bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuro-environmental interactions: a time sensitive matter
Authors: Invernizzi Azzurra , Renzetti Stefano , Rechtman Elza , Ambrosi Claudia , Mascaro Lorella , Corbo Daniele , Gasparotti Roberto , Tang Cheuk Y. , Smith Donald R. , Lucchini Roberto G. , Wright Robert O. , Placidi Donatella , Horton Megan K. , Curtin Paul
Published: January 2024

Introduction

The assessment of resting state (rs) neurophysiological dynamics relies on the control of sensory, perceptual, and behavioral environments to minimize variability and rule-out confounding sources of activation during testing conditions. Here, we investigated how temporally-distal environmental inputs, specifically metal exposures experienced up to several months prior to scanning, affect functional dynamics measured using rs functional magnetic resonance imaging (rs-fMRI).

Methods

We implemented an interpretable XGBoost-shapley additive explanation (SHAP) model that integrated information from multiple exposure biomarkers to predict rs dynamics in typically developing adolescents. In 124 participants (53% females, ages, 13–25 years) enrolled in the public health impact of metals exposure (PHIME) study, we measured concentrations of six metals (manganese, lead, chromium, copper, nickel, and zinc) in biological matrices (saliva, hair, fingernails, toenails, blood, and urine) and acquired rs-fMRI scans. Using graph theory metrics, we computed global efficiency (GE) in 111 brain areas (Harvard Oxford atlas). We used a predictive model based on ensemble gradient boosting to predict GE from metal biomarkers, adjusting for age and biological sex.

Results

Model performance was evaluated by comparing predicted versus measured GE. SHAP scores were used to evaluate feature importance. Measured versus predicted rs dynamics from our model utilizing chemical exposures as inputs were significantly correlated (p < 0.001, r = 0.36). Lead, chromium, and copper contributed most to the prediction of GE metrics.

Discussion

Our results indicate that a significant component of rs dynamics, comprising approximately 13% of observed variability in GE, is driven by recent metal exposures. These findings emphasize the need to estimate and control for the influence of past and current chemical exposures in the assessment and analysis of rs functional connectivity.
The combination of accent method and phonemic contrast: an innovative strategy to improve speech production on post-stroke dysarthria
Authors: Ge Shengnan , Wan Qin , Wang Yongli , Yin Minmin , Huang Zhaoming
Published: January 2024

Introduction

Speech production includes segmental and suprasegmental features, which interact and cooperate with each other. Impaired speech production is common in individuals with post-stroke dysarthria. The commonly used phonemic contrast therapy and Accent Method in clinical practice can improve the segmental and suprasegmental aspects, respectively. This study aimed to explore the feasibility and immediate effectiveness of the combination of specific rhythm patterns of the Accent Method and phonemic contrast on speech production.

Methods

Fifteen poststroke dysarthria patients (12 males and three females) first received accentuation task of three rhythm patterns (Largo-slow, Andante-medium, Allegro-fast) and later received speech task in appropriate rhythm patterns combined with phonemic contrast materials and non-phonemic contrast materials. Speech parameters were analyzed by considering speech clarity and prosody.

Results

The results showed that the number of correct target syllables, sentence clarity, and standard deviation of intensity increased significantly, and the average length of pauses and abnormal pause times decreased significantly in Andante (medium) compared to other rhythms. The number of correct target syllables, sentence clarity, and standard deviation of intensity increased significantly compared with those in the non-phonemic contrast in Andante (medium).

Conclusion

The combination of phonemic contrast and Accent Method was verified to have an immediate effect on speech production in Mandarin speakers with post-stroke dysarthria and could be further validated in other diseases with impaired speech production in the clinic in the future.
Minding the gut: extending embodied cognition and perception to the gut complex
Authors: Boem Federico , Greslehner Gregor P. , Konsman Jan Pieter , Chiu Lynn
Published: January 2024

Scientific and philosophical accounts of cognition and perception have traditionally focused on the brain and external sense organs. The extended view of embodied cognition suggests including other parts of the body in these processes. However, one organ has often been overlooked: the gut. Frequently conceptualized as merely a tube for digesting food, there is much more to the gut than meets the eye. Having its own enteric nervous system, sometimes referred to as the “second brain,” the gut is also an immune organ and has a large surface area interacting with gut microbiota. The gut has been shown to play an important role in many physiological processes, and may arguably do so as well in perception and cognition. We argue that proposals of embodied perception and cognition should take into account the role of the “gut complex,” which considers the enteric nervous, endocrine, immune, and microbiota systems as well as gut tissue and mucosal structures. The gut complex is an interface between bodily tissues and the “internalized external environment” of the gut lumen, involved in many aspects of organismic activity beyond food intake. We thus extend current embodiment theories and suggest a more inclusive account of how to “mind the gut” in studying cognitive processes.
SHIP: a computational framework for simulating and validating novel technologies in hardware spiking neural networks
Authors: Gemo Emanuele , Spiga Sabina , Brivio Stefano
Published: January 2024

Investigations in the field of spiking neural networks (SNNs) encompass diverse, yet overlapping, scientific disciplines. Examples range from purely neuroscientific investigations, researches on computational aspects of neuroscience, or applicative-oriented studies aiming to improve SNNs performance or to develop artificial hardware counterparts. However, the simulation of SNNs is a complex task that can not be adequately addressed with a single platform applicable to all scenarios. The optimization of a simulation environment to meet specific metrics often entails compromises in other aspects. This computational challenge has led to an apparent dichotomy of approaches, with model-driven algorithms dedicated to the detailed simulation of biological networks, and data-driven algorithms designed for efficient processing of large input datasets. Nevertheless, material scientists, device physicists, and neuromorphic engineers who develop new technologies for spiking neuromorphic hardware solutions would find benefit in a simulation environment that borrows aspects from both approaches, thus facilitating modeling, analysis, and training of prospective SNN systems. This manuscript explores the numerical challenges deriving from the simulation of spiking neural networks, and introduces SHIP, Spiking (neural network) Hardware In PyTorch, a numerical tool that supports the investigation and/or validation of materials, devices, small circuit blocks within SNN architectures. SHIP facilitates the algorithmic definition of the models for the components of a network, the monitoring of states and output of the modeled systems, and the training of the synaptic weights of the network, by way of user-defined unsupervised learning rules or supervised training techniques derived from conventional machine learning. SHIP offers a valuable tool for researchers and developers in the field of hardware-based spiking neural networks, enabling efficient simulation and validation of novel technologies.
Bi-directional electrical recording and stimulation of the intact retina with a screen-printed soft probe: a feasibility study
Authors: Vėbraitė Ieva , Bar-Haim Chen , David-Pur Moshe , Hanein Yael
Published: January 2024

Introduction

Electrophysiological investigations of intact neural circuits are challenged by the gentle and complex nature of neural tissues. Bi-directional electrophysiological interfacing with the retina, in its intact form, is particularly demanding and currently there is no feasible approach to achieve such investigations. Here we present a feasibility study of a novel soft multi-electrode array suitable for bi-directional electrophysiological study of the intact retina.

Methods

Screen-printed soft electrode arrays were developed and tested. The soft probes were designed to accommodate the curvature of the retina in the eye and offer an opportunity to study the retina in its intact form.

Results

For the first time, we show both electrical recording and stimulation capabilities from the intact retina. In particular, we demonstrate the ability to characterize retina responses to electrical stimulation and reveal stable, direct, and indirect responses compared with ex-vivo conditions.

Discussion

These results demonstrate the unique performances of the new probe while also suggesting that intact retinas retain better stability and robustness than ex-vivo retinas making them more suitable for characterizing retina responses to electrical stimulation.
Impact of respiratory viral infections during pregnancy on the neurological outcomes of the newborn: current knowledge
Authors: Manti Sara , Spoto Giulia , Nicotera Antonio Gennaro , Di Rosa Gabriella , Piedimonte Giovanni
Published: January 2024

Brain development is a complex process that begins during pregnancy, and the events occurring during this sensitive period can affect the offspring’s neurodevelopmental outcomes. Respiratory viral infections are frequently reported in pregnant women, and, in the last few decades, they have been related to numerous neuropsychiatric sequelae. Respiratory viruses can disrupt brain development by directly invading the fetal circulation through vertical transmission or inducing neuroinflammation through the maternal immune activation and production of inflammatory cytokines. Influenza virus gestational infection has been consistently associated with psychotic disorders, such as schizophrenia and autism spectrum disorder, while the recent pandemic raised some concerns regarding the effects of severe acute respiratory syndrome coronavirus 2 on neurodevelopmental outcomes of children born to affected mothers. In addition, emerging evidence supports the possible role of respiratory syncytial virus infection as a risk factor for adverse neuropsychiatric consequences. Understanding the mechanisms underlying developmental dysfunction allows for improving preventive strategies, early diagnosis, and prompt interventions.
Bridging the evidence-to-action gap: enhancing alignment of national nutrition strategies in Cambodia, Laos, and Vietnam with global and regional recommendations
Authors: Nguyen Tuan Thanh , Huynh Ngoc Long , Huynh Phuong Nam , Zambrano Paul , Withers Mellissa , Cashin Jennifer , Chin Sedtha , Mathisen Roger
Published: January 2024

Nutrition policies are critical frameworks for tackling the triple burden of malnutrition, including undernutrition (i.e., stunting and wasting), overweight, and hidden hunger (i.e., micronutrient deficiencies). We examined (1) the alignment of recent National Nutrition Strategies and Action Plans (NNS) in Cambodia, Laos, and Vietnam with recent global and regional recommendations and standards with a focus on maternal, infant, and young child nutrition and (2) changes compared to the previous NNS. We extracted information regarding the context, objectives, interventions, indicators, strategies, and coordination mechanisms from the most recent NNSs in Cambodia (2019–2023), Laos (2021–2025), and Vietnam (2021–2030). Recent NNSs aimed to reduce malnutrition among priority populations and described program development, monitoring, and evaluation plans for the following interventions: breastfeeding promotion, improved complementary feeding, dietary diversity, safe water, food security, nutritional/health campaigns, strategies for vulnerable groups, and strengthening of policies related to food and nutrition. Direct interventions to improve women’s general nutrition (outside of pregnancy) and adolescent nutrition were not the focus of any NNSs. Although some indicators (e.g., wasting and exclusive breastfeeding) were covered in all recent NNSs, other indicators (e.g., low birth weight and childhood overweight and obesity) were inconsistently incorporated. In comparison to the previous NNS, the following interventions were discontinued in three countries: dietary counseling, maintaining physical activity, monitoring weight gain during pregnancy, maternal micronutrient supplementation, and nutrition and HIV. Despite similarities in structure and content, the recent NNSs of Cambodia, Laos, and Vietnam do not consistently align with global and regional recommendations. Variations in the types of interventions and indicators included may reflect a shift in priorities, attention, or resources. In conclusion, the NNSs of Cambodia, Laos, and Vietnam exhibit both structural and content similarities; however, certain interventions and indicators vary across countries and differ from global and regional recommendations. Enhancing alignment while prioritizing country-specific needs, optimizing coordination, ensuring policy efficacy, and updating nutrition strategy data for cross-country comparisons and knowledge exchange is critical to ensure progress on reducing malnutrition in the region.
Analysis of Vaccenic and Elaidic acid in foods using a silver ion cartridge applied to GC × GC-TOFMS
Authors: Yoo Miyoung , Lee Hyun Jeong , Lee Kwang-Won , Seo Dongwon
Published: January 2024

Background

Trans fatty acids (TFAs) are unsaturated fatty acids, with vaccenic acid (VA) and elaidic acid (EA) being the major constituents. While VA has been associated with beneficial effects on health and anti-cancer properties, EA is found in hardened vegetable oils and is linked to an increased risk of cardiovascular diseases. Therefore, this study aimed to develop a novel method for the quantitative measurement of VA and EA, aiming to accurately analyze individual TFA and apply it for the assessment of products containing TFAs.

Methods

The ratio of VA to EA (V/E ratio) was evaluated using a silver ion cartridge (SIC) solid phase extraction method removing cis-fatty acids (cis-FAs). Additionally, comparative analysis of the V/E ratio was conducted by the two methods (SIC treatment and untreated) using comprehensive two-dimensional gas chromatography combined with time-of-flight mass spectrometry (GC × GC-TOFMS).

Results

The removal efficiency of cis-FAs was greater than 97.8%. However, the total TFA contents were not so different from SIC treatment. Moreover, this approach not only allowed for a more precise determination of the V/E ratio but also revealed a significant distinction between natural trans fatty acids (N-TFAs) and hydrogenated trans fatty acids (H-TFAs).

Conclusion

Therefore, the SIC coupled to the GC × GC-TOFMS presented in this study could be applied to discriminate N-TFA and H-TFA contents in dairy and fatty foods.
Investigating chromosomal instability in long-term survivors with glioblastoma and grade 4 astrocytoma
Authors: Spoor Jochem K. H. , den Braber May , Dirven Clemens M. F. , Pennycuick Adam , Bartkova Jirina , Bartek Jiri , van Dis Vera , van den Bosch Thierry P. P. , Leenstra Sieger , Venkatesan Subramanian
Published: January 2024

Background

Only a small group of patients with glioblastoma multiforme (GBM) survives more than 36 months, so-called long-term survivors. Recent studies have shown that chromosomal instability (CIN) plays a prognostic and predictive role among different cancer types. Here, we compared histological (chromosome missegregation) and bioinformatic metrics (CIN signatures) of CIN in tumors of GBM typical survivors (≤36 months overall survival), GBM long-term survivors and isocitrate dehydrogenase (IDH)-mutant grade 4 astrocytomas.

Methods

Tumor sections of all gliomas were examined for anaphases and chromosome missegregation. Further CIN signature activity analysis in the The Cancer Genome Atlas (TCGA)-GBM cohort was performed.

Results

Our data show that chromosome missegregation is pervasive in high grade gliomas and is not different between the 3 groups. We find only limited evidence of altered CIN levels in tumors of GBM long-term survivors relative to the other groups, since a significant depletion in CIN signature 11 relative to GBM typical survivors was the only alteration detected. In contrast, within IDH-mutant grade 4 astrocytomas we detected a significant enrichment of CIN signature 5 and 10 activities and a depletion of CIN signature 1 activity relative to tumors of GBM typical survivors.

Conclusions

Our data suggest that CIN is pervasive in high grade gliomas, however this is unlikely to be a major contributor to the phenomenon of long-term survivorship in GBM. Nevertheless, further evaluation of specific types of CIN (signatures) could have prognostic value in patients suffering from grade 4 gliomas.
Incidence of venous thromboembolism and association with PD-L1 expression in advanced non-small cell lung cancer patients treated with first-line chemo-immunotherapy
Authors: Aguiar De Azevedo Liliana , Orione Charles , Tromeur Cécile , Couturaud Francis , Descourt Renaud , Geier Margaux
Published: January 2024

Background

Venous thromboembolism (VTE) is a serious complication in non-small cell lung cancer (NSCLC) patients. The use of thromboprophylactic therapy is subject to an accurate assessment of the VTE risk depending on patients, tumor characteristics and type of systemic antineoplastic treatments. However, little is known concerning the risk of VTE in patients suffering from an advanced NSCLC treated with first-line chemo-immunotherapy and the impact of tumor biomarkers such as PD-L1 expression.

Methods

We performed a retrospective, observational, single-centre study in a cohort of advanced NSCLC patients treated with first-line chemo-immunotherapy. The primary endpoint was the incidence of VTE. Secondary endpoints were the cumulative incidence of VTE, the impact of PD-L1 on VTE occurrence, overall survival, the rate of VTE recurrence under anticoagulant treatment and the rate of bleeding complications.

Results

109 patients were included, of whom 21 (19.3%) presented a VTE event during a median follow-up of 13 months. VTE incidence at 3, 6 and 12 months was 12.1%, 15.1% and 17.5% respectively. 61% were pulmonary embolisms, 9.5% were isolated deep vein thrombosis and 14.3% were central venous catheter-related thrombosis. Our study did not show a significant impact of PD-L1 on VTE occurrence. Overall survival at 6, 12 and 24 months was 81.9%, 74.4% and 70.3% respectively. Four patients developed a recurrent VTE under anticoagulation therapy 3 to 5 months after the first VTE event. One patient suffered from a major bleeding complication while under anticoagulation therapy, leading to death.

Conclusion

VTE is a common complication in advanced NSCLC patients treated with concomitant chemo-immunotherapy. In our study, 19.3% of patients developed a VTE during a median follow-up of 13 months. PD-L1 did not appear to be associated with VTE occurrence. We recorded high VTE recurrence rates despite anticoagulant treatment. Further investigations are needed to determine if high PD-L1 expression is associated with VTE.
A continuous learning approach to brain tumor segmentation: integrating multi-scale spatial distillation and pseudo-labeling strategies
Authors: Li Ruipeng , Ye Jianming , Huang Yueqi , Jin Wei , Xu Peng , Guo Lilin
Published: January 2024

Introduction

This study presents a novel continuous learning framework tailored for brain tumour segmentation, addressing a critical step in both diagnosis and treatment planning. This framework addresses common challenges in brain tumour segmentation, such as computational complexity, limited generalisability, and the extensive need for manual annotation.

Methods

Our approach uniquely combines multi-scale spatial distillation with pseudo-labelling strategies, exploiting the coordinated capabilities of the ResNet18 and DeepLabV3+ network architectures. This integration enhances feature extraction and efficiently manages model size, promoting accurate and fast segmentation. To mitigate the problem of catastrophic forgetting during model training, our methodology incorporates a multi-scale spatial distillation scheme. This scheme is essential for maintaining model diversity and preserving knowledge from previous training phases. In addition, a confidence-based pseudo-labelling technique is employed, allowing the model to self-improve based on its predictions and ensuring a balanced treatment of data categories.

Results

The effectiveness of our framework has been evaluated on three publicly available datasets (BraTS2019, BraTS2020, BraTS2021) and one proprietary dataset (BraTS_FAHZU) using performance metrics such as Dice coefficient, sensitivity, specificity and Hausdorff95 distance. The results consistently show competitive performance against other state-of-the-art segmentation techniques, demonstrating improved accuracy and efficiency.

Discussion

This advance has significant implications for the field of medical image segmentation. Our code is freely available at https://github.com/smallboy-code/A-brain-tumor-segmentation-frameworkusing-continual-learning.
Melatonin: a modulator in metabolic rewiring in T-cell malignancies
Authors: Rai Seema , Roy Gunja , Hajam Younis Ahmad
Published: January 2024

Melatonin, (N-acetyl-5-methoxytryptamine) an indoleamine exerts multifaced effects and regulates numerous cellular pathways and molecular targets associated with circadian rhythm, immune modulation, and seasonal reproduction including metabolic rewiring during T cell malignancy. T-cell malignancies encompass a group of hematological cancers characterized by the uncontrolled growth and proliferation of malignant T-cells. These cancer cells exhibit a distinct metabolic adaptation, a hallmark of cancer in general, as they rewire their metabolic pathways to meet the heightened energy requirements and biosynthesis necessary for malignancies is the Warburg effect, characterized by a shift towards glycolysis, even when oxygen is available. In addition, T-cell malignancies cause metabolic shift by inhibiting the enzyme pyruvate Dehydrogenase Kinase (PDK) which in turn results in increased acetyl CoA enzyme production and cellular glycolytic activity. Further, melatonin plays a modulatory role in the expression of essential transporters (Glut1, Glut2) responsible for nutrient uptake and metabolic rewiring, such as glucose and amino acid transporters in T-cells. This modulation significantly impacts the metabolic profile of T-cells, consequently affecting their differentiation. Furthermore, melatonin has been found to regulate the expression of critical signaling molecules involved in T-cell activations, such as CD38, and CD69. These molecules are integral to T-cell adhesion, signaling, and activation. This review aims to provide insights into the mechanism of melatonin’s anticancer properties concerning metabolic rewiring during T-cell malignancy. The present review encompasses the involvement of oncogenic factors, the tumor microenvironment and metabolic alteration, hallmarks, metabolic reprogramming, and the anti-oncogenic/oncostatic impact of melatonin on various cancer cells.
Case report: A safeguard in the sea of variants of uncertain significance: a case study on child with high risk neuroblastoma and acute myeloid leukemia
Authors: Fabozzi Francesco , Carrozzo Rosalba , Lodi Mariachiara , Di Giannatale Angela , Cipri Selene , Rosignoli Chiara , Giovannoni Isabella , Stracuzzi Alessandra , Rizza Teresa , Montante Claudio , Agolini Emanuele , Di Nottia Michela , Galaverna Federica , Del Baldo Giada , Del Bufalo Francesco , Mastronuzzi Angela , De Ioris Maria Antonietta
Published: January 2024

The increased availability of genetic technologies has significantly improved the detection of novel germline variants conferring a predisposition to tumor development in patients with malignant disease. The identification of variants of uncertain significance (VUS) represents a challenge for the clinician, leading to difficulties in decision-making regarding medical management, the surveillance program, and genetic counseling. Moreover, it can generate confusion and anxiety for patients and their family members. Herein, we report a 5-year-old girl carrying a VUS in the Succinate Dehydrogenase Complex Subunit C (SHDC) gene who had been previously treated for high-risk neuroblastoma and subsequently followed by the development of secondary acute myeloid leukemia. In this context, we describe how functional studies can provide additional insight on gene function determining whether the variant interferes with normal protein function or stability.
Simulating an intra-fraction adaptive workflow to enable PTV margin reduction in MRIgART volumetric modulated arc therapy for prostate SBRT
Authors: Snyder Jeffrey , Smith Blake , Aubin Joel St. , Shepard Andrew , Hyer Daniel
Published: January 2024

Purpose

This study simulates a novel prostate SBRT intra-fraction re-optimization workflow in MRIgART to account for prostate intra-fraction motion and evaluates the dosimetric benefit of reducing PTV margins.

Materials and methods

VMAT prostate SBRT treatment plans were created for 10 patients using two different PTV margins, one with a 5 mm margin except 3 mm posteriorly (standard) and another using uniform 2 mm margins (reduced). All plans were prescribed to 36.25 Gy in 5 fractions and adapted onto each daily MRI dataset. An intra-fraction adaptive workflow was simulated for the reduced margin group by synchronizing the radiation delivery with target position from cine MRI imaging. Intra-fraction delivered dose was reconstructed and prostate DVH metrics were evaluated under three conditions for the reduced margin plans: Without motion compensation (no-adapt), with a single adapt prior to treatment (ATP), and lastly for intra-fraction re-optimization during delivery (intra). Bladder and rectum DVH metrics were compared between the standard and reduced margin plans.

Results

As expected, rectum V18 Gy was reduced by 4.4 ± 3.9%, D1cc was reduced by 12.2 ± 6.8% (3.4 ± 2.3 Gy), while bladder reductions were 7.8 ± 5.6% for V18 Gy, and 9.6 ± 7.3% (3.4 ± 2.5 Gy) for D1cc for the reduced margin reference plans compared to the standard PTV margin. For the intrafraction replanning approach, average intra-fraction optimization times were 40.0 ± 2.9 seconds, less than the time to deliver one of the four VMAT arcs (104.4 ± 9.3 seconds) used for treatment delivery. When accounting for intra-fraction motion, prostate V36.25 Gy was on average 96.5 ± 4.0%, 99.1 ± 1.3%, and 99.6 ± 0.4 for the non-adapt, ATP, and intra-adapt groups, respectively. The minimum dose received by the prostate was less than 95% of the prescription dose in 84%, 36%, and 10% of fractions, for the non-adapt, ATP, and intra-adapt groups, respectively.

Conclusions

Intra-fraction re-optimization improves prostate coverage, specifically the minimum dose to the prostate, and enables PTV margin reduction and subsequent OAR sparing. Fast re-optimizations enable uninterrupted treatment delivery.
Optimal treatment strategy and prognostic analysis for patients with non-metastatic pT4 colon adenocarcinoma
Authors: Zhao Xinyue , Meng Qinghong , Zhou Mengyun , Luo Judong , Hu Lijun
Published: January 2024

Objective

This study endeavored to explore the optimal treatment strategy and conduct a prognostic analysis for patients diagnosed with pT4M0 (pathologic stage T4) colon adenocarcinoma (COAD).

Methods and materials

A total of 8,843 patients diagnosed with pT4M0 COAD between January 2010 and December 2015 were included in this study from the Surveillance, Epidemiology, and End Results (SEER) database. These patients were randomly divided into a training set and an internal validation set using a 7:3 ratio. Variables that demonstrated statistical significance (P<0.05) in univariate COX regression analysis or held clinical significance were incorporated into the multivariate COX regression model. Subsequently, this model was utilized to formulate a nomogram. The predictive accuracy and discriminability of the nomogram were assessed using the C-index, area under the curve (AUC), and calibration curves. Decision curve analysis (DCA) was conducted to confirm the clinical validity of the model.

Results

In the entire SEER cohort, the 3-year overall survival (OS) rate (74.22% vs. 63.20%, P<0.001) and the 3-year cancer-specific survival (CSS) rate (76.25% vs. 66.98%, P<0.001) in the surgery combined with postoperative adjuvant therapy (S+ADT) group surpassed those in the surgery (S) group. Multivariate COX regression analysis of the training set unveiled correlations between age, race, N stage, serum CEA (carcinoembryonic antigen), differentiation, number of resected lymph nodes, and treatment modalities with OS and CSS. Nomograms for OS and CSS were meticulously crafted based on these variables, achieving C-indexes of 0.692 and 0.690 in the training set, respectively. The robust predictive ability of the nomogram was further affirmed through receiver operating characteristic (ROC) and calibration curves in both the training and validation sets.

Conclusion

In individuals diagnosed with pT4M0 COAD, the integration of surgery with adjuvant chemoradiotherapy demonstrated a substantial extension of long-term survival. The nomogram, which incorporated key factors such as age, race, differentiation, N stage, serum CEA level, tumor size, and the number of resected lymph nodes, stood as a dependable tool for predicting OS and CSS rates. This predictive model held promise in aiding clinicians by identifying high-risk patients and facilitating the development of personalized treatment plans.
Topical anesthetics for needle-related pain in adults and children (TOPIC): a mini-review
Authors: Le May Sylvie , Wu Wenjia , Francoeur Maxime , Dodin Philippe , Doyon-Trottier Evelyne , Hung Nicole , Guingo Estelle , Vu An Kateri , Sylfra Annie , Lessard Laurence , Cara-Slavich Stephany , DeKoven Kathryn
Published: January 2024

Purpose

Healthcare professionals (HCP) perform various needle procedures that can be distressing and painful for children and adults. Even though many strategies have been proven effective in reducing distress and pain, topical anesthetic use before needle procedures is uncommon. However, there are limited studies in the existing literature comparing specifically liposomal lidocaine and tetracaine hydrochloride topical creams.

Source

This systematic review analyzed studies on the use of two anesthetic creams, Liposomal Lidocaine (Maxilene®) and Tetracaine hydrochloride (Ametop™), in children and adults undergoing a needle-related procedure. Databases searched: PubMed, CINAHL, ClinicalTrials. Only randomized controlled trials (RCT) and Controlled Clinical Trials (CCT) studies were included. Cochrane Collaboration's Risk of Bias assessment tool was used. Strictly minimally invasive procedures were included to standardize different skin needle interventions.

Principal findings

Only one study with 60 participants was available to be included in this review. No statistically significant difference was found in the mean pain score among both interventions. The outcomes of self-reported distress during cannulation and on HCP satisfaction were not reported. However, physiological characteristics associated with stress/anxiety and on cannulation success rate were reported and did not show statistical significance.

Conclusion

Little to no evidence regarding the most efficient cream between liposomal lidocaine and tetracaine hydrochloride for pain management during needle-related procedures was found. Further studies, particularly RCT with larger sample sizes and standardized outcome measures, are needed to confirm the relative efficacy of either anesthetic cream.
Role of cholinergic innervation in biliary remnants of patients with biliary atresia
Authors: Yang Jixin , Chen Xiaoqing , Wang Wenjing , Su Yanwei , Liu Keqin , Abudusalamu Adila , Li Dandan , He Ying , Wang Pusu , Xiong Xiaofeng , Feng Jiexiong
Published: January 2024

Objective

Biliary innervation is considered important in regulating the function of bile ducts, whereas the role of innervation in the hepatobiliary system of patients with biliary atresia (BA) remains unknown. This current study aims to investigate the role of innervation in biliary remnants and analyze the relationship between the innervation and prognosis of BA after surgery.

Methods

Eighty-seven patients with type III BA who underwent the Kasai procedure were consecutively enrolled from January 2017 to September 2020. Innervation and ductules in remnants were examined by pathologists. Liver function, onset of cholangitis, jaundice clearance, and survival with the native liver were recorded. Patients were followed up for 24 months. The relationship between innervation and prognosis was analyzed.

Results

In total, 67 patients had bile drainage postoperatively, and 21 biliary remnants contained neuronal plexuses where there was no neuron but nerve fiber bundles. Acetylcholinesterase staining was positive in all plexuses. In patients with bile drainage, those with plexuses had improved postoperative liver function, significantly better jaundice clearance 3 or 6 months postoperatively (50.0% vs. 19.1%, or 90.0% vs. 63.8%, respectively), fewer episodes of early cholangitis (10.0% vs. 34.0%), and better survival (80.0% vs. 61.7%) compared to those without. In addition, a larger area of plexuses was associated with a larger area of ductules (R2 = 0.786, p = 0.000), less frequent (p = 0.000) and later cholangitis onset (p = 0.012), and better jaundice clearance (p = 0.063).

Conclusions

Increased cholinergic innervation in biliary remnants may help reduce the onset of cholangitis and lead to better and earlier jaundice clearance. Thus, it improves the postoperative prognosis of patients with BA.
A rare concomitance of Wilson’s disease and systemic lupus erythematosus in a teenage girl: a case report and literature review
Authors: Yang Zigui , Su Yashuang , Liu Meilu , Sun Lijun , Zhang Fengxiao , Lin Wei
Published: January 2024

Background

Wilson's disease (WD) is an inherited disorder characterized by impaired biliary excretion of copper and excessive copper accumulation in multiple organs, primarily leading to hepatic, neurological, and psychiatric manifestations. The coexistence of WD and systemic lupus erythematosus (SLE) has rarely been reported, posing challenges in accurately diagnosing these two conditions because of overlapping clinical symptoms.

Case presentation

We presented the case of a 17-year-old girl initially suspected of having SLE due to positive anti-nuclear antibodies and lupus anticoagulants, decreased platelet count, hypocomplementemia, and pleural effusion. However, the patient also exhibited an unusual manifestation of decompensated liver cirrhosis, which is not typical of SLE. Further investigation revealed low serum ceruloplasmin levels, high 24-h urine copper levels, the presence of Kayser–Fleischer rings, and a compound heterozygous mutation in the ATP7B gene, confirming the diagnosis of WD.

Conclusion

The co-occurrence of WD and SLE poses a significant diagnostic challenge, often leading to misdiagnosis and delayed diagnosis. Therefore, in patients with well-controlled SLE presenting with unexplained liver fibrosis, neurological involvement, or psychiatric symptoms, it is crucial to consider the possibility of WD. However, further studies are required to elucidate the underlying pathophysiological mechanisms.
Efficacy and safety of docetaxel plus S-1-based therapy in gastric cancer: a quantitative evidence synthesis of randomized controlled trials
Authors: Lv Hui-Fen , Qin Li-Feng , Ran Rui-Zhi , Jiang Xue-Ping , Zhao Fang-Yu , Li Bo
Published: January 2024

Objective: To systematically evaluate the safety and efficacy of docetaxel plus S-1-based therapy in gastric cancer treatment.

Methods: PubMed, Embase, The Cochrane Library, and Web of Science electronic databases were searched for randomized controlled trials on docetaxel plus S-1-based therapy in the treatment of gastric cancer from the establishment of the database to 1 September 2022. Relevant studies were included per pre-defined eligibility criteria, and two researchers independently screened and assessed the included literature using Review Manager v5. Outcome measures and statistics related with efficacy and safety profiles were extracted from the included studies, and Stata v15.1 was used for pooled analysis.

Results: Objective response rate (odds ratio = 2.34, 95% CI = [1.32, 4.13], p = 0.003), relapse-free survival (HR = 0.68, 95% CI = [0.58, 0.79], p < 0.001), progression-free survival (HR = 0.81, 95% CI = [0.68, 0.96], p = 0.016), and overall survival (HR = 0.86, 95% CI = [0.79, 0.95], p = 0.002) of docetaxel plus S-1-based therapy (DS-based therapy) in gastric cancer treatment were better than those of the non-DS-based therapy. However, DS-based therapy was associated with increased risk of certain adverse drug effects, such as alopecia, leukopenia, and oral mucositis. Further studies are warranted to validate the efficacy superiority of DS-based versus non-DS-based regimens as per our trial sequential analysis findings.

Conclusion: DS-based therapy significantly improves patients’ clinical outcomes in gastric cancer, albeit at the cost of increased toxicity. Further RCTs are needed to confirm the efficacy superiority of DS-based regimens.
Prevalence and factors associated with medication adherence in children with central precocious puberty: a cross-sectional study
Authors: Yang Chunsong , Song Xia , Wu Jin , Zhang Lingli
Published: January 2024

Objectives: This study aimed to investigate the prevalence and influencing factors of medication adherence in children with central precocious puberty (CPP), and provide references for clinical practice.

Methods: Children under 12 years of age with CPP and their caregivers at a women’s and children’s hospital were selected for a cross-sectional study from February to May 2023, and a questionnaire was used to collect basic characteristics of pediatric patients and their caregivers, information of medication, cognition of medication, and medication adherence. The 8-item Morisky Medication Adherence Scale (MMAS-8) was adopted to assess medication adherence, and the potential influencing factors were explored by univariate and multivariate analyses.

Results: A total of 125 valid questionnaires were collected. The medication adherence rate of children with CPP reported by caregivers was 76.0%. The univariate analysis showed that the percentage of parental caregivers (p = 0.027), the age of caregivers (p = 0.029), the education level of caregivers (p = 0.001), the financial burden (p < 0.000), the incidence of adverse effects (p = 0.008), and the cognition of medication including the importance of medication (p = 0.002), the dosage of medication (p = 0.002), the adverse effects of medication (p = 0.007), the harm of non-compliance with medication (p < 0.000), and the evaluation of the price of medication (p = 0.003) in the poor adherence group were significantly inferior to those in the better adherence group. The multivariate analysis showed that the higher incidence of adverse effects (p = 0.20), not understanding the harm of non-compliance with medication (p = 0.004), and evaluation of the price of medication as expensive (p = 0.043) were independent risk factors for poor medication adherence.

Conclusion: Medication adherence in children with CPP is relatively better, and the factors leading to poor medication adherence are mainly on the caregivers of pediatric patients. It is recommended to increase the health education among caregivers of children with CPP to enhance the cognition of the condition and medication, and further improve the therapeutic efficacy for CPP.
Identification of the main flavonoids of Abelmoschus manihot (L.) medik and their metabolites in the treatment of diabetic nephropathy
Authors: Diao Zhipeng , Yu Hongmei , Wu Yapeng , Sun Yuanbo , Tang Haitao , Wang Mei , Li Nan , Ge Haitao , Sun Jianguo , Gu Harvest F.
Published: January 2024

Introduction: Huangkui capsule (HKC) is made from the ethanol extract of Abelmoschus manihot (L.) Medik [Malvaceae; abelmoschi corolla] and received approval from the China Food and Drug Administration (Z19990040) in 1999. Currently, HKC is used for treatment of the patients with diabetic nephropathy (DN) in China. The bioactive chemical constituents in HKC are total flavonoids of A. manihot (L.) Medik (TFA). The present study aims to identify the primary flavonoid metabolites in HKC and TFA and their metabolism fates in db/db mice, the animal model for the study of type 2 diabetes and DN.

Methods: HKC (0.84 g/kg/d) and TFA (0.076 g/kg/d) or vehicle were respectively administered daily via oral gavage in db/db mice for 4 weeks. The metabolism fate of the main metabolites of HKC in serum, liver, kidney, heart, jejunum, colon, jejunal contents, colonic contents, and urine of db/db mice were analyzed with a comprehensive metabolite identification strategy.

Results and Discussion: In db/db mice administered with HKC and TFA, 7 flavonoid prototypes and 38 metabolites were identified. The related metabolic pathways at Phases I and II reactions included dehydroxylation, deglycosylation, hydrogenation, methylation, glucuronidation, sulphation, and corresponding recombined reactions. Quercetin, isorhamnetin, quercetin sulphate, quercetin monoglucuronide, and isorhamnetin monoglucuronide presented a high exposure in the serum and kidney of db/db mice. Thereby, the present study provides a pharmacodynamic substance basis for better understanding the mechanism of A. manihot (L.) Medik for medication of DN.
Anti-seizure effects of JNJ-54175446 in the intra-amygdala kainic acid model of drug-resistant temporal lobe epilepsy in mice
Authors: Mamad Omar , Heiland Mona , Lindner Andreas U. , Hill Thomas D. M. , Ronroy Ronan M. , Rentrup Kilian , Sanz-Rodriguez Amaya , Langa Elena , Heller Janosch P. , Moreno Oscar , Llop Jordi , Bhattacharya Anindya , Palmer James A. , Ceusters Marc , Engel Tobias , Henshall David C.
Published: January 2024

There remains a need for new drug targets for treatment-resistant temporal lobe epilepsy. The ATP-gated P2X7 receptor coordinates neuroinflammatory responses to tissue injury. Previous studies in mice reported that the P2X7 receptor antagonist JNJ-47965567 suppressed spontaneous seizures in the intraamygdala kainic acid model of epilepsy and reduced attendant gliosis in the hippocampus. The drug-resistance profile of this model is not fully characterised, however, and newer P2X7 receptor antagonists with superior pharmacokinetic profiles have recently entered clinical trials. Using telemetry-based continuous EEG recordings in mice, we demonstrate that spontaneous recurrent seizures in the intraamygdala kainic acid model are refractory to the common anti-seizure medicine levetiracetam. In contrast, once-daily dosing of JNJ-54175446 (30 mg/kg, intraperitoneal) resulted in a significant reduction in spontaneous recurrent seizures which lasted several days after the end of drug administration. Using a combination of immunohistochemistry and ex vivo radiotracer assay, we find that JNJ-54175446-treated mice at the end of recordings display a reduction in astrogliosis and altered microglia process morphology within the ipsilateral CA3 subfield of the hippocampus, but no difference in P2X7 receptor surface expression. The present study extends the characterisation of the drug-resistance profile of the intraamygdala kainic acid model in mice and provides further evidence that targeting the P2X7 receptor may have therapeutic applications in the treatment of temporal lobe epilepsy.
CYP3A5 influences oral tacrolimus pharmacokinetics and timing of acute kidney injury following allogeneic hematopoietic stem cell transplantation
Authors: Seligson Nathan D. , Zhang Xunjie , Zemanek Mark C. , Johnson Jasmine A. , VanGundy Zachary , Wang Danxin , Phelps Mitch A. , Roddy Julianna , Hofmeister Craig C. , Li Junan , Poi Ming J.
Published: January 2024

Introduction: Polymorphisms in genes responsible for the metabolism and transport of tacrolimus have been demonstrated to influence clinical outcomes for patients following allogeneic hematologic stem cell transplant (allo-HSCT). However, the clinical impact of germline polymorphisms specifically for oral formulations of tacrolimus is not fully described.

Methods: To investigate the clinical impact of genetic polymorphisms in CYP3A4, CYP3A5, and ABCB1 on oral tacrolimus pharmacokinetics and clinical outcomes, we prospectively enrolled 103 adult patients receiving oral tacrolimus for the prevention of graft-versus-host disease (GVHD) following allo-HSCT. Patients were followed in the inpatient and outpatient phase of care for the first 100 days of tacrolimus therapy. Patients were genotyped for CYP3A5 *3 (rs776746), CYP3A4 *1B (rs2740574), ABCB1 exon 12 (rs1128503), ABCB1 exon 21 (rs2032582), ABCB1 exon 26 (rs1045642).

Results: Expression of CYP3A5 *1 was highly correlated with tacrolimus pharmacokinetics in the inpatient phase of care (p < 0.001) and throughout the entirety of the study period (p < 0.001). Additionally, Expression of CYP3A5 *1 was associated with decreased risk of developing AKI as an inpatient (p = 0.06). Variants in ABCB1 were not associated with tacrolimus pharmacokinetics in this study. We were unable to discern an independent effect of CYP3A4 *1B or *22 in this population.

Conclusion: Expression of CYP3A5 *1 is highly influential on the pharmacokinetics and clinical outcomes for patients receiving oral tacrolimus as GVHD prophylaxis following allo-HSCT.
Chemistry does general relativity: reaction-diffusion waves can model gravitational lensing
Authors: Cohen-Cobos Daniel , Sanders Kiyomi , DeGroot Laura , Guarnera Heather , Leary Cody , Lindner John F. , Manz Niklas
Published: January 2024

Gravitational lensing is a general relativistic (GR) phenomenon where a massive object redirects light, deflecting, magnifying, and sometimes multiplying its source. We use reaction-diffusion (RD) Belousov-Zhabotinsky (BZ) chemistry to study this astronomical effect in a table-top experiment. We experimentally observe BZ waves passing through non-planar, quasi-two-dimensional molds and reproduce the waveforms in computer simulations using planar RD waves propagating with variable diffusion. We tune the variable diffusion to match the Schwarzschild-coordinate light speed near a spherical mass so the RD propagation approximates Einstein’s famous light deflection relation. We discuss varying the diffusion or reaction rates with a gel matrix or with illumination, electric field, or temperature gradients.