bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental pollution liability insurance pilot policy and enterprise green transformation: evidence from Chinese listed corporates
Authors: Hu Ling , Liu Ziming , Liu Pengzhen
Published: November 2023

In the context of dual-carbon, corporate green transformation, a significant measure of the green effect of Environmental Pollution Liability Insurance (EPLI), garners substantial attention in current research. By leveraging the 2008 EPLI pilot policy as an exogenous event, this paper employs a difference-in-difference model to scrutinize the influence of the EPLI pilot on the green transformation of listed companies. We find that: (1) The EPLI pilot actively promotes corporate green transformation. (2) The pilot policy’s impact on green transformation is mediated through regional green development and enterprise investment efficiency. (3) The pilot policy manifests asymmetric effects on green transformation, influenced by regional, industrial, and enterprise-specific pollution levels, as well as government environmental concerns. (4) The EPLI pilot policy engenders enduring financial implications and contributes to the governance of information. This study is beneficial to enrich the research on the EPLI system and green transformation of enterprises that provide policy suggestions for improving the green financial system and promoting the green transformation of enterprises.
Advances in colon capsule endoscopy: a review of current applications and challenges
Authors: Gibbons E. , Kelly O. B. , Hall B.
Published: November 2023

Colon capsule endoscopy (CCE) has been demonstrated to be comparable to traditional colonoscopy and better than CT colonography (CTC) for the detection of colonic pathology. It has been shown to have a high incremental yield after incomplete colonoscopy. It is a safe test with good patient acceptability. Challenges currently include great variability in completion rates and high rates of re-investigation. In this review, we will discuss the evidence to date regarding CCE in symptomatic and surveillance populations, and in those post incomplete colonoscopy. We will discuss current challenges faced by CCE and areas for further research.
Takinib inhibits microglial M1 polarization and oxidative damage after subarachnoid hemorrhage by targeting TAK1-dependent NLRP3 inflammasome signaling pathway
Authors: Wang Weihan , Pang Cong , Zhang Jiaxing , Peng Lei , Zhang Xianghua , Shi Lin , Zhang Hao
Published: November 2023

Transforming growth factor-β-activated kinase 1 (TAK1) positively regulates oxidative stress and inflammation in different diseases. Takinib, a novel and specific TAK1 inhibitor, has beneficial effects in a variety of disorders. However, the effects of takinib on early brain injury (EBI) after subarachnoid hemorrhage (SAH) and the underlying molecular mechanisms remain unknown. Our study showed that takinib administration significantly inhibited phosphorylated TAK1 expression after SAH. In addition, takinib suppressed M1 microglial polarization and promoted M2 microglial polarization. Furthermore, blockade of TAK1 by takinib reduced neuroinflammation, oxidative damage, brain edema, and neuronal apoptosis, and improved neurological behavior after SAH. Mechanistically, we revealed that TAK1 inhibition by takinib mitigated reactive oxygen species (ROS) production and ROS-mediated nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation. In contrast, NLRP3 activation by nigericin abated the neuroprotective effects of takinib against EBI after SAH. In general, our study demonstrated that takinib could protect against EBI by targeting TAK1-ROS-NLRP3 inflammasome signaling. Inhibition of TAK1 might be a promising option in the management of SAH.
Olink proteomics analysis uncovers the landscape of inflammation-related proteins in patients with acute compartment syndrome
Authors: Wang Tao , Yang Shuo , Long Yubin , Li Yiran , Wang Ting , Hou Zhiyong
Published: November 2023

Purpose

Our primary purpose was to explore the landscape of inflammation-related proteins, and our second goal was to investigate these proteins as potential biomarkers of acute compartment syndrome (ACS), which is a serious complication of tibial fractures.

Methods

We collected sera from 15 healthy subjects (control group, CG) and 30 patients with tibial fractures on admission day, comprising 15 patients with ACS (ACS group, AG) and 15 patients without ACS (fracture group, FG). Ten samples in each group were analyzed by the inflammation panel of Olink Proteomics Analysis, and all samples were verified by an ELISA. Receiver-operating characteristic (ROC) curve analysis was performed to identify the diagnostic ability and cutoff values of potential biomarkers.

Results

Our findings showed that the levels of IL6, CSF-1, and HGF in the FG were significantly higher than those in the CG. Similar results were found between the AG and CG, and their cutoff values for predicting ACS compared with the CG were 9.225 pg/ml, 81.04 pg/ml, and 0.3301 ng/ml, respectively. Furthermore, their combination had the highest diagnostic accuracy. Notably, compared with FG, we only found a higher expression of CCL23 in the AG. Additionally, we identified 35.75 pg/ml as the cutoff value of CCL23 for predicting ACS in patients with tibial fractures.

Conclusion

We identified CCL23 as a potential biomarker of ACS in comparison with tibial fracture patients and the significance of the combined diagnosis of IL6, CSF-1, and HGF for predicting ACS compared with healthy individuals. Furthermore, we also found their cutoff values, providing clinicians with a new method for rapidly diagnosing ACS. However, we need larger samples to verify our results.
Factors associated with urinary tract infection in the early phase after performing intermittent catheterization in individuals with spinal cord injury: a retrospective study
Authors: Xing Huayi , Dai Hongyue , Li Baohua , Yuan Xiaoning , Liu Xiaoxuan , Cui Guoqing , Liu Nan , Biering-Sørensen Fin
Published: November 2023

Objectives

To investigate the occurrence rate of urinary tract infections (UTIs) in the early phase after performing intermittent catheterization (IC) and to explore the possible factors associated with UTIs after performing IC among people with spinal cord injury (SCI).

Setting

An inpatient rehabilitation department of a teaching hospital in China.

Design

Retrospective chart review.

Methods

A retrospective chart review was carried out for traumatic and non-traumatic SCI patients after performing IC during their inpatient stay. Demographic information, comorbidity of diabetes, urine analysis results before IC, method of IC (sterile or clean), use of bladder irrigation, cessation of IC and its reasons, and UTI events were collected.

Results

A total of 183 adult individuals were included, of which 60 (32.8%) of them were women. The median age was 49.0 years. The median time post-injury was 2 months. The overall occurrence rate of UTI after performing IC was 1.31 (95% confidence intervals: 0.96–1.77) events per 100 days. Sixty-nine (37.7%) patients discontinued IC during hospitalization, and UTIs were the leading reason for cessation (50.7%). Female sex, use of antibiotics for infections other than UTI, and use of bladder irrigation were found to be associated with a lower occurrence rate of UTI in the early phase after performing IC, with an odds ratio of 0.38 (p = 0.019), 0.20 (p = 0.022), and 0.24 (p < 0.001), respectively.

Conclusion

UTI after performing IC is prevalent among people with SCI. The study indicated that antibiotic prophylaxis and routine bladder irrigation might be associated with the reduction in UTI in the early phase after performing IC. Further research is needed to provide more evidence.
Somatic comorbidity and the progression of cognitive impairment
Authors: Bidzan Leszek , Jurek Paweł , Olech Michał , Bidzan-Wiącek Monika , Bidzan-Bluma Ilona , Bidzan Mariola
Published: November 2023

Background

There are usually multiple factors underlying dementia in old age. Somatic comorbidity is one important element that influences the progression of cognitive impairment.

Objective

The goal of this study was to assess the relationship between the progression of cognitive impairment and the presence and severity of comorbidities based on a four-year observation.

Material

Out of 128 patients from the Clinic for Outpatients in Gdansk, who were recruited into the study based on the criteria of the Working Group on Mild Cognitive Impairment, a total of 93 participants completed the four-year observation. Only the data from participants who completed the full period of observations were analysed. The mean age of the group was M = 75.93 (SD = 9.43). The level of progression of cognitive impairment was measured using the Clinical Dementia Rating Scale – Sum of Boxes, the severity of comorbidities was measured using the modified Cumulative Illness Rating Scale, and, additionally, at the time of inclusion in the study, participants were assessed using the MMSE scale and the Activity Scale, and sociodemographic data were collected. The Generalized Estimating Equations method was employed to fit a marginal model for analyzing the data collected in a repeated measures design. The tested model elucidated the role of the overall severity of comorbidities in explaining the progression of cognitive impairment, while controlling for everyday activity and basic demographic variables.

Results

During the four-year observation, a significant decline in cognitive function (B = 1.86, p < 0.01) was observed in the examined sample. The statistical analysis revealed that individuals with higher overall severity of comorbidities exhibited significantly more pronounced progression of cognitive impairment over time. Regarding particular comorbidities, metabolic diseases were found to be associated with a poorer prognosis (rho = 0.41, p < 0.05). Furthermore, a time physical activity interaction was identified as predicting cognitive impairment, indicating that individuals who were more physically active at the beginning of the study exhibited significantly less pronounced progression of cognitive impairment over the course of the 4 years.

Conclusion

This study suggests the important roles of comorbidities and physical activity for the prognosis of mild cognitive impairment.
Case report: Ultrasound-guided median nerve electrical stimulation on functional recovery of hemiplegic upper limb after stroke
Authors: Li Rui , Zhang Ping , Lu Jingyi , Zhuang Jianlin , Wang Meiqi , Fang Hongmei , Zhang Xiaowei , Gao Ying , Yang Zhufen , Chin Kai Ling
Published: November 2023

Background

Functional restoration of hemiplegic upper limbs is a difficult area in the field of neurological rehabilitation. Electrical stimulation is one of the treatments that has shown promising advancements and functional improvements. Most of the electrical stimulations used in clinical practice are surface stimulations. In this case, we aimed to investigate the feasibility of a minimally invasive, ultrasound-guided median nerve electrical stimulation (UG-MNES) in improving the upper limb motor function and activity of a patient with right-sided hemiparesis.

Case presentation

A 65-year-old male recovering from a left massive intracerebral hemorrhage after open debridement hematoma removal had impaired right limb movement, right hemianesthesia, motor aphasia, dysphagia, and complete dependence on his daily living ability. After receiving 3 months of conventional rehabilitation therapy, his cognitive, speech, and swallowing significantly improved but the Brunnstrom Motor Staging (BMS) of his right upper limb and hand was at stage I-I. UG-MNES was applied on the right upper limb for four sessions, once per week, together with conventional rehabilitation. Immediate improvement in the upper limb function was observed after the first treatment. To determine the effect of UG-MNES on long-term functional recovery, assessments were conducted a week after the second and fourth intervention sessions, and motor function recovery was observed after 4-week of rehabilitation. After completing the full rehabilitation course, his BMS was at stage V-IV, the completion time of Jebsen Hand Function Test (JHFT) was shortened, and the scores of Fugl-Meyer Assessment for upper extremity (FMA-UE) and Modified Barthel Index (MBI) were increased. Overall, the motor function of the hemiplegic upper limb had significantly improved, and the right hand was the utility hand. Electromyography (EMG) and nerve conduction velocity (NCV) tests were normal before and after treatment.

Conclusion

The minimally invasive, UG-MNES could be a new alternative treatment in stroke rehabilitation for functional recovery of the upper limbs.
Sudden unexpected death in epilepsy disclosure causes anxiety in patients with epilepsy: a Chinese questionnaire survey
Authors: Pan Yuanhang , Hu Gengyao , Wang Zezhi , Yuan Na , Wei Zihan , Li Xia , Hou Xiaohua , Wang Jian , Zhang Xinbo , Chen Ze , Qu Shuyi , Bao Junxiang , Liu Yonghong
Published: November 2023

Background and objective

Sudden unexpected death in epilepsy (SUDEP) has been regarded as a leading cause of premature death in patients with epilepsy (PWE). Although patients, relatives and caregivers have the right to be informed of SUDEP, neurologists prefer not to release the facts for fear of associated anxiety. In the study, a Chinese questionnaire survey was carried out to elucidate effect of SUDEP disclosure on anxiety in PWE and variables determining the anxiety of patients and provided suggestions for SUDEP disclosure.

Methods

A survey study in China was conducted. We recruited 305 PWE from 3 tertiary epilepsy centers who attended outpatient clinic from December 2021 to February 2022. Two hundred and thirty-two PWE completed the screening evaluation, survey and Hamilton anxiety rating scale (HAMA) twice with 171 PWE completing third HAMA at follow-up. HAMA scores at baseline, T1, T2 were compared using analysis of variance and dependent samples t-test. The variables related to anxiety were screened out by univariate analysis and used for multivariate logistic regression.

Result

We found 127 (54.7%) among the 232 participants experienced anxiety after SUDEP disclosure. HAMA scores at T1 were significantly higher than at baseline and T2, while there was no statistical difference between baseline and T2. Medical insurance, seizure severity, and whether the PWE supported SUDEP being disclosed to their relatives and caregivers only were associated with the occurrence of anxiety.

Conclusion

SUDEP disclosures may cause short-term acute anxiety, but have no long-term effects in PWE. Acute anxiety caused by SUDEP disclosure may be more common in PWE with NCMI and severe seizures. Meanwhile, compared with indirect SUDEP disclosure to their relatives and caregivers, direct SUDEP disclosure to PWE reduces the risk of anxiety. Recommendations are provided to avoid anxiety caused by SUDEP disclosure.
Do multiple physiological OCT biomarkers indicate age-related decline in rod mitochondrial function in C57BL/6J mice?
Authors: Goodman Cole , Podolsky Robert H. , Childers Karen Lins , Roberts Robin , Katz Ryan , Waseem Rida , Paruchuri Anuhya , Stanek Josh , Berkowitz Bruce A.
Published: November 2023

Purpose

To test the hypothesis that rod photoreceptor mitochondria function in vivo progressively declines over time.

Methods

2, 12, and 24 month-old dark- and light-adapted C57BL/6J (B6J) mice were examined by OCT. We measured (i) an index of mitochondrial configuration within photoreceptors measured from the profile shape aspect ratio (MCP/AR) of the hyperreflective band posterior to the external limiting membrane (ELM), (ii) a proxy for energy-dependent pH-triggered water removal, the thickness of the ELM-retinal pigment epithelium (ELM-RPE), and its correlate (iii) the hyporeflective band (HB) signal intensity at the photoreceptor tips. Visual performance was assessed by optokinetic tracking.

Results

In 2 and 24 month-old mice, MCP/AR in both inferior and superior retina was smaller in light than in dark; no dark–light differences were noted in 12 month-old mice. Dark-adapted inferior and superior, and light-adapted superior, ELM-RPE thickness increased with age. The dark–light difference in ELM-RPE thickness remained constant across all ages. All ages showed a decreased HB signal intensity magnitude in dark relative to light. In 12 month-old mice, the dark–light difference in HB magnitude was greater than in younger and older mice. Anatomically, outer nuclear layer thickness decreased with age. Visual performance indices were reduced at 24 month-old compared to 2 month-old mice.

Conclusion

While the working hypothesis was not supported herein, the results raise the possibility of a mid-life adaptation in rod mitochondrial function during healthy aging in B6J mice based on OCT biomarkers, a plasticity that occurred prior to declines in visual performance.
Impact of healthcare inequities on survival in Mexican patients with metastatic renal cell carcinoma
Authors: Bourlon Maria T. , Remolina-Bonilla Yuly A. , Acosta-Medina Aldo A. , Saldivar-Oviedo Bruno I. , Perez-Silva Antonio , Martinez-Ibarra Nayeli , Castro-Alonso Francisco Javier , Martín-Aguilar Ana E. , Rivera-Rivera Samuel , Mota-Rivero Fernando , Pérez-Pérez Perla , Díaz-Alvarado María G. , Ruiz-Morales José M. , Campos-Gómez Saúl , Martinez-Cannon Bertha Alejandra , Lam Elaine T. , Sobrevilla-Moreno Nora
Published: November 2023

Introduction

The survival of patients with metastatic renal cell carcinoma (mRCC) has improved dramatically due to novel systemic treatments. However, mRCC mortality continues to rise in Latin America.

Methods

A retrospective, multicenter study of patients diagnosed with mRCC between 2010-2018 in Mexico City was conducted. The aim of the study was to evaluate the impact of healthcare insurance on access to treatment and survival in patients with mRCC.

Results

Among 924 patients, 55.4%, 42.6%, and 1.9% had no insurance (NI), social security, (SS) and private insurance (PI), respectively. De novo metastatic disease was more common in NI patients (70.9%) compared to SS (47.2%) and PI (55.6%) patients (p<0.001). According to IMDC Prognostic Index, 20.2% were classified as favorable, 49% as intermediate, and 30.8% as poor-risk disease. Access to systemic treatment differed by healthcare insurance: 36.1%, 99.5%, and 100% for the NI, SS, and PI patients, respectively (p<0.001). NI patients received fewer lines of treatment, with 24.8% receiving only one line of treatment (p<0.001). Median overall survival (OS) was 13.9 months for NI, 98.9 months for SS, and 147.6 months for NI patients (p<0.001). In multivariate analysis, NI status, brain metastases, sarcomatoid features, bone metastases, no treatment were significantly associated with worse OS.

Conclusion

OS in mRCC was affected by insurance availability in this resource-limited cohort of Mexican patients. These results underscore the need for effective strategies to achieve equitable healthcare access in an era of effective, yet costly systemic treatments.
CPX-351 in FLT3-mutated acute myeloid leukemia
Authors: Andrews Claire , Pullarkat Vinod , Recher Christian
Published: November 2023

CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a 1:5 molar ratio, is approved for the treatment of newly diagnosed therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes. In a pivotal phase III trial, CPX-351 significantly improved overall survival compared with standard-of-care 7 + 3 chemotherapy (7 days cytarabine; 3 days daunorubicin) in adults aged 60–75 years with newly diagnosed high-risk or secondary AML (median = 9.56 months vs. 5.95 months; hazard ratio = 0.69; 95% confidence interval = 0.52–0.90; p = 0.003). Approximately 30% of patients with newly diagnosed AML have mutations in the FLT3 gene, which may be associated with poor outcomes. Here, we review the current in vitro, clinical, and real-world evidence on the use of CPX-351 in patients with AML and mutations in FLT3. Additionally, we review preliminary data from clinical trials and patient case reports that suggest the combination of CPX-351 with FLT3 inhibitors may represent another treatment option for patients with FLT3 mutation-positive AML.
Development and validation of a nomogram for predicting prostate cancer based on combining contrast-enhanced transrectal ultrasound and biparametric MRI imaging
Authors: Nong Wanxian , Huang Qun , Gao Yong
Published: November 2023

Objectives

This study was to explore the feasibility of combining contrast-enhanced transrectal ultrasound (CE-TRUS) with biparametric MRI (CEUS-BpMRI) score for diagnosing prostate cancer (PCa).

Methods

A total of 183 patients with suspected PCa who underwent multiparametric MRI (Mp-MRI) and CE-TRUS were included. CEUS-BpMRI score was developed based on the results of Mp-MRI and CE-TRUS. The diagnostic performance was evaluated by the area under the curve (AUC). The diagnostic efficacy of the CEUS-BpMRI score, BpMRI score, and PI-RADS v2.1 score were compared. Total patients were randomly assigned to a training cohort (70%) or validation cohort (30%). A nomogram was constructed based on univariate and multivariate logistic regression. The model was evaluated by AUC and calibration curve.

Results

The diagnostic performance of CEUS-BpMRI score (AUC 0.857) was comparable to that of PI-RADS v2.1 (AUC 0.862) (P = 0.499), and both were superior to Bp-MRI score (AUC 0.831, P < 0.05). In peripheral zone lesions with Bp-MRI score of 3, there was no statistically significant difference between PI-RADS v2.1 score (AUC 0.728) and CEUS-BpMRI score (AUC 0.668) (P = 0.479). Multivariate analysis showed that age, total prostate specific antigen/free prostate specific antigen (F/T), time to peak (TTP), and CEUS-BpMRI score were independent factors. The AUC of the nomogram was 0.909 in the training cohort and 0.914 in the validation cohort.

Conclusions

CEUS-BpMRI score has high diagnostic efficacy for diagnosing PCa. A nomogram model established by combining age, F/T, TTP, and CEUS-BpMRI score can achieve the best predictive accuracy for PCa.
Endoscopic submucosal dissection of endobronchial leiomyoma with a hybrid knife in an adolescent patient: a case report
Authors: Wang Zilin , Hou Gang
Published: November 2023

Endobronchial leiomyomas are uncommon benign tracheobronchial tumors. Bronchoscopic intervention is a safe and effective strategy for patients with contraindications for surgery or refusal to undergo surgery. Endoscopic submucosal dissection (ESD) is widely used to treat early gastrointestinal tumors. The novel hybrid knife is useful during ESD owing to functions of submucosal injections, lesion dissection and hemostasis, and makes ESD more convenient. Here, we report a case of a benign leiomyoma at the orifice of RB7 in an adolescent boy. The diagnosis was confirmed based on bronchoscopic and pathological findings. The patient was successfully treated with combined electrocautery snare and cryoresection, ESD using a hybrid knife and the wound was managed with argon plasma coagulation. The postoperative course was satisfactory, with a good general condition and no severe respiratory symptoms. This is, to our knowledge, the first reported case of ESD using a hybrid knife to treat an endobronchial leiomyoma in an adolescent patient.
Longitudinal study of cross-reactive antigenemia in individuals with high Loa loa microfilarial density reveals promising biomarkers for distinguishing lymphatic filariasis from loiasis
Authors: Djune-Yemeli Linda , Hertz Marla , Nana-Djeunga Hugues C. , Rush Amy , Erdmann-Gilmore Petra , Sprung Robert , Bopda Jean Gabin , Townsend Reid , Netongo Palmer Masumbe , Kamgno Joseph , Budge Philip J.
Published: November 2023

Background and methods

Circulating Loa loa antigens are often detected in individuals with heavy L. loa infections by diagnostic tests for lymphatic filariasis (LF) caused by Wuchereria bancrofti. This is a major challenge to LF mapping and elimination efforts in loiasis co-endemic areas. However, it also provides an opportunity to identify antigen biomarkers for loiasis. To determine which L. loa antigens might be promising biomarkers for distinguishing true LF from loiasis, we screened for L. loa antigens in a group of individuals with heavy L. loa infections living in the Okola Health District of Cameroon. In this longitudinal study, participants were tested for cross-reactive antigenemia by filariasis test strip (FTS), ELISA, and western blot, and were monitored for FTS status at 6, 9, 12, and 15 months post-enrollment. We then identified specific circulating L. loa antigens by liquid chromatography-tandem mass spectrometry (LC-MS/MS) from baseline and 15-month plasma samples.

Principal findings and conclusions

Among 73 FTS-positive (FTS+) and 13 FTS-negative (FTS-) participants with high L. loa microfilarial loads, 83% maintained their FTS status over the course of the study, while 17% experienced at least one FTS conversion event (from FTS+ to FTS- or vice versa). Cross-reactive antigens were detected in both FTS+ and FTS- sera by western blot, and there was poor agreement in antigen detection by FTS, western blot, and ELISA methods. One protein family, a group of Nas-14 metalloproteases, was detected by LC MS/MS in >80% of tested samples, including FTS- samples. These data identify Nas-14 as a promising loiasis biomarker potentially capable of distinguishing loiasis from lymphatic filariasis.
Comparison of pharmacokinetics and safety between CE-fosphenytoin sodium, fosphenytoin sodium, and phenytoin sodium after intravenous and intramuscular administration in healthy volunteers
Authors: Li Xiaojiao , Wu Min , Sun Jixuan , Jin Weili , Han Lei , Xu Jia , Liu Jingrui , Zhang Hong , Wang Jing , Wang Daidi , Zhang Hanyi , Zhang Qing , Liu Nini , Ding Yanhua
Published: November 2023

Background: Captisol®-enabled-fosphenytoin sodium (CE-fosphenytoin sodium) injection is a modified formulation of fosphenytoin sodium.

Objective: We aim to compare the intravenous and intramuscular bioavailability and safety between CE-fosphenytoin sodium, fosphenytoin sodium (Cerebyx®), and phenytoin sodium (intravenous injection only).

Methods: In pivotal study 1, 54 subjects were divided into three sequence groups that receive intravenous injection of 250 mg of phenytoin sodium equivalent (PE), CE-fosphenytoin sodium (T), or fosphenytoin sodium (R1) and 250 mg of phenytoin sodium (R2) in period 1. After a 14-day washout period, 36 subjects were randomized to two treatment sequence groups (T-R1 or R1-T, n = 18 per group) in period 2, in which the subjects who received R2 in period 1 were removed, those who received T in period 1 used R1 (T-R1), while those who previously received R1 used T (R1-T). In pivotal study 2, a single intramuscular dose of T (400 mg PE) or R1 (400 mg PE) was administered according to the individual sequential treatment assignment in each period. There was a washout (14 days) period before receiving the next period study drug.

Results: T and R1 have similar pharmacokinetic characteristics regarding total and free phenytoin, showing bioequivalence of both drugs in the intravenous and intramuscular administration. The geometric mean ratio was close to 1 (0.98–1.06). The AUC of total and free phenytoin in subjects who intravenously received T and R1 was very similar to those who received R2, although their Cmax was lower than that of the subjects who received R2. Overall, treatment with T and R1 was safe and well-tolerated, without serious adverse events (SAEs) or grade III adverse events (AEs). With intravenous (i.v.) or intramuscular (i.m.) treatment, the incidence of drug-related AEs using T was similar to that using R1. Treatment with T and R1 had clearly superior tolerability than that with R2.

Conclusion: CE-fosphenytoin sodium is a promising substitute for fosphenytoin sodium.

Clinical Trial Registration:http://www.chinadrugtrials.org.cn/, CTR20202154 (11 November 2020).
Myrrh protects against IL-13-induced epithelial barrier breakdown in HT-29/B6 cells
Authors: Hader Helena , Hering Nina A. , Schulzke Jörg-Dieter , Bücker Roland , Rosenthal Rita
Published: November 2023

The oleoresin myrrh has been used for centuries as an anti-inflammatory remedy for a variety of diseases and is said to have a protective effect on the intestinal epithelium. An intact epithelial barrier function is the prerequisite for a healthy gut. Inflammatory and infectious diseases of the intestine, in particular, lead to barrier impairment resulting in leak-flux diarrhea and mucosal immune responses. Therefore, the aim of the present study was to investigate the protective effect of myrrh in an experimental inflammatory situation, namely, under the influence of IL-13, one of the key cytokines in ulcerative colitis. We used human intestinal epithelial HT-29/B6 cell monolayers for functional and molecular assessment of the epithelial barrier under IL-13 and myrrh treatment. IL-13 induced a loss in barrier function that was fully restored with myrrh treatment, as shown by transepithelial electrical resistance measurements. The molecular correlate of the IL-13-mediated barrier dysfunction could be assigned to an upregulation of the channel-forming tight junction (TJ) protein claudin-2 and to a subcellular redistribution of the TJ protein tricellulin, loosening the sealing of tricellular TJs. Moreover, IL-13 exposure leads to an increase in the number of apoptotic cells, contributing to the leak pathway of barrier dysfunction. Myrrh protected against changes in TJ deregulation and decreased the elevated apoptotic ratio under IL-13. The protective effects are mediated through the inhibition of the STAT3 and STAT6 pathway. In conclusion, our results demonstrate that myrrh exhibits antagonizing effects against IL-13-induced barrier impairment in a human intestinal cell model. These data suggest the use of myrrh as a promising option in the treatment of inflammatory bowel disease.
Cardiovascular benefits and safety of sotagliflozin in type 2 diabetes mellitus patients with heart failure or cardiovascular risk factors: a bayesian network meta-analysis
Authors: Li Jiyifan , Zhu Chenyang , Liang Jingru , Hu Jiarong , Liu Haiyang , Wang Zihan , Guan Ruifang , Chow Junwei , Yan Shiwei , Li Longzhou , Ma Fuyan , Ma Guo
Published: November 2023

Background: As an antidiabetic agent, sotagliflozin was recently approved for heart failure (HF). However, its cardiovascular benefits in type 2 diabetic mellitus (T2DM) patients with HF or cardiovascular (CV) risk factors have not been systematically evaluated. The aim of this study is to evaluate the cardiovascular benefits and safety of sotagliflozin in T2DM patients with HF or CV risk factors using Bayesian network meta-analysis.

Methods: Data were retrieved from PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Library from their inception to 16 August 2023. Randomized controlled trials (RCTs) comparing sotagliflozin with a placebo, dapagliflozin, and empagliflozin in adult T2DM patients with HF or CV risks for at least 12 weeks were included in the study. Data analysis was conducted using R 4.2.3 and Stata 17.0. Cardiovascular efficacy outcomes included HF events (hospitalization or urgent visits for HF), MACE (deaths from CV causes, hospitalizations for HF, nonfatal myocardial infarctions, and strokes), cardiovascular death, the decrease in SBP, and weight loss. Safety outcomes are urinary tract infection, diarrhea, and diabetic ketoacidosis.

Results: Eleven studies with 30,952 patients were included. Compared to dapagliflozin and empagliflozin, 200 mg of sotagliflozin showed the best effect in reducing HF events [OR (95% CI), 0.79 (0.66, 0.94) and 0.90 (0.63, 1.27)]. Compared to dapagliflozin, 200 mg of sotagliflozin [OR (95% CI), 0.76 (0.66, 0.87)] was superior in preventing MACE. Compared to empagliflozin, 200 mg of sotagliflozin [OR (95% CI), 1.46 (1.04, 2.05)] was inferior in preventing CV death. Sotagliflozin showed a poorer SBP decreasing effect than empagliflozin and dapagliflozin [MD (95% CI), 1.30 (0.03, 2.56) and 2.25 (0.35, 4.14), respectively]. There was no significant difference between sotagliflozin and other interventions in weight loss. Sotagliflozin exhibited no increased risk for diabetic ketoacidosis or urinary tract infection among all interventions, however, it showed a mild risk for diarrhea than placebo [OR (95% CI), 1.47 (1.28, 1.69)].

Conclusion: Sotagliflozin displayed moderate CV benefits and acceptable safety. Sotagliflozin can be one of the recommended options for T2DM patients with HF or CV risk factors, which will be important for evidence-based use of sotagliflozin as well as decision-making of T2DM medication.
Genome sequencing of Syzygium cumini (jamun) reveals adaptive evolution in secondary metabolism pathways associated with its medicinal properties
Authors: Chakraborty Abhisek , Mahajan Shruti , Bisht Manohar S. , Sharma Vineet K.
Published: November 2023

Syzygium cumini, also known as jambolan or jamun, is an evergreen tree widely known for its medicinal properties, fruits, and ornamental value. To understand the genomic and evolutionary basis of its medicinal properties, we sequenced S. cumini genome for the first time from the world’s largest tree genus Syzygium using Oxford Nanopore and 10x Genomics sequencing technologies. We also sequenced and assembled the transcriptome of S. cumini in this study. The tetraploid and highly heterozygous draft genome of S. cumini had a total size of 709.9 Mbp with 61,195 coding genes. The phylogenetic position of S. cumini was established using a comprehensive genome-wide analysis including species from 18 Eudicot plant orders. The existence of neopolyploidy in S. cumini was evident from the higher number of coding genes and expanded gene families resulting from gene duplication events compared to the other two sequenced species from this genus. Comparative evolutionary analyses showed the adaptive evolution of genes involved in the phenylpropanoid-flavonoid (PF) biosynthesis pathway and other secondary metabolites biosynthesis such as terpenoid and alkaloid in S. cumini, along with genes involved in stress tolerance mechanisms, which was also supported by leaf transcriptome data generated in this study. The adaptive evolution of secondary metabolism pathways is associated with the wide range of pharmacological properties, specifically the anti-diabetic property, of this species conferred by the bioactive compounds that act as nutraceutical agents in modern medicine.
Identification and physiological activity of (methoxymethyl)triphenylphosphonium chloride as a new phytotoxin isolated from Rhizoctonia solani AG-3 TB
Authors: Li Xinchun , Hou Huihui , Li Bin , Guo Shiping , Jiang Lianqiang , Xu Chuantao , Xie Yunbo , An Mengnan , Zhang Chong , Wu Yuanhua
Published: November 2023

Rhizoctonia solani as a cosmopolitan fungus is the causative agent of many crop diseases and leads to significant economic losses in crop production. To explore the toxin structure and physiological activity of R. solani AG-3 TB, high-performance liquid chromatography (HPLC), infrared absorption spectrum (IR), and nuclear magnetic resonance spectrum (NMR) were required. Here, the compound (methoxymethyl)triphenylphosphonium chloride (MMC) with the molecular formula C20H20ClOP was purified and identified from R. solani AG-3 TB. The pure compound MMC treated at 20 μg/mL, 50 μg/mL, and 100 μg/mL can cause obvious necrosis on leaves, increase active oxygen species (AOS), decrease chlorophyll content, and damage cellular structure. The results enrich the understanding of toxin compounds for R. solani and provide valuable insights into the toxicology of R. solani AG-3 TB.
Tomato short internodes and pedicels encode an LRR receptor-like serine/threonine-protein kinase ERECTA regulating stem elongation through modulating gibberellin metabolism
Authors: Zhao Xueya , Zhang Kunpeng , Zhang Huidong , Bi Mengxi , He Yi , Cui Yiqing , Tan Changhua , Ma Jian , Qi Mingfang
Published: November 2023

Plant height is an important agronomic trait. Dwarf varieties present several advantages, such as lodging resistance, increased yield, and suitability for mechanized harvesting, which are crucial for crop improvement. However, limited research is available on dwarf tomato varieties suitable for production. In this study, we report a novel short internode mutant named “short internode and pedicel (sip)” in tomato, which exhibits marked internode and pedicel shortening due to suppressed cell elongation. This mutant plant has a compact plant structure and compact inflorescence, and has been demonstrated to produce more fruits, resulting in a higher harvest index. Genetic analysis revealed that this phenotype is controlled by a single recessive gene, SlSIP. BSA analysis and KASP genotyping indicated that ERECTA (ER) is the possible candidate gene for SlSIP, which encodes a leucine-rich receptor-like kinase. Additionally, we obtained an ER functional loss mutant using the CRISPR/Cas9 gene-editing technology. The 401st base A of ER is substituted with T in sip, resulting in a change in the 134th amino acid from asparagine (N) to isoleucine (I). Molecular dynamics(MD) simulations showed that this mutation site is located in the extracellular LRR domain and alters nearby ionic bonds, leading to a change in the spatial structure of this site. Transcriptome analysis indicated that the genes that were differentially expressed between sip and wild-type (WT) plants were enriched in the gibberellin metabolic pathway. We found that GA3 and GA4 decreased in the sip mutant, and exogenous GA3 restored the sip to the height of the WT plant. These findings reveal that SlSIP in tomatoes regulates stem elongation by regulating gibberellin metabolism. These results provide new insights into the mechanisms of tomato dwarfing and germplasm resources for breeding dwarfing tomatoes.
Transcriptome analysis of three medicinal plants of the genus Polygonatum: identification of genes involved in polysaccharide and steroidal saponins biosynthesis
Authors: Lu Jimei , Yao Jinchen , Pu Jingzhe , Wang Duomei , Liu Junling , Zhang Yazhong , Zha Liangping
Published: November 2023

Polysaccharides and saponins are the main active components of Polygonati Rhizoma. Studying the molecular mechanism of their synthesis pathway is helpful in improving the content of active components at the molecular level. At present, transcriptome analysis of three Polygonatum species (Polygonatum sibiricum Red., Polygonatum cyrtonema Hua, Polygonatum kingianum Coll. et Hemsl.) has been reported, but no comparative study has been found on the transcriptome data of the three species. Transcriptome sequencing was performed on the rhizomes of three Polygonatum species based on high-throughput sequencing technology, and all transcripts were assembled. A total of 168,108 unigenes were generated after the removal of redundancy, of which 121,642 were annotated in seven databases. Through differential analysis and expression analysis of key enzyme genes in the synthesis pathway of three Polygonatum polysaccharides and steroidal saponins, 135 differentially expressed genes encoding 18 enzymes and 128 differentially expressed genes encoding 28 enzymes were identified, respectively. Numerous transcription factors are involved in the carbohydrate synthesis pathway. Quantitative real-time PCR was used to further verify the gene expression level. In this paper, we present a public transcriptome dataset of three medicinal plants of the genus Polygonatum, and analyze the key enzyme genes of polysaccharide and steroidal saponins synthesis pathway, which lays a foundation for improving the active component content of Polygonati Rhizoma by molecular means.
Microbial community assembly and functional profiles along the soil-root continuum of salt-tolerant Suaeda glauca and Suaeda salsa
Authors: Tang Luyao , Zhan Le , Han Yanan , Wang Zhengran , Dong Lei , Zhang Zhong
Published: November 2023

Developing and planting salt-tolerant plants has become a promising way to utilize saline-alkali land resources and ensure food security. Root-associated microbes of salt-tolerant plants have been shown to promote plant growth and alleviate high salt stress, yet very little is known about the salt resistance mechanisms of core microbes in different niches. This study characterized the microbial community structures, assembly processes, and functional profiles in four root-related compartments of two salt-tolerant plants by amplicon and shotgun metagenomic sequencing. The results showed that both plants significantly altered the microbial community structure of saline soils, with greater microbial alpha diversity in the rhizosphere or rhizoplane compared with bulk soils. Stochastic process dominated the microbial assembly processes, and the impact was stronger in Suaeda salsa than in S. glauca, indicating that S. salsa may have stronger resistance abilities to changing soil properties. Keystone species, such as Pseudomonas in the endosphere of S. glauca and Sphingomonas in the endosphere of S. salsa, which may play key roles in helping plants alleviate salt stress, were identified by using microbial co-occurrence network analysis. Furthermore, the microbiomes in the rhizoplane soils had more abundant genes involved in promoting growth of plants and defending against salt stress than those in bulk soils, especially in salt-tolerant S. salsa. Moreover, microbes in the rhizoplane of S. salsa exhibited higher functional diversities, with notable enrichment of genes involved in carbon fixation, dissimilar nitrate reduction to ammonium, and sulfite oxidation. These findings revealed differences and similarities in the microbial community assembly, functional profiles and keystone species closely related to salt alleviation of the two salt-tolerant plants. Overall, our study provides new insights into the ecological functions and varied strategies of rhizosphere microbes in different plants under salt stress and highlights the potential use of keystone microbes for enhancing salt resistance of plants.
Comparison of high and low stunting reduction groups using IFE-EFE matrix analysis in Central Java Province, Indonesia
Authors: Samsudin Mohamad , Hapsari Pramesthi Widya , Kartasurya Martha Irene , Syauqy Ahmad , Isnawati Muflihah , Wati Erna Kusuma , Nurcahyani Yusi Dwi , Fuada Noviati , Suyatno Suyatno , Dewantiningrum Julian , Sunarto Sunarto , Nuryanto Nuryanto
Published: November 2023

Background

The results of the 2021 Indonesian Nutritional Status Study (Studi Status Gizi Indonesia, SSGI) showed a 6.8% declining prevalence of stunting in Central Java from 2019 to 2021. However, the prevalence decreases in the regency level of Central Java varied from 0.1 to 20.3%. This study aimed to analyze the external and internal factors that influenced the stunting reduction prevalence in Central Java Province, Indonesia.

Methods

This qualitative study was conducted over 2 months, from April to May 2022. In-depth interviews were used to explore the supporting factors (external, internal, and strategies) and the challenges (internal, external, and solutions) in implementing stunting reduction acceleration programs. The supporting factors and challenges were compared between the groups with high Gro, Sra, Kla, and Pek (GSKP) and low Sur, Mag, Teg, and Pat (SMTP) reduction prevalence. Data were analyzed using internal factor evaluation (IFE) and external factor evaluation (EFE).

Results

In quadrant II, the high-reduction group (GSKP) had IFE and EFE scores of 2.61 and 2.76, respectively. In quadrant IV, the low-reduction group (SMTP) had IFE and EFE scores of 1.86 and 1.62, respectively. The high-reduction group (GSKP) was better than the low-reduction group (SMTP) in using external opportunities and internal strengths by avoiding external threats and minimizing the weakness in the stunting reduction acceleration program in each area. The existence of superior programs and innovations were the strengths that differentiated the high and low groups. Conversely, the low-stunting reduction group struggled to overcome major challenges, especially lacking leadership capacity. From the outside, lack of program sustainability at the village level and budget restraint were the threats found in both groups.

Conclusion

Compared with the low-stunting reduction group, the high group could maximize their strengths and use the opportunities to implement stunting reduction programs.
Acceptance of medical drone technology and its determinant factors among public and healthcare personnel in a Malaysian urban environment: knowledge, attitude, and perception
Authors: Za’im Sahul Hameed Muhammad , Nordin Rosdiadee , Ismail Aniza , Zulkifley Muhammad Aidiel , Sham Aina Suraya Helmy , Sabudin Raja Zahratul Azma Raja , Zailani Mohamed Afiq Hidayat , Saiboon Ismail Mohd , Mahdy Zaleha Abdullah
Published: November 2023

Introduction

Unmanned aerial vehicles (UAVs) are used for commercial, medical, public safety, and scientific research purposes in various countries.

Methods

This study aimed to explore the acceptance of medical delivery drones among medical practitioners as well as the public community in Malaysia using a knowledge, attitude, and perception (KAP) model and statistical analysis to decrease uncertainty. Bivariate and multivariate analyses of the results were performed in SPSS.

Results

A total of 639 respondents took part in the survey, of which 557 complete responses were finally analyzed. The results showed that the overall acceptance rate for medical delivery drones was positive. The acceptance rate was significantly correlated with knowledge, attitude, and perception scores but not with sociodemographic factors.

Discussion

Raising awareness and educating the medical as well as public communities regarding the potential role and benefits of drones are therefore important in garnering support for drone usage for medical purposes.
Successful pandemic management through computer science: a case study of a financial corporation with workers on premises
Authors: Partida-Hanon Angélica , Díaz-Garrido Ramón , Mendiguren-Santiago José María , Gómez-Paredes Laura , Muñoz-Gutiérrrez Juan , Miguel-Rodríguez María Antonia , Reinoso-Barbero Luis
Published: November 2023

Background

In November 2019, an infectious agent that caused a severe acute respiratory illness was first detected in China. Its rapid spread resulted in a global lockdown with negative economic impacts. In this regard, we expose the solutions proposed by a multinational financial institution that maintained their workers on premises, so this methodology can be applied to possible future health crisis.

Objectives

To ensure a secure workplace for the personnel on premises employing biomedical prevention measures and computational tools.

Methods

Professionals were subjected to recurrent COVID-19 diagnostic tests during the pandemic. The sanitary team implemented an individual following to all personnel and introduced the information in databases. The data collected were used for clustering algorithms, decision trees, and networking diagrams to predict outbreaks in the workplace. Individualized control panels assisted the decision-making process to increase, maintain, or relax restrictive measures.

Results

55,789 diagnostic tests were performed. A positive correlation was observed between the cumulative incidence reported by Madrid’s Ministry of Health and the headcount. No correlation was observed for occupational infections, representing 1.9% of the total positives. An overall 1.7% of the cases continued testing positive for COVID-19 after 14 days of quarantine.

Conclusion

Based on a combined approach of medical and computational science tools, we propose a management model that can be extended to other industries that can be applied to possible future health crises. This work shows that this model resulted in a safe workplace with a low probability of infection among workers during the pandemic.