bluuebunny/crossref_metadata_2025 huggingface dataset:
Delirium detection using wearable sensors and machine learning in patients with intracerebral hemorrhage
Authors: Ahmed Abdullah , Garcia-Agundez Augusto , Petrovic Ivana , Radaei Fatemeh , Fife James , Zhou John , Karas Hunter , Moody Scott , Drake Jonathan , Jones Richard N. , Eickhoff Carsten , Reznik Michael E.
Published: June 2023

Objective

Delirium is associated with worse outcomes in patients with stroke and neurocritical illness, but delirium detection in these patients can be challenging with existing screening tools. To address this gap, we aimed to develop and evaluate machine learning models that detect episodes of post-stroke delirium based on data from wearable activity monitors in conjunction with stroke-related clinical features.

Design

Prospective observational cohort study.

Setting

Neurocritical Care and Stroke Units at an academic medical center.

Patients

We recruited 39 patients with moderate-to-severe acute intracerebral hemorrhage (ICH) and hemiparesis over a 1-year period [mean (SD) age 71.3 (12.20), 54% male, median (IQR) initial NIH Stroke Scale 14.5 (6), median (IQR) ICH score 2 (1)].

Measurements and main results

Each patient received daily assessments for delirium by an attending neurologist, while activity data were recorded throughout each patient's hospitalization using wrist-worn actigraph devices (on both paretic and non-paretic arms). We compared the predictive accuracy of Random Forest, SVM and XGBoost machine learning methods in classifying daily delirium status using clinical information alone and combined with actigraph data. Among our study cohort, 85% of patients (n = 33) had at least one delirium episode, while 71% of monitoring days (n = 209) were rated as days with delirium. Clinical information alone had a low accuracy in detecting delirium on a day-to-day basis [accuracy mean (SD) 62% (18%), F1 score mean (SD) 50% (17%)]. Prediction performance improved significantly (p < 0.001) with the addition of actigraph data [accuracy mean (SD) 74% (10%), F1 score 65% (10%)]. Among actigraphy features, night-time actigraph data were especially relevant for classification accuracy.

Conclusions

We found that actigraphy in conjunction with machine learning models improves clinical detection of delirium in patients with stroke, thus paving the way to make actigraph-assisted predictions clinically actionable.
Sympathetic skin response (SSR) in pediatric Guillain–Barré syndrome
Authors: Jin Mei , Liu Jing , Liu Kang , Zhao Libo , Zhao Ziwei , Sun Suzhen
Published: June 2023

Introduction

In the present study, sympathetic skin response (SSR) characteristics were explored in children with Guillain–Barré syndrome (GBS) and the value of early diagnosis and prognostic evaluation in GBS complicated by autonomic dysfunction (AD) was evaluated.

Methods

A total of 25 children with GBS and 30 healthy controls (HCs) were enrolled in this prospective study. SSR findings for the two groups were compared. SSR and nerve conduction study (NCS) results were compared among patients with GBS, and differences in clinical characteristics between the groups with abnormal and normal SSR were analyzed.

Results

Within the GBS group, six patients (24%) required mechanical ventilation, 17 patients (66.7%) had AD, 18 patients (72%) had an abnormal SSR, and 13 patients (52%) had AD combined with SSR abnormalities. There was a statistically significant difference in SSR latency in the lower limbs between the GBS group and HCs (P < 0.05). There was no statistically significant difference between SSR and NCS results in the acute phase of GBS (P > 0.05), and there was no significant difference in the rate of AD or in Hughes functional grade at nadir between the groups with abnormal and normal SSR (P>0.05). However, there was a statistically significant difference between the results of SSR and NCS tests during the recovery phase (P = 0.003). Abnormal SSR mainly occurred in cases of the acute inflammatory demyelinating polyradiculoneuropathy (AIDP) subtype. In addition, SSR was abnormal in all pediatric GBS patients with poor prognosis 1 month after onset of symptoms.

Conclusion

Two-thirds of the children with GBS have AD. SSR could be used for early diagnosis and follow-up of GBS and may also be helpful in evaluating disease severity and short-term prognosis.
Case report: Evolution of catatonic mutism and psychotic symptoms in an adolescent with Down syndrome: transition from Down syndrome disintegrative disorder to anti-N-methyl-D-aspartate receptor encephalitis
Authors: Minamisawa Yuki , Sato Mutsumi , Saito Yoshiaki , Takeuchi Fumikazu , Miyazaki Hidehito , Odaka Mao , Yamamoto Ayako , Oyama Yoshitaka , Watanabe Yoshihiro , Takeshita Saoko , Takahashi Yukitoshi
Published: June 2023

During her first year of junior high school, a 12-year-old Japanese girl with Down syndrome experienced dizziness, gait disruption, paroxysmal weakness in her hands, and sluggish speaking. Regular blood tests and a brain MRI revealed no abnormalities, and she was tentatively diagnosed with adjustment disorder. Nine months later, the patient experienced a subacute sickness of chest pain, nausea, sleep problem with night terrors, and delusion of observation. Rapid deterioration then developed with simultaneous fever, akinetic mutism, loss of facial expression, and urine incontinence. These catatonic symptoms improved after a few weeks after admission and treatment with lorazepam, escitalopram, and aripiprazole. After discharge, nonetheless, daytime slumber, empty eyes, paradoxical laughter, and declined verbal communication persisted. Upon confirmation of the cerebrospinal N-methyl-D-aspartate (NMDA) receptor autoantibody, methylprednisolone pulse therapy was tried, but it had little effect. Visual hallucinations and cenesthopathy, as well as suicidal thoughts and delusions of death, have predominated in the following years. Cerebrospinal IL-1ra, IL-5, IL-15, CCL5, G-CSF, PDGFbb, and VFGF were raised in the early stage of initial medical attention with nonspecific complaints, but were less prominent in the later stages of catatonic mutism and psychotic symptoms. We suggest a disease concept of progression from Down syndrome disintegrative disorder to NMDA receptor encephalitis, based on this experience.
Current analysis of hypoxic-ischemic encephalopathy research issues and future treatment modalities
Authors: She Hong-Qing , Sun Yi-Fei , Chen Li , Xiao Qiu-Xia , Luo Bo-Yan , Zhou Hong-Su , Zhou Di , Chang Quan-Yuan , Xiong Liu-Lin
Published: June 2023

Hypoxic-ischemic encephalopathy (HIE) is the leading cause of long-term neurological disability in neonates and adults. Through bibliometric analysis, we analyzed the current research on HIE in various countries, institutions, and authors. At the same time, we extensively summarized the animal HIE models and modeling methods. There are various opinions on the neuroprotective treatment of HIE, and the main therapy in clinical is therapeutic hypothermia, although its efficacy remains to be investigated. Therefore, in this study, we discussed the progress of neural circuits, injured brain tissue, and neural circuits-related technologies, providing new ideas for the treatment and prognosis management of HIE with the combination of neuroendocrine and neuroprotection.
Loss of Nicotinamide nucleotide transhydrogenase sensitizes embryos to ethanol-induced neural crest and neural apoptosis via generation of reactive oxygen species
Authors: Mazumdar Rayna , Eberhart Johann K.
Published: June 2023

Fetal alcohol spectrum disorders (FASD) are a continuum of birth defects caused by prenatal alcohol exposure. FASD are the most common environmentally induced birth defect and are highly variable. The genetics of an individual influence the severity of their FASD phenotype. However, the genes that sensitize an individual to ethanol-induced birth defects are largely unknown. The ethanol-sensitive mouse substrain, C57/B6J, carries several known mutations including one in Nicotinamide nucleotide transhydrogenase (Nnt). Nnt is a mitochondrial transhydrogenase thought to have an important role in detoxifying reactive oxygen species (ROS) and ROS has been implicated in ethanol teratogenesis. To directly test the role of Nnt in ethanol teratogenesis, we generated zebrafish nnt mutants via CRISPR/Cas9. Zebrafish embryos were dosed with varying concentrations of ethanol across different timepoints and assessed for craniofacial malformations. We utilized a ROS assay to determine if this could be a contributing factor of these malformations. We found that exposed and unexposed mutants had higher levels of ROS compared to their wildtype counterparts. When treated with ethanol, nnt mutants experienced elevated apoptosis in the brain and neural crest, a defect that was rescued by administration of the antioxidant, N-acetyl cysteine (NAC). NAC treatment also rescued most craniofacial malformations. Altogether this research demonstrates that ethanol-induced oxidative stress leads to craniofacial and neural defects due to apoptosis in nnt mutants. This research further supports the growing body of evidence implicating oxidative stress in ethanol teratogenesis. These findings suggest that antioxidants can be used as a potential therapeutic in the treatment of FASD.
Encapsulation of Heracleum persicum essential oil in chitosan nanoparticles and its application in yogurt
Authors: Yousefi Mojtaba , Khanniri Elham , Sohrabvandi Sara , Khorshidian Nasim , Mortazavian Amir M.
Published: June 2023

Heracleum percicum essential oil (HEO) at various levels was encapsulated in chitosan nanoparticles and its potential application in yogurt was investigated. The values obtained for encapsulation efficiency, loading capacity, mean particle size, and zeta potential of nanoparticles were 39.12–70.22%, 9.14–14.26%, 201.23–336.17 nm, and + 20.19–46.37 mV, respectively. The nanoparticles had spherical shape with some holes as a result of drying process. In vitro release studies in acidic solution and phosphate buffer solution indicated an initial burst effect followed by slow release with higher release rate in acidic medium. Results of antibacterial activity revealed that Staphylococcus aureus and Salmonella typhimurium with inhibition zones of 21.04–38.10 and 9.39–20.56 mm were the most sensitive and resistant bacteria to HEO, respectively. Incorporation of encapsulated HEO into yogurt decreased pH and increased titratable acidity due to stimulation of starters’ activity. Interaction of nanoparticles with proteins decreased syneresis in yogurt. Regarding antioxidant activity, a higher value was observed in yogurt containing encapsulated HEO after 14 days of storage due to degradation and release of essential oil from nanoparticles. In conclusion, application of HEO nanoparticles in yogurt could be a promising approach for development of functional food products such as yogurt with enhanced antioxidant properties.
Inequity in care delivery in cardio-oncology: dissecting disparities in underrepresented populations
Authors: Patel Shruti Rajesh , Suero-Abreu Giselle Alexandra , Ai Angela , Ramachandran Maya K. , Meza Kelly , Florez Narjust
Published: June 2023

It is well known that patients with cancer have a significantly higher cardiovascular mortality risk than the general population. Cardio-oncology has emerged to focus on these issues including risk reduction, detection, monitoring, and treatment of cardiovascular disease or complications in patients with cancer. The rapid advances in early detection and drug development in oncology, along with socioeconomic differences, racial inequities, lack of support, and barriers to accessing quality medical care, have created disparities in various marginalized populations. In this review, we will discuss the factors contributing to disparities in cardio-oncologic care in distinct populations, including Hispanic/Latinx, Black, Asian and Pacific Islander, indigenous populations, sex and gender minorities, and immigrants. Some factors that contribute to differences in outcomes in cardio-oncology include the prevalence of cancer screening rates, genetic cardiac/oncologic risk factors, cultural stressors, tobacco exposure rates, and physical inactivity. We will also discuss the barriers to cardio-oncologic care in these communities from the racial and socioeconomic context. Appropriate and timely cardiovascular and cancer care in minority groups is a critical component in addressing these disparities, and there need to be urgent efforts to address this widening gap.
Etoposide/platinum plus anlotinib for patients with transformed small-cell lung cancer from EGFR-mutant lung adenocarcinoma after EGFR-TKI resistance: a retrospective and observational study
Authors: Ding Jianghua , Leng Zhaohui , Gu Hong , Jing Xiang , Song Yun
Published: June 2023

Objective

The histological conversion of lung adenocarcinoma (LUAD) into small-cell lung cancer (SCLC) is an important resistance mechanism for epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-resistant LUAD. Anlotinib has been recommended as the third-line treatment for SCLC patients. The efficacy of etoposide/platinum (EP) as the main treatment is very limited for patients with transformed SCLC. However, little is known about EP plus anlotinib for transformed SCLC. The present study retrospectively explored the clinical response to EP combined with anlotinib in patients with transformed SCLC from LUAD after EGFR-TKI failure.

Methods

A total of 10 patients who underwent SCLC transformation from EGFR-TKI-resistant LUAD were retrospectively reviewed from September 1, 2019, to December 31, 2022, in three regional hospitals. All of the patients were treated with the combination regimen of EP and anlotinib for four to six cycles, followed by anlotinib maintenance therapy. The clinical efficacy indices including objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and toxicities were evaluated.

Results

The median time from EGFR-TKI treatment to SCLC conversion was 20.1 ± 2.76 months (17–24 months). Genetic examination after transformation showed that 90% of the patients retained their original EGFR gene mutations. Additional driver genes were found, including BRAF mutation (10%), PIK3CA mutation (20%), RB1 loss (50%), and TP53 mutation (60%). The ORR and DCR were 80% and 100%, respectively. The mPFS was 9.0 months (95% CI, 7.9–10.1 months), and the mOS was 14.0 months (95% CI, 12.0–15.9 months). Less than 10% of grade 3 toxicities were observed, and no grade 4 toxicity and death events were reported.

Conclusion

The EP plus anlotinib regimen appears to be a promising and safe strategy in transformed SCLC patients after EGFR-TKI resistance, which warrants further investigation.
Pulmonary microbiota signatures adjacent to adenocarcinoma, squamous cell carcinoma and benign lesion
Authors: Li Jinyou , Wu Gang , Yang Ju , Yan Jiai , Li Dan , Wang Qinyue , Xia Yanping , Zhu Jie , Guo Baoliang , Cheng Fengyue , Sun Jing , Cao Hong , Zhang Feng
Published: June 2023

Introduction

The occurrence and progression of lung cancer are influenced by pulmonary microbiota, yet the relationship between changes in the pulmonary microbiota and lung cancer remains unclear.

Methods

To investigate the correlation between pulmonary microbiota and the signature of lung lesions, we analyzed the microbial composition at sites adjacent to the stage 1 adenocarcinoma, squamous carcinoma and benign lesion tissues in 49 patients by using 16S ribosomal RNA gene sequencing. We then conducted Linear discriminant analysis, receiver operating characteristic (ROC) curve analysis and PICRUSt prediction based on 16S sequencing results.

Results

Overall, the microbiota composition at sites close to lung lesions showed significant differences between different lesion types. Based on the results of LEfSe analysis, Ralstonia, Acinetobacter and Microbacterium are the dominant genera of lung adenocarcinoma (LUAD), lung squamous carcinoma (LUSC) and benign lesions (BENL), respectively. Furthermore, we determined the diagnostic value of the abundance ratio of Ralstonia to Acinetobacter in adenocarcinoma patients through ROC curve analysis. The PICRUSt analysis revealed 15 remarkably different metabolic pathways in these lesion types. In LUAD patients, the increase of the pathway associated with xenobiotic biodegradation may be due to the continuous proliferation of microbe with degradation ability of xenobiotics, which implied that LUAD patients are often exposed to harmful environment.

Discussion

The abundance of Ralstonia was related to the development of lung cancer. By measuring the abundance of microbiota in diseased tissues, we can distinguish between different types of lesions. The differences in pulmonary microbiota between lesion types are significant in understanding the occurrence and development of lung lesions.
Dyslipidemia in diffuse large B-cell lymphoma based on the genetic subtypes: a single-center study of 259 Chinese patients
Authors: Xu Yi , Shen Huafei , Shi Yuanfei , Zhao Yanchun , Zhen Xiaolong , Sun Jianai , Li Xueying , Zhou De , Yang Chunmei , Wang Jinhan , Huang Xianbo , Wei Juying , Huang Jian , Meng Haitao , Yu Wenjuan , Tong Hongyan , Jin Jie , Xie Wanzhuo
Published: June 2023

Background

Diffuse large B-cell lymphoma (DLBCL) is a kind of highly heterogeneous non-Hodgkin lymphoma, both in clinical and genetic terms. DLBCL is admittedly categorized into six subtypes by genetics, which contain MCD, BN2, EZB, N1, ST2, and A53. Dyslipidemia is relevant to a multitude of solid tumors and has recently been reported to be associated with hematologic malignancies. We aim to present a retrospective study investigating dyslipidemia in DLBCL based on the molecular subtypes.

Results

This study concluded that 259 patients with newly diagnosed DLBCL and their biopsy specimens were available for molecular typing. Results show that the incidence of dyslipidemia (87.0%, p <0.001) is higher in the EZB subtype than in others, especially hypertriglyceridemia (78.3%, p = 0.001) in the EZB subtype. Based on the pathological gene-sequencing, patients with BCL2 gene fusion mutation are significantly correlative with hyperlipidemia (76.5%, p = 0.006) and hypertriglyceridemia (88.2%, p = 0.002). Nevertheless, the occurrence of dyslipidemia has no remarkable influence on prognosis.

Conclusion

In summary, dyslipidemia correlates with genetic heterogeneity in DLBCL without having a significant influence on survival. This research first connects lipids and genetic subtypes in DLBCL.
Survival benefit of active surveillance for papillary thyroid carcinoma: a propensity score matching analysis based on SEER database
Authors: Bi Jinzhe , Lyu Peng-fei , Wang Yu , Zhang Hao
Published: June 2023

Background

Over-treatment of papillary thyroid microcarcinoma (PTMC) has become a common issue. Although active surveillance (AS) has been proposed as an alternative treatment to immediate surgery for PTMC, its inclusion criteria and mortality risk have not been clearly defined. The purpose of this study was to investigate whether surgery can achieve significant survival benefits in patients with larger tumor diameter of papillary thyroid carcinoma (PTC), in order to evaluate the feasibility of expanding the threshold for active surveillance.

Methods

This study retrospectively collected data of patients with papillary thyroid carcinoma from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. The propensity score matching (PSM) method was used to minimize confounding factors and selection bias between the surgery and non-surgery groups, and to compare the clinical and pathological characteristics between the two groups based on the SEER cohort. Meanwhile, the impact of surgery on prognosis was compared using Kaplan-Meier estimates and Cox proportional hazard models.

Results

A total of 175,195 patients were extracted from the database, including 686 patients who received non-surgical treatment, and were matched 1:1 with patients who received surgical treatment using propensity score matching. The Cox proportional hazard forest plot showed that age was the most important factor affecting overall survival (OS) of patients, while tumor size was the most important factor affecting disease-specific survival (DSS) of patients. In terms of tumor size, there was no significant difference in DSS between PTC patients with tumor size of 0-1.0cm who underwent surgical treatment and those who underwent non-surgical treatment, and the relative survival risk began to increase after the tumor size exceeded 2.0cm. Additionally, the Cox proportional hazard forest plot showed that chemotherapy, radioactive iodine, and multifocality were negative factors affecting DSS. Moreover, the risk of death increased over time, and no plateau phase was observed.

Conclusion

For patients with papillary thyroid carcinoma (PTC) staged as T1N0M0, AS is a feasible management strategy. As the tumor diameter increases, the risk of death without surgical treatment gradually increases, but there may be a threshold. Within this range, a non-surgical approach may be a potentially viable management strategy. However, beyond this range, surgery may be more beneficial for patient survival. Therefore, it is necessary to conduct more large-scale prospective randomized controlled trials to further confirm these findings.
Immune dysregulation in Kabuki syndrome: a case report of Evans syndrome and hypogammaglobulinemia
Authors: Leonardi Lucia , Testa Alessia , Feleppa Mariavittoria , Paparella Roberto , Conti Francesca , Marzollo Antonio , Spalice Alberto , Giona Fiorina , Gnazzo Maria , Andreoli Gian Marco , Costantino Francesco , Tarani Luigi
Published: June 2023

Kabuki syndrome (KS) is a rare multisystemic disease due to mutations in the KMT2D or KDM6A genes, which act as epigenetic modulators of different processes, including immune response. The syndrome is characterized by anomalies in multiple organ systems, and it is associated with autoimmune and inflammatory disorders, and an underlying immunological phenotype characterized by immunodeficiency and immune dysregulation. Up to 17% of KS patients present with immune thrombocytopenia characterized by a severe, chronic or relapsing course, and often associated to other hematological autoimmune diseases including autoimmune hemolytic anemia, eventually resulting in Evans syndrome (ES). A 23-year-old woman, clinically diagnosed with KS and presenting from the age of 3 years with ES was referred to the Rare Diseases Centre of our Pediatric Department for corticosteroid-induced hyperglycemia. Several ES relapses and recurrent respiratory infections in the previous years were reported. Severe hypogammaglobulinemia, splenomegaly and signs of chronic lung inflammation were diagnosed only at the time of our observation. Supportive treatment with amoxicillin-clavulanate prophylaxis and recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin replacement were immediately started. In KS patients, the failure of B-cell development and the lack of autoreactive immune cells suppression can lead to immunodeficiency and autoimmunity that may be undiagnosed for a long time. Our patient's case is paradigmatic since she presented with preventable morbidity and severe lung disease years after disease onset. This case emphasizes the importance of suspecting immune dysregulation in KS. Pathogenesis and immunological complications of KS are discussed. Moreover, the need to perform immunologic evaluations is highlighted both at the time of KS diagnosis and during disease follow-up, in order to allow proper treatment while intercepting avoidable morbidity in these patients.
Pharmacokinetic interaction of voriconazole and clarithromycin in Pakistani healthy male volunteers: a single dose, randomized, crossover, open-label study
Authors: Mushtaq Mehwish , Fatima Kshaf , Ahmad Aneeqa , Mohamed Ibrahim Osama , Faheem Muhammad , Shah Yasar
Published: June 2023

Background: Voriconazole an antifungal drug, has a potential for drug-drug interactions (DDIs) with administered drugs. Clarithromycin is a Cytochromes P450 CYP (3A4 and 2C19) enzyme inhibitor, and voriconazole is a substrate and inhibitor of these two enzymes. Being a substrate of the same enzyme for metabolism and transport, the chemical nature and pKa of both interacting drugs make these drugs better candidates for potential pharmacokinetic drug-drug interactions (PK-DDIs). This study aimed to evaluate the effect of clarithromycin on the pharmacokinetic profile of voriconazole in healthy volunteers.

Methods: A single oral dose, open-label, randomized, crossover study was designed for assessing PK-DDI in healthy volunteers, consisting of 2 weeks washout period. Voriconazole, either alone (2 mg × 200 mg, tablet, P/O) or along with clarithromycin (voriconazole 2 mg × 200 mg, tablet + clarithromycin 500 mg, tablet, P/O), was administered to enrolled volunteers in two sequences. The blood samples (approximately 3 cc) were collected from volunteers for up to 24 h. Plasma concentrations of voriconazole were analyzed by an isocratic, reversed-phase high-performance-liquid chromatography ultraviolet-visible detector (RP HPLC UV-Vis) and a non-compartmental method.

Results: In the present study, when voriconazole was administered with clarithromycin versus administered alone, a significant increase in peak plasma concentration (Cmax) of voriconazole by 52% (geometric mean ratio GMR: 1.52; 90% CI 1.04, 1.55; p = 0.000) was observed. Similarly, the area under the curve from time zero to infinity (AUC0-∞) and the area under the concentration-time curve from time zero to time-t (AUC0-t) of voriconazole also significantly increased by 21% (GMR: 1.14; 90% CI 9.09, 10.02; p = 0.013), and 16% (GMR: 1.15; 90% CI 8.08, 10.02; p = 0.007), respectively. In addition, the results also showed a reduction in the apparent volume of distribution (Vd) by 23% (GMR: 0.76; 90% CI 5.00, 6.20; p = 0.051), and apparent clearance (CL) by 13% (GMR: 0.87; 90% CI 41.95, 45.73; p = 0.019) of voriconazole.

Conclusion: The alterations in PK parameters of voriconazole after concomitant administration of clarithromycin are of clinical significance. Therefore, adjustments in dosage regimens are warranted. In addition, extreme caution and therapeutic drug monitoring are necessary while co-prescribing both drugs.

Clinical Trial Registration:clinicalTrials.gov, Identifier NCT05380245.
Hypoglycemic effects of dendrobium officinale leaves
Authors: Lv Ming , Liang Qingqing , He Xiaofang , Du Xiaocui , Liu Yuhan , Liu Yan , Fang Chongye
Published: June 2023

Introduction: Numerous studies have demonstrated that the stems of D. officinale have the effect of lowering blood glucose, but the leaves of D. officinale have seldom been investigated. In this study, we mainly studied the hypoglycemic effect and mechanism of D. officinale leaves.

Methods: Initially in vivo, male C57BL/6 mice were administered either standard feed (10 kcal% fat) or high-fat feed (60 kcal% fat) along with either normal drinking water or drinking water containing 5 g/L water extract of D. officinale leaves (EDL) for 16 weeks, and changes in body weight, food intake, blood glucose, etc., were monitored weekly. Next in vitro, C2C12 myofiber precursor cells which were induced to differentiate into myofibroblasts and cultured with EDL to detect the expression of insulin signaling pathway related proteins. HEPA cells were also cultured with EDL to detect the expression of hepatic gluconeogenesis or hepatic glycogen synthesis related proteins. Eventually after separating the components from EDL by ethanol and 3 kDa ultrafiltration centrifuge tube, we conducted animal experiments using the ethanol-soluble fraction of EDL (ESFE), ethanol-insoluble fraction of EDL (EIFE), ESFE with a molecular weight of >3 kDa (>3 kDa ESFE), and ESFE with a molecular weight of <3 kDa (<3 kDa ESFE) for intensive study.

Results: The results in vivo revealed that the mice fed the high-fat diet exhibited significantly decreased blood glucose levels and significantly increased glucose tolerance after the EDL treatment, whereas the mice fed the low-fat diet did not. The results in vitro showed that EDL activated the expression of protein kinase B (AKT), the phosphorylation of AKT, and the expression of downstream GSK3β in the insulin signaling pathway. EDL treatment of HEPA cells confirmed that EDL did not affect hepatic gluconeogenesis or hepatic glycogen synthesis. In the experiment of studying the composition of EDL, we found that the >3 kDa ESFE displayed the effect of lowering blood glucose. In summary, the effect of EDL in lowering blood glucose may bethanole achieved by activating the insulin signaling pathway to increase insulin sensitivity, and the main functional substance was contained within the >3 kDa ESFE.

Discussion: The findings of this study represent a reference point for further exploration of the hypoglycemic effects of D. officinale leaves and may assist in both the identification of new molecular mechanisms to improve insulin sensitivity and the isolation of monomeric substances that lower blood glucose. Furthermore, the obtained results may provide a theoretical basis for the development of hypoglycemic drugs with D. officinale leaves as the main component.
Harnessing the potential of probiotics in the treatment of alcoholic liver disorders
Authors: Mishra Garima , Singh Pradeep , Molla Mulugeta , Yimer Yohannes Shumet , Dinda Subas Chandra , Chandra Phool , Singh Bhuvnesh Kumar , Dagnew Samuel Berihun , Assefa Abraham Nigussie , Ewunetie Amien
Published: June 2023

In the current scenario, prolonged consumption of alcohol across the globe is upsurging an appreciable number of patients with the risk of alcohol-associated liver diseases. According to the recent report, the gut-liver axis is crucial in the progression of alcohol-induced liver diseases, including steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Despite several factors associated with alcoholic liver diseases, the complexity of the gut microflora and its great interaction with the liver have become a fascinating area for researchers due to the high exposure of the liver to free radicals, bacterial endotoxins, lipopolysaccharides, inflammatory markers, etc. Undoubtedly, alcohol-induced gut microbiota imbalance stimulates dysbiosis, disrupts the intestinal barrier function, and trigger immune as well as inflammatory responses which further aggravate hepatic injury. Since currently available drugs to mitigate liver disorders have significant side effects, hence, probiotics have been widely researched to alleviate alcohol-associated liver diseases and to improve liver health. A broad range of probiotic bacteria like Lactobacillus, Bifidobacteria, Escherichia coli, Sacchromyces, and Lactococcus are used to reduce or halt the progression of alcohol-associated liver diseases. Several underlying mechanisms, including alteration of the gut microbiome, modulation of intestinal barrier function and immune response, reduction in the level of endotoxins, and bacterial translocation, have been implicated through which probiotics can effectively suppress the occurrence of alcohol-induced liver disorders. This review addresses the therapeutic applications of probiotics in the treatment of alcohol-associated liver diseases. Novel insights into the mechanisms by which probiotics prevent alcohol-associated liver diseases have also been elaborated.
Bibliometric visualization analysis of gut-kidney axis from 2003 to 2022
Authors: Ai Sinan , Li Yake , Tao JiaYin , Zheng Huijuan , Tian Lei , Wang Yaoxian , Wang Zhen , Liu Wei Jing
Published: June 2023

Background: The gut-kidney axis refers to the interaction between the gastrointestinal tract and the kidneys, and its disorders have become increasingly important in the development of kidney diseases. The aim of this study is to identify current research hotspots in the field of the gut-kidney axis from 2003 to 2022 and provide guidance for future research in this field.

Methods: We collected relevant literature on the gut-kidney axis from the Web of Science Core Collection (WoSCC) database and conducted bibliometric and visualization analyses using biblioshiny in R-Studio and VOSviewer (version 1.6.16).

Results: A total of 3,900 documents were retrieved from the WoSCC database. The publications have shown rapid expansion since 2011, with the greatest research hotspot emerging due to the concept of the “intestinal-renal syndrome,” first proposed by Meijers. The most relevant journals were in the field of diet and metabolism, such as Nutrients. The United States and China were the most influential countries, and the most active institute was the University of California San Diego. Author analysis revealed that Denise Mafra, Nosratola D. Vaziri, Fouque, and Denis made great contributions in different aspects of the field. Clustering analysis of the keywords found that important research priorities were “immunity,” “inflammation,” “metabolism,” and “urinary toxin,” reflecting the basis of research in the field. Current research frontiers in the field include “hyperuricemia,” “gut microbiota,” “diabetes,” “trimethylamine n-oxide,” “iga nephropathy,” “acute kidney injury,” “chronic kidney disease,” “inflammation,” all of which necessitate further investigation.

Conclusion: This study presents a comprehensive bibliometric analysis and offers an up-to-date outlook on the research related to the gut-kidney axis, with a specific emphasis on the present state of intercommunication between gut microbiota and kidney diseases in this field. This perspective may assist researchers in selecting appropriate journals and partners, and help to gain a deeper understanding of the field’s hotspots and frontiers, thereby promoting future research.
Effects of school-based physical activity interventions on physical fitness and cardiometabolic health in children and adolescents with disabilities: a systematic review
Authors: Manojlovic Marko , Roklicer Roberto , Trivic Tatjana , Milic Rade , Maksimović Nemanja , Tabakov Roman , Sekulic Damir , Bianco Antonino , Drid Patrik
Published: June 2023

Background: This study aimed to examine the influence of school-based physical exercise programs on physical fitness and cardiometabolic health in children and adolescents with disabilities.

Methods: Web of Science, Scopus, and PubMed were thoroughly searched to identify relevant investigations. To be included in the systematic review, studies needed to fulfill the following inclusion criteria: 1) performed school-based physical exercise interventions; 2) parameters evaluated referred to health-related physical fitness (HRPF), skill-related physical fitness (SRPF), and cardiometabolic health; 3) a sample of participants consisted of children and adolescents with disabilities; 4) the mean age of respondents was less than 18 years; and 5) were written in the English language.

Results: After searching the databases, a total of 474 studies have been identified, 18 of them met the eligibility criteria, and their outcomes were presented. Relating to the respondents’ characteristics, the investigations involved 681 children and adolescents with disabilities, out of which 440 were male and 241 female. Regarding types of physical exercise interventions, the most commonly implemented were combined aerobic and resistance training, aerobic exercise, sports games, adapted high-intensity interval training, as well as sprint interval training. The obtained results unambiguously demonstrated that applied exercise interventions improved HRPF components such as cardiorespiratory fitness, muscular fitness, and flexibility. In terms of the SRPF, agility, balance, coordination, and power were considerably enhanced following the school-based exercise. On the other hand, the influence on indices of body composition and cardiometabolic health is quite controversial. The majority of the available studies did not find favorable effects. Additionally, no adverse events were reported in 7 of 8 research, and adherence to exercise was approximately 92%.

Conclusion: School-based physical exercise programs were very efficient in improving HRPF and SRPF in children and adolescents with disabilities, while the evidence concerning the variables of body composition and cardiometabolic health is inconclusive and warrants further investigations.
Inflammatory mediators act at renal pericytes to elicit contraction of vasa recta and reduce pericyte density along the kidney medullary vascular network
Authors: Lilley Rebecca J. , Taylor Kirsti D. , Wildman Scott S. P. , Peppiatt-Wildman Claire M.
Published: June 2023

Introduction: Regardless of initiating cause, renal injury promotes a potent pro-inflammatory environment in the outer medulla and a concomitant sustained decrease in medullary blood flow (MBF). This decline in MBF is believed to be one of the critical events in the pathogenesis of acute kidney injury (AKI), yet the precise cellular mechanism underlying this are still to be fully elucidated. MBF is regulated by contractile pericyte cells that reside on the descending vasa recta (DVR) capillaries, which are the primary source of blood flow to the medulla.

Methods: Using the rat and murine live kidney slice models, we investigated the acute effects of key medullary inflammatory mediators TNF-α, IL-1β, IL-33, IL-18, C3a and C5a on vasa recta pericytes, the effect of AT1-R blocker Losartan on pro-inflammatory mediator activity at vasa recta pericytes, and the effect of 4-hour sustained exposure on immunolabelled NG2+ pericytes.

Results and discussion: Exposure of rat and mouse kidney slices to TNF-α, IL-18, IL-33, and C5a demonstrated a real-time pericyte-mediated constriction of DVR. When pro-inflammatory mediators were applied in the presence of Losartan the inflammatory mediator-mediated constriction that had previously been observed was significantly attenuated. When live kidney slices were exposed to inflammatory mediators for 4-h, we noted a significant reduction in the number of NG2+ positive pericytes along vasa recta capillaries in both rat and murine kidney slices. Data collected in this study demonstrate that inflammatory mediators can dysregulate pericytes to constrict DVR diameter and reduce the density of pericytes along vasa recta vessels, further diminishing the regulatory capacity of the capillary network. We postulate that preliminary findings here suggest pericytes play a role in AKI.
MRI-MECH: mechanics-informed MRI to estimate esophageal health
Authors: Halder Sourav , Johnson Ethan M. , Yamasaki Jun , Kahrilas Peter J. , Markl Michael , Pandolfino John E. , Patankar Neelesh A.
Published: June 2023

Dynamic magnetic resonance imaging (MRI) is a popular medical imaging technique that generates image sequences of the flow of a contrast material inside tissues and organs. However, its application to imaging bolus movement through the esophagus has only been demonstrated in few feasibility studies and is relatively unexplored. In this work, we present a computational framework called mechanics-informed MRI (MRI-MECH) that enhances that capability, thereby increasing the applicability of dynamic MRI for diagnosing esophageal disorders. Pineapple juice was used as the swallowed contrast material for the dynamic MRI, and the MRI image sequence was used as input to the MRI-MECH. The MRI-MECH modeled the esophagus as a flexible one-dimensional tube, and the elastic tube walls followed a linear tube law. Flow through the esophagus was governed by one-dimensional mass and momentum conservation equations. These equations were solved using a physics-informed neural network. The physics-informed neural network minimized the difference between the measurements from the MRI and model predictions and ensured that the physics of the fluid flow problem was always followed. MRI-MECH calculated the fluid velocity and pressure during esophageal transit and estimated the mechanical health of the esophagus by calculating wall stiffness and active relaxation. Additionally, MRI-MECH predicted missing information about the lower esophageal sphincter during the emptying process, demonstrating its applicability to scenarios with missing data or poor image resolution. In addition to potentially improving clinical decisions based on quantitative estimates of the mechanical health of the esophagus, MRI-MECH can also be adapted for application to other medical imaging modalities to enhance their functionality.
Stable isotopic analysis of water utilization characteristics of four xerophytic shrubs in the Hobq Desert, Northern China
Authors: Yongsheng Wu , Zilong Liao , Xiangqian Yu , Qiang Yin , Hui Wang , Li Gao
Published: June 2023

Quantitative identification of water utilization characteristics of xerophytic shrubs is an important prerequisite for the selection and optimization of a regional artificial sand-fixing vegetation system. In this study, a hydrogen (δD) stable isotope technique was used to study the changes in water use characteristics of four typical xerophytic shrubs, Caragana korshinskii, Salix psammophila, Artemisia ordosica, and Sabina vulgaris in the Hobq Desert under light (4.8 mm after 1 and 5 days) and heavy (22.4 mm after 1 and 8 days) rainfall events. Under light rainfall, C. korshinskii and S. psammophila primarily used the 80–140 cm layer of soil water (37–70%) and groundwater (13–29%), and the water use characteristics did not change significantly after the light rainfall event. However, the utilization ratio of A. ordosica to soil water in the 0–40 cm layer increased from less than 10% on the first day after rain to more than 97% on the fifth day after rain, whereas the utilization ratio of S. vulgaris to soil water in the 0–40 cm layer also increased from 43% to nearly 60%. Under heavy rainfall, C. korshinskii and S. psammophila still used the 60–140 cm layer (56–99%) and groundwater (~15%), while the main water utilization depth of A. ordosica and S. vulgaris expanded to 0–100 cm. Based on the above results, C. korshinskii and S. psammophila primarily use the soil moisture of the 80–140 cm layer and groundwater, while A. ordosica and S. vulgaris use the soil moisture of the 0–100 cm layer. Therefore, the co-existence of A. ordosica and S. vulgaris will increase the competition between artificial sand-fixing plants, while the combination of the two plants with C. korshinskii and S. psammophila will avoid competition between artificial sand-fixing plants to some extent. This study provides important guidance for regional vegetation construction and sustainable management of an artificial vegetation system.
A method for analyzing programmed cell death in xylem development by flow cytometry
Authors: Liu Ying-Li , Guo Ying-Hua , Song Xue-Qin , Hu Meng-Xuan , Zhao Shu-Tang
Published: June 2023

Programmed cell death (PCD) is a genetically regulated developmental process leading to the death of specific types of plant cells, which plays important roles in plant development and growth such as wood formation. However, an efficient method needs to be established to study PCD in woody plants. Flow cytometry is widely utilized to evaluate apoptosis in mammalian cells, while it is rarely used to detect PCD in plants, especially in woody plants. Here, we reported that the xylem cell protoplasts from poplar stem were stained with a combination of fluorescein annexin V-FITC and propidium iodide (PI) and then sorted by flow cytometry. As expected, living cells (annexin V-FITC negative/PI negative), early PCD cells (annexin V-FITC positive/PI negative), and late PCD cells (annexin V-FITC positive/PI positive) could be finely distinguished through this method and then subjected for quantitative analysis. The expression of cell-type- and developmental stages-specific marker genes was consistent with the cell morphological observation. Therefore, the newly developed fluorescence-activated cell sorting (FACS) method can be used to study PCD in woody plants, which will be beneficial for studying the molecular mechanisms of wood formation.
The framing of choice nudges prolonged processing in the evaluation of food images
Authors: Xu Ji , Jin Yimeng , Lauwereyns Johan
Published: June 2023

Previous research suggests that the type of choice framing for evaluation tasks can influence the relationship between response time and preference-based decision-making. Two separable factors may modulate the preference-based decision-making: The set of choice options (with or without an option to defer) and the constraint of choice (with high or low maximum for inclusion). To clarify how these factors influence the process of preference-based decision-making, we designed a virtual-shopping paradigm with a series of food images presented consecutively, while varying the set of choice options and the constraint of choice. For the set of choice options, subjects were asked to choose for each food image in either a two-options condition (i.e., “take it” or “leave it”), or a three-options condition (i.e., “take it,” “wait,” or “leave it”). For the constraint of choice, subjects were instructed to select a maximum of either five items out of 80 (i.e., highly constrained) or 15 items out of 80 (i.e., less constrained). As in previous findings, the response times were consistently longer for “take it” than for “leave it” options. Importantly, this difference was exacerbated under high constraint, when subjects could select only five items, suggesting a role for opportunity-cost consideration in the decision process. Furthermore, as compared to two-options tasks, subjects consistently spent more time overall in the three-options tasks (with the option to defer), displaying lower acceptance rates, and particularly long response times for the “wait” option. This finding suggests that choice framing with a defer option nudges prolonged processing.
Assembly-style making: How structured making serves as an on-ramp to creativity and engineering design
Authors: Lukowski Sarah , Goeke Megan , Schmit Bette , Bequette Marjorie
Published: June 2023

Makerspaces, workspaces where families can explore materials and tools collaboratively, can provide an opportunity for creative expression and early engineering learning in community spaces. The present study examined a cardboard-focused museum makerspace that included an assembly-style activity. Assembly-style making uses instructions to support makers. Such activities have been critiqued as limiting creativity and engineering thinking. However, makers who are less comfortable in makerspaces may benefit from assembly-style activities helping to scaffold their entry into the space. We explored these criticisms and potential benefits of assembly-style making through developing case studies of video data taken by families in a makerspace. Visitors made creative and personally meaningful creations when engaged in assembly style making. Moreover, assembly-style making mediated a family less comfortable with making to get started in the space alongside ample evidence of families following engineering design processes. Contrary to popular belief, assembly-style making offers an important support to novice makers, without eliminating creativity and engineering design processes, and should be considered in the mix of activities available in makerspaces to support makers of all levels of comfort in making.