bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive value of ischemia location on multimodal CT in thrombectomy-treated patients
Authors: Aguirre Clara , Trillo Santiago , Ramos Carmen , Zapata-Wainberg Gustavo , Sanz-García Ancor , Ximénez-Carrillo Álvaro , Barbosa Antonio , Caniego José L , Vivancos José
Published: October 2022

Objective

Alberta Stroke Program Early CT Score (ASPECTS) applied to CT-perfusion (CTP) and CT-angiography-source-images (CTA-SI) may improve outcome prediction in large vessel occlusion (LVO) stroke if compared to non-contrast CT (NCCT) alone. Besides, ischemia location may have enhanced capabilities, compared to ischemia volume alone, in predicting stroke outcomes. We aim to evaluate the association between ischemia location as measured by ASPECTS regions in NCCT, CTP maps and CTA-SI and 3 months outcome in patients with LVO treated with mechanical thrombectomy (MT).

Material and methods

Consecutive patients with anterior circulation stroke treated with MT were recorded in a prospectively maintained database at a single center. Modified Rankin scale (mRS) at 3 months >2 was considered a poor outcome. Association of patients’ characteristics, NCCT, CTP, and CTA-SI parameters with outcome was evaluated using single-variable analysis and binary logistic regression multivariate analysis for each imaging technique.

Results

177 patients were included. 115 (65%) patients reached a favorable outcome. The involvement of lenticular, caudate, M1, or M2 in all imaging techniques, insula in NCCT and CTA-SI and M5 in CBV maps and CTA-SI was related to functional outcome in bivariate analysis. However, in the multivariate analysis, none ischemia location was independently related to outcome, no matter the imaging technique studied. This finding remained unchanged when restricted to patients with good recanalization and when analyzing subpopulations according to hemisphere involvement or territories association.

Conclusions

Our study suggests ischemia location shouldn’t be used solely for decision-making in LVO stroke patients. Its predictive value may be taken in consideration together with other clinical and radiological variables.
Incidence and associated factors of acute postoperative pain within the first 24 h in women undergoing cesarean delivery at a resource-limited setting in Addis Ababa, Ethiopia: A prospective observational study
Authors: Bimrew Dagim , Misganaw Abebaw , Samuel Hirbo , Daniel Desta Tenbite , Bayable Samuel Debas
Published: October 2022

Objective:

This study aimed to assess the incidence and associated factors of acute postoperative pain after cesarean section within the first 24 h of postoperative period.

Methods:

An institutional-based prospective observational study was conducted on parturients who had undergone cesarean section in Gandhi Memorial Hospital from 1 December 2019 to 28 February 2020. A numerical rating scale was used to evaluate the incidence of acute postoperative pain. Patients having a pain score of >4 were considered having moderate-to-severe pain on numerical rating scale. Data were analyzed using SPSS version 20. Bivariable and multivariable logistic regression were used to assess the association of variables. A p value of less than 0.05 was taken as significant association with dependent variables.

Result:

In total, 290 parturients participated in the study with a response rate of 98%. Moderate-to-severe acute postoperative pain after cesarean section was 76.2% (95% confidence interval: 71%, 81%) in the first 24 h postoperatively. On multivariable analysis, previous cesarean section history (adjusted odds ratio: 2.80, 95% confidence interval: 1.40, 5.55; p = 0.003), preoperative anxiety (adjusted odds ratio: 2.70, 95% confidence interval: 1.45, 5.05; p = 0.003), transverse incision type (adjusted odds ratio: 3.35, 95% confidence interval: 1.67, 6.72; p = 0.002), and incision length (adjusted odds ratio: 2.46, 95% confidence interval: 1.24, 4.85; p = 0.009) were identified as risk factors for postoperative moderate-to-severe acute pain.

Conclusion:

The incidence of moderate-to-severe postoperative pain was high in the first 24-h postoperative period; this indicates that pain management after cesarean section was treated inadequately. History of previous cesarean section, preoperative anxiety, transverse incision, and incision length >10 cm were the factors of postoperative acute pain after cesarean section. Therefore, we suggest the study institution develop a protocol for pain management.
Covid-19 Protesters and the Far Right on Telegram: Co-Conspirators or Accidental Bedfellows?
Authors: Curley Cliona , Siapera Eugenia , Carthy Joe
Published: October 2022

The COVID-19 pandemic led to the creation of a new protest movement, positioned against government lockdowns, mandatory vaccines, and related measures. Efforts to control misinformation by digital platforms resulted in take downs of key accounts and posts. This led some of these protest groups to migrate to platforms with less stringent content moderation policies, such as Telegram. Telegram has also been one of the destinations of the far right, whose deplatforming from mainstream platforms began a few years ago. Given the co-existence of these two movements on Telegram, the article examines their connections. Empirically, the article focused on Irish Telegram groups and channels, identifying relevant protest movements and collecting their posts. Using computational social science methods, we examine whether far-right terms and discourses are present and how this varies across different clusters of Telegram Covid-19 protest groups. In addition, we examine which actors are posting far-right content and what kind of roles they play in the network of Telegram groups. The findings indicate the presence of far-right discourses among the COVID-19 groups. However, the existence of these groups was not solely driven by the extreme right, and the incidence of far-right discourses was not equal across all COVID-19 protest groups. We interpret these findings under the prism of the mediation opportunity structure: while the far right appears to have taken advantage of the network opportunity structure afforded by deplatforming and the migration to Telegram, it did not succeed in diffusing its ideas widely among the COVID-19 protest groups in the Irish Telegram.
Higher education beyond SDG 4: China’s scholarship provision in the Global South
Authors: Yuan Tingting
Published: October 2022

In international development of education, the United Nation’s Sustainable Development Goal four monitors the scholarships offered by Western donors to developing countries. This paper, based on a qualitative study with 43 students from 26 developing countries, examined the foreign students’ perceptions of Chinese scholarships. By looking at students’ scholarship application, university experience and post-study plans, the findings revealed a centralised multi-level scholarship system, in particular attracting post-graduate students. The language of instruction in both Chinese and English, knowledge in shared development contexts and the perceived good value for future career had a combined effect to the students’ experience. In considering education as a cultural political economic ensemble in the global context, the paper concluded that China’s scholarship and higher education practice, serving the country’s soft power and representing South-South Cooperation, contributed to the global education targets from both quantity and quality dimensions but could step further towards education for social and global justice.
Pain Is the Most Frequently Cited Reason Athletes Fail to Return to Sport After Ulnar Collateral Ligament Surgery: A Systematic Review and Meta-analysis
Authors: Fathi Amir , Haratian Aryan , Treloar Joshua , Bolia Ioanna K. , Hasan Laith K. , Weber Alexander E. , Petrigliano Frank A.
Published: October 2022

Background:

No previous systematic review to our knowledge has examined the reasons that athletes fail to return to sport (RTS) after ulnar collateral ligament (UCL) surgery.

Purpose:

To report the rate of failure to RTS after UCL surgery and identify reasons that preclude an athlete’s ability to successfully RTS.

Study Design:

Systematic review; Level of evidence, 4.

Methods:

This study was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched the PubMed, Scopus, and SPORTDiscus databases for studies on athletes who underwent either UCL reconstruction or repair that reported RTS rates and identified reasons for failure to RTS. Data were collected on the number of athletes included, average age, sport played, operative technique, average follow-up, rate of failure to RTS, and reasons for failure to return. A random-effects model was used to conduct the meta-analysis.

Results:

Included were 26 studies reporting on 1019 athletes. Primary or revision UCL reconstruction was performed in 913 patients (89.6%), while the remaining 106 patients (10.4%) underwent UCL repair. The pooled rate of failure to RTS after UCL reconstruction or repair was calculated to be 11.4% (95% CI, 8.4-14.7). A significantly higher estimated proportion of athletes failed to return because of elbow-related reasons compared with non–elbow-related reasons (55.3% vs 40.6%; P = .0352). Persistent pain (29/103; 28.2%) was the most common reason for failure to return, followed by elbow limitations and other unspecified elbow problems (19/103; 18.4%). There was moderate evidence for publication bias and study heterogeneity across the included studies.

Conclusion:

This meta-analysis estimated the rate of failure to RTS after UCL surgery as 11.4%, with the majority of athletes unable to return because of elbow pain. Future studies reporting outcomes and providing details as to why athletes are unable to RTS can better inform sport surgeons on factors precluding RTS and can guide clinical practice to better help athletes achieve their postoperative goals.
Operative Pediatric Hand Trauma
Authors: Lopes Rita Coelho , Carvalho Marcos , Ling Tah Pu , Balacó Inês , Cardoso Pedro , Tarquini Oliana , Cabral João , Alves Cristina
Published: October 2022

This study aims to describe the epidemiology of hand injuries in pediatric patients undergoing surgical treatment. A retrospective analysis of patients with traumatic hand injuries surgically treated over a 7-year period. A total of 155 patients were included. Fracture was the most common injury type (74.8%), most of which were open (54.3%). Incidence of articular fractures increased with age. The predominant mechanism of injury before age 10 was crush. In toddlers, only central digits were affected. Good functional results were achieved (Quick-DASH 1.37 ± 4.90). The incidence of hand injuries requiring surgery increased with age. The mechanism and segment affected varied with age groups. Although good functional results are expected, complications may occur 33% and secondary surgical procedures in 7.7%.
Migrating to New Contraceptive Contexts: The Case of Migrants from Turkey to France
Authors: Behrman Julia , Buyukakbas Elif , Weitzman Abigail
Published: October 2022

Do migrants adopt the contraceptive norms dominant in their destination context? To explore this question, the authors adopt a multisited analysis in which they standardize and integrate data on women’s contraceptive use from two different sources: the Trajectoires et Origines survey collected in France (the receiving country) and the Demographic and Health Survey collected in Turkey (the sending country). Descriptive analyses indicate that contraceptive use of migrant women from Turkey in France is more comparable with that of nonmigrant women in France compared with nonmigrant women in Turkey. To address migrant selectivity on observed characteristics in multivariate analyses, nonmigrant groups in France and Turkey are reweighted with entropy balancing to resemble migrants on observed characteristics. Multivariate results indicate that there are sizable differences in contraceptive use between Turkish migrants and nonmigrant Turkish women, which undermines the hypothesis of selection on observables. Yet there are no significant differences between migrants and nonmigrant French women in contraceptive methods, thus supporting an adaptation perspective. Supplementary analyses highlight several pathways that could help explain these findings.
Disaggregating Ethnicity and National Origin: Educational Heterogeneity among Vietnamese and Chinese Americans across Immigrant Generations
Authors: Li Jing , Min Jie
Published: October 2022

Scholars often treat immigrants from the same country as a monolithic group, but intranational ethnicity is usually associated with distinctive premigration backgrounds and migration experiences and plays a role in shaping immigrant adjustment and incorporation in the host country. The authors use census data to distinguish ethnic Chinese from the Vietnamese national group to analyze educational heterogeneity across immigration generations. The results show that first-generation Chinese Vietnamese exhibit much lower levels of education than their Vietnamese counterparts, but this disparity vanishes by the 1.5 generation. The authors also find that both Vietnamese subgroups contribute to the second-generation convergence with Chinese Americans, but Chinese Vietnamese are able to overcome disadvantages more quickly and have slightly higher educational achievement than ethnic Vietnamese. Our case study illustrates how ethnicity and national origin can be disaggregated using nationally representative data and how this approach can provide unique insights into immigration studies in general.
LncRNA FENDRR with m6A RNA methylation regulates hypoxia-induced pulmonary artery endothelial cell pyroptosis by mediating DRP1 DNA methylation
Authors: Wang Xiaoying , Li Qian , He Siyu , Bai June , Ma Cui , Zhang Lixin , Guan Xiaoyu , Yuan Hao , Li Yiying , Zhu Xiangrui , Mei Jian , Gao Feng , Zhu Daling
Published: October 2022

Background

Pyroptosis is a form of programmed cell death involved in the pathophysiological progression of hypoxic pulmonary hypertension (HPH). Emerging evidence suggests that N6-methyladenosine (m6A)-modified transcripts of long noncoding RNAs (lncRNAs) are important regulators that participate in many diseases. However, whether m6A modified transcripts of lncRNAs can regulate pyroptosis in HPH progression remains unexplored.

Methods

The expression levels of FENDRR in hypoxic pulmonary artery endothelial cells (HPAECs) were detected by using quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH). Western blot, Lactate dehydrogenase (LDH) release assay, Annexin V-FITC/PI double staining, Hoechst 33342/PI fluorescence staining and Caspase-1 activity assay were used to detect the role of FENDRR in HPAEC pyroptosis. The relationship between FENDRR and dynamin-related protein 1 (DRP1) was explored using bioinformatics analysis, Chromatin Isolation by RNA Purification (CHIRP), Electrophoretic mobility shift assay (EMSA) and Methylation-Specific PCR (MSP) assays. RNA immunoprecipitation (RIP) and m6A dot blot were used to detect the m6A modification levels of FENDRR. A hypoxia-induced mouse model of pulmonary hypertension (PH) was used to test preventive effect of conserved fragment TFO2 of FENDRR.

Results

We found that FENDRR was significantly downregulated in the nucleus of hypoxic HPAECs. FENDRR overexpression inhibited hypoxia-induced HPAEC pyroptosis. Additionally, DRP1 is a downstream target gene of FENDRR, and FENDRR formed an RNA–DNA triplex with the promoter of DRP1, which led to an increase in DRP1 promoter methylation that decreased the transcriptional level of DRP1. Notably, we illustrated that the m6A reader YTHDC1 plays an important role in m6A-modified FENDRR degradation. Additionally, conserved fragment TFO2 of FENDEE overexpression prevented HPH in vivo.

Conclusion

In summary, our results demonstrated that m6A-induced decay of FENDRR promotes HPAEC pyroptosis by regulating DRP1 promoter methylation and thereby provides a novel potential target for HPH therapy.
Tumour inhibitory activity on pancreatic cancer by bispecific nanobody targeting PD-L1 and CXCR4
Authors: Hao Shuai , Xu Shuyi , Li Liangzhu , Li Yaxian , Zhao Meiqi , Chen Junsheng , Zhu Shunying , Xie Yueqing , Jiang Hua , Zhu Jianwei , Wu Mingyuan
Published: October 2022

Background:

Antibodies and derivative drugs targeting immune checkpoints have been approved for the treatment of several malignancies, but there are fewer responses in patients with pancreatic cancer. Here, we designed a nanobody molecule with bi-targeting on PD-L1 and CXCR4, as both targets are overexpressed in many cancer cells and play important roles in tumorigenesis. We characterized the biochemical and anti-tumour activities of the bispecific nanobodies in vitro and in vivo.

Methods:

A nanobody molecule was designed and constructed. The nanobody sequences targeting PD-L1 and CXCR4 were linked by the (G4S)3 flexible peptide to construct the anti-PD-L1/CXCR4 bispecific nanobody. The bispecific nanobody was expressed in E. coli cells and purified by affinity chromatography. The purified nanobody was biochemically characterized by mass spectrometry, Western blotting and flow cytometry to confirm the molecule and its association with both PD-L1 and CXCR4. The biological function of the nanobody and its anti-tumour effects were examined by an in vitro tumour cell-killing assay and in vivo tumour inhibition in mouse xenograft models.

Results:

A novel anti-PD-L1/CXCR4 bispecific nanobody was designed, constructed and characterized. The molecule specifically bound to two targets on the surface of human cancer cells and inhibited CXCL12-induced Jurkat cell migration. The bispecific nanobody increased the level of IFN-γ secreted by T-cell activation. The cytotoxicity of human peripheral blood mononuclear cells (hPBMCs) against pancreatic cancer cells was enhanced by the molecule in combination with IL-2. In a human pancreatic cancer xenograft model, the anti-PD-L1/CXCR4 nanobody markedly inhibited tumour growth and was superior to the combo-treatment by anti-PD-L1 nanobody and anti-CXCR4 nanobody or treatment with atezolizumab as a positive control. Immunofluorescence and immunohistochemical staining of xenograft tumours showed that the anti-tumour effects were associated with the inhibition of angiogenesis and the infiltration of immune cells.

Conclusion:

These results clearly revealed that the anti-PD-L1/CXCR4 bispecific nanobody exerted anti-tumour efficacy in vitro and inhibited tumour growth in vivo. This agent can be further developed as a therapeutic reagent to treat human pancreatic cancer by simultaneously blocking two critical targets.
Perspectives on mental health services for medical students at a Ugandan medical school
Authors: Kihumuro Raymond Bernard , Kaggwa Mark Mohan , Nakandi Rachael Mukisa , Kintu Timothy Mwanje , Muwanga David Richard , Muganzi David Jolly , Atwau Pius , Ayesiga Innocent , Acai Anita , Najjuka Sarah Maria , Najjuma Josephine Nambi , Frazier-Koussai Susan , Ashaba Scholastic , Harms Sheila
Published: October 2022

Background

University-based mental health services for medical students remain a challenge, particularly in low-income countries, due to poor service availability. Prior studies have explored the availability of mental health services in high-income countries but little is known about mental health services in countries in sub-Saharan Africa, such as Uganda. Medical students are at a higher risk of developing mental health challenges during their course of study as compared with other students. Thus, there is a need for well-structured mental health services for this group of students. The aim of this study was to explore perspectives on mental health services for medical students at a public University in Uganda.

Methods

This was a qualitative study where key informant interviews were conducted among purposively selected university administrators (n = 4), student leaders (n = 4), and mental health employees of the university (n = 3), three groups responsible for the mental well-being of medical students at a public university in Uganda. Interviews were audio-recorded, transcribed, and thematically analyzed to identify relevant themes.

Results

The working experience of university administrators and mental health providers was between eight months to 20 years, while student leaders had studied at the university for over four years. We identified five broad themes: (1) Burden of medical school: A curriculum of trauma, (2) Negative coping mechanisms and the problem of blame, (3) The promise of services: Mixed Messages, (4) A broken mental health system for students, and (5) Barriers to mental health services.

Conclusion

Distinguishing between psychological distress that is anticipated because of the subject matter in learning medicine and identifying those students that are suffering from untreated psychiatric disorders is an important conceptual task for universities. This can be done through offering education about mental health and well-being for administrators, giving arm’s length support for students, and a proactive, not reactive, approach to mental health. There is also a need to redesign the medical curriculum to change the medical education culture through pedagogical considerations of how trauma informs the learning and the mental health of students.
Cost-effectiveness of folic acid therapy for primary prevention of stroke in patients with hypertension
Authors: Zhang Tiantian , Liang Zhuoru , Lin Tengfei , Cohen David J. , Arrieta Alejandro , Wang Xiaobin , Qin Xianhui , Wang Binyan , Huo Yong , Liu Gordon G. , Jiang Jie , Zhang Zugui
Published: October 2022

Background

For hypertensive patients without a history of stroke or myocardial infarction (MI), the China Stroke Primary Prevention Trial (CSPPT) demonstrated that treatment with enalapril-folic acid reduced the risk of primary stroke compared with enalapril alone. Whether folic acid therapy is an affordable and beneficial treatment strategy for the primary prevention of stroke in hypertensive patients from the Chinese healthcare sector perspective has not been thoroughly explored.

Methods

We performed a cost-effectiveness analysis alongside the CSPPT, which randomized 20,702 hypertensive patients. A patient-level microsimulation model based on the 4.5-year period of in-trial data was used to estimate costs, life years, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) for enalapril-folic acid vs. enalapril over a lifetime horizon from the payer perspective.

Results

During the in-trial follow-up period, patients receiving enalapril-folic acid gained an average of 0.016 QALYs related primarily to reductions in stroke, and the incremental cost was $706.03 (4553.92 RMB). Over a lifetime horizon, enalapril-folic acid treatment was projected to increase quality-adjusted life years by 0.06 QALYs or 0.03 life-year relative to enalapril alone at an incremental cost of $1633.84 (10,538.27 RMB), resulting in an ICER for enalapril-folic acid compared with enalapril alone of $26,066.13 (168,126.54 RMB) per QALY gained and $61,770.73 (398,421.21 RMB) per life-year gained, respectively. A probabilistic sensitivity analysis demonstrated that enalapril-folic acid compared with enalapril would be economically attractive in 74.5% of simulations at a threshold of $37,663 (242,9281 RMB) per QALY (3x current Chinese per capita GDP). Several high-risk subgroups had highly favorable ICERs < $12,554 (80,976 RMB) per QALY (1x GDP).

Conclusions

For both in-trial and over a lifetime, it appears that enalapril-folic acid is a clinically and economically attractive medication compared with enalapril alone. Adding folic acid to enalapril may be a cost-effective strategy for the prevention of primary stroke in hypertensive patients from the Chinese health system perspective.
Laparoscopy assisted abomasal cannulation in cadavers of bovine fetuses
Authors: Gurgel Heytor Jales , de Oliveira Monteiro Francisco Décio , Barroso João Pedro Monteiro , de Sousa Loise Araújo , dos Santos Gabriela Melo Alves , da Cunha Rossy Kayan , da Silva Verena Siqueira , do Espirito Santo Fernandes Camila , Silva Carla Rozilene Guimarães , dos Santos Albuquerque Rodrigo , Borges Luisa Pucci Bueno , Araújo Luiz Henrique Vilela , dos Santos Daniele Lira , da Câmara Barros Felipe Farias Pereira , Teixeira Pedro Paulo Maia
Published: October 2022

Background

Due to the complexity of ruminant digestion, cannulation of organs of the digestive tract has been carried out in order to advance the understanding of digestive physiology, nutrient degradability, gastrointestinal diseases and biotechnological research. The abomasal cannulation is interesting for nutritional studies, especially in suckling calves, to obtain fluid and abomasal content, evaluation of abomasal flow and function, and infusion of nutrients and drugs when it is intended to reach high concentrations in the organ. Conventionally, access and cannulation of digestive organs of ruminants has been performed by laparotomy, a method often criticized and classified as cruel by some sectors related to ethics and animal welfare. The aim of this present study is to describe and standardize a minimally invasive by laparoscopy assisted abomasal cannulation in bovine fetuses (cadavers), which had been previously slaughtered by accident and would be discarded in local slaughterhouses.

Results

The abomasal cannulation technique was feasible, simple and did not present major difficulties. The surgical time for cannulation of the abomasum, from the insertion of the trocars to the completion of the technique with fixation of the organ to the abdominal wall, ranged from 9 to 27 min, with an average of 15.5 ± 6.62 min.

Conclusions

The Laproscopic assisted abomasal cannulation in bovine fetuses was feasible and safe with minimal tissue injury to the abdominal wall and with short surgical time. More studies in the clinical routine related to minimally invasive abomasal content collection, abomasopexy and abomasotomy are required in order to demonstrate its impact and importance in bovine clinic.
Automated measurement of malaria parasitaemia among asymptomatic blood donors in Malawi using the Sysmex XN-31 analyser: could such data be used to complement national malaria surveillance in real time?
Authors: Kayange Michael , M’baya Bridon , Hwandih Talent , Saker Jarob , Coetzer Thérèsa L. , Münster Marion
Published: October 2022

Background

The recent worldwide increase in malaria cases highlights the need for renewed efforts to eliminate malaria. The World Health Organization advocates that malaria surveillance becomes a core intervention. Current methods to estimate the malaria burden rely on clinical malaria case reports and surveys of asymptomatic parasite infection mainly from children  < 5 years. In this study the hypothesis was that screening blood donors for malaria parasites would provide real-time information on the asymptomatic reservoir of parasites in the adult population and mirror other surveillance data.

Methods

This study was conducted in Malawi, a high malaria burden country, at the Malawi Blood Transfusion Service, which collects blood units at donation sites countrywide. A secondary analysis was conducted on data obtained from a prior Sysmex XN-31 analyser malaria diagnostic evaluation study utilizing residual donor blood samples. XN-31 malaria results, donor age, sex, geographical location, and collection date, were analysed using standard statistical methods.

Results

The malaria parasite prevalence in blood donors was 11.6% (614/5281 samples) increasing seasonally from December (8.6%) to April (18.3%). The median age was 21 years and 45.9% of donors were from urban areas, which showed a lower prevalence compared to non-urban regions. The Central administrative region had the highest and the Northern region the lowest malaria parasite prevalence. The donors were predominantly male (80.2%), 13.1% of whom had malaria parasites, which was significantly higher (p < 0.0001) than for female donors (7.4%). Multivariable logistic regression analysis showed that age, location, and collection month were significant predictors of malaria positivity in males, whereas in females only location was significant. There was no gender difference in parasite density nor gametocyte carriage.

Conclusions

This study demonstrates the powerful utility of screening blood donors for malaria parasites using the XN-31, which not only improves the safety of blood transfusion, but provides valuable complementary surveillance data for malaria control, especially targeting males, who are generally excluded from periodic household surveys. Blood donations are sourced countrywide, year-round, and thus provide dynamic, real-time information on the malaria burden. Furthermore, the XN-31 identifies the asymptomatic human reservoir of infectious gametocytes, which must be targeted to eliminate malaria.
Temperature-related mortality and associated vulnerabilities: evidence from Scotland using extended time-series datasets
Authors: Wan Kai , Feng Zhiqiang , Hajat Shakoor , Doherty Ruth M.
Published: October 2022

Background

Adverse health impacts have been found under extreme temperatures in many parts of the world. The majority of such research to date for the UK has been conducted on populations in England, whilst the impacts of ambient temperature on health outcomes in Scottish populations remain largely unknown.

Methods

This study uses time-series regression analysis with distributed lag non-linear models to characterise acute relationships between daily mean ambient temperature and mortality in Scotland including the four largest cities (Aberdeen, Dundee, Edinburgh and Glasgow) and three regions during 1974–2018. Increases in mortality risk under extreme cold and heat in individual cities and regions were aggregated using multivariate meta-analysis. Cold results are summarised by comparing the relative risk (RR) of death at the 1st percentile of localised temperature distributions compared to the 10th percentile, and heat effects as the RR at the 99th compared to the 90th percentile.

Results

Adverse cold effects were observed in all cities and regions, and heat effects were apparent in all cities and regions. Aggregate all-cause mortality risk in Scotland was estimated to increase by 9% (95% confidence interval, CI: 8%, 11%) under extreme cold and 4% (CI: 3%, 5%) under extreme heat. The elderly had the highest RR under both extreme cold and heat. Males experienced greater cold effects than females, whereas the reverse was true with heat effects, particularly among the elderly. Those who were unmarried had higher RR than those married under extreme heat, and the effect remained after controlling for age. The younger population living in the most deprived areas experienced higher cold and heat effects than in less deprived areas. Deaths from respiratory diseases were most sensitive to both cold and heat exposures, although mortality risk for cardiovascular diseases was also heightened, particularly in the elderly. Cold effects were lower in the most recent 15 years, which may be linked to policies and actions in preventing the vulnerable population from cold impacts. No temporal trend was found with the heat effect.

Conclusions

This study assesses mortality risk associated with extreme temperatures in Scotland and identifies those groups who would benefit most from targeted actions to reduce cold- and heat-related mortalities.
Intervention time decides the status of autophagy, NLRP3 activity and apoptosis in macrophages induced by ox‐LDL
Authors: Zheng Liang , Xu Hongbiao , Zheng Fufu , Lai Yuanhui , Li Jie , Lv Weiming , Hu Zuojun , Wang Wenjian
Published: October 2022

Background

It has been determined through extensive studies that autophagy, the Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome and apoptotic responses in macrophages jointly contribute to atherogenesis and its development in the presence of lipid abnormalities. Few studies have investigated in full-scale if the intervention time for lipids abnormality or NLRP3 activation have a significant effect on autophagy, NLRP3 or the apoptotic status in macrophages.

Methods

Human THP-1 monocyte-derived macrophages were established by challenging THP-1 monocytes with 80 µg/ml oxidized low-density lipoprotein (ox-LDL) for specific durations. Foam cell formation was observed by Oil Red O (ORO) staining. Western blots were employed to determine protein expression. Transmission electron microscope (TEM) and immunofluorescence microscopy were applied to observe the autophagic status of cells. Cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL).

Results

The cells were treated with ox-LDL for 12 h and 36 h, which were considered to represent early and advanced stages of atherogenesis for this study. The results showed that inhibition of ox-LDL phagocytosis by cytochalasin D in the early stage improved autophagic status, reduced NLRP3 activation and the apoptotic response significantly. In contrast, cytochalasin D had little effect on blocking the detrimental effect of ox-LDL at the advanced stage. Moreover, the changes in autophagy, apoptosis and NLRP3 expression after treatment with small interfering (si) RNA targeting NLRP3 in the early and advanced stages of atherogenesis were consistent with the above data.

Conclusions

Interventions against lipid disorders or inflammatory reactions in the early or advanced stages of atherogenesis may have different results depending on when they are applied during the process of atherosclerotic pathogenesis. These results may help improve therapeutic strategies for atherosclerosis prevention. Furthermore, a healthy lifestyle should still be recommended as the most important and inexpensive measure to prevent atherogenesis.
HB-EGF upregulates StAR expression and stimulates progesterone production through ERK1/2 signaling in human granulosa-lutein cells
Authors: Cheng Jung-Chien , Han Xiaoyu , Meng Qingxue , Guo Yanjie , Liu Boqun , Song Tinglin , Jia Yuanyuan , Fang Lanlan , Sun Ying-Pu
Published: October 2022

Background

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) belongs to the epidermal growth factor (EGF) family of growth factors. HB-EGF and its receptors, epidermal growth factor receptor (EGFR) and HER4, are expressed in the human corpus luteum. HB-EGF has been shown to regulate luteal function by preventing cell apoptosis. Steroidogenesis is the primary function of the human corpus luteum. Steroidogenic acute regulatory protein (StAR) plays a critical role in steroidogenesis. StAR expression and progesterone (P4) production in human granulosa-lutein (hGL) cells have been shown to be upregulated by a ligand of EGFR, amphiregulin. However, whether HB-EGF can achieve the same effects remains unknown.

Methods

A steroidogenic human ovarian granulosa-like tumor cell line, KGN, and primary culture of hGL cells obtained from patients undergoing in vitro fertilization treatment were used as experimental models. The underlying molecular mechanisms mediating the effects of HB-EGF on StAR expression and P4 production were explored by a series of in vitro experiments.

Results

Western blot showed that EGFR, HER2, and HER4 were expressed in both KGN and hGL cells. Treatment with HB-EGF for 24 h induced StAR expression but did not affect the expression of steroidogenesis-related enzymes, P450 side chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase, and aromatase. Using pharmacological inhibitors and a siRNA-mediated knockdown approach, we showed that EGFR, HER4, but not HER2, were required for HB-EGF-stimulated StAR expression and P4 production. In addition, HB-EGF-induced upregulations of StAR expression and P4 production were mediated by the activation of the ERK1/2 signaling pathway.

Conclusion

This study increases the understanding of the physiological role of HB-EGF in human luteal functions.
Genetic and epigenetic regulation of Catechol-O-methyltransferase in relation to inflammation in chronic fatigue syndrome and Fibromyalgia
Authors: Polli Andrea , Hendrix Jolien , Ickmans Kelly , Bakusic Jelena , Ghosh Manosij , Monteyne Dora , Velkeniers Brigitte , Bekaert Bram , Nijs Jo , Godderis Lode
Published: October 2022

Background

Catechol-O-methyltransferase (COMT) has been shown to influence clinical pain, descending modulation, and exercise-induced symptom worsening. COMT regulates nociceptive processing and inflammation, key pathophysiological features of Chronic Fatigue Syndrome and Fibromyalgia (CFS/FM). We aimed to determine the interactions between genetic and epigenetic mechanisms regulatingCOMTand its influence on inflammatory markers and symptoms in patients with CFS/FM.Methods.A case-control study with repeated-measures design was used to reduce the chance of false positive and increase the power of our findings. Fifty-four participants (28 patients with CFS/FM and 26 controls) were assessed twice within 4 days. The assessment included clinical questionnaires, neurophysiological assessment (pain thresholds, temporal summation, and conditioned pain modulation), and blood withdrawal in order to assess rs4818, rs4633, and rs4680COMTpolymorphisms and perform haplotype estimation, DNA methylation in theCOMTgene (both MB-COMT and S-COMT promoters), and cytokine expression (TNF-α, IFN-γ, IL-6, and TGF-β).Results.COMT haplotypes were associated with DNA methylation in the S-COMT promoter, TGF-β expression, and symptoms. However, this was not specific for one condition. Significant between-group differences were found for increased DNA methylation in the MB-COMT promoter and decreased IFN-γ expression in patients.

Discussion

Our results are consistent with basic and clinical research, providing interesting insights into genetic-epigenetic regulatory mechanisms. MB-COMT DNA methylation might be an independent factor contributing to the pathophysiology of CFS/FM. Further research on DNA methylation in complex conditions such as CFS/FM is warranted. We recommend future research to employ a repeated-measure design to control for biomarkers variability and within-subject changes.
CRISPR-KRISPR: a method to identify on-target and random insertion of donor DNAs and their characterization in knock-in mice
Authors: Tanaka Masayuki , Yokoyama Keiko , Hayashi Hideki , Isaki Sanae , Kitatani Kanae , Wang Ting , Kawata Hisako , Matsuzawa Hideyuki , Gurumurthy Channabasavaiah B. , Miura Hiromi , Ohtsuka Masato
Published: October 2022

CRISPR tools can generate knockout and knock-in animal models easily, but the models can contain off-target genomic lesions or random insertions of donor DNAs. Simpler methods to identify off-target lesions and random insertions, using tail or earpiece DNA, are unavailable. We develop CRISPR-KRISPR (CRISPR-Knock-ins and Random Inserts Searching PRotocol), a method to identify both off-target lesions and random insertions. CRISPR-KRISPR uses as little as 3.4 μg of genomic DNA; thus, it can be easily incorporated as an additional step to genotype founder animals for further breeding.
APOE ε4-dependent effects on the early amyloid pathology in induced neurons of patients with Alzheimer’s disease
Authors: Kim Hongwon , Kim Siyoung , Cho Byounggook , Shin Jaein , Kim Jongpil
Published: October 2022

Background

The ε4 allele of apolipoprotein E (APOE ε4) is the strongest known genetic risk factor for late-onset Alzheimer’s disease (AD), associated with amyloid pathogenesis. However, it is not clear how APOE ε4 accelerates amyloid-beta (Aβ) deposition during the seeding stage of amyloid development in AD patient neurons.

Methods

AD patient induced neurons (iNs) with an APOE ε4 inducible system were prepared from skin fibroblasts of AD patients. Transcriptome analysis was performed using RNA isolated from the AD patient iNs expressing APOE ε4 at amyloid-seeding and amyloid-aggregation stages. Knockdown of IGFBP3 was applied in the iNs to investigate the role of IGFBP3 in the APOE ε4-mediated amyloidosis.

Results

We optimized amyloid seeding stage in the iNs of AD patients that transiently expressed APOE ε4. Remarkably, we demonstrated that Aβ  pathology was aggravated by the induction of APOE ε4 gene expression at the amyloid early-seeding stage in the iNs of AD patients. Moreover, transcriptome analysis in the early-seeding stage revealed that IGFBP3 was functionally important in the molecular pathology of APOE ε4-associated AD.

Conclusions

Our findings suggest that the presence of APOE ε4 at the early Aβ-seeding stage in patient iNs is critical for aggravation of sporadic AD pathology. These results provide insights into the importance of APOE ε4 expression for the progression and pathogenesis of sporadic AD.
Gestão de riscos: o dilema do setor público
Authors: D'Andrea Ellen Rodrigues
Published: October 2022

O trabalho relata a implementação da metodologia de gerenciamento de crises em determinado órgão de segurança pública. Num movimento de vanguarda, o protagonista Salomão Falcone prospectou cenários de risco para neutralizar um evento de crise, antes mesmo que ele se configurasse. Em meio a história central, o caso destaca como a experiência profissional do gestor pode corroborar para o êxito na missão. Com o dilema retirado dos relatos do gestor envolvido e das consultas a documentos institucionais, este caso contribui para que educadores possam debater os atributos de liderança, cultura organizacional e gerenciamento de crise no ambiente governamental
Inovação social na doação de alimentos? Gestão de uma mercearia social na Grande Lisboa
Authors: Sasaki Vasques Pacheco Anderson , Silveira Pereira Simon Vanessa , Vieira da Silva Karin
Published: October 2022

O Centro Comunitário da Paróquia de Carcavelos, na Grande Lisboa, desenvolveu uma nova maneira de distribuir alimentos para famílias socialmente vulneráveis. A longa espera em fila por cestas básicas, a diversidade cultural e o desperdício de alimentos foram aspectos importantes para que se questionasse a forma tradicional de doação. No entanto, o grande desafio vivenciado pela diretora Teresa e os gestores Amália e Nuno reside na mensuração da quantidade de alimento de cada família e na formação de parcerias para manter a mercearia em funcionamento. Eles desejam inovar, mas sem prejudicar as pessoas em situação de pobreza.
Reestruturando estratégias em tempos de crise: o caso da empresa Airbnb
Authors: Silva Jean Soares da , Silva Brena Carolina de Oliveira , Gohr Cláudia Fabiana
Published: October 2022

Este caso apresenta a trajetória da empresa Airbnb e tem como temática principal a tomada de decisão dos gestores diante da crise global causada pela Covid-19. Em março de 2020, quando a Organização Mundial de Saúde declarou o surto da Covid-19 como pandemia mundial, a mobilidade humana encontrava-se profundamente afetada, e a Airbnb precisava modificar suas estratégias e práticas e se adaptar a esse contexto global. Na tentativa de mitigar os conflitos, a empresa vê-se em uma circunstância em que mudanças drásticas e urgentes deveriam ser tomadas.
Antiproliferative activity of standardized herbal phytopreparation from Asclepias subulata
Authors: González Gutiérrez Francisco Humberto , Rascón Valenzuela Luisa Alondra , Meneses Sagrero Salvador Enrique , Dias-Silva Marcelo J. , Valenzuela Antelo Olivia , Velazquez Carlos , Vilegas Wagner , Robles Zepeda Ramón Enrique
Published: October 2022

Background: Several studies have shown that active compounds of Asclepias subulata (cardenolides) have antiproliferative effect on human cancer cells. Cardenolides isolated from A. subulata can be used as active chemical markers to elaborate phytopharmaceutical

preparations. The aim of this work was to evaluate the antiproliferative effect of a standardized extract of the aerial parts, based on Asclepias subulata cardenolides. Methods: Four standardized extracts were prepared by HPLC-DAD depending on the concentration of calotropin and the antiproliferative activity was measured for the MTT assay, on the A549, MCF-7, HeLa, PC3 and ARPE cell lines. The concentrations of calotropin used for the standardization of the extracts were 10, 7.6, 5 and 1 mg/dL. Results: Standardization of the A. subulata extract based on calotropin at 7.6 mg/g dry weight was achieved and the antiproliferative activity was evaluated over A549, HeLa and MCF-7 cell lines, obtaining proliferation percentages of 3.8 to 13.4%. Conclusions: The standardized extracts of A. subulata at different concentrations of calotropin showed antiproliferative activity against all the cell lines evaluated. The greatest effect was observed against the HeLa cell line.
Indigenous astronomical knowledge based seasonal weather forecast: evidence from Borana Oromo pastoralists of Southern Ethiopia
Authors: Dinsa Abera Bekele , Wakjira Feyera Senbeta , Demmesie Ermias Teferi , Negash Tamirat Tefera
Published: October 2022

Indigenous knowledge is still widely used by communities around the world to overcome social-ecological challenges. Borana Oromo pastoralists of Southern Ethiopia have been searching for future weather phenomena using their indigenous knowledge. This study examines indigenous knowledge-based seasonal weather forecasts through using observable physical and temporal patterns of astronomic objects. Data were generated through using focus group discussion, experimental knowledgeable groups and direct observation in the year 2021. The finding reveals that Borana Oromo pastoralists commonly define physical and temporal outlooks of the Moon that are changed and/ or displayed periodically within a range of varying contexts. The observation of the Moon features have been offering sufficient lapse time in a more than/within ahead of a season/ and is relatively more accurate than the other traditional forecasting objects. The study showed that both temporal and spatial dimensions of the forecasting were actually happened in Ganna (March to May rainfall), Adolessa dry season (June to September) and Hgayya rainfall (October to November) seasons of 2021. This indigenous weather forecasting practices are still regularly used in every livelihood decision making process. However, this indigenous weather knowledge of Borana Oromo pastoralists of Southern Ethiopia is not yet mainstreamed in the formal institutional structures. Curtailments of mobility, severity of drought, weakening of traditional institution, leaving of traditional life style and death of the knowledgeable elders are the major factors that are challenging the potential effects of the indigenous weather forecasting indicators of the features of moon in the study area.