bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased flow-mediated dilation in healthy Chinese adolescent with a family history of type 2 diabetes
Authors: Wang Yingwei , Li Guangxia , Qi Jing , Gong Ting , Li Xiudong , Liu Fanghe , Bi Xuejing , Zhao Yang , Liang Meihua , Zheng Xiaodong , Qiao Yuandong
Published: June 2022

Background

Endothelial dysfunction appears early in the development of cardiovascular disease and is associated with type 2 diabetes. We, therefore, tested the hypothesis that endothelial dysfunction is already present in healthy Chinese adolescent participants at risk of type 2 diabetes and associates with physical activity.

Methods

We investigated the flow-mediated dilation in 65 first-degree relatives (normal tension, normal glucose tolerance) and 62 age-, sex- and BMI-matched controls without a family history of type 2 diabetes by ultrasound. Physical activity level was assessed using the Global Physical Activity Questionaire and type 2 diabetes family history through self-reporting. The association between physical activity and flow-mediated dilation was evaluated by Pearson correlations and multiple regressions in adolescents with or without a family history of type 2 diabetes.

Results

Female adolescents display better flow-mediated dilation than males. Adolescents with a family history of type 2 diabetes had significantly impaired flow-mediated dilation than healthy controls. Among the parameter detection in the blood, the flow-mediated dilation is only positively associated with high-density lipoprotein cholesterol level, but not others. Interestingly, flow-mediated dilation is positively corrected with physical activity scores in both the male and female adolescents, while slightly impaired but not significant in adolescents with a family history of type 2 diabetes.

Conclusion

Studies in adolescents are important to understand the early pathogenesis of type 2 diabetes. Findings of this investigation suggest that family history of type 2 diabetes may play a role in regulating the vascular function in Chinese adolescents. Given the impaired flow-mediated dilation in individuals with family history and the effects of physical activity in improved flow-mediated dilation, people with a family history of type 2 diabetes may need higher physical activity levels to attenuate their susceptibility to impaired flow-mediated dilation.
Association between high serum Nogo-B and hypertension in Chinese Han
Authors: Li Shunuo , Zheng Jianmeng , Dong Xiaoxia , Bi Shasha , Duan Liqin , Zheng Wei , Yan Peishi
Published: June 2022

Background

Cellular and animal studies have shown that endoplasmic reticulum protein B (Nogo-B) is associated with hypertension, but that association has not been fully studied in humans. Therefore, the expression levels of Nogo-B were investigated in hypertensive patients.

Methods

The plasma Nogo-B levels of 74 patients with hypertension and 67 non-hypertensive patients were measured by enzyme-linked immunosorbent assay.

Results

The plasma Nogo-B levels in the hypertensive group [523.43(411.41−746.79)] were higher than in the non-hypertensive group [380.29(281.57−462.13)] (P < 0.01). Pearson’s correlation analysis indicated that systolic blood pressure and diastolic blood pressure were linearly and positively correlated with plasma Nogo-B levels. Multivariable logistic regression analysis was performed based on sex, age, BMI, smoking history, drinking history, and levels of TC, TG, LDL, and HDL. The results indicated that the plasma Nogo-B levels were independently associated with hypertension (OR = 1.007, 95%CI: 1.004–1.010,P < 0.01).

Conclusions

The present study suggests that hypertensive participants exhibited higher plasma Nogo-B levels than those without hypertension. Plasma Nogo-B levels are independently associated with hypertension.
Identifying and prioritizing do-not-do recommendations in Dutch primary care
Authors: van Dulmen Simone A. , Tran Ngoc Hue , Wiersma Tjerk , Verkerk Eva W. , Messaoudi Jasmine CL , Burgers Jako S. , Kool Rudolf B.
Published: June 2022

Background

Low-value care provides minimal or no benefit for the patient, wastes resources, and can cause harm. Explicit do-not-do recommendations in clinical guidelines are a first step in reducing low-value care. The aim of this study was to identify and prioritize do-not-do recommendations in general practice guidelines with priority for implementation.

Methods

We used a mixed method design in Dutch primary care. First, we identified do-not-do recommendations through a systematic assessment of 92 Dutch guidelines for general practitioners (GPs), resulting in 385 do-not-do recommendations. Second, we selected 146 recommendations addressing high prevalent conditions. Third, a random sample of 5000 Dutch GPs was invited for an online survey to prioritize recommendations based on the prevalence of the condition and low-value care practice, potential harm, and potential cost reduction on a scale from 1 to 5/6. Total scores could range from 4 to 22. Recommendations with a median score > 12 were included. In total, 440 GPs completed the survey.

Results

The selection process led to 30 prioritised recommendations. These covered drug treatments (n = 12), diagnostics (n = 10), referral to other healthcare professions (n = 5), and non-drug treatment (n = 3).

Conclusion

Dutch clinical guidelines include many do-not-do recommendations that are perceived as highly relevant by the GPs. The list of 30 high-priority do-not-do recommendations can be used to raise awareness of low-value care among GPs. As the recommendations are supported with the latest evidence from international studies, primary healthcare professionals and policy makers worldwide can use the list for further validating the list in their local context and designing strategies to reduce low-value care.
Retrograde coiled spring jejunal intussusception in an infant due to Foley catheter gastrostomy: a case report
Authors: Mehmetoğlu Feride
Published: June 2022

Background

For infants who need long-term enteral feeding but are unable to maintain sufficient oral intake, feeding gastrostomy tube placement is required. The use of a Foley catheter as a replacement catheter in a Stamm gastrostomy is indicated in the absence of dedicated gastrostomy feeding tubes; however, this approach has been associated with many morbidities. In this report, an unusual case of an infant who underwent a major operation due to coiled spring jejunal intussusception caused by Foley catheter migration is described.

Case presentation

A 6-month-old neurologically impaired premature female patient was admitted to the emergency unit with respiratory distress, nonbilious vomiting and an ineffective gastrostomy feeding tube. Her history revealed that, at the age of 2 months, she had undergone Stamm gastrostomy for enteral feeding with a Pezzer catheter. However, at the age of 5 months, the Pezzer catheter became dislodged and was replaced with a Foley catheter. The patient subsequently underwent emergent exploratory laparotomy due to intestinal obstruction. During the operation, retrograde coiled spring jejunal intussusceptions with multiple areas of local necrosis and perforations were observed. Resection of the affected jejunal segment and end-to-end anastomosis were performed. The postoperative period was long and very demanding due to the presence of several comorbidities. To our knowledge, this is the first operative demonstration of coiled spring intussusception.

Conclusion

This case report aims to increase clinical awareness of the possibility of coiled spring intussusception following the use of Foley catheter in a gastrostomy and the difficulties encountered in the surgical course of a premature infant.
Perspectives of older adults, caregivers, healthcare providers on frailty screening in primary care: a systematic review and qualitative meta-synthesis
Authors: Nan Jiahui , Duan Yunzhu , Wu Shuang , Liao Lulu , Li Xiaoyang , Zhao Yinan , Zhang Hongyu , Zeng Xianmei , Feng Hui
Published: June 2022

Background

Screening is often recommended as a first step in frailty management. Many guidelines call to implicate frailty screening into practice in the primary care setting. However, few countries or organizations implement it. Understanding and clarifying the stakeholders’ views and issues faced by the implementation is essential to the successful implementation of frailty screening. However, the systematic review on stakeholders’ views of frailty screening in primary care is decidedly limited. Our objective was to explore the perspective of older adults, caregivers, and healthcare providers on frailty screening and determine the enablers and barriers to implementing frailty screening in primary care.

Methods

A systematic search of six databases and other resources was conducted following JBI’s three-step search strategy. The search resulted in 7362 articles, of which 97 were identified for further assessment according to the inclusion criteria. After the full-text screening, quality assessment and data extraction were carried out using the tools from Joanna Briggs Institute (JBI). Moreover, reviewers used the approach of meta-aggregative of JBI to analyze data and synthesis the findings.

Results

Six studies were included. A total of 63 findings were aggregated into 12 categories and then further grouped into three synthesized findings:1) capacity of healthcare providers and older adults; 2) opportunity in the implementation of frailty screening; 3) motivation in the implementation of frailty screening. These themes can help identify what influences the implementation of screening from the perspective of stakeholders.

Conclusions

This meta-synthesis provides evidence on the barriers and enablers of frailty screening in primary care, from the aspects of psychological, physical, social, material, etc. However, stakeholder perspectives of frailty screening have not been adequately studied. More research and efforts are needed to explore the influencing factors and address the existing barriers.
“If somebody had told me I’d feel like I do now, I wouldn’t have believed them…” older adults’ experiences of the BELL trial: a qualitative study
Authors: Meigh Neil J. , Davidson Alexandra R. , Keogh Justin W. L. , Hing Wayne
Published: June 2022

Objectives

This study examined older adults’ experiences of participating in the Ballistic Exercise of the Lower Limb (BELL) trial, involving 12-weeks of group-based hardstyle kettlebell training.

Methods

In the BELL trial, 28 insufficiently active older adults (15 women, 13 men, 59–79 years) completed six weeks of face-to-face group training, and six weeks of home-based training. In-depth semi-structured interviews were audio recorded, transcribed, and inductively coded, with themes constructed from patterns of shared meaning.

Results

Four higher-order themes were developed that reflect older adults’ experiences participating in a group-exercise program of hardstyle kettlebell training. These included: (1) “It’s one of the best things we’ve done”—enjoying the physical and psychosocial benefits, (2) “It’s improved it tremendously!”—change in a long-term health condition, (3) “It put me on a better course”—overcoming challenges, and (4) “I wasn’t just a number”—feeling part of a group/community.

Discussion

Findings highlight the perceived physical and psychological benefits of older adults participating in hardstyle group kettlebell training, and the value attributed to being part of an age-matched community of like-minded people engaged in group exercise. Implications for program design and delivery, and future research, are discussed.
Sigmoid colon perforation in a SARS-CoV-2 positive neonate: a uniqueness report and a brief review
Authors: Jamali Zahra , Sinaei Reza , Estabragh Elahe Raeisi , Ahangaran Ahmad
Published: June 2022

Background

Despite the relative prevalence of small bowel and proximal colon perforation in the neonatal period, recto-sigmoid perforation is extremely rare. Full-term neonates experience intestinal perforation less frequently than premature infants. Here we report a neonate with sigmoid perforation and simultaneous Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection.

Case presentation

A 2550 g female neonate born at 38-weeks’ gestation from a coronavirus disease-2019 (COVID-19) infected mother by cesarean section. Despite a good Apgar score in the first and fifth minutes, she was admitted to the neonatal intensive care unit with grunting and mild respiratory distress. She underwent antibiotics and oxygen by head box resulting in an Oxygen Saturation rate of 94%. The patients’ respiratory distress decreased during the second day, resulting once breastfeeding without tolerance. While she passed meconium in the first 2 days, she developed abdominal distention on day 3. The nasopharyngeal SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) was performed with positive results. Surgical consultation was requested and a thoraco-abdominal X-Ray was performed at this stage, which suspected to be a gastrointestinal perforation.

Due to clinical deterioration and persistent abdominal distention, a contrast study was performed with water-soluble contrast, which confirmed intestinal perforation. However, the surgical exploration revealed perforation of the sigmoid colon at the posterior segment. The patient underwent antibiotic therapy, abdominal lavage, and colostomy, immediately. She was discharged in good condition approximately 14-days later.

Conclusion

To our knowledge, this is the first report of sigmoid colon perforation in a term neonate following COVID-19.
Trends in emergency department visits for mental health disorder diagnoses before and during the COVID-19 pandemic: a retrospective cohort study 2018–2021
Authors: Ramadan Majed , Fallatah Alaa M. , Batwa Yara F. , Saifaddin Ziyad , Mirza Mohammed S. , Aldabbagh Mona , Alhusseini Noara
Published: June 2022

Background

As the pandemic started, Saudi Arabia applied extreme measures in responses to the pandemic crises, which have adversely affected individuals’ mental health. Therefore, the aim of this study is to describe trends in mental health disorder ED visit before and after the pandemic in two medical centers in Saudi Arabia.

Methods

A retrospective cohort study using data from electronic health records in the Ministry of National Guard Health Affairs’ (MNG-HA) in Saudi Arabia. Multiple logistic regression model was used to examine the age and sex differences in mental health disorder ED visits before and during the COVID19 pandemic.

Results

A total of 1117 ED psychiatric visits, a sharp increase in the number of psychiatric ED visits during the pandemic with an average increase of 25.66% was observed. During the pandemic, psychiatric ED visits were significantly higher in females (adjusted AOR 1.41, 95% CI 1.08, 1.83) than males. During the COVID19 pandemic, generalized anxiety disorder was the most common psychiatric ED disorder with reported increase of visits by 53.34% (p-value 0.005).

Conclusion

ED psychiatric visits have consistently increased before and during the COVID19 pandemic. Interventions for mental health related disorders are urgently needed for preventing mental health problems among females.
Digital use of standardised assessment tools for children and adolescents: can available paper-based questionnaires be used free of charge in electronic format?
Authors: Cottin Marianne , Blum Kathrin , Konjufca Jon , Quevedo Yamil , Kaaya Sylvia , Behn Alex , Schmeck Klaus , Sharp Carla , Zimmermann Ronan
Published: June 2022

Question

Most adolescents live in low- and middle-income countries (LMIC), and about 10% of them face mental problems. The mental health provision gap in low- and middle-income countries could be addressed by evidence-based practices, however costs are implementational barriers. Digitalization can improve the accessibility of these tools and constitutes a chance for LMIC to use them more easily at a low cost. We reviewed free and brief evidence-based mental health assessment tools available for digital use to assess psychopathology across different domains in youth.

Methods

For the current study, instruments from a recent review on paper-based instruments were re-used. Additionally, a systematic search was conducted to add instruments for the personality disorder domain. We searched and classified the copyright and license terms available from the internet in terms of free usage and deliverability in a digital format. In the case that this information was insufficient, we contacted the authors.

Results

In total, we evaluated 109 instruments. Of these instruments, 53 were free and digitally usable covering 11 mental health domains. However, retrieving information on copyright and license terms was very difficult.

Conclusions

Free and digitally adaptable instruments are available, supporting the strategy of using instruments digitally to increase access. The instrument’s authors support this initiative, however, the lack of copyright information and the difficulties in contacting the authors and licence holders are barriers to using this strategy in LMIC. A comprehensive, online instrument repository for clinical practice would be an appropriate next step to make the instruments more accessible and reduce implementation barriers.
The relative effects of non-pharmaceutical interventions on wave one Covid-19 mortality: natural experiment in 130 countries
Authors: Stokes Jonathan , Turner Alex James , Anselmi Laura , Morciano Marcello , Hone Thomas
Published: June 2022

Background

Non-pharmaceutical interventions have been implemented around the world to control Covid-19 transmission. Their general effect on reducing virus transmission is proven, but they can also be negative to mental health and economies, and transmission behaviours can also change voluntarily, without mandated interventions. Their relative impact on Covid-19 attributed mortality, enabling policy selection for maximal benefit with minimal disruption, is not well established due to a lack of definitive methods.

Methods

We examined variations in timing and strictness of nine non-pharmaceutical interventions implemented in 130 countries and recorded by the Oxford COVID-19 Government Response Tracker (OxCGRT): 1) School closing; 2) Workplace closing; 3) Cancelled public events; 4) Restrictions on gatherings; 5) Closing public transport; 6) Stay at home requirements (‘Lockdown’); 7) Restrictions on internal movement; 8) International travel controls; 9) Public information campaigns. We used two time periods in the first wave of Covid-19, chosen to limit reverse causality, and fixed country policies to those implemented: i) prior to first Covid-19 death (when policymakers could not possibly be reacting to deaths in their own country); and, ii) 14-days-post first Covid-19 death (when deaths were still low, so reactive policymaking still likely to be minimal). We then examined associations with daily deaths per million in each subsequent 24-day period, which could only be affected by the intervention period, using linear and non-linear multivariable regression models. This method, therefore, exploited the known biological lag between virus transmission (which is what the policies can affect) and mortality for statistical inference.

Results

After adjusting, earlier and stricter school (− 1.23 daily deaths per million, 95% CI − 2.20 to − 0.27) and workplace closures (− 0.26, 95% CI − 0.46 to − 0.05) were associated with lower Covid-19 mortality rates. Other interventions were not significantly associated with differences in mortality rates across countries. Findings were robust across multiple statistical approaches.

Conclusions

Focusing on ‘compulsory’, particularly school closing, not ‘voluntary’ reduction of social interactions with mandated interventions appears to have been the most effective strategy to mitigate early, wave one, Covid-19 mortality. Within ‘compulsory’ settings, such as schools and workplaces, less damaging interventions than closing might also be considered in future waves/epidemics.
Nonocclusive mesenteric ischemia caused by type B aortic dissection: a case report
Authors: Sheng Mengchao , Gong Wei , Zhao Kui , Li Wei , Qian Aimin , Chang Liuhui , Wu Yongyou , Chen Qiang , Chen Zhengrong , Yang Xiaodong , Zhong Fengyun , Xing Chungen
Published: June 2022

Background

Nonocclusive mesenteric ischemia (NOMI) is defined as acute intestinal ischemia because of decreased blood flow in mesenteric vessels. Only a few cases of NOMI that occur secondary to aortic dissection (AD) have been reported, resulting in the lack of sufficient knowledge of diagnosis and treatment.

Case presentation

We aimed to report a case of NOMI caused by type B Aortic Dissection. A 26-year-old male patient was transferred to our hospital with the diagnose of NOMI and aortic dissection in April 2018. The abdominal computed tomography (CT) assists the diagnosis of paralytic intestinal obstruction, intestinal wall pneumatosis, and perforation. Emergency laparotomy revealed that the bowel wall supplied by the superior mesenteric artery (SMA) was pale with the palpable but weak pulsation of the parietal artery. The small intestine was extremely dilated with a paper-thin, fragile wall that was ruptured easily and could not be sutured. In this case, extensive resection and segmental drainage were done. Postoperatively, the digestive tract was reconstructed. However, the patient suffered from iron deficiency anemia and short bowel syndrome eight months later, and unfortunately died from long-term complications.

Conclusion

Aortic dissection leads to continuous decrease in blood pressure and blood flow to the SMA, considering as a predisposing factor for NOMI. During the treatment, extensive resection and segmental drainage are the optimal surgical strategy, which can make benefit in emergencies especially.
Predictive factors associated with adjacent teeth root resorption of palatally impacted canines in Arabian population: a cone-beam computed tomography analysis
Authors: Al-Kyssi Hana’a A. , Al-Mogahed Naela M. , Altawili Zainab M. , Dahan Faiz N. , Almashraqi Abeer A. , Aldhorae Khalid , Alhammadi Maged S.
Published: June 2022

Background

This study aimed to evaluate three-dimensionally the factors associated with adjacent teeth root resorption of palatally impacted canines.

Methods

In this retrospective cross-sectional study, one-hundred and fourteen cone beam computed tomography scans with palatally impacted maxillary canines were evaluated for the presence of adjacent root resorption. Seven parameters were analyzed: alignment of maxillary incisors, presence of deciduous canines, first premolars’ roots configuration, impacted canines rotation, angulation of impacted canine to the midline, contact relationship, and area of contact with adjacent teeth. The association between dependent and independent qualitative and quantitative variables was analyzed using chi-square and independent student’s t-test, respectively. The multivariate analysis was performed using regression analysis. The significant value was set at P ≤ 0.05.

Results

The overall incidence of vertical, horizontal impaction and adjacent root resorption were 92, 8 and 77.2%, respectively. The apical third was the most involved area (57%); resorption of a single tooth was found in 21.9% of the total sample. The most common resorbed teeth were lateral first premolars (24.6%), followed by central lateral incisors (20.2%), and lateral incisors (15.8%) of the total sample. The severity of resorption was highest in grade I (31.5%) and lowest in grade III (7.6%). Three variables showed significant differences between resorption and non-resorption groups namely; canine rotation (P < 0.013), contact relationship (P < 0.001), and area of contact with adjacent teeth (P < 0.001). Regression analysis revealed an association between adjacent root resorption and permanent canine rotation, adjacent premolars’ roots configuration, contact relationship, and area of contact (P < 0.05).

Conclusion

Two-thirds of impacted maxillary canines showed a form of root resorption. The most commonly resorbed tooth was the lateral incisors while the least affected one was the central incisors with apical one-third being of the highest risk. The predisposing factors including the canine rotation, premolar with separated roots, contact relationship, and area of contact with adjacent teeth are to be considered for any interceptive treatment.
Applicability of polygenic risk scores in endometriosis clinical presentation
Authors: Svensson Agnes , Garcia-Etxebarria Koldo , Åkesson Anna , Borgfeldt Christer , Roth Bodil , Ek Malin , D’Amato Mauro , Ohlsson Bodil
Published: June 2022

Background

Risk prediction is an essential part of preventative medicine and in recent years genomic information has become an interesting factor in risk models. Polygenic risk scores (PRS) combine the effect of many genetic variations into a single score which has been shown to have predictive value for many diseases. This study aimed to investigate the association between PRS for endometriosis and the clinical presentation of the disease.

Methods

Women with endometriosis (N = 172) were identified at the Department of Gynecology. All participants answered questionnaires regarding sociodemographic factors, lifestyle habits and medical history, registered bowel symptoms on the Visual Analog Scale for Irritable Bowel Syndrome and passed blood samples. DNA was extracted and samples were genotyped, and a PRS was calculated based on previous genome-wide association studies of endometriosis. Inflammatory proteins and TSH receptor antibodies (TRAb) in serum were analyzed.

Results

Inverse associations were identified between PRS and spread of endometriosis, involvement of the gastrointestinal tract and hormone treatment. However, significance was lost when calculated as p for trend and the specificity and sensitivity were low. There were no correlations between PRS and TRAb or inflammatory proteins.

Conclusion

The findings indicate that specific PRS should be developed to predict clinical presentations in patient with endometriosis.
A new Eimeria coccidian species (Apicomplexa: Eimeriidae) from Père David’s deer (Elaphurus davidianus Milne-Edwards, 1866) in Dafeng Milu National Nature Reserve in Jiangsu Province, eastern China
Authors: Cai Weimin , Suding Zeyang , Wang Lele , Hou Zhaofeng , Liu Dandan , Huang Siyang , Xu Jinjun , Tao Jianping
Published: June 2022

Background

Eimeria coccidiosis is a significant intestinal parasitic disease, which can lead to weight loss, disease and even death of many animals. At present, there is no information about the prevalence of Eimeria among the world’s endangered species of Père David’s deer (Elaphurus davidianus). Therefore, the purpose of this study is to identify an unknown Eimeria genus in the Père David’s deer in Dafeng Milu National Nature Reserve, China.

Results

A new Eimeria species is described from Père David’s deer. Sporulated oocysts (n = 54) are pyriform, with a rough, yellowish brown, 2-layered oocyst wall (2.5 μm thick). A numerous small granules are dispersed randomly on the wall. Oocysts measured 41.2 (39.2–42.8) μm × 29.5 (27.9–30.5) μm, oocyst length/width (L/W) ratio, 1.4. Oocyst residuum, a polar granule and a polar cap are absent. The micropyle (3.5 μm wide) is present. Sporocysts are spindle shaped, 18.2 (16.5–20.0) μm × 10.5 (9.8–11.9) μm, sporocyst L/W ratio, 1.7 (1.5–1.9). A thin convex Stieda body is present and the sporocyst residuum is composed of numerous small granules less than 2.0 μm in diameter dispersed randomly. Each sporocyst contained 2 comma-shaped sporozoites in head-to-tail arrangement. A nucleus is located immediately anterior to the posterior, strong refractive and subspherical refractile body (~ 8 μm). Molecular analysis was conducted at the 18S, ITS-1 and COI loci.

Conclusion

Based on the morphological and molecular data, this isolate is a new species of coccidian parasite, which is named Eimeria davidianusi after its host, the Père David’s deer (Elaphurus davidianus).
Radiotherapy-activated NBTXR3 nanoparticles modulate cancer cell immunogenicity and TCR repertoire
Authors: Darmon Audrey , Zhang Ping , Marill Julie , Mohamed Anesary Naeemunnisa , Da silva Jordan , Paris Sébastien
Published: June 2022

Background

Radiotherapy is a powerful and widely used technique for the treatment of solid tumors. Beyond its ability to destroy tumor cells, it has been demonstrated that radiotherapy can stimulate the anti-tumor immune response. Unfortunately, this effect is mainly restricted to the irradiated lesion, as tumor control outside the treated field (called the ‘abscopal effect’) is rarely obtained. In addition, many pro-tumoral factors prevent this anti-tumor immune response from being sustained and efficient. We previously reported that radiotherapy-activated NBTXR3 produced a significant CD8-dependent abscopal effect in immunocompetent mice bearing CT26.WT tumors, while radiotherapy failed to generate such a response.

Methods

To identify the mechanisms that may explain this response, we evaluated the capacity of radiotherapy-activated NBTXR3 to modulate the immunogenicity of tumor cells by analysis of immunogenic cell death biomarkers and immunopeptidome sequencing. In vivo, we analyzed treated tumors for CD4+, CD8 + and CD68 + cell infiltrates by immunohistochemistry and digital pathology and sequenced the T cell receptor (TCR) repertoire in both treated and untreated distant tumors.

Results

We showed that NBTXR3 activated by radiotherapy both increased immunogenic cell death biomarkers and modulated the immunopeptidome profile of CT26.WT cells. Immunohistochemistry analysis of treated tumors revealed a significant increase in CD4+, CD8 + and CD68 + cell infiltrates for NBTXR3 activated by radiotherapy group, compared to radiotherapy. We also measured significant modifications in TCR repertoire diversity in the radiotherapy-activated NBTXR3 group, both in treated and distant untreated tumors, compared to radiotherapy alone.

Conclusions

These results indicate that radiotherapy-activated NBTXR3 can act as an effective immunomodulator, modifying tumor cell immunogenicity and impacting the lymphocyte population.

Graphical Abstract
Impact of a spatial repellent product on Anopheles and non-Anopheles mosquitoes in Sumba, Indonesia
Authors: Permana Dendi H. , Zubaidah Siti , Syahrani Lepa , Asih Puji B. S. , Syafruddin Din , Rozi Ismail E. , Hidayati Anggi P. N. , Kosasih Sully , Dewayanti Farahana K. , Rachmawati Nia , Risandi Rifqi , Bangs Michael J. , Bøgh Claus , Davidson Jenna R. , Hendershot Allison L. , Burton Timothy A. , Grieco John P. , Eugenio Evercita C. , Liu Fang , Achee Nicole L. , Lobo Neil F.
Published: June 2022

Background

The East Nusa Tenggara province, Indonesia, contributed to 5% of malaria cases nationally in 2020, with other mosquito-borne diseases, such as dengue and filariasis also being endemic. Monitoring of spatial and temporal vector species compositions and bionomic traits is an efficient method for generating evidence towards intervention strategy optimization and meeting disease elimination goals.

Methods

The impact of a spatial repellent (SR) on human biting mosquitoes was evaluated as part of a parent cluster-randomized, double-blinded, placebo-controlled trial, in Sumba, East Nusa Tenggara. A 10-month (June 2015–March 2016) baseline study was followed by a 24-month intervention period (April 2016 to April 2018)—where half the clusters were randomly assigned either a passive transfluthrin emanator or a placebo control.

Results

Human-landing mosquito catches documented a reduction in landing rates related to the SR. Overall, there was a 16.4% reduction (21% indoors, and 11.3% outdoors) in human biting rates (HBR) for Anopheles. For Aedes, there was a 44.3% HBR reduction indoors and a 35.6% reduction outdoors. This reduction was 38.3% indoors and 39.1% outdoors for Armigeres, and 36.0% indoors and 32.3% outdoors for Culex species. Intervention impacts on the HBRs were not significant and are attributed to large inter-household and inter cluster variation. Anopheles flavirostris, Anopheles balabacensis and Anopheles maculatus individually impacted the overall malaria infections hazard rate with statistically significance. Though there was SR-based protection against malaria for all Anopheles species (except Anopheles sundaicus), only five (Anopheles aconitus, Anopheles kochi, Anopheles tessellatus, An. maculatus and An. sundaicus) demonstrated statistical significance. The SR numerically reduced Anopheles parity rates indoors and outdoors when compared to the placebo.

Conclusion

Evidence demonstrating that Anopheles vectors bite both indoors and outdoors indicates that currently implemented indoor-based vector control tools may not be sufficient to eliminate malaria. The documented impact of the SR intervention on Aedes, Armigeres and Culex species points to its importance in combatting other vector borne diseases. Studies to determine the impact of spatial repellents on other mosquito-borne diseases is recommended.
The prevalence of symptomatic and asymptomatic malaria and its associated factors in Debre Elias district communities, Northwest Ethiopia
Authors: Abebaw Abtie , Aschale Yibeltal , Kebede Tadesse , Hailu Asrat
Published: June 2022

Background

Malaria is a major cause of morbidity and mortality worldwide. According to the World Health Organization 2021 malaria report, it is considered to be endemic in 85 countries and territories. Malaria elimination programmes have also faced many challenges, such as widespread asymptomatic carriers in endemic regions, and they should be considered in malaria-control programmes in endemic areas for successful transmission interruption. This study aimed to assess the prevalence of symptomatic and asymptomatic malaria infections, and associated factors in Debre Elias district communities, Northwest Ethiopia from May to Jun 2018.

Methods

A community-based cross-sectional study was conducted among selected kebeles in Debre Elias district, Amhara region, North-western Ethiopia. Multi-stage sampling technique was carried out to select representative households. A total of 440 randomly selected households were included, of which one individual per household was sampled for laboratory examination. Malaria prevalence was determined by light microscopy of stained blood films and using CareStart™ Malaria HRP2/pLDH (Pf/Pv) Combo rapid diagnostic test (RDT). A structured questionnaire was employed to collect socio-demographic data and associated risk factors. Data entry and analysis were carried out using Epi data 3.1 and SPSS version 23 software, respectively. The association between dependent and independent variables was explored by using bivariate and multivariate logistic regression analyses. Statistically significant association was declared at P-value of < 0.05.

Results

A total of 440 (333 asymptomatic and 107 symptomatic) individuals were included in this study. The overall prevalence of malaria was 5% with the majority (59.1%) of infections caused by Plasmodium falciparum. Among asymptomatic participants, 4.8% (n = 16, 95% CI = 2.6–7.3) and 4.2% (n = 14, 95% CI = 2.1–6.5) were diagnosed and confirmed by RDT and light microscopy respectively. Similarly, the prevalence of malaria among 107 symptomatic individuals was 7.5% (n = 8, 95% CI = 2.8–12.6) by either RDT or light microscopy. Utilization of insecticide-treated net (ITN), availability of ITN, house with eave, previous history of malaria infection, and family history of malaria infection were significantly associated with malaria infection (P < 0.05).

Conclusion

In this study, the prevalence of asymptomatic and symptomatic malaria was moderate. Screening of both symptomatic and asymptomatic malaria in the community is very important to scale up intervention programmes.
Material priority engineered metal-polyphenol networks: mechanism and platform for multifunctionalities
Authors: Cheng Xinxiu , Zhu Yaxin , Tang Sicheng , Lu Ruofei , Zhang Xiaoqiang , Li Na , Zan Xingjie
Published: June 2022

Engineering the surface of materials with desired multifunctionalities is an effective way to fight against multiple adverse factors during tissue repair process. Recently, metal-polyphenol networks (MPNs) have gained increasing attention because of their rapid and simple deposition process onto various substrates (silicon, quartz, gold and polypropylene sheets, etc.). However, the coating mechanism has not been clarified, and multifunctionalized MPNs remain unexplored. Herein, the flavonoid polyphenol procyanidin (PC) was selected to form PC-MPN coatings with Fe3+, and the effects of different assembly parameters, including pH, molar ratio between PC and Fe3+, and material priority during coating formation, were thoroughly evaluated. We found that the material priority (addition sequence of PC and Fe3+) had a great influence on the thickness of the formed PC-MPNs. Various surface techniques (e.g., ultraviolet–visible spectrophotometry, quartz crystal microbalance, X-ray photoelectron spectroscopy, atomic force microscopy, and scanning electron microscopy) were used to investigate the formation mechanism of PC-MPNs. Then PC-MPNs were further engineered with multifunctionalities (fastening cellular attachment in the early stage, promoting long-term cellular proliferation, antioxidation and antibacterial activity). We believe that these findings could further reveal the coating formation mechanism of MPNs and guide the future design of MPN coatings with multifunctionalities, thereby greatly broadening their application prospects, such as in sensors, environments, drug delivery, and tissue engineering.

Graphical Abstract
Processing mechanism of guanidinoacetate in choroid plexus epithelial cells: conversion of guanidinoacetate to creatine via guanidinoacetate N-methyltransferase and monocarboxylate transporter 12-mediated creatine release into the CSF
Authors: Jomura Ryuta , Akanuma Shin-ichi , Kubo Yoshiyuki , Tachikawa Masanori , Hosoya Ken-ichi
Published: June 2022

Background

Guanidinoacetate (GAA) induces epileptogenesis and neurotoxicity in the brain. As epileptic animal models have been reported to show elevated cerebral GAA levels, the processing mechanism of GAA in the brain is important for maintaining brain homeostasis. We have revealed that GAA in the cerebrospinal fluid (CSF) is removed by incorporation into the choroid plexus epithelial cells (CPxEpic), which form the blood-CSF barrier (BCSFB). However, the processing mechanism of GAA incorporated into CPxEpic remains unknown. We have reported that monocarboxylate transporter 12 (MCT12) functions as an efflux transporter of GAA and creatine, a metabolite of GAA, in the kidneys and liver. Therefore, we aimed to clarify the role of MCT12 in GAA dynamics in CPxEpic.

Methods

Protein expression and localization in CPxEpic were evaluated using immunohistochemistry. Metabolic analysis was performed using high-performance liquid chromatography (HPLC) 24 h after the addition of [14C]GAA to TR-CSFB3 cells, which are conditionally immortalized rat CPxEpic. The efflux transport of [14C]creatine was evaluated in TR-CSFB3 cells after transfection with MCT12 small interfering RNA (siRNA). The CSF-to-brain parenchyma transfer of creatine was measured after intracerebroventricular injection in rats.

Results

Immunohistochemical staining revealed that MCT12-derived signals merged with those of the marker protein at the apical membrane of CPxEpic, suggesting that MCT12 is localized on the apical membrane of CPxEpic. The expression levels of guanidinoacetate N-methyltransferase (GAMT), which catalyzes the conversion of GAA to creatine, in TR-CSFB3 cells was also indicated, and GAA was considered to be metabolized to creatine after influx transport into CPxEpic, after which creatine was released into the CSF. Creatine release from TR-CSFB3 cells decreased following MCT12 knockdown. The contribution ratio of MCT12 to the release of creatine was more than 50%. The clearance of CSF-to-brain parenchyma transfer of creatine was 4.65 µL/(min·g brain), suggesting that biosynthesized creatine in CPxEpic is released into the CSF and supplied to the brain parenchyma.

Conclusions

In CPxEpic, GAA is metabolized to creatine via GAMT. Biosynthesized creatine is then released into the CSF via MCT12 and supplied to the brain parenchyma.
DTX-P7, a peptide–drug conjugate, is highly effective for non-small cell lung cancer
Authors: Jiang Yao , Huang Wei , Sun Xiaojiao , Yang Xiaozhou , Wu Youming , Shi Jiaojiao , Zheng Ji , Fan Shujie , Liu Junya , Wang Jun , Liang Zhen , Yang Nan , Liu Zhenming , Liu Yanyong
Published: June 2022

Despite tremendous success of molecular targeted therapy together with immunotherapy, only a small subset of patients can benefit from them. Chemotherapy remains the mainstay treatment for most of tumors including non-small cell lung cancer (NSCLC); however, non-selective adverse effects on healthy tissues and secondary resistance are the main obstacles. Meanwhile, the quiescent or dormant cancer stem-like cells (CSLCs) are resistant to antimitotic chemoradiotherapy. Complete remission can only be realized when both proliferative cancer cells and quiescent cancer stem cells are targeted. In the present research, we constructed a cooperatively combating conjugate (DTX-P7) composed of docetaxel (DTX) and a heptapeptide (P7), which specifically binds to cell surface Hsp90, and assessed the anti-tumor effects of DTX-P7 on non-small cell lung cancer. DTX-P7 preferentially suppressed tumor growth compared with DTX in vivo with a favorable distribution to tumor tissues and long circulation half-life. Furthermore, we revealed a distinctive mechanism whereby DTX-P7 induced unfolded protein response and eventually promoted apoptosis. More importantly, we found that DTX-P7 promoted cell cycle reentry of slow-proliferating CSLCs and subsequently killed them, exhibiting a “proliferate to kill” pattern. Collecitvely, by force of active targeting delivery of DTX via membrane-bound Hsp90, DTX-P7 induces unfolded protein response and subsequent apoptosis by degrading Hsp90, meanwhile awakens and kills the dormant cancer stem cells. Thus, DTX-P7 deserves further development as a promising anticancer therapeutic for treatment of various membrane-harboring Hsp90 cancer types.

Graphical Abstract
Integrated proteogenomic characterization of urothelial carcinoma of the bladder
Authors: Xu Ning , Yao Zhenmei , Shang Guoguo , Ye Dingwei , Wang Haixing , Zhang Hailiang , Qu Yuanyuan , Xu Fujiang , Wang Yunzhi , Qin Zhaoyu , Zhu Jiajun , Zhang Fan , Feng Jinwen , Tian Sha , Liu Yang , Zhao Jianyuan , Hou Jun , Guo Jianming , Hou Yingyong , Ding Chen
Published: June 2022

Background

Urothelial carcinoma (UC) is the most common pathological type of bladder cancer, a malignant tumor. However, an integrated multi-omics analysis of the Chinese UC patient cohort is lacking.

Methods

We performed an integrated multi-omics analysis, including whole-exome sequencing, RNA-seq, proteomic, and phosphoproteomic analysis of 116 Chinese UC patients, comprising 45 non-muscle-invasive bladder cancer patients (NMIBCs) and 71 muscle-invasive bladder cancer patients (MIBCs).

Result

Proteogenomic integration analysis indicated that SND1 and CDK5 amplifications on chromosome 7q were associated with the activation of STAT3, which was relevant to tumor proliferation. Chromosome 5p gain in NMIBC patients was a high-risk factor, through modulating actin cytoskeleton implicating in tumor cells invasion. Phosphoproteomic analysis of tumors and morphologically normal human urothelium produced UC-associated activated kinases, including CDK1 and PRKDC. Proteomic analysis identified three groups, U-I, U-II, and U-III, reflecting distinct clinical prognosis and molecular signatures. Immune subtypes of UC tumors revealed a complex immune landscape and suggested the amplification of TRAF2 related to the increased expression of PD-L1. Additionally, increased GARS, related to subtype U-II, was validated to promote pentose phosphate pathway by inhibiting activities of PGK1 and PKM2.

Conclusions

This study provides a valuable resource for researchers and clinicians to further identify molecular pathogenesis and therapeutic opportunities in urothelial carcinoma of the bladder.
How we treat NK/T-cell lymphomas
Authors: Tse Eric , Zhao Wei-Li , Xiong Jie , Kwong Yok-Lam
Published: June 2022

Natural killer (NK)/T-cell lymphomas are aggressive malignancies with a predilection for Asian and South American populations. Epstein–Barr virus (EBV) infection in lymphoma cells is universal. Predominantly extranodal, NK/T-cell lymphomas are divided clinically into nasal (involving the nose and upper aerodigestive tract), non-nasal (involving the skin, gastrointestinal tract, testes, and other organs), and aggressive leukaemia/lymphoma (involving the marrow and multiple organs) subtypes. Initial assessment should include imaging with positron emission tomography computed tomography (PET/CT), quantification of plasma EBV DNA as a surrogate marker of lymphoma load, and bone marrow examination with in situ hybridization for EBV-encoded small RNA. Prognostication can be based on presentation parameters (age, stage, lymph node involvement, clinical subtypes, and EBV DNA), which represent patient factors and lymphoma load; and dynamic parameters during treatment (serial plasma EBV DNA and interim/end-of-treatment PET/CT), which reflect response to therapy. Therapeutic goals are to achieve undetectable plasma EBV DNA and normal PET/CT (Deauville score ≤ 3). NK/T-cell lymphomas express the multidrug resistance phenotype, rendering anthracycline-containing regimens ineffective. Stage I/II nasal cases are treated with non-anthracycline asparaginase-based regimens plus sequential/concurrent radiotherapy. Stage III/IV nasal, and non-nasal and aggressive leukaemia/lymphoma cases are treated with asparaginase-containing regimens and consolidated by allogeneic haematopoietic stem cell transplantation (HSCT) in suitable patients. Autologous HSCT does not improve outcome. In relapsed/refractory cases, novel approaches comprise immune checkpoint blockade of PD1/PD-L1, EBV-specific cytotoxic T-cells, monoclonal antibodies, and histone deacetylase inhibitors. Future strategies may include inhibition of signalling pathways and driver mutations, and immunotherapy targeting the lymphoma and its microenvironment.