bluuebunny/crossref_metadata_2025 huggingface dataset:
Persuasion or coercion? An empirical ethics analysis about the use of influence strategies in mental health community care
Authors: Valenti Emanuele , Giacco Domenico
Published: October 2022

Background

Influence strategies such as persuasion and interpersonal leverage are used in mental health care to influence patient behaviour and improve treatment adherence. One ethical concern about using such strategies is that they may constitute coercive behaviour ("informal coercion") and negatively impact patient satisfaction and the quality of care. However, some influence strategies may affect patients' perceptions, so an umbrella definition of “informal coercion” may be unsatisfactory. Furthermore, previous research indicates that professionals also perceive dissonance between theoretical explanations of informal coercion and their behaviours in clinical practice. This study analysed mental health professionals’ (MHPs) views and the perceived ethical implications of influence strategies in community care.

Methods

Qualitative secondary data analysis of a focus group study was used to explore the conflict between theoretical definitions and MHPs’ experiences concerning the coerciveness of influence strategies. Thirty-six focus groups were conducted in the main study, with 227 MHPs from nine countries participating.

Results

The findings indicate that not all the influence strategies discussed with participants can be defined as “informal coercion”, but they become coercive when they imply the use of a lever, have the format of a conditional offer and when the therapeutic proposal is not a patient’s free choice but is driven by professionals. MHPs are rarely aware of these tensions within their everyday practice; consequently, it is possible that coercive practices are inadvertently being used, with no standard regarding their application. Our findings suggest that levers and the type of leverage used in communications with the patient are also relevant to differentiating leveraged and non-leveraged influence.

Conclusion

Our findings may help mental health professionals working in community care to identify and discuss influence strategies that may lead to unintended coercive practices.
orsai, the Drosophila homolog of human ETFRF1, links lipid catabolism to growth control
Authors: Fernandez-Acosta Magdalena , Romero Juan I. , Bernabó Guillermo , Velázquez-Campos Giovanna M. , Gonzalez Nerina , Mares M. Lucía , Werbajh Santiago , Avendaño-Vázquez L. Amaranta , Rechberger Gerald N. , Kühnlein Ronald P. , Marino-Buslje Cristina , Cantera Rafael , Rezaval Carolina , Ceriani M. Fernanda
Published: October 2022

Background

Lipid homeostasis is an evolutionarily conserved process that is crucial for energy production, storage and consumption. Drosophila larvae feed continuously to achieve the roughly 200-fold increase in size and accumulate sufficient reserves to provide all energy and nutrients necessary for the development of the adult fly. The mechanisms controlling this metabolic program are poorly understood.

Results

Herein we identified a highly conserved gene, orsai (osi), as a key player in lipid metabolism in Drosophila. Lack of osi function in the larval fat body, the regulatory hub of lipid homeostasis, reduces lipid reserves and energy output, evidenced by decreased ATP production and increased ROS levels. Metabolic defects due to reduced Orsai (Osi) in time trigger defective food-seeking behavior and lethality. Further, we demonstrate that downregulation of Lipase 3, a fat body-specific lipase involved in lipid catabolism in response to starvation, rescues the reduced lipid droplet size associated with defective orsai. Finally, we show that osi-related phenotypes are rescued through the expression of its human ortholog ETFRF1/LYRm5, known to modulate the entry of β-oxidation products into the electron transport chain; moreover, knocking down electron transport flavoproteins EtfQ0 and walrus/ETFA rescues osi-related phenotypes, further supporting this mode of action.

Conclusions

These findings suggest that Osi may act in concert with the ETF complex to coordinate lipid homeostasis in the fat body in response to stage-specific demands, supporting cellular functions that in turn result in an adaptive behavioral response.
Neutrophil activation and NETosis are the predominant drivers of airway inflammation in an OVA/CFA/LPS induced murine model
Authors: Xia Mengling , Xu Fei , Ni Hangqi , Wang Qing , Zhang Ruhui , Lou Yafang , Zhou Jianying
Published: October 2022

Background

Asthma is one of the most common chronic diseases that affects more than 300 million people worldwide. Though most asthma can be well controlled, individuals with severe asthma experience recurrent exacerbations and impose a substantial economic burden on healthcare system. Neutrophil inflammation often occurs in patients with severe asthma who have poor response to glucocorticoids, increasing the difficulty of clinical treatment.

Methods

We established several neutrophil-dominated allergic asthma mouse models, and analyzed the airway hyperresponsiveness, airway inflammation and lung pathological changes. Neutrophil extracellular traps (NETs) formation was analyzed using confocal microscopy and western blot.

Results

We found that the ovalbumin (OVA)/complete Freund’s adjuvant (CFA)/low-dose lipopolysaccharide (LPS)-induced mouse model best recapitulated the complex alterations in the airways of human severe asthmatic patients. We also observed OVA/CFA/LPS-exposed mice produced large quantities of neutrophil extracellular traps (NETs) in lung tissue and bone marrow neutrophils. Furthermore, we found that reducing the production of NETs or increasing the degradation of NETs can reduce airway inflammation and airway hyperresponsiveness.

Conclusion

Our findings identify a novel mouse model of neutrophilic asthma. We have also identified NETs play a significant role in neutrophilic asthma models and contribute to neutrophilic asthma pathogenesis. NETs may serve as a promising therapeutic target for neutrophilic asthma.
Endometrial compaction after human chorionic gonadotrophin administration reduces ectopic pregnancy rate following fresh embryo transfer in vitro fertilization/intracytoplasmic sperm injection cycles in patients with non-thin endometrium: a retrospective cohort study
Authors: Li Qiuyuan , Liu Ahui , Shen Haofei , Zhang Xuehong
Published: October 2022

Background

This study aims to study whether the change of endometrial thickness between the day of human chorionic gonadotrophin (HCG) administration and the day of embryo transfer (ET) has any effect on ectopic pregnancy (EP) rate following fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles.

Methods

This study retrospectively analyzed 3134 patients who underwent fresh IVF/ICSI ET, including 3022 intrauterine, 112 ectopic cycles. Multiple logistic regression analysis and stratified analysis were used to study the effect of endometrial compaction after HCG administration on EP in patients with non-thin endometrium after adjusting for confounding factors.

Results

After adjusting for confounders, multiple logistic regression analysis found that the risk of EP in the compaction group was significantly lower than that in the non-compaction group (OR = 0.49; 95% CI: 0.31–0.78; P = 0.0023). The results of the stratified analysis demonstrated the EP rate in patients with an endometrial thickness ≥ 8 mm on the day of ET; the compaction group significantly reduced the incidence of EP (OR = 0.49; 95% CI: 0.31–0.79; P = 0.0036). In patients with an endometrial thickness ≥ 8 mm on the day of ET, the incidence of EP had no statistical significance in two group (OR = 1.02; 95% CI: 0.18–5.88; P = 9790).

Conclusion(s)

In patients with non-thin endometrium, endometrial thickness compaction from the day of HCG to the ET day reduced the risk of EP significantly.
Conducting national burden of disease studies and knowledge translation in eight small European states: challenges and opportunities
Authors: Cuschieri Sarah , Alkerwi Ala’a , Economou Mary , Idavain Jane , Lai Taavi , Lesnik Tina , Meyers Caine , Samouda Hanen , Sigfúsdóttir Inga Dóra , Terzic Natasa , Tzivian Lilian , Pallari Elena
Published: October 2022

Background

Several countries across Europe are engaging in burden of disease (BoD) studies. This article aims to understand the experiences of eight small European states in relation to their research opportunities and challenges in conducting national BoD studies and in knowledge translation of research outputs to policy-making.

Methods

Countries participating in the study were those outlined by the WHO/Europe Small Countries Initiative and members of the Cooperation in Science and Technology (COST) Action CA18218 European Burden of Disease Network. A set of key questions targeting the research landscape were distributed to these members. WHO’s framework approach for research development capacities was applied to gain a comprehensive understanding of shortages in relation to national BoD studies in order to help strengthen health research capacities in the small states of Europe.

Results

Most small states lack the resources and expertise to conduct BoD studies, but nationally representative data are relatively accessible. Public health officials and researchers tend to have a close-knit relationship with the governing body and policy-makers. The major challenge faced by small states is in knowledge generation and transfer rather than knowledge translation. Nevertheless, some policy-makers fail to make adequate use of knowledge translation.

Conclusions

Small states, if equipped with adequate resources, may have the capacity to conduct national BoD studies. This work can serve as a model for identifying current gaps and opportunities in each of the eight small European countries, as well as a guide for translating country BoD study results into health policy.
Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma
Authors: Toulmonde Maud , Cousin Sophie , Kind Michèle , Guegan Jean-Philippe , Bessede Alban , Le Loarer Francois , Perret Raul , Cantarel Coralie , Bellera Carine , Italiano Antoine
Published: October 2022

JX-594 is an oncolytic vaccinia virus genetically modified to replicate selectively in tumor cells. Metronomic chemotherapy has shown preclinical synergy with oncolytic viruses. We report here the results of the METROMAJX which is a randomized phase II clinical trial investigating the combination of JX-594 combined with metronomic cyclophosphamide (arm 1) or metronomic cyclophosphamide (arm 2) in patients with advanced STS. A two-stage Simon design was used. JX-594 was administered intra-venously at the dose 1.109 every 2 weeks for the first 3 injections and then every 3 weeks. Cyclophosphamide was given orally at the dose of 50 mg BID 1 week on 1 week off. The primary endpoint was the 6-month non progression rate. 20 patients were included (arm 1:15, arm 2:5). The two most frequent toxicities were grade 1 fatigue and fever and grade 2 fatigue and grade 2 lymphopenia in arms 1 and 2, respectively. In arm 1, 12 patients were assessable for the efficacy analysis. None of them were progression-free at 6 months indicating that the first stage of the Simon's design was not satisfied. One patient out 4 assessable for efficacy was progression-free at 6 months in arm 2. High throughput analysis of sequential plasma samples revealed an upregulation of protein biomarkers reflecting immune induction such as CXCL10 and soluble CD8 antigen in arm 1. Systemic treatment with JX-594 is safe in patients with advanced STS. Further investigations are needed to improve immune response to oncolytic viruses and define their therapeutic potential in patients with STS.
RETRACTED ARTICLE: Extremely Active Nano-formulation of Resveratrol (XAR™) attenuates and reverses chemotherapy-induced damage in mice ovaries and testes
Authors: Chhabria Sagar , Takle Vaishnavi , Sharma Nripen , Kharkar Prashant , Pansare Kshama , Tripathi Anish , Tripathi Ashish , Bhartiya Deepa
Published: October 2022

Background

Fertility preservation and restoration in cancer patients/survivors is the need of present times when increased numbers of patients get cured of cancer but face infertility as a serious side effect. Resveratrol has beneficial effects on chemoablated ovaries and testes in mice but has failed to enter the clinics because of extremely poor bioavailability. The present study was undertaken to evaluate the protective and curative effects of Extremely active Resveratrol (XAR™)- a nano-formulation of resveratrol with significantly improved bioavailability- on mouse ovary and testis after chemotherapy. Effects of XAR™ and FSH were compared on stimulation of follicle growth in adult mice ovaries. XAR™ (25 mg/kg) was administered for two days prior to chemotherapy to study the protective effects on the mouse gonads. XAR™ was also administered for 14 days post chemoablation to study the regenerative effects. Besides effect on numbers of primordial and growing follicles and spermatogenesis, the effect of XAR™ was also evaluated on the transcripts specific for ovarian/testicular stem/progenitor/germ cells, their proliferation, differentiation, meiosis, and the antioxidant indices.

Results

Similar to FSH, XAR™ increased the numbers of primordial follicles (PF) as well as growing follicles. It protected the gonads from the adverse effects of chemotherapy and showed the ability to regenerate non-functional, chemoablated gonads. Besides stimulating follicle growth in adult ovaries similar to FSH, XAR™ also protected the testes from the adverse effects of chemotherapy and improved spermatogenesis. This was accompanied by improved anti-oxidant indices.

Conclusions

The results of the present study potentiate the use of XAR™ in pilot clinical studies to protect gonadal function during oncotherapy and also regenerate non-functional gonads in cancer survivors by improving antioxidant indices and stem cell-based tissue regeneration.
A cross-sectional study of Simulium damnosum sensu lato breeding sites and species distribution in Sudan savanna, mixed savanna–forest and rainforest regions in Cameroon
Authors: Ayisi Franklin , Sedou Naniogué , Dieunang Stephanie Kouahou , Yaya Florent , Tchago Edmond François , Ndellejong Cosmas Ejong , Biholong Benjamin , Boakye Daniel Adjei
Published: October 2022

Background

The presence of breeding sites and distribution of species of Simulium damnosum sensu lato are critical in understanding the epidemiology of onchocerciasis and evaluating the impact of elimination interventions. Reports on breeding sites and species distribution of members of S. damnosum s.l. in Cameroon are scarce and the few ones available date back to more than three decades. The aim of this study is to provide information on S. damnosum breeding sites across the rainy (RS) and dry (DS) seasons and the species composition in three different regions in Cameroon: Southwest (SW), Northwest (NW) and North (N).

Methods

A cross-sectional two-season study was carried out in three regions with different ecological characteristics (SW—rainforest; NW—mixed forest–Guinea savanna; N—Sudan savanna). Pre-control onchocerciasis endemicity, relief maps and historical entomological information were used to identify potential rivers for purposive sampling. Sampled larvae were fixed in Carnoy’s solution and sorted, and S. damnosum s.l. larvae were stored until identification by cytotaxonomy. Geographical coordinates of potential breeding sites were recorded to produce maps using ArcGIS, while Chi-square tests in SPSS were used to test for any differences between black fly seasonal breeding rates.

Results

A total of 237 potential breeding sites were sampled (RS = 81; DS = 156) and 72 were found positive for S. damnosum s.l. The SW had the most positive sites [67 (RS = 24; DS = 43)], with a significant difference in the rate of breeding between the seasons (P < 0.05). Among 68 sites visited in both seasons, 16 (23.5%) were positive in one of the two seasons with more sites positive in DS(11) than RS(05), 14 (20.6%) and 38 (55.9%) respectively positive and negative in both seasons. Simulium damnosum sensu stricto and S. sirbanum were the main species in the N, while S. squamosum and S. mengense were the predominant species in the NW and SW. Simulium soubrense and S. yahense were uniquely recorded in the SW.

Conclusions

A comprehensive mapping of breeding sites requires rainy and dry seasons sampling. This study demonstrates that a breeding site survey of S. damnosum s.l. is achievable in forest as well as savanna zones. Not all potential breeding sites are actual breeding sites. Observation of S. soubrense in the SW indicates changes in species composition over time and could affect onchocerciasis epidemiology in this area.

Graphical abstract
Effect of a point-of-care ultrasound (POCUS) curriculum on emergency department soft tissue management
Authors: Nti Benjamin K. , Phillips Whitney , Sarmiento Elisa , Russell Frances
Published: October 2022

Background

Pediatric emergency department (ED) visits for superficial skin and soft tissue infections (SSTI) have steadily been increasing and point-of-care ultrasound (POCUS) continues to be an effective modality to improve management and shorter ED length of stays (LOS).

Objective

We sought to determine the impact of a soft tissue POCUS curriculum on POCUS utilization, ED LOS, and cost-effectiveness.

Methods

This was a retrospective pre- and post-interventional study of pediatric patients aged 0 to 17 years. Patients presenting to ED with international classification of disease 9 or 10 code for abscess or cellulitis were included. Data were collected a year before and after curriculum implementation with a 1-year washout training period. Training included continuing medical education, greater than 25 quality assured examinations, and a post-test. We compared diagnostic imaging type, ED LOS, and mean charges in patients with SSTI.

Results

We analyzed data on 119 total patients, 38 pre- and 81 post-intervention. We found a significant increase in the total number of POCUS examinations performed pre- to post-curriculum intervention, 26 vs. 59 (p = 0.0017). Mean total charges were significantly decreased from $3,762 (± 270) to $2,622 (± 158;p = 0.0009). There was a significant trend towards a decrease in average ED LOS 282 (standard error of mean [SEM] ± 19) vs 185 (± 13) minutes (p = 0.0001).

Conclusions

Implementation of a soft tissue POCUS curriculum in a pediatric ED was associated with increased POCUS use, decreased LOS, and lower cost. These findings highlight the importance of POCUS education and implementation in the management of pediatric SSTI.
The effects of olive leaf extract on cardiovascular risk factors in the general adult population: a systematic review and meta-analysis of randomized controlled trials
Authors: Razmpoosh Elham , Abdollahi Shima , Mousavirad Mahdieh , Clark Cain C. T. , Soltani Sepideh
Published: October 2022

Background

The aim of this systematic review and meta-analysis was to determine the effect of olive leaf extract (OLE) supplementation on cardiovascular-related variables, including lipid, glycemic, inflammatory, liver and renal-related factors, as well as blood pressure.

Methods

PubMed, ISI Web of Science, Scopus, and Cochrane library were searched, up to October 2021, for relevant controlled trials. Mean differences and standard deviations were pooled for all outcomes, using a random-effects model. The methodological quality, as well as quality of evidence were assessed using standard tools.

Results

Twelve studies (n = 819 participants) were included in our analyses. Overall analyses showed that OLE supplementation significantly decreased triglyceride (TG) levels (WMD = − 9.51 mg/dl, 95% CI − 17.83, − 1.18; P = 0.025; I2 = 68.7%; P-heterogeneity = 0.004), and systolic blood pressure (SBP) (WMD = − 3.86 mmHg, 95% CI − 6.44, − 1.28 mmHg; P = 0.003; I2 = 19.9%; P-heterogeneity = 0.28). Subgroup analyses also revealed a significant improvement in SBP (− 4.81 mmHg) and diastolic blood pressure (− 2.45 mmHg), TG (− 14.42 mg/dl), total cholesterol (TC) (− 9.14 mg/dl), and low-density lipoprotein-C (LDL-C) (− 4.6 mg/dl) measurements, in patients with hypertension. Significant reductions were also observed in TC (− 6.69 mg/dl), TG (− 9.21 mg/dl), and SBP (− 7.05 mmHg) in normal-weight individuals. However, no meaningful changes were seen in glucose hemostasis, liver and kidney, or inflammatory markers.

Conclusion

The present study revealed that supplementation with OLE yielded beneficial effects for blood pressure and lipid profile in adults, especially in patients with hypertension. As the quality of evidence for glucose hemostasis variables, liver, kidney, and inflammatory markers, were low-to-very low, higher quality RCTs may impact the overarching results.

This study was registered at PROSPERO with the code CRD42022302395.
Association between irisin and metabolic parameters in nondiabetic, nonobese adults: a meta-analysis
Authors: Li Yan , Xu Zhenbin
Published: October 2022

Background

Irisin has been proposed to have a beneficial influence on the metabolic status of animals and humans. However, the relationship between circulating irisin levels and the risks of metabolic components in humans remains unclear. In the present meta-analysis, we aimed to evaluate the association between circulating irisin and metabolic parameters in nonobese, nondiabetic adults.

Methods

We searched PubMed, Embase, the Cochrane Library, Web of Science and ClinicalTrial.gov using the main search terms and identified original articles published prior to March 7, 2022. Studies that met our inclusion criteria and reported the association between irisin and metabolic parameters were included in our meta-analysis. We used the Newcastle Ottawa scale to assess the quality of the included studies.

Results

A total of 14 studies (711 subjects) in 11 articles were included for qualitative and quantitative synthesis. The pooled results showed that circulating irisin was positively and significantly correlated with fasting blood glucose (r = 0.159), HOMA-IR (r = 0.217) and waist-to-hip ratio (WHR) (r = 0.168). However, no significant association was detected between irisin levels and other metabolic parameters.

Conclusions

Thus, these findings indicated the possible link between irisin levels and part of the metabolic parameters in apparently metabolically normal individuals. However, the regulation of irisin in metabolism in humans remains to be fully elucidated, and well-designed prospective studies will be needed in the future.

Trial registration The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42022315269.
Association of the gallbladder or biliary diseases with dipeptidyl peptidase 4 inhibitors in patients with type 2 diabetes: a meta-analysis of randomized controlled trials
Authors: Yu Meng , Yang Zheng , Chen Chongxin , Lv Yuhuan , Xiang Linyu , Zhao Subei , Li Rong
Published: October 2022

Background

Previous studies have shown inconsistent conclusions regarding the association between incretin-based therapies and the risk of developing gallbladder or biliary diseases. We conducted a meta-analysis to evaluate the risk of gallbladder or biliary diseases associated with dipeptidyl peptidase 4 inhibitors (DPP4i) in patients with type 2 diabetes.

Methods

The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched (from inception up to March 14, 2022) for published randomized controlled trials (RCTs) that compared DPP4i with placebo or other glucose-lowering drugs in patients with type 2 diabetes. The outcomes of interest were cholecystitis, cholangitis, cholelithiasis, bile duct stones, and biliary colic. Relative risks (RRs) and 95% confidence intervals (CI) were pooled using a random-effects model. Subgroup analyses were performed according to patient age, trial duration, and types of DPP4i.

Results

In total, 97,150 participants from 75 eligible RCTs were included in the meta-analysis. DPP4i were associated with an increased risk of composite of gallbladder or biliary diseases (RR 1.20 [95% CI 1.01–1.42]) and cholecystitis (RR 1.38 [95% CI 1.08–1.75]). Among all included trials, DPP4i showed no association with the following manifestations of gallbladder or biliary diseases: cholelithiasis (RR 1.00 [95% CI 0.76–1.32]), cholangitis (RR 0.81 [95% CI 0.39–1.66]), bile duct stones (RR 1.08 [95% CI 0.57–2.05]), and biliary colic (RR 0.72 [95% CI 0.23–2.25]). Subgroup analyses showed that DPP4i were associated with a higher risk of cholecystitis in older patients (RR 1.37 [95% CI 1.03–1.83]) compared with younger patients (RR 1.08 [95% CI 0.89–2.18]) and in those with a longer duration of drug use (RR 1.43 [95% CI 1.08–1.89]) compared with shorter use (RR 1.23 [95% CI 0.74–2.03]).

Conclusions

This systematic review and meta-analysis of RCTs found that the use of DPP4i was associated with an increased risk of cholecystitis, especially in patients of advanced age or in those who were exposed to the drugs for a long period of time.
Maternal and neonatal outcomes with the use of long acting, compared to intermediate acting basal insulin (NPH) for managing diabetes during pregnancy: a systematic review and meta-analysis
Authors: Wang Jijiao , Ji Xiaochen , Liu Ting , Zhao Nan
Published: October 2022

Background

To assess the impact of long-acting insulin analogues, compared to intermediate acting neutral protamine Hagedron (NPH), on maternal, perinatal and neonatal outcomes.

Methods

Studies for inclusion in the review were identified using a structured search strategy in PubMed, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) database. Studies that were randomized controlled trials or observational in design were considered for inclusion. Eligible studies should have compared the maternal, perinatal and neonatal outcomes between pregnant women with gestational diabetes mellitus (GDM) managed by intermediate acting (NPH) and by long-acting insulin analogues. Statistical analysis was performed using STATA software.

Results

We found 17 studies to be eligible for inclusion. The mean gestational weight gain and risk of maternal hypoglycaemia, hypertensive disorder, caesarean delivery, spontaneous abortion, endometritis and wound infection or dehiscence were similar among pregnant women with GDM managed using long-acting insulin analogues and NPH. Those receiving long-acting insulin analogues had significantly lower HbA1c values in the second (WMD − .09, 95% CI 0.12, − 0.06; N = 4) and third trimester (WMD − 0.08, 95% CI − 0.14, − 0.02; N = 12). The mean gestational age and birth weight and risk of perinatal mortality, prematurity, large for gestational age, small for gestational age, shoulder dystocia and congenital abnormalities was similar among babies in both groups. No statistically significant differences in risk of admission to neonatal intensive care unit, respiratory distress, neonatal hypoglycaemia, 5 min APGAR score of < 7, neonatal hyperbilirubinemia and sepsis was observed. The quality of pooled evidence, as per GRADE criteria, was judged to be “very low” for all the maternal and neonatal outcomes considered.

Conclusions

Findings suggest no significant differences in the maternal, perinatal and neonatal outcomes between intermediate and long-acting insulin analogues. The results provide support for use of long-acting insulin analogues in women with GDM. However, evidence is still needed from high quality randomized controlled trials to arrive at a recommendation for inclusion in routine clinical care.
Jatrorrhizine alleviates ulcerative colitis via regulating gut microbiota and NOS2 expression
Authors: Zhang Jia Ling , Zhang Min Na , Wang Hong Gang , Yang Xiao Zhong , Yu Cheng Gong
Published: October 2022

Background

The natural protoberberine jatrorrhizine (JA) is reported to have several medicinal properties and a significant effect on the gut microbiota of mice. The regulation of gut microbiota is generally known to play an important role in the intestinal mucosal immune response to ulcerative colitis (UC). However, whether JA can be used in the treatment of UC is still unclear. Our study aimed to investigate the underlying therapeutic effects and mechanisms of JA in treating colitis.

Results

Compared with the DSS-induced colitis model group, the JA + DSS treated group had more significant improvements in weight loss, disease activity index score, colon length shortening, and pathological inflammation. 16s rRNA sequencing analysis showed that JA treatment protected colitis mice against DSS-induced disturbance of gut microbiota. At the phylum level, reductions in Deferribacteres and Proteobacteria were observed in the JA-treated group; At the genus level, the JA-treated group showed an increased relative abundance of Akkermansia and decreased abundance of Escherichia-Shigella, Desulfovibrio, Mucispirillum, etc. Network pharmacology was then used to screen out five drug-disease target genes (NOS2, ESR1, CALM1, CALM2, CALM3). Transcriptomics analysis further validated that the NOS2 expression was significantly reduced in colon tissue of JA-administered mice compared with DSS control mice. Additionally, analysis of correlation suggested that NOS2 expression was negatively correlated with the relative abundance of AKKermansia and positively correlated with Desulfovibrio, Rikenella.

Conclusion

JA alleviates ulcerative colitis via regulating gut microbiota and NOS2 expression.
Gossypetin ameliorates 5xFAD spatial learning and memory through enhanced phagocytosis against Aβ
Authors: Jo Kyung Won , Lee Dohyun , Cha Dong Gon , Oh Eunji , Choi Yoon Ha , Kim Somi , Park Eun Seo , Kim Jong Kyoung , Kim Kyong-Tai
Published: October 2022

Background

Microglia are the resident immune cells found in our brain. They have a critical role in brain maintenance. Microglia constantly scavenge various waste materials in the brain including damaged or apoptotic neurons and Aβ. Through phagocytosis of Aβ, microglia prevent the accumulation of Aβ plaque in the brain. However, in Alzheimer’s disease (AD) patients, chronic exposure to Aβ makes microglia to become exhausted, which reduces their phagocytic activity against Aβ. Since microglia play an important role in Aβ clearance, enhancing microglial phagocytic activity against Aβ is a promising target for AD treatment. Therefore, there is a great need for therapeutic candidate that enhances microglial Aβ clearance while inhibiting microglia’s pathogenic properties.

Methods

In vivo studies were conducted with 5xFAD AD model mice by treating gossypetin for 13 weeks through intragastric administration. Their spatial learning and memory were evaluated through behavior tests such as Y-maze and Morris Water Maze test. Hippocampus and cortex were acquired from the sacrificed mice, and they were used for histological and biochemical analysis. Also, mouse tissues were dissociated into single cells for single-cell RNA sequencing (scRNA-seq) analysis. Transcriptome of microglial population was analyzed. Mouse primary microglia and BV2 mouse microglial cell line were cultured and treated with fluorescent recombinant Aβ to evaluate whether their phagocytic activity is affected by gossypetin.

Results

Gossypetin treatment improved the spatial learning and memory of 5xFAD by decreasing Aβ deposition in the hippocampus and cortex of 5xFAD. Gossypetin induced transcriptomic modulations in various microglial subpopulations, including disease-associated microglia. Gossypetin enhanced phagocytic activity of microglia while decreasing their gliosis. Gossypetin also increased MHC II+microglial population.

Conclusions

Gossypetin showed protective effects against AD by enhancing microglial Aβ phagocytosis. Gossypetin appears to be a novel promising therapeutic candidate against AD.
A comprehensive update on CIDO: the community-based coronavirus infectious disease ontology
Authors: He Yongqun , Yu Hong , Huffman Anthony , Lin Asiyah Yu , Natale Darren A. , Beverley John , Zheng Ling , Perl Yehoshua , Wang Zhigang , Liu Yingtong , Ong Edison , Wang Yang , Huang Philip , Tran Long , Du Jinyang , Shah Zalan , Shah Easheta , Desai Roshan , Huang Hsin-hui , Tian Yujia , Merrell Eric , Duncan William D. , Arabandi Sivaram , Schriml Lynn M. , Zheng Jie , Masci Anna Maria , Wang Liwei , Liu Hongfang , Smaili Fatima Zohra , Hoehndorf Robert , Pendlington Zoë May , Roncaglia Paola , Ye Xianwei , Xie Jiangan , Tang Yi-Wei , Yang Xiaolin , Peng Suyuan , Zhang Luxia , Chen Luonan , Hur Junguk , Omenn Gilbert S. , Athey Brian , Smith Barry
Published: October 2022

Background

The current COVID-19 pandemic and the previous SARS/MERS outbreaks of 2003 and 2012 have resulted in a series of major global public health crises. We argue that in the interest of developing effective and safe vaccines and drugs and to better understand coronaviruses and associated disease mechenisms it is necessary to integrate the large and exponentially growing body of heterogeneous coronavirus data. Ontologies play an important role in standard-based knowledge and data representation, integration, sharing, and analysis. Accordingly, we initiated the development of the community-based Coronavirus Infectious Disease Ontology (CIDO) in early 2020.

Results

As an Open Biomedical Ontology (OBO) library ontology, CIDO is open source and interoperable with other existing OBO ontologies. CIDO is aligned with the Basic Formal Ontology and Viral Infectious Disease Ontology. CIDO has imported terms from over 30 OBO ontologies. For example, CIDO imports all SARS-CoV-2 protein terms from the Protein Ontology, COVID-19-related phenotype terms from the Human Phenotype Ontology, and over 100 COVID-19 terms for vaccines (both authorized and in clinical trial) from the Vaccine Ontology. CIDO systematically represents variants of SARS-CoV-2 viruses and over 300 amino acid substitutions therein, along with over 300 diagnostic kits and methods. CIDO also describes hundreds of host-coronavirus protein-protein interactions (PPIs) and the drugs that target proteins in these PPIs. CIDO has been used to model COVID-19 related phenomena in areas such as epidemiology. The scope of CIDO was evaluated by visual analysis supported by a summarization network method. CIDO has been used in various applications such as term standardization, inference, natural language processing (NLP) and clinical data integration. We have applied the amino acid variant knowledge present in CIDO to analyze differences between SARS-CoV-2 Delta and Omicron variants. CIDO's integrative host-coronavirus PPIs and drug-target knowledge has also been used to support drug repurposing for COVID-19 treatment.

Conclusion

CIDO represents entities and relations in the domain of coronavirus diseases with a special focus on COVID-19. It supports shared knowledge representation, data and metadata standardization and integration, and has been used in a range of applications.
Patient journey and resources mapping to implement a praziquantel mass drug administration program for children aged 5 years and below in resource-limited settings
Authors: Ncube Mhlengi Vella , Kabuyaya Muhubiri , Chimbari Moses John
Published: October 2022

Background

The early childhood development of millions of children in some low- and medium-income countries may be compromised by schistosomiasis infections contracted at the age of 5 years and below. Currently, there are no standard guidelines for treating schistosomiasis in children that are 5 years and younger using praziquantel (PZQ), the only drug that the World Health Organization (WHO) recommends for treating schistosomiasis. The review is on processes and resources involved in the treatment of schistosomiasis in children aged 5 years and below.

Methods

An electronic search for peer-reviewed articles published in the period from January 2011 to August 2021 was done in the Academic Search Complete, CINAHL with Full Text, Health Source: Nursing/Academic Edition, and MEDLINE databases via EBSCOHost and Google Scholar databases. The search targeted journals that described the treatment of schistosomiasis in children 5 years and below using praziquantel.

Results

Thirteen studies met the inclusion criteria. The patient journey for treating schistosomiasis in children aged 5 years old and below using PZQ included the following activities: enrolment of the children into the treatment program; clinical examination; diagnosis; taking anthropometric measurements; feeding the children, making the PZQ palatable to the children; administration of PZQ; and monitoring of side effects. There was also a variation in the resources used to treat children aged 5 and below for schistosomiasis.

Conclusions

A PZQ mass drug administration program for children aged 5 years old and below in endemic areas should exclude the diagnosis of schistosomiasis before treatment. The resources required in the treatment process should be affordable, and should not require skills and maintenance resources that are beyond those that are available at the primary healthcare level.
Computing confined elasticae
Authors: Bartels Sören , Weyer Pascal
Published: October 2022

We devise a numerical scheme for computing arc-length parameterized curves of low bending energy that are confined to convex domains. We address the convergence of the discrete formulations to a continuous model and the unconditional stability of an iterative scheme. Numerical simulations confirm the theoretical results and lead to a classification of observed optimal curves within spheres.
Efficacy and safety of adjunctive therapy to lamotrigine, lithium, or valproate monotherapy in bipolar depression: a systematic review and meta-analysis of randomized controlled trials
Authors: Maruki Taku , Utsumi Tomohiro , Takeshima Masahiro , Fujiwara Yu , Matsui Marie , Aoki Yumi , Toda Hiroyuki , Watanabe Norio , Watanabe Koichiro , Takaesu Yoshikazu
Published: October 2022

Background

The efficacy and safety of adjunctive therapy are unclear in bipolar depression. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of second-generation antipsychotic, lamotrigine, lithium, or valproate therapy used in adjunction with lamotrigine, lithium, or valproate monotherapy in bipolar depression. A literature search of major electronic databases was conducted in February 2021, and all articles published until then were eligible. Two researchers independently screened relevant publications, extracted data, and evaluated methodological quality according to the Cochrane criteria.

Results

Five studies met the inclusion criteria. The meta-analysis revealed significant differences in the following outcomes: (i) remission rates from depressive episodes (risk ratio [RR]: 1.23, 95% confidence interval [CI] 1.01–1.50, p = 0.04), (ii) improvement in depressive symptoms (standardized mean difference [SMD]: 0.21, 95% CI 0.09–0.34, p = 0.001), (iii) improvement in quality of life (SMD: 0.22, 95% CI 0.06–0.37, p = 0.005), and (iv) rate of adverse events during the study period (RR: 1.12, 95% CI 1.03–1.22, p = 0.008). There was no significant difference between adjunctive therapy and monotherapy in the emergence of suicide-related behaviors, dropout rate during the study period, or rate of manic switching.

Conclusions

Our results suggest that adjunctive second-generation antipsychotics, lamotrigine, lithium, or valproate increase both the benefits and risks in patients with bipolar depression, although there is no significant difference in severe adverse events. Adjunctive therapy should be provided through shared decision-making while considering the patients’ condition in clinical settings.
Association between depression, happiness, and sleep duration: data from the UAE healthy future pilot study
Authors: Al Balushi Mitha , Al Balushi Sara , Javaid Syed , Leinberger-Jabari Andrea , Al-Maskari Fatma , Al-Houqani Mohammed , Al Dhaheri Ayesha , Al Nuaimi Abdullah , Al Junaibi Abdullah , Oumeziane Naima , Kazim Marina , Al Hamiz Aisha , Haji Muna , Al Hosani Ayesha , Abdel Wareth Leila , AlMahmeed Wael , Alsafar Habiba , AlAnouti Fatme , Al Zaabi Eiman , K. Inman Claire , Shahawy Omar El , Weitzman Michael , Schmidt Ann Marie , Sherman Scott , Abdulle Abdishakur , Ahmad Amar , Ali Raghib
Published: October 2022

Background

The United Arab Emirates Healthy Future Study (UAEHFS) is one of the first large prospective cohort studies and one of the few studies in the region which examines causes and risk factors for chronic diseases among the nationals of the United Arab Emirates (UAE). The aim of this study is to investigate the eight-item Patient Health Questionnaire (PHQ-8) as a screening instrument for depression among the UAEHFS pilot participants.

Methods

The UAEHFS pilot data were analyzed to examine the relationship between the PHQ-8 and possible confounding factors, such as self-reported happiness, and self-reported sleep duration (hours) after adjusting for age, body mass index (BMI), and gender.

Results

Out of 517 participants who met the inclusion criteria, 487 (94.2%) participants filled out the questionnaire and were included in the statistical analysis using 100 multiple imputations. 231 (44.7%) were included in the primary statistical analysis after omitting the missing values. Participants’ median age was 32.0 years (Interquartile Range: 24.0, 39.0). In total, 22 (9.5%) of the participant reported depression. Females have shown significantly higher odds of reporting depression than males with an odds ratio = 3.2 (95% CI:1.17, 8.88), and there were approximately 5-fold higher odds of reporting depression for unhappy than for happy individuals. For one interquartile-range increase in age and BMI, the odds ratio of reporting depression was 0.34 (95% CI: 0.1, 1.0) and 1.8 (95% CI: 0.97, 3.32) respectively.

Conclusion

Females are more likely to report depression compared to males. Increasing age may decrease the risk of reporting depression. Unhappy individuals have approximately 5-fold higher odds of reporting depression compared to happy individuals. A higher BMI was associated with a higher risk of reporting depression. In a sensitivity analysis, individuals who reported less than 6 h of sleep per 24 h were more likely to report depression than those who reported 7 h of sleep.
Diffraction imaging of discontinuities using migrated dip-angle gathers
Authors: Lin Peng , Peng Suping , Xiang Yang , Li Chuangjian , Cui Xiaoqin
Published: October 2022

Diffractions produced by subsurface geological features are an effective means of imaging small-scale discontinuities at high resolution. We developed a novel diffraction imaging approach that combines the geometric mode decomposition (GMD) algorithm and least-squares Gaussian distribution fitting (LSGDF) technique. In the dip-angle domain, reflections tend to look like smiles and are mainly focused in areas related to Fresnel zones, whereas diffractions spread over a wide illumination area due to their uniform radiation propagation. The GMD algorithm can effectively and simultaneously extract line-like components consisting of reflected energy in the Fresnel zone and diffracted energy in dip-angle gathers. The energy discrepancies between the reflection and diffraction events in the extracted line-like components allow for the separation of diffractions and suppression of reflections in dip-angle gathers using LSGDF. Numerical applications illustrate that the proposed method can eliminate large continuous reflectors and reveal discontinuous subsurface features. A real data example demonstrates the capability of the diffraction-imaging workflow in enhancing the resolving power of the imaging of subsurface geologic structures.
Automated hyperparameter optimization for simulating boundary conditions for acoustic and elastic wave propagation using deep learning
Authors: Kaur Harpreet , Fomel Sergey , Pham Nam
Published: October 2022

We have developed a deep learning framework to simulate the effect of boundary conditions for wave propagation in anisotropic media. To overcome the challenges associated with the stability of conventional implementation of boundary conditions for strongly anisotropic media, we develop an efficient algorithm using deep neural networks. We incorporate the hyperparameter optimization (HPO) workflow in the deep learning framework to automate the network training process. Hyperparameter selection is a crucial step in model building and has a direct impact on the performance of machine learning models. We implement three different HPO techniques, namely random search, Hyperband, and Bayesian optimization, for simulating boundary conditions and compare the strengths and drawbacks of these techniques. We train the network using a few shot locations and time slices enabling the network to learn how to remove boundary reflections and simulate wave propagation for unbounded media. The automated deep learning framework with HPO improves the performance of deep learning models by achieving the optimal minima and significantly improves the efficiency of the workflow. The benefit of this approach is its simple implementation and significant reduction of reflections at the boundaries, especially in the case of tilted transverse isotropic media. We validate our approach by comparing wave propagation at the boundaries using our algorithm with the output obtained using the unbounded media simulated by padding the model. Tests on different models with acoustic and elastic wave propagation verify the effectiveness of our approach.
Is decision-making impairment an endophenotype of anorexia nervosa?
Authors: Di Lodovico Laura , Versini Audrey , Lachatre Mathieu , Marcheselli Jacopo , Ramoz Nicolas , Gorwood Philip
Published: October 2022

Background

Patients with anorexia nervosa (AN) show impaired decision-making ability, but it is still unclear if this is a trait marker (i.e., being associated with AN at any stage of the disease) or a state parameter of the disease (i.e., being present only in acutely ill patients), and if it has endophenotypic characteristics. The aim of this study was to determine the endophenotypic, and state- or trait-associated nature of decision-making impairment in AN.

Methods

Ninety-one patients with acute AN (A-AN), 90 unaffected relatives (UR), 23 patients remitted from AN (R-AN), and 204 healthy controls (HC) carried out the Iowa gambling task (IGT). Prospective valence learning (PVL) model was employed to distinguish the cognitive dimensions underlying the decision-making process, that is, learning, consistency, feedback sensitivity, and loss aversion. IGT performance and decision-making dimensions were compared among groups to assess whether they had endophenotypic (i.e., being present in A-AN, UR, and R-AN, but not in HC) and/or trait-associated features (i.e., present in A-AN and R-AN but not in HC).

Results

Patients with A-AN had lower performance at the IGT (p < 0.01), while UR, R-AN, and HC had comparable results. PVL-feedback sensitivity was lower in patients with R-AN and A-AN than in HC (p < 0.01).

Conclusions

Alteration of decision-making ability did not show endophenotypic features. Impaired decision-making seems a state-associated characteristic of AN, resulting from the interplay between trait-associated low feedback sensitivity and state-associated features of the disease.