bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying substantial carcinogenesis of genetic and environmental factors from measurement error in the number of stem cell divisions
Authors: Liu Xinhui , Yang Jifeng , Li Hongkai , Wang Qing , Yu Yuanyuan , Sun Xiaoru , Si Shucheng , Hou Lei , Liu Lu , Yang Fan , Yan Ran , Yu Yifan , Fu Zhentao , Lu Zilong , Li Dejin , Xue Hao , Guo Xiaolei , Xue Fuzhong , Ji Xiaokang
Published: November 2022

Background

The relative contributions of genetic and environmental factors versus unavoidable stochastic risk factors to the variation in cancer risk among tissues have become a widely-discussed topic. Some claim that the stochastic effects of DNA replication are mainly responsible, others believe that cancer risk is heavily affected by environmental and hereditary factors. Some of these studies made evidence from the correlation analysis between the lifetime number of stem cell divisions within each tissue and tissue-specific lifetime cancer risk. However, they did not consider the measurement error in the estimated number of stem cell divisions, which is caused by the exposure to different levels of genetic and environmental factors. This will obscure the authentic contribution of environmental or inherited factors.

Methods

In this study, we proposed two distinct modeling strategies, which integrate the measurement error model with the prevailing model of carcinogenesis to quantitatively evaluate the contribution of hereditary and environmental factors to cancer development. Then, we applied the proposed strategies to cancer data from 423 registries in 68 different countries (global-wide), 125 registries across China (national-wide of China), and 139 counties in Shandong province (Shandong provincial, China), respectively.

Results

The results suggest that the contribution of genetic and environmental factors is at least 92% to the variation in cancer risk among 17 tissues. Moreover, mutations occurring in progenitor cells and differentiated cells are less likely to be accumulated enough for cancer to occur, and the carcinogenesis is more likely to originate from stem cells. Except for medulloblastoma, the contribution of genetic and environmental factors to the risk of other 16 organ-specific cancers are all more than 60%.

Conclusions

This work provides additional evidence that genetic and environmental factors play leading roles in cancer development. Therefore, the identification of modifiable environmental and hereditary risk factors for each cancer is highly recommended, and primary prevention in early life-course should be the major focus of cancer prevention.
All in a scent - naphthalene dependence confined to pregnancy: a case report
Authors: Wimalasiri Isuri , Suraweera Chathurie
Published: November 2022

Background

Inhalant or volatile substance use is a health issue with significant medical and psychiatric sequelae. Inhalants or volatile substances are volatile organic substances found in domestic and commercial products which are inhaled to obtain pleasurable effects. They are easily accessible, cheap, and legal. Common inhalants are spray, paints, glue and shoe polish whilst naphthalene or ‘mothball’ abuse is reported less commonly. We report a case of a 29-year-old female who inhaled and ingested naphthalene during her pregnancy. This case report is unique because the dependence on naphthalene was confined to pregnancy and resolved as soon as she delivered. This brings up the question whether pregnancy in general increases the risk of substance dependence in vulnerable populations or whether the dependence in this patient during pregnancy is due to individual factors.

Case presentation

The patient we report is a 29-year-old female who developed a strong desire to inhale mothballs during her third pregnancy. The pattern of use started in the first trimester meeting the criteria for dependence syndrome and resolved completely by the second day following delivery. She had features suggestive of harmful use in her second pregnancy as well.

Conclusions

The case report emphasizes that pregnant women should be screened for psychoactive substance use. Equally important is the need for adequate psychoeducation about the myths and cultural beliefs associated with pregnancy-related cravings and the potentially devastating consequences of harmful cravings on the neonate and the mother. The case highlights how chemicals used in day-to-day activities can lead to dependence.
The actual and anticipated effects of restrictions on flavoured electronic nicotine delivery systems: a scoping review
Authors: Cadham Christopher J. , Liber Alex C. , Sánchez-Romero Luz María , Issabakhsh Mona , Warner Kenneth E. , Meza Rafael , Levy David T.
Published: November 2022

Objective

To synthesize the outcomes of policy evaluations of flavoured electronic nicotine delivery systems (ENDS) restrictions.

Data sources

PubMed, Scopus, Embase and Web of Science before May 3, 2022.

Study selection

Studies that report sales, behaviour, or compliance outcomes related to implemented or hypothetical ENDS flavour restrictions.

Data extraction

Restriction details, whether implemented or hypothetical, whether additional products were restricted, jurisdictional level, study locations, and outcomes classified by sales, behaviour, and compliance.

Data synthesis

We included 30 studies. Of those, 26 were conducted exclusively in the US, two in India, and two surveyed respondents in multiple countries, including the US. Twenty-one evaluated implemented restrictions, while nine considered hypothetical restrictions. Five studies evaluated product sales, 17 evaluated behaviour, and 10 evaluated compliance, with two studies reporting multiple outcomes. Two studies reported an increase and one a reduction in cigarette sales following restrictions, while three reported reductions in ENDS sales. Behavioural studies presented a mixed view of the impacts of regulations on ENDS and cigarette use. However, the use of disparate outcomes limits the comparability of studies. Studies of hypothetical restrictions suggest decreased ENDS use, increased cigarette use, and increased use of illicit markets. Studies of compliance with flavoured product restrictions that included ENDS found that 6–39% of stores sold restricted flavoured products post-restrictions. Online stores remain a potential source of restricted products.

Conclusion

Our findings highlight the need for additional research on the impacts of ENDS restrictions. Research should further evaluate the impact of restrictions on youth and adult use of nicotine and tobacco products in addition to the effects of restrictions in countries beyond the US to enable a robust consideration of the harm-benefit trade-off of restrictions.
Nutritional quality and consumer health perception of online delivery food in the context of China
Authors: Dai Xiaoting , Wu Linhai , Hu Wuyang
Published: November 2022

Background

Today, the popularization of mobile internet technology has enabled the public’s need for food convenience and diversity arising from modern fast-paced lifestyles to be met at a relatively low cost. The digital age of the restaurant industry has arrived. Online food delivery (OFD) is rapidly developing globally. However, the public’s awareness of the nutritional quality of food through OFD and their knowledge of dietary nutrition remain to be investigated.

Methods

In the context of China, this study attempts to evaluate the nutritional quality of best-selling OFD set meals (i.e., meal combos) based on the current official Chinese dietary guidelines 2022. It accomplishes this by collecting data on popular OFD restaurants among consumers in 115 Chinese universities from the restaurants’ delivery addresses. Moreover, 20,430 valid questionnaires were collected online from undergraduates, graduate students, and other young groups aged 18–30 throughout China for descriptive analysis to investigate consumers’ perceptions of the nutritional quality of food through OFD and its health impact.

Results

The results of the nutritional quality evaluation of the OFD set meals ranged widely from 15 to 85, with a mean of 36.57 out of a possible maximum score of 100; and 89.56% scored less than 50. The nutritional quality of OFD foods was thus generally low. The nutritional quality of foods was negatively correlated with their popularity among consumers.

Conclusions

Young OFD consumers generally paid low attention to dietary nutrition knowledge and seldom paid attention to nutritional quality when choosing OFD foods while the nutritional quality of OFD foods was generally low. Respondents subjectively reported that long-term consumption of OFD food caused weight gain, increased blood lipids, and gastrointestinal discomfort. They thought that the reason might be excessive oil, salt, and sugar in the food, while ignoring the balance between different types of food.
A register-based study: cough - a frequent phenomenon in the adult population
Authors: Backer Vibeke , Porsborg Andreas , Hansen Victor , Skjold Tina , Schmid Johannes Martin , Kehlet Mette , Torp-Pedersen Christian , Aasbjerg Kristian
Published: November 2022

Background

Chronic cough, more than 8 weeks, can either be without co-morbidity called unexplained chronic cough (UCC) or with co-morbidity called refractory chronic cough (RCC). Using datasets from the Danish National Prescription Registry (Prescription Registry) and Danish National Patient Registry (Patient Registry) we wanted to investigate the prevalence and factors of importance of cough in a Nationwide registry.

Material and methods

Inclusion criteria were patients 18–90 years with at least one final cough diagnosis (ICD-10 DR05/DR059) in Patient registry or patients who have redeemed ≥2 prescriptions for relevant cough-medication within a 90-day harvest in the Prescription registry from 2008 to 2017. To validate this study’s chosen proxy on chronic cough an analysis of the Patient registry sub-population with a contact of ≥8 weeks and then final diagnosis code DR05/DR059 was also performed. The population was divided into UCC and RCC.

Results

Of the 104,216 patients from the Prescription registry, 52,727 were classified as having UCC and 51,489 were classified with RCC. From the Patient registry 34,260 were included, of whom 12,278 had UCC and 21,982 had RCC. Cough were frequently found among females (p < 0.0001). Both genders were around 2 years older in RCC than UCC (p < 0.0001) Spirometry was performed in 69 and 57%, X-ray in 73 and 58% and asthma challenge test performed in 13 and 5% (UCC and RCC, respectively, p < 0.0001). The frequency of co-morbidities such as heart failure, rheumatologic disease, pulmonary embolism, and diabetes was < 10%.

Conclusion

Many patients suffer from chronic cough or cough requiring medications, with or without co-morbidity; frequently found among menopausal women. Most patients had a substantial work-up performed. The high frequency and the resources consuming work-up program call for systematic coding of disease, systematic patient evaluation and more specific treatment options. The study was approved (ID: no. P-2019-191).
The narrow subspine space and relatively large labrum are radiographic features of subspine impingement: a case-control study
Authors: Liu Rongge , Zhao Yuqing , Xu Yan , Yuan Huishu
Published: November 2022

Background

Subspine impingement is considered a source of residual hip symptoms after primary hip arthroscopy, and the role of the subspine space and soft tissue is not clear. The purpose of this study was to analyze the relationship between the subspine space and labrum size in subspine impingement patients.

Methods

We performed a retrospective study of patients with femoroacetabular impingement between July 2016 and July 2020. Sixteen patients without hip symptom relief after primary hip arthroscopic treatment of femoroacetabular impingement and undergoing revision surgery for anterior inferior iliac spine compression were included as the study group. Forty-eight matched patients who underwent only primary surgery and whose hip discomfort was relieved without a diagnosis of subspine impingement were included as the control group. The patients’ preoperative computerized tomography data were reviewed, and the anterior inferior iliac spine dimensions and the size of the subspine space were measured. The size of the labrum at the 11:30, 1:30, and 3 o’clock positions was measured with the use of magnetic resonance imaging. The ratio of the subspine space to the labrum was also calculated.

Results

There was no significant difference in anterior inferior iliac spine dimensions between these two groups (p > 0.05). A relatively narrow subspine space was found in the study group, especially in the direction of the anterior inferior iliac spine. Compared with the control group, subspine impingement patients were identified with larger labrums at 11:30 (8.20 ± 1.95 mm vs. 6.81 ± 0.50 mm, p = 0.016), 1:30 (7.83 ± 1.61 mm and 6.25 ± 0.78 mm, p = 0.001) and 3:00 (9.50 ± 1.73 mm vs. 7.48 ± 0.99 mm, p = 0.001). A relative mismatch between the subspine space and the labrum was also identified in the study group. The ratios of the labrum width to the subspine area were significantly larger in the study group than in the control group.

Conclusion

This study reported potential additional criteria for subspine impingement—a large labrum and a relatively narrow subspine space—instead of abnormal anterior inferior iliac spine dimensions. For those with a large labrum and narrow subspine space, the diagnosis of subspine impingement should be carefully made, and arthroscopic anterior inferior iliac spine decompression may be important.
Dietary glycemic index and glycemic load mediate the effect of CARTPT rs2239670 gene polymorphism on metabolic syndrome and metabolic risk factors among adults with obesity
Authors: Khodarahmi Mahdieh , Siri Goli , Erahimzadeh Farnoosh , Farhangi Mahdieh Abbasalizad , Shanehbandi Dariush
Published: November 2022

Introduction

The importance of genetic and dietary factors in occurrence and progression of chronic diseases such as metabolic syndrome (MetS) has been established. However, complex interrelationships, including direct and indirect effects of these variables are yet to be clarified. So, our aim was to investigate the mediating role of glycemic indices in the relationship between CARTPT rs2239670 polymorphism, socio-demographic and psychological factors and metabolic risk factors and the presence of MetS in adults with obesity.

Methods

In a cross-sectional study of 288 apparently healthy adults with obesity aged 20–50 years, dietary glycemic index (GI) and glycemic load (GL) were measured using a validated semi-quantitative food frequency questionnaire (FFQ). Biochemical parameters, blood pressure and anthropometric indicators were assayed by standard methods. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) technique. Structural equation modeling (SEM) was used in the statistical analysis.

Results

CARTPT rs2239670 had a positive direct effect on MetS (B = 0.037 ± 0.022; P = 0.043) and, on the other hand, this variant was found to be indirectly associated with MetS presence through mediation of GI (B = 0.039 ± 0.017; P = 0.009). CARTPT was a significant predictor of both dietary GI and GL (B = 1.647 ± 0.080 and B = 3.339 ± 0.242, respectively). Additionally, glycemic indicators appeared to mediate the association of age and gender with LDL-C (B = 0.917 ± 0.332; P = 0.006) and HDL (B = 1.047 ± 0.484; P = 0.031), respectively. GI showed a positive relationship with LDL-C (P = 0.024) in men and similar relationships were found between GL and LDL-C (P = 0.050) and cholesterol (P = 0.022) levels in women.

Conclusion

The SEM findings suggest a hypothesis of the mediating effect of glycemic indices in the relationship between genetic susceptibility to obesity and MetS presence. Our findings need to be confirmed with large prospective studies.
A multi-country study on the impact of sex and age on oral features of COVID-19 infection in adolescents and young adults
Authors: Sabbagh Heba Jafar , Abdelaziz Wafaa , Quritum Maryam , Alamoudi Rana Abdullah , AlKhateeb Nada Abu Bakr , Abourdan Joud , Qureshi Nafeesa , Qureshi Shabnum , Hamoud Ahmed H. N. , Mahmoud Nada , Odeh Ruba , Al-Khanati Nuraldeen Maher , Jaber Rawiah , Balkhoyor Abdulrahman Loaie , Shabi Mohammed , Folayan Morenike Oluwatoyin , Alade Omolola , Gomaa Noha , Alnahdi Raqiya , Mahmoud Nawal A. , El Wazziki Hanane , Alnaas Manal , Samodien Bahia , Mahmoud Rawa A. , Assab Nour Abu , Saad Sherin , Alsayad Maha Mohamed , Alhachim Sondos G. , El Tantawi Maha
Published: November 2022

Background

Oral diseases are features of COVID-19 infection. There is, however, little known about oral diseases associated with COVID-19 in adolescents and young adults (AYA). Therefore, the aim of this study was to assess oral lesions’ association with COVID-19 infection in AYA; and to identify if sex and age will modify these associations.

Methodology

Data was collected for this cross-sectional study between August 2020 and January 2021 from 11-to-23 years old participants in 43-countries using an electronic validated questionnaire developed in five languages. Data collected included information on the dependent variables (the presence of oral conditions- gingival inflammation, dry mouth, change in taste and oral ulcers), independent variable (COVID-19 infection) and confounders (age, sex, history of medical problems and parents’ educational level). Multilevel binary logistic regression was used for analysis.

Results

Complete data were available for 7164 AYA, with 7.5% reporting a history of COVID-19 infection. A significantly higher percentage of participants with a history of COVID-19 infection than those without COVID-19 infection reported having dry mouth (10.6% vs 7.3%, AOR = 1.31) and taste changes (11.1% vs 2.7%, AOR = 4.11). There was a significant effect modification in the association between COVID-19 infection and the presence of dry mouth and change in taste by age and sex (P = 0.02 and < 0.001).

Conclusion

COVID-19 infection was associated with dry mouth and change in taste among AYA and the strength of this association differed by age and sex. These oral conditions may help serve as an index for suspicion of COVID-19 infection in AYA.
Follicular lymphoma manifests as multiple erosive and proliferative lesions of the oral mucosa: case report and brief literature review
Authors: Wu Yuqi , Zhang You , Li Chunyu , Xie Yulang , Jiang Sixin , Jiang Yuchen , Qiu Yan , Luo Xiaobo , Chen Qianming
Published: November 2022

Background

Erosion is one of the most common and basic lesions of oral mucosal diseases. Long-term refractory oral erosions, induced by autoimmune blistering diseases, infectious diseases, malignant diseases, and some rare conditions, may substantially reduce the quality of life of patients or even constitute a life-threatening condition, resulting in a clinical dilemma regarding the accurate diagnosis and precise management of these diseases. As a special type of malignant lymphoma, most lesions of follicular lymphoma (FL) in the oral mucosa present as masses or swelling of the oral mucosa, while emerging novel presentations lead to intractable diagnoses. Hence, diagnostic algorithms for such diseases are clinically required. 

Case presentation

A 55-year-old female patient presented to the clinic with long-lasting oral mucosal erosions and proliferative lesions. Blood tests, pathological examinations of oral lesions including haematoxylin–eosin (HE) staining, and direct immunofluorescence precluded all of the potential diagnoses described previously. Unexpectedly, positron emission tomography/computed tomography (PET/CT) and abdominal CT of the patient revealed a dense mass in the retroperitoneal area, and the final diagnosis of the retroperitoneal mass was FL. After three courses of chemotherapy conducted by the haematologist, the erosion and proliferative lesions in the patient's oral mucosa had significantly improved. HE and immunohistochemical staining results of intraoral lesions also confirmed it as oral FL. The successful diagnosis of FL in this case is of great clinical significance, as the oral and abdominal FL were treated in a timely manner to avoid unfavourable outcomes.

Conclusions

To the best of our knowledge, this is the first case of FL that exhibited widespread erosions interspersed with proliferative lesions. Clinicians should be aware of oral FL or seek systemic factors in the presence of similar refractory oral erosions when treatment is non-responsive and the diagnosis is intractable.
Relationship between DMFT index and reproductive history- a cross-sectional study on enrollment phase of Azar cohort study
Authors: Hefzollesan Sahra , Sharififard Nasrin , Mahboobi Zeinab , Faramarzi Elnaz
Published: November 2022

Background

Hormonal changes in women throughout life might affect the oral health. The aim of this study is to investigate the relationship between the Decayed, Missing, and Filled Teeth (DMFT) index and reproductive history.

Methods

The present cross-sectional study was performed using data of Azar Cohort Study conducted in 2014, in Shabestar city, East Azerbaijan Province, Iran. In the present study, the data of all 8294 women from the enrollment phase of the Azar cohort were included. All available data related on the variables of reproductive history (including age at the onset of menstruation, age of onset of menopause, age of first pregnancy, and frequency of pregnancy), age at interview, educational level, socioeconomic status, frequency of tooth brushing, chronic diseases, body mass index and DMFT were extracted. Negative binomial regression with loglink was used to analyze the relationship between variables. Three regression models have been applied to adjust the effect of confounding variables. Model 1 adjusted for education, socio-economic status, age, chronic diseases, body mass index and frequency of tooth brushing. Model 2 adjusted for education, socioeconomic status, age, chronic diseases and body mass index. Model 3 adjusted for education, socio-economic status and age.

Results

The mean DMFT of 8294 women was 20.99 ± 8.95. In model 1, there was no significant relationship between DMFT and frequency of pregnancy. However, model 2 and 3 showed that in women who had four or more pregnancies, the DMFT rate was significantly higher than those who did not have a history of pregnancy (P = 0.02, P = 0.04). Age at the onset of menopause, age at the onset of menstruation and age of first pregnancy had no significant relationship with DMFT in the models. Brushing less than once a day and increasing age at interview had significant relationship with DMFT in the models (P < 0.001).

Conclusion

Despite hormonal changes through the life, the history of reproductive showed no significant relationship with women’s DMFT. Oral health education for women is an important step in promoting oral health and it is necessary to pay special attention to preventive programs in oral health policy for women specially with increasing the age.
Evaluation of the marginal adaptation and gingival status of full-crown restorations using an intraoral camera
Authors: Chiu Shuting , Lee Yeh , Liu Min , Chen Hu , Ye Hongqiang , Liu Yunsong
Published: November 2022

Objective

The purpose of this study was to compare the usefulness of intraoral photographs, acquired with a household intraoral camera operating in conventional, calibrated, and polarized modes, with clinical examinations for assessing the marginal adaptation and gingival status of full-crown restorations.

Methods

Clinical examinations were performed by a prosthodontist who classified the marginal adaptation of full-crown restorations according to FDI World Dental Federation criteria, and a periodontal expert who classified gingival status according to the Modified Gingival Index (MGI). The margins and gingival status of the conventional, calibration, and polarization groups of full-crown restorations were independently assessed by three evaluators who obtained photographs using an intraoral camera. Cases where at least two of three assessors were in agreement were analyzed using Cohen’s kappa coefficient and the chi-square test, and the sensitivity and specificity were calculated.

Results

The conventional, calibration, and polarization groups differed significantly in marginal and gingival status of full-crown restorations. In the calibration group, there was good agreement between the camera-based and oral clinical examinations in terms of the gingival status of full-crown restorations (kappa = 0.945), with 100% sensitivity and 91.67% specificity; this was also the case in the polarization group with respect to the margins of full-crown restorations (kappa = 0.917, sensitivity = 97.22%, specificity = 94.44%).

Conclusions

An intraoral camera with black and white calibrated images is useful to assess the gingival status of full-crown restorations. Polarization mode can be used to assess the marginal adaptation of full-crown restorations. The camera is a feasible and valid diagnostic aid.
Applying technology to promote sexual and reproductive health and prevent gender based violence for adolescents in low and middle-income countries: digital health strategies synthesis from an umbrella review
Authors: Huang Keng-Yen , Kumar Manasi , Cheng Sabrina , Urcuyo Anya Elena , Macharia Paul
Published: November 2022

Aim

Adolescents in low-and-middle-income countries (LMICs) are facing numerous developmental, sexual and reproductive health (SRH) challenges including exposure to multidimensional violence. Gender-based violence (GBV) specifically intimate partner violence (IPV) are both highly prevalent in LMICs and are strongly linked with poor SRH outcomes. However, GBV and IPV interventions have not yet been adequately integrated in SRH due to individual, social, cultural, service, and resource barriers. To promote long-term SRH, a more holistic approach that integrates GBV and IPV, and adolescent development needs is imperative. Digital health has the potential to address multiple service setup, provision, and addressing access barriers through designing and providing integrated SRH care. However, there are no guidelines for an integrated digital SRH and development promotion for adolescents in LMICs.

Methods

An umbrella review was conducted to synthesize evidence in three inter-related areas of digital health intervention literature: (i) SRH, (ii) GBV specifically IPV as a subset, and (iii) adolescent development and health promotion. We first synthesize findings for each area of research, then further analyze the implications and opportunities to inform approaches to develop an integrated intervention that can holistically address multiple SRH needs of adolescents in LMICs. Articles published in English, between 2010 and 2020, and from PubMed were included.

Results

Seventeen review articles met our review inclusion criterion. Our primary finding is that application of digital health strategies for adolescent SRH promotion is highly feasible and acceptable. Although effectiveness evidence is insufficient to make strong recommendations for interventions and best practices suggestions, some user-centered design guidelines have been proposed for web-based health information and health application design for adolescent use. Additionally, several digital health strategies have also been identified that can be used to further develop integrated GBV-IPV-SRH-informed services to improve adolescent health outcomes. We generated several recommendations and strategies to guide future digital based SRH promotion research from our review.

Conclusions

Rigorous research that focuses on intervention effectiveness testing using a combination of digital health strategies and standardized albeit contextualized outcome measures would be important. Methodological improvement such as adoption of longitudinal experimental design will be crucial in generating evidence-based intervention and practice guidelines for adolescents in LMICs.
Service quality and accessibility of healthcare facilities: digital healthcare potential in Ho Chi Minh City
Authors: Le Khanh Hung , La Thi Xuan Phuong , Tykkyläinen Markku
Published: November 2022

Background

Effective delivery of health services requires adequate quality in healthcare facilities and easy accessibility to health services physically or virtually. The purpose of this study was to reveal how the quality of healthcare facilities varies across the different parts of Ho Chi Minh City and how well residents (N = 9 million) can reach healthcare facilities. By demarcating the deficiently served areas of low accessibility, the study shows where urban planning and digital healthcare could improve accessibility to health services and the quality of services efficiently.

Methods

The analysis utilised geocoded information on hospitals, clinics, roads and population and the data of the quality scores of healthcare facilities. Quality scores were analysed by hot spot analysis and inverse distance weighting. Accessibility and formation of travel time-based service areas by travel time distances were calculated using road network, driving speed and population data.

Results

The results unveiled a centripetal spatial pattern of healthcare facilities and a similar pattern in their quality. Outside the travel time of 30 min for hospitals and 15 min for clinics, the deficiently served areas have a population of 1.1 to 1.2 million. Based on the results and the evidence of digital healthcare, this paper highlights how to develop and plan spatially effective service provision. Especially, it gives grounds to discuss how cost-effective digital healthcare could be applied to improve the accessibility and quality of health services in an urban structure of extensively varying accessibility to health services.

Conclusions

The results bring up the need and the means for improving the quality of health services and their cost-efficient availability by location optimisation, road improvements and implementing digital healthcare provided by hospitals and clinics in the city. At the same, this study provides a multidisciplinary approach for planning more equal and efficient health service provision geographically.
Dutch public health professionals’ perspectives and needs regarding citizen involvement in COVID-19 contact tracing through digital support tools: an exploratory qualitative study
Authors: Helms Y. B. , Stein M. L. , Hamdiui N. , van der Meer A. , Baron R. , Eilers R. , Crutzen R. , Kretzschmar M. E. E. , Timen A.
Published: November 2022

Background

Contact tracing (CT) is an important, but resource-intensive tool to control outbreaks of communicable diseases. Under pandemic circumstances, public health services may not have sufficient resources at their disposal to effectively facilitate CT. This may be addressed by giving cases and their contact persons more autonomy and responsibility in the execution of CT by public health professionals, through digital contact tracing support tools (DCTS-tools). However, the application of this approach has not yet been systematically investigated from the perspective of public health practice. Therefore, we investigated public health professionals’ perspectives and needs regarding involving cases and contact persons in CT for COVID-19 through DCTS-tools.

Methods

Between October 2020 and February 2021, we conducted online semi-structured interviews (N = 17) with Dutch public health professionals to explore their perspectives and needs regarding the involvement of cases and contact persons in CT for COVID-19 through DCTS-tools, in the contact identification, notification, and monitoring stages of the CT-process. Interviews were audio recorded and transcribed verbatim. A thematic analysis was performed.

Results

Four main themes related to Dutch public health professionals’ perspectives and needs regarding involving cases and contact persons in CT for COVID-19 through DCTS-tools emerged from the data: ‘Distinct characteristics of CT with DCTS-tools’; ‘Anticipated benefits and challenges of CT for COVID-19 with DCTS- tools’; ‘Circumstances in CT for COVID-19 that permit or constrain the application of DCTS-tools’; and ‘Public health professionals’ needs regarding the development and application of DCTS-tools for CT’. Public health professionals seem to have a positive attitude towards involving cases and contact persons through DCTS-tools. Public health professionals’ (positive) attitudes seem conditional on the circumstances under which CT is performed, and the fulfilment of their needs in the development and application of DCTS-tools.

Conclusions

Dutch public health professionals seem positive towards involving cases and contact persons in CT for COVID-19 through DCTS-tools. Through adequate implementation of DCTS-tools in the CT-process, anticipated challenges can be overcome. Future research should investigate the perspectives and needs of cases and contact persons regarding DCTS-tools, and the application of DCTS-tools in practice.
The association of hyperketonemia with fecal and rumen microbiota at time of diagnosis in a case-control cohort of early lactation cows
Authors: Miles Asha M. , McArt Jessica A. A. , Lima Svetlana F. , Neves Rafael C. , Ganda Erika
Published: November 2022

Background

Many dairy cows experience a state of energy deficit as they transition from late gestation to early lactation. The aims of this study were to 1) determine if the development of hyperketonemia in early lactation dairy cows is indicated by their gut microbiome, and 2) to identify microbial features which may inform health status. We conducted a prospective nested case-control study in which cows were enrolled 14 to 7 days before calving and followed through their first 14 days in milk (DIM). Hyperketonemic cows (HYK, n = 10) were classified based on a blood β-hydroxybutyrate (BHB) concentration 1.2 mmol/L within their first 14 DIM. For each HYK cow, two non-HYK (CON, n = 20) cows were matched by parity and 3 DIM, with BHB < 1.2 mmol/L. Daily blood BHB measures were used to confirm CON cows maintained their healthy status; some CON cows displayed BHB 1.2 mmol/L after matching and these cows were reclassified as control-HYK (C-HYK, n = 9). Rumen and fecal samples were collected on the day of diagnosis or matching and subjected to 16S rRNA profiling.

Results

No differences in taxa abundance, or alpha and beta diversity, were observed among CON, C-HYK, and HYK health groups for fecal microbiomes. Similar microbiome composition based on beta diversity analysis was detected for all health statuses, however the rumen microbiome of CON and HYK cows were found to be significantly different. Interestingly, highly similar microbiome composition was observed among C-HYK cow rumen and fecal microbiomes, suggesting that these individual animals which initially appear healthy with late onset of hyperketonemia were highly similar to each other. These C-HYK cows had significantly lower abundance of Ruminococcus 2 in their rumen microbiome compared to CON and HYK groups. Multinomial regressions used to compute log-fold changes in microbial abundance relative to health status were not found to have predictive value, therefore were not useful to identify the role of certain microbial features in predicting health status.

Conclusions

Lower relative abundance of Ruminococcus 2 in C-HYK cow rumens was observed, suggesting these cows may be less efficient at degrading cellulose although the mechanistic role of Ruminococcus spp. in rumen metabolism is not completely understood. Substantial differences in fecal or rumen microbiomes among cows experiencing different levels of energy deficit were not observed, suggesting that hyperketonemia may not be greatly influenced by gut microbial composition, and vice versa. Further studies using higher resolution -omics approaches like meta-transcriptomics or meta-proteomics are needed to decipher the exact mechanisms at play.
Altered fecal microbiome and metabolome in adult patients with non-cystic fibrosis bronchiectasis
Authors: Wang Wen-Wen , Mao Bei , Liu Yang , Gu Shu-Yi , Lu Hai-Wen , Bai Jiu-Wu , Liang Shuo , Yang Jia-Wei , Li Jian-Xiong , Su Xiao , Hu Hai-Yang , Wang Chen , Xu Jin-Fu
Published: November 2022

Background

Emerging experimental and epidemiological evidence highlights a crucial cross-talk between the intestinal flora and the lungs, termed the “gut-lung axis”. However, the function of the gut microbiota in bronchiectasis remains undefined. In this study, we aimed to perform a multi-omics-based approach to identify the gut microbiome and metabolic profiles in patients with bronchiectasis.

Methods

Fecal samples collected from non-CF bronchiectasis patients (BE group, n = 61) and healthy volunteers (HC group, n = 37) were analyzed by 16 S ribosomal RNA (rRNA) sequencing. The BE group was divided into two groups based on their clinical status: acute exacerbation (AE group, n = 31) and stable phase (SP group, n = 30). Further, metabolome (lipid chromatography-mass spectrometry, LC-MS) analyses were conducted in randomly selected patients (n = 29) and healthy volunteers (n = 31).

Results

Decreased fecal microbial diversity and differential microbial and metabolic compositions were observed in bronchiectasis patients. Correlation analyses indicated associations between the differential genera and clinical parameters such as bronchiectasis severity index (BSI). Disease-associated gut microbiota was screened out, with eight genera exhibited high accuracy in distinguishing SP patients from HCs in the discovery cohort and validation cohort using a random forest model. Further correlation networks were applied to illustrate the relations connecting disease-associated genera and metabolites.

Conclusion

The study uncovered the relationships among the decreased fecal microbial diversity, differential microbial and metabolic compositions in bronchiectasis patients by performing a multi-omics-based approach. It is the first study to characterize the gut microbiome and metabolome in bronchiectasis, and to uncover the gut microbiota’s potentiality as biomarkers for bronchiectasis.

Trial registration: This study is registered with ClinicalTrials.gov, number NCT04490447.
Personalized medicine using omics approaches in acute respiratory distress syndrome to identify biological phenotypes
Authors: Battaglini Denise , Al-Husinat Lou’i , Normando Ana Gabriela , Leme Adriana Paes , Franchini Kleber , Morales Marcelo , Pelosi Paolo , Rocco Patricia RM
Published: November 2022

In the last decade, research on acute respiratory distress syndrome (ARDS) has made considerable progress. However, ARDS remains a leading cause of mortality in the intensive care unit. ARDS presents distinct subphenotypes with different clinical and biological features. The pathophysiologic mechanisms of ARDS may contribute to the biological variability and partially explain why some pharmacologic therapies for ARDS have failed to improve patient outcomes. Therefore, identifying ARDS variability and heterogeneity might be a key strategy for finding effective treatments. Research involving studies on biomarkers and genomic, metabolomic, and proteomic technologies is increasing. These new approaches, which are dedicated to the identification and quantitative analysis of components from biological matrixes, may help differentiate between different types of damage and predict clinical outcome and risk. Omics technologies offer a new opportunity for the development of diagnostic tools and personalized therapy in ARDS. This narrative review assesses recent evidence regarding genomics, proteomics, and metabolomics in ARDS research.
Preclinical development of a long-acting trivalent bispecific nanobody targeting IL-5 for the treatment of eosinophilic asthma
Authors: Ma Linlin , Zhu Min , Li Guanghui , Gai Junwei , Li Yanfei , Gu Huaiyu , Qiao Peng , Li Xiaofei , Ji Weiwei , Zhao Rui , Wu Yue , Wan Yakun
Published: November 2022

Background

Eosinophilic asthma is a common subtype of severe asthma with high morbidity and mortality. The cytokine IL-5 has been shown to be a key driver of the development and progression of disease. Although approved monoclonal antibodies (mAbs) targeting IL-5/IL-5R have shown good safety and efficacy, some patients have inadequate responses and frequent dosing results in medication nonadherence.

Results

We constructed a novel trivalent bispecific nanobody (Nb) consisting of 3 VHHs that bind to 2 different epitopes of IL-5 and 1 epitope of albumin derived from immunized phage display libraries. This trivalent IL-5-HSA Nb exhibited similar IL-5/IL-5R blocking activities to mepolizumab (Nucala), an approved targeting IL-5 mAb. Surprisingly, this trivalent Nb was 58 times more active than mepolizumab in inhibiting TF-1-cell proliferation. In primate studies, the trivalent IL-5-HSA Nb showed excellent pharmacokinetic properties, and peripheral blood eosinophil levels remained significantly suppressed for two months after a single dose. In addition, the trivalent IL-5-HSA Nb could be produced on a large scale in a P. pastoris X-33 yeast system with high purity and good thermal stability.

Conclusions

These findings suggest that the trivalent bispecific IL-5-HSA Nb has the potential to be a next-generation therapeutic agent targeting IL-5 for the treatment of severe eosinophilic asthma.

Graphical Abstract
Characterization of the primary antibody response to Plasmodium falciparum antigens in infants living in a malaria-endemic area
Authors: Tassi Yunga Samuel , Siriwardhana Chathura , Fouda Genevieve G. , Bobbili Naveen , Sama Grace , Chen John J. , Leke Rose F. G. , Taylor Diane Wallace
Published: November 2022

Background

The primary antibody (Ab) response to Plasmodium falciparum is a critical step in developing immunity to malaria. Information on the initial Ab responses of babies in malaria-endemic areas is incomplete, in part, because babies receive maternal IgG via transplacental-transfer and usually become infected before maternal IgG wanes. The study aimed to identify the primary IgM and IgG Ab responses to malarial antigens in Cameroonian babies.

Methods

Infants (n = 70) living in a high malaria transmission area were followed from birth throughout the first year of life (mean 341 ± 42 days, an average of 8.5 time points per infant). Malaria infection was assessed by microscopy and PCR, and IgM and IgG antibodies (Abs) were measured using a multiplex immunoassay to AMA1, EBA-175, MSP1-42, MSP2, MSP3, RESA, LSA1, and CSP.

Results

The half-life of maternal IgG varied among the antigens, ranging from 0.7 to 2.5 months. The first infection of 41% of the babies was sub-microscopic and only 11 to 44% of the babies produced IgM to the above antigens; however, when the first infection was detected by microscopy, 59–82% of the infants made IgM Abs to the antigens. Infants were able to produce IgM even when maternal IgG was present, suggesting maternal Abs did not suppress the baby’s initial Ab response. Using longitudinal regression models that incorporated time-varying covariates, infants were found to produce IgG Ab to only AMA-1 when the first infection was sub-microscopic, but they produced IgG Abs to MSP1-42 (3D7, FVO), AMA1 (3D7, FVO) MSP2-FC27, MSP3, RESA, and LSA1, but not MSP 2-3D7, EBA-175, and CSP during their first slide-positive infection. Notably, the primary and secondary IgG responses were short-lived with little evidence of boosting.

Conclusions

The primary Ab response of babies who had maternal IgG was similar to that reported for primary infections in malaria-naïve adults.
Filtration-processed biomass nanofiber electrodes for flexible bioelectronics
Authors: Ando Daiki , Teshima Tetsuhiko F. , Zurita Francisco , Peng Hu , Ogura Kota , Kondo Kenji , Weiß Lennart , Hirano-Iwata Ayumi , Becherer Markus , Alexander Joe , Wolfrum Bernhard
Published: November 2022

An increasing demand for bioelectronics that interface with living systems has driven the development of materials to resolve mismatches between electronic devices and biological tissues. So far, a variety of different polymers have been used as substrates for bioelectronics. Especially, biopolymers have been investigated as next-generation materials for bioelectronics because they possess interesting characteristics such as high biocompatibility, biodegradability, and sustainability. However, their range of applications has been restricted due to the limited compatibility of classical fabrication methods with such biopolymers. Here, we introduce a fabrication process for thin and large-area films of chitosan nanofibers (CSNFs) integrated with conductive materials. To this end, we pattern carbon nanotubes (CNTs), silver nanowires, and poly (3,4-ethylenedioxythiophene):poly (styrenesulfonate) (PEDOT:PSS) by a facile filtration process that uses polyimide masks fabricated via laser ablation. This method yields feedlines of conductive material on nanofiber paper and demonstrates compatibility with conjugated and high-aspect-ratio materials. Furthermore, we fabricate a CNT neural interface electrode by taking advantage of this fabrication process and demonstrate peripheral nerve stimulation to the rapid extensor nerve of a live locust. The presented method might pave the way for future bioelectronic devices based on biopolymer nanofibers.
Self-assembly of DNA nanostructure containing cell-specific aptamer as a precise drug delivery system for cancer therapy in non-small cell lung cancer
Authors: Wang Ning , Yu Chang , Xu Tingting , Yao Dan , Zhu Lingye , Shen Zhifa , Huang Xiaoying
Published: November 2022

Background

As the most common subtype in lung cancer, the precise and efficient treatment for non-small cell lung cancer (NSCLC) remains an outstanding challenge owing to early metastasis and poor prognosis. Chemotherapy, the most commonly used treatment modality, is a difficult choice for many cancer patients due to insufficient drug accumulation in tumor sites and severe systemic side-effects. In this study, we constructed a cell-specific aptamer-modified DNA nanostructure (Apt-NS) as a targeting drug delivery system achieving the precision therapy for lung cancer.

Methods

The synthesis of DNA nanostructure and its stability were evaluated using gel electrophoresis. The targeting properties and internalization mechanism were investigated via flow cytometry and confocal analyses. Drug loading, release, and targeted drug delivery were determined by fluorescence detection, Zeta potentials assay, and confocal imaging. CCK8 assays, colony formation, cell apoptosis, metastasis analyses and in vivo experiments were conducted to assess the biological functions of DNA nanostructure.

Results

Self-assembled DNA nanoparticles (Apt-NS) had excellent stability to serum and DNase I and the ability to specifically recognize A549 cells. Upon specific binding, the drug-loaded nanoparticles (Apt-NS-DOX) were internalized into target cells by clathrin-mediated endocytosis. Subsequently, DOX could be released from Apt-NS-DOX based on the degradation of the lysosome. Apt-NS-DOX exerted significant suppression of cell proliferation, invasion and migration, and also enhanced cell apoptosis due to the excellent performance of drug delivery and intracellular release, while maintaining a superior biosafety. In addition, the antitumor effects of Apt-NS-DOX were further confirmed using in vivo models.

Conclusions

Our study provided cell-specific aptamer-modified DNA nanostructures as a drug-delivery system targeting A549 cells, which could precisely and efficiently transport chemotherapeutic drug into tumor cells, exerting enhanced antineoplastic efficacy. These findings highlight that DNA nanostructure serving as an ideal drug delivery system in cancer treatment appears great promise in biomedical applications.