bluuebunny/crossref_metadata_2025 huggingface dataset:
Hospital length of stay and readmission after elective surgery: a comparison of current and former smokers with non-smokers
Authors: Arena Gina , Cumming Craig , Lizama Natalia , Mace Hamish , Preen David B.
Published: January 2024

Background

The purpose of this study was to investigate differences between non-smokers, ex-smokers and current smokers in hospital length of stay (LOS), readmission (seven and 28 days) and cost of readmission for patients admitted for elective surgery.

Methods

A retrospective cohort study of administrative inpatient data from 24, 818 patients admitted to seven metropolitan hospitals in Western Australia between 1 July 2016 and 30 June 2019 for multiday elective surgery was conducted. Data included smoking status, LOS, procedure type, age, sex and Indigenous status. LOS for smoking status was compared using multivariable negative binomial regression. Odds of readmission were compared for non-smokers and both ex-smokers and current smokers using separate multivariable logistic regression models.

Results

Mean LOS for non-smokers (4.7 days, SD=5.7) was significantly lower than both ex-smokers (6.2 days SD 7.9) and current smokers (6.1 days, SD=8.2). Compared to non-smokers, current smokers and ex-smokers had significantly higher odds of readmission within seven (OR=1.29; 95% CI: 1.13, 1.47, and OR=1.37; 95% CI: 1.19, 1.59, respectively) and 28 days (OR=1.35; 95% CI: 1.23, 1.49, and OR=1.53; 95% CI: 1.39, 1.69, respectively) of discharge. The cost of readmission for seven and 28-day readmission was significantly higher for current smokers compared to non-smokers (RR=1.52; 95% CI: 1.1.6, 2.0; RR=1.39; 95% CI: 1.18, 1.65, respectively).

Conclusion

Among patients admitted for elective surgery, hospital LOS, readmission risk and readmission costs were all higher for smokers compared with non-smokers. The findings indicate that provision of smoking cessation treatment for adults undergoing elective surgery is likely to produce multiple benefits.
Self- and interviewer-reported cognitive problems in relation to cognitive decline and dementia: results from two prospective studies
Authors: Huang Yuhui , Chen Hui , Gao Mengyan , Lv Xiaozhen , Pang Ting , Rong Shuang , Xu Xin , Yuan Changzheng
Published: January 2024

Background

Little is known regarding the association of interviewer-reported cognitive problems (ICP) with age-related cognitive decline. We aimed to investigate the independent associations of ICP and the combined associations of ICP and self-reported cognitive problems (SCP) with subsequent cognitive decline and dementia in two prospective cohort studies.

Methods

We included 10,976 Chinese (age = 57.7 ± 8.7) and 40,499 European (age = 64.6 ± 9.4) adults without dementia from the China Health and Retirement Longitudinal Study (CHARLS) and the Survey of Health, Ageing, and Retirement in Europe (SHARE). Self-rated memory (5-point scale) and interviewer-rated frequencies of asking for clarification (6-point scale) were used to define SCP and ICP (dichotomized). Outcomes included objective cognitive test scores (z-score transformation) and incident dementia. Generalized estimating equation models were performed to evaluate mean differences in objective cognitive decline. Logistic and Cox regression models were used to estimate the relative risk of dementia. Results from two cohorts were pooled using the random-effects models.

Results

ICP was associated with faster cognitive decline in CHARLS (βCHARLS = −0.025 [−0.044, −0.006] z-score/year). ICP and SCP were also independently associated with higher risk of dementia in two cohorts (pooled relative risk for SCP = 1.73 [1.30, 2.29]; pooled relative risk for ICP = 1.40 [1.10, 1.79]). In the joint analysis, participants with coexistence of SCP and ICP had the fastest cognitive decline (βCHARLS = −0.051 [−0.080, −0.021]; βSHARE = −0.024 [−0.043, −0.004]; pooled β = −0.035 [−0.061, −0.009] z-score/year) and highest risk of dementia (ORCHARLS = 1.77 [1.42, 2.20]; HRSHARE = 2.94 [2.42, 3.59]; pooled relative risk = 2.29 [1.38, 3.77]).

Conclusions

The study suggested that interviewer-reported cognitive problems may be early indicators of cognitive decline and dementia in middle-aged and older adults. A combination of self- and interviewer-reported cognitive problems showed the strongest associations with cognitive decline and dementia.
Attenuation of neurovirulence of chikungunya virus by a single amino acid mutation in viral E2 envelope protein
Authors: Chen Huixin , Phuektes Patchara , Yeo Li Sze , Wong Yi Hao , Lee Regina Ching Hua , Yi Bowen , Hou Xinjun , Liu Sen , Cai Yu , Chu Justin Jang Hann
Published: January 2024

Background

Chikungunya virus (CHIKV) has reemerged as a major public health concern, causing chikungunya fever with increasing cases and neurological complications.

Methods

In the present study, we investigated a low-passage human isolate of the East/ Central/South African (ECSA) lineage of CHIKV strain LK(EH)CH6708, which exhibited a mix of small and large viral plaques. The small and large plaque variants were isolated and designated as CHIKV-SP and CHIKV-BP, respectively. CHIKV-SP and CHIKV-BP were characterized in vitro and in vivo to compare their virus production and virulence. Additionally, whole viral genome analysis and reverse genetics were employed to identify genomic virulence factors.

Results

CHIKV-SP demonstrated lower virus production in mammalian cells and attenuated virulence in a murine model. On the other hand, CHIKV-BP induced higher pro-inflammatory cytokine levels, compromised the integrity of the blood–brain barrier, and led to astrocyte infection in mouse brains. Furthermore, the CHIKV-SP variant had limited transmission potential in Aedesalbopictus mosquitoes, likely due to restricted dissemination. Whole viral genome analysis revealed multiple genetic mutations in the CHIKV-SP variant, including a Glycine (G) to Arginine (R) mutation at position 55 in the viral E2 glycoprotein. Reverse genetics experiments confirmed that the E2-G55R mutation alone was sufficient to reduce virus production in vitro and virulence in mice.

Conclusions

These findings highlight the attenuating effects of the E2-G55R mutation on CHIKV pathogenicity and neurovirulence and emphasize the importance of monitoring this mutation in natural infections.
Household air pollution and risk of pulmonary tuberculosis in HIV-Infected adults
Authors: Katoto Patrick D.M.C. , Bihehe Dieudonné , Brand Amanda , Mushi Raymond , Kusinza Aline , Alwood Brian W. , van Zyl-Smit Richard N. , Tamuzi Jacques L. , Sam-Agudu Nadia A. , Yotebieng Marcel , Metcalfe John , Theron Grant , Godri Pollitt Krystal J. , Lesosky Maia , Vanoirbeek Jeroen , Mortimer Kevin , Nawrot Tim , Nemery Benoit , Nachega Jean B.
Published: January 2024

Background

In low- and middle-income countries countries, millions of deaths occur annually from household air pollution (HAP), pulmonary tuberculosis (PTB), and HIV-infection. However, it is unknown whether HAP influences PTB risk among people living with HIV-infection.

Methods

We conducted a case-control study among 1,277 HIV-infected adults in Bukavu, eastern Democratic Republic of Congo (February 2018 – March 2019). Cases had current or recent (<5y) PTB (positive sputum smear or Xpert MTB/RIF), controls had no PTB. Daily and lifetime HAP exposure were assessed by questionnaire and, in a random sub-sample (n=270), by 24-hour measurements of personal carbon monoxide (CO) at home. We used multivariable logistic regression to examine the associations between HAP and PTB.

Results

We recruited 435 cases and 842 controls (median age 41 years, [IQR] 33-50; 76% female). Cases were more likely to be female than male (63% vs 37%). Participants reporting cooking for >3h/day and ≥2 times/day and ≥5 days/week were more likely to have PTB (aOR 1·36; 95%CI 1·06-1·75) than those spending less time in the kitchen. Time-weighted average 24h personal CO exposure was related dose-dependently with the likelihood of having PTB, with aOR 4·64 (95%CI 1·1-20·7) for the highest quintile [12·3-76·2 ppm] compared to the lowest quintile [0·1-1·9 ppm].

Conclusion

Time spent cooking and personal CO exposure were independently associated with increased risk of PTB among people living with HIV. Considering the high burden of TB-HIV coinfection in the region, effective interventions are required to decrease HAP exposure caused by cooking with biomass among people living with HIV, especially women.
Regulation of tissue factor activity by interaction with the first PDZ domain of MAGI1
Authors: Mohammad Mohammad A. , Featherby Sophie , Ettelaie Camille
Published: January 2024

Background

Tissue factor (TF) activity is stringently regulated through processes termed encryption. Post-translational modification of TF and its interactions with various protein and lipid moieties allows for a multi-step de-encryption of TF and procoagulant activation. Membrane-associated guanylate kinase-with inverted configuration (MAGI) proteins are known to regulate the localisation and activity of a number of proteins including cell-surface receptors.

Methods

The interaction of TF with MAGI1 protein was examined as a means of regulating TF activity. MDA-MB-231 cell line was used which express TF and MAGI1, and respond well to protease activated receptor (PAR)2 activation. Proximity ligation assay (PLA), co-immunoprecipitation and pull-down experiments were used to examine the interaction of TF with MAGI1-3 proteins and to investigate the influence of PAR2 activation. Furthermore, by cloning and expressing the PDZ domains from MAGI1, the TF-binding domain was identified. The ability of the recombinant PDZ domains to act as competitors for MAGI1, allowing the induction of TF procoagulant and signalling activity was then examined.

Results

PLA and fluorescence microscopic analysis indicated that TF predominantly associates with MAGI1 and less with MAGI2 and MAGI3 proteins. The interaction of TF with MAGI1 was also demonstrated by both co-immunoprecipitation of TF with MAGI1, and co-immunoprecipitation of MAGI1 with TF. Moreover, activation of PAR2 resulted in reduction in the association of these two proteins. Pull-down assays using TF-cytoplasmic domain peptides indicated that the phosphorylation of Ser253 within TF prevents its association with MAGI1. Additionally, the five HA-tagged PDZ domains of MAGI1 were overexpressed separately, and the putative TF-binding domain was identified as PDZ1 domain. Expression of this PDZ domain in cells significantly augmented the TF activity measured both as thrombin-generation and also TF-mediated proliferative signalling.

Conclusions

Our data indicate a stabilising interaction between TF and the PDZ-1 domain of MAGI1 and demonstrate that the activation of PAR2 disrupts this interaction. The release of TF from MAGI1 appears to be an initial step in TF de-encryption, associated with increased TF-mediated procoagulant and signalling activities. This mechanism is also likely to lead to further interactions and modifications leading to further enhancement of procoagulant activity, or the release of TF.
Egr-1 is a key regulator of the blood-brain barrier damage induced by meningitic Escherichia coli
Authors: Yang Ruicheng , Wang Xinyi , Liu Hulin , Chen Jiaqi , Tan Chen , Chen Huanchun , Wang Xiangru
Published: January 2024

Bacterial meningitis remains a leading cause of infection-related mortality worldwide. Although Escherichia coli (E. coli) is the most common etiology of neonatal meningitis, the underlying mechanisms governing bacterial blood-brain barrier (BBB) disruption during infection remain elusive. We observed that infection of human brain microvascular endothelial cells with meningitic E. coli triggers the activation of early growth response 1 (Egr-1), a host transcriptional activator. Through integrated chromatin immunoprecipitation sequencing and transcriptome analysis, we identified Egr-1 as a crucial regulator for maintaining BBB integrity. Mechanistically, Egr-1 induced cytoskeletal changes and downregulated tight junction protein expression by directly targeting VEGFA, PDGFB, and ANGPTL4, resulting in increased BBB permeability. Meanwhile, Egr-1 also served as a master regulator in the initiation of neuroinflammatory response during meningitic E. coli infection. Our findings support an Egr-1-dependent mechanism of BBB disruption by meningitic E. coli, highlighting a promising therapeutic target for bacterial meningitis.
Post-exposure intranasal IFNα suppresses replication and neuroinvasion of Venezuelan Equine Encephalitis virus within olfactory sensory neurons
Authors: Cain Matthew D. , Klein N. Rubin , Jiang Xiaoping , Salimi Hamid , Wu Qingping , Miller Mark J. , Klimstra William B. , Klein Robyn S.
Published: January 2024

Background

Venezuelan Equine Encephalitis virus (VEEV) may enter the central nervous system (CNS) within olfactory sensory neurons (OSN) that originate in the nasal cavity after intranasal exposure. While it is known that VEEV has evolved several mechanisms to inhibit type I interferon (IFN) signaling within infected cells, whether this inhibits virologic control during neuroinvasion along OSN has not been studied.

Methods

We utilized an established murine model of intranasal infection with VEEV and a repository of scRNAseq data from IFN-treated OSN to assess the cellular targets and IFN signaling responses after VEEV exposure.

Results

We found that immature OSN, which express higher levels of the VEEV receptor LDLRAD3 than mature OSN, are the first cells infected by VEEV. Despite rapid VEEV neuroinvasion after intranasal exposure, olfactory neuroepithelium (ONE) and olfactory bulb (OB) IFN responses, as assessed by evaluation of expression of interferon signaling genes (ISG), are delayed for up to 48 h during VEEV neuroinvasion, representing a potential therapeutic window. Indeed, a single intranasal dose of recombinant IFNα triggers early ISG expression in both the nasal cavity and OB. When administered at the time of or early after infection, IFNα treatment delayed onset of sequelae associated with encephalitis and extended survival by several days. VEEV replication after IFN treatment was also transiently suppressed in the ONE, which inhibited subsequent invasion into the CNS.

Conclusions

Our results demonstrate a critical and promising first evaluation of intranasal IFNα for the treatment of human encephalitic alphavirus exposures.
Effect of breast milk intake volume on early behavioral neurodevelopment of extremely preterm infants
Authors: Gao Ying , Lu Xiaoyu , Pan Mengqing , Liu Chuntian , Min Yuxiao , Chen Xiaochun
Published: January 2024

Background

This study aimed to explore the effects of breast milk feeding volume on the early behavioral neurodevelopment of extremely preterm infants (gestational age < 28 weeks).

Methods

The study was conducted from 1 January 2021 to 31 March 2023. A total of 187 preterm infants from a neonatal intensive care unit (NICU) in a Grade III Class A hospital in Zhejiang, China, were divided based on the proportion of breast milk in their total enteral nutrition: high proportion (≥ 80%, including exclusive breast milk feeding), medium proportion (20% ~ < 80%), and low proportion (< 20%). The study investigated motor performance and behavioral neurodevelopment at 37 weeks of corrected gestational age, as well as the total incidence of intracranial hemorrhage within the first four weeks postpartum.

Results

The low breast milk feeding group had significantly lower scores in infant motor performance (31.34 ± 5.85) and elicited item scores (19.89 ± 5.55) compared to the medium and high groups (33.52 ± 4.33, 22.13 ± 4.22; and 35.86 ± 5.27, 23.91 ± 4.98), p < 0.05, respectively. Despite no significant difference in behavioral ability, the low proportion group exhibited lower passive muscle tension and primitive reflex scores than the medium and high proportion groups. The high proportion group showed higher active muscle tension scores. Ultrasound results revealed varying incidences of intracranial hemorrhage: 72.9% in low, 52.5% in medium, and 19.6% in the high proportion groups.

Conclusions

Medium to high levels of breast milk feeding contribute positively to motor and behavioral neurological development in extremely preterm infants and decrease the likelihood of ventricular hemorrhage. However, it does not have a significant effect on the development of behavioral abilities. Due to the limited sample size, the next step will be to expand the sample size and further investigate the extent of the impact on various aspects of the nervous system.
LeTra: a leaf tracking workflow based on convolutional neural networks and intersection over union
Authors: Jurado-Ruiz Federico , Nguyen Thu-Phuong , Peller Joseph , Aranzana María José , Polder Gerrit , Aarts Mark G. M.
Published: January 2024

Background

The study of plant photosynthesis is essential for productivity and yield. Thanks to the development of high-throughput phenotyping (HTP) facilities, based on chlorophyll fluorescence imaging, photosynthetic traits can be measured in a reliable, reproducible and efficient manner. In most state-of-the-art HTP platforms, these traits are automatedly analyzed at individual plant level, but information at leaf level is often restricted by the use of manual annotation. Automated leaf tracking over time is therefore highly desired. Methods for tracking individual leaves are still uncommon, convoluted, or require large datasets. Hence, applications and libraries with different techniques are required. New phenotyping platforms are initiated now more frequently than ever; however, the application of advanced computer vision techniques, such as convolutional neural networks, is still growing at a slow pace. Here, we provide a method for leaf segmentation and tracking through the fine-tuning of Mask R-CNN and intersection over union as a solution for leaf tracking on top-down images of plants. We also provide datasets and code for training and testing on both detection and tracking of individual leaves, aiming to stimulate the community to expand the current methodologies on this topic.

Results

We tested the results for detection and segmentation on 523 Arabidopsis thaliana leaves at three different stages of development from which we obtained a mean F-score of 0.956 on detection and 0.844 on segmentation overlap through the intersection over union (IoU). On the tracking side, we tested nine different plants with 191 leaves. A total of 161 leaves were tracked without issues, accounting to a total of 84.29% correct tracking, and a Higher Order Tracking Accuracy (HOTA) of 0.846. In our case study, leaf age and leaf order influenced photosynthetic capacity and photosynthetic response to light treatments. Leaf-dependent photosynthesis varies according to the genetic background.

Conclusion

The method provided is robust for leaf tracking on top-down images. Although one of the strong components of the method is the low requirement in training data to achieve a good base result (based on fine-tuning), most of the tracking issues found could be solved by expanding the training dataset for the Mask R-CNN model.
cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment
Authors: Zhang Hongying , Liu Yongliang , Liu Jieya , Chen Jinzhu , Wang Jiao , Hua Hui , Jiang Yangfu
Published: January 2024

Cancer is a complex disease resulting from abnormal cell growth that is induced by a number of genetic and environmental factors. The tumor microenvironment (TME), which involves extracellular matrix, cancer-associated fibroblasts (CAF), tumor-infiltrating immune cells and angiogenesis, plays a critical role in tumor progression. Cyclic adenosine monophosphate (cAMP) is a second messenger that has pleiotropic effects on the TME. The downstream effectors of cAMP include cAMP-dependent protein kinase (PKA), exchange protein activated by cAMP (EPAC) and ion channels. While cAMP can activate PKA or EPAC and promote cancer cell growth, it can also inhibit cell proliferation and survival in context- and cancer type-dependent manner. Tumor-associated stromal cells, such as CAF and immune cells, can release cytokines and growth factors that either stimulate or inhibit cAMP production within the TME. Recent studies have shown that targeting cAMP signaling in the TME has therapeutic benefits in cancer. Small-molecule agents that inhibit adenylate cyclase and PKA have been shown to inhibit tumor growth. In addition, cAMP-elevating agents, such as forskolin, can not only induce cancer cell death, but also directly inhibit cell proliferation in some cancer types. In this review, we summarize current understanding of cAMP signaling in cancer biology and immunology and discuss the basis for its context-dependent dual role in oncogenesis. Understanding the precise mechanisms by which cAMP and the TME interact in cancer will be critical for the development of effective therapies. Future studies aimed at investigating the cAMP-cancer axis and its regulation in the TME may provide new insights into the underlying mechanisms of tumorigenesis and lead to the development of novel therapeutic strategies.
Tacrolimus versus mycophenolate for AutoImmune hepatitis patients with incompLete response On first-line therapy (TAILOR study): a study protocol for a phase III, open-label, multicentre, randomised controlled trial
Authors: Stoelinga Anna E. C. , Tushuizen Maarten E. , van den Hout Wilbert B. , Girondo Mar D. M. Rodriguez , de Vries Elsemieke S. , Levens Amar D. , Moes Dirk-Jan A. R. , Gevers Tom J. G. , van der Meer Suzanne , Brouwer Hans T. , de Jonge Hendrik J. M. , de Boer Ynte S. , Beuers Ulrich H. W. , van der Meer Adriaan J. , van den Berg Aad P. , Guichelaar Maureen M. J. , Drenth Joost P. H. , van Hoek Bart ,   on behalf of the Dutch Autoimmune Hepatitis Group, Bakker Sjoerd F. , Vrolijk JM , van der Veek Patrick , van Gerven Nicole F.
Published: January 2024

Background

Autoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. The treatment goal is reaching complete biochemical response (CR), defined as the normalisation of aspartate and alanine aminotransferases and immunoglobulin gamma. Ongoing AIH activity can lead to fibrosis and (decompensated) cirrhosis. Incomplete biochemical response is the most important risk factor for liver transplantation or liver-related mortality. First-line treatment consists of a combination of azathioprine and prednisolone. If CR is not reached, tacrolimus (TAC) or mycophenolate mofetil (MMF) can be used as second-line therapy. Both products are registered for the prevention of graft rejection in solid organ transplant recipients. The aim of this study is to compare the effectiveness and safety of TAC and MMF as second-line treatment for AIH.

Methods

The TAILOR study is a phase IIIB, multicentre, open-label, parallel-group, randomised (1:1) controlled trial performed in large teaching and university hospitals in the Netherlands. We will enrol 86 patients with AIH who have not reached CR after at least 6 months of treatment with first-line therapy. Patients are randomised to TAC (0.07 mg/kg/day initially and adjusted by trough levels) or MMF (max 2000 mg/day), stratified by the presence of cirrhosis at inclusion. The primary endpoint is the difference in the proportion of patients reaching CR after 12 months. Secondary endpoints include the difference in the proportion of patients reaching CR after 6 months, adverse effects, difference in fibrogenesis, quality of life and cost-effectiveness.

Discussion

This is the first randomised controlled trial comparing two second-line therapies for AIH. Currently, second-line treatment is based on retrospective cohort studies. The rarity of AIH is the main issue in clinical research for alternative treatment options. The results of this trial can be implemented in existing international clinical guidelines.

Trial registration

ClinicalTrials.gov NCT05221411. Retrospectively registered on 3 February 2022; EudraCT number 2021–003420-33. Prospectively registered on 16 June 2021.
Safety and tolerability of intravenous immunoglobulin in patients with active dermatomyositis: results from the randomised, placebo-controlled ProDERM study
Authors: Aggarwal Rohit , Schessl Joachim , Charles-Schoeman Christina , Bata-Csörgő Zsuzsanna , Dimachkie Mazen M. , Griger Zoltan , Moiseev Sergey , Oddis Chester V. , Schiopu Elena , Vencovský Jiri , Beckmann Irene , Clodi Elisabeth , Levine Todd ,   the ProDERM investigators
Published: January 2024

Background

Dermatomyositis is an idiopathic inflammatory myopathy characterised by rashes and progressive muscle weakness. The recent ProDERM (Progress in DERMatomyositis) study is the first large randomised, placebo-controlled trial to establish the efficacy and safety of intravenous immunoglobulin (IVIg) in adult patients with dermatomyositis. Objectives of this analysis were to closely examine the safety and tolerability of IVIg in patients from the ProDERM study.

Methods

ProDERM was a double-blind, randomised, placebo-controlled, multicentre, phase 3 study. In the first period (weeks 0–16), adults with active dermatomyositis received 2.0 g/kg IVIg (Octagam 10%; Octapharma AG) or placebo every 4 weeks. In the open-label extension period (weeks 16–40), all patients received IVIg for 6 additional cycles; dose reduction (1.0 g/kg) was permitted if patients were stable. Treatment-emergent adverse events (TEAEs) were documented.

Results

The 95 patients enrolled were randomised to receive IVIg (N = 47) or placebo (N = 48) in the first period, with 5 switching from placebo to IVIg. Overall, 664 IVIg infusion cycles were administered. During the first period, 113 TEAEs were possibly/probably related to treatment in 30/52 patients (57.7%) receiving IVIg and 38 in 11 patients (22.9%) on placebo. Eight patients discontinued therapy due to IVIg-related TEAEs. Eight thromboembolic events (TEEs) occurred in six patients on IVIg; six in five patients were deemed possibly/probably related to IVIg. Patients with TEEs exhibited more baseline TEE risk factors than those without TEEs (2.4–15.2-fold higher). Lowering infusion rate reduced the rate of TEEs, and none occurred at the lower IVIg dose. No haemolytic transfusion reactions or deaths occurred.

Conclusions

Results from this study demonstrate that IVIg has a favourable safety profile for treatment of adult dermatomyositis patients and provides evidence that will help to inform treatment choice for these patients. Dermatomyositis patients receiving high-dose IVIg should be monitored for TEEs, and a low rate of infusion should be used to minimise TEE risk, particularly in those with pre-existing risk factors.

Trial registration

ProDERM study (NCT02728752).
Children systemic lupus erythematosus-associated pancreatitis
Authors: Zhang Dan , Lai Jianming , Su Gaixiu , Zhu Jia , Min  , Kang  , Li Ming , Xu Yingjie , Meng Li
Published: January 2024

Objective

To early recognise and improve the prognosis of children systemic lupus erythematosus (cSLE)-associated pancreatitis by summarising and analysing clinical features and prognosis data from 12 cases.

Methods

Retrospective analysis of clinical data from 12 cases of cSLE-associated pancreatitis diagnosed and treated from January 2016 to December 2021 at hospitals such as Children’s Hospital of Capital Institute of Paediatrics.

Results

The median SLEDAI-2K score for disease activity was 18.00 (range 12.25–21.00) in the case group and 10.00 (range 7.00–18.00) in the control group, with a statistically significant difference (P < 0.05) between the two groups. The case group had a higher proportion of abdominal pain, vomiting, abdominal distension, pleural effusion, Raynaud’s phenomenon (RP), splenic infarction, and concurrent macrophage activation syndrome (MAS) than the control group, with a statistically significant difference (P < 0.05). Serum ferritin (SF), alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), amylase, and increased 24-h urine protein levels were statistically different between the two groups (P < 0.05); platelet counts (PLT) reduction was also statistically different (P < 0.05). The case group had a higher proportion of methylprednisolone pulse therapy, cyclophosphamide pulse therapy during remission induction, and therapeutic plasma exchange than the control group, with a statistically significant difference (P < 0.05) between the two.

Conclusion

CSLE-associated pancreatitis has a high fatality rate. The presence of RP, splenic infarction, pleural effusion, and MAS warrants attention from clinicians regarding the possibility of pancreatitis. Once pancreatitis is detected, the primary disease needs active treatment for better prognosis.
Vitamin C facilitates direct cardiac reprogramming by inhibiting reactive oxygen species
Authors: Fang Juntao , Yang Qiangbing , Maas Renée G. C. , Buono Michele , Meijlink Bram , Lotgerink Bruinenberg Dyonne , Benavente Ernest Diez , Mokry Michal , van Mil Alain , Qian Li , Goumans Marie-José , Schiffelers Raymond , Lei Zhiyong , Sluijter Joost P. G.
Published: January 2024

Background

After myocardial infarction, the lost myocardium is replaced by fibrotic tissue, eventually progressively leading to myocardial dysfunction. Direct reprogramming of fibroblasts into cardiomyocytes via the forced overexpression of cardiac transcription factors Gata4, Mef2c, and Tbx5 (GMT) offers a promising strategy for cardiac repair. The limited reprogramming efficiency of this approach, however, remains a significant challenge.

Methods

We screened seven factors capable of improving direct cardiac reprogramming of both mice and human fibroblasts by evaluating small molecules known to be involved in cardiomyocyte differentiation or promoting human-induced pluripotent stem cell reprogramming.

Results

We found that vitamin C (VitC) significantly increased cardiac reprogramming efficiency when added to GMT-overexpressing fibroblasts from human and mice in 2D and 3D model. We observed a significant increase in reactive oxygen species (ROS) generation in human and mice fibroblasts upon Doxy induction, and ROS generation was subsequently reduced upon VitC treatment, associated with increased reprogramming efficiency. However, upon treatment with dehydroascorbic acid, a structural analog of VitC but lacking antioxidant properties, no difference in reprogramming efficiency was observed, suggesting that the effect of VitC in enhancing cardiac reprogramming is partly dependent of its antioxidant properties.

Conclusions

Our findings demonstrate that VitC supplementation significantly enhances the efficiency of cardiac reprogramming, partially by suppressing ROS production in the presence of GMT.

Graphical abstract
The infimum values of two probability functions for the Gamma distribution
Authors: Sun Ping , Hu Ze-Chun , Sun Wei
Published: January 2024

Let α, β be positive real numbers and let $X_{\alpha ,\beta}$

X

α
,
β

be a Gamma random variable with shape parameter α and scale parameter β. We study infimum values of the function $(\alpha ,\beta )\mapsto P\{X_{\alpha ,\beta}\le \kappa E[X_{\alpha ,\beta}] \}$
(
α
,
β
)
↦
P
{

X

α
,
β

≤
κ
E
[

X

α
,
β

]
}
for any fixed $\kappa >0$
κ
>
0
and the function $(\alpha ,\beta )\mapsto P\{|X_{\alpha ,\beta}-E[X_{\alpha ,\beta}]| \le \sqrt{\operatorname{Var}(X_{\alpha ,\beta})}\}$
(
α
,
β
)
↦
P
{
|

X

α
,
β

−
E
[

X

α
,
β

]
|
≤

Var
(

X

α
,
β

)

}
. We show that $\inf_{\alpha ,\beta}P\{X_{\alpha ,\beta}\le E[X_{\alpha ,\beta}]\}= \frac{1}{2}$

inf

α
,
β

P
{

X

α
,
β

≤
E
[

X

α
,
β

]
}
=

1

2

and $\inf_{\alpha ,\beta}P\{|X_{\alpha ,\beta}-E[X_{\alpha ,\beta}]|\le \sqrt{\operatorname{Var}(X_{\alpha ,\beta})}\}=P\{|Z|\le 1\}\approx 0.6827$

inf

α
,
β

P
{
|

X

α
,
β

−
E
[

X

α
,
β

]
|
≤

Var
(

X

α
,
β

)

}
=
P
{
|
Z
|
≤
1
}
≈
0.6827
, where Z is a standard normal random variable.
Knowledge, attitudes and practices towards community-acquired pneumonia and COVID-19 among general population: a cross-sectional study
Authors: Hong Er , Mao Jia , Ke Zhicheng , Tao Wei
Published: January 2024

Background

This study aimed to assess the knowledge, attitudes, and practices (KAP) of the general population to community-acquired pneumonia (CAP) and COVID-19.

Methods

A cross-sectional study was conducted between September 2022 and February 2023, involving the general population from Ningbo Municipal Hospital of Traditional Chinese Medicine with a self-developed questionnaire.

Results

A total of 637 valid questionnaires were collected, with the majority of participants being female (62.48%). The mean score for knowledge, attitudes, and practices were 7.60 ± 2.39 (possible range: 0–12), 43.20 ± 4.57 (possible range: 11–55), and 34.57 ± 4.95 (possible range: 10–50), respectively. Multivariate logistic regression analysis indicated that master’s degree or above (OR = 6.04, 95% CI: 1.80-20.31, P = 0.004) and occupation in business or service careers (OR = 0.28, 95% CI: 0.17–0.48, P < 0.001) were independent associated with knowledge. The knowledge (OR = 1.32, 95%CI: 1.20–1.44, P < 0.001) and female gender (OR = 1.48, 95%CI: 1.03–2.14, P = 0.036) were independently associated with positive attitudes. Attitudes (OR = 1.34, 95%CI: 1.26–1.43, P < 0.001) and a monthly household income greater than 20,000 RMB (OR = 0.31, 95%CI: 0.15–0.64, P = 0.001) were independent associated with practices. Pearson correlation analysis revealed that knowledge positively correlated with attitude scores (r = 0.348, P < 0.001) and practice scores (r = 0.259, P < 0.001), and attitude and practice scores were also positively correlated (r = 0.563, P < 0.001). Structural equation modeling showed that knowledge predicted attitudes (β = 0.67, P < 0.001) and practices (β = 0.17, P = 0.017), while attitudes predicted practices (β = 0.58, P < 0.001).

Conclusion

General population had moderate knowledge, positive attitudes and average practices towards CAP and COVID-19.
The rare Fuegian fox (Lycalopex culpaeus) from the Tierra del Fuego Archipelago: history of discovery, geographic distribution, and socio-ecological aspects
Authors: Jaksic Fabian M. , Zurita Carlos , Briceño Cristóbal , Jiménez Jaime E.
Published: January 2024

Background

The Fuegian fox (Lycalopex culpaeus) is a rare inhabitant of the Tierra del Fuego Archipelago on account of: (a) It is the southernmost Canid in the world. (b) It is the second largest, heaviest, and tallest native Canid in South America. (c) It is currently scarce in northern Tierra del Fuego. (d) It may have been tamed by the Selk’nam natives.

Methods and results

Based on chronicles and scientific reports we document the timeline since discovery of the distinctive and island-confined Fuegian fox. We pay attention to its patchwork distribution within the Fuegian archipelago, with populations spread on the large Tierra del Fuego Island (Fuegia) and on two smaller ones, Hoste and Gable. This fox seems to have disappeared recently from the latter and historic records from Navarino Island are dubious. We provide new distributional records and unpublished photographs. Among the socio-ecological aspects studied, we highlight the relationships of this fox with two local indigenous people: The Yahgan and the Selk´nam.

Discussion

The introduction of sheep Ovis aries in 1885 and the ensuing persecution of its putative predators apparently caused the fox decline from the northern half of Fuegia. The introduction of the continental Chilla fox Lycalopex griseus in 1951 further impacted the Fuegian fox, apparently by competition for food but perhaps also by diseases. It is currently concentrated in the southern half of Tierra del Fuego Island. The possibility that the Selk’nam introduced this fox from the mainland and that they tamed it, is also discussed.
SPiRIT study protocol (Shoulder Pain: Randomised trial of Injectable Treatments): a randomised feasibility and pilot study of autologous protein solution (APS) vs corticosteroids for treating subacromial shoulder pain
Authors: Howard A. , Woods A. , Rombach I. , Achten J. , Appelbe D. , Athwal A. , Jones E. , Draper K. , Gwilym S.
Published: January 2024

Background

The management of subacromial shoulder pain represents a significant challenge and is typically managed through either physiotherapy, joint injection or surgical intervention. Recent surgical trials have questioned the efficacy and there is a need to improve the evidence base for the non-surgical management of this condition.

The study aims to provide evidence of the feasibility of conducting a randomised controlled trial to compare the efficacy of autologous protein solution (APS) against the current standard of care, corticosteroid injection (CSI) for subacromial shoulder pain. Autologous protein solution (APS) is a blood-derived biological injection which has been shown to have anti-inflammatory effects.

Methods

A parallel-group two-arm randomised control trial will be conducted, comparing APS and CSI for shoulder pain. Fifty patients will be recruited. Feasibility will be assessed by examination of the conversion rate of eligible participants to the total number of participants recruited, whether it is possible to collect the appropriate outcome measures and the levels of retention/data compliance at follow-up dates.

Discussion

CSI is the mainstay of conservative management of subacromial shoulder pain. Trials and systematic reviews have reported differing conclusions, but the consensus view is that any benefits seen from CSI use are most likely to be short-term and there remains a significant number of patients who go on to have surgical intervention despite CSI.

Biological injections, such as APS are being increasingly used, in the anticipation they may offer improved longer lasting outcomes for shoulder pain. However, the evidence to demonstrate the comparative efficacy of CSI versus APS does not currently exist. If feasible, a fully powered study will offer clarity to the treatment pathway of thousands of patients each year with subacromial pain.

Trial registration

The study is funded by the National Institute for Health Research–Research for Patient Benefit, NIHR 201473, Trial Registration Number (ISRCTN12536844: SPiRIT. Shoulder pain: randomised trial of injectable treatments–date of Registration 15/9/2021). Protocol Version V1.0_30Jul2021. IRAS Project ID: 294,982.
Participant comprehension and acceptability of enhanced versus text-only electronic informed consent: an innovative qualitative pilot study
Authors: Corneli Amy , Starling Summer , Choi Yujung , Vosylius Jurgis , Madre Leanne , Mackinnon Andrew , Tenaerts Pamela
Published: January 2024

Background

The use of electronic informed consent (eIC) in decentralized trials offers a pragmatic approach to enrolling participants across multiple geographic areas.

Methods

Using a randomized, cross-over study design, we conducted a qualitative descriptive evaluation of two eIC approaches—text-only eIC and enhanced eIC—in a mock hypertension Phase III clinical trial. We assessed participant comprehension and acceptability (usability, satisfaction, and eIC preference).

Results

A total of 24 individuals with hypertension participated in the study: 12 reviewed the text-only eIC first, followed by the enhanced eIC, and 12 reviewed the enhanced eIC first, followed by the text-only eIC. The study population was diverse in gender, age, race, and geographic location. We found no descriptive differences in participant comprehension and satisfaction between the two eIC approaches. However, more participants preferred the enhanced eIC, and participants indicated that the digital elements were personable and made them feel more informed, engaged, comfortable, and prepared to participate in clinical research.

Conclusions

Our findings suggest that enhancing the eIC process with digital elements may have beneficial outcomes among potential participants beyond comprehension and satisfaction.
Nematode egg parasitic fungus, Purpureocillium lilacinum: efficacy of indigenous strains for the management of Meloidogyne incognita in chickpea
Authors: Rajendran Jagadeeswaran , Dubey Jyotirmay , Kumar Vaibhav , Sujayanand G. K.
Published: January 2024

Background

Nematode egg parasitic fungus,Purpureocillium lilacinumis the most effective biocontrol agent and has been widely used commercially in many countries for the management of root-knot nematode,Meloidogyne incognita. Availability of indigenous potential strains specific to an agro ecosystem is very crucial for their successful commercial exploitation for suppression of nematode population. Hence, an attempt was made to isolate, characterize, evaluate and identify potential indigenous strains ofP. lilacinumfrom pulse ecosystem for root-knot nematode management in chickpea.

Results

The fungal colony was initially white and when spore was formed it turned into pink colour in 72 to 96 h. Hyphae was hyaline and septate, conidiophore was blunt, and phialides were with wide base and long neck bearing round to oval conidia in chains. Molecular identification of the species,P. lilacinumwas carried out based on ITS1-5.8S-ITS2 region of the genomic DNA. In vitro bioassay of cultural filtrates on juvenile mortality revealed that maximum percentage of mortality was observed in IIPR-Pl-11 (88.36%). Spectrophotometric assay on chitinolytic activity showed that the strain IIPR-Pl-11 produced significantly high chitinolytic activity, chitinase enzyme and total protein content (0.139, 51.1 and173.75 µg/ml at 5days); (0.245, 90.1 and 272.67 µg/ml at 10 days) and (0.273, 100.4 and 306.25 µg/ml), respectively, at 15 days of culturing in colloidal chitin-enriched medium C. 2D gel electrophoresis of the crude chitinase suspension showed the presence of chitinase (32, 46 kDa size) in the sample from chitinase-induced medium C. In vitro bioassay of the cultural filtrates of the fungus grown in chitin-enriched medium C on inhibition on egg hatching revealed that the highest percent inhibition on egg hatching showed by IIPR-Pl-8 strain at 5 days of inoculation (42.6%) and IIPR-Pl-11 at 10 and 20 days of inoculation (62.80 and 93.50%), respectively. In vivo pot experiment revealed that among all strains, IIPR-Pl-11 was efficient in promoting plant growth very effectively by reducing gall number (41.3 per plant), egg mass (28.3 per plant) and soil population (284.3 per 200cc of soil) compared to control.

Conclusion

P. lilacinumstrain IIPR-Pl-11 was the highest potential strain from pulse rhizosphere for the management of root-knot nematode,M. incognitain chickpea.
Mobilising transformative community-based climate change adaptation
Authors: Nath Subhashree
Published: January 2024

Under-resourced and marginalised communities often have limited government support, and therefore, must decide by themselves if and how they adapt to the uncertainties of climate change. Community-based climate change adaptation (CbA) forms a plausible approach here. In practice, however, CbA projects often fail to address the underlying causes of vulnerability like power relations and sociocultural structures that influence adaptation measures adopted and outcomes. In response, this perspective paper explores the concept of transformative community-based climate change adaption (TCbA), a reflexive approach that focuses on empowering communities by reframing the decision-making context. It discusses pathways of mobilising this shift to transformative CbA in three steps: (1) specifying the characteristics of a TCbA; (2) exploring the leverage points to mobilise it, and (3) recommending a set of actions and processes that facilitate co-decided interventions at the identified leverage points. These leverage points include "the structure of information flow", "rules of the system" and “power to change system structure or self-organise". The paper concludes by emphasising that the shift to transformative CbA begins when facilitators and members of the community undertaking a CbA project are reflexive about how the societal context of decision processes, like power relations, influence community adaptation decision-making, planning and implementation.
A study on textbook use and its effects on students’ academic performance
Authors: Li Fangfang , Wang Lei
Published: January 2024

Curriculum education reforms are being carried out in various countries, in which great research interest has been generated in the use of textbooks and the effectiveness of their use. In this study, the focus is on the actual use of textbooks by the first students to use the 2019 edition of general high school chemistry textbooks (students graduating in summer 2022 and summer 2023) and its relationship with students’ interest and attitudes, and their academic achievements in chemistry. In this study, two questionnaires and one test with a standardized reliability and validity were developed. A quantitative analysis method was used to determine how the students (N = 2874) used the new textbooks. Correlation analysis was used to explore the correlation between the use of new textbooks and students’ interest, attitudes, and academic achievements among students (N = 250).

The results show that students rate the new textbooks highly, but there is still much room for improvement in the functional value of the new textbooks. Correlation analysis and regression analyse showed that there was a significant correlation between students’ use of chemistry textbooks and their interest and attitudes, but the correlation between them and their academic achievements in chemistry was not directly significant. At the same time, the use of the new textbooks revealed a different dynamic and atmosphere in the chemistry classroom, with more classroom student activities taking place and students being able to participate more deeply and actively in them. This contributed more to students’ interest and attitudes, and improved their performance in chemistry. In this study, we strongly argue for the importance and value of textbook use for student learning on the one hand and for the enrichment of student-centred textbook use research on the other.