bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimized electroencephalogram and functional near-infrared spectroscopy-based mental workload detection method for practical applications
Authors: Chu Hongzuo , Cao Yong , Jiang Jin , Yang Jiehong , Huang Mengyin , Li Qijie , Jiang Changhua , Jiao Xuejun
Published: February 2022

Background

Mental workload is a critical consideration in complex man–machine systems design. Among various mental workload detection techniques, multimodal detection techniques integrating electroencephalogram (EEG) and functional near-infrared spectroscopy (fNIRS) signals have attracted considerable attention. However, existing EEG–fNIRS-based mental workload detection methods have certain defects, such as complex signal acquisition channels and low detection accuracy, which restrict their practical application.

Methods

The signal acquisition configuration was optimized by analyzing the feature importance in mental workload recognition model and a more accurate and convenient EEG–fNIRS-based mental workload detection method was constructed. A classical Multi-Task Attribute Battery (MATB) task was conducted with 20 participating volunteers. Subjective scale data, 64-channel EEG data, and two-channel fNIRS data were collected.

Results

A higher number of EEG channels correspond to higher detection accuracy. However, there is no obvious improvement in accuracy once the number of EEG channels reaches 26, with a four-level mental workload detection accuracy of 76.25 ± 5.21%. Partial results of physiological analysis verify the results of previous studies, such as that the θ power of EEG and concentration of O2Hb in the prefrontal region increase while the concentration of HHb decreases with task difficulty. It was further observed, for the first time, that the energy of each band of EEG signals was significantly different in the occipital lobe region, and the power of $$\beta_{1}$$

β
1

and $$\beta_{2}$$

β
2

bands in the occipital region increased significantly with task difficulty. The changing range and the mean amplitude of O2Hb in high-difficulty tasks were significantly higher compared with those in low-difficulty tasks.

Conclusions

The channel configuration of EEG–fNIRS-based mental workload detection was optimized to 26 EEG channels and two frontal fNIRS channels. A four-level mental workload detection accuracy of 76.25 ± 5.21% was obtained, which is higher than previously reported results. The proposed configuration can promote the application of mental workload detection technology in military, driving, and other complex human–computer interaction systems.
Lanthanide-based metal–organic frameworks solidified by gelatin-methacryloyl hydrogels for improving the accuracy of localization and excision of small pulmonary nodules
Authors: Ji Haoran , Wang Xiaofeng , Wang Pei , Gong Yan , Wang Yun , Liu Chang , Ji Guangyu , Wang Xiansong , Wang Mingsong
Published: February 2022

The localization of invisible and impalpable small pulmonary nodules has become an important concern during surgery, since current widely used techniques for localization have a number of limitations, such as invasive features of hookwires and microcoils, and rapid diffusion after injection of indocyanine green (ICG). Lanthanide-based metal–organic frameworks (MOFs) have been proven as potential fluorescent agents because of their prominent luminescent characteristics, including large Stokes shifts, high quantum yields, long decay lifetimes, and undisturbed emissive energies. In addition, lanthanides, such as Eu, can efficiently absorb X-rays for CT imaging. In this study, we synthesized Eu-UiO-67-bpy (UiO = University of Oslo, bpy = 2,2'-bipyridyl) as a fluorescent dye with a gelatin-methacryloyl (GelMA) hydrogel as a liquid carrier. The prepared complex exhibits constant fluorescence emission owing to the luminescent characteristics of Eu and the stable structure of UiO-67-bpy with restricted fluorescence diffusion attributed to the photocured GelMA. Furthermore, the hydrogel provides stiffness to make the injection site tactile and improve the accuracy of localization and excision. Finally, our complex enables fluorescence-CT dual-modal imaging of the localization site.
Angiogenic and molecular diversity determine hepatic melanoma metastasis and response to anti-angiogenic treatment
Authors: Wohlfeil Sebastian A. , Häfele Verena , Dietsch Bianca , Weller Céline , Sticht Carsten , Jauch Anna Sophia , Winkler Manuel , Schmid Christian David , Irkens Anna Lena , Olsavszky Ana , Schledzewski Kai , Reiners-Koch Philipp-Sebastian , Goerdt Sergij , Géraud Cyrill
Published: February 2022

Background

Cutaneous melanoma exhibits heterogeneous metastatic patterns and prognosis. In this regard, liver metastasis, which is detected in ~ 10–20% of stage 4 patients, came to the fore of melanoma research, as it recently evolved as decisive indicator of treatment resistance to immune checkpoint inhibition.

Methods

Hepatic metastases were induced by intrasplenic injection of five different murine melanoma cell lines. The efficiencies of hepatic colonization, morphologic patterns, gene expression profiles and degree of vascularization were analyzed and Sorafenib was applied as anti-angiogenic treatment.

Results

WT31 melanoma showed the highest efficiency of hepatic colonization, while intermediate efficiencies were observed for B16F10 and RET, and low efficiencies for D4M and HCmel12. RNAseq-based gene expression profiles of high and intermediate metastatic melanomas in comparison to low metastatic melanomas indicated that this efficiency predominantly associates with gene clusters involved in cell migration and angiogenesis. Indeed, heterogeneous vascularization patterns were found in the five models. Although the degree of vascularization of WT31 and B16F10 metastases differed, both showed a strong response to Sorafenib with a successful abrogation of the vascularization.

Conclusion

Our data indicate that molecular heterogeneity of melanomas can be associated with phenotypic and prognostic features of hepatic metastasis paving the way for organ-specific anti-angiogenic therapeutic approaches.
Administration of Maresin-1 ameliorates the physiopathology of experimental autoimmune encephalomyelitis
Authors: Sánchez-Fernández Alba , Zandee Stephanie , Mastrogiovanni Mauricio , Charabati Marc , Rubbo Homero , Prat Alexandre , López-Vales Rubèn
Published: February 2022

Background

Resolution of inflammation is an active and regulated process that leads to the clearance of cell debris and immune cells from the challenged tissue, facilitating the recovery of homeostasis. This physiological response is coordinated by endogenous bioactive lipids known as specialized pro-resolving mediators (SPMs). When resolution fails, inflammation becomes uncontrolled leading chronic inflammation and tissue damage, as occurs in multiple sclerosis (MS).

Methods

SPMs and the key biosynthetic enzymes involved in SPM production were analysed by metabololipidomics and qPCR in active brain lesions, serum and peripheral blood mononuclear cells (PBMC) of MS patients as well as in the spinal cord of mice with experimental autoimmune encephalomyelitis (EAE). We also tested the therapeutic actions of the SPM coined Maresin-1 (MaR1) in EAE mice and studied its impact on inflammation by doing luminex and flow cytometry analysis.

Results

We show that levels of MaR1 and other SPMs were below the limit of detection or not increased in the spinal cord of EAE mice, whereas the production of pro-inflammatory eicosanoids was induced during disease progression. Similarly, we reveal that SPMs were undetected in serum and active brain lesion samples of MS patients, which was linked to impaired expression of the enzymes involved in the biosynthetic pathways of SPMs. We demonstrate that exogenous administration of MaR1 in EAE mice suppressed the protein levels of various pro-inflammatory cytokines and reduced immune cells counts in the spinal cord and blood. MaR1 also decreased the numbers of Th1 cells but increased the accumulation of regulatory T cells and drove macrophage polarization towards an anti-inflammatory phenotype. Importantly, we provide clear evidence that administration of MaR1 in mice with clinical signs of EAE enhanced neurological outcomes and protected from demyelination.

Conclusions

This study reveals that there is an imbalance in the production of SPMs in MS patients and in EAE mice, and that increasing the bioavailability of SPMs, such as MaR1, minimizes inflammation and mediates therapeutic actions. Thus, these data suggest that immunoresolvent therapies, such as MaR1, could be a novel avenue for the treatment of MS.
Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease
Authors: van Kooten Harmke A. , Ditters Imke A. M. , Hoogeveen-Westerveld Marianne , Jacobs Edwin H. , van den Hout Johanna M. P. , van Doorn Pieter A. , Pijnappel W. W. M. Pim , van der Ploeg Ans T. , van der Beek Nadine A. M. E.
Published: February 2022

Background

Enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA, alglucosidase alfa) has improved survival, motor outcomes, daily life activity and quality of life in Pompe patients. However, ERT in Pompe disease often induces formation of antibodies, which may reduce the efficacy of treatment and can lead to adverse events. In this study antibody formation and their effect on clinical outcome in patients with childhood onset Pompe disease treated with enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA) are analyzed.

Methods

Enzyme-linked immunosorbent assay (ELISA) was used to determine anti-rhGAA antibody titers at predefined time points. The effect of antibodies on rhGAA activity (neutralizing effects) was measured in vitro. Clinical effects were evaluated by assessing muscle strength (MRC score) and function (QMFT-score), pulmonary function and infusion associated reactions (IARs).

Results

Twenty-two patients were included (age at start ERT 1.1–16.4 years, median treatment duration 12.4 years). Peak antibody titers were low (< 1:1250) in 9%, intermediate (1:1250–1:31,250) in 68% and high (≥ 1:31250) in 23% of patients; three patients (14%) had more than one titer of ≥ 1:31,250. Four patients (18%) experienced IARs; two patients from the high titer group had 86% of all IARs. Inhibition of intracellular GAA activity (58%) in vitro was found in one sample. The clinical course did not appear to be influenced by antibody titers.

Conclusions

Ninety-one percent of childhood onset Pompe patients developed anti-rhGAA antibodies (above background level), a minority of whom had high antibody titers at repeated time points, which do not seem to interfere with clinical outcome. High antibody titers may be associated with the occurrence of IARs. Although the majority of patients does not develop high titers; antibody titers should be determined in case of clinical deterioration.
The association between dietary phytochemical index with depression and quality of life in iranian adolescent girls
Authors: Sangouni Abbas Ali , Vasmehjani Azam Ahmadi , Ghayour-Mobarhan Majid , Ferns Gordon A. , Khayyatzadeh Sayyed Saeid
Published: February 2022

Background

There is increasing evidence that the dietary intake of phytochemicals is inversely associated with severity of depression and positively associated with quality of life (QoL). The present study investigated the relationship between dietary phytochemical index (DPI) with depression and QoL scores in Iranian adolescent girls.

Methods

A total of 733 adolescent girls from Mashhad and Sabzevar cities in northeastern Iran were entered into this cross-sectional study. Assessment of depression and QoL was performed utilizing the Beck Depression Inventory (BDI) and SF-12v2 questionnaire, respectively. Assessment of dietary intake was undertaken by a qualified dietitian, using a validated food-frequency questionnaire (FFQ) containing 168 food items. To explore the association between DPI with QoL and depression, logistic regression was used in crude and adjusted models.

Results

The participants in the fourth quartile of DPI compared with the first quartile had a 50% lower odds of depression (OR: 0.50; 95% CI: 0.30-0.84, P = 0.009) This relation remained significant in all adjusted models. The adolescents in highest quartile of DPI compared with the first quartile had 38% lower odds of poor QoL (OR: 0.62; 95% CI: 0.41-0.94, P = 0.02). This association remained significant in adjusted models I and II, but not after adjusting for all confounding variables (OR: 0.67; 95% CI: 0.43-1.02, P = 0.06) (Model III).

Conclusions

DPI was inversely associated with risk of depression. The association between DPI score and QoL remained unclear. Further prospective and interventional studies are required.
Aggressive variants of prostate cancer: underlying mechanisms of neuroendocrine transdifferentiation
Authors: Merkens Lina , Sailer Verena , Lessel Davor , Janzen Ella , Greimeier Sarah , Kirfel Jutta , Perner Sven , Pantel Klaus , Werner Stefan , von Amsberg Gunhild
Published: February 2022

Prostate cancer is a hormone-driven disease and its tumor cell growth highly relies on increased androgen receptor (AR) signaling. Therefore, targeted therapy directed against androgen synthesis or AR activation is broadly used and continually improved. However, a subset of patients eventually progresses to castration-resistant disease. To date, various mechanisms of resistance have been identified including the development of AR-independent aggressive variant prostate cancer based on neuroendocrine transdifferentiation (NED). Here, we review the highly complex processes contributing to NED. Genetic, epigenetic, transcriptional aberrations and posttranscriptional modifications are highlighted and the potential interplay of the different factors is discussed.

Background

Aggressive variant prostate cancer (AVPC) with traits of neuroendocrine differentiation emerges in a rising number of patients in recent years. Among others, advanced therapies targeting the androgen receptor axis have been considered causative for this development. Cell growth of AVPC often occurs completely independent of the androgen receptor signal transduction pathway and cells have mostly lost the typical cellular features of prostate adenocarcinoma. This complicates both diagnosis and treatment of this very aggressive disease. We believe that a deeper understanding of the complex molecular pathological mechanisms contributing to transdifferentiation will help to improve diagnostic procedures and develop effective treatment strategies. Indeed, in recent years, many scientists have made important contributions to unravel possible causes and mechanisms in the context of neuroendocrine transdifferentiation. However, the complexity of the diverse molecular pathways has not been captured completely, yet. This narrative review comprehensively highlights the individual steps of neuroendocrine transdifferentiation and makes an important contribution in bringing together the results found so far.
Efficacy and safety of traditional Chinese medicine in patients with acute exacerbation of idiopathic pulmonary fibrosis: study protocol for randomized, controlled, exploratory clinical trial
Authors: Hailong Zhang , Jiansheng Li , Wen Guo , Lu Wang , Dong Zhang , Limin Zhao , Miao Zhou , Weixian Luo
Published: February 2022

Background

At present, there is short of effective treatment for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). The treatment of IPF with traditional Chinese medicine (TCM) has some advantages. However, the evidence is unclear whether TCM can be recommended as an effective therapy to treat AE-IPF. The purpose of the study is to explore the efficacy and safety of TCM for patients with AE-IPF.

Methods

A randomized, double-blind, placebo-controlled, exploratory clinical trial will be performed. A total of 80 patients diagnosed with AE-IPF will be randomized into the intervention or control group. In addition to conventional treatment, the intervention group will be treated with Kangxianhuanji granule, and the control group will be given a placebo granule. The administration frequency is 10 g each time and two times daily. After 4 weeks of treatment, the patients were followed up for 12 weeks. The primary outcomes are treatment failure rate and all-cause mortality. Secondary outcome measures will include the length of hospitalization, overall survival, acute exacerbation rate, intubation rate, Modified British Medical Research Council (mMRC) score, the St George’s Respiratory Questionnaire idiopathic pulmonary fibrosis (SGRQ-I) score, and arterial blood gas analysis.

Discussion

TCM may be beneficial in IPF. However, it has never been evaluated in patients with AE-IPF, who are incredibly prone to respiratory failure and have a high mortality rate. It is the first clinical trial to explore the efficacy and safety of TCM in the treatment of AE-IPF. This result will provide a basis for further study, which provides a high-quality evidence for the treatment of AE-IPF with TCM.

Trial registration

Chinese Clinical Trial Registry ChiCTR1900026289. Registered on 29 September 2019.
Cocaine-related cervical spinal cord infarction: a case report and review of the literature
Authors: Pichiorri F. , Masciullo M. , Foti C. , Molinari M. , Scivoletto G.
Published: February 2022

Study design

Case report.

Objectives

To report a clinical case of spinal cord infarction due to cocaine use.

Setting

Spinal Center, IRCCS Fondazione S. Lucia, Rome (Italy).

Case presentation

Two days after recreational use of cocaine, a 27-year-old Caucasic man was admitted to the emergency department for acute cervical pain, weakness in all four limbs, and urinary retention. A cervical spinal magnetic resonance imaging scan, performed after 2 days, showed a “pencil-like” lesion extending from C4 to T1 metamer, compatible with acute ischemia in the anterior spinal artery territory. Other causes of vascular disorders, as well as inflammatory and infectious disorders were ruled out. At admission in our department, the patient had an incomplete tetraplegia at level C6, an indwelling catheter, and was unable to stand and walk. After 3 months of rehabilitation, he had an AIS score D tetraplegia at level C7, was able to stand and walk using parallel bars, and indwelling catheter was replaced by intermittent catheterization.

Discussion and conclusions

The etiology of medullary infarction may remain unexplained in nearly 30–40% of cases. Even if rare, cocaine-induced ischemic myelopathy should be considered and ruled out in the differential diagnosis of any acute nontraumatic myelopathy, especially in young patients.
Machine learning approaches to optimize small-molecule inhibitors for RNA targeting
Authors: Grimberg Hadar , Tiwari Vinay S. , Tam Benjamin , Gur-Arie Lihi , Gingold Daniela , Polachek Lea , Akabayov Barak
Published: February 2022

In the era of data science, data-driven algorithms have emerged as powerful platforms that can consolidate bioisosteric rules for preferential modifications on small molecules with a common molecular scaffold. Here we present complementary data-driven algorithms to minimize the search in chemical space for phenylthiazole-containing molecules that bind the RNA hairpin within the ribosomal peptidyl transferase center (PTC) ofMycobacterium tuberculosis. Our results indicate visual, geometrical, and chemical features that enhance the binding to the targeted RNA. Functional validation was conducted after synthesizing 10 small molecules pinpointed computationally. Four of the 10 were found to be potent inhibitors that target hairpin 91 in the ribosomal PTC ofM. tuberculosisand, as a result, stop translation.

Graphical Abstract
Inflammatory markers and long term hematotoxicity of holmium-166-radioembolization in liver-dominant metastatic neuroendocrine tumors after initial peptide receptor radionuclide therapy
Authors: Ebbers Sander C. , Brabander Tessa , Tesselaar Margot E. T. , Hofland Johannes , Braat Manon N. G. J. A. , Wessels Frank J. , Barentsz Maarten W. , Lam Marnix G. E. H. , Braat Arthur J. A. T.
Published: February 2022

Purpose

In patients with neuroendocrine tumor liver metastases, additional tumor reduction can be achieved by sequential treatment with [166Ho]-radioembolization after peptide receptor radionuclide therapy (PRRT). The aim of this study was to analyze hematotoxicity profiles, (i.e. lymphocyte and neutrophile toxicity) and the prognostic value of neutrophil-to-lymphocyte ratio (NLR) and thrombocyte-to-lymphocyte ratio (TLR).

Methods

All patients included in the prospective HEPAR PLuS study were included in this study. Blood testing was performed at baseline (before radioembolization) and at regular intervals during 1-year follow-up. Radiological response was assessed at 3, 6, 9, and 12 months according to RECIST 1.1. Logistic regression was used to analyze the prognostic value of NLR and TLR on response.

Results

Thirty-one patients were included in the toxicity analysis; thirty were included in the response analysis. Three weeks after radioembolization, a significant decrease in lymphocyte count (mean change − 0.26 × 109/L) was observed. Ten patients (32.2%) experienced grade 3–4 lymphocyte toxicity. This normalized at 6 weeks and 3 months after treatment, while after 6 months a significant increase in lymphocyte count was observed. An increase in NLR and TLR at 3 weeks, compared to baseline, significantly predicted response at 3 months (AUC = 0.841 and AUC = 0.839, respectively) and at 6 months (AUC = 0.779 and AUC = 0.765). No significant relation with survival was found.

Conclusions

Toxicity after sequential treatment with PRRT and [166Ho]-radioembolization is limited and temporary, while significant additional benefit can be expected. Change in NLR and TLR at 3-weeks follow-up may be valuable early predictors of response.

Trial registration ClinicalTrials.gov, NCT02067988. Registered 20 February 2014, https://clinicaltrials.gov/ct2/show/record/NCT02067988.
YBX1 mediates alternative splicing and maternal mRNA decay during pre-implantation development
Authors: Deng Mingtian , Chen Baobao , Liu Zifei , Wan Yongjie , Li Dongxu , Yang Yingnan , Wang Feng
Published: February 2022

Background

In mammals, maternal gene products decay and zygotic genome activation (ZGA) during maternal to zygotic transition (MZT) is critical for the early embryogenesis. Y-box binding protein YBX1 plays vital roles in RNA stabilization and transcriptional regulation, but its roles remain to be elucidated during pre-implantation development.

Methods

In the present study, we re-analyzed transcriptional level of YBX1 in mice, human, bovine, and goat embryos using public RNA-seq datasets. We further performed siRNA microinjection to knock down the expression of YBX1, and RNA sequencing of the 8-cell stage embryos in the control and YBX1 knockdown group. To reveal the regulation mechanisms of YBX1, we conducted differentially expression analysis, alternative splicing (AS) analysis, enrichment analysis, and 5-EU staining using DESeq2, rMATs, clusterProfiler, and immunofluorescence technique, respectively.

Results

The expression of YBX1 was increased during MZT in goat, bovine, human, and mice, but significantly decreased in YBX1 knockdown embryos compared with the controls, suggesting successfully knockdown of YBX1. The percentage of blastocyst was decreased, while embryos blocked at the 2- and 4-cell stage were increased in YBX1 knockdown embryos compared to the controls. Using RNA-seq, we identified 1623 up-regulated and 3531 down-regulated genes in the 8-cell stage YBX1 knockdown embryos. Of note, the down-regulated genes were enriched in regulation of RNA/mRNA stability and spliceosome, suggesting that YBX1 might medicate RNA stability and AS. To this end, we identified 3284 differential AS events and 1322 differentially expressed maternal mRNAs at the 8-cell stage YBX1 knockdown embryos. Meanwhile, the splicing factors and mRNA decay-related genes showed aberrant expression, and the transcriptional activity during ZGA in goat and mice was compromised when YBX1 was knocked down.

Conclusion

YBX1 serves an important role in maternal mRNA decay, alternative splicing, and the transcriptional activity required for early embryogenesis, which will broaden the current understanding of YBX1 functions during the stochastic reprogramming events.
Insights into the present and future of cartilage regeneration and joint repair
Authors: Evenbratt H. , Andreasson L. , Bicknell V. , Brittberg M. , Mobini R. , Simonsson S.
Published: February 2022

Knee osteoarthritis is the most common joint disease. It causes pain and suffering for affected patients and is the source of major economic costs for healthcare systems. Despite ongoing research, there is a lack of knowledge regarding disease mechanisms, biomarkers, and possible cures. Current treatments do not fulfill patients’ long-term needs, and it often requires invasive surgical procedures with subsequent long periods of rehabilitation. Researchers and companies worldwide are working to find a suitable cell source to engineer or regenerate a functional and healthy articular cartilage tissue to implant in the damaged area. Potential cell sources to accomplish this goal include embryonic stem cells, mesenchymal stem cells, or induced pluripotent stem cells. The differentiation of stem cells into different tissue types is complex, and a suitable concentration range of specific growth factors is vital. The cellular microenvironment during early embryonic development provides crucial information regarding concentrations of signaling molecules and morphogen gradients as these are essential inducers for tissue development. Thus, morphogen gradients implemented in developmental protocols aimed to engineer functional cartilage tissue can potentially generate cells comparable to those within native cartilage. In this review, we have summarized the problems with current treatments, potential cell sources for cell therapy, reviewed the progress of new treatments within the regenerative cartilage field, and highlighted the importance of cell quality, characterization assays, and chemically defined protocols.
Improved vehicle detection systems with double-layer LSTM modules
Authors: Yang Wei-Jong , Liow Wan-Ju , Chen Shao-Fu , Yang Jar-Ferr , Chung Pau-Choo , Mao Songan
Published: February 2022

The vision-based smart driving technologies for road safety are the popular research topics in computer vision. The precise moving object detection with continuously tracking capability is one of the most important vision-based technologies nowadays. In this paper, we propose an improved object detection system, which combines a typical object detector and long short-term memory (LSTM) modules, to further improve the detection performance for smart driving. First, starting from a selected object detector, we combine all vehicle classes and bypassing low-level features to improve its detection performance. After the spatial association of the detected objects, the outputs of the improved object detector are then fed into the proposed double-layer LSTM (dLSTM) modules to successfully improve the detection performance of the vehicles in various conditions, including the newly-appeared, the detected and the gradually-disappearing vehicles. With stage-by-stage evaluations, the experimental results show that the proposed vehicle detection system with dLSTM modules can precisely detect the vehicles without increasing computations.
Factors associated with patient-reported experiences and outcomes of substance use disorder treatment in Cape Town, South Africa
Authors: Myers Bronwyn , Koch J. Randy , Johnson Kim , Harker Nadine
Published: February 2022

Background

Interventions are needed to improve the quality of South Africa’s substance use disorder (SUD) treatment system. This study aimed to identify factors associated with patient-reported suboptimal access, quality, and outcomes of SUD treatment to guide the design of targeted quality improvement initiatives.

Method

We analysed clinical record and patient survey data routinely collected by SUD services in the Western Cape Province, South Africa. The sample included 1097 treatment episodes, representing 32% of all episodes in 2019. Using multivariate logistic regression, we modelled socio-demographic, substance use and treatment correlates of patient-reported suboptimal access to, quality and outcomes of SUD treatment.

Results

Overall, 37.9% of patients reported substantial difficulties in accessing treatment, 28.8% reported suboptimal quality treatment, and 31.1% reported suboptimal SUD outcomes. The odds of reporting poor access were elevated for patients identifying as Black/African, in residential treatment, with comorbid mental health problems, and longer histories of substance use. Length of substance use, comorbid mental health problems, and prior SUD treatment were associated with greater likelihood of reporting suboptimal quality treatment. Patients with comorbid mental health problems, polysubstance use, who did not complete treatment, and who perceived treatment to be of poor quality were more likely to report suboptimal outcomes.

Conclusion

This study is among the first to use patient-reported experiences and outcome measures to identify targets for SUD treatment improvement. Findings suggest substantial room to improve South African SUD treatment services, with targeted efforts needed to reduce disparities in outcomes for patients of Black/African descent, for those with comorbid mental health problems, and for patients who have chronic substance use difficulties. Interventions to enhance the relevance, appropriateness, and acceptability of SUD services for these patient sub-groups are needed to improve system performance.
Factors associated to neurocognitive impairment in older adults living with HIV
Authors: Gutierrez-San-Juan Júlia , Arrieta-Aldea Itziar , Arnau-Barrés Isabel , García-Escobar Greta , Lerma-Chipirraz Elisabet , Pérez-García Paula , Marcos Agustin , Blasco-Hernando Fabiola , Gonzalez-Mena Alicia , Cañas Esperanza , Knobel Hernando , Güerri-Fernández Robert
Published: February 2022

Objective

The HIV infection is a chronic disease that causes neurocognitive impairment (NI) and has been related with early development of frailty. We aimed to study the main risk factors for neurocognitive disorders and frailty in HIV older adults.

Materials and methods

Cross-sectional study with 40 HIV individuals older than 65 years under antiretroviral therapy in Hospital del Mar (Barcelona) recruited between November 2019 and October 2020. Data has been obtained through clinical scores and a blood sample to evaluate NI and frailty and has been analyzed with non-parametric tests and a multivariate logistic regression model.

Results

Among the 40 patients admitted for the study, 14 (35%) had positive screening for NI. We found that HIV individuals with nadir CD4+ T-cell count lower than 350 cells/mm3 had 39.7 more risk for NI (95% CI 2.49–632.10; p = 0.009). Those with a lower education level had 22.78 more risk for neurocognitive disorders (95% CI 2.13–242.71; p = 0.01) and suffering any comorbidity with a punctuation ≥ 1 in the Charlson Comorbidity index had an increased risk of 18.26 of developing NI and frailty (95% CI 1.30–256.33; p = 0.031), among them diabetes was significantly more frequent in NI.

Conclusion

We observed that the main risk factors for a positive NI screening in HIV older adults were low education level, a nadir CD4+ T-cell count < 350 cells/mm3 and the presence of any comorbidity, highlighting diabetes among them.
Understanding the drivers of food security among agriculture-based households in Gurué District, Central Mozambique
Authors: Matavel Custodio , Hoffmann Harry , Rybak Constance , Steinke Jonathan , Sieber Stefan , Müller Klaus
Published: February 2022

Background

The prevalence of food insecurity in Mozambique is alarming, despite progress made during the 2010s. Several studies apply different proxy indicators of food security (FS) to assess the FS situation. However, these studies overlook the factors affecting FS, using only a single data point that results in an incomplete picture of FS. Food security is expected to fluctuate, being better and worse than what studies suggest. Using a sample of 296 households to assess FS, key drivers conditioning households’ capacity to achieve FS in Gurué District, Central Mozambique, are identified. Data were collected in the pre-harvest period and during the harvest period to capture relevant interseasonal variation of FS. Household FS is assessed using three standard indicators: Household Dietary Diversity Score (HDDS), Household Food Consumption Score (HFCS), and Months of Adequate Household Food Provisioning (MAHFP).

Results

Each household was classified into a specific FS status depending on the indicator applied. Generally, most households were classified as being severely or moderately food insecure during the pre-harvest season, while during the harvest season, medium and high levels of FS predominated. Nevertheless, varying outcomes were found depending on the indicator used to assess FS. MAHFP and HDDS are more related to the consumption of farm-sourced food, while HFCS responds more strongly to purchased food. Gender and age of the household head, geographic location, size and quality of land, staples production (especially cassava), livestock and crop diversity, as well as cash crops had a statistically significant effect on FS indicators.

Conclusions

The study concludes that the decision whether farmers should rely on staple foods production for increasing their FS status or specialize on cash crops production to generate income and buy food depends on the indicator used to assess FS, since each indicator captures a specific domain of food security. Thus, one central recommendation derived from our results is that policy makers should promote a balance between market-oriented agriculture and subsistence production to achieve FS.
Novel humanized monoclonal antibodies for targeting hypoxic human tumors via two distinct extracellular domains of carbonic anhydrase IX
Authors: Zatovicova Miriam , Kajanova Ivana , Barathova Monika , Takacova Martina , Labudova Martina , Csaderova Lucia , Jelenska Lenka , Svastova Eliska , Pastorekova Silvia , Harris Adrian L. , Pastorek Jaromir
Published: February 2022

Background

Hypoxia in the tumor microenvironment (TME) is often the main factor in the cancer progression. Moreover, low levels of oxygen in tumor tissue may signal that the first- or second-line therapy will not be successful. This knowledge triggers the inevitable search for different kinds of treatment that will successfully cure aggressive tumors. Due to its exclusive expression on cancer cells, carbonic anhydrase IX belongs to the group of the most precise targets in hypoxic tumors. CA IX possesses several exceptional qualities that predetermine its crucial role in targeted therapy. Its expression on the cell membrane makes it an easily accessible target, while its absence in healthy corresponding tissues makes the treatment practically harmless. The presence of CA IX in solid tumors causes an acidic environment that may lead to the failure of standard therapy.

Methods

Parental mouse hybridomas (IV/18 and VII/20) were humanized to antibodies which were subsequently named CA9hu-1 and CA9hu-2. From each hybridoma, we obtained 25 clones. Each clone was tested for antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activity, affinity, extracellular pH measurement, multicellular aggregation analysis, and real-time monitoring of invasion with the xCELLigence system.

Results

Based on the results from in vivo experiments, we have selected mouse monoclonal antibodies VII/20 and IV/18. The first one is directed at the conformational epitope of the catalytic domain, internalizes after binding to the antigen, and halts tumor growth while blocking extracellular acidification. The second targets the sequential epitope of the proteo-glycan domain, does not internalize, and is able to block the attachment of cancer cells to the matrix preventing metastasis formation. In vitro experiments prove that humanized versions of the parental murine antibodies, CA9hu-1 and CA9hu-2, have preserved these characteristics. They can reverse the failure of standard therapy as a result of an acidic environment by modulating the TME, and both are able to induce an immune response and have high affinity, as well as ADCC and CDC activity.

Conclusion

CA9hu-1 and CA9hu-2 are the very first humanized antibodies against CA IX that are likely to become suitable therapies for hypoxic tumors. These antibodies can be applied in the treatment therapy of primary tumors and suppression of metastases formation.
Clinical and antibody characteristics reveal diverse signatures of severe and non-severe SARS-CoV-2 patients
Authors: Wang Hongye , Yan Dongshan , Li Ya , Gong Yanfei , Mai Yulin , Li Bingxiang , Zhu Xiaoyong , Wan Xinrui , Xie Liyun , Jiang HuaKe , Zhang Min , Sun Ming , Yao Yufeng , Zhu Yongzhang
Published: February 2022

Background

COVID-19 pandemic continues, clarifying signatures in clinical characters and antibody responses between severe and non-severe COVID-19 cases would benefit the prognosis and treatment.

Methods

In this study, 119 serum samples from 37 severe or non-severe COVID-19 patients from the First People's Hospital of Yueyang were collected between January 25 and February 18 2020. The clinical features, antibody responses targeting SARS-CoV-2 spike protein (S) and its different domains, SARS-CoV-2-specific Ig isotypes, IgG subclasses, ACE2 competitive antibodies, binding titers with FcγIIa and FcγIIb receptors, and 14 cytokines were comprehensively investigated. The differences between severe and non-severe groups were analyzed using Mann–Whitney U test or Fisher’s exact test.

Results

Severe group including 9 patients represented lower lymphocyte count, higher neutrophil count, higher level of LDH, total bile acid (TBA) (P < 1 × 10–4), r-glutaminase (P = 0.011), adenosine deaminase (P < 1 × 10–4), procalcitonin (P = 0.004), C-reactive protein (P < 1 × 10–4) and D-dimer (P = 0.049) compared to non-severe group (28 patients). Significantly, higher-level Igs targeting S, different S domains (RBD, RBM, NTD, and CTD), FcγRIIa and FcγRIIb binding capability were observed in a severe group than that of a non-severe group, of which IgG1 and IgG3 were the main IgG subclasses. RBD-IgG were strongly correlated with S-IgG both in severe and non-severe group. Additionally, CTD-IgG was strongly correlated with S-IgG in a non-severe group. Positive RBD-ACE2 binding inhibition was strongly associated with high titers of antibody (S-IgG1, S-IgG3, NTD-IgG, RBD-IgA, NTD-IgA, and CTD-IgA) especially RBD-IgG and CTD-IgG in the severe group, while in the non-severe group, S-IgG3, RBD-IgG, NTD-IgG, and NTD-IgM were correlated with ACE2 blocking rate. S-IgG1, NTD-IgM and S-IgM were negatively associated with illness day in a severe group, while S-IgG3, RBD-IgA, CTD-IgA in the severe group (r = 0.363, P = 0.011) and S-IgG1, NTD-IgA, CTD-IgA in the non-severe group were positively associated with illness day. Moreover, GRO-α, IL-6, IL-8, IP-10, MCP-1, MCP-3, MIG, and BAFF were also significantly elevated in the severe group.

Conclusion

Antibody detection provides important clinical information in the COVID-19 process. The different signatures in Ig isotypes, IgG subclasses, antibody specificity between the COVID-19 severe and non-severe group will contribute to future therapeutic and preventive measures development.

Graphical Abstract
Suitability of Rice Husk Ash (RHA) with lime as a soil stabilizer in geotechnical applications
Authors: Pushpakumara B. H. J. , Mendis W. S. W.
Published: February 2022

Soils containing significant levels of silt or clay generally exhibit unacceptable engineering properties (i.e. low strength, high compressibility and high level of volumetric changes) when exposed to variation in moisture content. Chemical stabilizers such as cement and lime which are currently practiced, are often high-priced and unhygienic in terms of environmental sustainability. The prevailing study intended to explore the potential of the local Rice Husk Ash (RHA) which is an agricultural waste, with lime as a soil stabilizer. This experimental study was conducted on clayey soil with high plasticity. Different mixture proportions of RHA (i.e. 5%, 10%, 20% and 30%) and lime (i.e. 10% and 20%) were used to treat the parent soil. Observations were made for variations in index (i.e. liquid limit, plastic limit, sieve analysis, etc.) and mechanical properties (i.e. compressibility, permeability and shear strength) of treated soils soon and 28 days after mixing. It was found that 10% of RHA and 20% of lime by dry soil weight as the optimum dosage for the treatment. This optimum dosage increases the unconfined compressive strength and internal friction angle by 54.05% and 60.48%, respectively and reduces plasticity index by 56.67% at 28 days after mixing. It could be identified that RHA and lime mixture was capable of improving index and mechanical properties of soil, positively.
Shape-controlled synthesis of zinc nanostructures mediating macromolecules for biomedical applications
Authors: Mousavi Seyyed Mojtaba , Behbudi Gity , Gholami Ahmad , Hashemi Seyyed Alireza , Nejad Zohre Mousavi , Bahrani Sonia , Chiang Wei-Hung , Wei Lai Chin , Omidifar Navid
Published: February 2022

Zinc nanostructures (ZnONSs) have attracted much attention due to their morphological, physicochemical, and electrical properties, which were entailed for various biomedical applications such as cancer and diabetes treatment, anti-inflammatory activity, drug delivery. ZnONS play an important role in inducing cellular apoptosis, triggering excess reactive oxygen species (ROS) production, and releasing zinc ions due to their inherent nature and specific shape. Therefore, several new synthetic organometallic method has been developed to prepare ZnO crystalline nanostructures with controlled size and shape. Zinc oxide nanostructures’ crystal size and shape can be controlled by simply changing the physical synthesis condition such as microwave irradiation time, reaction temperature, and TEA concentration at reflux. Physicochemical properties which are determined by the shape and size of ZnO nanostructures, directly affect their biological applications. These nanostructures can decompose the cell membrane and accumulate in the cytoplasm, which leads to apoptosis or cell death. In this study, we reviewed the various synthesis methods which affect the nano shapes of zinc particles, and physicochemical properties of zinc nanostructures that determined the shape of zinc nanomaterials. Also, we mentioned some macromolecules that controlled their physicochemical properties in a green and biological approaches. In addition, we present the recent progress of ZnONSs in the biomedical fields, which will help centralize biomedical fields and assist their future research development.
Evaluation of quality and utility of YouTube vitreoretinal surgical videos
Authors: Lucatto Luiz Filipe Adami , Prazeres Juliana Moura Bastos , Guerra Ricardo Luz Leitão , Arantes Rafael , Barbosa Gabriel Castilho Sandoval , Badaró Emmerson , Lima Luiz H. , Rodrigues Eduardo
Published: February 2022

Background

We evaluated the utility and quality of surgical videos posted on the main retinal YouTube channels by surgeons at different career stages and assessed how well the steps of the vitrectomy videos conformed to the parameters in the Casey Eye Institute Vitrectomy Indices Tool for Skills assessment (CEIVITS) scale.

Methods

Forty-five videos were included from nine retinal YouTube channels posted from 2011 to 2021. For each surgeon, 10 videos were randomized and the utility, quality, and educational content were assessed. For each video, the surgeons also assessed how the validated CEIVITS items were presented in the videos. The surgeons were divided based on years of experience: fellows (0–3 years), young surgeons (4–10 years), and senior surgeons (more than 10 years).

Results

The video image quality was rated as good in 63.52% of evaluations, moderate in 30.37%, and poor in 6.11%. The quality assessment of the videos among the groups did not differ. The fellows rated the use of the videos as educational tools higher (3.99) than the young (3.87) and senior surgeons (3.47) (p  < 0.0002, Kruskal–Wallis test); 34.76% of the fellows reported learning something new from the videos compared with 19.17% of the senior surgeons (p  < 0.05). The CEIVITS scale item that was seen more frequently was related to core vitrectomies (72.29%) and the least represented was about checking infusion lines (80.17%).

Conclusions

Vitreoretinal surgical videos are useful educational tools during all stages of surgeons’ careers, and the evaluation of the quality of the images did not differ significantly among the groups, however, surgeons with expertise shorter than 10 years report significantly greater use of videos than experienced surgeons. Videos posted to the public domain on different social media, most often YouTube, are widespread and unregulated for providing complimentary surgical education. Retinal societies should formulate guidelines and improve the educational value of the surgical videos posted on the Internet.

Trial Registration The Federal University of São Paulo institution’s Research Ethics Committee reviewed and approved this study protocol (Approval Number, 4.726.589).
Health-Related Quality of Life in people with Multiple Sclerosis: How does this Population Compare to Population-based Norms in Different Health Domains?
Authors: Faraclas Erin , Lynn Jeff , Lau Jeffery D. , Merlo Angela
Published: February 2022

Purpose

The purposes of this investigation were to (1) identify the domains of health-related quality of life most impacted in people with RRMS, (2) compare the health-related QOL in people with RRMS to general population norms, and (3) to describe subgroups within the RRMS population that have similar health and wellness needs.

Methods

This was a cross-sectional QOL investigation of adults with RRMS. The SF-36v2 survey and demographic information were collected electronically via Qualtrics. Participants (n = 120) were recruited through social media and the National Multiple Sclerosis Society of the United States. One-sample Z-tests were completed for all subscales, and component mean scores to determine if a difference between the sample and population norms existed.

Results

All values of z were statistically significant, p < .01, for all subscale and composite scores. Social function, physical function, and the mental health component scores had the lowest subscale means. A first stage depression screen revealed that 49% of the surveyed population were at risk for depression, compared to 18% in the general population. Further dividing the sample into years since MS diagnosis, the recently diagnosed group had 61% at risk for depression.

Conclusions

Challenges related to the mental health of individuals with RRMS are influencing overall health-related QOL. Early on in the disease course (0–3 years), mental health affected QOL more than physical health. More attention must be given to the nonphysical domains of health to advance the QOL for people with RRMS.