bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence, predictors, and outcomes of early hospital readmissions after kidney transplantation: Systemic review and meta-analysis
Authors: Iqbal Kinza , Hasanain Muhammad , Rathore Sawai Singh , Iqbal Ayman , Kazmi Syeda Kanza , Yasmin Farah , Koritala Thoyaja , Thongprayoon Charat , Surani Salim
Published: November 2022

Background

Early hospital readmission (EHR) within 30 days after kidney transplantation is a significant quality indicator of transplant centers and patient care. This meta-analysis aims to evaluate the incidence, predictors, and outcomes of EHR after kidney transplantation.

Methods

We comprehensively searched the databases, including PubMed, Cochrane CENTRAL, and Embase, from inception until December 2021 to identify studies that assessed incidence, risk factors, and outcome of EHR. The outcomes included death-censored graft failure and mortality. Data from each study were combined using the random effect to calculate the pooled incidence, mean difference (MD), odds ratio (OR), and hazard ratio (HR) with 95% confidence interval (CI).

Results

A total of 17 studies were included. The pooled EHR incidence after kidney transplant was 24.4% (95% CI 21.7–27.3). Meta-analysis showed that recipient characteristics, including older recipient age (MD 2.05; 95% CI 0.90–3.20), Black race (OR 1.31; 95% CI 1.11, 1.55), diabetes (OR 1.32; 95% CI 1.22–1.43), and longer dialysis duration (MD 0.85; 95% CI 0.41, 1.29), donor characteristics, including older donor age (MD 2.02; 95% CI 0.93–3.11), and transplant characteristics, including delayed graft function (OR 1.75; 95% CI 1.42–2.16) and longer length of hospital stay during transplantation (MD 1.93; 95% CI 0.59–3.27), were significantly associated with the increased risk of EHR. EHR was significantly associated with the increased risk of death-censored graft failure (HR 1.70; 95% CI 1.43–2.02) and mortality (HR 1.46; 95% CI 1.27–1.67) within the first year after transplantation.

Conclusion

Almost one-fourth of kidney transplant recipients had EHR within 30 days after transplant, and they had worse post-transplant outcomes. Several risk factors for EHR were identified. This calls for future research to develop and implement for management strategies to reduce EHR in high-risk patients.
Non-contrast and contrast enhanced computed tomography radiomics in preoperative discrimination of lung invasive and non-invasive adenocarcinoma
Authors: Sun Yingli , Zhao Wei , Kuang Kaiming , Jin Liang , Gao Pan , Duan Shaofeng , Xiao Yi , Liu Jun , Li Ming
Published: November 2022

Objective

This study aimed to assess the value of radiomics based on non-contrast computed tomography (NCCT) and contrast-enhanced computed tomography (CECT) images in the preoperative discrimination between lung invasive adenocarcinomas (IAC) and non-invasive adenocarcinomas (non-IAC).

Methods

We enrolled 1,185 pulmonary nodules (478 non-IACs and 707 IACs) to build and validate radiomics models. An external testing set comprising 63 pulmonary nodules was collected to verify the generalization of the models. Radiomic features were extracted from both NCCT and CECT images. The predictive performance of radiomics models in the validation and external testing sets were evaluated and compared with radiologists’ evaluations. The predictive performances of the radiomics models were also compared between three subgroups in the validation set (Group 1: solid nodules, Group 2: part-solid nodules, and Group 3: pure ground-glass nodules).

Results

The NCCT, CECT, and combined models showed good ability to discriminate between IAC and non-IAC [respective areas under the curve (AUCs): validation set = 0.91, 0.90, and 0.91; Group 1 = 0.82, 0.79, and 0.81; Group 2 = 0.93, 0.92, and 0.93; and Group 3 = 0.90, 0.90, and 0.89]. In the external testing set, the AUC of the three models were 0.89, 0.91, and 0.89, respectively. The accuracies of these three models were comparable to those of the senior radiologist and better those that of the junior radiologist.

Conclusion

Radiomic models based on CT images showed good predictive performance in discriminating between lung IAC and non-IAC, especially in part solid nodule group. However, radiomics based on CECT images provided no additional value compared to NCCT images.
Prone positioning reduces frontal and hippocampal neuronal dysfunction in a murine model of ventilator-induced lung injury
Authors: Sparrow Nicklaus A. , Guidry Gena , Anwar Faizan , Darwish Sonja , Kelly Scott A. , Karumanchi S. Ananth , Lahiri Shouri
Published: November 2022

Prone positioning is an established treatment for severe acute lung injury conditions. Neuronal dysfunction frequently occurs with mechanical ventilation-induced acute lung injury (VILI) and clinically manifests as delirium. We previously reported a pathological role for systemic interleukin 6 (IL-6) in mediating neuronal injury. However, currently no studies have investigated the relationship between prone or supine positioning and IL-6 mediated neuronal dysfunction. Here, we hypothesize that prone positioning mitigates neuronal injury, via decreased IL-6, in a model of VILI. VILI was induced by subjecting C57BL/6J mice to high tidal volume (35 cc/kg) mechanical ventilation. Neuronal injury markers [cleaved caspase-3 (CC3), c-fos, heat shock protein 90 (Hsp90)] and inflammatory cytokines (IL-6, IL-1β, TNF-α) were measured in the frontal cortex and hippocampus. We found statistically significantly less neuronal injury (CC3, c-Fos, Hsp90) and inflammatory cytokines (IL-6, IL-1β, TNF-α) in the frontal cortex and hippocampus with prone compared to supine positioning (p < 0.001) despite no significant group differences in oxygen saturation or inflammatory infiltrates in the bronchoalveolar fluid (p > 0.05). Although there were no group differences in plasma IL-6 concentrations, there was significantly less cortical and hippocampal IL-6 in the prone position (p < 0.0001), indicating supine positioning may enhance brain susceptibility to systemic IL-6 during VILI via the IL-6 trans-signaling pathway. These findings call for future clinical studies to assess the relationship between prone positioning and delirium and for investigations into novel diagnostic or therapeutic paradigms to mitigate delirium by reducing expression of systemic and cerebral IL-6.
Mining associations between glycemic variability in awake-time and in-sleep among non-diabetic adults
Authors: Liang Zilu
Published: November 2022

It is often assumed that healthy people have the genuine ability to maintain tight blood glucose regulation. However, a few recent studies revealed that glucose dysregulation such as hyperglycemia may occur even in people who are considered normoglycemic by standard measures and were more prevalent than initially thought, suggesting that more investigations are needed to fully understand the within-day glucose dynamics of healthy people. In this paper, we conducted an analysis on a multi-modal dataset to examine the relationships between glycemic variability when people were awake and that when they were sleeping. The interstitial glucose levels were measured with a wearable continuous glucose monitoring (CGM) technology FreeStyle Libre 2 at every 15 min interval. In contrast to the traditional single-time-point measurements, the CGM data allow the investigation into the temporal patterns of glucose dynamics at high granularity. Sleep onset and offset timestamps were recorded daily with a Fitbit Charge 3 wristband. Our analysis leveraged the sleep data to split the glucose readings into segments of awake-time and in-sleep, instead of using fixed cut-off time points as has been done in existing literature. We combined repeated measure correlation analysis and quantitative association rules mining, together with an original post-filtering method, to identify significant and most relevant associations. Our results showed that low overall glucose in awake time was strongly correlated to low glucose in subsequent sleep, which in turn correlated to overall low glucose in the next day. Moreover, both analysis techniques identified significant associations between the minimal glucose reading in sleep and the low blood glucose index the next day. In addition, the association rules discovered in this study achieved high confidence (0.75–0.88) and lift (4.1–11.5), which implies that the proposed post-filtering method was effective in selecting quality rules.
Clinicopathological differences of high Fusobacterium nucleatum levels in colorectal cancer: A review and meta-analysis
Authors: Wang Yi , Wen Yuting , Wang Jiayin , Lai Xin , Xu Ying , Zhang Xuanping , Zhu Xiaoyan , Ruan Chenglin , Huang Yao
Published: November 2022

Objective

To systematically evaluate the significance of Fusobacterium nucleatum (Fn) levels the clinicopathological impacts of cancer.

Methods

Literature from Pubmed, Embase, and Web of Science was retrieved to collect all English literatures on the correlation between Fn and cancer, and the quality of literatures collected was assessed based on the Newcastle-Ottawa Quality Assessment Scale. The heterogeneity and sensitivity were detected by Stata 14.0 software, and the correlation between Fn and cancer clinicopathological as the effect variables was assessed according to the odds ratio (OR) and 95% confidence interval (CI). The forest plot was drawn.

Results

A total of 19 articles meeting the inclusion criteria were selected. The incidence of Fn prevalence varied considerably (range: 6.1 to 83.3%) and was greater than 10% in 13 of 19 studies. Compared with those with no/low Fn levels, the high levels of Fn was positively associated with vascular invasion, nerve invasion, depth of invasion, and distant metastasis [vascular invasion: OR = 1.66, 95%CI(1.07, 2.57), I2 = 21.9%, fixed effect model; nerve invasion: OR = 1.36, 95%CI(1.00, 1.84), I2 = 43.1%, fixed effect model; infiltration depth: OR = 1.94, 95%CI(1.20, 3.15), I2 = 67.2%, random effect model; distant metastasis: OR = 1.80, 95%CI(1.23, 2.64), I2 = 3.4%, fixed effect model]. Patients with MLH1 methylation always present a higher Fn levels than those without methylation [OR = 2.53, 95%CI(1.42, 4.53), P = 0.01, I2 = 57.5%, random effect model]. Further, Fn was associatedwith the molecular characteristics of cancers [MSI-H Vs. MSS/MSI-low: OR = 2.92, 95%CI(1.61, 5.32), P = 0.01, I2 = 63.2%, random effect model; High Vs. Low/Negative CIMP: OR = 2.23, 95%CI(1.64, 3.03), P = 0.01, I2 = 64.2%, random effect model; KRAS mutation Vs. wild-type: OR = 1.24, 95%CI(1.04, 1.48), P = 0.02, I2 = 27.0%, fixed effect model; Present Vs. Abscent BRAF mutations: OR = 1.88, 95%CI(1.44, 2.45), P = 0.01, I2 = 24.2%, fixed effect model]. The cancer patients with high levels of Fn often have worse RFS than those with no/low Fn levels[OR = 1.14, 95%CI(0.61, 1.68), P = 0.01, I2 = 80.7%, random effect model].

Conclusion

This review and meta-analysis showed that Fn could be used to predict unfavorable prognosis and function as potential prognostic biomarkers in colorectal cancer (CRC). Our data may have implications for targeting Fn to develop strategies for cancer prevention and treatment.
The maturation of exploratory behavior in adolescent Mus spicilegus on two photoperiods
Authors: Cryns Noah G. , Lin Wan Chen , Motahari Niloofar , Krentzman Oliver J. , Chen Weihang , Prounis George , Wilbrecht Linda
Published: November 2022

Dispersal from the natal site or familial group is a core milestone of adolescent development in many species. A wild species of mouse,Mus spicilegus, presents an exciting model in which to study adolescent development and dispersal because it shows different life history trajectory depending on season of birth.M. spicilegusborn in spring and summer on long days (LD) disperse in the first 3 months of life, whileM. spicilegusborn on shorter autumnal days (SD) delay dispersal through the wintertime. We were interested in using these mice in a laboratory context to compare age-matched mice with differential motivation to disperse. To first test if we could find a proxy for dispersal related behavior in the laboratory environment, we measured open field and novel object investigation across development inM. spicilegusraised on a LD 12 h:12 h light:dark cycle. We found that between the first and second month of life, distance traveled and time in center of the open field increased significantly with age inM. spicilegus. Robust novel object investigation was observed in all age groups and decreased between the 2nd and 3rd month of life in LD males. Compared to male C57BL/6 mice, maleM. spicilegustraveled significantly longer distances in the open field but spent less time in the center of the field. However, when a novel object was placed in the center of the open field, MaleM. spicilegus, were significantly more willing to contact and mount it. To test if autumnal photoperiod affects exploratory behavior inM. spicilegusin a laboratory environment, we reared a cohort ofM. spicileguson a SD 10 h:14 h photoperiod and tested their exploratory behavior at P60-70. At this timepoint, we found SD rearing had no effect on open field metrics, but led to reduced novel object investigation. We also observed that in P60-70 males, SD rearedM. spicilegusweighed less than LD rearedM. spicilegus. These observations establish that SD photoperiod can delay weight gain and blunt some, but not all forms of exploratory behavior in adolescentM. spicilegus.
Altered cortical thickness, degree centrality, and functional connectivity in middle-age type 2 diabetes mellitus
Authors: Kang Shangyu , Chen Yuna , Wu Jinjian , Liang Yi , Rao Yawen , Yue Xiaomei , Lyu Wenjiao , Li Yifan , Tan Xin , Huang Haoming , Qiu Shijun
Published: November 2022

Purpose

This study aimed to investigate the changes in brain structure and function in middle-aged patients with type 2 diabetes mellitus (T2DM) using morphometry and blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI).

Methods

A total of 44 middle-aged patients with T2DM and 45 matched healthy controls (HCs) were recruited. Surface-based morphometry (SBM) was used to evaluate the changes in brain morphology. Degree centrality (DC) and functional connectivity (FC) were used to evaluate the changes in brain function.

Results

Compared with HCs, middle-aged patients with T2DM exhibited cortical thickness reductions in the left pars opercularis, left transverse temporal, and right superior temporal gyri. Decreased DC values were observed in the cuneus and precuneus in T2DM. Hub-based FC analysis of these regions revealed lower connectivity in the bilateral hippocampus and parahippocampal gyrus, left precuneus, as well as left frontal sup.

Conclusion

Cortical thickness, degree centrality, as well as functional connectivity were found to have significant changes in middle-aged patients with T2DM. Our observations provide potential evidence from neuroimaging for analysis to examine diabetes-related brain damage.
Performance in information processing speed is associated with parietal white matter tract integrity in multiple sclerosis
Authors: Grothe Matthias , Jochem Katharina , Strauss Sebastian , Langner Sönke , Kirsch Michael , Hoffeld Kai , Penner Iris Katharina , Nagels Guy , Klepzig Kai , Domin Martin , Lotze Martin
Published: November 2022

Background

The Symbol Digit Modalities Test (SDMT) is most frequently used to test processing speed in patients with multiple sclerosis (MS). Functional imaging studies emphasize the importance of frontal and parietal areas for task performance, but the influence of frontoparietal tracts has not been thoroughly studied. We were interested in tract-specific characteristics and their association with processing speed in MS patients.

Methods

Diffusion tensor imaging was obtained in 100 MS patients and 24 healthy matched controls to compare seed-based tract characteristics descending from the superior parietal lobule [Brodman area 7A (BA7A)], atlas-based tract characteristics from the superior longitudinal fasciculus (SLF), and control tract characteristics from the corticospinal tract (CST) and their respective association with ability on the SDMT.

Results

Patients had decreased performance on the SDMT and decreased white matter volume (each p < 0.05). The mean fractional anisotropy (FA) for the BA7A tract and CST (p < 0.05), but not the SLF, differed between MS patients and controls. Furthermore, only the FA of the SLF was positively associated with SDMT performance even after exclusion of the lesions within the tract (r = 0.25, p < 0.05). However, only disease disability and total white matter volume were associated with information processing speed in a linear regression model.

Conclusions

Processing speed in MS is associated with the structural integrity of frontoparietal white matter tracts.
Ameliorative effect of vanillin on scopolamine-induced dementia-like cognitive impairment in a mouse model
Authors: Anand Abhinav , Khurana Navneet , Ali Nemat , AlAsmari Abdullah F. , Alharbi Metab , Waseem Mohammad , Sharma Neha
Published: November 2022

Background

Alzheimer’s disease (AD) is the most common form of dementia, which is among the top five causes of death in the United States. It is a neurodegenerative disorder that causes permanent loss of memory and cognition. The current pharmacotherapy for AD is based on providing symptomatic relief only and has many side effects. There is a need for a safer, disease-modifying drug for the treatment of AD.

Experimental approach

The PASS online software was used to screen phytoconstituents based on their predicted effects on various AD-related targets. Vanillin was selected as the compound of interest, as it has not been researched elaborately on any animal model of AD. The acetylcholinesterase inhibitory activity of vanillin was established in vitro. Thereafter, ameliorative effect of vanillin was evaluated using the exteroceptive memory model in scopolamine-induced cognitive impairment mice model.

Results

Vanillin showed an acetylcholinesterase inhibitory activity in vitro, and the IC50 value was calculated to be 0.033 mM. Vanillin significantly reversed the memory and behavioral deficits caused by scopolamine as demonstrated by significant improvement in memory in negative reinforcement, elevated plus maze, and spatial learning paradigms. Vanillin also proved to have a nootropic effect. Also, vanillin proved to have significantly better antioxidant and acetylcholinesterase inhibitory effects in vivo than donepezil hydrochloride. The potential anti-AD activity of vanillin was also confirmed by the reduction in IL-6 levels and TNF-α levels.

Conclusion

Our results suggest that vanillin is a safe and effective natural drug candidate having a great potential for the treatment of AD. However, more research is required to evaluate its effect on A beta plaques and Tau neurofibrillary tangles in vivo.
Predicting the tissue outcome of acute ischemic stroke from acute 4D computed tomography perfusion imaging using temporal features and deep learning
Authors: Winder Anthony J. , Wilms Matthias , Amador Kimberly , Flottmann Fabian , Fiehler Jens , Forkert Nils D.
Published: November 2022

Predicting follow-up lesions from baseline CT perfusion (CTP) datasets in acute ischemic stroke patients is important for clinical decision making. Deep convolutional networks (DCNs) are assumed to be the current state-of-the-art for this task. However, many DCN classifiers have not been validated against the methods currently used in research (random decision forests, RDF) and clinical routine (Tmax thresholding). Specialized DCNs have even been designed to extract complex temporal features directly from spatiotemporal CTP data instead of using standard perfusion parameter maps. However, the benefits of applying deep learning to source or deconvolved CTP data compared to perfusion parameter maps have not been formally investigated so far. In this work, a modular UNet-based DCN is proposed that separates temporal feature extraction from tissue outcome prediction, allowing for both model validation using perfusion parameter maps as well as end-to-end learning from spatiotemporal CTP data. 145 retrospective datasets comprising baseline CTP imaging, perfusion parameter maps, and follow-up non-contrast CT with manual lesion segmentations were assembled from acute ischemic stroke patients treated with intravenous thrombolysis alone (IV; n = 43) or intra-arterial mechanical thrombectomy (IA; n = 102) with or without combined IV. Using the perfusion parameter maps as input, the proposed DCN (mean Dice: 0.287) outperformed the RDF (0.262) and simple Tmax-thresholding (0.249). The performance of the proposed DCN was approximately equal using features optimized from the deconvolved residual curves (0.286) compared to perfusion parameter maps (0.287), while using features optimized from the source concentration-time curves (0.296) provided the best tissue outcome predictions.
From the origins to the stream of consciousness and its neural correlates
Authors: Yurchenko Sergey B.
Published: November 2022

There are now dozens of very different theories of consciousness, each somehow contributing to our understanding of its nature. The science of consciousness needs therefore not new theories but a general framework integrating insights from those, yet not making it a still-born “Frankenstein” theory. First, the framework must operate explicitly on the stream of consciousness, not on its static description. Second, this dynamical account must also be put on the evolutionary timeline to explain the origins of consciousness. The Cognitive Evolution Theory (CET), outlined here, proposes such a framework. This starts with the assumption that brains have primarily evolved as volitional subsystems of organisms, inherited from primitive (fast and random) reflexes of simplest neural networks, only then resembling error-minimizing prediction machines. CET adopts the tools of critical dynamics to account for metastability, scale-free avalanches, and self-organization which are all intrinsic to brain dynamics. This formalizes the stream of consciousness as a discrete (transitive, irreflexive) chain of momentary states derived from critical brain dynamics at points of phase transitions and mapped then onto a state space as neural correlates of a particular conscious state. The continuous/discrete dichotomy appears naturally between the brain dynamics at the causal level and conscious states at the phenomenal level, each volitionally triggered from arousal centers of the brainstem and cognitively modulated by thalamocortical systems. Their objective observables can be entropy-based complexity measures, reflecting the transient level or quantity of consciousness at that moment.
Associations between maternal adiposity and appetite-regulating hormones in human milk are mediated through maternal circulating concentrations and might affect infant outcomes
Authors: Christensen Sophie Hilario , Lewis Jack Ivor , Larnkjær Anni , Frøkiær Hanne , Allen Lindsay H. , Mølgaard Christian , Michaelsen Kim F.
Published: November 2022

Background

Appetite-regulating hormones (ARH) in human milk (HM) are suggested to affect infants’ milk intake and possibly infant growth. Maternal adiposity might contribute to higher levels of ARH in HM, either from the mammary gland or from raised circulating levels due to higher adiposity. Counterfactual-based mediation analysis can define indirect and direct effects between HM ARH and maternal and infant factors, and might be an important tool when investigating the mother-milk-infant triad.

Objective

We aim to investigate whether potential associations between (1) maternal adiposity and HM ARH and (2) HM ARH and infant milk intake and growth are mediated through maternal and infant plasma ARH, respectively.

Materials and methods

Maternal and infant anthropometry and body composition, HM and blood samples were collected from 223 mother-infant dyads participating in the Mother, Infant and Lactation Quality study at three postpartum visits from 1 to 8.49 months. Leptin, insulin and adiponectin were analyzed using immunoassays. Mediation analyses using linear mixed-effect models were applied to investigate the direct and indirect effects through maternal and infant plasma hormone concentrations.

Results

A positive association between maternal body-mass-index (BMI) and HM leptin was mediated by maternal plasma leptin by 29% when fixing BMI to < 25 kg/m2, and through 51% when fixing BMI to ≥ 25 kg/m2 (pinteraction < 0.01). There was no mediated effect through plasma insulin in the association between BMI and HM insulin (p = 0.068). We found negative and positive associations between HM insulin and total milk intake and infant weight, respectively, however, these diminished in mediation analyses with reduced sample sizes.

Conclusion

Our main results suggest that the association between maternal adiposity and HM leptin was mediated through circulating leptin to a stronger degree for mothers with overweight compared to mothers with normal-weight. This indicates that excess maternal adiposity, and the resulting rise of circulating leptin and possible concomitant low-grade inflammation, may be reflected in HM composition.

Clinical trials registry number

NCT03254329.
PD0166285 sensitizes esophageal squamous cell carcinoma to radiotherapy by dual inhibition of WEE1 and PKMYT1
Authors: Zhang Qingyi , Lin Xu , Jiang Kan , Deng Jun , Ke Lei , Wu Ziheng , Xia Pinghui , Li Qi , Yu Li , Ni Pengzhi , Lv Wang , Hu Jian
Published: November 2022

Background

Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with a 5-year survival rate of only 20%. More than 80% of ESCC patients possess TP53 mutation, which abolishes the G1/S checkpoint and accelerates the cell cycle. Thus, WEE1 and PKMYT1, regulators of G2/M phase in cell cycle, play essential roles in TP53-mutated cancer cells. PD0166285(PD) is a pyridopyrimidine compound that can inhibit WEE1 and PKMYT1 simultaneously, however, the effects of PD on ESCC, either as monotherapy or in combination therapy with radiotherapy, remain unclear.

Methods

To measure the anti-tumor efficacy of PD in ESCC cells, cell viability, cell cycle and cell apoptosis assays were examined in KYSE150 and TE1 cells with PD treatment. The combination therapy of PD and irradiation was also performed in ESCC cells to find whether PD can sensitize ESCC cells to irradiation. Vivo assays were also performed to investigate the efficacy of PD.

Results

We found that the IC50 values of PD among ESCC cells ranged from 234 to 694 nM, PD can regulate cell cycle and induce cell apoptosis in ESCC cells in a dose-dependent manner. When combined with irradiation, PD sensitized ESCC cells to irradiation by abolishing G2/M phase arrest, inducing a high ratio of mitosis catastrophe, eventually leading to cell death. We also demonstrated that PD can attenuate DNA damage repair by inhibiting Rad51, further research also found the interaction of WEE1 and Rad51. In vivo assays, PD inhibited the tumor growth in mice, combination therapy showed better therapeutic efficacy.

Conclusion

PD0166285 can exert antitumor effect by inhibiting the function of WEE1 and PKMYT1 in ESCC cells, and also sensitize ESCC cells to irradiation not only by abolishing G2/M arrest but also attenuating DNA repair directly. We believe PD0166285 can be a potent treatment option for ESCC in the future.
Endothelial dysfunction in preterm infants: The hidden legacy of uteroplacental pathologies
Authors: Amelio Giacomo Simeone , Provitera Livia , Raffaeli Genny , Tripodi Matteo , Amodeo Ilaria , Gulden Silvia , Cortesi Valeria , Manzoni Francesca , Cervellini Gaia , Tomaselli Andrea , Pravatà Valentina , Garrido Felipe , Villamor Eduardo , Mosca Fabio , Cavallaro Giacomo
Published: November 2022

Millions of infants are born prematurely every year worldwide. Prematurity, particularly at lower gestational ages, is associated with high mortality and morbidity and is a significant global health burden. Pregnancy complications and preterm birth syndrome strongly impact neonatal clinical phenotypes and outcomes. The vascular endothelium is a pivotal regulator of fetal growth and development. In recent years, the key role of uteroplacental pathologies impairing endothelial homeostasis is emerging. Conditions leading to very and extremely preterm birth can be classified into two main pathophysiological patterns or endotypes: infection/inflammation and dysfunctional placentation. The first is frequently related to chorioamnionitis, whereas the second is commonly associated with hypertensive disorders of pregnancy and fetal growth restriction. The nature, timing, and extent of prenatal noxa may alter fetal and neonatal endothelial phenotype and functions. Changes in the luminal surface, oxidative stress, growth factors imbalance, and dysregulation of permeability and vascular tone are the leading causes of endothelial dysfunction in preterm infants. However, the available evidence regarding endothelial physiology and damage is limited in neonates compared to adults. Herein, we discuss the current knowledge on endothelial dysfunction in the infectious/inflammatory and dysfunctional placentation endotypes of prematurity, summarizing their molecular features, available biomarkers, and clinical impact. Furthermore, knowledge gaps, shadows, and future research perspectives are highlighted.
Aicardi–Goutières syndrome with SAMHD1 deficiency can be diagnosed by unscheduled DNA synthesis test
Authors: Senju Chikako , Nakazawa Yuka , Shimada Mayuko , Iwata Dai , Matsuse Michiko , Tanaka Katsumi , Miyazaki Yasushi , Moriwaki Shinichi , Mitsutake Norisato , Ogi Tomoo
Published: November 2022

Aicardi–Goutières syndrome (AGS) is a rare genetic disorder characterised by progressive encephalopathy, involving microcephaly, intracranial calcification, and cerebrospinal fluid lymphocytosis with increased interferon-α concentrations. The clinical features of AGS overlap with fetal cerebral anomalies caused by congenital infections, such as TORCH (toxoplasmosis, other, rubella, cytomegalovirus, and herpes), or with those of other genetic disorders showing neonatal microcephaly, including Cockayne syndrome (CS) with transcription-coupled DNA repair deficiency, and Seckel syndrome (SS) showing aberrant cell-cycle checkpoint signaling. Therefore, a differential diagnosis to confirm the genetic cause or a proof of infection should be considered. In this report, we describe an individual who showed primordial dwarfism and encephalopathy, and whose initial diagnosis was CS. First, we conducted conventional DNA repair proficiency tests for the patient derived fibroblast cells. Transcription-coupled nucleotide excision repair (TC-NER) activity, which is mostly compromised in CS cases, was slightly reduced in the patient's cells. However, unscheduled DNA synthesis (UDS) was significantly diminished. These cellular traits were inconsistent with the diagnosis of CS. We further performed whole exome sequencing for the case and identified a compound heterozygous loss-of-function variants in the SAMHD1 gene, mutations in which are known to cause AGS. As SAMHD1 encodes deoxyribonucleoside triphosphate triphosphohydrolase, we reasoned that the deoxyribonucleoside triphosphate (dNTP) pool size in the patient's cells was elevated, and the labeling efficiency of UDS-test was hindered due to the reduced concentration of phosphorylated ethynyl deoxyuridine (EdU), a nucleoside analogue used for the assay. In conclusion, UDS assay may be a useful diagnostic tool to distinguish between AGS with SAMHD1 mutations and other related diseases.
Indoleamine 2, 3-dioxygenase 1 inhibitory compounds from natural sources
Authors: Tan Ying , Liu Miaomiao , Li Ming , Chen Yujuan , Ren Meng
Published: November 2022

L-tryptophan metabolism is involved in the regulation of many important physiological processes, such as, immune response, inflammation, and neuronal function. Indoleamine 2, 3-dioxygenase 1 (IDO1) is a key enzyme that catalyzes the first rate-limiting step of tryptophan conversion to kynurenine. Thus, inhibiting IDO1 may have therapeutic benefits for various diseases, such as, cancer, autoimmune disease, and depression. In the search for potent IDO1 inhibitors, natural quinones were the first reported IDO1 inhibitors with potent inhibitory activity. Subsequently, natural compounds with diverse structures have been found to have anti-IDO1 inhibitory activity. In this review, we provide a summary of these natural IDO1 inhibitors, which are classified as quinones, polyphenols, alkaloids and others. The overview of in vitro IDO1 inhibitory activity of natural compounds will help medicinal chemists to understand the mode of action and medical benefits of them. The scaffolds of these natural compounds can also be used for further optimization of potent IDO1 inhibitors.
Safety, tolerability and pharmacokinetics of WXFL10203614 in healthy Chinese subjects: A randomized, double-blind, placebo-controlled phase Ⅰ study
Authors: Huang Kai , Ding Ying , Que Linling , Chu Nannan , Shi Yunfei , Qian Zhenzhong , Qin Wei , Chen Yuanxin , Gu Xianghong , Wang Jiakun , Zhang Zhiwei , Xu Jianguo , He Qing
Published: November 2022

Objective: This study was conducted to investigate the safety, tolerability and pharmacokinetics (PK) of WXFL10203614 after single and multiple oral doses in healthy Chinese subjects.

Methods: A single-center, randomized, double-blind, placebo-controlled phase Ⅰ study was performed on healthy Chinese subjects. In the single-dose study, Subjects were randomized into 7 dose levels of WXFL10203614 (1 mg group, n = 2; 2, 5, 10, 17, 25 and 33 mg groups with placebo, 8 subjects per group, 2 of them given placebo). In the multiple-dose study, subjects received 5 or 10 mg WXFL10203614 once daily (QD), 5 mg twice daily (BID) or placebo for 7 consecutive days. Safety, tolerability and PK of WXFL10203614 were all assessed.

Results: A total of 592 subjects were screened, 50 subjects were enrolled in the single-dose study and 30 in the multiple-dose study. All adverse events (AEs) were mild or moderate and resolved spontaneously. No Serious Adverse Events (SAEs) or deaths were reported during the study. WXFL10203614 was absorbed rapidly after dosing with Tmax of 0.48–0.98 h, Cmax, AUC0-t and AUC0-∞ were all increased in a dose-related manner over the range of 1–33 mg. Renal excretion was the major route of elimination of WXFL10203614. Steady-state PK parameters (Cmax,ss, AUC0-t,ss and AUC0-∞,ss) were elevated after once-daily administration of 5–10 mg WXFL10203614 and non- and weak drug accumulations were observed, whereas moderate drug accumulation occurred in the 5 mg BID group.

Conclusion: WXFL10203614 exhibited good safety, tolerability and favorable PK profiles in healthy Chinese subjects, supporting further clinical development in patients with rheumatoid arthritis.

Clinical Trials Registration Number:http://www.chinadrugtrials.org.cn/index.html, #CTR20190069 and CTR20200143.
The benefits of propofol on cancer treatment: Decipher its modulation code to immunocytes
Authors: Gu Long , Pan Xueqi , Wang Chongcheng , Wang Lei
Published: November 2022

Anesthetics are essential for cancer surgery, but accumulated research have proven that some anesthetics promote the occurrence of certain cancers, leading to adverse effects in the lives of patients. Although anesthetic technology is mature, there is no golden drug selection standard for surgical cancer treatment. To afford the responsibility of human health, a more specific regimen for cancer resection is indeed necessary. Immunosuppression in oncologic surgery has an adverse influence on the outcomes of patients. The choice of anesthetic strategies influences perioperative immunity. Among anesthetics, propofol has shown positive effects on immunity. Apart from that, propofol’s anticancer effect has been generally reported, which makes it more significant in oncologic surgery. However, the immunoregulative function of propofol is not reorganized well. Herein, we have summarized the impact of propofol on different immunocytes, proposed its potential mechanism for the positive effect on cancer immunity, and offered a conceivable hypothesis on its regulation to postoperative inflammation. We conclude that the priority of propofol is high in oncologic surgery and propofol may be a promising immunomodulatory drug for tumor therapy.
The efficacy and safety of mecobalamin combined with Chinese medicine injections in the treatment of diabetic peripheral neuropathy: A systematic review and Bayesian network meta-analysis of randomized controlled trials
Authors: Ma Yuqi , Chen Ji , Huang Xinggui , Liu Yuan
Published: November 2022

Background: In recent years, people pay more and more attention to diabetic peripheral neuropathy (DPN). As a neurotrophic agent, mecobalamin is able to repaire nerves, which has already become a consensus among experts. However, it has been found that mecobalamin has poor effect to increase nerve conduction velocity, which is an important indicator. Clinical data have shown that Chinese medicine injection, combined with mecobalamin injection, can significantly improve nerve conduction velocity of the limbs. Nevertheless, several kinds of Chinese medicine injections have been used to treat DPN. The effect of these Chinese medicine injections for DPN are various. Therefore, it is necessary to evaluate the effectiveness of Chinese medicine injections combined with mecobalamin in the treatment of DPN.

Methods: All relevant articles published before 12 March 2022 were searched in eight electronic databases. Randomized controlled trials (RCTs) on Chinese medicine injections plus Mecobalamin for DPN were identified according to inclusion criteria, and were assessed using the revised Cochrane risk of bias tool (ROB2.0). R software and stata15 was used to create the ranking probabilities and network meta-analysis.

Results: A total of 80 RCTs involving 6,980 patients were included. The results showed that mecobalamin plus Dengzhanxixin injection (ME + DZXX) ranked first in overall response rate [RR = 1.64, 95% CI (1.26, 2.21)] and median motor nerve conduction velocity [MD = 9.46, 95% CI (5.67, 13.28)]. Then, mecobalamin plus Kudiezi Injection (ME + KDZ) had the best effect in median sensory nerve conduction velocity [MD = 10.41, 95% CI (−13.31, −7.52)], and mecobalamin plus Honghua injection (ME + HH) ranked highest in common peroneal motor nerve conduction velocity [MD = 6.8, 95% CI (4.13, 9.49)] and common peroneal sensory nerve conduction velocity [MD = −6.25, 95% CI (−8.85, −3.65)].

Conclusion: This study determined the efficacy of different Chinese medicine injections combined with mecobalamin. DZXX may be the best adjunctive Chinese medicine injection for DPN patients. However, due to potential risk of bias and limited RCTs, our results need to be treated with reservations.
Understanding Chinese EFL learners’ anxiety in second language writing for the sustainable development of writing skills
Authors: Yu Yue , Zhou Dandan
Published: November 2022

To add to the currently limited research on the degree of cultural uniqueness of Chinese EFL learners’ anxiety and the multidimensional nature of second language writing anxiety (SLWA), the present qualitative study used think-aloud protocol and interview to examine Chinese EFL learners’ three dimensions of SLWA and the related variables, so as to probe into this problem that could pose an obstacle to sustainable second language writing. Findings showed that Chinese EFL learners experienced much Cognitive Anxiety, but relatively little Avoidance Behavior. Learner-internal, teacher-related, and human-external variables interacted with SLWA in a dynamic way. To a certain degree, Chinese EFL learners showcased uniqueness in some aspects of SLWA, under cultural influences, regarding ethnic culture, local culture, academic culture, and disciplinary culture.
Informal financial education and consumer financial capability: The mediating role of financial knowledge
Authors: Chen Fuzhong , Lu Xiuli , Wang Wenting
Published: November 2022

With the development of the economy, family wealth continues to accumulate, and more and more consumers participate in financial management affairs. As an important way to improve financial knowledge, informal financial education is vital to consumer financial capability. Utilizing data from the 2012, 2015, and 2018 US National Financial Capability Study and the approaches of ordinary least squares and ordered probit regression are employed to produce more accurate estimates. Meanwhile, the study also explores the mediating effects of financial knowledge between informal financial education and consumer financial capability. The results show that informal financial education has a positive effect on the improvement of consumer financial capability. Besides, financial knowledge partially mediates the nexus between informal financial education and consumer financial capability. Therefore, policymakers are encouraged to formulate measures to promote financial education programs not only in schools and universities but also in workplaces or communities. Companies also should offer more opportunities for their employees to receive financial education and further enhance their financial capability. Consumers should be aware of the importance of financial education and actively learn financial knowledge to improve financial capability and further enhance financial satisfaction.
Organizational and psychological features of successful democratic enterprises: A systematic review of qualitative research
Authors: Unterrainer Christine , Weber Wolfgang G. , Höge Thomas , Hornung Severin
Published: November 2022

In organizational psychology the positive effects of democratically structured enterprises on their employees are well documented. However, the longstanding viability as well as economic success of democratic enterprises in a capitalistic market environment has long been contested. For instance, this has given rise to widespread endorsement of the “degeneration thesis” and the so-called “iron law of oligarchy”. By reviewing 77 qualitative studies that examined 83 democratic enterprises (including 15 studies on nine enterprises of the Mondragon Cooperative Cooperation network) within the last 50 years, the present systematic review provides evidence that such enterprises are able to economically survive and prosper. The majority of studied enterprises (63.5%) either resisted pressures toward degeneration or subsequently regenerated after undergoing degenerative processes. Only 9.5% fully degenerated in accordance with the degeneration thesis and the “iron law of oligarchy”, while 27.0% of the democratic enterprises showed diverse and mixed forms of degeneration tendencies, indicating that the notion of an “iron law” needs to be revised. Within the nine investigated cases of Mondragon not one single enterprise or group fully degenerated. Three cases showed degenerative tendencies, another three one degeneration tendencies and simultaneously regeneration, one case fully resisted degeneration tendencies (retention) and two cases regenerated. Further, this systematic review provides an overview of organizational and external conditions, non-/democratic or non-/participative practices and psychological phenomena that contribute to the degeneration, regeneration, or resistance to degeneration (i.e., retention). The described examples of such practices may help practitioners to implement and maintain democratic structures and processes in contemporary organizations.
Meaning in life among Chinese undergraduate students in the post-epidemic period: A qualitative interview study
Authors: Ge Ying , Lu Cun Yang , Shuai Mei Qiong , Wenger Jay L. , Peng Chun Hua , Wang Hong
Published: November 2022

Background

COVID-19 epidemic has lasted for nearly 3 years, and revolutionized social life. In the study, in-depth interviews were conducted with Chinese undergraduate students to explore their understanding and experience of meaning in life. Meaning of life is interpreted from four aspects: life goals, life value, life enthusiasm, and life freedom. These four aspects are independent yet interrelated. Based on the free grasp of life, individuals explore and pursue the true meaning of life goals, acquire life value in evaluating the completion of life goals, and subsequently experience enthusiasm for life. Life enthusiasm and the perception of life value can help individuals to further understand and possess their meaning of life.

Materials and methods

The present study adopts the qualitative method to understand the experience of meaning in life among Chinese undergraduate students. Semi-structured interviews were conducted, and six people participated the study. The Grounded Theory was adopted to analyze the qualitative data.

Results

(1) Chinese undergraduates had clear life goals and obtained a certain sense of achievement and satisfaction when striving for these goals. (2) The life value of Chinese undergraduates was mainly to their families, but there was also a willingness to make due contributions to the country and society. (3) Chinese undergraduates’ feelings about life were polarized, but they all expressed the view of “living in the moment and cherishing the present.” (4) Chinese undergraduate students see life freedom as freedom of choice and generally believed that COVID-19 did not restrict their lives very much. (5) Chinese undergraduate students gained a deeper understanding of meaning in life after this major public health emergency.
Self-care behaviors in older adults suffering from knee osteoarthritis: Application of theory of planned behavior
Authors: Jormand Hanieh , Mohammadi Nasim , Khani Jeihooni Ali , Afzali Harsini Pooyan
Published: November 2022

Background

Osteoarthritis is one of the main reasons causing disablement. Educational intervention for self-care behaviors of patients suffering from knee osteoarthritis is important because its effect on quality of patient life decreases the economic burden of disorder on society and family. This study aimed to investigate the effect of educational intervention based on the theory of planned behavior (TPB) on promoting self-care behaviors in elderly patients suffering from knee osteoarthritis.

Methods

This quasi-experimental study was performed on 200 elderlies suffering from knee osteoarthritis in the rheumatology clinics of Shiraz, Iran, in 2019. The subjects were divided into two groups (100 experimental and 100 control). Before and after 4 months, both experimental and control groups filled a questionnaire. After administering a pre-test to both groups, only the experimental group was trained based on the TPB constructs on self-care behaviors in elderly people suffering from knee osteoarthritis in eight sessions by presenting educational films and images, power points, and group discussions for solving problems.

Results

The mean age of the experimental group was 67.25 ± 3.64, and the mean age of the control group was 66.12 ± 3.50. The average scores of attitudes, subjective norms, perceived behavioral control, intention, and behavior before the educational intervention did not have significant differences in experimental and control groups, however, 4 months after the educational intervention, the pairedt-test indicated significant enhancement in every construct in the experimental group, but no significant changes in the control group.

Conclusion

According to the results, the educational intervention increased the self-care behaviors of patients suffering from knee osteoarthritis based on the theory of planned behavior. Therefore, the results of this study can be used in theory-based intervention strategies for self-care behaviors of patients suffering from knee osteoarthritis.