of the model was evaluated using the area under the curve (AUC) of the receiver operating characteristic. 5-fold cross-validation was used to validate the machine learning models. Feature importance and SHAP plots were used to interpret the model’s performance and key drivers. Results: We identified 88 patients (41.51%) at high risk of circuit coagulation within 24 h of CRRT. Our machine learning models showed excellent predictive performance, with ensemble learning achieving an AUC of 0.863 (95% CI: 0.860–0.868), outperforming individual algorithms. Random forest was the best single-algorithm model, with an AUC of 0.819 (95% CI: 0.814–0.823). The top three features identified as most important by the SHAP summary plot and feature importance graph are platelet, filtration fraction (FF), and triglycerides. Conclusion: We created a model using machine learning to predict the risk of circuit coagulation during anticoagulant-free CRRT therapy. Our model performs well (AUC 0.863) and identifies key factors like platelets, FF, and triglycerides. This facilitates the development of personalized treatment strategies by clinicians aimed at reducing circuit coagulation risk, thereby enhancing patient outcomes and reducing healthcare expenses.
Acute Effect of Imeglimin Add-on Therapy on 24-h Glucose Profile and Glycemic Variability in Patients with Type 2 Diabetes Receiving Metformin
Authors: Shinohara Yasutake , Jojima Teruo , Kamiga Yusuke , Sakurai Shintaro , Iijima Toshie , Tomaru Takuya , Akutsu Ikuo , Inoue Teruo , Usui Isao , Aso Yoshimasa
Published: August 2024

Introduction: Imeglimin is a novel antidiabetic drug with insulinotropic and insulin-sensitizing effects that targets mitochondrial bioenergetics. We investigated acute effects of add-on therapy with imeglimin to preceding metformin on the 24-h glucose profile and glycemic variability assessed by continuous glucose monitoring (CGM) in patients with type 2 diabetes. Methods: We studied 30 outpatients with type 2 diabetes inadequately controlled with metformin. CGM was used for 14 days straight during the research period. Imeglimin 2,000 mg/day was started on day 7 after initiating CGM. Several CGM parameters were compared between days 4–6 (prior to imeglimin treatment) and 11–13 (following the initiation of imeglimin treatment). Results: After treatment with imeglimin, 24-h mean glucose was acutely decreased from 161.6 ± 48.0 mg/dL to 138.9 ± 32.2 mg/dL (p < 0.0001), while time in range (i.e., at a glucose level of 70–180 mg/dL) was significantly increased from 69.9 ± 23.9% to 80.6 ± 21.0% (p < 0.0001). Addition of imeglimin to metformin significantly decreased the standard deviation (SD) of 24-h glucose and mean amplitude of glycemic excursions, 2 indexes of glycemic variability. Baseline serum high-density lipoprotein (HDL) cholesterol was negatively correlated with changes in mean 24-h glucose (r = −0.3859, p = 0.0352) and those in SD (r = −0.4015, p = 0.0309). Conclusions: Imeglimin add-on therapy to metformin acutely lowered 24-h glucose levels and improved glycemic variability in patients with type 2 diabetes on metformin. A higher serum HDL cholesterol at baseline was associated with a better response to acute effects of imeglimin on 24-h glucose levels and glycemic variability.
The Latin-American Experience in POEMS Syndrome: A Study of the GELAMM (Grupo de Estudio Latinoamericano de Mieloma Múltiple)
Authors: Gallardo-Pérez Moisés Manuel , Negrete-Rodríguez Paola , Gertz Morie A. , Peña Camila , Riva Eloisa , Gilli Virginia , Rodríguez Gloritza , Samánez César , Ferreira Joaquín , Portiño Sergio , Montaña Jacqueline , León Pilar , Gutiérrez Yaima , Del-Castanhel Caroline , Seehaus Cristian , Funes Maria Eugenia , Meneces-Bustillo Rodrigo , Duarte Patricio , Shanley Claudia , Elvira Giannini , Ochoa Paola , López-Vidal Hernán , Martinez-Cordero Humberto , Vasquez Jule , von-Glasenapp Alana , Donoso Javiera , Viñuela Jose Luis , Ruiz-Delgado Guillermo J. , Ruiz-Argüelles Guillermo J.
Published: August 2024

Introduction: POEMS syndrome is a rare paraneoplastic syndrome caused by an underlying plasma cell disorder. The acronym refers to the following features: polyradiculoneuropathy, organomegaly, endocrinopathy, monoclonal paraproteinemia, and skin changes. Methods: The study was conducted at 24 hematological centers across 8 Latin-American countries. The study included a total of 46 patients {median age was 52 years (interquartile range [IQR]: 42–61.5), 30 males and 16 females} fulfilling the POEMS syndrome criteria diagnosed over a period of 12 years (January 1, 2011, through July 31, 2023). Epidemiological and clinical data were collected in an ad hoc database sent to the members of GELAMM, as well as the Kolmogorov-Smirnov test and Kaplan-Meier estimates. Results: All patients had polyneuropathy and monoclonal gammopathy; 89% had bone marrow plasma cell infiltration, 33% had sclerotic bone lesions. Only 10 patients underwent vascular endothelial growth factor (VEGF) testing in plasma samples. The paraproteinemia was IgG λ in 32% and IgA λ in 30%. 59% patients presented with cutaneous changes, mainly hyperpigmentation, 54% had organomegaly, and 74% endocrinopathy. The median interval from symptom onset to diagnosis was 7.7 months (IQR: 4.0–12.6). 69% of patients received a single line of treatment. The median follow-up period was 25 months (IQR: 9.37–52.0) and the 2-year overall survival rate was 100%. All patients who underwent transplantation (43%) are alive, with a median follow-up of 45.62 months (IQR: 15.46–70). Conclusion: This study investigates POEMS syndrome in Latin America and presents an initial overview of the disease in the region. VEGF usage is recommended for accurate diagnosis, but only 7 hematology centers in the region used it. Survival rate in Latin America is comparable with those observed internationally.
A ascensão do romance na periferia celta: um estudo sobre a composição política, didática e antirromanesca de Castle Rackrent
Authors: Souza Michelle Andressa Alvarenga de
Published: August 2024

O presente artigo demonstra como a percepção da união na diferença pode ser identificada no romance Castle Rackrent de Maria Edgeworth, publicado em 1800. Esta breve investigação se debruça sobre o didatismo dessa obra ficcional, classificada como National Tale. Este trabalho ainda explora a mediação proporcionada por sua estrutura formal, sobretudo o aparato paratextual, e reflete acerca do desafio da formação de uma dimensão conciliatória no romance, que não traz o casamento como superação do conflito narrativo. Mostra-se, ainda, como os desafios sociais impostos pela conturbada realidade da periferia celta impedem a composição de um romance realista e resultam em uma espécie de antirromance, que evidencia as contradições e ambivalências da realidade irlandesa em um momento crítico da história. Conclui-se demonstrando como o romance estudado apresenta uma solução ideológica que pode ser percebida em duas frentes: a de uma reforma feita pela elite da ascendência anglo-irlandesa, capaz de manter o status quo preservando as tradições do país; e uma atitude assimilativa por parte da Grã-Bretanha na ocasião da União com a Irlanda, que incorpore a alteridade ao invés de rejeitá-la.
A Review of Narratives of the Unspoken in Contemporary Irish Fiction: Silences that Speak
Authors: Borges Esther
Published: August 2024

Published in 2023 by Palgrave Macmillan, Narratives of the Unspoken in Contemporary Irish Fiction: Silences that Speak proposes to explore the topic of silence by analysing how it is embedded in language, culture, society and institutions and providing a forum for the discussion of the uses (and abuses) of silence in the context of Irish ﬁction. The essays cover a span of different well-known authors in the Irish literary sphere such as Donal Ryan, Emma Donoghue, Colm Tóibín, Evelyn Conlon, Kevin Barry, Edna O’Brien, William Trevor, Claire Keegan, Maeve Kelly, Eibhear Walshe, Emer Martin and Sally Rooney
Abstract 4341: Dyssynchrony is a Prerequisite condition for Beta Reserve Upregulation By Cardiac Resynchronization Therapy
Authors: Chakir Khalid , Tunin Richard S , Aiba Takeshi , Tomaselli Gordon , Kass David A
Published: August 2024

Background
Dyssynchronous Heart failure (DHF) versus synchronous is characterized by unique cellular and molecular substrates involving stress kinase and cell survival signaling (

Chakir et al.

Circulation

2008
;
117
:
1369
–77

).

Hypothesis
The impact of CRT may depend upon whether there was a preceding dyssynchrony. Here, we tested such dyssynchrony dependence on basal and beta-adrenergic stimulated myocyte function in a canine HF model.

Methods
Adult dogs (n=8) underwent LBB radio-frequency ablation; half then subjected to atrial tachypacing-induced dyssynchronous HF (DHF) for 6wks, while the others had 3 weeks DHF followed by 3-wks bi-ventricular tachypacing (CRT). 5 additional dogs were subjected to RV freewall tachypacing for 3wks (dyssynchrony) followed by 3 weeks right atrial tachypacing (resynchronization; V3A3), and 3 more were subjected to synchronous heart failure (RA tachypacing for 6 wks; A6). 3 non-paced dogs served as controls. Myocytes were enzymatically isolated from the LV free wall and field stimulated in a perfusion chamber. Sarcomere shortening and calcium transient were determined with and without 10
−7
M isoproterenol.

Results:
DHF, V3A3, A6 and CRT hearts had similar global failure, with dP/dtmax 1190.2±139.8 vs. 1111.8±131.6 vs. 1333.0±205.2 vs. 1195.3±137.6 mmHg/s, respectively (1900.3±176.8 in control). However, there were marked differences in basal and β-stimulated myocyte calcium transients and sarcomere shortening (Table

, n=8 –30 cells/ group). Intriguingly, both DHF and A6 cells had reduced basal and β-AR stimulated sarcomere shortening and Ca transients versus control. In contrast, both V3A3 and CRT displayed enhanced rest and β-AR responses.

Conclusion:
HF resynchronization improves rest and β-AR cellular function over those never dyssynchronous. A particular substrate develops with DHF that when offset by CRT enhances cellular function beyond that with synchronous HF; explaining the CRT impact in targeted patients.
Limitations of 2-dimensional line-scan MRI for directly measuring neural activity
Authors: Wilson Joshua M. , Wu Hua , Kerr Adam B. , Wandell Brian A. , Gardner Justin L.
Published: August 2024

A 2D-line-scan MRI sequence has been reported to directly measure neural responses to stimuli (the “DIANA response”). Attempts to replicate the DIANA response have failed, even with higher field strength and more repetitions. Part of this discrepancy is likely due to a limited understanding of how physiological noise manifests in 2D-line-scan acquisition sequences. Specifically, it is unclear what the consequences are of breaking the assumption that the imaging substrate remains constant between each line acquisition. To answer this question, we collected 2D-line-scan data at 3T from human subjects viewing a blank screen. We found temporal fluctuations in the reconstructed time series that could easily be confused with neural responses to stimuli. These fluctuations were present both in the head and in the surrounding empty volume along the span of the phase-encoding direction from the head. The timing of these fluctuations varied systematically and smoothly along the phase-encoding direction. These artifacts are similar to well-known phase-encoding artifacts in EPI and GRE images, but are exacerbated due to longer acquisition times in the 2D-line-scan sequence (seconds vs. milliseconds). We explain these artifacts with a model that accounts for the acquisition sequence and incorporates time-varying contrast fluctuations and movement in the imaging substrate. Using the model, we quantify the amount of cortical- and scan-averaging one might need to reliably distinguish a DIANA response from noise, and show that navigator echoes might help in reducing phase-encode noise in the 2D-line-scan sequence.
Toward an Understanding of a Misconceived Igbo Deity
Authors: Onah Tobias Chibuike , Uwaegbute Kingsley Ikechukwu , Eze Virginus Uchenna
Published: August 2024

This ethnographic study investigates the misconception among Christians and adherents of African Traditional Religion in their view and understanding of the deity ‘ekwensu’, commonly called Satan in Christian theology. The study area is Nsukka, a culture area in Nigeria. The adherents of the two religions use the words ‘Satan’ and ‘devil’ for ekwensu interchangeably. Many Christians claim that Satan is the sole equivalent of the traditional deity ekwensu in the Igbo cosmology. The aim of the work is to compare the Christian views of ekwensu as Satan, bringing out the origin, attributes, and activities of the two concepts ekwensu and Satan. The findings show significant differences between Satan and ekwensu, that Satan and ekwensu vary in their origin and attributes, and that they have different geographical locations. It is shown that some shrines and forests were dedicated to the ekwensu deity in Nsukka, and that masquerades also honour the festival of ekwensu (afor ekwensu). It is also evident that Christianity had a significant impact on the culture of the Nsukka people, which engendered the misconception of the ekwensu deity. This was partly based on Igbo Christian theolinguistics occasioned by Christian missionary activities in the area.
DNA barcodes and morphology reveal new species within the Cryptochironomus Kieffer from Oriental China (Diptera: Chironomidae)
Authors: LIU WEN-BIN , WANG CHENG-YAN , TANG YA-NING , PEI WEN-XUAN , YAN CHUN-CAI
Published: August 2024

The genus Cryptochironomus has a cosmopolitan distribution including over 140 valid described species worldwide. The morphological characteristics and DNA barcode data of Cryptochironomus inflatus Liu, sp. nov. based on specimens collected from Oriental China. DNA barcode analysis including the partial COI sequences of species of genus Cryptochironomus is conducted. An updated key to adult males of the genus is provided.
New genus and new species of the tribe Elicini Melichar (Hemiptera: Fulgoroidea, Tropiduchidae) with sternal sensory pits in imago from Western Australia
Authors: GNEZDILOV VLADIMIR M.
Published: August 2024

A new genus, Petocica gen. n., with a type species, Petocica perforata sp. nov., is described from vicinity of Leinster in Western Australia. A new species is peculiar by the presence of sensory pits on abdominal sternites IV–VI in adult female. The taxa of Fulgoroidea with sensory pits in adults and possible function of the pits are briefly discussed.