bluuebunny/crossref_metadata_2025 huggingface dataset:
Emergence of distinct syntenic density regimes is associated with early metazoan genomic transitions
Authors: Robert Nicolas S. M. , Sarigol Fatih , Zimmermann Bob , Meyer Axel , Voolstra Christian R. , Simakov Oleg
Published: February 2022

Background

Animal genomes are strikingly conserved in terms of local gene order (microsynteny). While some of these microsyntenies have been shown to be coregulated or to form gene regulatory blocks, the diversity of their genomic and regulatory properties across the metazoan tree of life remains largely unknown.

Results

Our comparative analyses of 49 animal genomes reveal that the largest gains of synteny occurred in the last common ancestor of bilaterians and cnidarians and in that of bilaterians. Depending on their node of emergence, we further show that novel syntenic blocks are characterized by distinct functional compositions (Gene Ontology terms enrichment) and gene density properties, such as high, average and low gene density regimes. This is particularly pronounced among bilaterian novel microsyntenies, most of which fall into high gene density regime associated with higher gene coexpression levels. Conversely, a majority of vertebrate novel microsyntenies display a low gene density regime associated with lower gene coexpression levels.

Conclusions

Our study provides first evidence for evolutionary transitions between different modes of microsyntenic block regulation that coincide with key events of metazoan evolution. Moreover, the microsyntenic profiling strategy and interactive online application (Syntenic Density Browser, available at: http://synteny.csb.univie.ac.at/) we present here can be used to explore regulatory properties of microsyntenic blocks and predict their coexpression in a wide-range of animal genomes.
Multi-omics data integration reveals link between epigenetic modifications and gene expression in sugar beet (Beta vulgaris subsp. vulgaris) in response to cold
Authors: Gutschker Sindy , Corral José María , Schmiedl Alfred , Ludewig Frank , Koch Wolfgang , Fiedler-Wiechers Karin , Czarnecki Olaf , Harms Karsten , Keller Isabel , Martins Rodrigues Cristina , Pommerrenig Benjamin , Neuhaus H. Ekkehard , Zierer Wolfgang , Sonnewald Uwe , Müdsam Christina
Published: February 2022

Background

DNA methylation is thought to influence the expression of genes, especially in response to changing environmental conditions and developmental changes. Sugar beet (Beta vulgaris ssp. vulgaris), and other biennial or perennial plants are inevitably exposed to fluctuating temperatures throughout their lifecycle and might even require such stimulus to acquire floral competence. Therefore, plants such as beets, need to fine-tune their epigenetic makeup to ensure phenotypic plasticity towards changing environmental conditions while at the same time steering essential developmental processes. Different crop species may show opposing reactions towards the same abiotic stress, or, vice versa, identical species may respond differently depending on the specific kind of stress.

Results

In this study, we investigated common effects of cold treatment on genome-wide DNA methylation and gene expression of two Beta vulgaris accessions via multi-omics data analysis. Cold exposure resulted in a pronounced reduction of DNA methylation levels, which particularly affected methylation in CHH context (and to a lesser extent CHG) and was accompanied by transcriptional downregulation of the chromomethyltransferase CMT2 and strong upregulation of several genes mediating active DNA demethylation.

Conclusion

Integration of methylomic and transcriptomic data revealed that, rather than methylation having directly influenced expression, epigenetic modifications correlated with changes in expression of known players involved in DNA (de)methylation. In particular, cold triggered upregulation of genes putatively contributing to DNA demethylation via the ROS1 pathway. Our observations suggest that these transcriptional responses precede the cold-induced global DNA-hypomethylation in non-CpG, preparing beets for additional transcriptional alterations necessary for adapting to upcoming environmental changes.
Case series of coronary artery aneurysms after Everolimus eluting stent implantation and comparison with Sirolimus eluting stents
Authors: Sharma Raghav , Ruia Aditya Vikram , Mahant Tek Singh
Published: February 2022

Background

Coronary artery aneurysms after drug eluting stents are rare. We present a case series of type II coronary aneurysms after implantation of Everolimus eluting stents including patients developing giant aneurysms with a toxic course.

Case presentation

Over a span of 3.5 years at our center 2572 patients were implanted Everolimus eluting stents out of which 4 patients developed coronary type II aneurysms an incidence of 0.00156 whereas 5838 patients were implanted Sirolimus eluting 2nd generation stents out of which 2 patients developed similar aneurysms with an incidence of 0.00034. The slight increase in incidence in Everolimus stents does not reach statistical significance (p = 0.054) and is limited by single centre non randomized study. We also propose a hypothesis that the slight increase in the incidence maybe due to allergy to Methacrylate present in Everolimus eluting Xience stent’s primer which is absent in other Sirolimus eluting stents used at our center but that needs to be further investigated. We also found some patients who developed giant aneurysms including Left main aneurysms. In our series operative repair of these patients had better outcomes than covered stent deployment but larger trials maybe needed to confirm the same.

Conclusions

Coronary artery aneurysms after stent implantation are rare but occasionally giant aneurysms are formed with a toxic course. The incidence and morphology of aneurysms after Everolimus and Sirolimus eluting stent deployment do not differ much.
Influence of angle alpha on visual quality after implantation of extended depth of focus intraocular lenses
Authors: Qin Miaomiao , Ji Min , Zhou Tianqiu , Yuan Yurong , Luo Jiawei , Li Pengfei , Wang Ying , Chen Xiaojuan , Chen Wei , Guan Huaijin
Published: February 2022

Background

To assess postoperative changes in angle alpha, and to evaluate the postoperative visual quality of patients with different angle alpha values after implantation of extended depth of focus (EDOF) intraocular lenses (IOLs).

Methods

Seventy-nine eyes of 79 patients who had phacoemulsification with EDOF IOLs implantation were enrolled. A cut-off value of 0.3 mm, 0.4 mm, and 0.5 mm in preoperative angle alpha was chosen to divide eyes into groups. Distance, intermediate, and near visual acuities, modulation transfer function (MTF), and aberrations were recorded during a 6-month follow-up. A patient questionnaire was completed.

Results

There were no significant differences in angle alpha postoperatively compared to preoperatively. No significant differences were found in visual acuity and MTF between all groups. With 5 mm pupil diameter, there were significant differences of higher-order aberrations and spherical aberration in ocular aberration and internal aberration between angle alpha<0.4 mm and angle alpha≥0.4 mm. Additionally, significant differences of coma were also added in cut-off value of 0.5 mm. When the value of angle alpha is 0.4 mm or higher, there were significant differences in the score of halos and glare.

Conclusions

Angle alpha did not affect visual acuity, but the value of 0.4 mm or higher in angle alpha affected the visual quality under scotopic conditions and occurrence of halos and glare. For patients with 0.4 mm or higher in angle alpha, the choice to implant a EDOF IOL should be carefully considered.
A novel approach to button battery removal in a two-and-half year-old patient’s esophagus after ingestion: a case report
Authors: Wang Hung-Chun , Hu Shu-wei , Lin Ke Jian , Chen An-Chyi
Published: February 2022

Background

Accidental swallowing of a foreign body occurs more frequently in children than in adults. Among these cases, button battery impaction in the esophagus may cause severe complications. While prevention is always ideal, if button battery impaction is suspected, immediate diagnosis and retrieval are important.

Case presentation

We introduce a novel method for retrieval of a button battery after ingestion by a 2.5-year-old child. When the patient arrived at our center, the battery was incarcerated in the upper esophagus. The battery could not be removed, despite the use of several methods such as alligator forceps under endoscopy and net retrieval. We decided to use a novel method that combined endoscopic balloon extraction and forceps retrieval. This resulted in a push-and-pull effect, creating synergy and easy removal of the battery. There were no long term complications based on the follow-up endoscopy examination.

Conclusions

This new procedure was very effective for removing the esophageal foreign body. When button battery in esophagus was too tight to be removed by the traditional retrieval methods, this procedure was suggested to use. It could be performed at medical institutions. If it fails or esophageal perforation (iatrogenic or spontaneous) occurs, pediatric surgeons could take over immediately.
Determinants of never-treated status in rural versus urban contexts for individuals with schizophrenia in a population-based study in China
Authors: Yang Lawrence H. , Phillips Michael R. , Li Xianyun , Yu Gary , Grivel Margaux M. , Zhang Jingxuan , Shi Qichang , Ding Zhijie , Pang Shutao , Susser Ezra
Published: February 2022

Background

A goal of China’s 2012 National Mental Health Law is to improve access to services and decrease urban versus rural disparities in services. However, pre-reform data is needed for objective evaluation of these reforms’ effectiveness. Accordingly, this study compares the pre-reform utilization of medical services for the treatment of schizophrenia in rural and urban communities in China.

Methods

In a large community-based study in four provinces representing 12% of China’s population conducted from 2001 to 2005, we identified 326 individuals with schizophrenia (78 never treated). Comparing those living in urban (n = 86) versus rural (n = 240) contexts, we used adjusted Poisson regression models to assess the relationship of ‘never treated’ status with family-level factors (marital status, family income, and number of co-resident family members) and illness severity factors (age of onset, symptom severity and functional impairment).

Results

Despite similar impairments due to symptoms, rural patients were less likely to have received intensive mental health services (i.e., use psychiatric inpatient services), and appeared more likely to be ‘never treated’ or to only have received outpatient care. Among rural patients, only having more than four co-resident family members was independently associated with ‘never-treated’ status (RR = 0.34; 95% CI, 0.12–0.94; p = 0.039). Among urban patients, only older age of onset was independently associated with ‘never-treated’ status (RR = 1.06; 95% CI 1.02–1.10, p = 0.003).

Conclusions

Identifying differential drivers of service utilization in urban and rural communities is needed before implementing policies to improve the utilization and equity of services and to define metrics of program success.
Maternal mortality trends in Spain during the 2000-2018 period: the role of maternal origin
Authors: García-Tizón Larroca Santiago , Arévalo-Serrano Juan , Ruiz Minaya Maria , Paya Martinez Pilar , Perez Fernandez Pacheco Ricardo , Lizarraga Bonelli Santiago , De Leon Luis Juan
Published: February 2022

Background

The available literature indicates that there are significant differences in maternal mortality according to maternal origin in high income countries. The aim of this study was to examine the trend in the maternal mortality rate and its most common causes in Spain in recent years and to analyse its relationship with maternal origin.

Methods

This was a cross-sectional study of all live births as well as those resulting in maternal death in Spain during the period between 2000 and 2018. A descriptive analysis of the maternal mortality rate by cause, region of birth, maternal age, marital status, human development index and continent of maternal origin was performed. The risk of maternal death was calculated using univariate and multivariate logistic regression analyses, with adjustment for certain variables included in the descriptive analysis.

Results

There was a total of 293 maternal deaths and 8,439,324 live births during the study period. The most common cause of maternal death was hypertensive disorders of pregnancy. The average maternal death rate was 3.47 per 100,000 live births. The risk of suffering from this complication was higher for immigrant women from less developed countries. The adjusted effect of maternal HDI score over maternal mortality was OR = 0.976; 95% CI 0.95 – 0.99; p = 0.048; therefore, a decrease of 0.01 in the maternal human development index score significantly increased the risk of this complication by 2.4%.

Conclusions

The results of this study indicate that there are inequalities in maternal mortality according to maternal origin in Spain. The human development index of the country of maternal origin could be a useful tool when estimating the risk of this complication, taking into account the origin of the pregnant woman.
Bone transport combined with bone graft and internal fixation versus simple bone transport in the treatment of large bone defects of lower limbs after trauma
Authors: Huang Qiang , Xu Yi Bo , Ren Cheng , Li Ming , Zhang Cheng Cheng , Liu Lu , Wang Qian , Lu Yao , Lin Hua , Li Zhong , Xue Han Zhong , Zhang Kun , Ma Teng
Published: February 2022

Background

Bone transport has been successfully applied for the management of large segmental bone defects. However, its main shortcoming is the long-lasting consolidation period, which may cause lots of related complications. To overcome this shortcoming, we developed bone transport combined with bone graft and internal fixation technique. The purpose of this study was to compare the clinical effects of this modified technique with simple bone transport in the treatment of large segmental bone defects of lower limbs after trauma.

Methods

Eighty-four patients with large segmental bone defects treated in our institution from January 2014 to January 2017 were selected for retrospective study. A total of 77 cases were completely followed. Among them, 35 patients were treated by bone transport combined with bone graft and internal fixation technique (Group A), and 42 by simple bone transport technique (Group B). Patients with open injuries were classified according to Gustilo-Anderson (GA) classification. The general data of Group A and B were compared. The time in external fixator, total cure time and operation times of two groups were recorded. Ennecking score was used to evaluate the recovery of limb functions while self-rating anxiety scale (SAS) for the postoperative anxiety evaluation. In addition, the total complication incidence was compared between Group A and B.

Results

There was no significant difference in demographic data between Group A and B (p > 0.05). The time in external fixator of Group A and B was (4.8 ± 1.6) and (18.2 ± 3.9) months, respectively (p < 0.05). The total cure time was (17.6 ± 2.2) and (20.4 ± 2.8) months in Group A and B (p < 0.05). The number of operations in Group A and B was (4.9 ± 1.2) and (4.8 ± 1.0) (p > 0.05). Ennecking score of Group A and B was 84.7 and 75.7% (p < 0.05). SAS score and total complication incidence in Group A were significantly lower than those in Group B (p < 0.05).

Conclusions

The clinical effects of bone transport combined with bone graft and internal fixation technique were better than that of simple bone transport technique, including shorter time in external fixator, shorter total cure time, lower anxiety score and better limb functions.
Endoscopic surgery suturing techniques: a randomized study on learning
Authors: Voskens F. J. , van der Schans E. M. , Ruurda J. P. , Broeders I. A. M. J.
Published: February 2022

Background

Surgeons have widely adopted endoscopic suturing techniques using conventional laparoscopic instruments and the more advanced robotic systems. The FlexDex is a novel articulating laparoscopic needle driver providing enhanced dexterity in laparoscopic surgery. This study evaluates and compares the learning curve of endoscopic suturing with conventional laparoscopy, the FlexDex and robotic suturing in novices.

Methods

Participants performed a minimal invasive suturing task in three different ways in a randomized order: with a conventional laparoscopic needle driver, using the FlexDex needle driver and third, using the Da Vinci Si surgical system. Primary outcome was suturing task time. Secondary outcome parameters were assessment of suturing quality and workload perception.

Results

A total of 10 novice participants were included and completed a total of 300 sessions. Median (IQR) suturing time of the first 5 sessions was 231 s (188–291) in the laparoscopic group versus 378 s (282–471) in the FlexDex group versus 189 s (160–247) in the DaVinci Si group. The last 5 sessions showed significant reduction of median suturing time of 143 s (120–190), 232 s (180–265) and 172 s (134–199) respectively. Analysis identified that the learning curve for the laparoscopic needle driver and Da Vinci Si was reached in 5 sessions, compared to 8 sessions for the Flexdex. The laparoscopic needle driver and Da Vinci Si showed a significant shorter median suturing time compared to the FlexDex (p = 0.00). The FlexDex quality assessment scores were significantly lower compared to the laparoscopic (p = 0.00) and robotic (p = 0.00) scores and perceived workload remains high for the FlexDex users.

Conclusions

Ex vivo endoscopic suturing with the FlexDex demonstrated a prolonged learning curve compared to laparoscopic and robotic suturing. The learning curve of the FlexDex is fundamentally different from conventional laparoscopic and robotic instruments. This study provides further insights in the implementation and training of endoscopic suturing techniques.
Effectiveness of problem-based learning methodology in undergraduate medical education: a scoping review
Authors: Trullàs Joan Carles , Blay Carles , Sarri Elisabet , Pujol Ramon
Published: February 2022

Background

Problem-based learning (PBL) is a pedagogical approach that shifts the role of the teacher to the student (student-centered) and is based on self-directed learning. Although PBL has been adopted in undergraduate and postgraduate medical education, the effectiveness of the method is still under discussion. The author’s purpose was to appraise available international evidence concerning to the effectiveness and usefulness of PBL methodology in undergraduate medical teaching programs.

Methods

The authors applied the Arksey and O’Malley framework to undertake a scoping review. The search was carried out in February 2021 in PubMed and Web of Science including all publications in English and Spanish with no limits on publication date, study design or country of origin.

Results

The literature search identified one hundred and twenty-four publications eligible for this review. Despite the fact that this review included many studies, their design was heterogeneous and only a few provided a high scientific evidence methodology (randomized design and/or systematic reviews with meta-analysis). Furthermore, most were single-center experiences with small sample size and there were no large multi-center studies. PBL methodology obtained a high level of satisfaction, especially among students. It was more effective than other more traditional (or lecture-based methods) at improving social and communication skills, problem-solving and self-learning skills. Knowledge retention and academic performance weren’t worse (and in many studies were better) than with traditional methods. PBL was not universally widespread, probably because requires greater human resources and continuous training for its implementation.

Conclusion

PBL is an effective and satisfactory methodology for medical education. It is likely that through PBL medical students will not only acquire knowledge but also other competencies that are needed in medical professionalism.
Attitudes about withholding or withdrawing life-prolonging treatment, euthanasia, assisted suicide, and physician assisted suicide: a cross-sectional survey among the general public in Croatia
Authors: Borovecki Ana , Curkovic Marko , Nikodem Krunoslav , Oreskovic Stjepan , Novak Milivoj , Rubic Filip , Vukovic Jurica , Spoljar Diana , Gordijn Bert , Gastmans Chris
Published: February 2022

Background

There has been no in-depth research of public attitudes on withholding or withdrawing life-prolonging treatment, euthanasia, assisted suicide and physician assisted suicide in Croatia. The aim of this study was to examine these attitudes and their correlation with sociodemographic characteristics, religion, political orientation, tolerance of personal choice, trust in physicians, health status, experiences with death and caring for the seriously ill, and attitudes towards death and dying.

Methods

A cross-sectional study was conducted on a three-stage random sample of adult citizens of the Republic of Croatia, stratified by regions, counties, and locations within those counties (N = 1203). In addition to descriptive statistics, ANOVA and Chi-square tests were used to determine differences, and factor analysis (component model, varimax rotation and GK dimensionality reduction criterion), correlation analysis (Bivariate correlation, Pearson’s coefficient) and multiple regression analysis for data analysis.

Results

38.1% of the respondents agree with granting the wishes of dying people experiencing extreme and unbearable suffering, and withholding life-prolonging treatment, and 37.8% agree with respecting the wishes of such people, and withdrawing life-prolonging treatment. 77% of respondents think that withholding and withdrawing procedures should be regulated by law because of the fear of abuse. Opinions about the practice and regulation of euthanasia are divided. Those who are younger and middle-aged, with higher levels of education, living in big cities, and who have a more liberal worldview are more open to euthanasia. Assisted suicide is not considered to be an acceptable practice, with only 18.6% of respondents agreeing with it. However, 40.1% think that physician assisted suicide should be legalised. 51.6% would support the dying person’s autonomous decisions regarding end-of-life procedures.

Conclusions

The study found low levels of acceptance of withholding or withdrawing life-prolonging treatment, euthanasia, assisted suicide and physician assisted suicide in Croatia. In addition, it found evidence that age, level of education, political orientation, and place of residence have an impact on people’s views on euthanasia. There is a need for further research into attitudes on different end-of-life practices in Croatia.
Clinical and operational insights from data-driven care pathway mapping: a systematic review
Authors: Manktelow Matthew , Iftikhar Aleeha , Bucholc Magda , McCann Michael , O’Kane Maurice
Published: February 2022

Background

Accumulated electronic data from a wide variety of clinical settings has been processed using a range of informatics methods to determine the sequence of care activities experienced by patients. The “as is” or “de facto” care pathways derived can be analysed together with other data to yield clinical and operational information. It seems likely that the needs of both health systems and patients will lead to increasing application of such analyses. A comprehensive review of the literature is presented, with a focus on the study context, types of analysis undertaken, and the utility of the information gained.

Methods

A systematic review was conducted of literature abstracting sequential patient care activities (“de facto” care pathways) from care records. Broad coverage was achieved by initial screening of a Scopus search term, followed by screening of citations (forward snowball) and references (backwards snowball). Previous reviews of related topics were also considered. Studies were initially classified according to the perspective captured in the derived pathways. Concept matrices were then derived, classifying studies according to additional data used and subsequent analysis undertaken, with regard for the clinical domain examined and the knowledge gleaned.

Results

254 publications were identified. The majority (n = 217) of these studies derived care pathways from data of an administrative/clinical type. 80% (n = 173) applied further analytical techniques, while 60% (n = 131) combined care pathways with enhancing data to gain insight into care processes.

Discussion

Classification of the objectives, analyses and complementary data used in data-driven care pathway mapping illustrates areas of greater and lesser focus in the literature. The increasing tendency for these methods to find practical application in service redesign is explored across the variety of contexts and research questions identified. A limitation of our approach is that the topic is broad, limiting discussion of methodological issues.

Conclusion

This review indicates that methods utilising data-driven determination of de facto patient care pathways can provide empirical information relevant to healthcare planning, management, and practice. It is clear that despite the number of publications found the topic reviewed is still in its infancy.
Diagnosis and treatment of vulnerable migrants: a retrospective study at a Doctors of the World clinic in Stockholm
Authors: Nordenskiöld Klas Ytterbrink , Olsson Jan-Eric , Bertilson Bo C
Published: February 2022

Background

At Doctors of the World Medical Clinic in Stockholm (DWMCS), medical care is offered to migrants who live under particularly vulnerable conditions and who lack access to subsidized care. The demographic, diagnostic and therapeutic panorama of vulnerable migrants is unknown.

Methods

A quantitative, retrospective study mapping gender, age, diagnostic group, primary diagnosis, therapeutics, referrals, and session timing (whether the care session took place in summer -April to September, or winter - October to March) by reading all patients’ electronic journals at DWMCS between 2014-04-01 and 2017-12-31. Diagnostic groups were classified according to the classification system ICPC-2 which contains six diagnostic groups: symptoms/complaints, infections, neoplasms, injuries, congenital anomalies and other diagnoses. Primary diagnosis was defined as the diagnosis that was first in the diagnosis list for the visit. Difference in median age was calculated with the Mann-Whitney test (MW), and two-group analysis of nominal data was performed with Monte Carlo simulations (MC) and chi square test´s (X2).

Results

The study included 1323 patients: 838 women and 485 men. The median age for women 37 years (29-47) was slightly lower than for men, 40 years (31-47) MW (p = 0.002). The largest diagnostic group was symptoms / complaints. The five most common primary diagnoses were cough (4%), back symptom / complaint (4%), cystitis (3%), upper respiratory infection acute (3%) and abdominal pain epigastric (2%). The most common therapeutic (55%) was pharmaceutical. Referrals accounted for 12% of the therapeutics and 25% of the referrals were to an emergency room. Tests of significance indicated an uneven distribution of diagnostic groups MC (p = 0.003), infectious primary diagnoses MC (p = 0.0001) and referrals MC (p = 0.006) between men and women and an uneven seasonal distribution among the Other diagnoses MC (0.04) and ten most common drug treatments MC (p=0.002).

Conclusions

The demographic, diagnostic and therapeutic panorama of vulnerable migrants at DWMCS was elucidated. Vulnerable migrants have differences in morbidity depending on gender and season, differences in therapeutics depending on gender and differences among their most common drug treatments depending on season. This knowledge is important when addressing the health problems of vulnerable migrants.
Empagliflozin does not reverse lipotoxicity-induced impairment in human myeloid angiogenic cell bioenergetics
Authors: Cinquegrani Gloria , Spigoni Valentina , Fantuzzi Federica , Bonadonna Riccardo C. , Dei Cas Alessandra
Published: February 2022

Background

Empagliflozin can curb inflammation and oxidative stress, through sodium-proton exchanger (NHE) inhibition, in a model of lipotoxicity in human myeloid angiogenic cells (MAC), which mediate endothelial repairing processes. Aim of this study is to assess in human MAC whether: (1) Stearic acid (SA) induced inflammation and increase in oxidant stress is accompanied by bioenergetic alterations; (2) empagliflozin anti-lipotoxic action is concomitant with coherent changes in bioenergetic metabolism, possibly via NHE blockade.

Methods

MAC were isolated from peripheral blood of healthy volunteers and incubated in the presence/absence of SA (100 μM for 3 h) with/without empagliflozin (EMPA 100 μM) or amiloride (Ami 100 μM) for 1 h. Cell respiration (oxygen consumption rate OCR) and anaerobic glycolysis (measured as proton production rate) were recorded in real-time by Seahorse technology, and ATP production (anaerobic glycolysis- and oxphos-derived) rates were calculated.

Results

SA, at the concentration causing inflammation and increased oxidant stress, altered cell bioenergetics of human MAC, with overall reductions in basal OCR and oxphos-derived ATP production (all p < 0.05), pointing to mitochondrial alterations. EMPA, at the concentration counteracting SA-induced lipotoxicity, both alone and in the presence of SA, caused NHE-independent extensive bioenergetic alterations (from p < 0.05 to p < 0.01), greater than those induced by SA alone.

Conclusions

In human MAC: (1) SA altered cell bioenergetics, concomitantly with inflammation and oxidant stress; (2) EMPA possibly inhibited mitochondrial respiration, (3) the protective effect of EMPA against SA-induced lipotoxicity was unlikely to be mediated through bioenergetic metabolism.
Ideational factors associated with net care behaviour: a multi-country analysis
Authors: Kumoji E. ‘Kuor , Awantang Grace N. , Toso Michael , Kamara Diarra , Bleu Thérèse , Lahai Wani , Sillah-Kanu Musa , Dosso Abdul , Achu Dorothy , Babalola Stella
Published: February 2022

Background

Malaria is endemic to sub-Saharan African countries. Mass and routine distribution, promotion, and use of ITNs are critical components of malaria prevention programmes. Correct and consistent use of insecticide-treated mosquito nets (ITN) is an effective strategy for malaria prevention. To extend bed-net lifespan, the World Health Organization recommends folding or tying up ITNs when they are not in use. This study analyses factors associated with net care practices in three African countries.

Methods

Researchers collected household data nationwide in Côte d’Ivoire, from the North and Far North regions of Cameroon, and from Port Loko and Bo districts in Sierra Leone, between 2018 and 2019. The dependent variable was respondents reporting that they fold or tie up their nets. The study adjusted for selected sociodemographic, ideational (psychosocial), and household variables using multilevel models. The analysis was limited to women of reproductive age and their male spouses/partners from households with at least one ITN: 2,940 respondents in Cameroon, 6,105 in Côte d’Ivoire, and 2,730 in Sierra Leone.

Results

Among respondents, 50.2% in Cameroon, 52.0% in Côte d’Ivoire and 75.6% in Sierra Leone reported folding or tying up their net when it was not in use. In all three countries, the data showed significant clustering at both household and community levels, indicating the influence of factors operating at these levels on net-care behaviour. The odds of reporting the behaviour varied significantly by geographic unit in each country. Consistent use of nets was strongly correlated with net-care behaviour. Furthermore, five ideational variables were positively associated with the outcome behaviour in all three countries: positive attitude towards net care, perceived susceptibility for malaria, response-efficacy of ITNs, perceived self-efficacy for net use, and the perception that net use was a community norm. Additional significant ideational variables included positive attitudes towards net use (Cameroon and Côte d’Ivoire), perceived severity of malaria (Côte d’Ivoire), and interpersonal communication about malaria (Côte d’Ivoire).

Conclusions

The study identified ideational variables associated with recommended net-care practice. Programme efforts designed to promote net-care practices and extend average lifespan of ITNs may be more effective if they emphasize positive attitudes towards net care, perceived susceptibility of malaria infection, response-efficacy of ITNs, perceived self-efficacy for net use, and promote net-care behaviour as a positive community norm.
Homologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular mechanisms
Authors: Wang Yang , Zhang Liang , Zhao Guosheng , Zhang Yuan , Zhan Fangbiao , Chen Zhiyu , He Tao , Cao Yang , Hao Lan , Wang Zhigang , Quan Zhengxue , Ou Yunsheng
Published: February 2022

Background

No prominent advancements in osteosarcoma (OS) treatment have been made in the past 20 years. Although photodynamic therapy (PDT) is an emerging technique for cancer therapy, the lack of targeted photosensitizers for OS treatment severely limits its applications.

Results

In this study, we constructed a potential theranostic nanoplatform by using (poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) encapsulating IR780 into the shell (PLGA-IR780 NPs), which were further camouflaged with human OS cell membranes from the HOS cell line (MH-PLGA-IR780 NPs). These constructed NPs showed the capacity for homologous targeting with excellent photoacoustic (PA)/fluorescence (FL) imaging ability. Benefitting from their homologous targeting capacity, MH-PLGA-IR780 NPs obviously promoted cell endocytosis in vitro and tumor accumulation in vivo, which could further improve PDT performance under near-infrared (NIR) irradiation. In addition, to their homologous targeting and PA/FL dual-mode imaging ability, MH-PLGA-IR780 NPs had advantages in penetrating deeper into tumor tissues and in real-time dynamic distribution monitoring in vivo, which laid a foundation for further clinical applications in OS. Moreover, we demonstrated that PDT guided by the constructed NPs could significantly induce HOS cells apoptosis and ferroptosis via excessive accumulation of reactive oxygen species (ROS), and further determined that the potential anticancer molecular mechanism of apoptosis was triggered by the release of cytochrome c-activated mitochondrial apoptosis (endogenous apoptosis), and that ferroptosis caused the activation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and the inactivation of glutathione peroxidase 4 (GPX4), synergistically leading to excessive accumulation of Lipid-ROS and Lipid peroxides (LPOs). Concurrently, MH-PLGA-IR780 NPs-guided PDT also showed an obvious inhibitory effect on tumor growth in vivo.

Conclusion

These results suggest that this homologous targeting-based theranostic nanoplatform provides an effective method to improve PDT performance in OS and contributes a new and promising approach for OS therapy.

Graphical Abstract
Engineered a dual-targeting biomimetic nanomedicine for pancreatic cancer chemoimmunotherapy
Authors: Wang Meng , Hu Qida , Huang Junmin , Zhao Xinyu , Shao Shiyi , Zhang Fu , Yao Zhuo , Ping Yuan , Liang Tingbo
Published: February 2022

The therapeutic effect of chemotherapeutics such as gemcitabine against pancreatic cancer is considerably attenuated by immune-suppressive tumor microenvironment. Improvement of chemotherapeutic efficacy by targeting tumor-associated macrophage and reprograming tumor microenvironment to enhance their efficacy may become a promising strategy. To this end, we developed a biomimetic dual-targeting nanomedicine (PG@KMCM) where gemcitabine-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles are coated with a layer of bioengineered cancer cell membrane that stably expresses peptides targeting M2-like macrophages (M2pep) while reserving tumor-associated antigens (TAAs). The PG@KMCM nanomedicine enables the simultaneous targeted delivery of gemcitabine to pancreatic tumor sites and TAMs to potentiate its therapeutic effects. Furthermore, the combination of an immune checkpoint inhibitor (PD-L1 antibody) with PG@KMCM synergistically enhanced the anti-tumoral effect by reprogramming the immune-suppressive tumor microenvironment, including the elimination of PD-L1-positive macrophages and the downregulation of PD-L1 expression. Our study proved dual-targeting PG@KMCM nanomedicine in combination with PD-L1 immune checkpoint inhibitor therapy is able to effectively reprogram the tumor microenvironment and kill pancreatic cancer cells to enhance overall therapeutic potential.

Graphical Abstract
The MULTI-ACT model: the path forward for participatory and anticipatory governance in health research and care
Authors: Zaratin Paola , Bertorello Deborah , Guglielmino Roberta , Devigili Danilo , Brichetto Giampaolo , Tageo Valentina , Dati Gabriele , Kramer Stephanie , Battaglia Mario Alberto , Di Luca Monica
Published: February 2022

The COVID-19 pandemic has unmasked even more clearly the need for research and care to form a unique and interdependent ecosystem, a concept which has emerged in recent years. In fact, to address urgent and unexpected missions such as “fighting all together the COVID-19 pandemic”, the importance of multi-stakeholder collaboration, mission-oriented governance and flexibility has been demonstrated with great efficacy. This calls for a policy integration strategy and implementation of responsible research and innovation principles in health, promoting an effective cooperation between science and society towards a shared mission. This article describes the MULTI-ACT framework and discusses how its innovative approach, encompassing governance criteria, patient engagement and multidisciplinary impact assessment, represents a holistic management model for structuring responsible research and innovation participatory governance in brain conditions research.
Intrinsically disordered proteins play diverse roles in cell signaling
Authors: Bondos Sarah E. , Dunker A. Keith , Uversky Vladimir N.
Published: February 2022

Signaling pathways allow cells to detect and respond to a wide variety of chemical (e.g. Ca2+or chemokine proteins) and physical stimuli (e.g., sheer stress, light). Together, these pathways form an extensive communication network that regulates basic cell activities and coordinates the function of multiple cells or tissues. The process of cell signaling imposes many demands on the proteins that comprise these pathways, including the abilities to form active and inactive states, and to engage in multiple protein interactions. Furthermore, successful signaling often requires amplifying the signal, regulating or tuning the response to the signal, combining information sourced from multiple pathways, all while ensuring fidelity of the process. This sensitivity, adaptability, and tunability are possible, in part, due to the inclusion of intrinsically disordered regions in many proteins involved in cell signaling. The goal of this collection is to highlight the many roles of intrinsic disorder in cell signaling. Following an overview of resources that can be used to study intrinsically disordered proteins, this review highlights the critical role of intrinsically disordered proteins for signaling in widely diverse organisms (animals, plants, bacteria, fungi), in every category of cell signaling pathway (autocrine, juxtacrine, intracrine, paracrine, and endocrine) and at each stage (ligand, receptor, transducer, effector, terminator) in the cell signaling process. Thus, a cell signaling pathway cannot be fully described without understanding how intrinsically disordered protein regions contribute to its function. The ubiquitous presence of intrinsic disorder in different stages of diverse cell signaling pathways suggest that more mechanisms by which disorder modulates intra- and inter-cell signals remain to be discovered.

Graphical abstract
Comparing different machine learning techniques for predicting COVID-19 severity
Authors: Xiong Yibai , Ma Yan , Ruan Lianguo , Li Dan , Lu Cheng , Huang Luqi ,   the National Traditional Chinese Medicine Medical Team
Published: February 2022

Background

Coronavirus disease 2019 (COVID-19) is still ongoing spreading globally, machine learning techniques were used in disease diagnosis and to predict treatment outcomes, which showed favorable performance. The present study aims to predict COVID-19 severity at admission by different machine learning techniques including random forest (RF), support vector machine (SVM), and logistic regression (LR). Feature importance to COVID-19 severity were further identified.

Methods

A retrospective design was adopted in the JinYinTan Hospital from January 26 to March 28, 2020, eighty-six demographic, clinical, and laboratory features were selected with LassoCV method, Spearman’s rank correlation, experts’ opinions, and literature evaluation. RF, SVM, and LR were performed to predict severe COVID-19, the performance of the models was compared by the area under curve (AUC). Additionally, feature importance to COVID-19 severity were analyzed by the best performance model.

Results

A total of 287 patients were enrolled with 36.6% severe cases and 63.4% non-severe cases. The median age was 60.0 years (interquartile range: 49.0–68.0 years). Three models were established using 23 features including 1 clinical, 1 chest computed tomography (CT) and 21 laboratory features. Among three models, RF yielded better overall performance with the highest AUC of 0.970 than SVM of 0.948 and LR of 0.928, RF also achieved a favorable sensitivity of 96.7%, specificity of 69.5%, and accuracy of 84.5%. SVM had sensitivity of 93.9%, specificity of 79.0%, and accuracy of 88.5%. LR also achieved a favorable sensitivity of 92.3%, specificity of 72.3%, and accuracy of 85.2%. Additionally, chest-CT had highest importance to illness severity, and the following features were neutrophil to lymphocyte ratio, lactate dehydrogenase, and D-dimer, respectively.

Conclusions

Our results indicated that RF could be a useful predictive tool to identify patients with severe COVID-19, which may facilitate effective care and further optimize resources.

Graphical Abstract
The clinical and radiological effectiveness of autologous bone marrow derived osteoblasts (ABMDO) in the management of avascular necrosis of femoral head (ANFH) in sickle cell disease (SCD)
Authors: Sadat-Ali Mir , Al-Omran Abdallah S. , AlTabash Khalid , Acharya Sadananda , Hegazi Tarek M. , Al Muhaish Mona I.
Published: February 2022

Purpose

Avascular necrosis of the femoral head is a common issue faced by orthopaedic surgeons that ranges between 10 and 18%, but in patients with SCD, the incidence reaches 30%. There is no definite treatment except joint arthroplasty. Regenerative medicine is an option to cure or delay joint arthroplasty. We report here our experience with the injection of ABMDO to manage ANFH and report our medium-term results, the progression of the ANFH if any and the delay in total hip arthroplasty. (THA).

Methods

Sixty-Three (63) patients with SCD and ANFH were examined and thoroughly investigated, and those who had ANFH < grade II were consented to receive ABMDO. Patients were clinically assessed preoperatively using the Visual analogue scale (VAS), Modified Harris Hips Score (MHHS) and Azam-Sadat Score (ASS) for Quality of Life Score for Chronic Hip Disease. Ten millilitres of bone marrow were aspirated under local anaesthesia and placed in 20 CC of culture media. Osteoblasts were cultured from the aspirated bone marrow. Under anaesthesia, the osteonecrosed lesion was drilled using a 3-mm cannulated drill, and 5 million osteoblasts were injected at the lesion site. Patients were evaluated in the outpatient clinic after 2 weeks. At 4 months, a repeat MRI was done, and patients were followed for a minimum of 2 years.

Results

The average age of patients was 25.93 ± 5.48 years. There were 41 (65%) females and 22 (35%) males. The mean hemoglobin S was 83.2 ± 5.1%. The average follow-up was 49.05 ± 12.9 (range: 24–60) months. TheVAS significantly improved from 7.79 ± 1.06 initially to 4.07 ± 1.08 (p < 0.0001) at 2 weeks and continued to improve for the next 24 months, when it was 2.38 ± 0.55 (p < 0.0001). The MHHS improved from 41.77 ± 5.37 initially to 73.19 ± 6.48 at 4 months (p < 0.001), and at 24 months, it was 88.93 ± 3.6 (p < 0.001). The ASS also significantly improved from 2.76 ± 0.49 preoperatively to 7.92 ± 0.09 (p < 0.0001) at 24 months. A comparison of the MRI’s from before and after the osteoblast implantation revealed new bone formation and amelioration of the avascular lesions. Three patients were unsatisfied with their outcomes. and one patient suffered a repeat attack of the vaso-occlusive crisis within 6 months of the osteoblast injection.

Conclusions

The results give credence to our earlier short follow-up results showing that osteoblast transplantation has great potential in the healing of avascular lesions. Our study fits the criteria of a Phase II clinical trial, and we believe a larger study equivalent to Phase III numbers should be conducted and include patients with not only SCD but also steroid-induced and idiopathic avascular necrosis.

Level of evidence

II
Use of the painDETECT to discriminate musculoskeletal pain phenotypes
Authors: Bittencourt Juliana Valentim , Bezerra Márcia Cliton , Pina Mônica Rotondo , Reis Felipe José Jandre , de Sá Ferreira Arthur , Nogueira Leandro Alberto Calazans
Published: February 2022

Background

Musculoskeletal pain patients present similar pain characteristics regardless of the clinical diagnosis. PainDETECT questionnaire is useful for screening neuropathic-like symptoms in many musculoskeletal conditions. However, no previous studies compared pain phenotypes of patients with musculoskeletal pain using the painDETECT. Therefore, the current study aimed to compare the pain characteristics of patients with musculoskeletal pain classified according to the painDETECT as nociceptive pain, unclear, and neuropathic-like symptoms.

Methods

A cross-sectional study was conducted in 308 participants with musculoskeletal pain. Demographic and clinical characteristics of the participants were examined. Neuropathic-like symptoms, pain intensity, pain area, Central Sensitization-related sign and symptoms, functional limitation, and conditioned pain modulation were assessed in patients with musculoskeletal pain. Independent one-way analysis of variance (ANOVA) was used to test for between-group differences for the outcome measures with continuous variables and Pearson chi-square test verified between-group differences on the efficiency of the conditioned pain modulation.

Results

Participants had a mean age of 52.21 (±15.01) years old and 220 (71.42%) were females. One hundred seventy-three (56.16%) participants present nociceptive pain, 69 (22.40%) unclear, and 66 (21.42%) neuropathic-like symptoms. A one-way ANOVA showed differences for the pain intensity [F (2,305) = 20.097; p < .001], pain area [F (2,305) = 28.525; p < .001], Central Sensitization-related sign and symptoms [F (2,305) = 54.186; p < .001], and functional limitation [F (2,256) = 8.061; p < .001]. However, conditioned pain modulation was similarly impaired among the three groups (X2 = 0.333, p = 0.847).

Conclusion

Patients with neuropathic-like symptoms revealed unfavorable pain characteristics compared to their counterparts, including pain intensity, generalized pain, Central Sensitization-related sign and symptoms, and functional limitation.