bluuebunny/crossref_metadata_2025 huggingface dataset:
Peripheral clock disruption and metabolic disease: moving beyond the anatomy to a functional approach
Authors: Marino Gabriella M. , Arble Deanna M.
Published: May 2023

Sleep and circadian disruption are associated with an increased risk of metabolic disease, including obesity and diabetes. Mounting evidence indicates that misaligned and/or non-functional clock proteins in peripheral tissues critically contribute to the presentation of metabolic disease. Many of the foundational studies which led to this conclusion have focused on specific tissues such as the adipose, pancreas, muscle, and liver. While these studies have greatly advanced the field, the use of anatomical markers to manipulate tissue-specific molecular clocks may not be representative of the circadian disruption that occurs within the clinical population. In this manuscript, we argue that investigators can gain a better understanding of the consequences of sleep and circadian disruption by targeting groups of cells with a functional relationship, even if those cells go beyond anatomical boundaries. This approach is especially important when considering metabolic outcomes which rely on endocrine signaling molecules, such as leptin, that have multiple sites of action. Through the review of several studies, as well as our own work, this article reframes peripheral clock disruption from a functional approach. We additionally present new evidence that disruption of the molecular clock within all cells expressing the leptin receptor affects leptin sensitivity in a time-dependent manner. Taken together, this perspective aims to provide new insight into the mechanisms leading to metabolic disease associated with circadian disruption and various sleep disorders.
Genetically predicted vitamin C levels significantly affect patient survival and immunotypes in multiple cancer types
Authors: Yuan Jing , Zhang Yu-hong , Hua Xin , Hong Hui-qi , Shi Wei , Liu Kun-xiang , Liu Ze-xian , Huang Peng
Published: May 2023

Background

Recent observational studies and meta-analyses have shown that vitamin C reduces cancer incidence and mortality, but the underlying mechanisms remain unclear. We conducted a comprehensive pan-cancer analysis and biological validation in clinical samples and animal tumor xenografts to understand its prognostic value and association with immune characteristics in various cancers.

Methods

We used the Cancer Genome Atlas gene expression data involving 5769 patients and 20 cancer types. Vitamin C index (VCI) was calculated using the expression of 11 genes known to genetically predict vitamin C levels, which were classified into high and low subgroups. The correlation between VCI and patient overall survival (OS), tumor mutational burden (TMB), microsatellite instability (MSI), and immune microenvironment was evaluated, using Kaplan-Meier analysis method and ESTIMATE (https://bioinformatics.mdanderson.org/estimate/). Clinical samples of breast cancer and normal tissues were used to validate the expression of VCI-related genes, and animal experiments were conducted to test the impact of vitamin C on colon cancer growth and immune cell infiltration.

Results

Significant changes in expression of VCI-predicted genes were observed in multiple cancer types, especially in breast cancer. There was a correlation of VCI with prognosis in all samples (adjusted hazard ratio [AHR] = 0.87; 95% confidence interval [CI] = 0.78–0.98; P = 0.02). The specific cancer types that exhibited significant correlation between VCI and OS included breast cancer (AHR = 0.14; 95% CI = 0.05–0.40; P < 0.01), head and neck squamous cell carcinoma (AHR = 0.20; 95% CI = 0.07–0.59; P < 0.01), kidney clear cell carcinoma (AHR = 0.66; 95% CI = 0.48–0.92; P = 0.01), and rectum adenocarcinoma (AHR = 0.01; 95% CI = 0.001–0.38; P = 0.02). Interestingly, VCI was correlated with altered immunotypes and associated with TMB and MSI negatively in colon and rectal adenocarcinoma (P < 0.001) but positively in lung squamous cell carcinoma (P < 0.05). In vivo study using mice bearing colon cancer xenografts demonstrated that vitamin C could inhibit tumor growth with significant impact on immune cell infiltration.

Conclusion

VCI is significantly correlated with OS and immunotypes in multiple cancers, and vitamin C might have therapeutic potential in colon cancer.
Revisiting the interleukin 17 family of cytokines in psoriasis: pathogenesis and potential targets for innovative therapies
Authors: Brembilla Nicolo Costantino , Boehncke Wolf-Henning
Published: May 2023

Psoriasis is a common chronic inflammatory skin disease, associated with substantial comorbidity. TH17 lymphocytes, differentiating under the influence of dendritic cell-derived IL-23, and mediating their effects via IL-17A, are believed to be central effector cells in psoriasis. This concept is underlined by the unprecedented efficacy of therapeutics targeting this pathogenetic axis. In recent years, numerous observations made it necessary to revisit and refine this simple “linear” pathogenetic model. It became evident that IL-23 independent cells exist that produce IL-17A, that IL-17 homologues may exhibit synergistic biological effects, and that the blockade of IL-17A alone is clinically less effective compared to the inhibition of several IL-17 homologues. In this review, we will summarize the current knowledge around IL-17A and its five currently known homologues, namely IL-17B, IL-17C, IL-17D, IL-17E (also known as IL-25) and IL-17F, in relation to skin inflammation in general and psoriasis in particular. We will also re-visit the above-mentioned observations and integrate them into a more comprehensive pathogenetic model. This may help to appreciate current as well as developing anti-psoriatic therapies and to prioritize the selection of future drugs’ mode(s) of action.
Cardiovascular involvement in Epstein–Barr virus infection
Authors: Chen Xinying , Li Yingying , Deng Lijun , Wang Lianyu , Zhong Wenting , Hong Junbin , Chen Liyu , Yang Jinghua , Huang Bin , Xiao Xiaolan
Published: May 2023

Cardiovascular involvement is an uncommon but severe complication of Epstein–Barr virus (EBV) infection caused by direct damage and immune injury. Recently, it has drawn increasing attention due to its dismal prognosis. It can manifest in various ways, including coronary artery dilation (CAD), coronary artery aneurysm (CAA), myocarditis, arrhythmias, and heart failure, among others. If not treated promptly, cardiovascular damage can progress over time and even lead to death, which poses a challenge to clinicians. Early diagnosis and treatment can improve the prognosis and reduce mortality. However, there is a lack of reliable large-scale data and evidence-based guidance for the management of cardiovascular damage. Consequently, in this review, we attempt to synthesize the present knowledge of cardiovascular damage associated with EBV and to provide an overview of the pathogenesis, classification, treatment, and prognosis, which may enhance the recognition of cardiovascular complications related to EBV and may be valuable to their clinical management.
Quantification of the zymogenicity and the substrate-induced activity enhancement of complement factor D
Authors: Dani Ráhel , Oroszlán Gábor , Martinusz Róbert , Farkas Bence , Dobos Bernadett , Vadas Evelin , Závodszky Péter , Gál Péter , Dobó József
Published: May 2023

Complement factor D (FD) is a serine protease present predominantly in the active form in circulation. It is synthesized as a zymogen (pro-FD), but it is continuously converted to FD by circulating active MASP-3. FD is a unique, self-inhibited protease. It has an extremely low activity toward free factor B (FB), while it is a highly efficient enzyme toward FB complexed with C3b (C3bB). The structural basis of this phenomenon is known; however, the rate enhancement was not yet quantified. It has also been unknown whether pro-FD has any enzymatic activity. In this study, we aimed to measure the activity of human FD and pro-FD toward uncomplexed FB and C3bB in order to quantitatively characterize the substrate-induced activity enhancement and zymogenicity of FD. Pro-FD was stabilized in the proenzyme form by replacing Arg25 (precursor numbering) with Gln (pro-FD-R/Q). Activated MASP-1 and MASP-3 catalytic fragments were also included in the study for comparison. We found that the complex formation with C3b enhanced the cleavage rate of FB by FD approximately 20 million-fold. C3bB was also a better substrate for MASP-1, approximately 100-fold, than free FB, showing that binding to C3b renders the scissile Arg-Lys bond in FB to become more accessible for proteolysis. Though easily measurable, this cleavage by MASP-1 is not relevant physiologically. Our approach provides quantitative data for the two-step mechanism characterized by the enhanced susceptibility of FB for cleavage upon complex formation with C3b and the substrate-induced activity enhancement of FD upon its binding to C3bB. Earlier MASP-3 was also implicated as a potential FB activator; however, MASP-3 does not cleave C3bB (or FB) at an appreciable rate. Finally, pro-FD cleaves C3bB at a rate that could be physiologically significant. The zymogenicity of FD is approximately 800, i.e., the cleavage rate of C3bB by pro-FD-R/Q was found to be approximately 800-fold lower than that by FD. Moreover, pro-FD-R/Q at approximately 50-fold of the physiological FD concentration could restore half-maximal AP activity of FD-depleted human serum on zymosan. The observed zymogen activity of pro-FD might be relevant in MASP-3 deficiency cases or during therapeutic MASP-3 inhibition.
Modeling the radiative, thermal and chemical microenvironment of 3D scanned corals
Authors: Murthy Swathi , Picioreanu Cristian , Kühl Michael
Published: May 2023

Reef building corals are efficient biological collectors of solar radiation and consist of a thin stratified tissue layer spread over a light scattering calcium carbonate skeleton surface that together construct complex three dimensional (3D) colony structures forming the foundation of coral reefs. They exhibit a vast diversity of structural forms to maximize photosynthesis of their dinoflagellate endosymbionts (Symbiodiniaceae), while simultaneously minimizing photodamage, offer resistance to hydrodynamic stress, reduce attack by predators and increase prey capture and heterotrophic feeding. The symbiosis takes place in the presence of dynamic gradients of light, temperature and chemical species that are affected by the interaction of incident irradiance and water flow with the coral colony. We developed a multiphysics modelling approach to simulate the microscale spatial distribution of light, temperature and O2 in a coral fragment with its morphology determined by 3D scanning techniques. Model results compared well with spatial measurements of light, O2 and temperature under similar flow and light conditions. The model enabled us to infer the effect of coral morphology and light scattering in tissue and skeleton on the internal light environment experienced by the endosymbionts, as well as the combined contribution of light, water flow and ciliary movement on O2 and temperature distributions in the coral.
Fecundity, an overlooked life-history trait for coastal management of commercial molluscs?
Authors: Vasconcelos Joana , Sousa Ricardo , Ferro João , Pinto Ana Rita , Freitas Mafalda , Riera Rodrigo
Published: May 2023

Gonadal development in limpets is well-known. However, the integration of fecundity data on coastal management actions remains overlooked. Here, we use fecundity of two exploited limpets (Patella ordinaria and P. aspera) to demonstrate its potential as a conservation tool to preserve the harvested populations of both species. From October 2021 to June 2022, 158 females of P. ordinaria and 70 of P. aspera were collected from the coastal rocky shores of the archipelago of Madeira (NE Atlantic Ocean). The fecundity in both species appears to be determinate, and estimated batch fecundity 365,638 ± 204,462 oocytes for P. ordinaria and 73,029 ± 43,496 oocytes for P. aspera. The presence of spawning individuals of both species until May is of significant relevance to their management and conservation. A harvest-ban (November-March) is currently implemented in the coastal governance actions of P. ordinaria and P. aspera. Based on the fecundity results, small adjustments can be made to further improve the conservation of adult individuals, which are important for the continuity of future generations. So far, fecundity data constitute an overlooked life trait of key importance to preserve populations of exploited species, primarily those with limited mobility such as semi-sessile littoral limpets.
Acute kidney disease following COVID-19 vaccination: a single-center retrospective study
Authors: Chen Chien-Chou , Yang Sung-Sen , Hsu Yu-Juei , Sung Chih-Chien , Chu Pauling , Wu Chia-Chao , Hsu Shun-Neng , Wang Han-En , Lee Ding-Jie , Lin Shih-Hua
Published: May 2023

Background

Rare cases of de novo or relapsed kidney diseases associated with vaccination against coronavirus disease 2019 (COVID-19) have been increasingly reported. The aim of this study was to report the incidence, etiologies, and outcomes of acute kidney disease (AKD) following COVID-19 vaccination.

Methods

This retrospective study extracted cases from renal registry of a single medical center from 1 March 2021 to 30 April 2022, prior to the significant surge in cases of the Omicron variant of COVID-19 infection in Taiwan. Adult patients who developed AKD after COVID-19 vaccination were included. We utilized the Naranjo score as a causality assessment tool for adverse vaccination reactions and charts review by peer nephrologists to exclude other causes. The etiologies, characteristics, and outcomes of AKD were examined.

Results

Twenty-seven patients (aged 23 to 80 years) with AKD were identified from 1,897 vaccines (estimated rate of 13.6 per 1000 patient-years within the renal registry). A majority (77.8%) of vaccine received messenger RNA-based regimens. Their median (IQR) Naranjo score was 8 (6-9) points, while 14 of them (51.9%) had a definite probability (Naranjo score ≥ 9). The etiologies of AKD included glomerular disease (n = 16) consisting of seven IgA nephropathy, four anti-neutrophil cytoplasmic antibodies-associated glomerulonephritis (AAN), three membranous glomerulonephritis, two minimal change diseases, and chronic kidney disease (CKD) with acute deterioration (n = 11). Extra-renal manifestations were found in four patients. Over a median (IQR) follow-up period of 42 (36.5–49.5) weeks, six patients progressed to end-stage kidney disease (ESKD).

Conclusion

Besides glomerulonephritis (GN), the occurrence of AKD following COVID-19 vaccination may be more concerning in high-risk CKD patients receiving multiple doses. Patients with the development of de novo AAN, concurrent extra-renal manifestations, or pre-existing moderate to severe CKD may exhibit poorer kidney prognosis.
Modeling the development of cortical responses in primate dorsal (“where”) pathway to optic flow using hierarchical neural field models
Authors: Gundavarapu Anila , Chakravarthy V. Srinivasa
Published: May 2023

Although there is a plethora of modeling literature dedicated to the object recognition processes of the ventral (“what”) pathway of primate visual systems, modeling studies on the motion-sensitive regions like the Medial superior temporal area (MST) of the dorsal (“where”) pathway are relatively scarce. Neurons in the MST area of the macaque monkey respond selectively to different types of optic flow sequences such as radial and rotational flows. We present three models that are designed to simulate the computation of optic flow performed by the MST neurons. Model-1 and model-2 each composed of three stages: Direction Selective Mosaic Network (DSMN), Cell Plane Network (CPNW) or the Hebbian Network (HBNW), and the Optic flow network (OF). The three stages roughly correspond to V1-MT-MST areas, respectively, in the primate motion pathway. Both these models are trained stage by stage using a biologically plausible variation of Hebbian rule. The simulation results show that, neurons in model-1 and model-2 (that are trained on translational, radial, and rotational sequences) develop responses that could account for MSTd cell properties found neurobiologically. On the other hand, model-3 consists of the Velocity Selective Mosaic Network (VSMN) followed by a convolutional neural network (CNN) which is trained on radial and rotational sequences using a supervised backpropagation algorithm. The quantitative comparison of response similarity matrices (RSMs), made out of convolution layer and last hidden layer responses, show that model-3 neuron responses are consistent with the idea of functional hierarchy in the macaque motion pathway. These results also suggest that the deep learning models could offer a computationally elegant and biologically plausible solution to simulate the development of cortical responses of the primate motion pathway.
Multiomics technologies for comprehensive tumor microenvironment analysis in triple-negative breast cancer under neoadjuvant chemotherapy
Authors: Wang Gang , Yao Yao , Huang Huanhuan , Zhou Jun , Ni Chao
Published: May 2023

Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancer subtypes and is characterized by abundant infiltrating immune cells within the microenvironment. As standard care, chemotherapy remains the fundamental neoadjuvant treatment in TNBC, and there is increasing evidence that supplementation with immune checkpoint inhibitors may potentiate the therapeutic efficiency of neoadjuvant chemotherapy (NAC). However, 20-60% of TNBC patients still have residual tumor burden after NAC and require additional chemotherapy; therefore, it is critical to understand the dynamic change in the tumor microenvironment (TME) during treatment to help improve the rate of complete pathological response and long-term prognosis. Traditional methods, including immunohistochemistry, bulk tumor sequencing, and flow cytometry, have been applied to elucidate the TME of breast cancer, but the low resolution and throughput may overlook key information. With the development of diverse high-throughput technologies, recent reports have provided new insights into TME alterations during NAC in four fields, including tissue imaging, cytometry, next-generation sequencing, and spatial omics. In this review, we discuss the traditional methods and the latest advances in high-throughput techniques to decipher the TME of TNBC and the prospect of translating these techniques to clinical practice.
EGFR and ERBB2 exon 20 insertion/duplication in advanced non–small cell lung cancer: genomic profiling and clinicopathologic features
Authors: Sompallae Ramakrishna R. , Dundar Bilge , Guseva Natalya V. , Bossler Aaron D. , Ma Deqin
Published: May 2023

Background

Exon 20 (ex20) in-frame insertions or duplications (ins/dup) in epidermal growth factor receptor (EGFR) and its analog erb-b2 receptor tyrosine kinase 2 (ERBB2) are each detected in 1.5% of non–small cell lung cancer (NSCLC). Unlike EGFR p.L858R or ex19 deletions, ex20 ins/dup is associated with de novo resistance to classic EGFR inhibitors, lack of response to immune checkpoint inhibitors, and poor prognosis. US Food and Drug Administration has approved mobocertinib and amivantamab for targeting tumors with this aberration, but the number of comprehensive studies on ex20 ins/dup NSCLC is limited. We identified 18 cases of NSCLCs with EGFR/ERBB2 ex20 ins/dup and correlated the findings with clinical and morphologic information including programed death-ligand 1 (PD-L1) expression.

Methods

A total of 536 NSCLC cases tested at our institution between 2014 and 2023 were reviewed. A custom-designed 214-gene next-generation sequencing panel was used for detecting DNA variants, and the FusionPlex CTL panel (ArcherDx) was used for the detection of fusion transcripts from formalin-fixed, paraffin-embedded tissue. Immunohistochemistry (IHC)for PD-L1 was performed using 22C3 or E1L3N clones.

Results

Nine EGFR and nine ERBB2 ex20 ins/dup variants were identified from an equal number of men and women, 14 were non- or light smokers, and 15 had stage IV disease. All 18 cases were adenocarcinomas. Seven of the 11 cases with available primary tumors had acinar predominant pattern, two had lepidic predominant pattern, and the remainder had papillary (one case) and mucinous (one case) patterns. Ex20 ins/dup variants were heterogenous in-frame one to four amino acids spanning A767–V774 in EGFR and Y772–P780 in ERBB2 and were clustered in the loop following the C-helix and α C-helix. Twelve cases (67%) had co-existing TP53 variants. Copy number variation in CDK4 amplification was identified in one case. No fusion or microsatellite instability was identified in any case. PD-L1 was positive in two cases, low positive in four cases, and negative in 11 cases.

Conclusions

NSCLCs harboring EGFR/ERBB2 ex20 ins/dup are rare and tend to be acinar predominant, negative for PD-L1, more frequent in non- or light smokers, and mutually exclusive with other driver mutations in NSCLC. The correlation of different EGFR/ERBB2 ex20 ins/dup variants and co-existing mutations with response to targeted therapy and the possibility of developing resistant mutations after mobocertinib treatment warrants further investigation.
The pharmacogenomic landscape of an Indigenous Australian population
Authors: Samarasinghe Sumudu Rangika , Hoy Wendy , Jadhao Sudhir , McMorran Brendan J. , Guchelaar Henk-Jan , Nagaraj Shivashankar H.
Published: May 2023

Background: Population genomic studies of individuals of Indigenous ancestry have been extremely limited comprising <0.5% of participants in international genetic databases and genome-wide association studies, contributing to a “genomic gap” that limits their access to personalised medicine. While Indigenous Australians face a high burden of chronic disease and associated medication exposure, corresponding genomic and drug safety datasets are sorely lacking.

Methods: To address this, we conducted a pharmacogenomic study of almost 500 individuals from a founder Indigenous Tiwi population. Whole genome sequencing was performed using short-read Illumina Novaseq6000 technology. We characterised the pharmacogenomics (PGx) landscape of this population by analysing sequencing results and associated pharmacological treatment data.

Results: We observed that every individual in the cohort carry at least one actionable genotype and 77% of them carry at least three clinically actionable genotypes across 19 pharmacogenes. Overall, 41% of the Tiwi cohort were predicted to exhibit impaired CYP2D6 metabolism, with this frequency being much higher than that for other global populations. Over half of the population predicted an impaired CYP2C9, CYP2C19, and CYP2B6 metabolism with implications for the processing of commonly used analgesics, statins, anticoagulants, antiretrovirals, antidepressants, and antipsychotics. Moreover, we identified 31 potentially actionable novel variants within Very Important Pharmacogenes (VIPs), five of which were common among the Tiwi. We further detected important clinical implications for the drugs involved with cancer pharmacogenomics such as thiopurines and tamoxifen, immunosuppressants like tacrolimus and certain antivirals used in the hepatitis C treatment due to potential differences in their metabolic processing.

Conclusion: The pharmacogenomic profiles generated in our study demonstrate the utility of pre-emptive PGx testing and have the potential to help guide the development and application of precision therapeutic strategies tailored to Tiwi Indigenous patients. Our research provides valuable insights on pre-emptive PGx testing and the feasibility of its use in ancestrally diverse populations, emphasizing the need for increased diversity and inclusivity in PGx investigations.
The effect of the social support on PTSD and PTG about university student volunteers in the prevention and controlling of coronavirus: with coping style as the intermediary
Authors: Hao Ranran , Han Peiyu , Wang Liangsheng , Zhang Yong
Published: May 2023

To investigate the relationship among post-traumatic stress disorder (PTSD), posttraumatic growth (PTG), social support, and coping style of university student volunteers in the prevention and control of the coronavirus in 2020, a total of 2,990 university student volunteers (students who are enrolled in a university and involved in volunteer activities) from 20 universities in Sichuan Province participated in the prevention and control of the epidemic were investigated when March 20–31, 2020 when the coronavirus first occurred using the post-traumatic stress disorder questionnaire, posttraumatic growth questionnaire, university student social support questionnaire and coping style questionnaire. The results showed that (1) 7.06% of university student volunteers had some degree of PTSD symptoms (the total PCL-C score was 38–49), and 2.88% had obvious PTSD symptoms, (2) PTSD level of university student volunteers was significantly positively correlated with negative coping style, and significantly negatively correlated with social support and positive coping style; on the contrary, the PTG level is significantly positively correlated with social support and positive coping styles, and (3) Positive coping style plays a partial mediating role in the influence of social support on PTG; in the influence of social support on PTSD, the mediating effect of positive or negative coping style was not significant. These results show that in the prevention and control of the coronavirus, the positive coping style and social support of university student volunteers can positively predict the PTG level of them, while the negative coping style can positively predict the severity of their PTSD symptoms. Among them, a positive coping style plays a partial mediating role in the influence of social support on the PTG level.
Non-problem gamblers show the same cognitive distortions while playing slot machines as problem gamblers, with no loss of control and reduced reality control, though – An experimental study on gambling
Authors: Krébesz Róbert , Ötvös Dóra Kata , Fekete Zita
Published: May 2023

Background

Cognitive distortions can result in maladaptive interpretations of events and maladaptive behavior. In the case of gambling, such distortions can contribute to the maintenance of the disorder. Our current research aimed to conduct an experiment to possibly detect cognitive biases characteristic of persons with gambling addiction in a non-gambling sample of the general population, and to study the effect of “big win” on cognitive distortions.

Methods

A specifically designed and preprogrammed slot machine simulation was carried out, with 90 rounds split into 3 sections. During the simulation every participant verbalized their thoughts and feelings; the verbalizations were recorded. Then a content analysis was conducted to search for indications of cognitive distortions. The sample was separated into two experimental groups: one of the groups experienced the “big wins” in the first section, while the other group had them in the second section of the experiment.

Results

Content analysis revealed numerous cognitive biases. Cognitive distortions usually present in problem gambling were detected in our sample from the general population as well. However, we could not distinguish cognitive biases indicating serious loss of control, or distortion of reality control. A further finding is that early losses provoke the emergence of more cognitive distortions, while early big win leads to more intense loss-chasing in the later stages of gambling.

Conclusion

The appearance of reality-checking uncertainty or loss of control can be alarming for the development of gambling. Losses and big wins can provoke different cognitive distortions, encouraging the person into further gambling behavior.
A modified two-dimensional sensory organization test that assesses both anteroposterior and mediolateral postural control
Authors: Wagner Andrew R. , Merfeld Daniel M.
Published: May 2023

Background

The Sensory Organization Test (SOT) was designed to measure changes in postural control in response to unreliable visual and/or proprioceptive feedback. However, secondary to the manipulation of sensory cues in only the sagittal plane, the SOT is capable of only describing postural control in a single direction. The present study aimed to characterize postural responses to a modified SOT designed to concurrently challenge both anteroposterior and mediolateral postural control.

Methods

Twenty-one healthy adult volunteers (30.6 ± 10.2 years) completed the standard anteroposterior one-dimensional (1D) SOT, in addition to a modified SOT with the support surface sway-referenced to both anteroposterior and mediolateral postural sway (two-dimensional, 2D). Our primary analysis concerned a comparison of mediolateral, as well as anteroposterior postural sway measured during the standard one-dimensional (i.e., pitch tilt) and the novel two-dimensional (i.e., roll and pitch tilt) sway-referenced paradigms. Here, postural sway was quantified by calculating the root mean square distance (RMSD) of the center of pressure (CoP) during each trial.

Results

Our data showed that the 2D sway-referenced conditions yielded a selective increase in mediolateral postural sway relative to the standard 1D conditions for both wide (η2 = 0.66) and narrow (η2 = 0.78) stance conditions, with anteroposterior postural sway being largely unaffected (η2 = 0.001 to 0.103, respectively). The ratio between mediolateral postural sway in the sway-referenced conditions and postural sway in the corresponding stable support surface conditions was greater for the 2D (2.99 to 6.26 times greater) compared to 1D paradigms (1.25 to 1.84 times greater), consistent with a superior degradation of viable proprioceptive feedback in the 2D paradigm.

Conclusion

A modified 2D version of the SOT was shown to provide a greater challenge to mediolateral postural control relative to the standard 1D SOT protocol, putatively as a result of a superior capacity to degrade proprioceptive feedback in the mediolateral direction. Given these positive findings, future studies should investigate the clinical utility of this modified SOT as a means by which to better characterize sensory contributions to postural control in the presence of various sensorimotor pathologies, including vestibular hypofunction.
Comparison of non-invasive ventilation use and outcomes in children with Down syndrome and other children using this technology
Authors: Valji Rafiaa , Castro-Codesal Maria L. , Lewis Melanie , MacLean Joanna E.
Published: May 2023

Rationale

Children with Down syndrome (DS) make up a substantial portion of long-term non-invasive ventilation (LT-NIV) users though it is unclear if their unique features alter LT-NIV efficacy or use. The aim of this study is to compare the use and outcomes of LT-NIV for children with DS and a matched comparison (MCG).

Methods

This is a sub-study of a 10-year retrospective review of children initiated on LT-NIV in Alberta, Canada (N = 622). Children with DS (n = 106) were matched in a 1:2 ratio with other children using LT-NIV based on age and therapy start date. Data was collected from medical and sleep laboratory records.

Results

Upper airway disease was the most common indication for LT-NIV in both groups, though was higher in children with DS (DS: 90% vs. MCG: 50%, OR 8.64 [95% CI 4.38–17.04]). Sleep and respiratory parameters, at the baseline diagnostic sleep study and the change from baseline to treatment study, did not differ between groups. Nasal masks were the predominant mask type in both children with DS (55%) and the MCG (66%) with more children with DS, compared to the MCG, using full face masks (DS: 45 vs. MCG: 33%, p < 0.05). Continuous positive airway pressure was used more often in children with DS (93.3% vs. 69.2%, p < 0.001) while bilevel-positive airway pressure was more common in the MCG (DS: 6.7% vs. MCG 30.8%, p < 0.001). Children with DS were followed longer than children in the MCG (DS: 2.4 [IQR 2.8] vs. MCG: 1.8 [IQR 2.7] years, p < 0.05). Adherence was lower in children with DS at both 6–12 month follow-up and most recent visit with a similar decrease in adherence in both groups over the follow-up period (0.0 [IQR 1.4] vs. −0.3 [IQR 2.0]. Despite this, 66% and 49% of children with DS used LT-NIV for more than 4 h/night at the 6–12 month and most current visit, respectively. Discontinuation of LT-NIV and mortality did not differ between groups.

Conclusion

LT-NIV is a common and efficacious treatment in children with DS used predominantly for upper airway obstruction. While adherence is lower, the majority of children with DS are successful at using LT-NIV.
Application of infraorbital rim augmentation with pocket fat filling to correct tear trough deformity
Authors: Liu Yukun , Wang Yi , Cai Changqi , Wu Xiuying , Wang Haiping
Published: May 2023

Background

Tear trough deformity is one of the most common complaints in clinical settings. The correction of this groove is challenging in facial rejuvenation. The lower eyelid blepharoplasty varies with different conditions. A novel approach of using orbital fat in the lower eyelid to increase the volume of the infraorbital rim with granule fat injection has been applied in our institution for more than 5 years.

Objectives

This article aims to describe the detailed steps of our technique and verify its effectiveness by a cadaveric head dissection after surgical simulation.

Methods

In this study, a total of 172 patients with tear trough deformity underwent lower eyelid orbital rim augmentation with fat filling in the sub-periosteum pocket. According to Barton's grades, 152 patients underwent lower eyelid orbital rim augmentation with orbital fat filling, 12 patients had it combined with autologous granule fat from other body parts, and 8 patients received only transconjunctival fat removal to correct tear trough.

Results

The modified Goldberg score system was used to compare preoperative and postoperative photographs. Patients were satisfied with the cosmetic results. Excessive protruding fat was released, and the tear trough groove was flattened by using autologous orbital fat transplantation. The lower eyelid sulcus deformities were well-corrected. To further illustrate the anatomical structure of the lower eyelid area and injection layers, six cadaveric heads were used for surgical simulation and demonstrated the effectiveness of our technique.

Conclusions

This study indicated that the infraorbital rim could be increased by transplanting orbital fat to the pocket, which was dissected under the periosteum, and the procedure has been verified as reliable and effective.

Evidence-based medicine (EBM) level

Level II.
Imperializm i państwo kapitalistyczne – wyzwania teoretyczne w kontekście wojny w Ukrainie
Authors: Ilkowski Filip
Published: May 2023

The aim of the article is to analyze the theory of capitalist imperialism in the context of the challenges of the war in Ukraine. The main theoretical positions in the face of this war, related debates and doubts are outlined. A thesis is put forward about the adequacy of the diagnosis treating capitalist imperialism as a phenomenon rooted in the essence of capitalist states and the specificity of their rivalry. When analyzing the war in Ukraine against the backdrop of multipolar imperialism, an attempt is also made to concrete the analysis of Russian imperialism in relation to the failure of Russia’s economic reconstruction and attempts to change this state’s place in global capitalism.
Społeczne postrzeganie i ocena samorządu terytorialnego w Polsce
Authors: Godlewski Tomasz
Published: May 2023

The political transformation initiated in 1989 brought far-reaching changes not only in the economic and social sphere, but also in the local dimension, which seems to be a symbolic sign of the creation of local government administration. Against this background, the social perception and assessment of the perception and functioning of local governments in Poland seem to be particularly interesting cognitively. It depends on whether Poles define local authority as an element of public authority – an efficient manager and administrator who is de facto a “local extension of central authority”, or whether it becomes an important point of reference for local activities using the synergy effect consisting in stimulating various actors and entities present in the social space for the good of the local community? The conducted analyses allow to unequivocally reject the veracity of the alternative defined in this way. Local government performs both functions, which synergistically increase its importance and impact. This is also a social expectation. Local communities want to see in local authorities both “good hosts” and “animators and creators” of social reality. This is also confirmed by the analyzed case studies. This may be explained, at least in part, by the high social expectation of decentralisation and the transfer of competences and resources to local authorities.
Ład przestrzenny jako zadanie własne gminy. Kryzys w zarządzaniu przestrzenią
Authors: Pelc Marcin
Published: May 2023

The spatial order constitutes the first commune’s own task among those listed exhaustively by the legislator. In fact, the full responsibility for defining areas has been entrusted to the commune authorities as they have been equipped with appropriate spatial planning tools, which make it possible to realize their sovereign competencies. However, space disharmony is raised in the scientific discourse as well as in media reports and political disputes. The aim of this article is an attempt to perform a synthetic analysis of both theoretical and practical significance and the use of spatial planning tools by commune authorities.
Investigations of the Crystallographic Orientation on the Martensite Variant Reorientation of the Single-Crystal Ni-Mn-Ga Cube and Its Composites for Actuator Applications
Authors: Chiu Wan-Ting , Okuno Motoki , Tahara Masaki , Inamura Tomonari , Hosoda Hideki
Published: May 2023

High-speed actuators are greatly required in this decade due to the fast development of future technologies, such as Internet-of-Things (IoT) and robots. The ferromagnetic shape memory alloys (FSMAs), whose shape change could be driven by applying an external magnetic field, possess a rapid response. Hence, these materials are considered promising candidates for the applications of future technologies. Among the FSMAs, the Ni-Mn-Ga-based materials were chosen for their large shape deformation strain and appropriate phase transformation temperatures for near-room temperature applications. Nevertheless, it is widely known that both the intrinsic brittleness of the Ni-Mn-Ga alloy and the constraint of shape deformation strain due to the existence of grain boundaries in the polycrystal inhibit the applications. Therefore, various Ni-Mn-Ga-based composite materials were designed in this study, and their shape deformation behaviors induced by compressive or magnetic fields were examined by the in situ micro CT observations. In addition, the dependence of the martensite variant reorientation (MVR) on the crystallographic directions was also investigated. It was found that most of the MVRs are active within the magnetic field range applied in the regime of the <100>p, <110>p, and <111>p of the single-crystal {100}p Ni-Mn-Ga cubes.
A New Approach for Deviation Modeling in Compressors: Sensitivity-Correlated Principal Component Analysis
Authors: Li Mingzhi , Yu Xianjun , Meng Dejun , An Guangfeng , Liu Baojie
Published: May 2023

Studies on the geometry variation-related compressor uncertainty quantification (UQ) have often used dimension reduction methods, such as the principal component analysis (PCA), for the modeling of deviations. However, in the PCA method, the main eigenmodes were determined based only on the statistical behavior of geometry variations. While this process can cause some missing modes with a small eigenvalue, it is much more sensitive to blade aerodynamic performances, and thereby reducing the reliability of the UQ analysis. Hence, a novel geometry variation modeling method, named sensitivity-correlated principal component analysis (SCPCA), has been proposed. In addition, by means of the blade sensitivity analysis, the weighting factors for each eigenmode were determined and then used to modify the process of the PCA. As a result, by considering the covariance of geometry variations and the performance sensitivity, the main eigenmodes could be determined and used to reconstruct the blade samples in the UQ analysis. With 98 profile samples measured at the midspan of a high-pressure compressor rotor blade, both the PCA and SCPCA methods were employed for the UQ analysis. The results showed that, compared to the PCA method, the SCPCA method provided a more accurate reconstruction of sensitive deviations, leading to an 11.8% improvement in evaluating the scatter of the positive incidence range, while also maintaining the accuracy of the uncertainty assessment for other performances.
Review on Biomass Pyrolysis with a Focus on Bio-Oil Upgrading Techniques
Authors: Lachos-Perez Daniel , Martins-Vieira João Cláudio , Missau Juliano , Anshu Kumari , Siakpebru Odiri K. , Thengane Sonal K. , Morais Ana Rita C. , Tanabe Eduardo Hiromitsu , Bertuol Daniel Assumpção
Published: May 2023

This review provides insights into the current research on pyrolytic bio-oil obtained from different feedstock regarding upgrading techniques and applications such as energy, fuels, chemicals, and carbon materials. Raw bio-oil is not appropriate for transportation and ignition due to undesired properties; therefore, several challenges have been reported regarding its suitable market application. For liquid biofuel production, thermochemical pathways, particularly hydrogenation and deoxygenation, must be carried out, and for chemical production, liquid solvents are mostly used via physical separation. The main issues related to downstream processes with environmental and economic assessment are also covered. The analysis indicates that the major bottlenecks for commercial applications of upgraded bio-oil are the initial stage (upgrading techniques), high production costs, and pilot scale production. Finally, future directions are addressed for the improvement of bio-oil upgrading.
Outcome of Irrigation and Debridement with Topical Antibiotic Delivery Using Antibiotic-Impregnated Calcium Hydroxyapatite for the Management of Periprosthetic Hip Joint Infection
Authors: Wakabayashi Hiroki , Hasegawa Masahiro , Naito Yohei , Tone Shine , Sudo Akihiro
Published: May 2023

We assessed the clinical results of irrigation and debridement (I&D) with antibiotic-impregnated calcium hydroxyapatite (CHA) as a novel antibiotic delivery system for the treatment of prosthetic-joint-associated infection (PJI) after total hip arthroplasty (THA). Thirteen patients (14 hips) treated with I&D for PJI after THA at our institution between 1997 and 2017 were retrospectively evaluated. The study group included four men (five hips) and nine women, with an average age of 66.3 years. Four patients (five hips) had symptoms of infection within less than 3 weeks; however, nine patients had symptoms of infection over 3 weeks. All patients received I&D with antibiotic-impregnated CHA in the surrounding bone. In two hips (two cups and one stem), cup and/or stem revision were performed with re-implantation because of implant loosening. In ten patients (11 hips), vancomycin hydrochloride was impregnated in the CHA. The average duration of follow-up was 8.1 years. Four patients included in this study died of other causes, with an average follow-up of 6.7 years. Eleven of thirteen patients (12 of 14 hips) were successfully treated, and no signs of infection were observed at the latest follow-up. In two patients (two hips) for whom treatment failed, infection was successfully treated with two-stage re-implantation. Both patients had diabetes mellitus and symptoms of infection over 3 weeks. Eighty-six percent of patients were successfully treated. No complications were observed with this antibiotic-impregnated CHA. I&D treatment with antibiotic-impregnated CHA produced a higher rate of success in patients with PJI after THA.
Chemical Composition of the Cinnamomum malabatrum Leaf Essential Oil and Analysis of Its Antioxidant, Enzyme Inhibitory and Antibacterial Activities
Authors: Kuttithodi Aswathi Moothakoottil , Narayanankutty Arunaksharan , Visakh Naduvilthara U. , Job Joice Tom , Pathrose Berin , Olatunji Opeyemi Joshua , Alfarhan Ahmed , Ramesh Varsha
Published: May 2023

Cinnamomum species are a group of plants belonging to the Lauraceae family. These plants are predominantly used as spices in various food preparations and other culinary purposes. Furthermore, these plants are attributed to having cosmetic and pharmacological potential. Cinnamomum malabatrum (Burm. f.) J. Presl is an underexplored plant in the Cinnamomum genus. The present study evaluated the chemical composition by a GC-MS analysis and antioxidant properties of the essential oil from C. malabatrum (CMEO). Further, the pharmacological effects were determined as radical quenching, enzyme inhibition and antibacterial activity. The results of the GC-MS analysis indicated the presence of 38.26 % of linalool and 12.43% of caryophyllene in the essential oil. Furthermore, the benzyl benzoate (9.60%), eugenol (8.75%), cinnamaldehyde (7.01%) and humulene (5.32%) were also present in the essential oil. The antioxidant activity was indicated by radical quenching properties, ferric-reducing potential and lipid peroxidation inhibition ex vivo. Further, the enzyme-inhibitory potential was confirmed against the enzymes involved in diabetes and diabetic complications. The results also indicated the antibacterial activity of these essential oils against different Gram-positive and Gram-negative bacteria. The disc diffusion method and minimum inhibitory concentration analysis revealed a higher antibacterial potential for C. malabatrum essential oil. Overall, the results identified the predominant chemical compounds of C. malabatrum essential oil and its biological and pharmacological effects.
COVID-19: Focusing on the Link between Inflammation, Vitamin D, MAPK Pathway and Oxidative Stress Genetics
Authors: Cusato Jessica , Manca Alessandra , Palermiti Alice , Mula Jacopo , Costanzo Martina , Antonucci Miriam , Chiara Francesco , De Vivo Elisa Delia , Maiese Domenico , Ferrara Micol , Bonora Stefano , Di Perri Giovanni , D’Avolio Antonio , Calcagno Andrea
Published: May 2023

An uncontrolled inflammatory response during SARS-CoV-2 infection has been highlighted in several studies. This seems to be due to pro-inflammatory cytokines whose production could be regulated by vitamin D, ROS production or mitogen-activated protein kinase (MAPK). Several genetic studies are present in the literature concerning genetic influences on COVID-19 characteristics, but there are few data on oxidative stress, vitamin D, MAPK and inflammation-related factors, considering gender and age. Therefore, the aim of this study was to evaluate the role of single nucleotide polymorphisms in these pathways, clarifying their impact in affecting COVID-19-related clinical features. Genetic polymorphisms were evaluated through real-time PCR. We prospectively enrolled 160 individuals: 139 patients were positive for SARS-CoV-2 detection. We detected different genetic variants able to affect the symptoms and oxygenation. Furthermore, two sub-analyses were performed considering gender and age, showing a different impact of polymorphisms according to these characteristics. This is the first study highlighting a possible contribution of genetic variants of these pathways in affecting COVID-19 clinical features. This may be relevant in order to clarify the COVID-19 etiopathogenesis and to understand the possible genetic contribution for further SARS infections.