bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of anesthesia assistance on the detection rate of precancerous lesions and early esophageal squamous cell cancer in esophagogastroduodenoscopy screening: A retrospective study based on propensity score matching
Authors: Liang Min , Xu Chunhong , Zhang Xinyan , Zhang Zongwang , Cao Junli
Published: March 2023

Background

Esophagogastroduodenoscopy (EGD) screening is vital for the early diagnosis of esophageal squamous cell cancer (ESCC). However, improvement in the detection rate of precancerous lesions and early ESCC with anesthesia assistance (AA) has not yet been investigated. This retrospective study aimed to evaluate the effect of AA on the detection rate of precancerous lesions and early ESCC in patients undergoing EGD screening and identify risk factors affecting the detection rate.

Methods

We reviewed patients’ electronic medical records who underwent EGD screening between May 2019 and August 2020. Patients were divided into two groups based on whether they received AA: those in Group A underwent EGD screening with AA, and patients in Group O underwent EGD screening without AA. Propensity score matching (PSM) was used to account for differences in baseline characteristics. Detection rates of precancerous lesions and early ESCC were compared between the two groups following PSM. Binary logistic regression was used to identify risk factors affecting the detection rate.

Results

The final analysis included 21,835 patients (Group A = 13,319, Group O = 8,516) from 28,985 patients who underwent EGD screening during the study period. Following PSM, 6009 patients remained in each group for analysis. There was no significant difference in the detection rate of precancerous lesions and early ESCC between Groups A and O (1.1% vs. 0.8%, p > 0.05). Binary logistic regression showed that age (50–59 years, 60–69 years and 70–79 years), higher endoscopist seniority, high-definition (HD) endoscopy, narrow-band imaging (NBI), and number of endoscopic images were all independent risk factors that affected the detection rate of precancerous lesions and early ESCC.

Conclusion

There was no statistically significant difference in the detection rate of precancerous lesions and early ESCC between patients who underwent EGD screening with and without AA. All independent risk factors that affected the detection rate of precancerous lesions and early ESCC included the following: age (50–59 years, 60–69 years and 70–79 years), higher endoscopist seniority, HD endoscopy, NBI, and number of endoscopic images. Endoscopists should consider all these factors as much as possible when performing EGD screening.
Evasion of toll-like receptor recognition by Escherichia coli is mediated via population level regulation of flagellin production
Authors: Tan Aaron , Alsenani Qusai , Lanz Marcello , Birchall Christopher , Drage Lauren K. L. , Picton David , Mowbray Catherine , Ali Ased , Harding Christopher , Pickard Robert S. , Hall Judith , Aldridge Phillip D.
Published: March 2023

Uropathogenic Escherichia coli is a major cause of urinary tract infections. Analysis of the innate immune response in immortalized urothelial cells suggests that the bacterial flagellar subunit, flagellin, is key in inducing host defenses. A panel of 48 clinical uro-associated E. coli isolates recovered from either cystitis, pyelonephritis asymptomatic bacteriuria (ABU) or UTI-associated bacteraemia infections were characterized for motility and their ability to induce an innate response in urothelial cells stably transfected with a NF-κB luciferase reporter. Thirty-two isolates (67%) were identified as motile with strains recovered from cystitis patients exhibiting an uneven motility distribution pattern; seven of the cystitis isolates were associated with a  > 5-fold increase in NF-κB signaling. To explore whether the NF-κB signaling response reflected antigenic variation, flagellin was purified from 14 different isolates. Purified flagellin filaments generated comparable NF-κB signaling responses, irrespective of either the source of the isolate or H-serotype. These data argued against any variability between isolates being related to flagellin itself. Investigations also argued that neither TLR4 dependent recognition of bacterial lipopolysaccharide nor growth fitness of the isolates played key roles in leading to the variable host response. To determine the roles, if any, of flagellar abundance in inducing these variable responses, flagellar hook numbers of a range of cystitis and ABU isolates were quantified. Images suggested that up to 60% of the isolate population exhibited flagella with the numbers averaging between 1 and 2 flagella per bacterial cell. These data suggest that selective pressures exist in the urinary tract that allow uro-associated E. coli strains to maintain motility, but exploit population heterogeneity, which together function to prevent host TLR5 recognition and bacterial killing.
Complete genome sequences and comparative secretomic analysis for the industrially cultivated edible mushroom Lyophyllum decastes reveals insights on evolution and lignocellulose degradation potential
Authors: Xu Lili , Yang Wujie , Qiu Tianmei , Gao Xia , Zhang Hongyong , Zhang Shuliang , Cui Hui , Guo Lizhong , Yu Hailong , Yu Hao
Published: March 2023

Lyophyllum decastes, also known as Luronggu in China, is a culinary edible and medicinal mushroom that was widely cultivated in China in recent years. In the present study, the complete high-quality genome of two mating compatible L. decastes strain was sequenced. The L. decastes LRG-d1-1 genome consists of 47.7 Mb in 15 contigs with a contig N90 of 2.08 Mb and 14,499 predicted gene models. Phylogenetic analysis revealed that L. decastes exhibits a close evolutionary relationship to the Termitomyces and Hypsizygus genus and was diverged from H. marmoreus  ~ 45.53 Mya ago. Mating A loci of L. decastes compose of five and four HD genes in two monokaryotic strains, respectively. Mating B loci compose of five STE genes in both two monokaryotic strains. To accelerate the cross-breeding process, we designed four pairs of specific primers and successfully detected both mating types in L. decastes. As a wood-rotting mushroom, a total of 541 genes accounting for 577 CAZymes were identified in the genome of L. decastes. Proteomic analysis revealed that 1,071 proteins including 182 CAZymes and 258 secreted enzymes were identified from four groups (PDB, PDB + bran, PDB + cotton hull, and PDB + sawdust). Two laccases and a quinone reductase were strongly overproduced in lignin-rich cultures, and the laccases were among the top-3 secreted proteins, suggesting an important role in the synergistic decomposition of lignin. These results revealed the robustness of the lignocellulose degradation capacity of L. decastes. This is the first study to provide insights into the evolution and lignocellulose degradation of L. decastes.
Human brain organoid code of conduct
Authors: Hoppe Meagan , Habib Ahmed , Desai Riya , Edwards Lincoln , Kodavali Chowdari , Sherry Psy Natalie Sandel , Zinn Pascal O.
Published: March 2023

Human brain organoids are models derived from human embryonic or induced pluripotent stem cells that mimic basic cerebral microanatomy and demonstrate simple functional neuronal networks. Brain organoids have been a rapidly expanding avenue for biomedical research in general and specifically: neural development, regeneration, and central nervous system pathophysiology. However, technology replicating functional aspects of the human brain, including electrically active neural networks, requires a responsible code of conduct. In this review, we focus the discussion on intrinsic and extrinsic ethical factors associated with organoids: intrinsic considerations arise with the growing complexity of human brain organoids, including human-animal chimerism, consciousness development, and questions of where these human-like beings fall in a moral hierarchy. Extrinsic considerations explore ethics on obtainment, manufacturing, and production of sophisticated human products. In summary, a thoughtful code of conduct using human brain organoids towards the advancement of science and medicine is crucial. This article shall facilitate a structured thought process approaching the moral landscape of organoid technology.
Use of anti-seizure medications in different types of autoimmune encephalitis: A narrative review
Authors: Du Jinyuan , Guo Yi , Zhu Qiong
Published: March 2023

Seizures are the main manifestation of the acute phase of autoimmune encephalitis (AE). Anti-seizure medications (ASMs) play an important role in controlling seizures in AE patients, but there is currently a lack of consensus regarding the selection, application, and discontinuation of ASMs. This narrative review focuses on the use of ASMs in patients with AE driven by different antibodies. The PubMed, Embase, and MEDLINE databases were searched up until 30 October 2022 using prespecified search terms. We identified 2,580 studies; 23 retrospective studies, 2 prospective studies and 9 case reports were evaluated based on our inclusion criteria. Anti-N-methyl-D-aspartic-acid-receptor (anti-NMDAR) encephalitis is the type of AE that responds best to ASMs, and long-term or combined use of ASMs may be not required in most patients with seizures; these results apply to both adults and children. Sodium channel blockers may be the best option for seizures in anti-leucine-rich-glioma-inactivated-1 (anti-LGI1) encephalitis, but patients with anti-LGI1 encephalitis are prone to side effects when using ASMs. Cell surface antibody-mediated AE patients are more likely to use ASMs for a long period than patients with intracellular antibody-mediated AE. Clinicians can score AE patients’ clinical characteristics on a scale to identify those who may require long-or short-term use of ASMs in the early stage. This review provides some recommendations for the rational use of ASMs in encephalitis mediated by different antibodies with the aim of controlling seizures and avoiding overtreatment.
TMEM100, a regulator of TRPV1-TRPA1 interaction, contributes to temporomandibular disorder pain
Authors: Wang Peng , Zhang Qiaojuan , Dias Fabiana C. , Suttle Abbie , Dong Xinzhong , Chen Yong
Published: March 2023

There is an unmet need to identify new therapeutic targets for temporomandibular disorder (TMD) pain because current treatments are limited and unsatisfactory. TMEM100, a two-transmembrane protein, was recently identified as a regulator to weaken the TRPA1-TRPV1 physical association, resulting in disinhibition of TRPA1 activity in sensory neurons. Recent studies have also shown that Tmem100, Trpa1, and Trpv1 mRNAs were upregulated in trigeminal ganglion (TG) after inflammation of the temporomandibular joint (TMJ) associated tissues. These findings raise a critical question regarding whether TMEM100 in TG neurons is involved in TMD pain via regulating the TRPA1-TRPV1 functional interaction. Here, using two mouse models of TMD pain induced by TMJ inflammation or masseter muscle injury, we found that global knockout or systemic inhibition of TRPA1 and TRPV1 attenuated pain. In line with their increased genes, mice exhibited significant upregulation of TMEM100, TRPA1, and TRPV1 at the protein levels in TG neurons after TMD pain. Importantly, TMEM100 co-expressed with TRPA1 and TRPV1 in TG neurons-innervating the TMJ and masseter muscle and their co-expression was increased after TMD pain. Moreover, the enhanced activity of TRPA1 in TG neurons evoked by TMJ inflammation or masseter muscle injury was suppressed by inhibition of TMEM100. Selective deletion of Tmem100 in TG neurons or local administration of TMEM100 inhibitor into the TMJ or masseter muscle attenuated TMD pain. Together, these results suggest that TMEM100 in TG neurons contributes to TMD pain by regulating TRPA1 activity within the TRPA1-TRPV1 complex. TMEM100 therefore represents a potential novel target-of-interest for TMD pain.
Association of geriatric nutritional risk index with all-cause hospital mortality among elderly patients in intensive care unit
Authors: Peng Jiang-Chen , Zhu Yi-Wei , Xing Shun-Peng , Li Wen , Gao Yuan , Gong Wen-Wen
Published: March 2023

Background

Malnutrition is associated with poor outcomes for geriatric patients in intensive care unit (ICU). It is important to identify patients at risk of malnutrition and provide individual nutrition support. The assessment of malnutrition risk is not easy for these patients due to their cognitive impairment. Geriatric nutrition risk index (GNRI) is a simple and objective scoring tool to evaluate the risk of malnutrition in elderly patients. In this study, we aimed to see whether GNRI score was appropriate to predict clinical outcomes among geriatric patients in the setting of ICU.

Materials and methods

Elderly patients with age ≥ 65 years were extracted from Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Categories based on GNRI were classified as major risk (GNRI <82), moderate risk (GNRI 82 to <92), low risk (GNRI 92 to ≤98), and no risk (GNRI >98). The primary outcome was all-cause hospital mortality. Multivariable Cox proportional hazards regression models and restricted cubic spline were used to investigate associations of GNRI with hospital mortality, respectively. A two-piecewise linear regression model was applied to examine the inflection point of GNRI on hospital mortality. To reduce selection bias, propensity score matching (PSM) was used in a 1:1 ratio.

Results

A total of 3,696 geriatric patients were finally included with median age 75 (69, 81) years. The prevalence of major risk was 28.6%. In the fully adjusted model, GNRI categories featured a negative trend with hospital mortality (p for trend = 0.037). Restricted cubic spline analysis demonstrated an L-shaped relationship between GNRI and hospital mortality before and after matching. The inflection point was 78.7. At the left side of inflection point, GNRI levels were significantly negatively associated with hospital mortality (HR = 0.96, 95% CI: 0.94–0.98; p < 0.001) and featured no significant relations at the right side. Multiple linear regression also showed that GNRI was negatively associated with length of stay in hospital.

Conclusion

The major risk of malnutrition defined by GNRI was able to predict poor prognosis for geriatric patients admitted to ICU.
Regulatory roles of copper metabolism and cuproptosis in human cancers
Authors: Wang Zhe , Jin Dekui , Zhou Shuaishuai , Dong Niujing , Ji Yuting , An Peng , Wang Jiaping , Luo Yongting , Luo Junjie
Published: March 2023

Copper is an essential micronutrient for human body and plays a vital role in various biological processes including cellular respiration and free radical detoxification. Generally, copper metabolism in the body is in a stable state, and there are specific mechanisms to regulate copper metabolism and maintain copper homeostasis. Dysregulation of copper metabolism may have a great connection with various types of diseases, such as Wilson disease causing copper overload and Menkes disease causing copper deficiency. Cancer presents high mortality rates in the world due to the unlimited proliferation potential, apoptosis escape and immune escape properties to induce organ failure. Copper is thought to have a great connection with cancer, such as elevated levels in cancer tissue and serum. Copper also affects tumor progression by affecting angiogenesis, metastasis and other processes. Notably, cuproptosis is a novel form of cell death that may provide novel targeting strategies for developing cancer therapy. Copper chelators and copper ionophores are two copper coordinating compounds for the treatment of cancer. This review will explore the relationship between copper metabolism and cancers, and clarify copper metabolism and cuproptosis for cancer targeted therapy.
Diagnostic performance of transperineal prostate targeted biopsy alone according to the PI-RADS score based on bi-parametric magnetic resonance imaging
Authors: Noh Tae Il , Shim Ji Sung , Kang Seok Ho , Cheon Jun , Kang Sung Gu
Published: March 2023

Purpose

To compare the diagnostic performance of transperineal targeted biopsy (TB) or systematic biopsy (SB) alone based on combined TB+SB and radical prostatectomy (RP) specimen for detecting prostate cancer (PCa) according to the prostate imaging reporting and data system (PI-RADS) score.

Materials and methods

This study included 1077 men who underwent transperineal bi-parametric (bp) magnetic resonance imaging (MRI)–ultrasound (US) fusion TB+SB (bpMRI-US FTSB) between April 2019 and March 2022. To compare the performance of each modality (TB, SB, and combined TB+SB) with the RP specimen (as the standard) for detecting PCa and clinically significant PCa (csPCa), receiver operating characteristic (ROC) curves were plotted.

Results

PCa was detected in 581 of 1077 men (53.9%) using bpMRI-US FTSB. CsPCa was detected in 383 of 1077 men (35.6%), 17 of 285 (6.0%) with PI-RADS 0 to 2, 35 of 277 (12.6%) with PI-RADS 3, 134 of 274 (48.9%) with PI-RADS 4, and 197 of 241 (81.7%) with PI-RADS 5, respectively. The additional diagnostic value of TB vs. SB compared to combined TB+SB for diagnosing csPCa were 4.3% vs. 3.2% (p=0.844), 20.4% vs 5.1% (p<0.001), and 20.3% vs. 0.7% (p<0.001) with PI-RADS 3, 4, and 5, respectively. TB alone showed no significant difference in diagnostic performance for csPCa with combined TB+SB based on RP specimens in patients with PI-RADS 5 (p=0.732).

Conclusion

A need for addition of SB to TB in patients with PI-RADS 3 and 4 lesions, however, TB alone may be performed without affecting the management of patients with PI-RADS 5.
Case Report: Clinical response to anaplastic lymphoma kinase inhibitor-based targeted therapy in uterine inflammatory myofibroblastic tumor harboring ALK-IGFBP5 fusion
Authors: Zhao Ting , Zhang Xiaowei , Liu Xin , Ren Min , Cheng Yufan , Wang Jian , Luo Zhiguo
Published: March 2023

Background

An inflammatory myofibroblastic tumor (IMT) is a mesenchymal tumor with a prevalence ranging from 0.04% to 0.7% worldwide, in which the lung is the most common predilection site, accounting for 33% of cases, followed by the abdomen, pelvis, mesentery, and uterus. Approximately 50% of uterine IMTs present as anaplastic lymphoma kinase (ALK) positive along with ALK gene fusion, which lays a solid foundation for the development of ALK-based target therapy to optimize treatment strategies.

Case presentation

Herein we describe a 57-year-old woman who presented with a slow-growing mass in the uterus for over 10 years and then received surgical resection because of significant progressive enlargement of the mass during follow-up. She was diagnosed with uterine leiomyosarcoma (LMS) with no further interventions until recurrence. We revised the diagnosis to uterine IMT based on diffuse ALK expression, ALK-IGFBP5 gene fusion, and the morphologic features of the tumors by pathology consultation. Based on these, we recommended an ALK tyrosine kinase inhibitor (TKI) treatment, crizotinib (250 mg bid), and she achieved a complete response (CR) with at least 18 months of progression-free survival (PFS). We monitored the dynamics of target lesions and peripheral blood cells at regular intervals through CT scans and routine blood tests during the treatment process. We present patient responses to ALK inhibitor-based targeted therapy with uterine IMT harboring ALK-IGFBP5 fusion, and the neutrophil-to-lymphocyte ratio (NLR) may be an effective indicator to predict prognosis.
Case report: A case of epidermolysis bullosa complicated with pyloric atresia and a literature review
Authors: Luo Caiyun , Yang Liucheng , Huang Zhaorong , Su Yuqian , Lu Yi , Yu Daiyue , Zhang Mengzhen , Wu Kai
Published: March 2023

Objective

This article aims to explore the diagnosis, molecular characteristics, treatment, and prognosis of epidermolysis bullosa with pyloric atresia (EB-PA).

Methods

The clinical manifestations, diagnosis and treatment, and genetic characteristics of a patient with EB-PA admitted to our hospital were analysed. The disease subtypes, concomitant abnormalities, molecular characteristics, and prognosis of patients with EB-PA were summarized by searching the EB-PA-related literature since 2011.

Results

We present a very low birth weight female infant with skin blisters and pyloric obstruction. Exome sequencing revealed heterozygous mutations in the ITGB4 gene: c.794dupC (p. S265fs*5) and c.2962G > A (p.A988T). This infant was diagnosed with EB-PA. Coverage of the wounds and Penicillin were used to prevent infection, but the patient eventually developed severe sepsis. A literature review was carried out including 49 cases of EB-PA; among these cases, 34 were preterm infants, weighing between 930 and 3,640 g. Of these EB-PA patients, 28 had accompanying malformations, including urinary system malformations and aplasia cutis congenita (ACC). Thirty-two patients identified the subtype of EB-PA, of whom 25 were diagnosed with junctional epidermolysis bullosa (JEB), 6 with epidermolysis bullosa simplex (EBS), and 1 with dystrophic epidermolysis bullosa (DEB). Genetic testing was conducted on 23 patients, of whom 15 carried Integrin Beta-4 (ITGB4) gene mutations and one JEB patient carried an Integrin Alpha-6 (ITGA6) gene mutation; 4 of the 5 EBS patients had Plectin (PLEC) gene mutations, and the other had an ITGB4 mutation. ITGB4 mutation cases involved 29 mutation sites, primarily concentrated in the region encoding the integrin beta subunit; PLEC mutation cases involved 7 mutation sites. Among all cases, 43 underwent pyloric atresia surgery, of whom 24 died postoperatively, and 6 without surgery therapy died within a short period.

Conclusion

EB-PA is a rare genetic disorder characterized by increased skin fragility and PA involving mutations in the ITGB4, PLEC, or ITGA6 genes. EB-PA has a high incidence of complications and mortality, surgery and supportive therapy are currently the most common treatment options.
Optic disc and retinal vascular features in first 6 years of Chinese children
Authors: Liu Guina , Jiang Anna , Cao Le , Ling Saiguang , Wang Xi , Bu Shaochong , Lu Fang
Published: March 2023

Purpose

Retinal microvasculature plays an important role in children's fundus lesions and even in their later life. However, little was known on the features of normal retina in early life. The purpose of this study was to explore the normal retinal features in the first 6 years of life and provide information for future research.

Methods

Children, aged from birth to 6 years old and diagnosed with various unilateral ocular diseases were included. Venous phase fundus fluorescein angiography images with the optic disc at the center were collected. Based on the ResUNet convolutional neural network, optic disc and retinal vascular features in the posterior retina were computed automatically.

Results

A total of 146 normal eyes of 146 children were included. Among different age groups, no changes were shown in the optic disc diameter (y = −0.00002x + 1.362, R2 = 0.025, p = 0.058). Retinal vessel density and fractal dimension are linearly and strongly correlated (r = 0.979, p < 0.001). Older children had smaller value of fractal dimension (y = −0.000026x + 1.549, R2 = 0.075, p = 0.001) and narrower vascular caliber if they were less than 3 years old (y = −0.008x + 84.861, R2 = 0.205, p < 0.001). No differences were in the density (y = −0.000007x + 0.134, R2 = 0.023, p = 0.067) and the curvature of retinal vessels (lnC = −0.00001x − 4.657, R2 = 0.001, p = 0.667).

Conclusions

Age and gender did not impact the optic disc diameter, vessel density, and vessel curvature significantly in this group of children. Trends of decreased vessel caliber in the first 3 years of life and decreased vessel complexity with age were observed. The structural characteristics provide information for future research to better understand the developmental origin of the healthy and diseased retina.
Targeted neonatal echocardiography and lung ultrasound in preterm infants with chronic lung disease with and without pulmonary hypertension, screened using a standardized algorithm
Authors: Sánchez-Becerra Janneth Cristina , Guillén-Torres Rogelio , Becerra-Becerra Rosario , Márquez-González Horacio , Ibarra-Ríos Daniel
Published: March 2023

Introduction

Increased recognition of the development of chronic pulmonary hypertension (cPH) in preterm infants with chronic lung disease (CLD) has prompted enhanced monitoring for the identification of different phenotypes.

Methods

All newborns consulted for oxygen/respiratory support dependency (CLD assessment) from January 2018 to December 2021 were included. TnECHO and LUS screening for cPH-CLD were performed at 36 weeks postmenstrual age. Cases of cPH related to increased pulmonary blood flow (cPH-IPBF) were referred to Pediatric Cardiology. The objective of the study was to identify all cases of cPH (cPH-CLD/IPBF) in the CLD patients screened and to compare outcomes. Following a standardized algorithm, cPH-CLD patients were treated with diuretics; ultrasounds taken before and after treatment were analyzed.

Results

Seventy-two patients with CLD were screened. Twenty-two (30%) had cPH-CLD, and nine (12%) had cPH-IPBF. cPH infants underwent more days of mechanical ventilation, were more likely to have retinopathy of prematurity, and showed increased mortality. The LUS pattern observed in the 72 CLD patients consisted of a thickened pleural line and a B-line interstitial heterogeneous pattern; 29% of patients were found to have lung consolidations. After diuretic therapy, step-down in respiratory support occurred in 59% of neonates with cPH-CLD. A decrease in respiratory rate (RR), right ventricular output (RVO), markers of pulmonary vascular resistance (PVR), and B-line pattern was observed. In tissue Doppler imaging, biventricular diastolic function was found to be modified after diuretics.

Conclusions

CLD infants with cPH showed increased morbidity and mortality. In cPH-CLD patients, a decrease in RR and step-down in respiratory support was observed after diuretic treatment. Follow-up ultrasound showed a decrease in RVO, markers of PVR, and B-lines.
Fraxetin attenuates disrupted behavioral and central neurochemical activity in a model of chronic unpredictable stress
Authors: Ahmed Zainab , Tokhi Ahmed , Arif Mehreen , Rehman Naeem Ur , Sheibani Vahid , Rauf Khalid , Sewell Robert D. E.
Published: March 2023

Purpose: Chronic unpredictable stress (CUS) induces long-term neuronal and synaptic plasticity with a neurohormonal disbalance leading to the development of co-existing anxiety, depression, and cognitive decline. The side effects and delayed onset of current clinically used antidepressants has prompted a quest for antidepressants with minimum drawbacks. Fraxetin is a natural coumarin derivative with documented antioxidant and neuroprotective activity though its effects on stress are unknown. This study therefore aimed to investigate any possible acute effect of fraxetin in behavioral tests including a CUS paradigm in correlation with brain regional neurochemical changes.

Methods: Mice were subjected to a series of mild stressors for 14 days to induce CUS. Furthermore, behavioral performance in the open field test, forced swim test (FST), Y-maze and elevated plus-maze were evaluated. Postmortem frontal cortical, hippocampal and striatal tissues were analyzed via high-performance liquid chromatography (HPLC) for neurochemical changes.

Result: Acute administration of fraxetin (20–60 mg/kg, orally) decreased depression-like behavior in the FST and behavioral anxiety in both the open field test and elevated plus-maze. Memory deficits induced during the CUS paradigm were markedly improved as reflected by enhanced Y maze performance. Concurrent biochemical and neurochemical analyses revealed that only the two higher fraxetin doses decreased elevated serum corticosterone levels while diminished serotonin levels in the frontal cortex, striatum and hippocampus were reversed, though noradrenaline was only raised in the striatum. Concomitantly, dopamine levels were restored by fraxetin at the highest dose exclusively in the frontal cortex.

Conclusion: Acute treatment with fraxetin attenuated CUS-induced behavioral deficits, ameliorated the increased corticosterone level and restored altered regional neurotransmitter levels and this may indicate a potential application of fraxetin in the management of anxiety and depression modeled by CUS. However, further studies are warranted regarding the chronic effects of fraxetin behaviorally and neurochemically.
Medicinal plant-based drug delivery system for inflammatory bowel disease
Authors: Li Ningcen , Wang Meijuan , Lyu Zhongxi , Shan Kai , Chen Zelin , Chen Bo , Chen Yong , Hu Xiyou , Dou Baomin , Zhang Jingyu , Wang Lifen , Zhao Tianyi , Li Hongjiao
Published: March 2023

Inflammatory bowel disease (IBD) is a chronic recurrent intestinal disease. The incidence rate of IBD is increasing year by year, which seriously endangers human health worldwide. More and more studies have shown that medicinal plants or their main phytochemicals have great potential in the treatment of intestinal diseases. However, the disadvantages of low oral absorption rate, low biological distribution and low systemic bioavailability limit their clinical application to a certain extent. In recent years, the application of nanotechnology has made it possible to treat IBD. Nanoparticles (NPs) drug delivery system has attracted special attention in the treatment of IBD due to its small size, low immunogenicity, surface modification diversity, targeting and other advantages. Synthetic nanoparticles and extracellular vehicles (EVs) can deliver drug components to colon, and play a role in anti-inflammation, regulation of oxidative stress, improvement of intestinal flora, etc. In addition, some medicinal plants can secrete EVs by themselves, and carry biological molecules with therapeutic effects to act on the intestine. Some clinical trials to evaluate the safety, tolerance, toxicity and effectiveness of EVs-loaded drugs in IBD are also progressing steadily. This review introduces that synthetic nanoparticles and medicinal plants derived EVs can play an important role in the treatment of IBD by carrying the effective active phytochemicals of medicinal plants, and discuss the limitations of current research and future research needs, providing a scientific and reliable basis and perspective for further clinical application and promotion.
Association between maternal second-trimester stress and adverse pregnancy outcomes according to pre-pregnancy body mass index and gestational weight gain
Authors: Zhang Lixia , Zhu Shuqi , Wu Yihui , Chen Danqing , Liang Zhaoxia
Published: March 2023

Objective

To investigate the impact of maternal second-trimester stress on pregnancy outcomes according to pre-pregnancy body mass index (BMI) and gestational weight gain (GWG).

Methods

We did a prospective study in Women’s Hospital, School of Medicine, Zhejiang University and included 960 pregnant women in our final analysis. Obstetric characteristics and the incidence of adverse pregnancy outcomes were examined in stressed and non-stressed women. The associations between maternal prenatal stress with adverse pregnancy outcomes were analyzed by logistic regression.

Results

The incidence of premature rupture of membranes (PROM) was significantly higher in stressed pregnant women than non-stressed pregnant women (p = 0.035), whereas no significant difference in the incidence rates of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), primary cesarean delivery, preterm birth, macrosomia, low birth weight, fetal stress, admission into neonatal intensive care unit (NICU) or neonatal jaundice was found between two groups. Maternal second-trimester stress was an independent risk factor for the development of PROM (aOR = 1.468, 95% CI 1.037–2.079). Moreover, maternal second-trimester stress was significantly associated with PROM in pregnant women with normal pre-pregnancy BMI (aOR = 1.587, 95% CI 1.068–2.357) while no association was observed in either underweight or overweight and obese pregnant women. Meanwhile, no difference was found in the odds of PROM with maternal second-trimester stress in all GWG subgroups.

Conclusion

Maternal second-trimester stress is associated with a higher risk of PROM and it is significant in pregnant women with normal pre-pregnancy BMI. Therefore, interventions to reduce stress during second-trimester of pregnancy might be essential for lowering the prevalence of PROM in pregnant women with normal pre-pregnancy BMI.
Determinants of severe QTc prolongation in a real-world gerontopsychiatric setting
Authors: Schulze Westhoff Martin , Schröder Sebastian , Heck Johannes , Pfister Tabea , Jahn Kirsten , Krause Olaf , Wedegärtner Felix , Bleich Stefan , Kahl Kai G. , Krüger Tillmann H. C. , Groh Adrian
Published: March 2023

Introduction

QTc prolongation carries the risk of ventricular tachyarrhythmia (Torsades de Pointes) and sudden cardiac death. Psychotropic drugs can affect ventricular repolarization and thus prolong the QTc interval. The present study sought to investigate the risk factors (pharmacological and non-pharmacological) of severe QTc prolongation in gerontopsychiatric patients.

Methods

Electrocardiograms of patients on a gerontopsychiatric ward were screened for QTc prolongation. Medication lists were examined utilizing the AzCERT classification. Potential drug interactions were identified with the electronic drug interaction program mediQ.

Results

The overall prevalence of QTc prolongation was 13.6%, with 1.9% displaying severe QTc prolongation (≥ 500 ms). No statistically significant differences between patients with moderate and severe QTc prolongation were identified; however, patients with severe QTc prolongation tended to take more drugs (p = 0.063). 92.7% of patients with QTc prolongation took at least one AzCERT-listed drug, most frequently risperidone and pantoprazole. Risperidone and pantoprazole, along with pipamperone, were also most frequently involved in potential drug interactions. All patients displayed additional risk factors for QTc prolongation, particularly cardiac diseases.

Conclusion

In addition to the use of potentially QTc-prolonging drugs, other risk factors, especially cardiac diseases, appear to be relevant for the development of QTc prolongation in gerontopsychiatric patients. Pantoprazole was frequently involved in potential drug interactions and should generally not be used for more than 8 weeks in geriatric populations. As clinical consequences of QTc prolongation were rare, potentially QTc-prolonging drugs should not be used overcautiously; their therapeutic benefit should be considered as well. It is paramount to perform diligent benefit–risk analyses prior to the initiation of potentially QTc-prolonging drugs and to closely monitor their clinical (side) effects.
The relationship between parental neglect and cyberbullying perpetration among Chinese adolescent: The sequential role of cyberbullying victimization and internet gaming disorder
Authors: Gan Xiong , Qin Ke-Nan , Xiang Guo-Xing , Jin Xin
Published: March 2023

Cyberbullying perpetration and victimization have been common public health issues that have impaired the development of adolescent physical and mental health. Abundant research has proven associations between negative parental factors and cyberbullying perpetration. However, there is a paucity of research exploring the impact of parental neglect on cyberbullying and its internal mechanisms. Based on the parental acceptance-rejection theory (PARTheory) and the general aggression model (GAM), the present study constructs a sequential mediation model in which parental neglect is related to adolescent cyberbullying perpetration through cyberbullying victimization and internet gaming disorder (IGD). Using random cluster sampling, a total of 699 middle school students (Mage= 14.18 years, SD = 1.22, and 324 boys) were recruited from five schools in three provinces on mainland China. The participants completed questionnaires regarding parental neglect, cyberbullying perpetration, cyberbullying victimization, and IGD. The results of structural equation modeling indicated that parental neglect was positively associated with cyberbullying perpetration. The mediating effects of cyberbullying victimization and IGD in this relationship are significant both individually and jointly. The current findings have important implications for enlightening families and schools to pay particular attention to adolescents' experiences of parental neglect and provide them with timely feedback and assistance. This will contribute to the prevention and reduction of adolescent involvement in cyberbullying perpetration.
Competencies of hospital managers – A systematic scoping review
Authors: Ndayishimiye Costase , Dubas-Jakóbczyk Katarzyna , Holubenko Anastasia , Domagała Alicja
Published: March 2023

Hospital managers around the world work under constant pressure to adapt their organizations to new challenges and health policy goals. This requires a comprehensive set of competencies. The objective of this scoping review was to identify, map, and systematize the literature on hospital manager competencies. The review involved six steps: (1) defining research questions; (2) identifying relevant literature; (3) selecting publications; (4) data extraction; (5) data analysis and result reporting; and (6) consultations. A total of 57 full-text publications were included (46 empirical studies, six literature reviews, four expert opinions/guidelines, and one dissertation). Interest in this topic has grown in recent years, with most of the identified studies published since 2015. The empirical studies fall into three major groups: 34.8% (16/46) examined hospital managers’ competencies in terms of their types or classifications; 30.4% (14/46) focused on their measurement; and 30.4% (14/46) examined both aspects. In majority of studies, both ‘hard competencies,’ such as specific technical knowledge or skills acquired through practical training, and ‘soft competencies,’ e.g., adaptability, leadership, communication, teamwork, are echoed for effective hospital management. These point out the importance of both ‘external’ formal education trainings as well as ‘internal’ peer-support and/or coaching as complementary competency improvement approaches. This scoping review helps build a knowledge base around the topic and provides implications for future research. The latter can involve: a targeted systematic review addressing the methods for measuring the level of competence of hospital managers or studies focused on identifying the need for new types of competencies.
Assessing the impact of local context and priorities regarding domestic disease outbreaks and imported risk on early pandemic response: Cross-continental comparisons
Authors: Kuo Fei-Ying , Wen Tazi-Hung
Published: March 2023

Introduction

Containment and closure policies are effective measures used in the early stages of a highly transmissible global pandemic such as COVID-19 to mitigate the spread and reduce transmissions. However, these policies can have negative impacts on the economy and personal freedom. Governments must carefully consider the necessity of increasing their stringency. Local contexts and priorities regarding domestic disease outbreaks and the risk of imported cases from other countries may vary among different countries, and could influence the decision to increase containment measures. Thus, this study aimed to differentiate the impacts of these affecting factors on the stringency of governmental containment measures through cross-continental comparisons.

Methods

This study utilized a zero/one inflated beta (ZOIB) regression model to investigate how domestic epidemic, imported risk, and local context affect government responses to a pandemic. We used a country’s weekly confirmed case and death numbers as a measure of its domestic threat. The imported risk was measured using a combination of weekly new cases in each country and the air passenger traffic between countries.

Results

The findings indicate that domestic case numbers are a primary concern for governments when deciding to increase policy stringency. Countries with higher development levels tend to implement stricter policies as they can better handle the negative impacts. Additionally, there is an interaction between case numbers and development level, with countries at the second or third highest development level focusing more on domestic outbreaks than imported risks, while those at the highest level have similar concerns for both.

Conclusions

We concluded that most countries adjust policies’ stringency majorly based on the variation of domestic case number rather than the other pandemic factors and the countries with a high development level tend to implement strict policies since their socio-economical condition could afford such policies. These insights can aid policymakers in improving containment and closure policies for future pandemics.
What information is contained in experimentally determined lipid profiles?
Authors: Schwudke Dominik
Published: March 2023

Hundreds of molecular species make up the cellular lipidome. In this minireview, considerations for interpreting membrane and storage lipid profile changes that are often the focal point of lipidomic studies are discussed. In addition, insights how the most conserved molecular patterns are formed in eukaryotic systems and the consequences for the perturbation of lipid homeostasis are addressed. The implications of lipid identification specificity and experimental variability on modeling membrane structure and systemic responses are also discussed. The profile changes of membrane and storage lipids are bound to the kinetics of the metabolic system, and experimental design and functional interpretation in lipidomic research should be adapted accordingly.
Co-producing rapid research: Strengths and challenges from a lived experience perspective
Authors: Machin Karen , Shah Prisha , Nicholls Vicky , Jeynes Tamar , TK  , Trevillion Kylee , Vera San Juan Norha
Published: March 2023

The Lived Experience Researchers (LERs) of the Mental Health Policy Research Unit (MHPRU) reflect on the experience of conducting rapid co-produced research, particularly during the first year of the COVID-19 pandemic. Throughout this perspective article, we introduce requirements for co-production applying the 4Pi Framework, reflect on specific characteristics of co-production in rapid research, discuss strengths and challenges for involvement of LERs in rapid research, and lastly provide recommendations to achieve meaningful involvement. Incorporating meaningful co-production is an augmentation to any research project, with several benefits to the research, to the team, and to individual researchers. Particularly in the case of rapid research, that aims for efficient translation of knowledge into practice, involvement of experts by experience will be key. The work conducted by the MHPRU LERs presented in this paper demonstrates the viability, value, and potential of this way of working.
Temporal Trends in the Incidence and Mortality of Major Reproductive-Related Cancers in Women in Guangzhou From 2010 to 2020: A Joinpoint and Age-Period-Cohort Study
Authors: Wang Suixiang , Liu Shan , Nie Zhiqiang , Li Yexin , Li Ke , Liang Huanzhu , Chen Qian , Wen Lin , Xu Huan , Liang Boheng , Qin Pengzhe , Jing Chunxia
Published: March 2023

Objective: To understand the temporal trends of cancer incidence and mortality in women in Guangzhou during the past 11 years and provide clues for future research.

Methods: Data were obtained from the Guangzhou Cancer and Death Registry. Average annual percentage changes (AAPCs) in age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were obtained by joinpoint regression. The age-period-cohort (APC) model was generated to quantify the effects of age, period, and cohort.

Results: The ASIRs for cervical (AAPC = −4.3%) and ovarian (AAPC = −3.2%) cancers showed a downward trend during 2010–2020, and that for uterine cancer showed an upward trend. The ASMRs of breast (APC = 5.0%) and cervical (APC = 8.8%) cancers increased. The APC model highlights different age, period, and birth cohort effects depending on the cancer site.

Conclusion: The ASIRs for cervical and ovarian cancers among women in Guangzhou showed a decreasing trend during the period. The APC model showed mortality for 4 cancers increased with age. Incidence and mortality decreased with increasing birth cohort. Annual reproductive cancer screening is recommended for women of appropriate age to reduce the disease burden.
Management and Outcome After Early Renal Transplant Vein Thrombosis: A French Multicentre Observational Study of Real-Life Practice Over 24 Years
Authors: Cambou Ludivine , Millet Clémentine , Terrier Nicolas , Malvezzi Paolo , Timsit Marc-Olivier , Anglicheau Dany , Badet Lionel , Morelon Emmanuel , Prudhomme Thomas , Kamar Nassim , Lejay Anne , Perrin Peggy , Uro-Coste Charlotte , Pereira Bruno , Heng Anne Elisabeth , Garrouste Cyril , Guy Laurent
Published: March 2023

Early (<14 days) renal transplant vein thrombosis posttransplant (eRVTPT) is a rare but threatening complication. We aimed to assess eRVTPT management and the rate of functional renal transplantation. Of 11,172 adult patients who had undergone transplantation between 01/1997 and 12/2020 at 6 French centres, we identified 176 patients with eRVTPT (1.6%): 16 intraoperative (Group 1, G1) and 160 postoperative (Group 2, G2). All but one patient received surgical management. Patients in group G2 had at least one imaging test for diagnostic confirmation (N = 157, 98%). During the operative management of the G2 group, transplantectomy for graft necrosis was performed immediately in 59.1% of cases. In both groups, either of two techniques was preferred, namely, thrombectomy by renal venotomy or thrombectomy + venous anastomosis repair, with no difference in the functional graft rate (FGR) at hospital discharge (p = NS). The FGR was 62.5% in G1 and 8.1% in G2 (p < 0.001). Numerous complications occurred during the initial hospitalization: 38 patients had a postoperative infection (21.6%), 5 experienced haemorrhagic shock (2.8%), 29 exhibited a haematoma (16.5%), and 97 (55.1%) received a blood transfusion. Five patients died (2.8%). Our study confirms the very poor prognosis of early renal graft venous thrombosis.
Suitability of Biowaste and Green Waste Composts for Organic Farming in Germany and the Resulting Utilization Potentials
Authors: Gottschall Ralf , Thelen-Jüngling Maria , Kranert Martin , Kehres Bertram
Published: March 2023

In this study, the suitability of biowaste and green waste composts in organic farming is presented based on quality assurance data of approximately 21,000 compost analyses from 2015 to 2020. The evaluation of compost suitability was based on both the legal regulations of the EU 2021/1165 and the requirements of the two largest German organic farming associations Bioland and Naturland. In 2020, 70.1% of the composts agreed with the above-mentioned regulations, 21.6% exceeded the limits for heavy metals and 7.3% exceeded the limits for foreign matter. The negative influence of the single elements regarding the suitability of composts for organic agriculture declined in the order Zn > Pb > Cd > Ni > Cu. In the bio-waste composts, the impurity content subsequently decreased by more than 50% from 2015 to 2020. In 2019 and 2020, approximately 2.5 million Mg fresh mass (FM) of the analyzed composts were suitable for organic farming. With an average compost application of 5 Mg FM per hectare (ha) and year, about 500,000 ha of arable land could have been supplied in 2020.