bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct physical activity and sedentary behavior trajectories in older adults during participation in a physical activity intervention: a latent class growth analysis
Authors: Ratz Tiara , Pischke Claudia R. , Voelcker-Rehage Claudia , Lippke Sonia
Published: January 2022

Background

This study aimed to identify latent moderate-to-vigorous intensity physical activity (MVPA) and sedentary behavior (SB) trajectories in older adults participating in a randomized intervention trial and to explore associations with baseline social-cognitive predictors.

Methods

Data were assessed at baseline (T0, participants were inactive or had recently become active), after a ten-week physical activity intervention (T1), and a second 24-week intervention phase (T2). Latent class growth analysis was used on accelerometer-assessed weekly MVPA and daily SB, respectively (n = 215 eligible participants). Activity changes within trajectory classes and baseline social-cognitive predictor differences between trajectory classes were analyzed.

Results

A “stable insufficient MVPA” (n = 197, p for difference in MVPA level at T0 and T2 (pT0-T2) = .789, effect size (Cohen’s d) = .03) and a “stable high MVPA” trajectory (n = 18, pT0-T2 = .137, d = .39), as well as a “slightly decreasing high SB” (n = 63, p for difference in SB (pT0-T2) = .022, d = .36) and a “slightly increasing moderate SB” trajectory (n = 152, pT0-T2 = .019, d = .27) emerged. Belonging to the “stable high MVPA” trajectory was associated with higher action planning levels compared to the “stable insufficient MVPA” trajectory (M = 5.46 versus 4.40, d = .50). Belonging to the “decreasing high SB” trajectory was associated with higher action self-efficacy levels compared to the “increasing moderate SB” trajectory (M = 5.27 versus 4.72, d = .33).

Conclusions

Change occurred heterogeneously in latent (not directly observed) subgroups, with significant positive trajectories only observed in the highly sedentary.

Trial registration

German Registry of Clinical Trials, DRKS00016073, Registered 10 January 2019.
Identification and expression analysis of histone modification gene (HM) family during somatic embryogenesis of oil palm
Authors: Zhou Lixia , Yarra Rajesh , Jin Longfei , Yang Yaodong , Cao Hongxing , Zhao Zhihao
Published: January 2022

Background

Oil palm (Elaeis guineensis, Jacq.) is an important vegetable oil-yielding plant. Somatic embryogenesis is a promising method to produce large-scale elite clones to meet the demand for palm oil. The epigenetic mechanisms such as histone modifications have emerged as critical factors during somatic embryogenesis. These histone modifications are associated with the regulation of various genes controlling somatic embryogenesis. To date, none of the information is available on the histone modification gene (HM) family in oil palm.

Results

We reported the identification of 109 HM gene family members including 48 HMTs, 27 HDMs, 13 HATs, and 21 HDACs in the oil palm genome. Gene structural and motif analysis of EgHMs showed varied exon–intron organization and with conserved motifs among them. The identified 109 EgHMs were distributed unevenly across 16 chromosomes and displayed tandem duplication in oil palm genome. Furthermore, relative expression analysis showed the differential expressional pattern of 99 candidate EgHM genes at different stages (non-embryogenic, embryogenic, somatic embryo) of somatic embryogenesis process in oil palm, suggesting the EgHMs play vital roles in somatic embryogenesis. Our study laid a foundation to understand the regulatory roles of several EgHM genes during somatic embryogenesis.

Conclusions

A total of 109 histone modification gene family members were identified in the oil palm genome via genome-wide analysis. The present study provides insightful information regarding HM gene’s structure, their distribution, duplication in oil palm genome, and also their evolutionary relationship with other HM gene family members in Arabidopsis and rice. Finally, our study provided an essential role of oil palm HM genes during somatic embryogenesis process.
Structural and functional changes in the fungal community of plant detritus in an invaded Atlantic Forest
Authors: Bail Jaqueline , Gomez Jose Alejandro Morales , de Oliveira Vaz Giselle Cristina , de Castro Wagner Antonio Chiba , Bonugli-Santos Rafaella Costa
Published: January 2022

Background

Changes in the fungal community in the litter decomposition by invasive plants can negatively impact nutrient cycling in natural ecosystems. One still does not know the dimension of this hypothesis, but apparently, it is not despicable. This study evaluated the assemblage composition of fungi during litter decomposition in areas of Atlantic Forest invaded or not invaded byTradescantia zebrinausing Illumina MiSeq and metabarcoding analysis.

Results

The invaded sample showed significantly higher richness and a difference in the species dominance than the invaded litter. Ascomycota was the first most abundant phylum in both areas. Even so, the dissimilarity between areas can be evidenced. The fungal from Basidiomycota were very representative in the non-invaded areas (ranged from an abundance of 43.29% in the non-invaded to 2.35% in the invaded sample). The genusLepiotacan indicate the primary functional group related to biomass degradation and showed the might difference about the invaded areas due to its essential reduction by the invader. In the invaded sample, there was a total absence of the endophyte-undefined saprotroph guild. Also, some genera not taxonomically characterized were eliminated in the invaded sample, revealing that the fungal biodiversity of areas has not yet been thoroughly characterized.

Conclusions

Hence, makes impossible the real interpretation of the invasive plant impact, showing the importance of continuing research on fungal biodiversity. It is important to emphasize that the replacement of the native species byT. zebrinamay be responsible for the elimination of fungal groups that have not yet been identified.
Predictive determinants of overall survival among re-infected COVID-19 patients using the elastic-net regularized Cox proportional hazards model: a machine-learning algorithm
Authors: Ebrahimi Vahid , Sharifi Mehrdad , Mousavi-Roknabadi Razieh Sadat , Sadegh Robab , Khademian Mohammad Hossein , Moghadami Mohsen , Dehbozorgi Afsaneh
Published: January 2022

Background

Narrowing a large set of features to a smaller one can improve our understanding of the main risk factors for in-hospital mortality in patients with COVID-19. This study aimed to derive a parsimonious model for predicting overall survival (OS) among re-infected COVID-19 patients using machine-learning algorithms.

Methods

The retrospective data of 283 re-infected COVID-19 patients admitted to twenty-six medical centers (affiliated with Shiraz University of Medical Sciences) from 10 June to 26 December 2020 were reviewed and analyzed. An elastic-net regularized Cox proportional hazards (PH) regression and model approximation via backward elimination were utilized to optimize a predictive model of time to in-hospital death. The model was further reduced to its core features to maximize simplicity and generalizability.

Results

The empirical in-hospital mortality rate among the re-infected COVID-19 patients was 9.5%. In addition, the mortality rate among the intubated patients was 83.5%. Using the Kaplan-Meier approach, the OS (95% CI) rates for days 7, 14, and 21 were 87.5% (81.6-91.6%), 78.3% (65.0-87.0%), and 52.2% (20.3-76.7%), respectively. The elastic-net Cox PH regression retained 8 out of 35 candidate features of death. Transfer by Emergency Medical Services (EMS) (HR=3.90, 95% CI: 1.63-9.48), SpO2≤85% (HR=8.10, 95% CI: 2.97-22.00), increased serum creatinine (HR=1.85, 95% CI: 1.48-2.30), and increased white blood cells (WBC) count (HR=1.10, 95% CI: 1.03-1.15) were associated with higher in-hospital mortality rates in the re-infected COVID-19 patients.

Conclusion

The results of the machine-learning analysis demonstrated that transfer by EMS, profound hypoxemia (SpO2≤85%), increased serum creatinine (more than 1.6 mg/dL), and increased WBC count (more than 8.5 (×109 cells/L)) reduced the OS of the re-infected COVID-19 patients. We recommend that future machine-learning studies should further investigate these relationships and the associated factors in these patients for a better prediction of OS.
Development, implementation and evaluation of an evidence-based paediatric early warning system improvement programme: the PUMA mixed methods study
Authors: Allen Davina , Lloyd Amy , Edwards Dawn , Hood Kerenza , Huang Chao , Hughes Jacqueline , Jacob Nina , Lacy David , Moriarty Yvonne , Oliver Alison , Preston Jennifer , Sefton Gerri , Sinha Ian , Skone Richard , Strange Heather , Taiyari Khadijeh , Thomas-Jones Emma , Trubey Rob , Tume Lyvonne , Powell Colin , Roland Damian
Published: January 2022

Background

Paediatric mortality rates in the United Kingdom are amongst the highest in Europe. Clinically missed deterioration is a contributory factor. Evidence to support any single intervention to address this problem is limited, but a cumulative body of research highlights the need for a systems approach.

Methods

An evidence-based, theoretically informed, paediatric early warning system improvement programme (PUMA Programme) was developed and implemented in two general hospitals (no onsite Paediatric Intensive Care Unit) and two tertiary hospitals (with onsite Paediatric Intensive Care Unit) in the United Kingdom. Designed to harness local expertise to implement contextually appropriate improvement initiatives, the PUMA Programme includes a propositional model of a paediatric early warning system, system assessment tools, guidance to support improvement initiatives and structured facilitation and support.

Each hospital was evaluated using interrupted time series and qualitative case studies. The primary quantitative outcome was a composite metric (adverse events), representing the number of children monthly that experienced one of the following: mortality, cardiac arrest, respiratory arrest, unplanned admission to Paediatric Intensive Care Unit, or unplanned admission to Higher Dependency Unit. System changes were assessed qualitatively through observations of clinical practice and interviews with staff and parents. A qualitative evaluation of implementation processes was undertaken.

Results

All sites assessed their paediatric early warning systems and identified areas for improvement. All made contextually appropriate system changes, despite implementation challenges. There was a decline in the adverse event rate trend in three sites; in one site where system wide changes were organisationally supported, the decline was significant (ß = -0.09 (95% CI: − 0.15, − 0.05); p = < 0.001). Changes in trends coincided with implementation of site-specific changes.

Conclusions

System level change to improve paediatric early warning systems can bring about positive impacts on clinical outcomes, but in paediatric practice, where the patient population is smaller and clinical outcomes event rates are low, alternative outcome measures are required to support research and quality improvement beyond large specialist centres, and methodological work on rare events is indicated. With investment in the development of alternative outcome measures and methodologies, programmes like PUMA could improve mortality and morbidity in paediatrics and other patient populations.
Exploring relationships between in-hospital mortality and hospital case volume using random forest: results of a cohort study based on a nationwide sample of German hospitals, 2016–2018
Authors: Roessler Martin , Walther Felix , Eberlein-Gonska Maria , Scriba Peter C. , Kuhlen Ralf , Schmitt Jochen , Schoffer Olaf
Published: January 2022

Background

Relationships between in-hospital mortality and case volume were investigated for various patient groups in many empirical studies with mixed results. Typically, those studies relied on (semi-)parametric statistical models like logistic regression. Those models impose strong assumptions on the functional form of the relationship between outcome and case volume. The aim of this study was to determine associations between in-hospital mortality and hospital case volume using random forest as a flexible, nonparametric machine learning method.

Methods

We analyzed a sample of 753,895 hospital cases with stroke, myocardial infarction, ventilation > 24 h, COPD, pneumonia, and colorectal cancer undergoing colorectal resection treated in 233 German hospitals over the period 2016–2018. We derived partial dependence functions from random forest estimates capturing the relationship between the patient-specific probability of in-hospital death and hospital case volume for each of the six considered patient groups.

Results

Across all patient groups, the smallest hospital volumes were consistently related to the highest predicted probabilities of in-hospital death. We found strong relationships between in-hospital mortality and hospital case volume for hospitals treating a (very) small number of cases. Slightly higher case volumes were associated with substantially lower mortality. The estimated relationships between in-hospital mortality and case volume were nonlinear and nonmonotonic.

Conclusion

Our analysis revealed strong relationships between in-hospital mortality and hospital case volume in hospitals treating a small number of cases. The nonlinearity and nonmonotonicity of the estimated relationships indicate that studies applying conventional statistical approaches like logistic regression should consider these relationships adequately.
Avian haemosporidian parasites of accipitriform raptors
Authors: Harl Josef , Himmel Tanja , Valkiūnas Gediminas , Ilgūnas Mikas , Nedorost Nora , Matt Julia , Kübber-Heiss Anna , Alic Amer , Konicek Cornelia , Weissenböck Herbert
Published: January 2022

Background

The order Accipitriformes comprises the largest group of birds of prey with 260 species in four families. So far, 21 haemosporidian parasite species have been described from or reported to occur in accipitriform birds. Only five of these parasite species have been characterized molecular genetically. The first part of this study involved molecular genetic screening of accipitriform raptors from Austria and Bosnia-Herzegovina and the first chromogenic in situ hybridization approach targeting parasites in this host group. The aim of the second part of this study was to summarize the CytB sequence data of haemosporidian parasites from accipitriform raptors and to visualize the geographic and host distribution of the lineages.

Methods

Blood and tissue samples of 183 accipitriform raptors from Austria and Bosnia-Herzegovina were screened for Plasmodium, Haemoproteus and Leucocytozoon parasites by nested PCR, and tissue samples of 23 PCR-positive birds were subjected to chromogenic in situ hybridization using genus-specific probes targeting the parasites’ 18S rRNAs. All published CytB sequence data from accipitriform raptors were analysed, phylogenetic trees were calculated, and DNA haplotype network analyses were performed with sequences from clades featuring multiple lineages detected in this host group.

Results

Of the 183 raptors from Austria and Bosnia-Herzegovina screened by PCR and sequencing, 80 individuals (44%) were infected with haemosporidian parasites. Among the 39 CytB lineages detected, 18 were found for the first time in the present study. The chromogenic in situ hybridization revealed exo-erythrocytic tissue stages of Leucocytozoon parasites belonging to the Leucocytozoon toddi species group in the kidneys of 14 infected birds. The total number of CytB lineages recorded in accipitriform birds worldwide was 57 for Leucocytozoon, 25 for Plasmodium, and 21 for Haemoproteus.

Conclusion

The analysis of the DNA haplotype networks allowed identifying numerous distinct groups of lineages, which have not yet been linked to morphospecies, and many of them likely belong to yet undescribed parasite species. Tissue stages of Leucocytozoon parasites developing in accipitriform raptors were discovered and described. The majority of Leucocytozoon and Haemoproteus lineages are specific to this host group, but most Plasmodium lineages were found in birds of other orders. This might indicate local transmission from birds kept at the same facilities (raptor rescue centres and zoos), likely resulting in abortive infections. To clarify the taxonomic and systematic problems, combined morphological and molecular genetic analyses on a wider range of accipitriform host species are needed.
Vector composition, abundance, biting patterns and malaria transmission intensity in Madang, Papua New Guinea: assessment after 7 years of an LLIN-based malaria control programme
Authors: Keven John B. , Katusele Michelle , Vinit Rebecca , Rodríguez-Rodríguez Daniela , Hetzel Manuel W. , Robinson Leanne J. , Laman Moses , Karl Stephan , Walker Edward D.
Published: January 2022

Background

A malaria control programme based on distribution of long-lasting insecticidal bed nets (LLINs) and artemisinin combination therapy began in Papua New Guinea in 2009. After implementation of the programme, substantial reductions in vector abundance and malaria transmission intensity occurred. The research reported here investigated whether these reductions remained after seven years of sustained effort.

Methods

All-night (18:00 to 06:00) mosquito collections were conducted using human landing catches and barrier screen methods in four villages of Madang Province between September 2016 and March 2017. Anopheles species identification and sporozoite infection with Plasmodium vivax and Plasmodium falciparum were determined with molecular methods. Vector composition was expressed as the relative proportion of different species in villages, and vector abundance was quantified as the number of mosquitoes per barrier screen-night and per person-night. Transmission intensity was quantified as the number of sporozoite-infective vector bites per person-night.

Results

Five Anopheles species were present, but vector composition varied greatly among villages. Anopheles koliensis, a strongly anthropophilic species was the most prevalent in Bulal, Matukar and Wasab villages, constituting 63.7–73.8% of all Anopheles, but in Megiar Anopheles farauti was the most prevalent species (97.6%). Vector abundance varied among villages (ranging from 2.8 to 72.3 Anopheles per screen-night and 2.2–31.1 Anopheles per person-night), and spatially within villages. Malaria transmission intensity varied among the villages, with values ranging from 0.03 to 0.5 infective Anopheles bites per person-night. Most (54.1–75.1%) of the Anopheles bites occurred outdoors, with a substantial proportion (25.5–50.8%) occurring before 22:00.

Conclusion

The estimates of vector abundance and transmission intensity in the current study were comparable to or higher than estimates in the same villages in 2010–2012, indicating impeded programme effectiveness. Outdoor and early biting behaviours of vectors are some of the likely explanatory factors. Heterogeneity in vector composition, abundance and distribution among and within villages challenge malaria control programmes and must be considered when planning them.
Association between dietary choline and betaine intake and 10.6-year cardiovascular disease in adults
Authors: Golzarand Mahdieh , Mirmiran Parvin , Azizi Fereidoun
Published: January 2022

Background

Several studies have assessed the association between dietary choline and betaine and cardiovascular disease (CVD), but their results are inconsistent. The present study aimed to determine the association between dietary intake of choline and betaine and the risk of CVD in the general population over a 10.6-year period of follow-up.

Methods

The present cohort study was conducted on participants in the third wave of the Tehran Lipid and Glucose Study (2006–2008) and was followed-up until March 2018. Dietary intake of choline and betaine was calculated using the United States Department of Agriculture (USDA) database. Patients’ medical records were used to collect data on CVD.

Results

In this study, 2606 subjects with no previous CVD participated and were followed-up for a median of 10.6 years. During the follow-up periods, 187 incidences of CVD were detected. Results of the Cox proportional hazards regression indicated that neither energy-adjusted total choline nor betaine was associated with the incidence of CVD. Among individual choline forms, only higher intake of free choline (FC) was associated with a lower risk of CVD (HR: 0.64, 95% CI: 0.42–0.98). There was no significant association between each 10 mg/d increase in choline and betaine content of each food category and CVD.

Conclusion

Our investigation indicates no association between energy-adjusted total choline and betaine and a 10.6-year risk of CVD among adults. Besides, we found no relationship between individual choline forms (except FC) and CVD. We also found energy-adjusted choline and betaine obtained from food categories were not associated with the risk of CVD.
Combination of extramural venous invasion and lateral lymph node size detected with magnetic resonance imaging is a reliable biomarker for lateral lymph node metastasis in patients with rectal cancer
Authors: Abe Tomoki , Yasui Masayoshi , Imamura Hiroki , Matsuda Chu , Nishimura Junichi , Haraguchi Naotsugu , Nakai Nozomu , Wada Hiroshi , Takahashi Hidenori , Omori Takeshi , Miyata Hiroshi , Ohue Masayuki
Published: January 2022

Purpose

Pathological extramural venous invasion (EMVI) is defined as the active invasion of malignant cells into veins beyond the muscularis propria in colorectal cancer. It is associated with poor prognosis and increases the risk of disease recurrence. Specific findings on MRI (termed MRI-EMVI) are reportedly associated with pathological EMVI. In this study, we aimed to identify risk factors for lateral lymph node (LLN) metastasis related to rectal cancer and to evaluate whether MRI-EMVI could be a new and useful imaging biomarker to help LLN metastasis diagnosis besides LLN size.

Methods

We investigated 67 patients who underwent rectal resection and LLN dissection for rectal cancer. We evaluated MRI-EMVI grading score and examined the relationship between MRI-EMVI and LLN metastasis.

Results

Pathological LLN metastasis was detected in 18 cases (26.9%), and MRI-EMVI was observed in 32 cases (47.8%). Patients were divided into two cohorts, according to LLN metastasis. Multivariate analyses demonstrated that higher risk of LLN metastasis was significantly associated with MRI-EMVI (P = 0.0112) and a short lateral lymph node axis (≥ 5 mm) (P = 0.0002). The positive likelihood ratios of MRI-EMVI alone, LLN size alone, and the combination of both factors were 2.12, 4.84, and 16.33, respectively. Patients negative for both showed better 2-year relapse-free survival compared to other patients (84.4% vs. 62.1%, P = 0.0374).

Conclusions

MRI-EMVI was a useful imaging biomarker for identifying LLN metastasis in patients with rectal cancer. The combination of MRI-EMVI and LLN size can improve diagnostic accuracy.
Skin damage induced by zinc oxide nanoparticles combined with UVB is mediated by activating cell pyroptosis via the NLRP3 inflammasome–autophagy–exosomal pathway
Authors: Chen Yu-Ying , Lee Yu-Hsuan , Wang Bour-Jr , Chen Rong-Jane , Wang Ying-Jan
Published: January 2022

Background

Zinc oxide nanoparticles (ZnONPs) are widely used nanomaterial in personal cosmetics, such as skin creams and sunscreens, due to their whitening properties and strong UV light absorption. However, the safety issues and the hazards of ZnONPs, which can be taken up by the skin and cause skin toxicity, are still unclear. From a chemoprevention point of view, pterostilbene (PT) has been reported to prevent skin damage effectively by its anti-inflammatory and autophagy inducer effect. This study aims to determine the skin toxicity and the potential mechanisms of UVB and ZnONPs exposure and the preventive effect of PT.

Results

The co-exposure of UVB and ZnONPs elicit NLRP3 inflammasome activation and pyroptosis in keratinocytes. Furthermore, exposure to both UVB and ZnONPs also disrupts cellular autophagy, which increases cell exosome release. In vivo UVB and ZnONPs exposure triggers skin toxicity, as indicated by increased histological injury, skin thickness and transepidermal water loss. Notably, the NLRP3 inflammasome-mediated pyroptosis are also activated during exposure. Topical application of pterostilbene attenuates NLRP3 inflammasome activation and pyroptosis by decreasing ROS generation and mitochondrial ROS (mtROS) levels. In addition to its antioxidant effect, PT also reversed autophagy abnormalities by restoring normal autophagic flux and decreasing NLRP3 inflammasome-loaded exosome release.

Conclusions

Our findings reveal that ZnONPs induce skin damage in conjunction with UVB exposure. This process involves an interplay of inflammasomes, pyroptosis, autophagy dysfunction, and exosomes in skin toxicity. PT alleviates skin inflammation by regulating the inflammasome–autophagy–exosome pathway, a finding which could prove valuable when further evaluating ZnONPs effects for cosmetic applications.
Echinacoside exhibits antidepressant-like effects through AMPAR–Akt/ERK–mTOR pathway stimulation and BDNF expression in mice
Authors: Chuang Han-Wen , Wang Tse-Yen , Huang Chih-Chia , Wei I-Hua
Published: January 2022

Background

Several natural products have been demonstrated to be effective in the treatment of depressive disorders. Echinacoside, a naturally occurring phenol extracted from Cistanche tubulosa, Echinacea angustifolia, and Cistanche spp, has a wide range of physiological effects, such as antioxidation, neuroprotection, anti-inflammatory, and immunoregulation, which are closely related to depression. In addition, echinacoside can activate protein kinase B (Akt), extracellular signal–regulated kinase (ERK), and brain-derived neurotrophic factor (BDNF) in the brain. A key downstream event of the Akt, ERK, and BDNF signaling pathways, namely mechanistic target of rapamycin (mTOR) signaling, plays a crucial role in generating an rapid antidepressant effect. Thus, echinacoside is a promising therapeutic agent for depression. However, research regarding the role of echinacoside in antidepressant effect and brain mTOR activation remains lacking.

Materials and methods

The forced swimming test and Western blot analysis in C57BL/6 mice was used to investigate the antidepressant-like activities of echinacoside and the underlying mechanism involved inα-amino3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)–Akt/ERK–mTOR pathway.

Results

We confirmed the suggestions by previous reports that echinacoside activates Akt/ERK signaling and further demonstrated that echinacoside could provide antidepressant-like effects in mice via the activation of AMPAR–Akt/ERK–mTOR pathway in the hippocampus.

Conclusions

To the best of our knowledge, our study is the first to reveal that echinacoside is a potential treatment for depressive disorders. Moreover, the present study suggests a mechanism for the neuroprotective effect of echinacoside.
Traditional Chinese medicine Lingguizhugan decoction ameliorate HFD-induced hepatic-lipid deposition in mice by inhibiting STING-mediated inflammation in macrophages
Authors: Cao Lin , Xu Erjin , Zheng Rendong , Zhangchen Zhili , Zhong Rongling , Huang Fei , Ye Juan , Sun Hongping , Fan Yaofu , Xie Shaofeng , Chen Yu , Xu Yijiao , Cao Jing , Cao Wen , Liu Chao
Published: January 2022

Background

Stimulator of IFN genes (STING) is highly expressed in the livers of non-alcoholic fatty liver disease (NAFLD) patients and high fat diet (HFD) induced NAFLD mice model. The STING signaling-mediated inflammation has been shown to play a critical role in metabolic disorders. Lingguizhugan decoction (LGZG), a Traditional Chinese herbal decoction, has been applied to treat metabolic disorders for many years. However, whether LGZG can alleviate the progression of NAFLD through inhibiting inflammation remains unclear. This study was to determine the role of STING-mediated inflammation in the HFD-induced hepatic-lipid deposition treated with LGZG.

Methods

The anti-inflammatory and anti-steatotic effects of LGZG in vivo were detected by H&E staining, immunofluorescence and immuno-chemistry. Mice bone-marrow-derived macrophages (BMDMs) and primary liver macrophages were treated with STING-specific agonist (DMXAA), LGZG and its critical components respectively. The treated culture supernatant of BMDMs and primary liver macrophages from each group was co-cultured with palmitic acid-treated mouse primary hepatocytes or mouse liver cell line AML-12 respectively to detect whether the activation of STING-mediated pathway is involved in the anti-steatotic effect of LGZG. The hepatocyte lipid deposition in vivo and in vitro were detected by oil red staining. Mitochondrial DNA release of mouse liver extracts were detected by real time PCR. The expression of proteins and inflammatory cytokines related to STING-TBK1-NF-κB pathway was detected by western blotting and ELISA.

Results

LGZG significantly ameliorated HFD induced hepatic steatosis, oxidative stress, hepatic mitochondrial damage and mitochondrial DNA release, which was correlated with reduction of the expression level of STING as well as the infiltration of STING-positive macrophages in the livers of HFD fed mice. The critical components of LGZG directly inhibited the activation of STING-TBK1-NF-κB pathway in liver macrophages induced by DMXAA, LPS, thereby reducing the release of IFNβ and TNFα. Co-incubating the culture supernatant of LGZG treated liver macrophages and PA-stimulated hepatocytes significantly inhibited the PA-induced lipid deposition.

Conclusion

This study demonstrates that LGZG can ameliorate HFD-induced hepatic-lipid deposition through inhibiting STING-TBK1-NF-κB pathway in liver macrophages, which provides novel insight for elucidating the molecular mechanism of LGZG alleviating HFD induced hepatic steatosis.
Marimo actuated rover systems
Authors: Phillips Neil , Draper Thomas C. , Mayne Richard , Reynolds Darren M. , Adamatzky Andrew
Published: January 2022

Background

The potential to directly harness photosynthesis to make actuators, biosensors and bioprocessors has been previously demonstrated in the literature. Herein, this capability has been expanded to more advanced systems — Marimo Actuated Rover Systems (MARS) — which are capable of autonomous, solar powered, movement.

Results

We demonstrate this ability is both a practical and viable alternative to conventional mobile platforms for exploration and dynamic environmental monitoring. Prototypes have been successfully tested to measure their speed of travel and ability to automatically bypass obstacles. Further, MARS is electromagnetically silent, thus avoiding the background noise generated by conventional electro/mechanical platforms which reduces instrument sensitivity. The cost of MARS is significantly lower than platforms based on conventional technology.

Conclusions

An autonomous, low-cost, lightweight, compact size, photosynthetically powered rover is reported. The potential for further system enhancements are identified and under development.
Statistical analysis plan for the Dual mTorc Inhibition in advanCed/recurrent Epithelial ovarian, fallopian tube or primary peritoneal cancer (of clear cell, endometrioid and high-grade serous type, and carcinosarcoma) trial (DICE)
Authors: de la Rosa Consuelo Nóhpal , Krell Jonathan , Day Emily , Clarke Aaron , Reddi Meena , Webber Lee , Fiorentino Francesca
Published: January 2022

Background

Treatment for ovarian cancer includes platinum-based chemotherapy, but many women become resistant to chemotherapy, becoming platinum-resistant. Standard of care for these women is weekly paclitaxel chemotherapy, but cancers can often become paclitaxel resistant. TAK228, an investigational dual TORC1/2 inhibitor, is an oral therapy that can be added to standard treatment. The DICE trial is a phase II international multicentre, parallel-group, superiority clinical trial with 1:1, open label randomisation which has the aim of investigating the effectiveness of TAK228 plus weekly paclitaxel. The planned sample size is 124 women (62 per treatment arm) with platinum-resistant ovarian cancer.

Objective

To outline the planned analyses for DICE in a statistical analysis plan (SAP) before database hard lock and the start of analysis. This ensures that bias is minimised during the analysis phase.

Results

This SAP provides detailed descriptions of the analysis principles and statistical procedures for analysing primary and secondary outcomes of the trial. The primary outcome is overall progression-free survival (PFS). Secondary outcomes include progression-free survival (PFS) at 24 weeks, overall response rate (ORR), duration of response (DoR), time to progression (TTP), clinical benefit rate (CBR) at 4 months, Cancer Antigen 125 (CA125) response according to Gynaecological Cancer Intergroup (GCIG) criteria, overall survival (OS), safety and tolerability as assessed by adverse events and the quality-of-life questionnaires (EORTC QLQ-C30 and EORTC QLQ-OV28). This detailed description includes significance levels, sensitivity analyses and compliance analysis.

Discussion

The DICE trial will determine whether the addition of TAK228 to weekly paclitaxel chemotherapy shows a statistically significant improvement to participant’s progression free and overall survival and that the adverse events (AEs) and quality of life (QoL) are not significantly worse than the standard treatment.

The study commenced recruitment in September 2018. An interim analysis was performed in early 2021, the results of which advised continuation of the trial. The study recruitment is ongoing and is due to complete by the end of 2021.

Trial registration

ClinicalTrials.govNCT03648489. Registered on 27 August 2018
Integrative blood-derived epigenetic and transcriptomic analysis reveals the potential regulatory role of DNA methylation in ankylosing spondylitis
Authors: Xiao Min , Zheng Xuqi , Li Xiaomin , Wu Xinyu , Huang Yefei , Wei Qiujing , Cao Shuangyan , Gu Jieruo
Published: January 2022

Background

The currently known risk loci could explain a small proportion of the heritability of ankylosing spondylitis (AS). Epigenetics might account for the missing heritability. We aimed to seek more novel AS-associated DNA methylation alterations and delineate the regulatory effect of DNA methylation and gene expression with integrated analysis of methylome and transcriptome.

Methods

Epigenome-wide DNA methylation and mRNA expression were profiled in peripheral blood mononuclear cells (PBMCs) from 45 individuals (AS: health controls (HCs) = 30:15) with high-throughput array. The methylome was validated in an independent cohort (AS: HCs = 12:12). Pearson correlation analysis and causal inference tests (CIT) were conducted to determine potentially causative regulatory effects of methylation on mRNA expression.

Results

A total of 4794 differentially methylated positions (DMPs) were identified associated with AS, 2526 DMPs of which were validated in an independent cohort. Both cohorts highlighted T cell receptor (TCR) signaling and Th17 differentiation pathways. Besides, AS patients manifested increased DNA methylation variability. The methylation levels of 158 DMPs were correlated with the mRNA expression levels of 112 genes, which formed interconnected network concentrated on Th17 cell differentiation and TCR signaling pathway (LCK, FYN, CD3G, TCF7, ZAP70, CXCL12, and PLCG1). We also identified several cis-acting DNA methylation and gene expression changes associated with AS risk, which might regulate the cellular mechanisms underlying AS.

Conclusions

Our studies outlined the landscapes of epi-signatures of AS and several methylation-gene expression-AS regulatory axis and highlighted the Th17 cell differentiation and TCR signaling pathway, which might provide innovative molecular targets for therapeutic interventions for AS.
The sustained adverse impact of COVID-19 pandemic on mental health among pregnant women in Sri Lanka: a reassessment during the second wave
Authors: Patabendige Malitha , Wanniarachchi Dhanushka , Weerasinghe Malika , Ruwanpathirana Pramith , Jayasundara DMCS , Jayawardane Asanka
Published: January 2022

Objective

To study the change in trend of antenatal mental health and associated factors among a cohort of pregnant women during the second wave of COVID-19 using Hospital Anxiety and Depression Scale (HADS). Previous study using the same scale, during the first wave reported a higher prevalence of anxiety and depression.

Results

A descriptive cross-sectional study was carried out at the two large maternity hospitals in Colombo, Sri Lanka: Castle Street Hospital for Women (CSHW) and De Soysa Hospital for Women (DSHW). Consecutively recruited 311 women were studied. Out of which, 272 (87.5%) were having uncomplicated pregnancies at the time of the survey and 106 (34.1%) were either anxious, depressed, or both. Prevalence of anxiety was 17.0% and depression 27.0%. Overall, continuing COVID-19 pandemic increased antenatal anxiety and depression. The trend was to aggravate depression more intensively compared to anxiety in this cohort of women studied. Special support is needed for pregnant mothers during infectious epidemics taking more attention to antenatal depression.
Mild behavioral impairment: measurement and clinical correlates of a novel marker of preclinical Alzheimer’s disease
Authors: Creese Byron , Ismail Zahinoor
Published: January 2022

Background

Late-life onset neuropsychiatric symptoms are established risk factors for dementia. The mild behavioral impairment (MBI) diagnostic framework was designed to standardize assessment to determine dementia risk better. In this Mini Review, we summarize the emerging clinical and biomarker evidence, which suggests that for some, MBI is a marker of preclinical Alzheimer’s disease.

Main

MBI is generally more common in those with greater cognitive impairment. In community and clinical samples, frequency is around 10–15%. Mounting evidence in cognitively normal samples links MBI symptoms with known AD biomarkers for amyloid, tau, and neurodegeneration, as well as AD risk genes. Clinical studies have found detectable differences in cognition associated with MBI in cognitively unimpaired people.

Conclusion

The emerging evidence from biomarker and clinical studies suggests MBI can be an early manifestation of underlying neurodegenerative disease. Future research must now further validate MBI to improve identification of those at the very earliest stages of disease.
Weighted Ostrowski type inequalities for co-ordinated convex functions
Authors: Budak Hüseyin
Published: January 2022

In this paper, utilizing an identity given by Yıldız and Sarıkaya in (Yildiz and Sarikaya in Int. J. Anal. Appl. 13(1):64–69, 2017), we establish some weighted Ostrowski type inequalities for co-ordinated convex functions in a rectangle from the plane $\mathbb{R} ^{2}$

R
2

. Moreover, as special cases of our main results, we give some weighted Hermite–Hadamard type inequalities. The results given in this paper provide generalizations of some result established in earlier works.
The availability of priority medicines for children under 5 years in eThekwini, South Africa
Authors: Mahadeo Shannice , Narain Keshmika , Mhlongo Lungelo , Chetty Desmaine , Masondo Lindelani , Zungu Mandla , Suleman Fatima , Perumal-Pillay Velisha Ann
Published: January 2022

Background

Globally, an estimated 8.1 million children under 5 years die annually in developing countries. Ensuring essential medicines are accessible and affordable to the population is key to saving lives. This study investigated accessibility, availability and affordability of a basket of priority medicines for children under 5 years in public and private healthcare sector pharmacies in the eThekwini Metropolitan area in Durban, South Africa.

Methods

The WHO/HAI survey tool for assessing medicine prices, availability and affordability was adapted and employed for a basket of WHO Priority life-saving medicines for children under 5 years. Six district hospitals in the north, south and central eThekwini Metropolitan were selected as major facility reference points and for data collection and pharmacies within a 5 km radius from each major facility were also invited to participate in the study, as outlined in the WHO/HAI tool methodology. Of the 58 pharmacies selected, a total of 27 pharmacies from both private and public healthcare sectors agreed to participate and were surveyed, representing a 47% response rate. Data was analysed using Microsoft excel.

Results

All participating pharmacies (and hence the selected basket of priority medicines at these facilities) were deemed accessible. Overall the public sector had more medicines available on the shelf (averaging 64%) than the private sector (48%) which had more medicines available on order (84%). At least one medicine for each of the eight (8) conditions was available at both sectors which meant patients could be treated for these conditions. Medicines for priority conditions (except HIV, which was a 28-day course) were deemed affordable as these regimens were obtainable within a day’s wage for the lowest paid unskilled worker. Priority medicines for children under 5 years were more available and more affordable in the public sector.

Conclusion

The basket of WHO essential medicines for priority conditions for children under 5 years were accessible, available and affordable in the eThekwini Metropolitan areas. This was the first study in eThekwini to determine access to the WHO basket of priority medicines for children and can be scaled-up to a national study to provide a holistic comparison of these medicines in the country, and also for global comparison.
Efficiency of earthquake forecast models based on earth tidal correlation with background seismicity along the Tonga–Kermadec trench
Authors: Hirose Fuyuki , Maeda Kenji , Kamigaichi Osamu
Published: January 2022

The correlation between Earth’s tides and background seismicity has been suggested to become stronger before great earthquakes and weaker after. However, previous studies have only retrospectively analyzed this correlation after individual large earthquakes; it thus remains vague (i) whether such variations might be expected preceding future large earthquakes, and (ii) the strength of the tidal correlation during interseismic periods. Therefore, we retrospectively investigated whether significant temporal variations of the tidal correlation precede large interplate earthquakes along the Tonga–Kermadec trench, where Mw 7-class earthquakes frequently occurred from 1977 to 31 December 2020. We evaluated a forecast model based on the temporal variations of the tidal correlation via Molchan’s error diagram, using the tidal correlation value itself as well as its rate of change as threshold values. For Mw ≥ 7.0 earthquakes, this model was as ineffective as random guessing. For Mw ≥ 6.5, 6.0, or 5.5 earthquakes, the forecast model performed better than random guessing in some cases, but even the best forecast only had a probability gain of about 1.7. Therefore, the practicality of this model alone is poor, at least in this region. These results suggest that changes of the tidal correlation are not reliable indicators of large earthquakes along the Tonga–Kermadec trench.

Graphical Abstract
Hip joint motion does not change one year after arthroscopic osteochondroplasty in patients with femoroacetabular impingement evaluated with dynamic radiostereometry
Authors: Hansen Lars , de Raedt Sepp , Jørgensen Peter Bo , Mygind-Klavsen Bjarne , Rømer Lone , Kaptein Bart , Søballe Kjeld , Stilling Maiken
Published: January 2022

Purpose

Dynamic radiostereometric analysis (dRSA) enables precise non-invasive three-dimensional motion-tracking of bones for assessment of joint kinematics. Hereby, the biomechanical effects of arthroscopic osteochondroplasty of the hip (ACH) can be evaluated in patients with femoroacetabular impingement (FAI).

The aim was to investigate the pre- and postoperative range of motion (ROM) and the CT bone volume removed (BV) after ACH. We hypothesize increase in ROM 1 year after surgery.

Methods

Thirteen patients (6 female) with symptomatic FAI were included prospectively. The patient’s hips were CT-scanned and CT-bone models were created. Preoperative dRSA recordings were acquired during passive flexion to 90°, adduction, and internal rotation (FADIR). ACH was performed, CT and dRSA were repeated 3 months and 1 year postoperatively. Hip joint kinematics before, and 3 months and 1 year after ACH were compared pairwise. The bone volume removal was quantified and compared to change in ROM.

Results

Mean hip internal rotation, adduction and flexion were all unchanged after ACH at 1-year follow-up (p > 0.84). HAGOS scores revealed improvement of quality of life (QOL) from 32 to 60 (p = 0.02). The BV was between 406 and 1783 mm3and did not correlate to post-operative ROM.

Conclusions

ACH surgery in FAI patients had no impact of ROM at 1-year follow-up. QOL improved significantly. This indicates that the positive clinical effects reported after ACH might be a result of reduced labral stress and cartilage pressure during end-range motion rather than increased ROM.

Level of evidence

Therapeutic prospective cohort study, level II.
Time difference between the 1854 CE Ansei–Tokai and Ansei–Nankai earthquakes estimated from distant tsunami waveforms on the west coast of North America
Authors: Kusumoto Satoshi , Imai Kentaro , Hori Takane
Published: January 2022

We estimated the time difference between the 1854 CE Ansei–Tokai and Ansei–Nankai earthquakes from tidal records of two tide gauge stations (San Francisco and San Diego) on the west coast of North America. The first signals of the Ansei–Tokai tsunami were apparent, whereas those of the Ansei–Nankai tsunami were obscured by the later waves of the Ansei–Tokai tsunami. Waveforms of the Ansei–Nankai tsunami simulated with nonlinear dispersive wave theory by assuming an origin time of 07:00 GMT on 24 December arrived earlier than in the observations. The normalized root mean square and the misfit between the simulated and observed waveforms of the Ansei–Nankai tsunami showed a time difference between them of approximately 0.4 h. This finding suggests that the actual origin time of the Ansei–Nankai tsunami was approximately 07:24 GMT on 24 December. A previous study estimated the origin time of the Ansei–Tokai tsunami to be about 00:30 GMT on 23 December. Thus, we concluded that the time difference between the 1854 CE Ansei–Tokai and Ansei–Nankai tsunamis was 30.9 h. Despite the significant difference in the time resolution between the seasonal timekeeping system used in Japan in 1854 and waveform digitization, our result is roughly in agreement with historical descriptions of the tsunamis, suggesting that such information can be effectively used to determine the origin times of historical earthquakes.