bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic diversity and signatures of selection in meat and fancy rabbit breeds based on high-density marker data
Authors: Ballan Mohamad , Bovo Samuele , Schiavo Giuseppina , Schiavitto Michele , Negrini Riccardo , Fontanesi Luca
Published: January 2022

Background

Domestication of the rabbit (Oryctolagus cuniculus) has led to a multi-purpose species that includes many breeds and lines with a broad phenotypic diversity, mainly for external traits (e.g. coat colours and patterns, fur structure, and morphometric traits) that are valued by fancy rabbit breeders. As a consequence of this human-driven selection, distinct signatures are expected to be present in the rabbit genome, defined as signatures of selection or selective sweeps. Here, we investigated the genome of three Italian commercial meat rabbit breeds (Italian Silver, Italian Spotted and Italian White) and 12 fancy rabbit breeds (Belgian Hare, Burgundy Fawn, Champagne d’Argent, Checkered Giant, Coloured Dwarf, Dwarf Lop, Ermine, Giant Grey, Giant White, Rex, Rhinelander and Thuringian) by using high-density single nucleotide polymorphism data. Signatures of selection were identified based on the fixation index (FST) statistic with different approaches, including single-breed and group-based methods, the latter comparing breeds that are grouped based on external traits (different coat colours and body sizes) and types (i.e. meat vs. fancy breeds).

Results

We identified 309 genomic regions that contained signatures of selection and that included genes that are known to affect coat colour (ASIP, MC1R and TYR), coat structure (LIPH), and body size (LCORL/NCAPG, COL11A1 and HOXD) in rabbits and that characterize the investigated breeds. Their identification proves the suitability of the applied methodologies for capturing recent selection events. Other regions included novel candidate genes that might contribute to the phenotypic variation among the analyzed breeds, including genes for pigmentation-related traits (EDNRA, EDNRB, MITF and OCA2) and body size, with a strong candidate for dwarfism in rabbit (COL2A1).

Conclusions

We report a genome-wide view of genetic loci that underlie the main phenotypic differences in the analyzed rabbit breeds, which can be useful to understand the shift from the domestication process to the development of breeds in O. cuniculus. These results enhance our knowledge about the major genetic loci involved in rabbit external traits and add novel information to understand the complexity of the genetic architecture underlying body size in mammals.
Effect of initial COVID-19 outbreak during first trimester on pregnancy outcome in Wuxi, China
Authors: Liu Yun , Dai Ming , Tang Shaidi
Published: January 2022

Background

A hospital-based retrospective study was conducted to examine the effect of initial COVID-19 outbreak during first trimester on pregnancy outcome in Wuxi, China.

Methods

Women who delivered children at our hospital during June 2020 to July 2020 (control group), and October 2020 to December 2020 (exposure group) were recruited in the present study. All of the participants were not infected with COVID-19. The last menstrual period (LMP) of the exposure group was between January 24th, 2020 and March 12th, 2020, whilst in the control group, the LMP was between May 12th and October 31st, 2019.

Results

There were 1,456 women in the exposure group and 1,816 women in the control group. Women in the exposure group were more susceptible to hypertension during pregnancy (HDP, P = 0.004, OR[95%CI] = 1.90[1.22–2.95]) and gestational diabetes mellitus (GDM, P = 0.008, OR[95%CI] = 1.31[1.08–1.60]) compared to those in the control group. Mothers diagnosed with HDP were more likely to deliver premature infants, leading to a higher rate of low birth weight (all P < 0.05). The other common outcomes of pregnancy showed no statistical differences between the two groups.

Conclusions

The initial COVID-19 outbreak might increase the incidence rates of HDP and GDM among pregnant women whose first trimesters were during that period, resulting in higher percentages of premature delivery and low birth weight. These results should be confirmed by studies from other hospitals or cities.
Dietary patterns and severity of symptom with the risk of esophageal squamous cell carcinoma and its histological precursor lesions in China: a multicenter cross-sectional latent class analysis
Authors: Zang Zhaoping , Liu Yong , Wang Jialin , Liu Yuqin , Zhang Shaokai , Zhang Yongzhen , Zhang Liwei , Zhao Deli , Liu Fugang , Chao Lina , Wang Xinzheng , Zhang Chunli , Song Guohui , Zhang Zhiyi , Li Youpeng , Yan Zheng , Wen Yongxiu , Ge Yinyin , Niu Chen , Feng Wei , Nakyeyune Rena , Shen Yi , Shao Yi , Guo Xiuhua , Yang Aiming , Liu Fen , Wang Guiqi
Published: January 2022

Background

Dietary patterns and symptoms research among Chinese with esophageal squamous cell carcinoma (ESCC) and its precursor lesions is limited, especially as it relates to multiple food consumption and multiple co-occurring symptoms. The aim of our study was to identify the dietary patterns and severity of symptom classes with the risk of esophageal squamous cell carcinoma and its histological precursor lesions, and develop a risk prediction model for different stages of esophageal disease.

Methods

We analyzed data from a multicenter cross-sectional study carried out in ESCC high incidence areas between 2017 and 2018, which included 34,707 individuals aged 40–69 years. Dietary patterns and severity of symptom classes were derived by applying a latent class analysis (LCA). A multiple logistic regression model was used to derive the odds ratio (ORs) and corresponding 95% confidence intervals (CIs) for ESCC and the different stages of esophageal disease according to the dietary patterns and severity of symptom classes identified. We built the risk prediction model by using a nomogram.

Results

We identified five dietary patterns and three severity of symptom classes. The dietary patterns were classified as follows: “Healthy”, “Western”, “Lower consumers-combination”, “Medium consumers-combination” and “Higher consumers-combination” patterns based on the intake of foods such as red meat, vegetables and fruits. The severity of symptoms was categorized into “Asymptomatic”, “Mild symptoms” and “Overt symptoms” classes based on health-related symptoms reported by the participants. Compared to the “Healthy” pattern, the other four patterns were all associated with an increased risk of esophageal disease. Similarly, the other two symptom classes present different degrees of increased risk of esophageal disease compared to the “Asymptomatic”. The nomograms reflect the good predictive ability of the model.

Conclusion

Among individuals aged 40–69 years in high incidence regions of upper gastrointestinal cancer, the results supplied that subjects with diets rich in livestock and poultry meat and low in fruits and vegetables and subjects with typical symptoms were at increased ESCC risk. The findings highlight the importance of considering food and symptom combinations in cancer risk evaluation.
Serum cholinesterase may independently predict prognosis in non-small-cell lung cancer
Authors: Ran Hailiang , Ma Jie , Cai Le , Zhou Hai , Yuan Zhongqin , Chen Ying , Chang Wei , Huang Yunchao , Xiao Yuanyuan
Published: January 2022

Background

Serum cholinesterase (ChE) was found to be involved in cancer initiation and progression. However, the survival association between serum ChE and non-small cell lung cancer (NSCLC) has not been extensively discussed. In the present study, we aim to elevate the role of ChE in overall survival (OS) of NSCLC patients.

Methods

A total of 961 histologically confirmed NSCLC patients diagnosed between 2013 and 2018 in a provincial cancer hospital in southwestern China were retrospectively selected. Relevant information, such as histological type, clinical stage, chemotherapy, smoking status, body mass index (BMI), important serum indicators (albumin, neutrophil-to-lymphocyte ratio, ChE), date of death of the patients was extracted from the computerized hospital information system. Univariate and multivariate Cox proportional hazards models were used to determine the association between baseline serum ChE measured at the diagnosis and the OS of NSCLC patients.

Results

The median of baseline ChE (7700 units/liter) was used as a cut-off to dichotomize NSCLC patients. After controlling for possible confounding factors, serum ChE at diagnosis was significantly associated with OS of NSCLC: patients with higher level of ChE were observed a better prognosis (hazard ratio, HR: 0.77, 95% CI: 0.67–0.93, p = 0.006). Subgroup analysis revealed significant ChE-OS association for NSCLC patients: with lower systemic inflammation level (baseline NLR < 2.95, HR: 0.71, 95% CI: 0.56–0.89, p = 0.003), of adenocarcinoma (HR: 0.66, 95% CI: 0.54–0.80, p < 0.001), in advanced stage (HR: 0.77, 95% CI: 0.66–0.92, p < 0.01), and received chemotherapy (HR: 0.75, 95% CI: 0.59–0.96, p < 0.02).

Conclusion

Baseline ChE may have independent prognostic value for NSCLC patients. Longitudinal studies should be performed to corroborate this finding.
Epstein-Barr viral corneal stromal keratitis occurring during rheumatoid arthritis treatment: a case report
Authors: Yamashita Kazuya , Sato Rio , Fukumoto Ryuki , Ofuji Yoshiko , Nagamoto Takashi , Kubono Hirohisa , Kawamura Mari , Suzuki Kotaro
Published: January 2022

Background

A case of Epstein-Barr viral (EBV) corneal stromal keratitis during rheumatoid arthritis (RA) treatment is presented.

Case presentation

A 74-year-old female undergoing RA treatment was previously treated for bacterial corneal ulcer and herpetic keratitis and healed with antibiotic eye drops and topical anti-herpes ointment. At the first visit to our hospital, she presented with findings of monocular posterior interstitial keratitis with neovascularization mostly located in the inferior cornea with a corneal epithelial defect. The right eye showed no thinning of the corneal periphery and anterior uveitis. Her RA had subsided with oral steroid treatment, and infectious mononucleosis (IM) had not developed. EBV DNA could be detected in her corneal sample. After an extended but ineffective period to antibiotic treatment the corneal infiltrate responded rapidly to topical corticosteroids.

Conclusion

EBV can cause stromal keratitis without IM during treatment for RA.
Evaluating ‘Power 4 a Healthy Pregnancy’ (P4HP) – protocol for a cluster randomized controlled trial and process evaluation to empower pregnant women towards improved diet quality
Authors: van Lonkhuijzen Renske M. , Cremers Susanne , de Vries Jeanne H. M. , Feskens Edith J. M. , Wagemakers Annemarie
Published: January 2022

Background

In general during pregnancy, women are aware of the importance of good diet quality, interested in nutrition, and receptive to changing dietary intake. However, adherence to dietary guidelines is sub-optimal. A pregnant woman’s first information source regarding nutrition information is her midwife. Healthy nutrition promotion by midwives may therefore be very promising, but midwives face multiple barriers in providing nutritional support. Empowering pregnant women to improve their diet quality is expected to improve their health. Therefore an empowerment intervention has been developed to improve diet quality among pregnant women. The objective of this study is to evaluate the effectiveness and feasibility of Power 4 a Healthy Pregnancy (P4HP). P4HP aims to empower pregnant women to have a healthier diet quality.

Methods/design

This study applies a mixed methodology consisting of a non-blinded cluster randomized trial with an intervention (P4HP) group and a control group and a process evaluation. Midwifery practices, the clusters, will be randomly allocated to the intervention arm (n = 7) and control arm (n = 7). Participating women are placed in intervention or control conditions based on their midwifery practice. Each midwifery practice includes 25 pregnant women, making 350 participants in total. Health related outcomes, diet quality, empowerment, Sense of Coherence, Quality of Life, and Self-Rated Health of participants will be assessed before (T0) and after (T1) the intervention. The process evaluation focuses on multidisciplinary collaboration, facilitators, and barriers, and consists of in-depth interviews with midwives, dieticians and pregnant women.

Discussion

This study is the first to evaluate an empowerment intervention to improve diet quality in this target population. This mixed method evaluation will contribute to knowledge about the effectiveness and feasibility regarding diet quality, empowerment, health-related outcomes, multidisciplinary collaboration, facilitators and barriers of the empowerment intervention P4HP. Results will help inform how to empower pregnant women to achieve improved diet quality by midwives and dieticians. If proven effective, P4HP has the potential to be implemented nationally and scaled up to a long-term trajectory from preconception to the postnatal phase.

Trial registration

The trial is prospectively registered at the Netherlands Trial Register (NL9551). Date registered: 19/05/2021.
Heart rate and heart rate variability in patients with chronic inflammatory joint disease: the role of pain duration and the insular cortex
Authors: Danilin Leona Katharin , Spindler Melanie , Sörös Peter , Bantel Carsten
Published: January 2022

Background

Chronic inflammatory joint diseases (CIJD) have been linked to increased cardiovascular morbidity and mortality. A decisive reason could be a dysregulation of the autonomic nervous system, which is responsible for the control of cardiovascular function. So far, the cause of changes in autonomic nervous system functions remains elusive. In this study, we investigate the role of chronic pain and the insular cortex in autonomic control of cardiac functioning in patients with CIJD.

Methods

We studied the autonomic nervous system through the assessment of heart rate and heart rate variability (HRV) at rest and under cognitive stimulation. Furthermore, we investigated insular cortex volume by performing surface-based brain morphometry with FreeSurfer. For this study, 47 participants were recruited, 22 individual age- and sex-matched pairs for the magnetic resonance imaging analyses and 14 for the HRV analyses. All available patients’ data were used for analysis.

Results

Pain duration was negatively correlated with the resting heart rate in patients with chronic inflammatory joint diseases (n = 20). In a multiple linear regression model including only CIJD patients with heart rate at rest as a dependent variable, we found a significant positive relationship between heart rate at rest and the volume of the left insular cortex and a significant negative relationship between heart rate at rest and the volume of the right insular cortex. However, we found no significant differences in HRV parameters or insular cortex volumes between both groups.

Conclusions

In this study we provide evidence to suggest insular cortex involvement in the process of ANS changes due to chronic pain in CIJD patients.

The study was preregistered with the German Clinical Trials Register (https://www.drks.de; DRKS00012791; date of registration: 28 July 2017).
Interprofessional identity: an ethnography of clinical simulation learning in New Zealand
Authors: Cooper-Ioelu Pauline , Jowsey Tanisha
Published: January 2022

Background

This article explores the experiences of clinical healthcare students on an interprofessional simulation course in Auckland, New Zealand. The four-day course aims to provide a formative learning experience for final year medical, pharmacy, nursing, and paramedicine students. It focuses on building skills in professionalism, communication, leadership and interprofessional safe teamwork through structured learning activities and clinical simulation scenarios.

Methods

In 2018, we commenced focused ethnographic research involving participant observation, field notes, interviews, photography and ethnographic film.

Results

A total of 112 students participated in this research from the disciplines of medicine (n = 53), nursing (n = 27), pharmacy (n = 17), and paramedicine (n = 15). In a revisit to Van Gennep’s (1972) seminal work on liminality, we suggest that the course represents a liminal space where students’ ideas about what it means to be a healthcare ‘professional’ are challenged, disrupted and reconstructed. We observed students emerging from the course with transformed professional and interprofessional identities.

Conclusions

We posit that the ritualised and liminal nature of the course plays a role in the development of interprofessional identities by interrupting the reproduction of siloed biomedical culture. Students are challenged to become effective team members alongside other students and experts from other professions. We discuss these findings as they relate to medical and health sciences education.
Association of a longitudinal, preclinical ultrasound curriculum with medical student performance
Authors: Haidar David A , Kessler Ross , Khanna Neil K , Cover Michael T , Burkhardt John C , Theyyunni Nik , Tucker Ryan V , Huang Rob D , Holman Elizabeth , Bridge Patrick D , Klein Katherine A , Fung Christopher M
Published: January 2022

Introduction

Point-of-care ultrasound (US) is used in clinical practice across many specialties. Ultrasound (US) curricula for medical students are increasingly common. Optimal timing, structure, and effect of ultrasound education during medical school remains poorly understood. This study aims to retrospectively determine the association between participation in a preclinical, longitudinal US curriculum and medical student academic performance.

Methods

All first-year medical students at a medical school in the Midwest region of the United States were offered a voluntary longitudinal US curriculum. Participants were selected by random lottery. The curriculum consisted of five three-hour hands on-sessions with matching asynchronous content covering anatomy and pathologic findings. Content was paired with organ system blocks in the standard first year curriculum at our medical school. Exam scores between the participating and non-participating students were compared to evaluate the objective impact of US education on performance in an existing curriculum. We hypothesized that there would be an association between participation in the curriculum and improved medical student performance. Secondary outcomes included shelf exam scores for the surgery, internal medicine, neurology clerkships and USMLE Step 1. A multivariable linear regression model was used to evaluate the association of US curriculum participation with student performance. Scores were adjusted for age, gender, MCAT percentile, and science or engineering degree.

Results

76 of 178 students applied to participate in the curriculum, of which 51 were accepted. US curriculum students were compared to non-participating students (n = 127) from the same class. The US curriculum students performed better in cardiovascular anatomy (mean score 92.1 vs. 88.7, p = 0.048 after adjustment for multiple comparisons). There were no significant differences in cumulative cardiovascular exam scores, or in anatomy and cumulative exam scores for the gastroenterology and neurology blocks. The effect of US curriculum participation on cardiovascular anatomy scores was estimated to be an improvement of 3.48 points (95% CI 0.78-6.18). No significant differences were observed for USMLE Step 1 or clerkship shelf exams. There were no significant differences in either preclinical, clerkship or Step 1 score for the 25 students who applied and were not accepted and the 102 who did not apply.

Conclusions

Participation in a preclinical longitudinal US curriculum was associated with improved exam performance in cardiovascular anatomy but not examination of other cardiovascular system concepts. Neither anatomy or comprehensive exam scores for neurology and gastrointestinal organ system blocks were improved.
Understanding low-value care and associated de-implementation processes: a qualitative study of Choosing Wisely Interventions across Canadian hospitals
Authors: Parker Gillian , Kastner Monika , Born Karen , Shahid Nida , Berta Whitney
Published: January 2022

Background

Choosing Wisely (CW) is an international movement comprised of campaigns in more than 20 countries to reduce low-value care (LVC). De-implementation, the reduction or removal of a healthcare practice that offers little to no benefit or causes harm, is an emerging field of research. Little is known about the factors which (i) sustain LVC; and (ii) the magnitude of the problem of LVC. In addition, little is known about the processes of de-implementation, and if and how these processes differ from implementation endeavours. The objective of this study was to explicate the myriad factors which impact the processes and outcomes of de-implementation initiatives that are designed to address national Choosing Wisely campaign recommendations.

Methods

Semi-structured interviews were conducted with individuals implementing Choosing Wisely Canada recommendations in healthcare settings in four provinces. The interview guide was developed using concepts from the literature and the Implementation Process Model (IPM) as a framework. All interviews were conducted virtually, recorded, and transcribed verbatim. Data were analysed using thematic analysis.

Findings

Seventeen Choosing Wisely team members were interviewed. Participants identified numerous provider factors, most notably habit, which sustain LVC. Contrary to reporting in recent studies, the majority of LVC in the sample was not ‘patient facing’; therefore, patients were not a significant driver for the LVC, nor a barrier to reducing it. Participants detailed aspects of the magnitude of the problems of LVC, providing insight into the complexities and nuances of harm, resources and prevalence. Harm from potential or common infections, reactions, or overtreatment was viewed as the most significant types of harm. Unique factors influencing the processes of de-implementation reported were: influence of Choosing Wisely campaigns, availability of data, lack of targets and hard-coded interventions.

Conclusions

This study explicates factors ranging from those which impact the maintenance of LVC to factors that impact the success of de-implementation interventions intended to reduce them. The findings draw attention to the significance of unintentional factors, highlight the importance of understanding the impact of harm and resources to reduce LVC and illuminate the overstated impact of patients in de-implementation literature. These findings illustrate the complexities of de-implementation.
Humoral immune response after different SARS-CoV-2 vaccination regimens
Authors: Rose Ruben , Neumann Franziska , Grobe Olaf , Lorentz Thomas , Fickenscher Helmut , Krumbholz Andi
Published: January 2022

Background

The humoral immune response after primary immunisation with a SARS-CoV-2 vector vaccine (AstraZeneca AZD1222, ChAdOx1 nCoV-19, Vaxzevria) followed by an mRNA vaccine boost (Pfizer/BioNTech, BNT162b2; Moderna, m-1273) was examined and compared with the antibody response after homologous vaccination schemes (AZD1222/AZD1222 or BNT162b2/BNT162b2).

Methods

Sera from 59 vaccinees were tested for anti-SARS-CoV-2 immunoglobulin G (IgG) and virus-neutralising antibodies (VNA) with three IgG assays based on (parts of) the SARS-CoV-2 spike (S)-protein as antigen, an IgG immunoblot (additionally contains the SARS-CoV-2 nucleoprotein (NP) as an antigen), a surrogate neutralisation test (sVNT), and a Vero-cell-based virus-neutralisation test (cVNT) with the B.1.1.7 variant of concern (VOC; alpha) as antigen. Investigation was done before and after heterologous (n = 30 and 42) or homologous booster vaccination (AZD1222/AZD1222, n = 8/9; BNT162b2/BNT162b2, n = 8/8). After the second immunisation, a subgroup of 26 age- and gender-matched sera (AZD1222/mRNA, n = 9; AZD1222/AZD1222, n = 9; BNT162b2/BNT162b2, n = 8) was also tested for VNA against VOC B.1.617.2 (delta) in the cVNT. The strength of IgG binding to separate SARS-CoV-2 antigens was measured by avidity.

Results

After the first vaccination, the prevalence of IgG directed against the (trimeric) SARS-CoV-2 S-protein and its receptor binding domain (RBD) varied from 55–95% (AZD1222) to 100% (BNT162b2), depending on the vaccine regimen and the SARS-CoV-2 antigen used. The booster vaccination resulted in 100% seroconversion and the occurrence of highly avid IgG, which is directed against the S-protein subunit 1 and the RBD, as well as VNA against VOC B.1.1.7, while anti-NP IgGs were not detected. The results of the three anti-SARS-CoV-2 IgG tests showed an excellent correlation to the VNA titres against this VOC. The agreement of cVNT and sVNT results was good. However, the sVNT seems to overestimate non- and weak B.1.1.7-neutralising titres. The anti-SARS-CoV-2 IgG concentrations and the B.1.1.7-neutralising titres were significantly higher after heterologous vaccination compared to the homologous AZD1222 scheme. If VOC B.1.617.2 was used as antigen, significantly lower VNA titres were measured in the cVNT, and three (33.3%) vector vaccine recipients had a VNA titre < 1:10.

Conclusions

Heterologous SARS-CoV-2 vaccination leads to a strong antibody response with anti-SARS-CoV-2 IgG concentrations and VNA titres at a level comparable to that of a homologous BNT162b2 vaccination scheme. Irrespective of the chosen immunisation regime, highly avid IgG antibodies can be detected just 2 weeks after the second vaccine dose indicating the development of a robust humoral immunity. The reduction in the VNA titre against VOC B.1.617.2 observed in the subgroup of 26 individuals is remarkable and confirms the immune escape of the delta variant.
Gender difference in the incidence of malaria diagnosed at public health facilities in Uganda
Authors: Okiring Jaffer , Epstein Adrienne , Namuganga Jane F. , Kamya Emmanuel V. , Nabende Isaiah , Nassali Martha , Sserwanga Asadu , Gonahasa Samuel , Muwema Mercy , Kiwuwa Steven M. , Staedke Sarah G. , Kamya Moses R. , Nankabirwa Joaniter I. , Briggs Jessica , Jagannathan Prasanna , Dorsey Grant
Published: January 2022

Background

Routine malaria surveillance data in Africa primarily come from public health facilities reporting to national health management information systems. Although information on gender is routinely collected from patients presenting to these health facilities, stratification of malaria surveillance data by gender is rarely done. This study evaluated gender difference among patients diagnosed with parasitological confirmed malaria at public health facilities in Uganda.

Methods

This study utilized individual level patient data collected from January 2020 through April 2021 at 12 public health facilities in Uganda and cross-sectional surveys conducted in target areas around these facilities in April 2021. Associations between gender and the incidence of malaria and non-malarial visits captured at the health facilities from patients residing within the target areas were estimated using poisson regression models controlling for seasonality. Associations between gender and data on health-seeking behaviour from the cross-sectional surveys were estimated using poisson regression models controlling for seasonality.

Results

Overall, incidence of malaria diagnosed per 1000 person years was 735 among females and 449 among males (IRR = 1.72, 95% CI 1.68–1.77, p < 0.001), with larger differences among those 15–39 years (IRR = 2.46, 95% CI 2.34–2.58, p < 0.001) and over 39 years (IRR = 2.26, 95% CI 2.05–2.50, p < 0.001) compared to those under 15 years (IRR = 1.46, 95% CI 1.41–1.50, p < 0.001). Female gender was also associated with a higher incidence of visits where malaria was not suspected (IRR = 1.77, 95% CI 1.71–1.83, p < 0.001), with a similar pattern across age strata. These associations were consistent across the 12 individual health centres. From the cross-sectional surveys, females were more likely than males to report fever in the past 2 weeks and seek care at the local health centre (7.5% vs. 4.7%, p = 0.001) with these associations significant for those 15–39 years (RR = 2.49, 95% CI 1.17–5.31, p = 0.018) and over 39 years (RR = 2.56, 95% CI 1.00–6.54, p = 0.049).

Conclusions

Females disproportionately contribute to the burden of malaria diagnosed at public health facilities in Uganda, especially once they reach childbearing age. Contributing factors included more frequent visits to these facilities independent of malaria and a higher reported risk of seeking care at these facilities for febrile illnesses.
Ezidi voices: The communication of COVID-19 information amongst a refugee community in rural Australia- a qualitative study
Authors: Healey Sunita Joann Rebecca , Ghafournia Nafiseh , Massey Peter D , Andrich Karinne , Harrison Joy , Taylor Kathryn , Bolsewicz Katarzyna
Published: January 2022

Background

There is growing evidence that government health information related to COVID-19 has failed to adequately reach culturally and linguistically diverse (CALD) populations in Australia. Refugees are a unique sub-set of the CALD communities and are subject to numerous barriers preventing adequate health care, both pre- and post-migration. The barriers are accentuated during emergencies, such as a pandemic, as a result of an intersection of various social and economic inequalities. The recently resettled Ezidi refugee community in a regional area of Australia is an example of a community sitting at the intersection of various inequities and thus at greater risk from COVID-19. The purpose of this study is to describe the experiences of the Ezidi in a regional area with COVID-19 information and how this has been communicated to and shared within this group; what barriers the community may experience in accessing COVID-19 information; and how the government-led COVID-19 information communication could be improved.

Methods

This qualitative study was designed to explore the perceptions and views of the Ezidi and service providers regarding COVID-19 messaging. Multicultural and Refugee Health staff facilitated interviews with four local service providers and ten Ezidi community members, including seven influential leaders. Thematic analysis was employed across individual, pair and group data analysis. Similar categories were grouped into themes.

Results

The main findings of the study are: the refugee experience influences the communication of COVID-19 messages; cultural, social and gender norms influence responses to COVID-19; trusted individuals and service providers are key in communities’ uptake of COVID-19 messages; currently available governmental COVID-19 information resources and sharing strategies were found unhelpful and inappropriate; COVID-19 communiqués and message delivery for this regional minority refugee community can be improved.

Conclusion

The recently resettled Ezidi community, and likely other similar communities, would benefit from tailored engagement by government organisations, as well as settlement services to improve the communication of COVID-19 health information and reduce related inequities.
Combination strategies with PD-1/PD-L1 blockade: current advances and future directions
Authors: Yi Ming , Zheng Xiaoli , Niu Mengke , Zhu Shuangli , Ge Hong , Wu Kongming
Published: January 2022

Antibodies targeting programmed cell death protein-1 (PD-1) or its ligand PD-L1 rescue T cells from exhausted status and revive immune response against cancer cells. Based on the immense success in clinical trials, ten α-PD-1 (nivolumab, pembrolizumab, cemiplimab, sintilimab, camrelizumab, toripalimab, tislelizumab, zimberelimab, prolgolimab, and dostarlimab) and three α-PD-L1 antibodies (atezolizumab, durvalumab, and avelumab) have been approved for various types of cancers. Nevertheless, the low response rate of α-PD-1/PD-L1 therapy remains to be resolved. For most cancer patients, PD-1/PD-L1 pathway is not the sole speed-limiting factor of antitumor immunity, and it is insufficient to motivate effective antitumor immune response by blocking PD-1/PD-L1 axis. It has been validated that some combination therapies, including α-PD-1/PD-L1 plus chemotherapy, radiotherapy, angiogenesis inhibitors, targeted therapy, other immune checkpoint inhibitors, agonists of the co-stimulatory molecule, stimulator of interferon genes agonists, fecal microbiota transplantation, epigenetic modulators, or metabolic modulators, have superior antitumor efficacies and higher response rates. Moreover, bifunctional or bispecific antibodies containing α-PD-1/PD-L1 moiety also elicited more potent antitumor activity. These combination strategies simultaneously boost multiple processes in cancer-immunity cycle, remove immunosuppressive brakes, and orchestrate an immunosupportive tumor microenvironment. In this review, we summarized the synergistic antitumor efficacies and mechanisms of α-PD-1/PD-L1 in combination with other therapies. Moreover, we focused on the advances of α-PD-1/PD-L1-based immunomodulatory strategies in clinical studies. Given the heterogeneity across patients and cancer types, individualized combination selection could improve the effects of α-PD-1/PD-L1-based immunomodulatory strategies and relieve treatment resistance.
Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma
Authors: Li Yong , Wang Yixuan , Gao Lun , Tan Yinqiu , Cai Jiayang , Ye Zhang , Chen Ann T. , Xu Yang , Zhao Linyao , Tong Shiao , Sun Qian , Liu Baohui , Zhang Shenqi , Tian Daofeng , Deng Gang , Zhou Jiangbing , Chen Qianxue
Published: January 2022

Background

Glioblastoma (GBM) is the most common and fatal primary tumor in the central nervous system (CNS). Due to the existence of blood–brain barrier (BBB), most therapeutics cannot efficiently reach tumors in the brain, and as a result, they are unable to be used for effective GBM treatment. Accumulating evidence shows that delivery of therapeutics in form of nanoparticles (NPs) may allow crossing the BBB for effective GBM treatment.

Methods

Betulinic acid NPs (BA NPs) were synthesized by the standard emulsion approach and characterized by electron microscopy and dynamic light scattering analysis. The resulting NPs were characterized for their anti-tumor effects by cell viability assay, EdU-DNA synthesis assay, cell cycle assay, mitochondrial membrane potential, and PI-FITC apoptosis assay. Further mechanistic studies were carried out through Western Blot and immunostaining analyses. Finally, we evaluated BA NPs in vivo for their pharmacokinetics and antitumor effects in intracranial xenograft GBM mouse models.

Results

BA NPs were successfully prepared and formed into rod shape. BA NPs could significantly suppress glioma cell proliferation, induce apoptosis, and arrest the cell cycle in the G0/G1 phase in vitro. Furthermore, BA NPs downregulated the Akt/NFκB-p65 signaling pathway in a concentration dependent manner. We found that the observed anti-tumor effect of BA NPs was dependent on the function of CB1/CB2 receptors. Moreover, in the intracranial GBM xenograft mouse models, BA NPs could effectively cross the BBB and greatly prolong the survival time of the mice.

Conclusions

We successfully synthesized BA NPs, which could cross the BBB and demonstrated a strong anti-tumor effect. Therefore, BA NPs may potentially be used for effective treatment of GBM.

Graphical Abstract
Mitochondria-targeting multifunctional nanoplatform for cascade phototherapy and hypoxia-activated chemotherapy
Authors: Lv Jie , Wang Shuangling , Qiao Duo , Lin Yulong , Hu Shuyang , Li Meng
Published: January 2022

Despite considerable progress has been achieved in hypoxia-associated anti-tumor therapy, the efficacy of utilizing hypoxia-activated prodrugs alone is not satisfied owing to the inadequate hypoxia within the tumor regions. In this work, a mitochondrial targeted nanoplatform integrating photodynamic therapy, photothermal therapy and hypoxia-activated chemotherapy has been developed to synergistically treat cancer and maximize the therapeutic window. Polydopamine coated hollow copper sulfide nanoparticles were used as the photothermal nanoagents and thermosensitive drug carriers for loading the hypoxia-activated prodrug, TH302, in our study. Chlorin e6 (Ce6) and triphenyl phosphonium (TPP) were conjugated onto the surface of the nanoplatform. Under the action of TPP, the obtained nanoplatform preferentially accumulated in mitochondria to restore the drug activity and avoid drug resistance. Using 660 nm laser to excite Ce6 can generate ROS and simultaneously exacerbate the cellular hypoxia. While under the irradiation of 808 nm laser, the nanoplatform produced local heat which can increase the release of TH302 in tumor cells, ablate cancer cells as well as intensify the tumor hypoxia levels. The aggravated tumor hypoxia then significantly boosted the anti-tumor efficiency of TH302. Both in vitro and in vivo studies demonstrated the greatly improved anti-cancer activity compared to conventional hypoxia-associated chemotherapy. This work highlights the potential of using a combination of hypoxia-activated prodrugs plus phototherapy for synergistic cancer treatment.

Graphical Abstract
A tumor microenvironment-responsive poly(amidoamine) dendrimer nanoplatform for hypoxia-responsive chemo/chemodynamic therapy
Authors: Hao Yingchao , Gao Yue , Fan Yu , Zhang Changchang , Zhan Mengsi , Cao Xueyan , Shi Xiangyang , Guo Rui
Published: January 2022

Background

Chemodynamic therapy is a promising cancer treatment with specific therapeutic effect at tumor sites, as toxic hydroxyl radical (·OH) could only be generated by Fenton or Fenton-like reaction in the tumor microenvironment (TME) with low pH and high level of endogenous hydrogen peroxide. However, the low concentration of catalytic metal ions, excessive glutathione (GSH) and aggressive hypoxia at tumor site seriously restrict the curative outcomes of conventional chemodynamic therapy.

Results

In this study, polyethylene glycol-phenylboronic acid (PEG-PBA)-modified generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers were synthesized as a targeted nanocarrier to chelate Cu(II) and then encapsulate hypoxia-sensitive drug tirapazamine (TPZ) by the formation of hydrophobic Cu(II)/TPZ complex for hypoxia-enhanced chemo/chemodynamic therapy. The formed G5.NHAc-PEG-PBA@Cu(II)/TPZ (GPPCT) nanoplatform has good stability and hemocompatibility, and could release Cu(II) ions and TPZ quickly in weakly acidic tumor sites via pH-sensitive dissociation of Cu(II)/TPZ. In vitro experiments showed that the GPPCT nanoplatforms can efficiently target murine breast cancer cells (4T1) cells overexpressing sialic acid residues, and show a significantly enhanced inhibitory effect on hypoxic cells by the activation of TPZ. The excessive GSH in tumors could be depleted by the reduction of Cu(II) to Cu(I), and abundant of toxic ·OH would be generated in tumor cells by Fenton reaction for chemodynamic therapy. In vivo experiments demonstrated that the GPPCT nanoplatform could specifically accumulate at tumors, effectively inhibit the growth and metastasis of tumors by the combination of CDT and chemotherapy, and be metabolized with no systemic toxicity.

Conclusions

The targeted GPPCT nanoplatform may represent an effective model for the synergistic inhibition of different tumor types by hypoxia-enhanced chemo/chemodynamic therapy.

Graphical Abstract
Nanocarriers surface engineered with cell membranes for cancer targeted chemotherapy
Authors: Lei Wen , Yang Chen , Wu Yi , Ru Guoqing , He Xianglei , Tong Xiangmin , Wang Shibing
Published: January 2022

Background

Inspired by nature, the biomimetic approach has been incorporated into drug nanocarriers for cancer targeted chemotherapy. The nanocarriers are cloaked in cell membranes, which enables them to incorporate the functions of natural cells.

Key scientific concepts of review

Nanocarriers surface engineered with cell membranes have emerged as a fascinating source of materials for cancer targeted chemotherapy. A distinctive characteristic of cell membrane-coated nanocarriers (CMCNs) is that they include carbohydrates, proteins, and lipids, in addition to being biocompatible. CMCNs are capable of interacting with the complicated biological milieu of the tumor because they contain the signaling networks and intrinsic functions of their parent cells. Numerous cell membranes have been investigated for the purpose of masking nanocarriers with membranes, and various tumor-targeting methods have been devised to improve cancer targeted chemotherapy. Moreover, the diverse structure of the membrane from different cell sources broadens the spectrum of CMCNs and offers an entirely new class of drug-delivery systems.

Aim of review

This review will describe the manufacturing processes for CMCNs and the therapeutic uses for different kinds of cell membrane-coated nanocarrier-based drug delivery systems, as well as addressing obstacles and future prospects.

Graphical Abstract
Bacteria-engineered porous sponge for hemostasis and vascularization
Authors: Bian Jie , Bao Luhan , Gao Xiaokang , Wen Xiao , Zhang Qiang , Huang Jinhua , Xiong Zhenghui , Hong Feng F. , Ge Zili , Cui Wenguo
Published: January 2022

Background

Hemostasis and repair are two essential processes in wound healing, yet early hemostasis and following vascularization are challenging to address in an integrated manner.

Results

In this study, we constructed a hemostatic sponge OBNC-DFO by fermentation of Komagataeibacterxylinus combined with TEMPO oxidation to obtain oxidized bacterial nanocellulose (OBNC). Then angiogenetic drug desferrioxamine (DFO) was grafted through an amide bond, and it promoted clot formation and activated coagulation reaction by rapid blood absorption due to the high total pore area (approximately 42.429 m2/g measured by BET). The further release of DFO stimulated the secretion of HIF-1α and the reconstruction of blood flow, thus achieving rapid hemostasis and vascularization in damaged tissue. This new hemostatic sponge can absorb water at a rate of approximate 1.70 g/s, rapidly enhancing clot formation in the early stage of hemostasis. In vitro and in vivo coagulation experiments (in rat tail amputation model and liver trauma model) demonstrated superior pro-coagulation effects of OBNC and OBNC-DFO to clinically used collagen hemostatic sponges (COL). They promoted aggregation and activation of red blood cells and platelets with shorter whole blood clotting time, more robust activation of endogenous coagulation pathways and less blood loss. In vitro cellular assays showed that OBNC-DFO prevailed over OBNC by promoting the proliferation of human umbilical vein endothelial cells (HUVECs). In addition, the release of DFO enhanced the secretion of HIF-1α, further strengthening vascularization in damaged skin. In the rat skin injury model, 28 days after being treated with OBNC-DFO, skin appendages (e.g., hair follicles) became more intact, indicating the achievement of structural and functional regeneration of the skin.

Conclusion

This hemostatic and vascularization-promoting oxidized bacterial nanocellulose hemostatic sponge, which rapidly activates coagulation pathways and enables skin regeneration, is a highly promising hemostatic and pro-regenerative repair biomaterial.

Graphical Abstract
Qualitative measures that assess functional disability and quality of life in ALS
Authors: Hartmaier Susan L. , Rhodes Thomas , Cook Suzanne F. , Schlusser Courtney , Chen Chao , Han Steve , Zach Neta , Murthy Venkatesha , Davé Shreya
Published: January 2022

Background

Selection of appropriate trial endpoints and outcome measures is particularly important in rare disease and rapidly progressing disease such as amyotrophic lateral sclerosis (ALS) where the challenges to conducting clinical trials, are substantial: patient and disease heterogeneity, limited understanding of exact disease pathophysiology, and lack of robust and available biomarkers. To address these challenges in ALS, the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised version (ALSFRS-R) was developed and has become a key primary endpoint in ALS clinical trials to assess functional disability and disease progression, often replacing survival as a primary outcome. However, increased understanding of the ALS disease journey and improvements in assistive technology for ALS patients have exposed issues with the ALSFRS-R, including non-linearity, multidimensionality and floor and ceiling effects that could challenge its continued utility as a primary outcome measure in ALS clinical trials. Recently, other qualitative scale measures of functioning disability have been developed to help address these issues. With this in mind, we conducted a literature search aimed at identifying both established and promising new measures for potential use in clinical trials.

Methods

We searched PubMed, Google, Google Scholar, and the reference sections of key studies to identify papers that discussed qualitative measures of functional status for potential use in ALS studies. We also searched clinicaltrials.gov to identify functional status and health-related quality of life (HRQoL) measures that have been used in ALS interventional studies.

Results

In addition to the ALSFRS-R, we identified several newer qualitative scales including ALSFRS-EX, ALS-MITOS, CNS-BFS, DALS-15, MND-DS, and ROADS. Strengths and limitations of each measure were identified and discussed, along with their potential to act as a primary or secondary outcome to assess patient functional status in ALS clinical trials.

Conclusion

This paper serves as a reference guide for researchers deciding which qualitative measures to use as endpoints in their ALS clinical trials to assess functional status. This paper also discusses the importance of including ALS HRQoL and ALS cognitive screens in future clinical trials to assess the value of a new ALS therapy more comprehensively.