bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing the implementation of a participant-collected, mail-based SARS-CoV-2 serological survey in university-affiliated populations: lessons learned and practical guidance
Authors: Cramer Estee Y. , Snyder Teah , Ravenhurst Johanna , Lover Andrew A.
Published: October 2022

The rapid spread of SARS-CoV-2 is largely driven by pre-symptomatic or mildly symptomatic individuals transmitting the virus. Serological tests to identify antibodies against SARS-CoV-2 are important tools to characterize subclinical infection exposure.

During the summer of 2020, a mail-based serological survey with self-collected dried blood spot (DBS) samples was implemented among university affiliates and their household members in Massachusetts, USA. Described are challenges faced and novel procedures used during the implementation of this study to assess the prevalence of SARS-CoV-2 antibodies amid the pandemic.

Important challenges included user-friendly remote and contact-minimized participant recruitment, limited availability of some commodities and laboratory capacity, a potentially biased sample population, and policy changes impacting the distribution of clinical results to study participants. Methods and lessons learned to surmount these challenges are presented to inform design and implementation of similar sero-studies.

This study design highlights the feasibility and acceptability of self-collected bio-samples and has broad applicability for other serological surveys for a range of pathogens. Key lessons relate to DBS sampling, supply requirements, the logistics of packing and shipping packages, data linkages to enrolled household members, and the utility of having an on-call nurse available for participant concerns during sample collection. Future research might consider additional recruitment techniques such as conducting studies during academic semesters when recruiting in a university setting, partnerships with supply and shipping specialists, and using a stratified sampling approach to minimize potential biases in recruitment.
Barriers to and facilitators of accessing HIV services for street-involved youth in Canada and Kenya
Authors: Khan Momina , MacEntee Katie , Kiptui Reuben , Van Berkum Amy , Oudshoorn Abe , Ayuku David O , Apondi Edith , Lee Edward Ou Jin , Abramovich Alex , MacDonald Sue-Ann , Braitstein Paula
Published: October 2022

Introduction

UNICEF estimates that there are as many as 100 million street-involved youth (SIY) globally. Marginalized conditions put SIY at higher risk of HIV and adverse outcomes once HIV-positive. The objective of this analysis was to describe barriers and facilitators of accessing HIV prevention, testing, and treatment services as Phase I of an implementation study evaluating the use of peer navigators to increase access to HIV services.

Methods

Semi-structured interviews, focus group discussions (FGD), and theatre testing were conducted with individuals who identify as SIY, health care providers, and community stakeholders living in Canada (Toronto, Montreal, London) and Kenya (Eldoret, Huruma, Kitale). Data were analyzed using a directed content approach, guided by the socio-ecological model (SEM).

Results

Across the six sites were 195 participants: 64 SIY, 42 healthcare providers, and 97 community-based stakeholders. Barriers were identified at the societal (e.g. intersectional stigma and discrimination), public policy (e.g., inadequate access to basic needs, legal documentation, lack of health insurance, and limited community-based funding), institutional (e.g. lack of inclusive education and training, inadequate HIV educational outreach, and restrictive service provision), interpersonal (e.g., ineffective communication from healthcare providers), and intrapersonal levels (e.g. lack of trust and associated fear, low perception for healthcare, and lack of self-esteem). These contributed to limited HIV services utilization among SIY. Conversely, numerous facilitators were also identified at the public policy (e.g. affordable HIV services and treatment), institutional (e.g. available and accessible HIV prevention tools, HIV education and awareness programs, and holistic models of care), interpersonal level (e.g., systems navigation support, peer support, and personal relationships), and intrapersonal levels (e.g. self-efficacy) as positively supporting SIY access to HIV services.

Conclusion

Intersectional stigma was a critical barrier in all sites, and policies and programs that foster welcoming environments for youth from diverse backgrounds and living circumstances may be better able to respond to the HIV service needs of this high risk population. Social support and navigation services were reported to facilitate access to HIV services in all sites.
Prevalence and predictors of advance directive among terminally ill patients in Taiwan before enactment of Patient Right to Autonomy Act: a nationwide population-based study
Authors: Chang Hui Yu , Takemura Naomi , Chau Pui Hing , Lin Chia-Chin
Published: October 2022

Background

Signing advance directives (ADs) ensures that terminally ill patients receive end-of-life care, according to their wishes, thereby promoting human dignity and sparing them from unnecessary suffering. Despite the enactment of the Hospice Palliative Care Act in Taiwan in 2000, the completion rates of ADs have been found to be low among patients with chronic illness conditions. To date, limited existing research is available regarding the factors associated with AD completion in terminally ill patients in Taiwan. To explore signed AD characteristics, compare differences in signing ADs between patients with and without cancer, and examine the factors associated with signing ADs in terminally ill patients.

Methods

A nationwide study was conducted using data collected via a retrospective review of medical death records from 18 randomly selected hospitals in the northern, central, and southern parts of Taiwan. We collected 200 records, including both cancer and non-cancer-related deaths, from each hospital. Univariate and multivariate logistics regressions were conducted to examine factors associated with signing advance directives among all patients- with and without cancer.

Results

Among the 3004 reviewed medical records, 79% had signed ADs, with most (95%) being signed by patients’ caregivers. A higher education level (OR = 1.52, 95% CI = 1.10, 2.08, p = 0.010); cancer diagnosis (OR = 2.37, 95% CI = 1.79, 3.16, p < 0.001); having family members (OR = 5.62, 95% CI = 2.95, 10.69, p < 0.001), care homes (OR = 4.52, 95% CI = 1.97, 10.38, p < 0.001), friends, or maids (OR = 3.82, 95% CI = 1.76, 8.29, p = 0.001) as primary caregivers; and patients knowing about their poor prognosis (OR = 15.39, 95% CI = 5.66, 41.83, p < 0.001) were associated with a higher likelihood of signing ADs.

Conclusions

Patients with non-malignant chronic illnesses were less likely to have ADs signed by either patients or family caregivers than those with cancer, with the lowest likelihood observed in patients with cardiovascular diseases. Whenever possible, primary caregivers should be involved in discussing ADs with patients, and the importance of truth telling should be reinforced. Following these principles, each patient’s end-of-life care preferences can be respected, thereby promoting quality of care before the patient’s death.
Antimalarial potential of compounds isolated from Mammea siamensis T. Anders. flowers: in vitro and molecular docking studies
Authors: Chaniad Prapaporn , Chukaew Arnon , Payaka Apirak , Phuwajaroanpong Arisara , Techarang Tachpon , Plirat Walaiporn , Punsawad Chuchard
Published: October 2022

Background:

The emergence of antimalarial drug resistance encourages the search for new antimalarial agents.Mammea siamensisbelongs to the Calophyllaceae family, which is a medicinal plant that is used in traditional Thai preparations. The hexane and dichloromethane extracts of this plant were found to have potent antimalarial activity. Therefore, this study aimed to isolate active compounds fromM. siamensisflowers and evaluate their antimalarial potential and their interactions withPlasmodium falciparumlactate dehydrogenase (PfLDH).

Methods:

The compounds fromM. siamensisflowers were isolated by chromatographic techniques and evaluated for their antimalarial activity against chloroquine (CQ)-resistantP. falciparum(K1) strains using a parasite lactate dehydrogenase (pLDH) assay. Interactions between the isolated compounds and thePfLDH enzyme were investigated using a molecular docking method.

Results:

The isolation produced the following thirteen compounds: two terpenoids, lupeol (1) and a mixture of β-sitosterol and stigmasterol (5); two mammea coumarins, mammea A/AA cyclo D (6) and mammea A/AA cyclo F (7); and nine xanthones, 4,5-dihydroxy-3-methoxyxanthone (2), 4-hydroxyxanthone (3), 1,7-dihydroxyxanthone (4), 1,6-dihydroxyxanthone (8), 1-hydroxy-5,6,7-trimethoxyxanthone (9), 3,4,5-trihydroxyxanthone (10), 5-hydroxy-1-methoxyxanthone (11), 2-hydroxyxanthone (12), and 1,5-dihydroxy-6-methoxyxanthone (13). Compound9exhibited the most potent antimalarial activity with an IC50value of 9.57 µM, followed by10,1,2and13with IC50values of 15.48, 18.78, 20.96 and 22.27 µM, respectively. The molecular docking results indicated that9, which exhibited the most potent activity, also had the best binding affinity to thePfLDH enzyme in terms of its low binding energy (-7.35 kcal/mol) and formed interactions with ARG109, ASN140, and ARG171.

Conclusion:

These findings revealed that isolated compounds fromM. siamensisflowers exhibited antimalarial activity. The result suggests that 1-hydroxy-5,6,7-trimethoxyxanthone is a possible lead structure as a potent inhibitor of thePfLDH enzyme.
Immersive educational curriculum on intracoronary optical coherence tomography image analysis among naïve readers
Authors: Kassis Nicholas , Weber Joseph R. , Adams William , Burke Lucas , Laubham Matthew P. , Pelka Mark , Osude Nkiru , Schreier Matthew , Robertson Samuel , Janak Emily , Lopez John J.
Published: October 2022

Background

Optical coherence tomography (OCT) is an intravascular imaging modality for analysing coronary vessels. Image interpretation remains an obstacle for novice readers due to technical artefacts and uncertainty in tissue characterization. Despite an expanding clinical and research role for OCT, few training efforts exist, and there is an absence of a national standardized educational curriculum. We sought to determine whether an interactive, feedback-based OCT curriculum improved image interpretation among naive readers.

Methods

Naive OCT readers completed both a Standard curriculum, comprised of self-directed didactics and consensus statements, and an Augmented curriculum, which provided real-time digital feedback of feature identification and measurements. Modules were separated by a minimum one-week washout period. After each module, and blinded to the exam answers, subjects completed an identical expert-designed 413-item exam to assess technical knowledge and ability to identify and measure vessel features. Performances were compared using Exact Wilcoxon signed-rank tests.

Results

Among the 7 included subjects were 3 medical students, 3 internal medicine residents, and 1 cardiovascular medicine fellow with no prior OCT experience. The technical knowledge score (maximum 13) was significantly higher with the Augmented compared with the Standard curriculum (median 11 vs. 7, p = 0.03). After undergoing the Augmented curriculum, all 7 subjects were able to identify features of plaque rupture (Standard curriculum: 5/7 subjects, p = 0.5) and macrophages (Standard curriculum: 6/7 subjects, p = 0.99), differentiate the components between red and white thrombus (Standard curriculum: 6/7 subjects, p = 0.99), and characterize lipid plaque by attenuation, signal, homogeneity, and borders (Standard curriculum: 5/7 subjects, p = 0.5). Performances on the remaining exam portions did not differ between curricula.

Conclusions

The need for standardized, effective training in OCT image interpretation is increasingly essential as the intravascular imaging modality becomes widely utilized among interventional cardiologists and trainees. A novel interactive OCT curriculum enhanced naive readers’ technical knowledge and may supplement traditional self-learning in refining analytic skills.
The correlation between spiritual care competence and spiritual health among Iranian nurses
Authors: Heidari Akram , Afzoon Zahra , Heidari Morteza
Published: October 2022

Background

Considering the importance of spiritual aspects of human beings, spiritual care provision is increasingly recognized as a major duty of healthcare providers, particularly nursing staff. Spiritual care competence is necessary for the nurses to be able to provide spiritual care, but the competence itself is associated with other variables. This study aimed to investigate if the spiritual care competence of nurses is related to their spiritual health.

Methods

A cross-sectional study was conducted with the participation of 172 practicing nurses in hospitals affiliated with Qom University of Medical Sciences, selected through stratified random sampling. Participants completed the Persian versions of the Spiritual Health Questionnaire (Amiri) and the Spiritual Care Competence Scale (Van Leeuwen). To examine the correlation between nurses’ spiritual health and spiritual care competence, a Spearman coefficient was used and a linear regression analysis was done to determine the predictability of the spiritual care competence of the nurses. The data were analyzed using SPSS v.23 and the significance level was set at 0.05.

Results

The participants showed a mean (SD) score of 108.93 (19.04) on spiritual care competence and 213.38 (16.49) on spiritual health. Spiritual care competence of nurses showed no significant relationship with demographic characteristics and their spiritual health had a significant relationship with gender only. Correlation analysis revealed a significant relationship between spiritual health and spiritual care competence and their subscales. Moreover, the linear regression analysis indicated that the nurses’ performance regarding spiritual health can predict their spiritual care competence.

Conclusion

The study revealed that the spiritual care competence of nurses is correlated with their spiritual health and performance as a subscale of spiritual health can predict their spiritual care competence. Thus, it can be concluded that the spiritual health of nurses is an important factor in providing spiritual care for patients and meeting their spiritual needs.
Population genomics of an icefish reveals mechanisms of glacier-driven adaptive radiation in Antarctic notothenioids
Authors: Lu Ying , Li Wenhao , Li Yalin , Zhai Wanying , Zhou Xuming , Wu Zhichao , Jiang Shouwen , Liu Taigang , Wang Huamin , Hu Ruiqin , Zhou Yan , Zou Jun , Hu Peng , Guan Guijun , Xu Qianghua , Canário Adelino V. M. , Chen Liangbiao
Published: October 2022

Background

Antarctica harbors the bulk of the species diversity of the dominant teleost fish suborder—Notothenioidei. However, the forces that shape their evolution are still under debate.

Results

We sequenced the genome of an icefish,Chionodraco hamatus, and used population genomics and demographic modelling of sequenced genomes of 52C. hamatusindividuals collected mainly from two East Antarctic regions to investigate the factors driving speciation. Results revealed four icefish populations with clear reproduction separation were established 15 to 50 kya (kilo years ago) during the last glacial maxima (LGM). Selection sweeps in genes involving immune responses, cardiovascular development, and photoperception occurred differentially among the populations and were correlated with population-specific microbial communities and acquisition of distinct morphological features in the icefish taxa. Population and species-specific antifreeze glycoprotein gene expansion and glacial cycle-paced duplication/degeneration of the zona pellucida protein gene families indicated fluctuating thermal environments and periodic influence of glacial cycles on notothenioid divergence.

Conclusions

We revealed a series of genomic evidence indicating differential adaptation ofC. hamatuspopulations and notothenioid species divergence in the extreme and unique marine environment. We conclude that geographic separation and adaptation to heterogeneous pathogen, oxygen, and light conditions of local habitats, periodically shaped by the glacial cycles, were the key drivers propelling species diversity in Antarctica.
Characterising social contacts under COVID-19 control measures in Africa
Authors: Dobreva Zlatina , Gimma Amy , Rohan Hana , Djoudalbaye Benjamin , Tshangela Akhona , Jarvis Christopher I. , van Zandvoort Kevin , Quaife Matthew
Published: October 2022

Background

Early in the COVID-19 pandemic, countries adopted non-pharmaceutical interventions (NPIs) such as lockdowns to limit SARS-CoV-2 transmission. Social contact studies help measure the effectiveness of NPIs and estimate parameters for modelling SARS-CoV-2 transmission. However, few contact studies have been conducted in Africa.

Methods

We analysed nationally representative cross-sectional survey data from 19 African Union Member States, collected by the Partnership for Evidence-based Responses to COVID-19 (PERC) via telephone interviews at two time points (August 2020 and February 2021). Adult respondents reported contacts made in the previous day by age group, demographic characteristics, and their attitudes towards COVID-19. We described mean and median contacts across these characteristics and related contacts to Google Mobility reports and the Oxford Government Response Stringency Index for each country at the two time points.

Results

Mean reported contacts varied across countries with the lowest reported in Ethiopia (9, SD=16, median = 4, IQR = 8) in August 2020 and the highest in Sudan (50, SD=53, median = 33, IQR = 40) in February 2021. Contacts of people aged 18–55 represented 50% of total contacts, with most contacts in household and work or study settings for both surveys. Mean contacts increased for Ethiopia, Ghana, Liberia, Nigeria, Sudan, and Uganda and decreased for Cameroon, the Democratic Republic of Congo (DRC), and Tunisia between the two time points. Men had more contacts than women and contacts were consistent across urban or rural settings (except in Cameroon and Kenya, where urban respondents had more contacts than rural ones, and in Senegal and Zambia, where the opposite was the case). There were no strong and consistent variations in the number of mean or median contacts by education level, self-reported health, perceived self-reported risk of infection, vaccine acceptance, mask ownership, and perceived risk of COVID-19 to health. Mean contacts were correlated with Google mobility (coefficient 0.57, p=0.051 and coefficient 0.28, p=0.291 in August 2020 and February 2021, respectively) and Stringency Index (coefficient −0.12, p = 0.304 and coefficient −0.33, p=0.005 in August 2020 and February 2021, respectively).

Conclusions

These are the first COVID-19 social contact data collected for 16 of the 19 countries surveyed. We find a high reported number of daily contacts in all countries and substantial variations in mean contacts across countries and by gender. Increased stringency and decreased mobility were associated with a reduction in the number of contacts. These data may be useful to understand transmission patterns, model infection transmission, and for pandemic planning.
Detection of SARS-CoV-2 in a dog with hemorrhagic diarrhea
Authors: Padilla-Blanco Miguel , Vega Santiago , Enjuanes Luis , Morey Alfonso , Lorenzo Teresa , Marín Clara , Ivorra Carmen , Maiques Elisa , Rubio Vicente , Rubio-Guerri Consuelo
Published: October 2022

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has infected several animal species, including dogs, presumably via human-to-animal transmission. Most infected dogs reported were asymptomatic, with low viral loads. However, in this case we detected SARS-CoV-2 in a dog from the North African coastal Spanish city of Ceuta presenting hemorrhagic diarrhea, a disease also reported earlier on in an infected dog from the USA.

Case presentation

In early January 2021, a West Highland Terrier pet dog from Ceuta (Spain) presented hemorrhagic diarrhea with negative tests for candidate microbial pathogens. Since the animal was in a household whose members suffered SARS-CoV-2 in December 2020, dog feces were analyzed for SARS-CoV-2, proving positive in a two-tube RT-PCR test, with confirmation by sequencing a 399-nucleotide region of the spike (S) gene. Furthermore, next-generation sequencing (NGS) covered > 90% SARS-CoV-2 genome sequence, allowing to classify it as variant B.1.177. Remarkably, the sequence revealed the Ile402Val substitution in the spike protein (S), of potential concern because it mapped in the receptor binding domain (RBD) that mediates virus interaction with the cell. NGS reads mapping to bacterial genomes showed that the dog fecal microbiome fitted best the characteristic microbiome of dog’s acute hemorrhagic diarrhea.

Conclusion

Our findings exemplify dog infection stemming from the human SARS-CoV-2 pandemic, providing nearly complete-genome sequencing of the virus, which is recognized as belonging to the B.1.177 variant, adding knowledge on variant circulation in a geographic region and period for which there was little viral variant characterization. A single amino acid substitution found in the S protein that could have been of concern is excluded to belong to this category given its rarity and intrinsic nature. The dog’s pathology suggests that SARS-CoV-2 could affect the gastrointestinal tract of the dog.
Identification of human MHC-I HPV18 E6/E7-specific CD8 + T cell epitopes and generation of an HPV18 E6/E7-expressing adenosquamous carcinoma in HLA-A2 transgenic mice
Authors: Peng Shiwen , Xing Deyin , Ferrall Louise , Tsai Ya-Chea , Hung Chien-Fu , Wu T.-C.
Published: October 2022

Background

Human Papillomavirus type 18 (HPV18) is a high-risk HPV that is commonly associated with cervical cancer. HPV18 oncogenes E6 and E7 are associated with the malignant transformation of cells, thus the identification of human leukocyte antigen (HLA)-restricted E6/E7 peptide-specific CD8 + T cell epitopes and the creation of a HPV18 E6/E7 expressing cervicovaginal tumor in HLA-A2 transgenic mice will be significant for vaccine development.

Methods

In the below study, we characterized various human HLA class I-restricted HPV18 E6 and E7-specific CD8 + T cells mediated immune responses in HLA class I transgenic mice using DNA vaccines encoding HPV18E6 and HPV18E7. We then confirmed HLA-restricted E6/E7 specific CD8 + T cell epitopes using splenocytes from vaccinated mice stimulated with HPV18E6/E7 peptides. Furthermore, we used oncogenic DNA plasmids encoding HPV18E7E6(delD70), luciferase, cMyc, and AKT to create a spontaneous cervicovaginal carcinoma model in HLA-A2 transgenic mice.

Results

Therapeutic HPV18 E7 DNA vaccination did not elicit any significant CD8 + T cell response in HLA-A1, HLA-24, HLA-B7, HLA-B44 transgenic or wild type C57BL/6 mice, but it did generate a strong HLA-A2 and HLA-A11 restricted HPV18E7-specific CD8 + T cell immune response. We found that a single deletion of aspartic acid (D) at location 70 in HPV18E6 DNA abolishes the presentation of HPV18 E6 peptide (aa67-75) by murine MHC class I. We found that the DNA vaccine with this mutant HPV18 E6 generated E6-specific CD8 + T cells in HLA-A2. HLA-A11, HLA-A24 and HLA-b40 transgenic mice. Of note, HLA-A2 restricted, HPV18 E7 peptide (aa7-15)- and HPV18 E6 peptide (aa97-105)-specific epitopes are endogenously processed by HPV18 positive Hela-AAD (HLA-A*0201/Dd) cells. Finally, we found that injection of DNA plasmids encoding HPV18E7E6(delD70), AKT, cMyc, and SB100 can result in the development of adenosquamous carcinoma in the cervicovaginal tract of HLA-A2 transgenic mice.

Conclusions

We characterized various human HLA class I-restricted HPV18 E6/E7 peptide specific CD8 + T cell epitopes in human HLA class I transgenic mice. We demonstrated that HPV18 positive Hela cells expressing chimeric HLA-A2 (AAD) do present both HLA-A2-restricted HPV18 E7 (aa7-15)- and HPV18 E6 (aa97-105)-specific CD8 + T cell epitopes. A mutant HPV18E6 that had a single deletion at location 70 obliterates the E6 presentation by murine MHC class I and remains oncogenic. The identification of these human MHC restricted HPV antigen specific epitopes as well as the HPV18E6/E7 expressing adenosquamous cell carcinoma model may have significant future translational potential.
The choice of reference chart affects the strength of the association between malaria in pregnancy and small for gestational age: an individual participant data meta-analysis comparing the Intergrowth-21 with a Tanzanian birthweight chart
Authors: Mtove George , Minja Daniel T. R. , Abdul Omari , Gesase Samwel , Maleta Kenneth , Divala Titus H. , Patson Noel , Ashorn Ulla , Laufer Miriam K. , Madanitsa Mwayiwawo , Ashorn Per , Mathanga Don , Chinkhumba Jobiba , Gutman Julie R. , ter Kuile Feiko O. , Møller Sofie Lykke , Bygbjerg Ib C. , Alifrangis Michael , Theander Thor , Lusingu John P. A. , Schmiegelow Christentze
Published: October 2022

Background

The prevalence of small for gestational age (SGA) may vary depending on the chosen weight-for-gestational-age reference chart. An individual participant data meta-analysis was conducted to assess the implications of using a local reference (STOPPAM) instead of a universal reference (Intergrowth-21) on the association between malaria in pregnancy and SGA.

Methods

Individual participant data of 6,236 newborns were pooled from seven conveniently identified studies conducted in Tanzania and Malawi from 2003–2018 with data on malaria in pregnancy, birthweight, and ultrasound estimated gestational age. Mixed-effects regression models were used to compare the association between malaria in pregnancy and SGA when using the STOPPAM and the Intergrowth-21 references, respectively.

Results

The 10th percentile for birthweights-for-gestational age was lower for STOPPAM than for Intergrowth-21, leading to a prevalence of SGASTOPPAM of 14.2% and SGAIG21 of 18.0%, p < 0.001. The association between malaria in pregnancy and SGA was stronger for STOPPAM (adjusted odds ratio (aOR) 1.30 [1.09–1.56], p < 0.01) than for Intergrowth-21 (aOR 1.19 [1.00–1.40], p = 0.04), particularly among paucigravidae (SGASTOPPAM aOR 1.36 [1.09–1.71], p < 0.01 vs SGAIG21 aOR 1.21 [0.97–1.50], p = 0.08).

Conclusions

The prevalence of SGA may be overestimated and the impact of malaria in pregnancy underestimated when using Intergrowth-21. Comparing local reference charts to global references when assessing and interpreting the impact of malaria in pregnancy may be appropriate.
Two circPPFIA1s negatively regulate liver metastasis of colon cancer via miR-155-5p/CDX1 and HuR/RAB36
Authors: Ji Haein , Kim Tae Won , Lee Woo Joo , Jeong Seong Dong , Cho Yong Beom , Kim Hyeon Ho
Published: October 2022

Background

Circular RNAs (circRNAs) play a critical role in colorectal cancer (CRC) progression, including metastasis. However, the detailed molecular mechanism is not fully understood.

Methods

Differentially expressed circRNAs between primary KM12C and liver metastatic KM12L4 colon cancer cells were identified by microarray. The expression of circRNAs was measured by semi-quantitative (semi-qPCR) and real time-quantitative PCR (RT-qPCR). Metastatic potential including invasive and migratory abilities, and liver metastasis were examined by transwell assays and intrasplenic injection, respectively. CircPPFIA1-associated microRNA (miRNA) and RNA-binding protein (RBP) were screened by an antisense oligonucleotide (ASO) pulldown experiment. The effects of circPPFIA1 on target gene expression were evaluated by RT-qPCR and western blot analyses.

Results

By analyzing circRNA microarray data, we identified two anti-metastatic circRNAs generated from PPFIA1 with different length, which named circPPFIA1-L (long) and -S (short). They were significantly downregulated in liver metastatic KM12L4 cells compared to primary KM12C cells. The knockdown of circPPFIA1s in KM12C enhanced metastatic potential and increased liver metastasis. Conversely, overexpression of circPPFIA1s weakened metastatic potential and inhibited liver metastasis. circPPFIA1s were found to function as sponges of oncogenic miR-155-5p and Hu antigen R (HuR) by an ASO pulldown experiment. circPPFIA1s upregulated tumor-suppressing CDX1 expression and conversely downregulated oncogenic RAB36 by decoying miR-155-5p and by sequestering HuR, respectively.

Conclusion

Our findings demonstrate that circPPFIA1s inhibit the liver metastasis of CRC via the miR-155-5p/CDX1 and HuR/RAB36 pathways.
Clinical and experimental study of a terahertz time-domain system for the determination of the pathological margins of laryngeal carcinoma
Authors: Ke Jing , Jia Lifeng , Hu Yaqin , Jiang Xu , Mo Hailan , An Xiang , Yuan Wei
Published: October 2022

Objective

Laryngeal cancer is a common malignancy in otorhinolaryngological head and neck surgery, accounting for approximately one-third of all head and neck malignancies. Terahertz time-domain spectroscopy (THz-TDS) has recently been found to be useful for the detection of tumors. This study was conducted to investigate the application of THz-TDS in the diagnosis of pathological resection margins of laryngeal cancer.

Methods

Fresh laryngeal cancer tissues from 10 patients with laryngeal cancer were extracted, and after simultaneous HE staining and terahertz imaging, the tumor area, paracancerous area, and normal tissue area of each laryngeal cancer tissue sample were located under a microscope according to the pathological results of HE staining.

Results

The shape contours of the tumor region revealed by terahertz imaging maps and HE staining were similar. In the terahertz spectrum in the frequency range of 0.5–1.9 THz, both the absorption coefficient and refractive index values followed the order tumor > para cancer > normal tissue, with statistically significant differences (P < 0.01). When the terahertz frequency was 1.5 THz, the absorption coefficient of terahertz light waves by laryngeal cancer tissue and the percentage of nuclei showed an extremely high positive correlation (P < 0.01, r = 0.971). In the frequency ranges of 0.5–1.2 THz and 1.6–1.9 THz, the absorption coefficients of the highly differentiated group were higher than those of the moderately differentiated group. In the frequency range of 1.2–1.6 THz, the results were reversed, with statistically significant differences (P < 0.05). In the frequency range of 0.5–1.9 THz, the highly differentiated group had a higher refractive index than the moderately differentiated group, with a statistically significant difference (P < 0.05).

Conclusions

THz-TDS can be used to determine the pathological margins of laryngeal cancer based on the absorption coefficient and refractive index, and the magnitudes of the absorption coefficient and refractive index are related to the percentage of nuclei. The degree of differentiation of laryngeal cancer tissue can be assessed by THz-TDS. The study shows that the terahertz time-domain system is promising for applications in the diagnosis of laryngeal cancer, especially for the more accurate identification of intraoperative margins.
Analysis of gene expression levels and their impact on survival in 31 cancer-types patients identifies novel prognostic markers and suggests unexplored immunotherapy treatment options in a wide range of malignancies
Authors: Giampietri Claudia , Scatozza Francesca , Crecca Elena , Vigiano Benedetti Virginia , Natali Pier Giorgio , Facchiano Antonio
Published: October 2022

Background

Immunotherapy has dramatically improved cancer treatment by inhibiting or activating specific cell receptors, thus unleashing the host anti-tumor response. However, the engagement of the three main immune checkpoints so far identified, CTLA4, PD-1 and PD-L1, is effective in a fraction of patients, therefore novel targets must be identified and tested.

Methods

We focused our attention on the following nine highly relevant immune checkpoint (ICR) receptors: CTLA4, PD1, PD-L1, LAG3, TIM3, OX40, GITR, 4-1BB and TIGIT. All of them are targets of existing drugs currently under clinical scrutiny in several malignancies. Their expression levels were evaluated in patient tissues of 31 different cancer types vs. proper controls, in a total of 15,038 individuals. This analysis was carried out by interrogating public databases available on GEPIA2 portal and UALCAN portal. By the Principal Component Analysis (PCA) their ability to effectively discriminate patients form controls was then investigated. Expression of the nine ICRs was also related to overall survival in 31 cancer types and expressed as Hazard Ratio, on the GEPIA2 portal and validated, for melanoma patients, in patients-datasets available on PROGgene V2 portal.

Results

Significant differential expression was observed for each ICR molecule in many cancer types. A 7-molecules profile was found to specifically discriminate melanoma patients from controls, while two different 6-molecules profiles discriminate pancreatic cancer patients and Testicular Germ Cell Tumors from matched controls. Highly significant survival improvement was found to be related to the expression levels of all nine ICRs in a wide spectrum of malignancies. For melanoma analysis, the relation with survival observed in TCGA datasets was validated in independent GSE melanoma datasets.

Conclusion

Analysis the nine ICR molecules demonstrates that their expression patterns may be considered as markers of disease and strong survival predictors in a variety of malignancies frequently associated to poor prognosis. Thus, the present findings are strongly advocating that exploratory clinical trials are worth to be performed, using available drugs, targeting these molecules.
TCF7/SNAI2/miR-4306 feedback loop promotes hypertrophy of ligamentum flavum
Authors: Duan Yang , Li Jianjun , Qiu Sujun , Ni Songjia , Cao Yanlin
Published: October 2022

Background

Hypertrophy of ligamentum flavum (HLF) is the mainly cause of lumbar spinal stenosis (LSS), but the precise mechanism of HLF formation has not been fully elucidated. Emerging evidence indicates that transcription factor 7 (TCF7) is the key downstream functional molecule of Wnt/β-catenin signaling, which participated in regulating multiple biological processes. However, the role and underlying mechanism of TCF7 in HLF is still unclear.

Methods

We used mRNAs sequencing analysis of human LF and subsequent confirmation with RT-qPCR, western blot and immunohistochemistry to identified the TCF7 in HLF tissues and cells. Then effect of TCF7 on HLF progression was investigated both in vitro and in vivo. Mechanically, chromatin immunoprecipitation, dual-luciferase reporter assays, and rescue experiments were used to validate the regulation of TCF7/SNAI2/miR-4306 feedback loop.

Results

Our results identified for first time that the TCF7 expression was obviously elevated in HLF tissues and cells compared with control, and also found that TCF7 expression had significant positive correlation with LF thickness and fibrosis score. Notably, TCF7 inhibition suppressed the hyper-proliferation and fibrosis phenotype of HLF cells in vitro and ameliorated progression of HLF in mice in vivo, whereas TCF7 overexpression promoted hyper-proliferation and fibrosis phenotype of HLF cells in vitro. Our data further revealed that TCF7 interacted with SNAI2 promoter to transactivated the SNAI2 expression, thereby promoting hyper-proliferation and fibrosis phenotype of HLF cells in vitro. Furthermore, miR-4036 negatively regulated by SNAI2 could negatively feedback regulate TCF7 expression by directly binding to TCF7 mRNA 3’-UTR, thus inhibiting the hyper-proliferation and fibrosis phenotype of HLF cells in vitro.

Conclusions

Our study demonstrated that TCF7 inhibition could suppress HLF formation by modulating TCF7/SNAI2/miR-4306 feedback loop, which might be considered as a novel potential therapeutic target for HLF.
Transmission and pathogenicity of canine H3N2 influenza virus in dog and guinea pig models
Authors: Tangwangvivat Ratanaporn , Chaiyawong Supassama , Nonthabenjawan Nutthawan , Charoenkul Kamonpan , Janethanakit Taveesak , Udom Kitikhun , Kesdangsakonwut Sawang , Tantilertcharoen Rachod , Thontiravong Aunyaratana , Amonsin Alongkorn
Published: October 2022

Background

Influenza A virus causes respiratory disease in many animal species as well as in humans. Due to the high human-animal interface, the monitoring of canine influenza in dogs and the study of the transmission and pathogenicity of canine influenza in animals are important.

Methods

Eight-week-old beagle dogs(Canis lupus familaris)(n = 13) were used for the intraspecies transmission model. The dogs were inoculated intranasally with 1 ml of 106EID50per ml of canine H3N2 influenza virus (A/canine/Thailand/CU-DC5299/2012) (CIV-H3N2). In addition, 4-week-old guinea pigs (Cavia porcellus)(n = 20) were used for the interspecies transmission model. The guinea pigs were inoculated intranasally with 300 µl of 106EID50per ml of CIV-H3N2.

Results

For the Thai CIV-H3N2 challenged in the dog model, the incoculated and direct contact dogs developed respiratory signs at 2 dpi. The dogs shed the virus in the respiratory tract at 1 dpi and developed an H3-specific antibody against the virus at 10 dpi. Lung congestion and histopathological changes in the lung were observed. For the Thai CIV-H3N2 challenge in the guinea pig model, the incoculated, direct contact and aerosol-exposed guinea pigs developed fever at 1–2 dpi. The guinea pigs shed virus in the respiratory tract at 2 dpi and developed an H3-specific antibody against the virus at 7 dpi. Mild histopathological changes in the lung were observed.

Conclusion

The result of this study demonstrated evidence of intraspecies and interspecies transmission of CIV-H3N2 in a mammalian model.
CRISPR/Cas9-mediated deletion of Interleukin-30 suppresses IGF1 and CXCL5 and boosts SOCS3 reducing prostate cancer growth and mortality
Authors: Sorrentino Carlo , D’Antonio Luigi , Ciummo Stefania Livia , Fieni Cristiano , Landuzzi Lorena , Ruzzi Francesca , Vespa Simone , Lanuti Paola , Lotti Lavinia Vittoria , Lollini Pier Luigi , Di Carlo Emma
Published: October 2022

Background

Metastatic prostate cancer (PC) is a leading cause of cancer death in men worldwide. Targeting of the culprits of disease progression is an unmet need. Interleukin (IL)-30 promotes PC onset and development, but whether it can be a suitable therapeutic target remains to be investigated. Here, we shed light on the relationship between IL30 and canonical PC driver genes and explored the anti-tumor potential of CRISPR/Cas9-mediated deletion of IL30.

Methods

PC cell production of, and response to, IL30 was tested by flow cytometry, immunoelectron microscopy, invasion and migration assays and PCR arrays. Syngeneic and xenograft models were used to investigate the effects of IL30, and its deletion by CRISPR/Cas9 genome editing, on tumor growth. Bioinformatics of transcriptional data and immunopathology of PC samples were used to assess the translational value of the experimental findings.

Results

Human membrane-bound IL30 promoted PC cell proliferation, invasion and migration in association with STAT1/STAT3 phosphorylation, similarly to its murine, but secreted, counterpart. Both human and murine IL30 regulated PC driver and immunity genes and shared the upregulation of oncogenes, BCL2 and NFKB1, immunoregulatory mediators, IL1A, TNF, TLR4, PTGS2, PD-L1, STAT3, and chemokine receptors, CCR2, CCR4, CXCR5. In human PC cells, IL30 improved the release of IGF1 and CXCL5, which mediated, via autocrine loops, its potent proliferative effect. Deletion of IL30 dramatically downregulated BCL2, NFKB1, STAT3, IGF1 and CXCL5, whereas tumor suppressors, primarily SOCS3, were upregulated. Syngeneic and xenograft PC models demonstrated IL30’s ability to boost cancer proliferation, vascularization and myeloid-derived cell infiltration, which were hindered, along with tumor growth and metastasis, by IL30 deletion, with improved host survival. RNA-Seq data from the PanCancer collection and immunohistochemistry of high-grade locally advanced PCs demonstrated an inverse association (chi-squared test,p = 0.0242) between IL30 and SOCS3 expression and a longer progression-free survival of patients with IL30NegSOCS3PosPC, when compared to patients with IL30PosSOCS3NegPC.

Conclusions

Membrane-anchored IL30 expressed by human PC cells shares a tumor progression programs with its murine homolog and, via juxtacrine signals, steers a complex network of PC driver and immunity genes promoting prostate oncogenesis. The efficacy of CRISPR/Cas9-mediated targeting of IL30 in curbing PC progression paves the way for its clinical use.
Neoadjuvant toripalimab combined with gemcitabine and cisplatin in resectable locally advanced head and neck squamous cell carcinoma (NeoTGP01): An open label, single-arm, phase Ib clinical trial
Authors: Huang Xiaotao , Liu Qiaodan , Zhong Guihua , Peng Yingpeng , Liu Ye , Liang Lizhong , Hong Haiyu , Feng Weineng , Yang Shuang , Zhang Yaqin , Xian Shiping , Li Zhanyu , Zhou Yuling , Zhang Zhaoyuan , Jiang Wen , Liang Jun , Liu Zhi-gang
Published: October 2022

Background

Neoadjuvant programmed death receptor-1 (PD-1) inhibitors have drawn increasing attention in locally advanced head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the safety and efficacy of gemcitabine and cisplatin (GP), combined with a PD-1 inhibitor, in patients with locally advanced HNSCC.

Materials and methods

A total of 23 eligible patients were administered two cycles of toripalimab and GP followed by surgical resection. The primary endpoints were safety, treatment-related adverse events (TRAEs), and non-operation delay rates. The secondary endpoints consisted of pathological complete response (pCR) rate, major pathological response (MPR) rate, objective response rate (ORR), and R0 resection rate.

Results

The incidence of TRAEs from grades 1 to 4 was 43.5%, 34.8%, 13.0%, and 8.7%, respectively. Grade 3/4 TRAEs included neutropenia, fatigue, hyperglycemia, nausea and vomiting, decreased appetite, rash, and diarrhea. No treatment-related surgical delay was observed. The radiographic response rates were 5.0% (CR), 40.0% (PR), and 55.0% (SD). The ORR reached 45.0%. Eighteen patients underwent successful surgical resection. The R0 resection rate was 100%. The pathological response rates were 16.7% (pCR), 27.8% (MPR, two of five near-pCR), 16.7% (PPR), and 38.8% (NPR). CD4, CD8, CD20, and CD38 expression in the tumors significantly increased after neoadjuvant chemotherapy. The increase in CD20 levels after neoadjuvant treatment in patients with pCR/MPR was significantly higher than in patients with PPR/NPR.

Conclusion

Triweekly neoadjuvant toripalimab-GP is feasible and achieves promising pCR and MPR rates in patients with resectable locally advanced HNSCC.

Trial registration

Chinese clinical trial registry, ChiCTR2100043743, Registered 27 Febrary 2021- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=120570
Development of a core outcome set for hypertensive intracerebral hemorrhage in clinical trials of traditional Chinese medicine: a study protocol
Authors: Jia Min , Lu Yan , Liang Xiao , Tong Chenguang , Wang Jian , Tang Jun , Yang Jian , Wang Min , Jiao Weiwei , Du Wanqing , Wei Jingjing , Zeng Zixiu , Xu Zhenmin , Chen Qian , Lei Lin , Liao Xing , Zhang Yunling
Published: October 2022

Background

Intracerebral hemorrhage (ICH) is a devastating disease, its mortality and disability rate are high. In China, hypertensive intracerebral hemorrhage (HICH) is responsible for 75% of all the cases of primary ICH. A lot of randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) for treating HICH have been carried out. However, these RCTs have a lot of problems, such as heterogeneous outcomes, non-uniform point of measurement. These lead to systematic review/meta-analysis only can include a small number of studies. And outcome measures did not take the wishes of patients and other stakeholders into account. The aim of this study is to establish the core outcome set (COS) for future TCM clinical trials of HICH.

Methods and analysis

First, we will develop a long list of general outcomes by making systematic literature review and semi-structured interviews. Then healthcare professionals and patients with HICH will be invited to participate in two rounds of the Delphi survey to determine the importance of the outcome. Finally, a face-to-face consensus meeting will be conducted to determine the final COS of HICH, including what outcomes should be measured and when and how to measure the outcomes.

Results

We aim to develop a COS that includes TCM core syndrome for HICH to determine what outcomes should be reported and when and how to measure them.

Conclusion

By doing this, we can increase the reporting consistency and reduce the reporting bias in the outcome, which leads to the reuse of research data in meta-analysis and the making of informed healthcare decisions.

Ethics and dissemination

The entire project has received approval from the Ethics Committee of Xiyuan Hospital, China Academy of Chinese Medical Sciences. The final COS will be published and reported at the national and international conferences.

Trial registration

This study is registered with the Core Outcome Measures in Effectiveness Trials database as study 1475. Registered on December 2019.