bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncovering terra incognita in the AHD design space: A review of affective haptic devices
Authors: Ipakchian Askari Sima , Haans Antal , IJsselsteijn Wijnand A.
Published: November 2022

Affective haptic devices (AHDs) have been developed with the aim of communicating touch acts, symbolic messages, emotions, and/or providing a sense of social awareness. Within AHDs, three categories can be distinguished: mediated social touch (MST), symbolic communication systems, and awareness systems. For each of these categories, prototypes have been developed and discussed in the literature. Each such prototype, however, describes but a small part of the design space of AHDs. What is lacking is a description of the design space itself—of all choices that can be considered during the design process. Such a description will allow for a more systematic exploration of AHD designs and provides a means of combining insights gained from individual point solutions (i.e., existing prototypes). Therefore, in this article, we provide a systematic description of the design space of AHDs and its underlying dimensions based on general (e.g., revisability or synchronicity) and AHD-specific (e.g., actuation type) communication system characteristics. This resulted in 17 design dimensions, each consisting of two or more categories (the design characteristics). Based on a systematic literature search from devices up to 2019, 89 AHD prototypes were identified, and each was classified on the design dimensions. The empirical analysis of where these AHDs are located in the design space revealed, first, that potentially interesting characteristics from mediated communication, such as revisability and reviewability, are underexplored in AHDs. Second, MST devices were found to often lack those system characteristics, such as real-time modalities, that seem crucial for providing the affordances needed to simulate social touch. In particular, when comparing symbolic and awareness devices to MST devices, we found the latter to more frequently lack some of the key characteristics of face-to-face communication (i.e., bi-directional and symmetric communication). Limitations and implications are discussed.
Association between serum Klotho concentration and all-cause and cardiovascular mortality among American individuals with hypertension
Authors: Yan Yuqin , Chen Jun
Published: November 2022

Background and aims

Evidence indicates that serum Klotho concentration is associated with mortality in patients with chronic kidney disease (CKD). However, evidence on this association among people with hypertension is scarce. Therefore, we aimed to examine the association between serum Klotho concentration and all-cause and cardiovascular mortality in American patients with hypertension.

Methods and results

We included 6,778 participants with hypertension from the National Health and Nutrition Examination Survey (NHANES) 2007–2014. A Cox proportional hazard model was used to compute the hazard ratios (HRs) and 95% confidence intervals (CIs). The correlation between serum Klotho concentration and mortality was determined using restricted cubic spline and piecewise linear regression analyses. During 36,714 person-years of follow-up, 575 deaths were documented. Lower serum Klotho concentration was associated with increased all-cause mortality, but not cardiovascular mortality after multivariate adjustment. According to spline analysis, the correlation between serum Klotho concentration and all-cause mortality was non-linear (P < 0.001), and the threshold value was 574 pg/mL. The HR below the threshold point was 0.79 (95% CI: 0.67–0.93); no significant difference was found above the threshold point.

Conclusion

Higher serum Klotho concentration was associated with lower all-cause mortality, but not cardiovascular mortality in patients with hypertension with or without chronic renal impairment.
Effect of levothyroxine replacement therapy in patients with subclinical hypothyroidism and chronic heart failure: A systematic review
Authors: Triggiani Vincenzo , Cittadini Antonio , Lisco Giuseppe
Published: November 2022

Background

Chronic heart failure (CHF) affects the health care system with high social and economic costs due to recurrent hospital admissions or frequent ambulatory reassessments. Subclinical hypothyroidism (SCH) is commonly observed in patients with CHF and negatively affects myocardial function and remodeling and, ultimately, increases the risk of hospitalizations and all-cause and cardiovascular (CV) mortality. The role of levothyroxine replacement on relevant CV outcomes in patients with SCH and CHF is unclear.

Objective

To assess the effect of levothyroxine (compared to placebo or no treatment) on the incidence of all-cause and CV mortality, major adverse CV events, and heart failure in patients with SCH and CHF.

Methods

PubMed/MEDLINE, Cochrane Library, and ClinicalTrial.gov were searched for randomized clinical trials, non-randomized observational, multicentric, and comparative studies. No language restrictions were included. After duplicate removal, articles were screened and extracted for the synthesis according to a hierarchical strategy that included title, abstract, and full-text appraisal. The risk of bias was assessed by RoB2 and ROBIN-I tools. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to rate the quality of evidence and grade the strength of recommendations.

Results

Two trials were included in the systematic review with considerable indirectness and inaccuracy that down-graded the level of evidence.

Discussion

No evidence supports the use of levothyroxine for treating SCH in CHF due to the lack of reliable and well-designed clinical trials.

Conclusion

CV outcome and dose-response trials are needed to understand better the role of levothyroxine replacement treatment for a safer prescription in this clinical setting.
Experimental Study on the Cyclic Steam Stimulation Assisted by Flue Gas Under Shallow Heavy-Oil Reservoir Conditions: Optimization of the Steam-Flue Gas Ratio
Authors: Li Songyan , Wang Zhoujie , Han Rui , Wang Lei , Hu Zukang
Published: November 2022

Normally, the recovery effect of a heavy-oil reservoir gradually deteriorates after multiple rounds of cyclic steam stimulation (CSS). However, the injection of flue gas can effectively increase the utilization degree of steam heat energy, which improves the recovery effect. In this paper, an experimental method for CSS using an energy storage container was established. Based on this method, a one-dimensional core physical simulation experiment for CSS under different flue gas ratios was performed. During the experiment, the changes in temperature field, oil production rate, increase in backpressure, and oil recovery factors were tested. In addition, differences in these data under different injection steam-flue gas ratios were compared. The results show that the flue gas provides a channel of fluids in porous media for steam, which is conducive to the heat transfer of steam to the deeper part of the sandpack. The sandpack has a higher temperature in each cycle than the CSS. The core temperature of each round of flue-gas-assisted CSS is higher than that of the CSS. The final oil recovery factors of flue-gas-assisted CSS using different steam-flue gas ratios are 22.2, 26.7, 30.8, 24.4, and 21.6%, while that of CSS is only 17.2%. According to the experiment, it is concluded that the best steam-flue gas ratio to optimize the flue-gas-assisted CSS is 1:10. With the combined effect of three factors (the temperature field of the sandpack, energizing effect of the flue gas, and degree of oil during recovery), the flue-gas-assisted CSS using the steam-flue gas ratio of 1:10 maximizes the steam heat transfer, increases the energy of return discharge, replenishes formation energy, and improves the oil recovery factor. Through the experiment, the research results provide theoretical guidance for improving the effectiveness of the CSS of heavy-oil reservoirs.
Parameter estimation of harmonics arising in electrical instruments of smart grids using cuckoo search heuristics
Authors: Malik Naveed Ahmed , Chang Ching-Lung , Chaudhary Naveed Ishtiaq , Khan Zeshan Aslam , Zahoor Raja Muhammad Asif , Kiani Adiqa Kausar , Milyani Ahmed H. , Azhari Abdullah Ahmed
Published: November 2022

The accurate estimation of power signal parameters allows smart grids to optimize power delivery efficiency, improve equipment utilization, and control power flow among generation nodes and loads. However, practically it becomes a challenging task because of the presence of harmonic distortions. In this study, a parameter estimation of the power system harmonics is investigated through swarm intelligence–based optimization strength of the cuckoo search algorithm. The performance evaluation is conducted in detail for different generations and particle sizes and for different signal-to-noise ratios. The simulation results reveal that the cuckoo search optimization heuristic accurately estimates the amplitude and phase parameters of the power system harmonics and is robust against different signal-to-noise ratios.
Spatial analysis of Varroa destructor and the relationship with surrounding landscape types in Southern Ontario
Authors: Sobkowich Kurtis Edward , Berke Olaf , Bernardo Theresa M. , Pearl David L. , Kozak Paul
Published: November 2022

Elevated colony losses have continued to be an issue for Canadian beekeepers for more than a decade. Numerous studies have identified unmanaged Apis mellifera colony infestation by the Varroa destructor mite as a main cause of the problem. V. destructor spread externally of the hive through a phoretic stage in their life cycle. Consequently, their movement outside the hive is influenced by honey bee flight behaviours, which can range to multiple kilometers from the originating hive in any direction. V. destructor are therefore of regional concern as neighboring colonies and yards share nearby forage which can serve as fomites. Additionally, mites can be transmitted through bee behaviours such as robbing and drifting, thus impacting surrounding colonies. Understanding the distribution of mites across a population is key for surveillance and equitable allocation of resources. Spatial patterns of V. destructor infestations in Southern Ontario, Canada, were investigated using a combination of cluster analysis, scan statistics, and geostatistical modelling, using 5 years of provincial apiary inspection data, from 2015 to 2019. A collection of disease clusters of V. destructor infestations was identified and found to be stable over multiple years with several other individual clusters occurring sporadically throughout Southern Ontario during the same study period. Universal kriging was applied to the V. destructor data in combination with regional colony density, and land use data as covariates, producing an isopleth map of the prevalence risk for V. destructor infestation. No substantial link between V. destructor infestation and environmental factors was found. This study highlights the need for more data and investigation to determine the cause of the identified clusters and areas of elevated risk. These results are hypothesis-generating but simultaneously provide information for government agencies, industry organizations, and beekeepers into the spatial distribution of V. destructor at a macro scale.
Gene family evolution and natural selection signatures in Datura spp. (Solanaceae)
Authors: De-la-Cruz Ivan M. , Kariñho-Betancourt Eunice , Núñez-Farfán Juan , Oyama Ken
Published: November 2022

Elucidating the diversification process of congeneric species makes it necessary to identify the factors promoting species variation and diversification. Comparative gene family analysis allows us to elucidate the evolutionary history of species by identifying common genetic/genomic mechanisms underlying species responses to biotic and abiotic environments at the genomic level. In this study, we analyzed the high-quality transcriptomes of four Datura species, D. inoxia, D. pruinosa, D. stramonium, and D. wrightii. We performed a thorough comparative gene family analysis to infer the role of selection in molecular variation, changes in protein physicochemical properties, and gain/loss of genes during their diversification processes. The results revealed common and species-specific signals of positive selection, physicochemical divergence and/or expansion of metabolic genes (e.g., transferases and oxidoreductases) associated with terpene and tropane metabolism and some resistance genes (R genes). The gene family analysis presented here is a valuable tool for understanding the genome evolution of economically and ecologically significant taxa such as the Solanaceae family.
Case report: An infant boy with X-linked sideroblastic anaemia successfully treated by umbilical cord blood haematopoietic stem cell transplantation
Authors: Ma Zhongyang , Li Dongjun , Yang Xue , Liang Juan , Zhu Yiping
Published: November 2022

X-linked sideroblastic anaemia (XLSA) is an inherited disorder caused by mutations in genes encoding proteins involved in the biosynthesis of haem. The pathogenic gene, as well as the pathogenesis and diagnosis of XLSA, have been fully elucidated in previous studies. However, only a few new advances have been made in managing XLSA in recent years, and blood transfusion remains the primary treatment. We report a case of umbilical cord blood haematopoietic stem cell transplantation in a male infant diagnosed with XLSA who was born with asphyxia due to severe anaemia. Early hepatic vein occlusion occurred after transplantation. However, this complication was rapidly controlled after active treatment, and the child’s quality of life improved significantly. Haematopoietic stem cell transplantation is a promising alternative treatment for XLSA.
Identification of a ferroptosis-related long noncoding RNA signature with a prognostic value in adrenocortical carcinoma
Authors: Wang Weixi , Chang Guilin , Zhuo Ran , Ye Cong
Published: November 2022

Background: Adrenocortical carcinoma (ACC) is an uncommon endocrine malignancy associated with poor clinical outcome. As a novel form of cell death, ferroptosis is reliant on the accumulation of iron and reactive oxygen species and is involved in the pathogenesis of various tumors, including ACC. Our study aimed to identify and characterize the prognostic ferroptosis-related lncRNA signature (FerRLSig) in ACC.

Methods: A regulatory network of ferroptosis-related lncRNAs (FerRLs) and mRNAs was constructed based on The Cancer Genome Atlas (TCGA). Univariate and multivariate Cox regression assays were performed to construct the FerRLSig.

Results: Twenty-four FerRLs were identified in the prognostic model, and the high-risk FerRLSig was related to the worse overall survival (OS) in ACC [hazard ratio (HR): 1.936 (1.484–2.526), p < 0.001]. The area under the curve (AUC) value of the FerRLSig was 0.936 according to the receiver operating characteristic (ROC) analyses, superior to other traditional clinicopathological features, further supported the utility in prognosis prediction of ACC. We further established a prognostic nomogram combining clinical factors with the FerRLSig, which showed favorable efficacy for survival prediction. Next, gene set enrichment analysis (GSEA) revealed that gene sets were involved in many immune regulatory biological processes related to malignancies. T-cell function of type II INF response and the immune checkpoints, including CD40, CD276, IDO2, NRP1, and CD80, were expressed with a significant difference between the low- and high-risk groups.

Conclusion: This study offered new insights into the pathogenesis of ACC. The novel FerRLSig could be useful in predicting survival and may provide information of immunological research and treatment for ACC patients.
Clinical characteristics of the host DNA-removed metagenomic next-generation sequencing technology for detecting SARS-CoV-2, revealing host local immune signaling and assisting genomic epidemiology
Authors: Zhaoyang Sun , Guowei Song , Jing Pan , Yundong Zhou , Xinhua Lu , Muyun Wei , Xiaowei Ma , Lixin Li , Xiaoying Chen
Published: November 2022

Background

Metagenomic next-generation sequencing (mNGS) technology has been central in detecting infectious diseases and helping to simultaneously reveal the complex interplay between invaders and their hosts immune response characteristics. However, it needs to be rigorously assessed for clinical utility. The present study is the first to evaluate the clinical characteristics of the host DNA-removed mNGS technology for detecting SARS-CoV-2, revealing host local immune signaling and assisting genomic epidemiology.

Methods

46 swab specimens collected from COVID-19 patients were assayed by two approved commercial RT-qPCR kits and mNGS. The evolutionary tree of SARS-CoV-2 was plotted using FigTree directly from one sample. The workflow of removing the host and retaining the host was compared to investigate the influence of host DNA removal on the performances of mNGS. Functional enrichment analysis of DEGs and xCell score were used to explore the characteristics of host local immune signaling.

Results

The detection rate of mNGS achieved 92.9% (26/28) for 28 samples with a Ct value ≤ 35 and 81.1% (30/37) for all 46 samples. The genome coverage of SARS-CoV-2 could reach up to 98.9% when the Ct value is about 20 in swab samples. Removing the host could enhance the sensitivity of mNGS for detecting SARS-CoV-2 from the swab sample but does not affect the species abundance of microbes RNA. Improving the sequencing depth did not show a positive effect on improving the detection sensitivity of SARS-CoV-2. Cell type enrichment scores found multiple immune cell types were differentially expressed between patients with high and low viral load.

Conclusions

The host DNA-removed mNGS has great potential utility and superior performance on comprehensive identification of SARS-CoV-2 and rapid traceability, revealing the microbiome’s transcriptional profiles and host immune responses.
Lower dose of ATG combined with basiliximab for haploidentical hematopoietic stem cell transplantation is associated with effective control of GVHD and less CMV viremia
Authors: Huang Zhenli , Yan Han , Teng Yao , Shi Wei , Xia Linghui
Published: November 2022

Currently, the graft-versus-host disease (GVHD) prophylaxis consists of an immunosuppressive therapy mainly based on antithymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy). GVHD remains a major complication and limitation to successful allogeneic haploidentical hematopoietic stem cell transplantation (haplo‐HSCT). We modified the ATG-based GVHD prophylaxis with the addition of basiliximab in the setting of haplo-HSCT and attempted to explore the appropriate dosages. We conducted a retrospective analysis of 239 patients with intermediate- or high-risk hematologic malignancies who received haplo-HSCT with unmanipulated peripheral blood stem cells combined or not with bone marrow. All patients received the same GVHD prophylaxis consisting of the combination of methotrexate, cyclosporine or tacrolimus, mycofenolate-mofetil, and basiliximab with different doses of ATG (5-9mg/kg). With a median time of 11 days (range, 7-40 days), the rate of neutrophil engraftment was 96.65%. The 100-day cumulative incidences (CIs) of grade II–IV and III–IV aGVHD were 15.8 ± 2.5% and 5.0 ± 1.5%, while the 2-year CIs of total cGVHD and extensive cGVHD were 9.8 ± 2.2% and 4.1 ± 1.5%, respectively. The 3-year CIs of treatment-related mortality (TRM), relapse, overall survival (OS), and disease-free survival (DFS) were 14.6 ± 2.6%, 28.1 ± 3.4%, 60.9 ± 3.4%, 57.3 ± 3.4%, respectively. Furthermore, the impact of the reduction of the ATG dose to 6 mg/kg or less in combination with basiliximab on GVHD prevention and transplant outcomes among patients was analyzed. Compared to higher dose of ATG(>6mg/kg), lower dose of ATG (≤6mg/kg) was associated with a significant reduced risk of CMV viremia (52.38% vs 79.35%, P<0.001), while the incidences of aGVHD and cGVHD were similar between the two dose levels. No significant effect was found with regard to the risk of relapse, TRM, and OS. ATG combined with basiliximab could prevent GVHD efficiently and safely. The optimal scheme of using this combined regimen of ATG and basiliximab is that administration of lower dose ATG (≤6mg/kg), which seems to be more appropriate for balancing infection control and GVHD prophylaxis.
Modulation of immunosuppressive cells and noncoding RNAs as immunotherapy in osteosarcoma
Authors: Xia Yidan , Wang Dongxu , Piao Yuting , Chen Minqi , Wang Duo , Jiang Ziping , Liu Bin
Published: November 2022

The most common bone cancer is osteosarcoma (OS), which mostly affects children and teenagers. Early surgical resection combined with chemotherapy significantly improves the prognosis of patients with OS. Existing chemotherapies have poor efficacy in individuals with distant metastases or inoperable resection, and these patients may respond better to novel immunotherapies. Immune escape, which is mediated by immunosuppressive cells in the tumour microenvironment (TME), is a major cause of poor OS prognosis and a primary target of immunotherapy. Myeloid-derived suppressor cells, regulatory T cells, and tumour-associated macrophages are the main immunosuppressor cells, which can regulate tumorigenesis and growth on a variety of levels through the interaction in the TME. The proliferation, migration, invasion, and epithelial–mesenchymal transition of OS cells can all be impacted by the expression of non-coding RNAs (ncRNAs), which can also influence how immunosuppressive cells work and support immune suppression in TME. Interferon, checkpoint inhibitors, cancer vaccines, and engineered chimeric antigen receptor (CAR-T) T cells for OS have all been developed using information from studies on the metabolic properties of immunosuppressive cells in TME and ncRNAs in OS cells. This review summarizes the regulatory effect of ncRNAs on OS cells as well as the metabolic heterogeneity of immunosuppressive cells in the context of OS immunotherapies.
The m6A methylation profiles of immune cells in type 1 diabetes mellitus
Authors: Wang Yimeng , Xu Linling , Luo Shuoming , Sun Xiaoxiao , Li Jiaqi , Pang Haipeng , Zhou Jun , Zhou Yuemin , Shi Xiajie , Li Xia , Huang Gan , Xie Zhiguo , Zhou Zhiguang
Published: November 2022

Background

Type 1 diabetes mellitus (T1DM) is caused by immune cell-mediated β-cell dysfunction. In recent decades, N6-methyladenosine (m6A) has attracted widespread attention in the scientific research field because it plays vital roles in the pathogenesis of immunity-related diseases, including autoimmune diseases. However, neither the m6A modification profile nor the potential role it plays in T1DM pathogenesis has been investigated to date.

Materials and Methods

An m6A mRNA epitranscriptomic microarray analysis was performed to analyze m6A regulator expression patterns and m6A methylation patterns in immune cells of T1DM patients (n=6) and healthy individuals (n=6). A bioinformatics analysis was subsequently performed to explore the potential biological functions and signaling pathways underlying T1DM pathogenesis. Furthermore, mRNA expression and m6A methylation levels were subsequently verified by qRT–PCR and methylated RNA immunoprecipitation–qPCR (MeRIP–qPCR), respectively, in the T1DM and healthy groups (n=6 per group).

Results

Among the multiple m6A regulators, METTL3 and IGF2BP2 had significantly downregulated expression, and YTHDC1 and HNRNPA2B1 had significantly upregulated expression in the T1DM group relative to the healthy group. The microarray analysis revealed 4247 differentially methylated transcripts, including 932 hypermethylated and 3315 hypomethylated transcripts, and 4264 differentially expressed transcripts, including 1818 upregulated transcripts and 2446 downregulated transcripts in the T1DM group relative to the healthy group. An association analysis between methylation and gene expression demonstrated that the expression of 590 hypermethylated transcripts was upregulated, and that of 1890 hypomethylated transcripts was downregulated. Pearson correlation analysis showed significant correlations between the expression levels of differentially expressed m6A regulators and the methylation levels of differentially methylated transcripts and significant correlations between the expression levels of differentially expressed m6A regulators and that of differentially expressed transcripts. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses demonstrated that differentially methylated transcripts were involved in pathways related to immunity, including some closely associated with T1DM.

Conclusions

Our study presents m6A regulator expression patterns and m6A methylation patterns of immune cells in T1DM, showing that the m6A mark and m6A regulators are promising targets for T1DM diagnosis and treatment.
Development and external validation of a novel nomogram model for predicting postoperative recurrence-free survival in non-muscle-invasive bladder cancer
Authors: Ding Li , Deng Xiaobin , Xia Wentao , Wang Kun , Zhang Yang , Zhang Yan , Shao Xianfeng , Wang Junqi
Published: November 2022

Background

Transurethral resection of the bladder tumor with or without adjuvant intravesical instillation (IVI) has been the standard treatment for non-muscle-invasive bladder cancer (NMIBC), whereas a high percentage of patients still experience local tumor recurrence and disease progression after receiving the standard treatment modalities. Unfortunately, current relevant prediction models for determining the recurrent and progression risk of NMIBC patients are far from impeccable.

Methods

Clinicopathological characteristics and follow-up information were retrospectively collected from two tertiary medical centers between October 2018 and June 2021. The least absolute shrinkage and selection operator (LASSO) and Cox regression analysis were used to screen potential risk factors affecting recurrence-free survival (RFS) of patients. A nomogram model was established, and the patients were risk-stratified based on the model scores. Both internal and external validation were performed by sampling the model with 1,000 bootstrap resamples.

Results

The study included 299 patient data obtained from the Affiliated Hospital of Xuzhou Medical University and 117 patient data obtained from the First Affiliated Hospital of Guangxi Medical University. Univariate regression analysis suggested that urine red blood cell count and different tumor invasion locations might be potential predictors of RFS. LASSO-Cox regression confirmed that prior recurrence status, times of IVI, and systemic immune-inflammation index (SII) were independent factors for predicting RFS. The area under the curve for predicting 1-, 2-, and 3-year RFS was 0.835, 0.833, and 0.871, respectively. Based on the risk stratification, patients at high risk of recurrence and progression could be accurately identified. A user-friendly risk calculator based on the model is deposited at https://dl0710.shinyapps.io/nmibc_rfs/.

Conclusion

Internal and external validation analyses showed that our model had excellent predictive discriminatory ability and stability. The risk calculator can be used for individualized assessment of survival risk in NMIBC patients and can assist in guiding clinical decision-making.
MSCs interaction with the host lung microenvironment: An overlooked aspect?
Authors: Weiss Daniel J. , Rolandsson Enes Sara
Published: November 2022

Mesenchymal stromal cells (MSCs) were identified more than 50 years ago, and research advances have promoted the translation of pre-clinical studies into clinical settings in several diseases. However, we are only starting to uncover the local factors that regulate cell phenotype, cell function, and cell viability across tissues following administration in different diseases. Advances in pre-clinical and translational studies suggest that the host environment, especially inflammatory active environments, plays a significant role in directing the infused MSCs towards different phenotypes with different functions. This can significantly effect their therapeutic efficacy. One way to study this interaction between the host environment and the infused cells is to expose MSCs ex vivo to patient samples such as serum or bronchoalveolar lavage fluid. Using this approach, it has been demonstrated that MSCs are very sensitive to different host factors such as pathogens, inflammatory cytokines, and extra cellular matrix properties. By understanding how different local host factors effect MSC function it will open possibilities to select specific patient sub-groups that are more likely to respond to this type of treatment and will also open possibilities to prime the local host environment to increase viability and to enrich for a specific MSC phenotype. Here, we aim to review the current understanding of the interaction of MSCs with the host microenvironment. To narrow the scope of this mini review, the focus will be on the pulmonary microenvironment, with a specific focus on the diseases acute respiratory distress syndrome (ARDS) and cystic fibrosis (CF).
SRSF1 acts as an IFN-I-regulated cellular dependency factor decisively affecting HIV-1 post-integration steps
Authors: Sertznig Helene , Roesmann Fabian , Wilhelm Alexander , Heininger Delia , Bleekmann Barbara , Elsner Carina , Santiago Mario , Schuhenn Jonas , Karakoese Zehra , Benatzy Yvonne , Snodgrass Ryan , Esser Stefan , Sutter Kathrin , Dittmer Ulf , Widera Marek
Published: November 2022

Efficient HIV-1 replication depends on balanced levels of host cell components including cellular splicing factors as the family of serine/arginine-rich splicing factors (SRSF, 1–10). Type I interferons (IFN-I) play a crucial role in the innate immunity against HIV-1 by inducing the expression of IFN-stimulated genes (ISGs) including potent host restriction factors. The less well known IFN-repressed genes (IRepGs) might additionally affect viral replication by downregulating host dependency factors that are essential for the viral life cycle; however, so far, the knowledge about IRepGs involved in HIV-1 infection is very limited. In this work, we could demonstrate that HIV-1 infection and the associated ISG induction correlated with low SRSF1 levels in intestinal lamina propria mononuclear cells (LPMCs) and peripheral blood mononuclear cells (PBMCs) during acute and chronic HIV-1 infection. In HIV-1-susceptible cell lines as well as primary monocyte-derived macrophages (MDMs), expression levels of SRSF1 were transiently repressed upon treatment with specific IFNα subtypes in vitro. Mechanically, 4sU labeling of newly transcribed mRNAs revealed that IFN-mediated SRSF1 repression is regulated on early RNA level. SRSF1 knockdown led to an increase in total viral RNA levels, but the relative proportion of the HIV-1 viral infectivity factor (Vif) coding transcripts, which is essential to counteract APOBEC3G-mediated host restriction, was significantly reduced. In the presence of high APOBEC3G levels, however, increased LTR activity upon SRSF1 knockdown facilitated the overall replication, despite decreased vif mRNA levels. In contrast, SRSF1 overexpression significantly impaired HIV-1 post-integration steps including LTR transcription, alternative splice site usage, and virus particle production. Since balanced SRSF1 levels are crucial for efficient viral replication, our data highlight the so far undescribed role of SRSF1 acting as an IFN-modulated cellular dependency factor decisively regulating HIV-1 post-integration steps.
Population estimates of photo-identified individuals using a modified POPAN model reveal that Raja Ampat’s reef manta rays are thriving
Authors: Setyawan Edy , Stevenson Ben C. , Erdmann Mark V. , Hasan Abdi W. , Sianipar Abraham B. , Mofu Imanuel , Putra Mochamad I. H. , Izuan Muhamad , Ambafen Orgenes , Fewster Rachel M. , Aldridge-Sutton Robin , Mambrasar Ronald , Constantine Rochelle
Published: November 2022

The 6.7-million-hectare Raja Ampat archipelago is home to Indonesia’s largest reef manta ray (Mobula alfredi) population and a representative network of nine marine protected areas (MPAs). However, the population dynamics ofM. alfrediin the region are still largely unknown. Using our photo-identification database, we fitted modified POPAN mark-recapture models with transience and per capita recruitment parameters to estimate key demographic characteristics ofM. alfredifrom two of Raja Ampat’s largest MPAs: Dampier Strait and South East (SE) Misool. A total of 1,041 unique individuals were photo-identified over an 11-year period (2009–2019) from Dampier Strait (n = 515) and SE Misool (n = 536). In our models, apparent survival probabilities and per capita recruitment rates were strongly linked with El Niño–Southern Oscillation (ENSO) events. Our models also estimated high apparent survival probabilities and significant increases in (sub)population sizes in both MPAs over a decade. In Dampier Strait, the estimated population size increased significantly (p = 0.018) from 226 (95% CI: 161, 283) to 317 (280, 355) individuals. Likewise, the estimated population size in SE Misool increased significantly (p = 0.008) from 210 (137, 308) to 511 (393, 618) individuals. Regardless of variation in the percentage change in population size between years throughout the study, the estimated overall population change shows a compound growth of 3.9% (0.7, 8.6) per annum in Dampier Strait and 10.7% (4.3, 16.1) per annum in SE Misool. Despite the global decline in oceanic sharks and rays due to fishing pressure in the last five decades, our study demonstrates the positive impact of a suite of long-term conservation efforts, coupled with the influence of ENSO events, on increasingM. alfrediabundance in Raja Ampat MPAs. Our study also underscores the importance of long-term monitoring to evaluate the effectiveness of conservation management measures on manta ray populations. Our modification of the standard POPAN model by incorporating per capita recruitment and transience parameters represents an important advance in mark-recapture modelling that should prove useful when examining other manta ray populations and other highly migratory species that are likely to have a substantial percentage of transient individuals.
RACE-SM: Reliability and adaptive cooperation for efficient UWSNs using sink mobility
Authors: Ahmad Irfan , Rahman Taj , Khan Inayat , Jan Salman , Musa Shahrulniza , Uddin M. Irfan
Published: November 2022

Underwater Wireless Sensor Networks (UWSNs) are the most crucial method for exploring the hidden resources under the water. It enables many underwater applications, such as military, commercial, disaster prevention, ocean sampling, and other emergencies. Data transmission through a single relay node creates a hotspot, which will minimize the network lifetime and reduce the network reliability. Therefore, the cooperative technique is essential for transferring data between the source and the destination. This research proposes an improved version of Reliability and Adaptive Cooperation for Efficient (RACE), a well-known cooperative routing protocol for UWSNs known as RACE-SM. RACE-SM solved the single relay node issues by using the sink mobility scheme. All sensor nodes transfer data directly to the sink node if the sink node is in the communication range. Otherwise, sensor nodes use the cooperative combining strategies scheme to send the data from the source to the destination or sink node. The performance of the proposed method is then compared with the current protocols. The simulation results show that the RACE-SM outperforms in average up to 40.60%, 59%, 278%, and 77% than current protocols in terms of alive nodes, energy consumption, packet delivery ratio (PDR), and end-to-end delay respectively.
High conopeptide diversity in Conus striatus: Revealed by integration of two transcriptome sequencing platforms
Authors: Liao Yanling , Peng Chao , Zhu Yabing , Fu Jinxing , Ruan Zhiqiang , Shi Qiong , Gao Bingmiao
Published: November 2022

Marine cone snail venoms represent a vast library of bioactive peptides with proven potential as research tools, drug leads, and therapeutics. In this study, a transcriptome library of four different organs, namely radular sheath, venom duct, venom gland, and salivary gland, from piscivorous Conus striatus was constructed and sequenced using both Illumina next-generation sequencing (NGS) and PacBio third-generation sequencing (TGS) technologies. A total of 428 conotoxin precursor peptides were retrieved from these transcriptome data, of which 413 conotoxin sequences assigned to 13 gene superfamilies, and 15 conotoxin sequences were classified as unassigned families. It is worth noting that there were significant differences in the diversity of conotoxins identified from the NGS and TGS data: 82 conotoxins were identified from the NGS datasets while 366 conotoxins from the TGS datasets. Interestingly, we found point mutations in the signal peptide sequences of some conotoxins with the same mature sequence. Therefore, TGS broke the traditional view of the conservation of conotoxin signal peptides and the variability of mature peptides obtained by NGS technology. These results shed light on the integrated NGS and TGS technologies to mine diverse conotoxins in Conus species, which will greatly contribute to the discovery of novel conotoxins and the development of new marine drugs.
Tumor growth inhibition and immune system activation following treatment with thorium-227 conjugates and PD-1 check-point inhibition in the MC-38 murine model
Authors: Berg-Larsen Axel , Mobergslien Anne , Moen Ingrid , Petros Gebregziabher , Kristian Alexander , Gunvaldsen Kristine Sponheim , Cruciani Véronique , Wickstroem Katrine , Bjerke Roger Malerbakken , Karlsson Jenny , Cuthbertson Alan
Published: November 2022

Targeted thorium-227 conjugates comprise the combination of a monoclonal antibody with specificity for a tumor cell antigen and a 3,2-HOPO chelator enabling complexation of thorium-227 (Th-227). The radiolabeled conjugate functions as an effective delivery system of alpha-particle radiation to the surface of the tumor cell inducing difficult to repair complex DNA damage and cell death. In addition, the mechanism of action of targeted alpha therapy (TAT) appears to involve a significant component linked to stimulation of the immune system. We report herein evidence of immune activation and long-lasting immune protection of a TAT in a syngeneic model using the MC-38 murine cell line. Firstly, MC-38 cells were irradiated ex vivo with the thorium labeled antibody before subcutaneous implantation into mice. These mice were then rechallenged with MC-38 cells contra-laterally. In the group receiving irradiated cells, 9 out of 10 animals had no measurable tumor growth compared to aggressive tumor growth in the control group. Secondly, in an efficacy study, 500 kBq/kg of thorium labeled antibody alone or in combination with PD-1 checkpoint inhibitor gave statistically significant tumor growth inhibition compared to vehicle control. Animals with no measurable tumors were once again rechallenged contra-laterally with MC-38 cells. The re-growth of tumors was significantly delayed (approx. 60 days) in the treatment group compared to age-matched controls (approx. 30 days) in the monotherapy group. Interestingly, in the TAT/ PD-1 combination group no re-growth was observed demonstrating the potential of combining a TAT with checkpoint inhibition therapy. Finally, tumors were excised from treated mice and analyzed by flow cytometry and immunohistochemistry (IHC). Analysis revealed significant infiltration of CD8+ T-cells and mature dendritic cells compared to vehicle controls. Together these results indicated that an ongoing immune response from treatment with alpha radiation could be enhanced by check-point inhibition.
Is esketamine-based opioid-free anesthesia more superior for postoperative analgesia in obstructive sleep apnea patients undergoing bariatric surgery? A study protocol
Authors: Guo Yongle , Chen Lina , Gao Zhongquan , Zhang Min , Liu Mengjie , Gao Xiaojun , Liu Yang , Zhang Xiaoning , Guo Na , Sun Yongtao , Wang Yuelan
Published: November 2022

Introduction

Opioid-free anesthesia (OFA) can certainly prevent nausea and vomiting after bariatric surgery (BS), but its postoperative analgesic effect is still controversial. Obstructive sleep apnea (OSA) is a prominent feature of morbid obesity in BS and accounts for a very high proportion, which significantly increases the difficulty of patients’ airway management. Those patients will be more representative and highlight the advantages of OFA. It is not clear whether esketamine can play a more prominent role in OFA for postoperative analgesia. Therefore, this study aims to explore the postoperative analgesic effect of esketamine-based OFA on BS patients with OSA.

Methods and analysis

This single-center, prospective, randomized, controlled, single-blind study is planned to recruit 48 participants to undergo BS from May 2022 to April 2023. Patients will be randomly assigned to the OFA group and opioid-based anesthesia (OBA) group in a ratio of 1:1. The primary outcome is the Numeric Rating Scale (NRS) at different times postoperatively. Secondary outcomes include analgesic intake, the incidence and severity of postoperative nausea and vomiting (PONV), Leiden Surgical Rating Scale (L-SRS), postoperative agitation and chills, PACU stay time, EuroQol five-dimensional questionnaire (EQ-5D), length of hospital stay, intraoperative awareness, and hemodynamically unstable treatments.

Discussion

The results of this study may explain the analgesic effect of esketamine-based OFA on patients undergoing BS combined with OSA, and provide evidence and insight for perioperative pain management.

Ethics and dissemination

This study is initiated by the Ethics Committee of The First Affiliated Hospital of Shandong First Medical University [YXLL-KY-2022(035)]. The trial results will be published in peer-reviewed journals and at conferences.

Clinical trial registration

[https://clinicaltrials.gov/ct2/show/NCT05386979], identifier [NCT 05386979].
The impact of zero markup drug policy on patients' healthcare utilization and expense: An interrupted time series study
Authors: Zhu Zheng , Wang Junfeng , Sun Yan , Zhang Jiawei , Han Peien , Yang Li
Published: November 2022

Objective

To curb the unreasonable growth of pharmaceutical expenditures, Beijing implemented the zero markup drug policy (ZMDP) in public hospitals in 2017, which focused on separating drug sales from hospital revenue. The purpose of this study is to evaluate the impacts of ZMDP on healthcare expenditures and utilization for inpatients.

Methods

The Beijing claims data of inpatients diagnosed with ischemic heart disease (IHD), chronic renal failure (CRF), and lung cancer (LC) was extracted from the China Health Insurance Research Association (CHIRA) database. The study employed an interrupted time series to evaluate the impacts of ZMDP on healthcare expenditures and utilization.

Results

The changes in total hospitalization expenses, health insurance expenses, and out-of-pocket expenses were not statistically significant neither in level change nor in trend change for inpatients diagnosed with IHD, CRF, or LC after implementing ZMDP (all P > 0.05). The Western medicine expenses for the treatment of inpatients diagnosed with IHD significantly decreased by 1,923.38 CNY after the reform (P < 0.05). The Chinese medicine expenses of inpatients diagnosed with CRF instantaneously increased by 1,344.89 CNY (P < 0.05). The service expenses of inpatients diagnosed with IHD and LC instantaneously increased by 756.52 CNY (p > 0.05) and 2,629.19 CNY (p < 0.05), respectively. However, there were no significant changes (P > 0.05) in out-of-pocket expenses, medical consumables, imaging, and laboratory test expenses of inpatients diagnosed with IHD, CRF, or LC. The initiation of the intervention immediately increased the number of inpatient admissions with LC by 2.293 per month (p < 0.05).

Conclusions

The ZMDP was effective in reducing drug costs, and the effects on healthcare utilization varied across diseases type. However, the increase in medical service and Chinese medicine expenses diminished the effect of containing healthcare expenses and relieving the financial burdens of patients. Policymakers are advised to take multiple and long-lasting measures, such as provider payment methods reform, volume-based drug procurement, and drug price negotiation to improve the affordability of patients thoroughly.
Specific decellularized extracellular matrix promotes the plasticity of human ocular surface epithelial cells
Authors: Ramos Tiago , Parekh Mohit , Meleady Paula , O’Sullivan Finbarr , Stewart Rosalind M. K. , Kaye Stephen B. , Hamill Kevin , Ahmad Sajjad
Published: November 2022

The ocular surface is composed of two phenotypically and functionally different epithelial cell types: corneal and the conjunctival epithelium. Upon injury or disease, ocular surface homeostasis is impaired resulting in migration of conjunctival epithelium on to the corneal surface. This can lead to incomplete transdifferentiation toward corneal epithelial-like cells in response to corneal basement membrane cues. We show that corneal extracellular matrix (ECM) proteins induce conjunctival epithelial cells to express corneal associated markers losing their conjunctival associated phenotype at both, mRNA and protein level. Corneal epithelial cells behave the same in the presence of conjunctival ECM proteins, expressing markers associated with conjunctival epithelium. This process of differentiation is accompanied by an intermediate step of cell de-differentiation as an up-regulation in the expression of epithelial stem cell markers is observed. In addition, analysis of ECM proteins by laminin screening assays showed that epithelial cell response is laminin-type dependent, and cells cultured on laminin-511 showed lower levels of lineage commitment. The phosphorylation and proteolysis levels of proteins mainly involved in cell growth and differentiation showed lower modifications in cells with lower lineage commitment. These observations showed that the ECM proteins may serve as tools to induce cell differentiation, which may have potential applications for the treatment of ocular surface injuries.