bluuebunny/crossref_metadata_2025 huggingface dataset:
A cost-effectiveness modeling study of treatment interventions for stage I to III esophageal squamous cell carcinoma
Authors: Daroudi Rajabali , Nahvijou Azin , Arab Mohammad , Faramarzi Ahmad , Kalaghchi Bita , Sari Ali Akbari , Javan-Noughabi Javad
Published: April 2022

Background

Esophageal cancer causes considerable costs for health systems. Appropriate treatment options for patients with esophageal squamous cell carcinoma (ESCC) can reduce medical costs and provide more improved outcomes for health systems and patients. This study evaluates the cost-effectiveness of treatment interventions for patients with ESCC according to the Iranian health system.

Material and methods

A five-state Markov model with a 15-year time horizon was performed to evaluate the cost-effectiveness of treatment interventions based on stage for ESCC patients. Costs ($US 2021) and outcomes were calculated from the Iranian health system, with a discount rate of 3%. One-way sensitivity analyses were performed to assess the potential effects of uncertain variables on the model results.

Results

In stage I, the Endoscopic Mucosal Resection (EMR) treatment yielded the lowest total costs and highest total QALY for a total of $1473 per QALY, making it the dominant strategy compared with esophagectomy and EMR followed by ablation. In stages II and III, chemoradiotherapy (CRT) followed by surgery dominated esophagectomy. CRT followed by surgery was also cost-effective with an incremental cost-effectiveness ratio (ICER) of $2172.8 per QALY compared to CRT.

Conclusion

From the Iranian health system’s perspective, EMR was the dominant strategy versus esophagectomy and EMR followed by ablation for ESCC patients in stage I. The CRT followed by surgery was a cost-effective intervention compared to CRT and esophagectomy in stages II and III.
Comparison of syndromic versus laboratory-confirmed diagnosis of Neisseria gonorrhoeae and Treponema pallidum, infections at the selected health centers in Addis Ababa, Ethiopia
Authors: Ayalew Enaniye , Fentaw Surafel , Ebrahim Semira , Seyoum Elias , Woldesenbet Zerihun , Wolde Mistire
Published: April 2022

Background

Sexually transmitted infections (STIs) are major infectious diseases worldwide. Around one million people get STIs every day and among them a high burden of the diseases seen in Sub-Saharan African countries. In most developing countries, including Ethiopia, STIs are diagnosed only using syndromic methods, although there seems to be no consensus between syndromic and laboratory-based research.

Objective

To compare the effectiveness of a syndromic versus laboratory-based approach in the diagnosis of sexually transmitted infections, especiallyNeisseria gonorrhoeae(NG) andTreponema pallidum (TP), infections among those attending a public health center in Addis Ababa, Ethiopia.

Methods

a cross-sectional study was conducted from April 2019 to March 2020, at selected health centers STIs clinics in Addis Ababa, Ethiopia. A total of 325 study participants were involved. From each participant after having socio-demographic data, additional blood, urethral and vaginal discharge was collected. Then serological, Gram stain, culture, and biochemical tests were performed. SPSS version 23 was used to enter and analyze data. All relevant bodies provided ethical approval, and each study participant gave written informed consent.

Results

Among the total participants 167 (51.4%) were males; 177 (54.5%) between ages of 26 and 35; and 178(54.8%) single. Of the total 325 NG, and 125 TP syndromic managed suspected cases, only 163 (50%) and 38 (30.4%) were laboratory- confirmed positive cases respectively. However, there was no statistically significant difference between NG and TP syndromic versus laboratory diagnostic confirmed cases (P-value > 0.005).

Conclusion

The present study indicated that even if, there were no statistical differences between syndromic versus Laboratory diagnosis confirmed NG and TP cases, more than half of syndromic cases could not be confirmed by laboratory diagnosed tests. Thus, to strengthen the present findings, further large-scale studies are recommended.
Is the healthcare provision in the Netherlands compliant with universal health coverage based on the right to health? A narrative literature review
Authors: Kuipers Thomas , van de Pas Remco , Krumeich Anja
Published: April 2022

Universal health coverage, as one of the targets of the Sustainable Development Goals, is the access to key promotive, preventive, curative and rehabilitative health interventions for all at an affordable cost. It is a practical expression of the concern for health equity and the right to health, and a goal for all countries. This review is a novel attempt to explore the healthcare provision in the Netherlands as an expression of universal health coverage based on the right to health.

The study adopted a narrative review approach using a framework that consists of 10 universal health coverage indicators which are derived from seven human rights principles. The techno-economic approach to healthcare provision by the Dutch state achieves a healthcare system where most of the population is covered for most of the services for most of the costs. The Dutch state complies with its minimum core obligations, while less attention is paid to participatory decision making and non-discrimination principles. However, with the fiscal sustainability of healthcare provision showing erosion, basing healthcare policy on values based on human rights principles might prevent a regressive policy.
Sorting biotic and abiotic stresses on wild rocket by leaf-image hyperspectral data mining with an artificial intelligence model
Authors: Navarro Alejandra , Nicastro Nicola , Costa Corrado , Pentangelo Alfonso , Cardarelli Mariateresa , Ortenzi Luciano , Pallottino Federico , Cardi Teodoro , Pane Catello
Published: April 2022

Background

Wild rocket (Diplotaxis tenuifolia) is prone to soil-borne stresses under intensive cultivation systems devoted to ready-to-eat salad chain, increasing needs for external inputs. Early detection of the abiotic and biotic stresses by using digital reflectance-based probes may allow optimization and enhance performances of the mitigation strategies.

Methods

Hyperspectral image analysis was applied to D. tenuifolia potted plants subjected, in a greenhouse experiment, to five treatments for one week: a control treatment watered to 100% water holding capacity, two biotic stresses: Fusarium wilting and Rhizoctonia rotting, and two abiotic stresses: water deficit and salinity. Leaf hyperspectral fingerprints were submitted to an artificial intelligence pipeline for training and validating image-based classification models able to work in the stress range. Spectral investigation was corroborated by pertaining physiological parameters.

Results

Water status was mainly affected by water deficit treatment, followed by fungal diseases, while salinity did not change water relations of wild rocket plants compared to control treatment. Biotic stresses triggered discoloration in plants just in a week after application of the treatments, as evidenced by the colour space coordinates and pigment contents values. Some vegetation indices, calculated on the bases of the reflectance data, targeted on plant vitality and chlorophyll content, healthiness, and carotenoid content, agreed with the patterns of variations observed for the physiological parameters. Artificial neural network helped selection of VIS (492–504, 540–568 and 712–720 nm) and NIR (855, 900–908 and 970 nm) bands, whose read reflectance contributed to discriminate stresses by imaging.

Conclusions

This study provided significative spectral information linked to the assessed stresses, allowing the identification of narrowed spectral regions and single wavelengths due to changes in photosynthetically active pigments and in water status revealing the etiological cause.
Self-assembling peptides with hBMP7 biological activity promote the differentiation of ADSCs into nucleus pulposus-like cells
Authors: Wang Chaofeng , Li Zhong , Zhang Kun , Zhang Congming
Published: April 2022

Functionalized self-assembling peptides, which display functional growth-factor bioactivity, can be designed by connecting the C-terminus of a pure self-assembling peptide with a short functional motif. In this study, we designed a novel functionalized peptide (RADA16-SNVI) in which an SNVI motif with hBMP-7 activity was conjugated onto the C-terminus of the RADA16 peptide via solid-phase synthesis. A mix of RADA16-SNVI and RADA16 solutions was used to create a functionalized peptide nanofiber scaffold (SNVI-RADA16). The hydrogels were analyzed by atomic force microscopy, circular dichroism, and scanning electron microscopy. The results showed that the SNVI-RADA16 solution effectively formed hydrogel. Next, we seeded the SNVI-RADA16 scaffold with adipose-derived stem cells (ADSCs) and investigated whether it displayed biological properties of nucleus pulposus tissue. SNVI-RADA16 displayed good biocompatibility with the ADSCs and induced their expression. Cells in SNVI-RADA16 gel had a greater secretion of the extracellular matrix marker collagen type II and aggrecan compared to ADSCs grown in monolayer and control gel (p < 0.05). The ratio of the aggrecan to collagen in cells in SNVI-RADA16 gel is approximately 29:1 after culture for 21 days. ADSCs in SNVI-RADA16 gels expressed the hypoxia-inducible factor 1α(HIF-1α) mRNA by real-time PCR. However, HIF-1 mRNA is absence in control gel and monolayer. The results suggested that the functionalized self-assembled peptide promotes the differentiation of ADSCs into nucleus pulposus-like cells. Thus, the designed SNVI-RADA16 self-assembling peptide hydrogel scaffolds may be suitable for application in nucleus pulposus tissue regeneration.
Ludangshen oral liquid for treatment of convalescent COVID-19 patients: a randomized, double-blind, placebo-controlled multicenter trial
Authors: An Xuedong , Peng Bo , Huang Xiaodong , Jiang Hongmei , Xiong Zhang’e , Zhang Hong , Lian Fengmei , Ba Yuanming , Tong Xiaolin
Published: April 2022

Objective

To explore the effect of Ludangshen oral liquid for treatment of convalescent patients with coronavirus disease 2019 (COVID-19) with randomized, double-blind, placebo-controlled multicenter method.

Methods

200 convalescent COVID-19 patients who had symptoms related to decreased digestive and respiratory function were randomly divided to either receive Ludangshen oral liquid or placebo for 2 weeks. The severity of clinical symptoms including fatigue, anorexia, abdominal distension, loose stools, and shortness of breath were assessed by visual analogue scale and observed at before and after treatment. The improvement and resolution rates of clinical symptoms were evaluated. Full analysis set (FAS) and per-protocol set (PPS) were used for statistical analyses. Adverse events were recorded during the study.

Results

8 patients did not complete the study. After 2 weeks of treatment, both FAS and PPS results showed that patients in Ludangshen group had significantly lower score of fatigue, anorexia, loose stools, and shortness of breath than placebo group (P < 0.05), while there was no significant difference in distention (P > 0.05). The improvement rate of fatigue, anorexia, distension, loose stools and shortness of breath were significantly higher in Ludangshen group (P < 0.05), as well as the resolution rates (P < 0.05) except for shortness of breath (P > 0.05). There were two cases of adverse events, with one nose bleeding in Ludangshen group and one headache in placebo group.

Conclusion

The study suggested that two weeks of Ludangshen oral liquid treatment may have certain effects for convalescent COVID-19 patients on improving digestive and respiratory symptoms including fatigue, anorexia, loose stools and shortness of breath, which may be one of the choices for management of convalescent COVID-19 patients with digestive and respiratory symptoms.
Dopamine use and its consequences in the intensive care unit: a cohort study utilizing the Japanese Intensive care PAtient Database
Authors: Suzuki Reina , Uchino Shigehiko , Sasabuchi Yusuke , Kawarai Lefor Alan , Sanui Masamitsu
Published: April 2022

Background

Dopamine is used to treat patients with shock in intensive care units (ICU) throughout the world, despite recent evidence against its use. The aim of this study was to identify the latest practice of dopamine use in Japan and also to explore the consequences of dopamine use in a large Asian population.

Methods

The Japanese Intensive Care PAtient Database (JIPAD), the largest intensive care database in Japan, was utilized. Inclusion criteria included: 1) age 18 years or older, 2) admitted to the ICU for reasons other than procedures, 3) ICU length of stay of 24 h or more, and 4) treatment with either dopamine or noradrenaline within 24 h of admission. The primary outcome was in-hospital mortality. Multivariable regression analysis was performed, followed by a propensity score-matched analysis.

Results

Of the 132,354 case records, 14,594 records from 56 facilities were included in this analysis. Dopamine was administered to 4,653 patients and noradrenaline to 11,844. There was no statistically significant difference in facility characteristics between frequent dopamine users (N = 28) and infrequent users (N = 28). Patients receiving dopamine had more cardiovascular diagnosis codes (70% vs. 42%; p < 0.01), more post-elective surgery status (60% vs. 31%), and lower APACHE III scores compared to patients given noradrenaline alone (70.7 vs. 83.0; p < 0.01). Multivariable analysis showed an odds ratio for in-hospital mortality of 0.86 [95% CI: 0.71–1.04] in the dopamine ≤ 5 μg/kg/min group, 1.46 [95% CI: 1.18–1.82] in the 5–15 μg/kg/min group, and 3.30 [95% CI: 1.19–9.19] in the > 15 μg/kg/min group. In a 1:1 propensity score matching for dopamine use as a vasopressor (570 pairs), both in-hospital mortality and ICU mortality were significantly higher in the dopamine group compared to no dopamine group (22.5% vs. 17.4%, p = 0.038; 13.3% vs. 8.8%, p = 0.018), as well as ICU length of stay (mean 9.3 days vs. 7.4 days, p = 0.004).

Conclusion

Dopamine is still widely used in Japan. The results of this study suggest detrimental effects of dopamine use specifically at a high dose.

Trial registration Retrospectively registered upon approval of the Institutional Review Board and the administration office of JIPAD.
The impact of a school backpack's weight, which is carried on the back of a 7-year-old students of both sexes, on the features of body posture in the frontal plane
Authors: Mrozkowiak Mirosław , Stępień-Słodkowska Marta
Published: April 2022

Background

The lifestyle of children has a significant impact on the future health of the whole society. Therefore, health education, prevention and monitoring of health determinants is important at every stage of ontogenesis. This requires a thorough knowledge of the schoolchild's environment, perceived as a wide set of stressors, including not only genetic but also epigenetic factors. One of them is the issue of the correct and abnormal body posture at school and on the way there. The goal of the study was to show the influence of the weight of the back carried container with school supplies on body posture.

Method

The research was carried out as part of a project that examined the impact of carrying weights, which are school supplies, by children on their posture. The research material consisted of data obtained from a group of 65 students (35 girls, 30 boys) aged 7 years. Body posture tests were carried out, using the projection moiré method in 4 positions: 1-habitual posture, 2-posture after 10-min of asymmetric axial load, 3-a posture after 1 min of the load removal, 4-a posture after two minutes of the load removal. Physical fitness was measured with the Sekita test. The obtained data were statistically analyzed.

Results

The significance of differences between the 1st and 2nd measurements was analyzed to determine the impact of the backpack load and the correlation with physical fitness, and to study its influence on the value of the differences in posture features. Considering the differences in the volume of posture features among boys between the 1st and 2nd measurement, the Wilcoxon’s rank test showed a statistically significant difference in the range of all analyzed variables, except for the torso bend angle to the right (KNT+), where no statistically significant change was noted. A statistically significant difference in the volume of all analyzed variables was observed among the girls.

Conclusions

Carrying school supplies on the back induces significant changes in the value of the features describing the body posture in the frontal plane. The greater weight of the container and carrying time, and intensity of physical effort is the greater the changes will be. Physical fitness has a various and sex-dependent influence on the value of changes in body posture features because of carrying school supplies. Among boys it significantly affects the asymmetry of the torso bend, shoulder height, the waist triangles height and width, whereas among girls it affects the asymmetry of the shoulders and the distance of the angles of the lower shoulder blades from the line of the spinous processes of the spine. Among boys the changes in the value of posture features are mostly influenced by endurance and speed, but strength, power and agility are of lower influence, whereas among girls only agility matters.
Physical activity trajectory in the first 10 months of the COVID-19 pandemic in Southern Brazil: a follow-up study
Authors: Caputo Eduardo L. , Feter Natan , Leite Jayne S. , Doring Igor R. , Cassuriaga Júlia , Delpino Felipe M. , Huckembeck Caroline M. , Alt Ricardo , da Silva Marcelo C. , Rombaldi Airton J. , Reichert Felipe F.
Published: April 2022

Background

A continuous tracking of the PA level during the COVID-19 pandemic is important to understand how people’s behaviour has varied along time. The aim of this study was to evaluate the physical activity (PA) trajectory over the first 10 months of the COVID-19 pandemic in the south of Brazil.

Methods

Data from three timepoints of the PAMPA Cohort were used, as follows: (1) pre-COVID-19 (retrospective); (2) Jun/Jul 2020; (3) Dec 2020/Jan 2021. Self-reported PA practice, frequency, duration, as well as place where activities were performed (at or out of home) were assessed.

Results

A reduction in any (from 68.7 to 47.7%), sufficient (from 41.5 to 22.1%) and out of home PA (from 59.4 to 30.1%) was observed from the first (pre-COVID-19) to the second (Jun/Jul 2020) timepoint, followed by an increase in the third timepoint (Dec 2020/Jan 2021) (60.1%, 37.9%, and 54.3% for any, sufficient, and out of home PA, respectively). The PA trajectory was similar, regardless of sex, educational level or income. Only any (p = 0.0007) and sufficient (p = 0.0012) PA showed significant interaction with time by sex. Female participants were less likely to engage in any (OR 0.45 95% CI 0.26; 0.77) and sufficient PA (OR 0.40 95% CI 0.24; 0.66).

Conclusion

During the first 10 months of COVID-19 pandemic there was a marked fluctuation on PA pattern in adults from southern Brazil. An ongoing tracking of PA behaviour during COVID-19 pandemic is important to understand how this behaviour varies. Public policies should focus on increasing PA in a higher standard than pre-COVID levels.
Bladder metastasis with additional metastases in multiple other organs 4 years after radical nephrectomy for clear cell renal cell carcinoma: a case report and review of the literature
Authors: Urushibara Masayasu , Nagata Masakazu , Okumura Taisuke , Kano Hideto , Matsumoto Yuuki , Tatsuoka Shinichiro , Nenohi Tsunehiro , Shirakawa Takeshi , Kato Daisuke , Kawamoto Masashi , Ishizaka Kazuhiro , Matsutani Noriyuki
Published: April 2022

Background

Renal cell carcinoma rarely metastasizes to the bladder, and its biological behavior is not yet fully understood.

Case presentation

In our case (54-year-old Japanese woman), computed tomography evaluation suggested the presence of a bladder metastasis, associated with additional metastases in the lungs, mediastinal lymph nodes, ribs, and renal bed, 4 years after radical nephrectomy for renal cell carcinoma. The histological findings of the metastatic bladder tumor were consistent with those of clear cell carcinoma. The mediastinal lymph node, rib, and renal bed metastases responded to treatment with an immune checkpoint inhibitor administered for 12 months after surgery for the bladder and lung metastases. In patients with bladder metastasis, absence of metastases in other organs and an interval of more than 1 year after nephrectomy are known to be favorable prognostic factors. Interestingly, in our case, the bladder metastasis was detected more than 1 year after nephrectomy, which was a favorable factor, but there were also metastases in other organs, which was an unfavorable factor. Therefore, we reviewed the literature, including that pertaining to targeted therapy and immune checkpoint inhibitor therapy published in the last two decades, to analyze the clinical significance of the presence of additional metastasis in other organs in renal cell carcinoma (clear cell type, which is the predominant subtype) patients with bladder metastasis.

Conclusions

Patients with bladder metastasis after nephrectomy for renal cell carcinoma also having metastases in other organs may respond to targeted therapy and immune checkpoint inhibitor therapy. This may suggest that the interval to relapse in the bladder after nephrectomy may be a more important prognostic factor than the presence of synchronous metastases in other organs.
A Bayesian evolutionary model towards understanding wildlife contribution to F4-family Mycobacterium bovis transmission in the South-West of France
Authors: Duault Hélène , Michelet Lorraine , Boschiroli Maria-Laura , Durand Benoit , Canini Laetitia
Published: April 2022

In two “départements” in the South-West of France, bovine tuberculosis (bTB) outbreaks due to Mycobacterium bovis spoligotype SB0821 have been identified in cattle since 2002 and in wildlife since 2013. Using whole genome sequencing, the aim of our study was to clarify badger contribution to bTB transmission in this area. We used a Bayesian evolutionary model, to infer phylogenetic trees and migration rates between two pathogen populations defined by their host-species. In order to account for sampling bias, sub-population structure was inferred using the marginal approximation of the structured coalescent (Mascot) implemented in BEAST2. We included 167 SB0821 strains (21 isolated from badgers and 146 from cattle) and identified 171 single nucleotide polymorphisms. We selected a HKY model and a strict molecular clock. We estimated a badger-to-cattle transition rate (median: 2.2 transitions/lineage/year) 52 times superior to the cattle-to-badger rate (median: 0.042 transitions/lineage/year). Using the maximum clade credibility tree, we identified that over 75% of the lineages from 1989 to 2000 were present in badgers. In addition, we calculated a median of 64 transition events from badger-to-cattle (IQR: 10–91) and a median of zero transition event from cattle-to-badger (IQR: 0–3). Our model enabled us to infer inter-species transitions but not intra-population transmission as in previous epidemiological studies, where relevant units were farms and badger social groups. Thus, while we could not confirm badgers as possible intermediaries in farm-to-farm transmission, badger-to-cattle transition rate was high and we confirmed long-term presence of M.bovis in the badger population in the South-West of France.
The association between area deprivation and COVID-19 incidence: a municipality-level spatio-temporal study in Belgium, 2020–2021
Authors: Meurisse Marjan , Lajot Adrien , Devleesschauwer Brecht , Van Cauteren Dieter , Van Oyen Herman , Van den Borre Laura , Brondeel Ruben
Published: April 2022

Background

In Belgium, current research on socio-economic inequalities in the coronavirus disease 2019 (COVID-19) crisis has mainly focused on excess mortality and data from the first epidemiological wave. The current study adds onto this by examining the association between COVID-19 incidence and area deprivation during the first five wave and interwave periods, thus adding a temporal gradient to the analyses.

Methods

We use all confirmed COVID-19 cases between March 2020 and June 2021 in Belgium, aggregated at the municipality-level. These data were collected by the national laboratory-based COVID-19 surveillance system. A level of area deprivation was assigned to each Belgian municipality using data of three socio-economic variables: the share of unemployed persons in the active population, the share of households without a car and the share of low-educated persons. The spatio-temporal association between COVID-19 incidence and area deprivation was assessed by performing multivariate negative-binomial regression analyses and computing population attributable fractions.

Results

A significant association between COVID-19 incidence and area deprivation was found over the entire study period, with the incidence in the most deprived areas predicted to be 24% higher than in the least deprived areas. This effect was dependent on the period during the COVID-19 crisis. The largest socio-economic inequalities in COVID-19 infections could be observed during wave 2 and wave 3, with a clear disadvantage for deprived areas.

Conclusion

Our results provide new insights into spatio-temporal patterns of socio-economic inequalities in COVID-19 incidence in Belgium. They reveal the existence of inequalities and a shift of these patterns over time.
The impact of school life and family involvement on Western China junior high school students’ wellbeing at multidimensional levels
Authors: Lv Yipeng , Gao Ye , Tang Bihan , Cheng Fan , Chen Zeqi , Wu Jing , Yang Hongyang , Liu Xu
Published: April 2022

Background

The focus of students’ health concerns has gradually progressed from the single factor of physical health to comprehensive health factors, and the physical and mental health of students are now generally considered together. This study focuses on exploring the status of junior high school students’ physical health and their subjective health assessment with the major societal factors that affect students’ lives: School Life and Family involvement. In addition, we explore the main factors influencing students’ subjective health.

Methods

A cross-sectional survey was conducted with 190 Tibetan junior high school students in the Maozhuang Township. The intentional sampling was used to choose the research object. The structured questionnaire comprised four parts, namely social and demographic information, family condition, school life, and subjective health quality which was assessed by PROMIS (Chinese version of the Pediatric Patient-Reported Outcomes Measurement Information System).

Result

The average height and weight of boys and girls are statistically different (p-values of 0.026 and 0.044, respectively), but there is no statistically significant difference in BMI (Body Mass Index) between boys and girls (p-value of 0.194). The average values of the five dimensions of depression, anger, anxiety, fatigue, and peer relationships in the PROMIS of the research subjects were 58.9 ± 5.3, 53.3 ± 8.0, 58.1 ± 7.3, 52.8 ± 8.0, 39.3 ± 6.6. In the demographic dimension, the grade was the main factor influencing anger (p < 0.01) and fatigue (p < 0.01), while gender was related to peer relationships (p = 0.02). In the family dimension, the father’s educational level was related to peer relationships (p = 0.05), while the family financial situation was related to depression (p = 0.01). In the school life dimension, relationship with classmates was found to affect anger (p = 0.05), while homework was related to anxiety (p = 0.02) and fatigue (p = 0.05).

Conclusion

the physical health index BMI and subjective health evaluation of students are worse than students of more developed areas in China. Their family environment and school life all have varying degrees of impact on the five subjective health outcomes. There are differences in gender and grade level. The government and society need to pay more attention to the physical and mental health of students in remote and underdeveloped areas and improve their health through a student nutrition plan and the establishment of mental health offices.
The GPIb-IX complex on platelets: insight into its novel physiological functions affecting immune surveillance, hepatic thrombopoietin generation, platelet clearance and its relevance for cancer development and metastasis
Authors: Bendas Gerd , Schlesinger Martin
Published: April 2022

The glycoprotein (GP) Ib-IX complex is a platelet receptor that mediates the initial interaction with subendothelial von Willebrand factor (VWF) causing platelet arrest at sites of vascular injury even under conditions of high shear. GPIb-IX dysfunction or deficiency is the reason for the rare but severe Bernard-Soulier syndrome (BSS), a congenital bleeding disorder. Although knowledge on GPIb-IX structure, its basic functions, ligands, and intracellular signaling cascades have been well established, several advances in GPIb-IX biology have been made in the recent years. Thus, two mechanosensitive domains and a trigger sequence in GPIb were characterized and its role as a thrombin receptor was deciphered. Furthermore, it became clear that GPIb-IX is involved in the regulation of platelet production, clearance and thrombopoietin secretion. GPIb is deemed to contribute to liver cancer development and metastasis. This review recapitulates these novel findings highlighting GPIb-IX in its multiple functions as a key for immune regulation, host defense, and liver cancer development.
The phyllosphere microbiome shifts toward combating melanose pathogen
Authors: Li Pu-Dong , Zhu Zeng-Rong , Zhang Yunzeng , Xu Jianping , Wang Hongkai , Wang Zhengyi , Li Hongye
Published: April 2022

Background

Plants can recruit beneficial microbes to enhance their ability to defend against pathogens. However, in contrast to the intensively studied roles of the rhizosphere microbiome in suppressing plant pathogens, the collective community-level change and effect of the phyllosphere microbiome in response to pathogen invasion remains largely elusive.

Results

Here, we integrated 16S metabarcoding, shotgun metagenomics and culture-dependent methods to systematically investigate the changes in phyllosphere microbiome between infected and uninfected citrus leaves by Diaporthe citri, a fungal pathogen causing melanose disease worldwide. Multiple microbiome features suggested a shift in phyllosphere microbiome upon D. citri infection, highlighted by the marked reduction of community evenness, the emergence of large numbers of new microbes, and the intense microbial network. We also identified the microbiome features from functional perspectives in infected leaves, such as enriched microbial functions for iron competition and potential antifungal traits, and enriched microbes with beneficial genomic characteristics. Glasshouse experiments demonstrated that several bacteria associated with the microbiome shift could positively affect plant performance under D. citri challenge, with reductions in disease index ranging from 65.7 to 88.4%. Among them, Pantoea asv90 and Methylobacterium asv41 identified as “recruited new microbes” in the infected leaves, exhibited antagonistic activities to D. citri both in vitro and in vivo, including inhibition of spore germination and/or mycelium growth. Sphingomonas spp. presented beneficial genomic characteristics and were found to be the main contributor for the functional enrichment of iron complex outer membrane receptor protein in the infected leaves. Moreover, Sphingomonas asv20 showed a stronger suppression ability against D. citri in iron-deficient conditions than iron-sufficient conditions, suggesting a role of iron competition during their antagonistic action.

Conclusions

Overall, our study revealed how phyllosphere microbiomes differed between infected and uninfected citrus leaves by melanose pathogen, and identified potential mechanisms for how the observed microbiome shift might have helped plants cope with pathogen pressure. Our findings provide novel insights into understanding the roles of phyllosphere microbiome responses during pathogen challenge.
Identification of potential pathways and microRNA-mRNA networks associated with benzene metabolite hydroquinone-induced hematotoxicity in human leukemia K562 cells
Authors: Yu Chun-Hong , Yang Shui-Qing , Li Lei , Xin Yu , Zhang Fang , Liu Xiao-Fan , Yi Zong-Chun
Published: April 2022

Background

Hydroquinone (HQ) is a phenolic metabolite of benzene with a potential risk for hematological disorders and hematotoxicity in humans. In the present study, an integrative analysis of microRNA (miRNA) and mRNA expressions was performed to identify potential pathways and miRNA-mRNA network associated with benzene metabolite hydroquinone-induced hematotoxicity.

Methods

K562 cells were treated with 40 μM HQ for 72 h, mRNA and miRNA expression changes were examined using transcriptomic profiles and miRNA microarray, and then bioinformatics analysis was performed.

Results

Out of all the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) induced by HQ, 1482 DEGs and 10 DEMs were up-regulated, and 1594 DEGs and 42 DEMs were down-regulated. HQ-induced DEGs were involved in oxidative stress, apoptosis, DNA methylation, histone acetylation and cellular response to leukemia inhibitory factor GO terms, as well as metabolic, Wnt/β-catenin, NF-κB, and leukemia-related pathways. The regulatory network of mRNAs and miRNAs includes 23 miRNAs, 1108 target genes, and 2304 potential miRNAs-mRNAs pairs. MiR-1246 and miR-224 had the potential to be major regulators in HQ-exposed K562 cells based on the miRNAs-mRNAs network.

Conclusions

This study reinforces the use of in vitro model of HQ exposure and bioinformatic approaches to advance our knowledge on molecular mechanisms of benzene hematotoxicity at the RNA level.
Vitamin D activates FBP1 to block the Warburg effect and modulate blast metabolism in acute myeloid leukemia
Authors: Xu Yi , Hino Christopher , Baylink David J. , Xiao Jeffrey , Reeves Mark E. , Zhong Jiang F. , Mirshahidi Saied , Cao Huynh
Published: April 2022

Acute myeloid leukemia (AML) has the lowest survival rate among the leukemias. Targeting intracellular metabolism and energy production in leukemic cells can be a promising therapeutic strategy for AML. Recently, we presented the successful use of vitamin D (1,25VD3) gene therapy to treat AML mouse models in vivo. In this study, recognizing the importance of 1,25VD3 as one of only 2 molecules (along with glucose) photosynthesized for energy during the beginning stage of life on this planet, we explored the functional role of 1,25VD3 in AML metabolism.

Transcriptome database (RNA-seq) of four different AML cell lines revealed 17,757 genes responding to 1,25VD3-treatment. Moreover, we discovered that fructose-bisphosphatase 1 (FBP1) noticeably stands out as the only gene (out of 17,757 genes) with a 250-fold increase in gene expression, which is known to encode the key rate-limiting gluconeogenic enzyme fructose-1,6-bisphosphatase. The significant increased expression of FBP1 gene and proteins induced by 1,25VD3 was confirmed by qPCR, western blot, flow cytometry, immunocytochemistry and functional lactate assay. Additionally, 1,25VD3 was found to regulate different AML metabolic processes including gluconeogenesis, glycolysis, TCA, de novo nucleotide synthesis, etc. In summary, we provided the first evidence that 1,25 VD3-induced FBP1 overexpression might be a novel therapeutic target to block the “Warburg Effect” to reduce energy production in AML blasts.
Citizenship and new urban realities
Authors: Indovina Francesco
Published: April 2022

Cities have always been the place where 'diversity' has settled, within a substantial ethnic, cultural, religious and linguistic identity. The author's emphasis on the need for a cultural policy on migration and welcoming not in 'moral' terms but in relation to a mutual interest between different peoples and cultures. A policy which highlights 'diversity' and allows for peaceful coexistence and sharing, provides the basis for what can be called a policy of coexistence, or a strategy for coexistence. Such a policy can only be the result of a collective debate and effort which can propose new ideas of citizenship.
Barriers to collecting student participation and completion data for a national STEM education grant program in the United States: a multiple case study
Authors: Ruhf Robert J. , Williams Cody T. , Zelinsky Megan , Becho Lyssa Wilson
Published: April 2022

Background

Billions of dollars are spent annually on grant-funded STEM (science, technology, engineering, and mathematics) education programs. These programs help students stay on track toward STEM careers when standard educational practices do not adequately prepare them for these careers. It is important to know that reliable and accurate student participation and completion data are being collected about these programs. This multiple case study investigates how student data are collected and reported for a national STEM education program in the United States, the National Science Foundation (NSF) Advanced Technological Education (ATE) program. Our overall aim is to provide insights to funding agencies, STEM education faculty, and others who are interested in addressing issues related to the collection and reporting of student participation and completion data within their own contexts. Emphasis is placed on the barriers encountered in collecting participation and completion data, particularly with regard to unduplicated participation counts and marketable credential data. The ATE program was selected for this study because there is already a mechanism (known as the ATE Survey) in place for annually collecting systematic data across all projects within the program.

Results

A multiple case study, including interviews of primary investigators, allowed for in-depth analysis of the ATE Survey’s point-in-time data on project-level participation in various activities, and for identification of the following barriers to tracking student-level data: lack of time and help to gather these data, lack of a consistent system for tracking students across different institutions, and a perceived lack of guidance from the funding agency about what data to track. We also saw that different data are needed from different projects to determine a project’s true impact. Defining “success” the same way across all projects is inadequate.

Conclusions

Although, due to the limited sample size, these findings cannot be generalized to the larger ATE population, they provide specific insights into the various barriers that projects encounter in collecting participation and completion data.
The chitosan/carboxymethyl cellulose/montmorillonite scaffolds incorporated with epigallocatechin-3-gallate-loaded chitosan microspheres for promoting osteogenesis of human umbilical cord-derived mesenchymal stem cell
Authors: Wang Jin , He Wubo , Tan Wen-Song , Cai Haibo
Published: April 2022

Epigallocatechin-3-gallate (EGCG) is a plant-derived flavonoid compound with the ability to promote the differentiation of human bone marrow-derived mesenchymal stem cells (MSCs) into osteoblasts. However, the effect of EGCG on the osteogenic differentiation of the human umbilical cord-derived mesenchymal stem cells (HUMSCs) is rarely studied. Therefore, in this study, the osteogenic effects of EGCG are studied in the HUMSCs by detecting cell proliferation, alkaline phosphatase (ALP) activity, calcium deposition and the expression of relevant osteogenic markers. The results showed that EGCG can promote the proliferation and osteogenic differentiation of the HUMSCs in vitro at a concentration of 2.5–5.0 μM. Unfortunately, the EGCG is easily metabolized by cells during cell culture, which reduces its bioavailability. Therefore, in this paper, EGCG-loaded microspheres (ECM) were prepared and embedded in chitosan/carboxymethyl cellulose/montmorillonite (CS/CMC/MMT) scaffolds to form CS/CMC/MMT-ECM scaffolds for improving the bioavailability of EGCG. The HUMSCs were cultured on CS/CMC/MMT-ECM scaffolds to induce osteogenic differentiation. The results showed that the CS/CMC/MMT-ECM scaffold continuously released EGCG for up to 22 days. In addition, CS/CMC/MMT-ECM scaffolds can promote osteoblast differentiation. Taken together, the present study suggested that entrainment of ECM into CS/CMC/MMT scaffolds was a prospective scheme for promotion osteogenic differentiation of the HUMSCs.

Graphical Abstract
Hierarchical intrinsically motivated agent planning behavior with dreaming in grid environments
Authors: Dzhivelikian Evgenii , Latyshev Artem , Kuderov Petr , Panov Aleksandr I.
Published: April 2022

Biologically plausible models of learning may provide a crucial insight for building autonomous intelligent agents capable of performing a wide range of tasks. In this work, we propose a hierarchical model of an agent operating in an unfamiliar environment driven by a reinforcement signal. We use temporal memory to learn sparse distributed representation of state–actions and the basal ganglia model to learn effective action policy on different levels of abstraction. The learned model of the environment is utilized to generate an intrinsic motivation signal, which drives the agent in the absence of the extrinsic signal, and through acting in imagination, which we call dreaming. We demonstrate that the proposed architecture enables an agent to effectively reach goals in grid environments.
Individual differences in skill acquisition and transfer assessed by dual task training performance and brain activity
Authors: Reddy Pratusha , Shewokis Patricia A. , Izzetoglu Kurtulus
Published: April 2022

Assessment of expertise development during training program primarily consists of evaluating interactions between task characteristics, performance, and mental load. Such a traditional assessment framework may lack consideration of individual characteristics when evaluating training on complex tasks, such as driving and piloting, where operators are typically required to execute multiple tasks simultaneously. Studies have already identified individual characteristics arising from intrinsic, context, strategy, personality, and preference as common predictors of performance and mental load. Therefore, this study aims to investigate the effect of individual difference in skill acquisition and transfer using an ecologically valid dual task, behavioral, and brain activity measures. Specifically, we implemented a search and surveillance task (scanning and identifying targets) using a high-fidelity training simulator for the unmanned aircraft sensor operator, acquired behavioral measures (scan, not scan, over scan, and adaptive target find scores) using simulator-based analysis module, and measured brain activity changes (oxyhemoglobin and deoxyhemoglobin) from the prefrontal cortex (PFC) using a portable functional near-infrared spectroscopy (fNIRS) sensor array. The experimental protocol recruited 13 novice participants and had them undergo three easy and two hard sessions to investigate skill acquisition and transfer, respectively. Our results from skill acquisition sessions indicated that performance on both tasks did not change when individual differences were not accounted for. However inclusion of individual differences indicated that some individuals improved only their scan performance (Attention-focused group), while others improved only their target find performance (Accuracy-focused group). Brain activity changes during skill acquisition sessions showed that mental load decreased in the right anterior medial PFC (RAMPFC) in both groups regardless of individual differences. However, mental load increased in the left anterior medial PFC (LAMPFC) of Attention-focused group and decreased in the Accuracy-focused group only when individual differences were included. Transfer results showed no changes in performance regardless of grouping based on individual differences; however, mental load increased in RAMPFC of Attention-focused group and left dorsolateral PFC (LDLPFC) of Accuracy-focused group. Efficiency and involvement results suggest that the Attention-focused group prioritized the scan task, while the Accuracy-focused group prioritized the target find task. In conclusion, training on multitasks results in individual differences. These differences may potentially be due to individual preference. Future studies should incorporate individual differences while assessing skill acquisition and transfer during multitask training.
Successful salvage surgery followed by second ALK–TKI after alectinib failure in a patient with ALK-positive NSCLC
Authors: Hashimoto Hiroshi , Komori Kazuyuki , Kameda Koji , Taguchi Shinichi , Ozeki Yuichi
Published: April 2022

Background

Anaplastic lymphoma kinase (ALK)–tyrosine kinase inhibitors (TKIs) have been approved for the therapy of locally advanced non-small cell lung cancer (NSCLC) caused by ALK rearrangement. However, its treatment after failure of initial ALK–TKI therapy remains controversial.

Case presentation

A 47-year-old woman with a hemosputum was diagnosed with adenocarcinoma of the left lung (cT2bN3M0, stage IIIB). Gene mutation analysis indicated positive ALK translocation. Alectinib was selected as the first-line treatment. Although the treatment effect was determined as a partial response, the main tumor regrew. Alectinib was discontinued, and salvage surgery was performed without causing morbidity. The pathological diagnosis was pleomorphic carcinoma without lymph node metastasis (yp-T2bN0). After surgery, lorlatinib was administered as the second-line treatment for 8 months until the patient could not tolerate continuation. Computed tomography scan revealed no lung cancer recurrence 14 months after discontinuation.

Conclusions

Our experience with this case suggests that salvage surgery after alectinib treatment followed by lorlatinib therapy may be effective for initially unresectable ALK-positive NSCLC.
Corporate pledgeable asset ownership and stock price crash risk
Authors: Jung Hail , Choi Sanghak , Lee Junyoup , Woo Sanggeum
Published: April 2022

We investigate how a firm’s corporate pledgeable asset ownership (CPAO) affects the risk of future stock price crashes. Using pledgeable asset ownership and crash risk data for a large sample of U.S. firms, we provide novel empirical evidence that a firm’s risk of a future stock price crash decreases with an increase in its pledgeable assets. Our main findings are valid after conducting various robustness tests. Further channel tests reveal that firms with pledgeable assets increase their collateral value, thereby enhancing corporate transparency and limiting bad news hoarding, resulting in lower stock price crash risk. Overall, the results show that having more pledgeable assets enables easier access to external financing, making it less likely that managers will hoard bad news.