bluuebunny/crossref_metadata_2025 huggingface dataset:
Amblyopic astigmatism characteristics and surgical outcomes in younger children with severe congenital ptosis after frontalis suspension surgery
Authors: Tan Yilan , Wang Xilang , Fu Jing , Tang Jing , Xiang Jianbo , Tao Lijuan , Luo Yulin
Published: February 2023

Background

To examine the astigmatism characteristics and surgical outcomes in patients with unilateral severe congenital ptosis following frontalis suspension surgery.

Methods

We included 53 congenital ptosis patients who underwent frontalis suspension surgery in Hunan Children's Hospital. Each patient underwent a refractive examination before and after surgery to assess astigmatism. We also evaluated the effects and complications associated with the procedure.

Results

Degree of astigmatism in ptotic and fellow eyes was − 1.45 ± 0.59 D and − 0.66 ± 0.51 D before surgery. Ratio of severe astigmatism in ptotic and fellow eyes was 51.3 and 12.8%. The fellow eyes presented with with-the-rule astigmatism (WR; 71.8%) and against-the-rule astigmatism (AR; 20.5%) types, with no cases of oblique astigmatism (OA). Ptotic eyes demonstrated higher frequencies of AR (59.0%) and OA (10.2%) than did fellow eyes. Furthermore, the former showed increased astigmatism, followed by a gradual decrease at the 6-month, before significantly decreasing at the 1-year postoperatively. The ratio of postoperative AR and OA astigmatism cases in ptotic eyes decreased to 35.9 and 7.7% 1 month postoperatively. However, there was a postoperative increase in the WR ratio from 30.8 to 56.4% after 1 month. Kaplan-Meier survival analysis showed a success rate of 81.4% at 6 months and 62.9% at 12 months which was influenced by the following complications: suture reaction, epithelial keratopathy, infection and granuloma, lid lag, and recurrence.

Conclusion

Monocular congenital ptosis could develop severe astigmatism and higher frequency of AR or OA, early surgery may ameliorate astigmatic amblyopia.
Exposure to interparental violence and intimate partner violence among women in Papua New Guinea
Authors: Ahinkorah Bright Opoku , Aboagye Richard Gyan , Cadri Abdul , Salihu Tarif , Seidu Abdul-Aziz , Yaya Sanni
Published: February 2023

Introduction

Evidence suggests that childhood exposure to interparental violence increases the risk of intimate partner violence (IPV) experience or perpetration in adolescence or adulthood. However, it is unclear if exposure to interparental violence increases the risk of IPV among women in Papua New Guinea. This study, therefore, seeks to fill this gap in the literature by examining the association between childhood exposure to interparental violence and IPV among women in Papua New Guinea.

Methods

We used data from the most recent 2016–18 Papua New Guinea Demographic and Health Survey. We included 3,512 women in our analyses. Past-year experience of IPV was the outcome variable in this study. Exposure to interparental violence was the key explanatory variable. We used a multilevel binary logistic regression to examine the association between exposure to interparental violence and IPV.

Results

We found a higher probability of experiencing IPV among women exposed to interparental violence [aOR = 1.45, 95% CI = 1.13, 1.86] relative to women who were not exposed. Furthermore, we found that women living in rural areas had a lower likelihood of IPV experience [aOR = O.50, 95% CI = 0.32, 0.80] compared to those in urban settings. Finally, a greater odd of IPV experience was found among women staying in the Highlands Region [aOR = 1.44, 95% CI = 1.06, 1.96] compared to those staying in the Southern Region.

Conclusion

Exposure to interparental violence was found to be significantly associated with IPV among women in Papua New Guinea. The findings of this study suggest the need for proven operational strategies to reduce IPV, such as improving anti-IPV laws in Papua New Guinea. We recommend the development and implementation of intercession strategies to reduce the experience and justification of violence among women exposed to interparental violence. In addition, health professionals should implement counseling and health education initiatives to tackle the consequences of IPV on women's well-being.
What is nursing professionalism? a concept analysis
Authors: Cao Huili , Song Yejun , Wu Yanming , Du Yifei , He Xingyue , Chen Yangjie , Wang Qiaohong , Yang Hui
Published: February 2023

Background

Nursing professionalism plays an important role in clinical nursing. However, a clear conceptual understanding of nursing professionalism is lacking.

Method

Walker and Avant’s strategy was used to analyse the concept of nursing professionalism. We searched electronic databases, including PubMed, Scopus, and CINAHL, for studies published from 1965 to 2021. Quantitative or qualitative studies published in English that focused on nursing professionalism were included in the study.

Results

The three attributes of nursing professionalism are multidimensional, dynamic, and culture oriented. Based on the analysis, nursing professionalism is defined as providing individuals care based on the principles of professionalism, caring, and altruism.

Conclusions

This study offers a theoretical definition and conceptual model of nursing professionalism that may be applied to develop standardized assessment tools or nursing professionalism training programs.
A nontuberculous mycobacterium could solve the mystery of the lady from the Franciscan church in Basel, Switzerland
Authors: Sarhan Mohamed S. , Wurst Christina , Tzankov Alexandar , Bircher Andreas J. , Wittig Holger , Briellmann Thomas , Augsburger Marc , Hotz Gerhard , Zink Albert , Maixner Frank
Published: February 2023

Background

In 1975, the mummified body of a female has been found in the Franciscan church in Basel, Switzerland. Molecular and genealogic analyses unveiled her identity as Anna Catharina Bischoff (ACB), a member of the upper class of post-reformed Basel, who died at the age of 68 years, in 1787. The reason behind her death is still a mystery, especially that toxicological analyses revealed high levels of mercury, a common treatment against infections at that time, in different body organs. The computed tomography (CT) and histological analysis showed bone lesions in the femurs, the rib cage, and the skull, which refers to a potential syphilis case.

Results

Although we could not detect any molecular signs of the syphilis-causing pathogenTreponema pallidumsubsp. pallidum, we realized high prevalence of a nontuberculous mycobacterium (NTM) species in brain tissue sample. The genome analysis of this NTM displayed richness of virulence genes and toxins, and similarity to other infectious NTM, known to infect immunocompromised patients. In addition, it displayed potential resistance to mercury compounds, which might indicate a selective advantage against the applied treatment. This suggests that ACB might have suffered from an atypical mycobacteriosis during her life, which could explain the mummy’s bone lesion and high mercury concentrations.

Conclusions

The study of this mummy exemplifies the importance of employing differential diagnostic approaches in paleopathological analysis, by combining classical anthropological, radiological, histological, and toxicological observations with molecular analysis. It represents a proof-of-concept for the discovery of not-yet-described ancient pathogens in well-preserved specimens, using de novo metagenomic assembly.
Palmitoyl-glucosamine co-micronized with curcumin for maintenance of meloxicam-induced pain relief in dogs with osteoarthritis pain
Authors: della Rocca Giorgia , Schievano Carlo , Di Salvo Alessandra , Conti Maria Beatrice , della Valle Maria Federica
Published: February 2023

Background

Osteoarthritis (OA) pain is the number one cause of chronic pain in dogs. Multimodal treatment, including combining safe and effective nutritional interventions with non-steroidal anti-inflammatory drugs (NSAIDs), is currently considered one of the most appropriate choices for managing OA pain. Palmitoyl-glucosamine is a feed material belonging to the ALIAmide family, whose parent molecule is the prohomeostatic lipid amide N-palmitoyl-ethanolamine. Curcumin is a promising plant antioxidant. The present study aimed at investigating whether 18-week dietary integration with palmitoyl-glucosamine co-micronized with curcumin was able to maintain pain relief in dogs with OA-associated chronic pain receiving meloxicam (1.5 mg/ml oral suspension) on a tapering regimen (progressive 25% decrease of the original 0.1 mg/kg/day dose, on a biweekly basis) during the first 8 weeks of treatment. Pain was assessed both by the owners and veterinary surgeons, with the first using both subjective evaluation and validated metrology instruments—i.e., Helsinki Chronic Pain Index (HCPI) and Canine Brief Pain Inventory (CBPI)—while the second rating the severity of lameness and pain on palpation on two previously used 5-point scales.

Results

A total of fifty-eight dogs with OA chronic pain entered the uncontrolled study. Pain on HCPI was considered severe at baseline (range 18–39). Based on owner’s assessment, 90% of dogs who responded to meloxicam at the full-dose regimen could reduce meloxicam up to 25% of the original dose without experiencing pain worsening. Moreover, 75% of dogs was assessed as having no pain increase ten weeks after meloxicam withdrawal. A statistically significant decrease of pain severity as scored by HCPI (P < 0.0001) was observed two and ten weeks after meloxicam withdrawal compared to study entry (17.0 ± 1.05 and 15.1 ± 1.02, respectively, vs 29.0 ± 0.74; mean ± SEM). After meloxicam withdrawal, no statistically significant change in the CBPI scores was recorded. Pain on palpation and lameness significantly changed to less severe distributions along the study period (P < 0.0001).

Conclusion

The findings appear to suggest that dietary integration with palmitoyl-glucosamine co-micronized with curcumin was able to maintain meloxicam-induced pain relief in dogs with severe OA chronic pain.
CXCR3 predicts the prognosis of endometrial adenocarcinoma
Authors: Dong He , Sun Mengzi , Li Hua , Yue Ying
Published: February 2023

Objectives

Currently, endometrial adenocarcinoma lacks an effective prognostic indicator. This study was to develop and validate a gene biomarker and a nomogram to predict the survival of endometrial adenocarcinoma, explore potential mechanisms and select sensitive drugs.

Methods

425 endometrial adenocarcinoma cases with RNA sequencing data from TCGA were used to identify the most immune-related module by WGCNA. As an external test set, 103 cases from GSE17025 were used. Immune-related genes were downloaded from Innate DB. The three sets of data were used to identify the prognostic genes. Based on 397 cases with complete clinical data from TCGA, randomly divided into the training set (n = 199) and test set (n = 198), we identified CXCR3 as the prognostic gene biomarker. Age, grade, FIGO stage, and risk were used to develop and validate a predictive nomogram. AUC, C-index, calibration curve and K–M estimate evaluated the model's predictive performance. KEGG enrichment analysis, immune functions, TMB, the effectiveness of immunotherapy, and drug sensitivity between the high-risk and low-risk groups.

Results

CXCR3 was identified as a prognostic biomarker. We calculated the risk score and divided the cases into the high-risk and low-risk groups by the median value of the risk score. The OS of the high-risk group was better than the low-risk group. The risk was the prognostic indicator independent of age, grade, and FIGO stage. We constructed the nomogram including age, grade, FIGO stage, and risk to predict the prognosis of endometrial adenocarcinoma. The top five KEGG pathways enriched by the DEGs between the high- and low-risk groups were viral protein interaction with cytokine and cytokine receptors, cytokine-cytokine receptor interaction, chemokine signaling pathway, natural killer cell-mediated cytotoxicity, and cell adhesion molecules. We analyzed the difference in immune cells and found that CD8+ T cells, activated CD4+ T cells, T helper cells, monocytes, and M1 macrophages were infiltrated more in the low-risk group. However, M0 macrophages and activated dendritic cells were more in the high-risk group. The immune function including APC coinhibition, APC costimulation, CCR, checkpoint, cytolytic activity, HLA, inflammation-promoting, MHC-I, parainflammation, T cell coinhibition, T cell costimulation, type I-IFN-response, and type II-IFN-response were better in the low-risk group. TMB and TIDE scores were both better in the low-risk group. By ‘the pRRophetic’ package, we found 56 sensitive drugs for different risk groups.

Conclusion

We identified CXCR3 as the prognostic biomarker. We also developed and validated a predictive nomogram model combining CXCR3, age, histological grade, and FIGO stage for endometrial adenocarcinoma, which could help explore the precise treatment.
The chromatin-associated RNAs in gene regulation and cancer
Authors: Tang Jun , Wang Xiang , Xiao Desheng , Liu Shuang , Tao Yongguang
Published: February 2023

Eukaryotic genomes are prevalently transcribed into many types of RNAs that translate into proteins or execute gene regulatory functions. Many RNAs associate with chromatin directly or indirectly and are called chromatin-associated RNAs (caRNAs). To date, caRNAs have been found to be involved in gene and transcriptional regulation through multiple mechanisms and have important roles in different types of cancers. In this review, we first present different categories of caRNAs and the modes of interaction between caRNAs and chromatin. We then detail the mechanisms of chromatin-associated nascent RNAs, chromatin-associated noncoding RNAs and emerging m6A on caRNAs in transcription and gene regulation. Finally, we discuss the roles of caRNAs in cancer as well as epigenetic and epitranscriptomic mechanisms contributing to cancer, which could provide insights into the relationship between different caRNAs and cancer, as well as tumor treatment and intervention.
Longitudinal associations of movement behaviours with body composition and physical fitness from 4 to 9 years of age: structural equation and mediation analysis with compositional data
Authors: Migueles Jairo H. , Delisle Nyström Christine , Dumuid Dorothea , Leppänen Marja H. , Henriksson Pontus , Löf Marie
Published: February 2023

Background

The associations of movement behaviours (physical activity [PA], sedentary behaviour [SB], and sleep) with body composition and physical fitness from pre-school to childhood, as well as the direction of the associations, could provide important information for healthy lifestyle promotion in children. This study investigated the longitudinal and bidirectional associations of movement behaviours with body composition and physical fitness measured at 4 and 9 years of age.

Methods

This longitudinal study included baseline (n = 315, 4.5 [SD = 0.1] years) and follow-up data (n = 231, 9.6 [SD = 0.1] years) from the MINISTOP study. Movement behaviours were measured for 7 days using wrist-worn accelerometers, body composition with air-displacement plethysmography, and physical fitness with the ALPHA health-related fitness test battery. Cross-lagged panel models and mediation analyses were performed in combination with compositional data analysis.

Results

We did not observe direct associations of the movement behaviours at 4 years with either body composition or physical fitness at 9 years (all P > 0.05). However, fat mass index at 4 years was negatively associated with vigorous PA (VPA), relative to remaining behaviours (VPA, β = − 0.22, P = 0.002) and light PA (LPA), relative to SB and sleep (β = − 0.19, P = 0.016) at 9 years. VPA (relative to remaining), moderate PA (MPA) (relative to LPA, SB, and sleep), and SB (relative to sleep) tracked from 4 to 9 years (all β ≥ 0.17, all P < 0.002), and these behaviours shared variance with fat mass index (all|β| ≥ 0.19, all P < 0.019), and aerobic, motor, and muscular fitness (all|β| ≥ 0.19, all P < 0.014) at 9 years. Mediation analysis suggested that the tracking of VPA (relative to remaining behaviours) from 4 to 9 years was negatively associated with fat mass index (β ≥ − 0.45, P = 0.012), and positively with aerobic fitness at 9 years (β ≥ 1.64, P = 0.016).

Conclusion

PA and SB tracked from the pre-school years into childhood. Fat mass index at 4 years of age was negatively associated with VPA (relative to remaining behaviours) and LPA (relative to SB and sleep) at 9 years of age. The tracking of VPA was associated with lower fat mass index and higher aerobic fitness at 9 years of age. These findings suggest that higher levels of VPA in pre-school age, if maintained throughout childhood, may support the development of healthy body composition and aerobic fitness levels in later childhood.
Shorter sleep among adolescents is associated with lower fruit and vegetable consumption the following day
Authors: Winpenny Eleanor M. , Rowthorn Harriet , Hollidge Stefanie , Westgate Kate , Goodyer Ian M. , Brage Soren , van Sluijs Esther M. F.
Published: February 2023

Abstract

Background

Insufficient sleep has been associated with weight gain and metabolic dysregulation, with one suggested mechanism being through reduction in diet quality. Experimental evidence supports a causal effect of sleep timings on diet but this may not be applicable to a free-living adolescent population. In this analysis we use daily measures of sleep timings and diet quality, to examine the effect of sleep duration and timing on diet quality the following day among free-living adolescents.

Methods

The ROOTS study is a prospective cohort recruited from secondary schools in Cambridgeshire and Suffolk (UK). Participants (n = 815) at mean age 15.0y (SD 0.3y) completed a diet diary and wore a combined heart rate and accelerometer device over 4 consecutive days. Sleep duration and timing (midpoint) were derived from acceleration and heart rate traces, while daily energy density and fruit and vegetable intake were calculated from dietary data. Analyses were performed at day-level (1815 person-days). Multilevel random effects models were used to test associations between sleep each night and subsequent day diet, with daily sleep and diet measures nested within individuals and schools, and adjusted for day-level and individual-level confounding variables.

Results

Adolescents slept a mean of 7.88 hrs (SD 1.10) per night, reporting a mean energy density of 2.12 kcal/g (SD 0.48) and median energy-adjusted daily fruit and vegetable intake of 137.3 g (IQR 130.4). One hour shorter sleep duration was associated with lower intake of fruit and vegetables (-6.42 g, 95%CI -1.84, -10.99) the following day. An association with higher dietary energy density (0.016 kcal/g, 95%CI 0.034, -0.002) the following day was observed but did not reach statistical significance. Sleep timing was not associated with either fruit and vegetable intake (-2.52 g/d, 95%CI -7.66, 2.62) or dietary energy density (-0.001 kcal/g, 95%CI -0.022, 0.020).

Conclusions

Our observational findings from a free-living adolescent population support the experimental evidence for a causal role of sleep on diet, with shorter sleep duration at night leading to a small decrease in diet quality the following day. These findings support experimental evidence to suggest inclusion of sleep duration as one component of interventions designed to improve diet quality and weight status in adolescents.
Association between sleep duration and metabolic syndrome: linear and nonlinear Mendelian randomization analyses
Authors: Liang Yannis Yan , Chen Jie , Peng Miaoguan , Zhou Jiajin , Chen Xinru , Tan Xiao , Wang Ningjian , Ma Huan , Guo Lan , Zhang Jihui , Wing Yun-Kwok , Geng Qingshan , Ai Sizhi
Published: February 2023

Background

Observational studies have found that both short and long sleep duration are associated with increased risk of metabolic syndrome (MetS). This study aimed to examine the associations of genetically determined sleep durations with MetS and its five components (i.e., central obesity, high blood pressure, dyslipidemia, hypertriglyceridemia, and hyperglycemia) among a group of elderly population.

Methods

In 335,727 participants of White British from the UK Biobank, linear Mendelian randomization (MR) methods were first employed to examine the causal association of genetically predicted continuous sleep duration with MetS and its each component. Nonlinear MR analyses were performed to determine the nonlinearity of these associations. The causal associations of short and long sleep duration with MetS and its components were further assessed by using genetic variants that associated with short (≤ 6 h) and long sleep (≥ 9 h) durations.

Results

Linear MR analyses demonstrated that genetically predicted 1-h longer sleep duration was associated with a 13% lower risk of MetS, a 30% lower risk of central obesity, and a 26% lower risk of hyperglycemia. Non-linear MR analyses provided evidence for non-linear associations of genetically predicted sleep duration with MetS and its five components (all P values < 0.008). Genetically predicted short sleep duration was moderately associated with MetS and its four components, including central obesity, dyslipidemia, hypertriglyceridemia, and hyperglycemia (all P values < 0.002), whereas genetically long sleep duration was not associated with MetS and any of its components.

Conclusions

Genetically predicted short sleep duration, but not genetically predicted long sleep duration, is a potentially causal risk factor for MetS.

Graphical Abstract
Robust SNP-based prediction of rheumatoid arthritis through machine-learning-optimized polygenic risk score
Authors: Lim Ashley J. W. , Tyniana C. Tera , Lim Lee Jin , Tan Justina Wei Lynn , Koh Ee Tzun ,   TTSH Rheumatoid Arthritis Study Group, Ang Andrea Ee Ling , Chan Grace Yin Lai , Chan Madelynn Tsu-Li , Chia Faith Li-Ann , Chng Hiok Hee , Chua Choon Guan , Howe Hwee Siew , Koh Li Wearn , Kong Kok Ooi , Law Weng Giap , Lee Samuel Shang Ming , Lian Tsui Yee , Lim Xin Rong , Loh Jess Mung Ee , Manghani Mona , Tan Sze-Chin , Teo Claire Min-Li , Thong Bernard Yu-Hor , Tjokrosaputro Paula Permatasari , Xu Chuanhui , Chong Samuel S. , Khor Chiea Chuen , Leong Khai Pang , Lee Caroline G.
Published: February 2023

Background

The popular statistics-based Genome-wide association studies (GWAS) have provided deep insights into the field of complex disorder genetics. However, its clinical applicability to predict disease/trait outcomes remains unclear as statistical models are not designed to make predictions. This study employs statistics-free machine-learning (ML)-optimized polygenic risk score (PRS) to complement existing GWAS and bring the prediction of disease/trait outcomes closer to clinical application. Rheumatoid Arthritis (RA) was selected as a model disease to demonstrate the robustness of ML in disease prediction as RA is a prevalent chronic inflammatory joint disease with high mortality rates, affecting adults at the economic prime. Early identification of at-risk individuals may facilitate measures to mitigate the effects of the disease.

Methods

This study employs a robust ML feature selection algorithm to identify single nucleotide polymorphisms (SNPs) that can predict RA from a set of training data comprising RA patients and population control samples. Thereafter, selected SNPs were evaluated for their predictive performances across 3 independent, unseen test datasets. The selected SNPs were subsequently used to generate PRS which was also evaluated for its predictive capacity as a sole feature.

Results

Through robust ML feature selection, 9 SNPs were found to be the minimum number of features for excellent predictive performance (AUC > 0.9) in 3 independent, unseen test datasets. PRS based on these 9 SNPs was significantly associated with (P < 1 × 10–16) and predictive (AUC > 0.9) of RA in the 3 unseen datasets. A RA ML-PRS calculator of these 9 SNPs was developed (https://xistance.shinyapps.io/prs-ra/) to facilitate individualized clinical applicability. The majority of the predictive SNPs are protective, reside in non-coding regions, and are either predicted to be potentially functional SNPs (pfSNPs) or in high linkage disequilibrium (r2 > 0.8) with un-interrogated pfSNPs.

Conclusions

These findings highlight the promise of this ML strategy to identify useful genetic features that can robustly predict disease and amenable to translation for clinical application.
Multi-omics data reveals the important role of glycerophospholipid metabolism in the crosstalk between gut and brain in depression
Authors: Xie Jing , Zhong Qi , Wu Wen-tao , Chen Jian-jun
Published: February 2023

Background

Gut microbiota plays a critical role in the onset and development of depression, but the underlying molecular mechanisms are unclear. This study was conducted to observe the characteristics of gut microbiota, lipid metabolism and neurotransmitters in Gut-Liver-Brain axis in depressed mice (DM), and identify some novel perceptions on relationships between gut microbiota and depression.

Methods

A mouse model of depression was built used chronic unpredictable mild stress (CUMS). Fecal samples (measuring gut microbiota compositions, microbial genes and lipid metabolites), liver samples (measuring lipid metabolites), and hippocampus (measuring neurotransmitters) were collected. Both univariate and multivariate statistical analyses were used to identify the differential gut microbiota, metabolic signatures and neurotransmitters in DM.

Results

There were significant differences on both microbial and metabolic signatures between DM and control mice (CM): 71 significantly changed operational taxonomic units (OTUs) (60.56% belonged to phylum Firmicutes) and 405 differential lipid metabolites (51.11% belonged to Glycerophospholipid (GP) metabolism) were identified. Functional analysis showed that depressive-like behaviors (DLB)-related differential microbial genes were mainly enriched in GP metabolism. Weighted correlation network analysis (WGCNA) showed that DLB-related differential metabolites mainly belonged to GPs. Meanwhile, seven differential neurotransmitters were identified. Comprehensive analysis found that Lachnospiraceae and gamma-aminobutyric acid (GABA) were significantly correlated with 94.20% and 53.14% differential GPs, respectively, and GABA was significantly correlated with three main DLB phenotypes.

Conclusion

Our results provided novel perceptions on the role of Gut-Liver-Brain axis in the onset of depression, and showed that GP metabolism might be the bridge between gut microbiota and depression. “Lachnospiraceae-GP metabolism-GABA” held the promise as a potential way between gut microbiota and brain functions in DM.
Stratum corneum hydration inversely correlates with certain serum cytokine levels in the elderly, possibly contributing to inflammaging
Authors: Yang Bin , Lv Chengzhi , Ye Li , Wang Zhen , Kim Yoon , Luo Wenhai , Elias Peter M. , Man Mao-Qiang
Published: February 2023

Background

Chronic, low-grade inflammation, also termed ‘inflammaging’, has been linked to the development of some aging-associated disorders. Recent studies suggest that inflammaging is attributable to aging-associated epidermal dysfunction. However, abnormality in which epidermal function contributes to inflammaging is not clear.

Objective

We delineated the correlation of epidermal functions with circulating levels of proinflammatory cytokines in the elderly.

Methods

Blood sample was collected from a total of 255 participants aged ≥ 65 years. Epidermal biophysical properties were measured on the left forearm and the right shin. Serum cytokine levels were measured by Multiplex Luminex Assays.

Results

Neither skin surface pH nor transepidermal water loss rates (TEWL) correlated with serum cytokine levels except TEWL on the right shin for TNFa (p < 0.05). In contrast, stratum corneum hydration levels on both the forearm and the shin correlated negatively with serum cytokine levels (p < 0.05).

Conclusion

Reduced stratum corneum hydration likely contributes to inflammaging.
Examining the role of intrinsic and reflexive contributions to ankle joint hyper-resistance treated with botulinum toxin-A
Authors: van’t Veld Ronald C. , Flux Eline , van Oorschot Wieneke , Schouten Alfred C. , van der Krogt Marjolein M. , van der Kooij Herman , Vos-van der Hulst Marije , Keijsers Noël L. W. , van Asseldonk Edwin H. F.
Published: February 2023

Background

Spasticity, i.e. stretch hyperreflexia, increases joint resistance similar to symptoms like hypertonia and contractures. Botulinum neurotoxin-A (BoNT-A) injections are a widely used intervention to reduce spasticity. BoNT-A effects on spasticity are poorly understood, because clinical measures, e.g. modified Ashworth scale (MAS), cannot differentiate between the symptoms affecting joint resistance. This paper distinguishes the contributions of the reflexive and intrinsic pathways to ankle joint hyper-resistance for participants treated with BoNT-A injections. We hypothesized that the overall joint resistance and reflexive contribution decrease 6 weeks after injection, while returning close to baseline after 12 weeks.

Methods

Nine participants with spasticity after spinal cord injury or after stroke were evaluated across three sessions: 0, 6 and 12 weeks after BoNT-A injection in the calf muscles. Evaluation included clinical measures (MAS, Tardieu Scale) and motorized instrumented assessment using the instrumented spasticity test (SPAT) and parallel-cascade (PC) system identification. Assessments included measures for: (1) overall resistance from MAS and fast velocity SPAT; (2) reflexive resistance contribution from Tardieu Scale, difference between fast and slow velocity SPAT and PC reflexive gain; and (3) intrinsic resistance contribution from slow velocity SPAT and PC intrinsic stiffness/damping.

Results

Individually, the hypothesized BoNT-A effect, the combination of a reduced resistance (week 6) and return towards baseline (week 12), was observed in the MAS (5 participants), fast velocity SPAT (2 participants), Tardieu Scale (2 participants), SPAT (1 participant) and reflexive gain (4 participants). On group-level, the hypothesis was only confirmed for the MAS, which showed a significant resistance reduction at week 6. All instrumented measures were strongly correlated when quantifying the same resistance contribution.

Conclusion

At group-level, the expected joint resistance reduction due to BoNT-A injections was only observed in the MAS (overall resistance). This observed reduction could not be attributed to an unambiguous group-level reduction of the reflexive resistance contribution, as no instrumented measure confirmed the hypothesis. Validity of the instrumented measures was supported through a strong association between different assessment methods. Therefore, further quantification of the individual contributions to joint resistance changes using instrumented measures across a large sample size are essential to understand the heterogeneous response to BoNT-A injections.
Impact of hybrid procedure on pulmonary arterial dimensions and right ventricular load after biventricular repair
Authors: Uhl Sebastian , Grieshaber Philippe , Arnold Raoul , Loukanov Tsvetomir , Gorenflo Matthias
Published: February 2023

Background

Hybrid procedure with ductal stenting and bilateral pulmonary banding offers a temporary approach in high-risk neonates with complex congenital heart defects aiming biventricular repair. This procedure may also have negative impact concerning post-banding pulmonary stenosis resulting in right ventricular pressure load.

Methods

Between 2010 and 2021 we identified 5 patients with interrupted aortic arch and complex congenital heart defect who underwent hybrid procedure and staged biventricular repair (“hybrid-group”). Other 7 cases with interrupted aortic arch were corrected in the neonatal phase without hybrid procedure (“nonhybrid-group”). Detailed intra- and extracardiac features and surgical procedures were documented as well as pulmonary interventions during follow up. Pulmonary vessel size was assessed by diameter of left and right pulmonary artery in absolute and indexed values. RV pressure was evaluated invasively via catheterization.

Results

Survival in cases with hybrid procedure and staged biventricular repair was 91% for a follow-up time of 40.7 months (95% CI 26–55 months) and 100% in the non-hybrid-group. Postoperative results concerning left ventricular function showed normal LV dimensions and systolic function without relevant stenosis on distal aortic arch. Hybrid procedure was associated with impaired local pulmonary arterial diameter after debanding resulting in increased right ventricular pressure and need for interventions (number intervention per patient: hybrid group 1.7 ± 0.95, non-hybrid group 0.17 ± 0.41; P 0.003).

Conclusions

Hybrid procedure in high-risk cases with interrupted aortic arch and staged biventricular repair shows good postoperative results with low perioperative mortality and normal left ventricular function. Due to potential risk of relevant pulmonary stenosis and right ventricular pressure load, follow up examinations must not only focus on left but also on the right heart.

Graphical Abstract
Potential molecular mechanisms of chronic fatigue in long haul COVID and other viral diseases
Authors: Gottschalk Carl Gunnar , Peterson Daniel , Armstrong Jan , Knox Konstance , Roy Avik
Published: February 2023

Historically, COVID-19 emerges as one of the most devastating diseases of humankind, which creates an unmanageable health crisis worldwide. Until now, this disease costs millions of lives and continues to paralyze human civilization's economy and social growth, leaving an enduring damage that will take an exceptionally long time to repair. While a majority of infected patients survive after mild to moderate reactions after two to six weeks, a growing population of patients suffers for months with severe and prolonged symptoms of fatigue, depression, and anxiety. These patients are no less than 10% of total COVID-19 infected individuals with distinctive chronic clinical symptomatology, collectively termed post-acute sequelae of COVID-19 (PASC) or more commonly long-haul COVID. Interestingly, Long-haul COVID and many debilitating viral diseases display a similar range of clinical symptoms of muscle fatigue, dizziness, depression, and chronic inflammation. In our current hypothesis-driven review article, we attempt to discuss the molecular mechanism of muscle fatigue in long-haul COVID, and other viral diseases as caused by HHV6, Powassan, Epstein–Barr virus (EBV), and HIV. We also discuss the pathological resemblance of virus-triggered muscle fatigue with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Graphical Abstract
The low-dose colchicine in patients after non-CABG cardiac surgery: a randomized controlled trial
Authors: Pan Tuo , Jiang Chen-Yu , Zhang He , Han Xi-Kun , Zhang Hai-Tao , Jiang Xin-Yi , Chen Wei , Wang Kuo , Fan Fu-Dong , Pan Jun , Zhou Qing , Wang Chuang-Shi , Zhang Li , Wang Dong-Jin
Published: February 2023

Background

Recent high-quality trials have shown that the anti-inflammatory effects of colchicine reduce the risk of cardiovascular events in patients suffering post-myocardial infarction and chronic coronary disease. The effect of colchicine in patients undergoing non-coronary artery bypass grafting (non-CABG) with cardiopulmonary bypass remains unclear. We aim to evaluate the effect of colchicine on myocardial protection in patients who underwent non-CABG cardiac surgery.

Method

Patients were randomly assigned to colchicine or placebo groups starting 72 h before scheduled cardiac surgery and for 5 days thereafter (0.5 mg daily).The primary outcome was the level of cardiac troponin T (cTnT) at postoperative 48 h. The secondary outcomes included troponin I (cTnI) and creatine kinase-MB (CK-MB), inflammatory biomarkers (procalcitonin and interleukin-6, etc.), and adverse events (30-day mortality, stroke, ECMO and IABP use, etc.).

Results

A total of 132 patients underwent non-CAGB cardiac surgery, 11were excluded because of diarrhea (n = 6) and long aortic cross-clamp time > 2 h (n = 5), 59 were assigned to the colchicine group and 62 to the placebo group. Compared with the placebo group, cTnT (median: 0.3 μg/L, IQR 0.2–0.4 μg/L vs. median: 0.4 μg/L, IQR 0.3–0.6 μg/L, P < 0.01), cardiac troponin I (median: 0.9 ng/ml, IQR 0.4–1.7 ng/ml vs. median: 1.3 ng/ml, IQR 0.6–2.3 ng/ml, P = 0.02), CK-MB (median: 1.9 ng/ml, IQR 0.7–3.2 ng/ml vs. median: 4.4 ng/ml, IQR 1.5–8.2 ng/ml, P < 0.01), and interleukin-6 (median: 73.5 pg/ml, IQR 49.6–125.8 pg/ml vs. median: 101 pg/ml, IQR 57.5–164.7 pg/ml, P = 0.048) were significantly reduced in colchicine group at postoperative 48 h. For safety evaluation, the colchicine (n = 65) significantly decreased post-pericardiotomy syndrome (3.08% vs. 17.7%, P < 0.01) and increased the rate of diarrhea (9.23% vs. 0, P = 0.01) compared with the placebo group (n = 62). No significant difference was observed in other adverse events between the two groups.

Conclusion

A short perioperative course of low-dose colchicine was effective to attenuate the postoperative biomarkers of myocardial injury and inflammation, and to decrease the postoperative syndrome compared with the placebo.

Trial registration ChiCTR2000040129. Registered 22nd Nov. 2020. This trial was registered before the first participant was enrolled. http://www.chictr.org.cn/showproj.aspx?proj=64370.
Identification of a prognostic cuproptosis-related signature in hepatocellular carcinoma
Authors: Chen Yuqiao , Tang Lu , Huang Wentao , Abisola Fakolade Hannah , Zhang Youyu , Zhang Gewen , Yao Lei
Published: February 2023

Background

Cuproptosis is a new type of copper-induced cell death that is characterized by the aggregation of lipoylated tricarboxylic acid (TCA) cycle proteins. However, its role in hepatocellular carcinoma (HCC) remains unclear. The goal of this research is to develop a cuproptosis-related signature predicting the prognosis of HCC.

Methods

The cuproptosis-related genes were defined using Pearson correlation coefficients. LASSO-Cox regression analysis was used to evaluate the prognostic values of cuproptosis-related genes to construct a cuproptosis-related prognostic model. The immune microenvironment analysis was performed by “ssGSEA” to reveal the associated immune cell infiltration patterns with the cuproptosis-related genes signature. The expression levels of one of the prognostic genes PDXK were then verified in HCC samples by Western Blot and immunohistochemistry. The potential roles of target genes in cuproptosis were further explored during in-vitro experiments.

Results

A total of 136 cuproptosis-related genes were discovered using Pearson correlation analysis in HCC. A cuproptosis-related signature that included 5 cuproptosis-related genes (PDXK, HPN, SLC25A28, RNFT1, CLEC3B) was established in the TCGA-LIHC training cohort. TCGA validation cohort and another two external validation cohorts confirmed the robustness of the signature’s predictive value. Moreover, a nomogram using the risk score was created to best predict the survival of HCC patients. The immune microenvironment analysis revealed distinct immune infiltrations patterns between different risk groups based on the signature model. Furthermore, the upregulation of PDXK was confirmed in HCC tumor tissues in 30 clinical HCC specimens. The knockdown of PDXK reduced the proliferation, migration and invasion of HCC cells. Besides, the expression of PDXK was upregulated after the induction of cuproptosis by elesclomol–CuCL2, which could be suppressed when pretreated with a copper ion chelator. And PDXK deficiency increased the sensitivity of HCC cells to cuproptosis inducer.

Conclusion

Our study identified a new cuproptosis-related gene signature that could predict the prognosis of HCC patient. Besides, the upregulated PDXK could promote the proliferation and metastasis of HCC. And PDXK deficiency facilities cuproptosis in HCC. Therefore, these fundings highlighted that PDXK might serve as a potential diagnostic and therapeutic target for HCC.
Using a patient-centred composite endpoint in a secondary analysis of the Control of Hypertension in Pregnancy Study (CHIPS) Trial
Authors: Metcalfe Rebecca K. , Harrison Mark , Singer Joel , Lewisch Mary , Lee Terry , von Dadelszen Peter , Magee Laura A. , Bansback Nick ,   the CHIPS Study Group
Published: February 2023

Background

Clinical trials commonly use multiple endpoints to measure the impact of an intervention. While this improves the comprehensiveness of outcomes, it can make trial results difficult to interpret. We examined the impact of integrating patient weights into a composite endpoint on the interpretation of Control of Hypertension in Pregnancy Study (CHIPS) Trial results.

Methods

Outcome weights were extracted from a previous patient preferences study in pregnancy hypertension (N = 183 women) which identified (i) seven outcomes most important to women (taking medication, severe hypertension, pre-eclampsia, blood transfusion, Caesarean, delivery < 34 weeks, and baby born smaller-than-expected) and (ii) three preference subgroups: (1) ‘equal prioritizers’, 62%; (2) ‘early delivery avoiders’, 23%; and (3) ‘medication minimizers’, 14%.

Outcome weights from the preference subgroups were integrated with CHIPS data for the seven outcomes identified in the preference study. A weighted composite score was derived for each participant by multiplying the preference weight for each outcome by the binary outcome if it occurred. Analyses considered equal weights and those from the preference subgroups. The mean composite scores were compared between trial arms (t-tests).

Results

Composite scores were similar between trial arms with the use of equal weights or those of subgroup (1) (95% confidence intervals [CIs]: − 0.03, 0.02; p > 0.50 for each). ‘Tight’ control was superior when using subgroup (2) weights (95% CIs: 0.002, 0.07; p = 0.03), and ‘less-tight’ control was superior when using subgroup (3) weights (95% CIs: − 0.11, − 0.04; p < 0.01).

Conclusions

Evidence-based recommendations for ‘tight’ control are consistent with most women’s preferences, but for a sixth of women, ‘less-tight’ control is more preference consistent. Depending on patient preferences, a single trial may support different interventions. Future trials should specify component weights to improve interpretation.

Trial registration

ClinicalTrials.gov NCT01192412
The effects of Digital Buddy programme on older adults’ mental well-being: study protocol for a multi-centre, cluster randomized controlled trial
Authors: Kwan Rick Yiu Cho , Ng Fowie , Lai Manfred , Wong David , Chan Sally
Published: February 2023

Introduction

Mental well-being is associated with many mental health symptoms, including depression and health-related quality of life. Digital divide could impact mental health, particularly during the COVID-19 pandemic. Information and communication technology (ICT)-based tools and interventions could effectively provide social support. Intergenerational mentoring between college students and older adults could promote eHealth literacy and self-efficacy, and it is advocated to bridge the digital divide for older adults. However, the effectiveness of an intervention which employs ICT-based tools and intergenerational mentoring strategies (i.e. Digital Buddy) on mental well-being is unclear.

Methods

This study will employ a multi-centre, cluster-randomized, two-parallel-group, noninferiority, controlled trial design with a 1:1 group allocation ratio. In the intervention group, a Digital Buddy (i.e. a young volunteer) is assigned to a group of older adults in a 1:10 ratio. A series of training sessions for a minimum of 23 h will be provided to the older adults by Digital Buddy, who will also follow through the intervention period with the older participants. The training contents include ICT and mental health care knowledge and skills. The whole intervention period will last for 6 months between 14 sessions. In the control group, participants will receive the usual care. The primary outcome measure is mental well-being. We aim to recruit 292 older participants. Generalized estimating equations (GEE) will be used to examine the effects of the intervention.

Ethics and dissemination

This trial has been registered at ClinicalTrials.gov (NCT05553730) on 23 September 2022, https://clinicaltrials.gov/ct2/show/NCT05553730, and all items come from the World Health Organization Trial Registration Data Set. It has been approved by the Research Ethics Committee of Tung Wah College, Hong Kong (reference number: REC2022143). The findings will be disseminated in peer-reviewed journals and presented at international conferences relevant to the subject fields.
Interaction between gut microbiota and sex hormones and their relation to sexual dimorphism in metabolic diseases
Authors: Santos-Marcos Jose Antonio , Mora-Ortiz Marina , Tena-Sempere Manuel , Lopez-Miranda Jose , Camargo Antonio
Published: February 2023

Metabolic diseases, such as obesity, metabolic syndrome (MetS) and type 2 diabetes (T2D), are now a widespread pandemic in the developed world. These pathologies show sex differences in their development and prevalence, and sex steroids, mainly estrogen and testosterone, are thought to play a prominent role in this sexual dimorphism. The influence of sex hormones on these pathologies is not only reflected in differences between men and women, but also between women themselves, depending on the hormonal changes associated with the menopause. The observed sex differences in gut microbiota composition have led to multiple studies highlighting the interaction between steroid hormones and the gut microbiota and its influence on metabolic diseases, ultimately pointing to a new therapy for these diseases based on the manipulation of the gut microbiota. This review aims to shed light on the role of sexual hormones in sex differences in the development and prevalence of metabolic diseases, focusing on obesity, MetS and T2D. We focus also the interaction between sex hormones and the gut microbiota, and in particular the role of microbiota in aspects such as gut barrier integrity, inflammatory status, and the gut–brain axis, given the relevance of these factors in the development of metabolic diseases.
Employing nanoparticle tracking analysis of salivary neuronal exosomes for early detection of neurodegenerative diseases
Authors: Sharma Vaibhav , Nikolajeff Fredrik , Kumar Saroj
Published: February 2023

Neurodegenerative diseases are a set of progressive and currently incurable diseases that are primarily caused by neuron degeneration. Neurodegenerative diseases often lead to cognitive impairment and dyskinesias. It is now well recognized that molecular events precede the onset of clinical symptoms by years. Over the past decade, intensive research attempts have been aimed at the early diagnosis of these diseases. Recently, exosomes have been shown to play a pivotal role in the occurrence and progression of many diseases including cancer and neurodegenerative diseases. Additionally, because exosomes can cross the blood–brain barrier, they may serve as a diagnostic tool for neural dysfunction. In this review, we detail the mechanisms and current challenges of these diseases, briefly review the role of exosomes in the progression of neurodegenerative diseases, and propose a novel strategy based on salivary neuronal exosomes and nanoparticle tracking analysis that could be employed for screening the early onset of neurodegenerative diseases.