bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the geographic pattern of the police reports for domestic violence in Girona (Spain)
Authors: Serra Laura , Vall-llosera Laura , Varga Diego , Saurina Carme , Saez Marc , Renart Gemma
Published: March 2022

Background

There are many studies that address the issue of gender-based violence, but few analyse the police-reported cases. It is as important to analyse the temporal and geographic distribution of these incidents as it is the sociodemographic profile of the accuser. To this effect, the present study aims to analyse the sociodemographic profile of the victims of the particular case of domestic violence that report the incident to the police and to evaluate the spatial–temporal distribution of these reports.

Methods

Using the data from a database containing the police-reported incidents of domestic violence in Girona in the period 2012–2018, the risk of a police-reported incident was estimated by adjusting the two-part Hurdle model.

Results

The risk of reporting incidents of domestic violence to the police is higher in the less deprived areas of the city, and the spatial distribution of these police reports corroborate this finding. Nevertheless, those areas with the greatest socio-economic deprivation were also the ones where there were less police reports filed. Also the prediction of less police reports in the census tract with the highest percentage of the population with an insufficient educational level coincides with the largest number of police reports made by women with a medium and university level education (56.1%) compared with 9.5% of police reports made by women with insufficient schooling.

Conclusions

These results can be useful for social protection services to design policies specifically aimed at women residing in those areas with the highest risk. Moreover, the use of spatial statistical techniques together with geographic information systems tools is a good strategy to analyse domestic violence and other types of offences because they not only allow to graphically identify the spatial distribution, but it is also a good tool to identify problems related to this type of offence.
Development of a simple and effective online training for health workers: results from a pilot in Nigeria
Authors: Thomas Marshall P. , Kozikott Samantha , Kamateeka Moreen , Abdu-Aguye Ramatu , Agogo Emmanuel , Bello Bakunawa Garba , Brudney Karen , Manzi Olivier , Patel Leena N. , Barrera-Cancedda Amy Elizabeth , Abraham Jobin , Lee Christopher T.
Published: March 2022

Background

Health workers (HWs) in Africa face challenges accessing and learning from existing online training opportunities. To address these challenges, we developed a modular, self-paced, mobile-ready and work-relevant online course covering foundational infection prevention and control (IPC) concepts. Here, we evaluate the first pilot of this course, conducted with HWs in Nigeria.

Methods

We used a learner-centered design and prototyping process to create a new approach to delivering online training for HWs. The resulting course comprised 10 self-paced modules optimized for use on mobile devices. Modules presented IPC vignettes in which learning was driven by short assessment questions with feedback. Learners were recruited by distributing a link to the training through Nigeria-based email lists, WhatsApp groups and similar networks of HWs, managers and allied professionals. The course was open to learners for 8 weeks. We tracked question responses and time on task with platform analytics and assessed learning gains with pre- and post-testing. Significance was evaluated with the Wilcoxon signed-rank test, and effect size was calculated using Cohen’s d.

Results

Three hundred seventy-two learners, with roles across the health system, enrolled in the training; 59% completed all 10 modules and earned a certificate. Baseline knowledge of foundational IPC concepts was low, as measured by pre-test scores (29%). Post-test scores were significantly higher at 54% (effect size 1.22, 95% confidence interval 1.00-1.44). Learning gains were significant both among learners with low pre-test scores and among those who scored higher on the pre-test. We used the Net Promoter Score (NPS), a common user experience metric, to evaluate the training. The NPS was + 62, which is slightly higher than published scores of other self-paced online learning experiences.

Conclusions

High completion rates, significant learning gains and positive feedback indicate that self-paced, mobile-ready training that emphasizes short, low-stakes assessment questions can be an effective, scalable way to train HWs who choose to enroll. Low pre-test scores suggest that there are gaps in IPC knowledge among this learner population.
The clustering of physical activity and screen time behaviours in early childhood and impact on future health-related behaviours: a longitudinal analysis of children aged 3 to 8 years
Authors: Martin Rosemarie , Murphy Joey , Molina-Soberanes Daniel , Murtagh Elaine M
Published: March 2022

Background

Meeting physical activity and screen time guidelines has been associated with improved health in children. Research has shown that lifestyle behaviours happen in combination and can be tracked into later life. Thus, a complex approach is needed to identify the effects of physical activity and screen time altogether. This study aims to identify clusters of both behaviours in a cohort of Irish 3-year-old children (n = 8833) and determine the association with sociodemographic characteristics and behaviours at age 5 and 7-8.

Methods

Data from the “Growing Up in Ireland” study collected between 2010 and 2016 was used in this study. Two-step cluster analysis was used to understand how physical activity and recreational screen time behaviours group together among 3-year-old children. Binary logistic regressions were conducted to examine if cluster placement at age 3 determined physical activity and recreational screen time behaviours at age 5 and 7-8 years, while controlling for gender of child, gender, age and employment status of the primary caregiver.

Results

Six clusters were identified in 9771 (49.3% female) 3-year-old children with the majority falling into a “High Active & Mixed Screen Time” (23.2%). Those in the “High Active & Mixed Screen Time” cluster at age 3 were more likely to engage in all physical activities reported at age 5 (p < 0.01) and age 7-8 (p < 0.01) when compared to a “Low Active & Screen Time Exceed” cluster. Children categorised in a “Moderate Active & Screen Time Below” and “Moderate Active & Screen Time Exceed” were more likely to engage in the same physical activities at age 5 and 7-8 (p < 0.05 - p < 0.01). However, children in the latter cluster were also more likely (p < 0.05) to play on a computer or tablet device.

Conclusions

This paper highlights the importance of establishing positive health-related behaviours during early childhood, as this predicts future engagement in health-promoting activities. Regardless of screen time level, being part of a cluster with moderate or high levels of physical activity positively influences a child’s future physical activity at age 5 and again at age 7 -8 years. The multiple layers of influence on a child’s development should be leveraged to support the adoption of health-enhancing behaviours.
Willingness and uptake of the COVID-19 testing and vaccination in urban China during the low-risk period: a cross-sectional study
Authors: Song Suhang , Zang Shujie , Gong Liubing , Xu Cuilin , Lin Leesa , Francis Mark R. , Hou Zhiyuan
Published: March 2022

Background

Regular testing and vaccination are effective measures to mitigate the ongoing COVID-19 pandemic. Evidence on the willingness and uptake of the COVID-19 testing is scarce, and the willingness and uptake of vaccination may change as the pandemic evolves. This study aims to examine willingness and uptake of COVID-19 testing and vaccination during a low-risk period of the COVID-19 pandemic in urban China.

Methods

A cross-sectional online survey was conducted among 2244 adults in urban China. Descriptive analyses were performed to compare the respondents’ willingness and uptake of COVID-19 testing and vaccination. Multivariate logistic regressions were fitted to investigate factors associated with the willingness and uptake of the two measures.

Results

In early 2021, about half (52.45%) of the respondents had received or scheduled a COVID-19 test at least once, and a majority (95.63%) of the respondents were willing to receive testing. About two-thirds (63.28%) of the respondents had received/scheduled or were willing to receive a COVID-19 vaccine. Willingness and uptake of COVID-19 testing were not associated with socio-demographic characteristics, except for occupation. Being of older age, migrants, having higher educational attainment and secure employment were associated with a higher uptake of COVID-19 vaccination among the surveyed respondents, while willingness to vaccinate was consistent across socio-demographic characteristics among those who had not been vaccinated.

Conclusions

By early 2021, Chinese adults expressed almost universal willingness of COVID-19 testing and over half of adults have been tested, while the willingness and uptake of COVID-19 vaccination were relatively low at the low-risk period of the COVID-19 pandemic. Maintaining willingness of COVID-19 vaccination is critical and necessary, especially when the pandemic evolved into a low-risk period.
A comparative analysis of lung function and spirometry parameters in genotype-controlled natives living at low and high altitude
Authors: Ortiz-Prado Esteban , Encalada Sebastián , Mosquera Johanna , Simbaña-Rivera Katherine , Gomez-Barreno Lenin , Duta Diego , Ochoa Israel , Izquierdo-Condoy Juan S. , Vasconez Eduardo , Burgos German , Calvopiña Manuel , Viscor Ginés
Published: March 2022

Background

The reference values for lung function are associated to anatomical and lung morphology parameters, but anthropometry it is not the only influencing factor: altitude and genetics are two important agents affecting respiratory physiology. Altitude and its influence on respiratory function has been studied independently of genetics, considering early and long-term acclimatization.

Objective

The objective of this study is to evaluate lung function through a spirometry study in autochthonous Kichwas permanently living at low and high-altitude.

Methodology

A cross-sectional study of spirometry differences between genetically matched lowland Kichwas from Limoncocha (230 m) at Amazonian basin and high-altitude Kichwas from Oyacachi (3180 m) in Andean highlands. The sample size estimates permitted to recruited 118 patients (40 men and 78 women) from Limoncocha and 95 (39 men and 56 women) from Oyacachi. Chi-square method was used to analyze association or independence of categorical variables, while Student’s t test was applied to comparison of means within quantitative variables. ANOVA, or in the case that the variables didn’t meet the criteria of normality, Kruskal Wallis test were used to compare more than two groups.

Results

The FVC and the FEV1 were significantly greater among highlanders than lowlanders (p value < 0.001), with a proportion difference of 15.2% for men and 8.5% for women. The FEV1/FVC was significantly higher among lowlanders than highlanders for men and women. A restrictive pattern was found in 12.9% of the participants.

Conclusion

Residents of Oyacachi had greater FVC and FEV1 than their peers from Limoncocha, a finding physiologically plausible according to published literature. Lung size and greater ventilatory capacities could be an adaptive mechanism developed by the highlander in response to hypoxia. Our results support the fact that this difference in FVC and FEV1 is a compensatory mechanism towards lower barometric and alveolar partial pressure of oxygen pressure.
How medical students co-regulate their learning in clinical clerkships: a social network study
Authors: Bransen Derk , Driessen Erik W. , Sluijsmans Dominique M. A. , Govaerts Marjan J. B.
Published: March 2022

Background

Self-regulated learning is a key competence to engage in lifelong learning. Research increasingly acknowledges that medical students in clerkships need others to regulate their learning. The concept of “co-regulated learning” captures this act of regulating one’s learning by interacting with others. To effectively cultivate such skills in students, we need to increase our understanding of co-regulated learning. This study aimed to identify the purposes for which students in different phases of clinical training engage others in their networks to regulate their learning.

Methods

In this social network study, we administered a questionnaire to 403 medical students during clinical clerkships (65.5% response rate). The questionnaire probed into the composition of students’ co-regulatory networks and the purpose for which they engaged others in specified self-regulated learning activities. We calculated the proportion of students that engaged others in their networks for each regulatory activity. Additionally, we conducted ANOVAs to examine whether first-, second-, and third-year students differed in how they used their networks to support self-regulation.

Results

Students used others within their co-regulatory networks to support a range of self-regulated learning activities. Whom students engaged, and the purpose of engagement, seemed to shift as students progressed through clinical training. Over time, the proportion of students engaging workplace supervisors to discuss learning goals, learning strategies, self-reflections and self-evaluations increased, whereas the proportion of students engaging peers to discuss learning strategies and how to work on learning goals in the workplace decreased. Of all purposes for which students engaged others measured, discussing self-reflections and self-evaluations were consistently among the ones most frequently mentioned.

Conclusions

Results reinforce the notion that medical students’ regulation of learning is grounded in social interactions within co-regulatory networks students construct during clerkships. Findings elucidate the extent to which students enact self-regulatory learning within their co-regulatory networks and how their co-regulatory learning behaviors develop over time. Explicating the relevance of interactions within co-regulatory networks might help students and supervisors to purposefully engage in meaningful co-regulatory interactions. Additionally, co-regulatory interactions may assist students in regulating their learning in clinical workplaces as well as in honing their self-regulated learning skills.
Spirometry parameters used to define small airways obstruction in population-based studies: systematic review
Authors: Knox-Brown Ben , Mulhern Octavia , Feary Johanna , Amaral Andre F. S.
Published: March 2022

Background

The assessment of small airways obstruction (SAO) using spirometry is practiced in population-based studies. However, it is not clear what are the most used parameters and cut-offs to define abnormal results.

Methods

We searched three databases (Medline, Web of Science, Google Scholar) for population-based studies, published by 1 May 2021, that used spirometry parameters to identify SAO and/or provided criteria for defining SAO. We systematically reviewed these studies and summarised evidence to determine the most widely used spirometry parameter and criteria for defining SAO. In addition, we extracted prevalence estimates and identified associated risk factors. To estimate a pooled prevalence of SAO, we conducted a meta-analysis and explored heterogeneity across studies using meta regression.

Results

Twenty-five studies used spirometry to identify SAO. The most widely utilised parameter (15 studies) was FEF25–75, either alone or in combination with other measurements. Ten studies provided criteria for the definition of SAO, of which percent predicted cut-offs were the most common (5 studies). However, there was no agreement on which cut-off value to use. Prevalence of SAO ranged from 7.5% to 45.9%. As a result of high heterogeneity across studies (I2 = 99.3%), explained by choice of spirometry parameter and WHO region, we do not present a pooled prevalence estimate.

Conclusion

There is a lack of consensus regarding the best spirometry parameter or defining criteria for identification of SAO. The value of continuing to measure SAO using spirometry is unclear without further research using large longitudinal data.

PROSPERO registration numberCRD42021250206
Association between mental illness and blood pressure variability: a systematic review
Authors: Shahimi Nur Husna , Lim Renly , Mat Sumaiyah , Goh Choon-Hian , Tan Maw Pin , Lim Einly
Published: March 2022

Background

Mental illness represents a major global burden of disease worldwide. It has been hypothesised that individuals with mental illness have greater blood pressure fluctuations that lead to increased cardiovascular risk and target organ damage. This systematic review aims to (i) investigate the association between mental illness and blood pressure variability (BPV) and (ii) describe methods of BPV measurements and analysis which may affect pattern and degree of variability.

Methods

Four electronic databases were searched from inception until 2020. The quality assessment was performed using STROBE criteria. Studies were included if they investigated BPV (including either frequency or time domain analysis) in individuals with mental illness (particularly anxiety/generalised anxiety disorder, depression/major depressive disorder, panic disorder and hostility) and without hypertension. Two authors independently screened titles, abstracts and full texts. A third author resolved any disagreements.

Results

Twelve studies met the inclusion criteria. Three studies measured short-term BPV, two measured long-term BPV and seven measured ultra-short-term BPV. All studies related to short-term BPV using ambulatory and home blood pressure monitoring found a higher BPV in individuals with depression or panic disorder. The two studies measuring long-term BPV were limited to the older population and found mixed results. Mental illness is significantly associated with an increased BPV in younger and middle-aged adults. All studies of ultra-short-term BPV using standard cardiac autonomic assessment; non-invasive continuous finger blood pressure and heart rate signals found significant association between BPV and mental illness. A mixed result related to degree of tilt during tilt assessment and between controlled and spontaneous breathing were observed in patients with psychological state.

Conclusions

Current review found that people with mental illness is significantly associated with an increased BPV regardless of age. Since mental illness can contribute to the deterioration of autonomic function (HRV, BPV), early therapeutic intervention in mental illness may prevent diseases associated with autonomic dysregulation and reduce the likelihood of negative cardiac outcomes. Therefore, these findings may have important implications for patients' future physical health and well-being, highlighting the need for comprehensive cardiovascular risk reduction.
CTHRC1 targeted by miR-30a-5p regulates cell adhesion, invasion and migration in lung adenocarcinoma
Authors: Yang Chaomian , Huang Tianxia , Liang Yue , Xue Yanlong , Liang Ying , Wei Xianqin , Meng Fangchan , Wei Qiu
Published: March 2022

The morbidity of lung cancer ranks first among all cancers. Lung adenocarcinoma (LUAD) is a classification of lung cancer, and cell invasion and migration of LUAD are the main causes for its high mortality. Therefore, further exploring the potential mechanism of LUAD metastasis may provide bases for following targeted drug development and treatment of LUAD. In this study, clinical data as well as gene expression profiles were obtained from TCGA-LUAD and GEO to analyze CTHRC1 expression. The result found that CTHRC1 was significantly high in LUAD. Similar results were also discovered in 4 cancer cell lines. Moreover, overexpressed/knock-down CTHRC1 cell lines were constructed. It was uncovered that overexpressing CTHRC1 promoted LUAD cell migration and invasion, and inhibited cell adhesion, while knocked down CTHRC1 had the opposite effect. Afterward, the upstream miRNAs that regulated CTHRC1 were predicted by several bioinformatics websites. It was testified by dual-luciferase method that CTHRC1 was negatively mediated by miR-30a-5p. Overexpressed miR-30a-5p suppressed cell invasion/migration, and increased cell adhesion, while overexpressing CTHRC1 as well reversed such impacts. In conclusion, it was disclosed in this study that CTHRC1 worked as a cancer promoter in LUAD, and miR-30a-5p could target and downregulate CTHRC1 to regulate cell adhesion, and inhibited LUAD cell invasion and migration. These results elucidated at cellular level that upregulated CTHRC1 may be a marker protein for LUAD metastasis.
Short (seven days) versus standard (fourteen days) oestrogen administration in a programmed frozen embryo transfer cycle: a retrospective cohort study
Authors: Jiang Wen-Jing , Song Jing-Yan , Sun Zhen-Gao
Published: March 2022

Research question

What influence does seven days of oestrogen administration versus fourteen days have on the reproductive outcomes of frozen-thawed embryo transfer (FET) in programmed endometrial preparation cycles?

Design

In a retrospective study, conducted at a university-affiliated tertiary hospital, a total of 2628 infertile patients (4142 FET cycles) were divided into one of two groups between January 2014 and December 2020: group A (n = 1406, seven days of oestrogen before progesterone (P4) supplementation) and group B (n = 2716, fourteen days of oestrogen before P4 supplementation). The primary outcome was cumulative live birth rate (CLBR). Secondary outcomes were other pregnancy-related outcomes, maternal and neonatal complications.

Results

No significant difference in CLBR was observed when comparing seven versus fourteen days of oestrogen administration before starting P4 supplementation (47.6% vs. 48.8%, P = 0.537). Furthermore, multivariable logistic regression analysis revealed that oestrogen administration in programmed FET cycles (7 days vs. 14 days) was not significantly associated with CLBR (OR 1.04, 95% CI 0.89–1.23). The risks of maternal and neonatal complications were comparable between the two groups.

Conclusions

Variation in the duration of oestradiol supplementation before P4 initiation does not impact FET reproductive outcomes. For infertile women who desire to conceive as soon as feasible, short (seven days) oestrogen administration in a programmed FET cycle may be a suitable alternative.
The relevance of the interpersonal theory of suicide for predicting past-year and lifetime suicidality in autistic adults
Authors: Moseley R. L. , Gregory N. J. , Smith P. , Allison C. , Cassidy S. , Baron-Cohen S.
Published: March 2022

Background

While there are known risk factors for suicidality in autistic adults, these are often unconnected from theoretical frameworks that might explainwhyrisk is elevated and guide clinical interventions. The present study investigated the relevance of constructs from the Interpersonal Theory of Suicide (ITS), including perceived burdensomeness, thwarted belongingness and acquired capability for suicide, and explored mechanisms through which certain risk factors (relationship status, age at diagnosis) might elevate suicide risk.

Methods

Autistic adults (n = 314) completed an online study including measures of depression, anxiety and constructs from the ITS. Linear and multinomial regression analysis disentangled contributions of ITS variables from effects of depression and anxiety for past-year suicide ideation, past-year and lifetime suicide attempts. Mediation analyses examined associations between risk factors and these suicide outcomes via mechanisms proposed by the ITS.

Results

Past-year suicide ideation was associated with burdensomeness, mental rehearsal of suicide plans (a facet of acquired capability), and depression. Greater feelings of burdensomeness, and reduced fear of death, marked out participants who had attempted suicide in comparison to those who had experienced suicide ideation in the past year. Relationship status was indirectly associated with past-year suicide ideation via the mediators of depression and burdensomeness, and was associated with past-year attempts via its effect on ideation. Age at diagnosis was unrelated to any variables.

Limitations

Cross-sectional research is insensitive to causality and temporal dynamics, which is likely why interaction hypotheses from the ITS were unsupported. Normative measures may be invalid in autistic samples. There was no control group. The autistic sample was unrepresentative of the whole population, particularly autistic people with intellectual disabilities, ethnic/racial minorities, and gender minorities.

Conclusions

Perceived burdensomeness and acquired capability appear potentially important to suicide in autistic people, and may mediate the effects of some risk factors. Future research should explore the temporal dynamics of suicide trajectories in longitudinal, prospective designs.
Prkg2 regulates alveolar type 2-mediated re-alveolarization
Authors: Zhang Mo , Ali Gibran , Komatsu Satoshi , Zhao Runzhen , Ji Hong-Long
Published: March 2022

Background

The cGMP-dependent type 2 protein kinase, encoded by the prkg2 gene, is highly expressed in alveolar type 2 epithelial (AT2) cells. It is unclear whether prkg2 regulates AT2 cell homeostasis and re-alveolarization of injured lungs. This study aimed to investigate the role of prkg2 in the regulation of the fate of AT2 in vitro.

Methods

Primary AT2 cells of wild-type (wt) and prkg2−/− mice were co-cultured with fibroblasts as three-dimensional organoids. The colony formation was analyzed between days 4 and 12 post-seeding. EdU assay was used to detect cells with active DNA synthesis. AT1 and AT2 cells in organoids were visualized with anti-podoplanin and anti-surfactant protein C antibodies, respectively.

Results

Prkg2−/− AT2 cells developed a greater number of organoids than wt controls. However, compared to wt organoids, a lower number of AT2 but a greater number of AT1 cells were visualized. In addition, a lower number of proliferated cells (EdU+) were observed in prkg2−/− organoids compared to wt controls. The numbers of organoids and EdU+ cells were significantly reduced in protein kinase A (PKA) inhibitor H89-treated wt and prkg2−/− cultures. Organoids and EdU+ cells were increased by lipopolysaccharides (LPS) in both wt and prkg2−/− groups. The increase in the proportion of AT1 and AT2 cells in organoids was only seen in wt controls.

Conclusions

Prkg2 may regulate the lineage of AT2 cells, which is affected by endotoxins and the interactive PKA signaling pathway.
Characteristics of SOX9-positive progenitor-like cells during cholestatic liver regeneration in biliary atresia
Authors: Lin Yuting , Zhang Fang , Zhang Ludi , Chen Lian , Zheng Shan
Published: March 2022

Background

The progression of Biliary Atresia (BA) is associated with the number of reactive ductular cells (RDCs) whose heterogeneity in origin and evolution in humans remains unknown. SOX9-positive liver progenitor-like cells (LPLCs) have been shown to participate in RDCs and new hepatocyte formation during cholestatic liver regeneration in an animal model, which implies the possibility that hepatocyte-reprogrammed LPLCs could be a source of RDCs in BA. The present study aimed to elucidate the characteristics of SOX9-positive LPLCs in BA for exploring new possible therapeutic targets by manipulating the bi-differentiation process of LPLCs to prevent disease progression.

Methods

Twenty-eight patients, including 24 patients with BA and 4 patients with Congenital Choledochal Cyst as the control group, were retrospectively recruited. Liver biopsy samples were classified histologically using a 4-point scale based on fibrosis severity. LPLCs were detected by SOX9 and HNF4A double positive staining. Single immunohistochemistry, double immunohistochemistry, and multiple immunofluorescence staining were used to determine the different cell types and characteristics of LPLCs.

Results

The prognostic predictors of BA, namely total bile acid (TBA), RDCs, and fibrosis, were correlated to the emergence of LPLCs. SOX9 and HNF4A double-positive LPLCs co-stained rarely with relevant markers of portal hepatic progenitor cells (portal-HPCs), including CK19, CK7, EPCAM, PROM1 (CD133), TROP2, and AFP. Under cholestasis conditions, LPLCs acquired superior proliferation and anti-senescence ability among hepatocytes. Moreover, LPLCs arranged as a pseudo-rosette structure appeared from the periportal parenchyma to the portal region, which implied the differentiation from hepatocyte-reprogrammed LPLCs to RDCs with the progression of cholestasis.

Conclusions

LPLCs are associated with disease progression and prognostic factors of BA. The bipotent characteristics of LPLCs are different from those of portal-HPCs. As cholestasis progresses, LPLCs appear to gain superior proliferation and anti-senescence ability and continually differentiate to RDCs.
Safety and long-term improvement of mesenchymal stromal cell infusion in critically COVID-19 patients: a randomized clinical trial
Authors: Rebelatto Carmen Lúcia Kuniyoshi , Senegaglia Alexandra Cristina , Franck Claudio Luciano , Daga Debora Regina , Shigunov Patrícia , Stimamiglio Marco Augusto , Marsaro Daniela Boscaro , Schaidt Bruna , Micosky Andressa , de Azambuja Ana Paula , Leitão Cleverson Alex , Petterle Ricardo Rasmussen , Jamur Valderez Ravaglio , Vaz Isadora May , Mallmann Antônio Paulo , Carraro Junior Hipólito , Ditzel Eduardo , Brofman Paulo Roberto Slud , Correa Alejandro
Published: March 2022

Background

COVID-19 is a multisystem disease that presents acute and persistent symptoms, the postacute sequelae (PASC). Long-term symptoms may be due to consequences from organ or tissue injury caused by SARS-CoV-2, associated clotting or inflammatory processes during acute COVID-19. Various strategies are being chosen by clinicians to prevent severe cases of COVID-19; however, a single treatment would not be efficient in treating such a complex disease. Mesenchymal stromal cells (MSCs) are known for their immunomodulatory properties and regeneration ability; therefore, they are a promising tool for treating disorders involving immune dysregulation and extensive tissue damage, as is the case with COVID-19. This study aimed to assess the safety and explore the long-term efficacy of three intravenous doses of UC-MSCs (umbilical cord MSCs) as an adjunctive therapy in the recovery and postacute sequelae reduction caused by COVID-19. To our knowledge, this is one of the few reports that presents the longest follow-up after MSC treatment in COVID-19 patients.

Methods

This was a phase I/II, prospective, single-center, randomized, double-blind, placebo-controlled clinical trial. Seventeen patients diagnosed with COVID-19 who require intensive care surveillance and invasive mechanical ventilation—critically ill patients—were included. The patient infusion was three doses of 5 × 105 cells/kg UC-MSCs, with a dosing interval of 48 h (n = 11) or placebo (n = 6). The evaluations consisted of a clinical assessment, viral load, laboratory testing, including blood count, serologic, biochemical, cell subpopulation, cytokines and CT scan.

Results

The results revealed that in the UC-MSC group, there was a reduction in the levels of ferritin, IL-6 and MCP1-CCL2 on the fourteen day. In the second month, a decrease in the levels of reactive C-protein, D-dimer and neutrophils and an increase in the numbers of TCD3, TCD4 and NK lymphocytes were observed. A decrease in extension of lung damage was observed at the fourth month. The improvement in all these parameters was maintained until the end of patient follow-up.

Conclusions

UC-MSCs infusion is safe and can play an important role as an adjunctive therapy, both in the early stages, preventing severe complications and in the chronic phase with postacute sequelae reduction in critically ill COVID-19 patients.

Trial registration Brazilian Registry of Clinical Trials (ReBEC), UTN code-U1111-1254-9819. Registered 31 October 2020—Retrospectively registered, https://ensaiosclinicos.gov.br/rg/RBR-3fz9yr
Toll-like receptors 2 and 4 differentially regulate the self-renewal and differentiation of spinal cord neural precursor cells
Authors: Sanchez-Petidier Marina , Guerri Consuelo , Moreno-Manzano Victoria
Published: March 2022

Background

Toll-like receptors (TLRs) represent critical effectors in the host defense response against various pathogens; however, their known function during development has also highlighted a potential role in cell fate determination and neural differentiation. While glial cells and neural precursor cells (NPCs) of the spinal cord express both TLR2 and TLR4, their influence on self-renewal and cell differentiation remains incompletely described.

Methods

TLR2, TLR4 knock-out and the wild type mice were employed for spinal cord tissue analysis and NPCs isolation at early post-natal stage. Sox2, FoxJ1 and Ki67 expression among others served to identify the undifferentiated and proliferative NPCs; GFAP, Olig2 and β-III-tubulin markers served to identify astrocytes, oligodendrocytes and neurons respectively after NPC spontaneous differentiation. Multiple comparisons were analyzed using one-way ANOVA, with appropriate corrections such as Tukey's post hoc tests used for comparisons.

Results

We discovered that the deletion of TLR2 or TLR4 significantly reduced the number of Sox2-expressing NPCs in the neonatal mouse spinal cord. While TLR2-knockout NPCs displayed enhanced self-renewal, increased proliferation and apoptosis, and delayed neural differentiation, the absence of TLR4 promoted the neural differentiation of NPCs without affecting proliferation, producing long projecting neurons. TLR4 knock-out NPCs showed significantly higher expression of Neurogenin1, that would be involved in the activation of this neurogenic program by a ligand and microenvironment-independent mechanism. Interestingly, the absence of both TLR2 and TLR4, which induces also a significant reduction in the expression of TLR1, in NPCs impeded oligodendrocyte precursor cell maturation to a similar degree.

Conclusions

Our data suggest that Toll-like receptors are needed to maintain Sox2 positive neural progenitors in the spinal cord, however possess distinct regulatory roles in mouse neonatal spinal cord NPCs—while TLR2 and TLR4 play a similar role in oligodendrocytic differentiation, they differentially influence neural differentiation.
The peripheral blood mononuclear cells versus purified CD34+ cells transplantation in patients with angiitis-induced critical limb ischemia trial: 5-year outcomes and return to work analysis—a randomized single-blinded non-inferiority trial
Authors: Liu Hao , Pan Tianyue , Liu Yifan , Fang Yuan , Fang Gang , Jiang Xiaolang , Chen Bin , Wei Zheng , Gu Shiyang , Liu Peng , Fu Weiguo , Dong Zhihui
Published: March 2022

Backgrounds

Patients with AICLI constitute a considerable proportion of NO-CLI patients and cannot be treated with surgical or endovascular treatment. Although cell therapy has shown satisfactory results in treating AICLI, research comparing the efficacy of treatment with the 2 kinds of cell products is rare. The aim of this study was to report the 5-year outcomes of a randomized single-blinded noninferiority trial (Number: NCT 02089828) on peripheral blood mononuclear cells (PBMNCs) and purified CD34+ cells (PCCs) transplantation for treating angiitis-induced critical limb ischemia (AICLI).

Methods

A randomized single-blinded non-inferiority trial (Number: NCT 02089828) was performed. Fifty patients were randomized 1:1 to the PBMNCs and PCCs groups. Efficacy outcomes, safety outcomes and patients’ work conditions were analyzed. The primary efficacy outcomes included major amputation and total amputation over 60 months.

Results

During the 60-month follow-up, 1 patient was lost to follow-up, 1 died, and 2 underwent major amputation. The major amputation-free survival rate (MAFS) was 92.0% (95% confidence interval [CI] 82.0%-100.0%) in the PBMNCs group and 91.7% (95% CI 81.3%-100.0%) in the PCCs group (P = 0.980). Compared with the PCCs group, the PBMNCs group had a significantly higher 5-year new lesion-free survival rate (100.0% vs. 83.3% [95% CI 69.7–99.7%], P = 0.039). All patients lost their ability to work before transplantation, and the 5-year cumulative return to work (RTW) rates were 88.0% in the PBMNCs group and 76.0% in the PCCs group (P = 0.085).

Conclusion

The long-term follow-up outcomes of this trial not only demonstrated similar efficacy and safety for the 2 types of autoimplants but also showed a satisfactory cumulative RTW rate in AICLI patients who underwent cell transplantation.

Trial registration: ClinicalTrials.gov, number NCT 02089828. Registered 14 March 2014, https://clinicaltrials.gov/ct2/show/record/NCT02089828.
Evaluation of lyophilized royal jelly and garlic extract emulgels using a murine model infected with methicillin-resistant Staphylococcus aureus
Authors: El-Gayar Mona H. , Ishak Rania A. H. , Esmat Ahmed , Aboulwafa Mohammad M. , Aboshanab Khaled M.
Published: March 2022

The limited therapeutic options associated with methicillin-resistant Staphylococcus aureus (MRSA) necessitate search for innovative strategies particularly, use of natural extracts such as lyophilized royal jelly (LRJ) and garlic extract (GE). Therefore, out study aimed to formulate emulgels containing different concentrations of both LRJ and GE and to evaluate their activities using a murine model infected with MRSA clinical isolate. Four plain emulgel formulas were prepared by mixing stearic acid/yellow soft paraffin-based O/W emulsion formulae based on Carbopol 940, Na alginate, Na carboxymethylcellulose or Hydroxypropyl methyl cellulose E4. Sodium alginate-based emulgel was selected for preparation of four medicated emulgel formulations combining LRJ and GE at four different concentrations. The selected medicated emulgels were used for the in vivo studies. The emulgel formulated with Na alginate and HPMC (MF3) exhibited optimum smooth homogeneous consistency, neutral pH, acceptable viscosity, spreadability, extrudability values and best storage stability properties. In vivo results revealed that, the wounds infected with MRSA isolate in rates were wet (oozing) and showed pus formation when compared to injured uninfected wounds. MF3 formula containing 4% LRJ and 50% GE showed the maximum wound healing properties, both in the apparent physical wound healing measurements and in the histopathological examination. In conclusion, the medicated emulgel formulation (MF3) prepared with Na alginate was found optimum for topical application. MF3 formula containing 4% LRJ and 50% GE has shown the highest in vivo wound healing capacities. Further clinical studies should be conducted to prove both its safety and efficacy and the potential use in human.
A novel high-dimensional trajectories construction network based on multi-clustering algorithm
Authors: Ren Feiyang , Han Yi , Wang Shaohan , Jiang He
Published: March 2022

A multiple clustering algorithm based on high-dimensional automatic identification system (AIS) data is proposed to extract the important waypoints in the ship’s navigation trajectory based on selected AIS attribute features and construct a route network using the waypoints. The algorithm improves the accuracy of route network planning by using the latitude and longitude of the historical voyage trajectory and the heading to the ground. Unlike the navigation clustering method that only uses ship latitude and longitude coordinates, the algorithm first calculates the major waypoints using Clustering in QUEst (CLIQUE) and Balance Iterative Reducing and Clustering Using Hierarchies (BIRCH) algorithms, and then builds the route network using network construction. Under the common PC specification (i5 processor), this algorithm forms 440 major waypoints from 220,133 AIS data and constructs a route network with directional features in 5 min, which is faster in computing speed and more suitable for complex ship trajectory differentiation and can extend the application boundary of ship route planning.
Enhancing biosynthesis and bioactivity of Trachyspermum ammi seed essential oil in response to drought and Azotobacter chroococcum stimulation
Authors: Hashemi Maryamolsadat , Behboodian Bita , Karimi Ehsan , Oskoueian Ehsan
Published: March 2022

Background

Plant growth-promoting bacteria have fundamental role in enhancing natural bioactive compounds and proved to increase the plant growth and mineral availability in soil. These phytochemicals, like phenolic and essential oils, illustrated wide range of biological properties. This study was designed to evaluate the effect of Azotobacter chroococcum (A. chroococcum) alone or in combination with slight (irrigation at 80% filed capacity) or moderate (irrigation at 60% filed capacity) drought stresses on the yield, phytochemicals, antioxidant, and the toxicity of Trachyspermum ammi (T. ammi) seeds essential oil.

Results

Overall, the application of A. chroococcum as plant growth-promoting agent together with slight drought stress significantly (p < 0.05) resulted in higher essential oil yield, total phenolic, total flavonoid, and higher antioxidant activity. The gene expression analysis in the developing seeds confirmed the up-regulation in the expression of antioxidant-related gene (SOD) and thymol synthesis gene (TSG) upon A. chroococcum bacteria treatment in combination with slight drought stress. The toxicity study showed no prominent signs of toxicity in mice upon oral administration of essential oil up to 100 mg/kg body weight for 28 days.

Conclusion

The slight drought stress (irrigation at 80% filed capacity) together with treatment of T. ammi plant with A. chroococcum bacteria as plant growth-promoting agent could be promising approach in improving the yield and medicinal value of the T. ammi seeds essential oil.

Graphical Abstract
Antibody-conjugated gold nanoparticles as nanotransducers for second near-infrared photo-stimulation of neurons in rats
Authors: Liu Jiansheng , Li Jiajia , Zhang Shu , Ding Mengbin , Yu Ningyue , Li Jingchao , Wang Xiuhui , Li Zhaohui
Published: March 2022

Infrared neural stimulation with the assistance of photothermal transducers holds great promise as a mini-invasive neural modulation modality. Optical nanoparticles with the absorption in the near-infrared (NIR) window have emerged as excellent photothermal transducers due to their good biocompatibility, surface modifiability, and tunable optical absorption. However, poor activation efficiency and limited stimulation depth are main predicaments encountered in the neural stimulation mediated by these nanoparticles. In this study, we prepared a targeted polydopamine (PDA)-coated gold (Au) nanoparticles with specific binding to thermo-sensitive ion channel as nanotransducers for second near-infrared (NIR-II) photo-stimulation of neurons in rats. The targeted Au nanoparticles were constructed via conjugation of anti-TRPV1 antibody with PEGylated PDA-coated Au nanoparticles and thus exhibited potent photothermal performance property in the second NIR (NIR-II) window and converted NIR-II light to heat to rapidly activate Ca2+ influx of neurons in vitro. Furthermore, wireless photothermal stimulation of neurons in living rat successfully evoke excitation in neurons in the targeted brain region as deep as 5 mm beneath cortex. This study thus demonstrates a remote-controlled strategy for neuromodulation using photothermal nanotransducers.
Construction of fatty acid derivatives from rubber seed oil as α-glucosidase inhibitors based on rubber seed oil
Authors: Liu Jiahao , Zhang Renwei , Nie Kaili , Liu Changsheng , Deng Li , Wang Fang
Published: March 2022

Natural free fatty acids show inhibitory effects on α-glucosidase and can hence have potential applications in diabetes treatment. This study indicated that the inhibitory effect of fatty acids showed a significant negative correlation with affinity energy (− 0.87) and melting point (− 0.88). Guided by this relationship, two promotion strategies of hydration and esterification were put forward to increase the inhibitory effect of fatty acids on α-glucosidase. The hydration can import an extra hydroxy group into the C=C bond of fatty acids, that will enhance the interaction with α-glucosidase, while the esterification will lower the melting point of fatty acids, and promote the inhibitory effect. Hydroxy fatty acids and fatty acid isopropyl esters possessed higher inhibitory effects than the natural fatty acids. Then, rubber seed oil was modified into novel fatty acid derivatives with higher inhibitory effect on α-glucosidase. The inhibitory IC50 of hydroxy products and isopropanol esters was 0.42 ± 0.01 μM and 0.57 ± 0.01 μM, respectively. The result reveals a feasible route to construct fatty acid derivatives from natural oil with α-glucosidase inhibitory effect.

Graphical Abstract
Laparoscopic liver resection for liver metastasis of leiomyosarcoma of the thigh: a case report
Authors: Tsuzaka Shoichi , Asahi Yoh , Kamiyama Toshiya , Kakisaka Tatsuhiko , Orimo Tatsuya , Nagatsu Akihisa , Aiyama Takeshi , Uebayashi Takeyuki , Kamachi Hirofumi , Matsuoka Masatake , Wakabayashi Kento , Otsuka Takuya , Matsuno Yoshihiro , Taketomi Akinobu
Published: March 2022

Background

Although there is no established treatment strategy for liver metastasis of leiomyosarcoma, liver resection has been reported to be effective in some cases. However, almost all liver resections performed for liver metastasis of primary leiomyosarcoma are reported to be open resections, and there are few reports of liver resection performed by laparoscopy. Here, we report a case of laparoscopic liver resection for liver metastasis of a leiomyosarcoma in the right thigh.

Case presentation

An 80-year-old man was diagnosed with leiomyosarcoma of the right thigh with liver metastasis. The primary tumor was first resected, and he was discharged on the 25th postoperative day. Four months after primary tumor resection, a laparoscopic right posterior sectionectomy was performed. There were no postoperative complications, and the patient was discharged on the 11th postoperative day with a histopathological diagnosis of liver metastasis of leiomyosarcoma and negative resection margins. Currently, 9 months have passed since the resection of the primary tumor, and 5 months have passed since the laparoscopic liver resection; there is no recurrence.

Conclusions

The liver metastasis of leiomyosarcoma was successfully removed, with good short-term outcomes after the laparoscopic liver resection. Laparoscopic liver resection seems to be effective for liver metastasis of leiomyosarcoma, which is characterized by a high recurrence rate after surgery. However, more case studies may be necessary to examine the effectiveness and long-term results of laparoscopic liver resection for the treatment of liver metastasis of leiomyosarcoma.