bluuebunny/crossref_metadata_2025 huggingface dataset:
EIF4A3-induced circTOLLIP promotes the progression of hepatocellular carcinoma via the miR-516a-5p/PBX3/EMT pathway
Authors: Liu Yachong , Song Jia , Zhang Hongwei , Liao Zhibin , Liu Furong , Su Chen , Wang Weijian , Han Mengzhen , Zhang Lu , Zhu He , Zhang Zhanguo , Liang Huifang , Zhang Lei , Zhang Bixiang , Chen Xiaoping
Published: May 2022

Background

Circular RNAs (circRNAs) function as crucial regulators in multiple cancers, including hepatocellular carcinoma (HCC). However, the roles of circRNAs in HCC remains largely unknown.

Methods

circTOLLIP was identified in HCC by screening of two public circRNA microarray datasets and detected in HCC cells and tissues through quantitative real-time PCR (qRT–PCR) and in situ hybridization (ISH). Gain- and loss-of-function assays were performed to confirm the biological effects of circTOLLIP on HCC in vitro and in vivo. Mechanistically, bioinformatics analysis of online databases, MS2-RNA pulldown, biotin-labeled circTOLLIP/miR-516a-5p RNA pulldown, RNA immunoprecipitation (RIP), luciferase reporter assay, fluorescence in situ hybridization assay (FISH) and RNA sequencing were used to confirm the regulation of Eukaryotic initiation factor 4A3 (EIF4A3) on circTOLLIP and the interaction among circTOLLIP, miR-516a-5p and PBX homeobox 3 (PBX3).

Results

circTOLLIP was significantly upregulated in HCC cells and tissues. High circTOLLIP expression was correlated with poor overall survival (OS) and disease-free survival (DFS) in patients. circTOLLIP promoted the proliferation and metastasis of HCC cells in vitro and in vivo. Mechanistically, EIF4A3 promoted the biogenesis of circTOLLIP without affecting its stability. Moreover, circTOLLIP sponged miR-516a-5p to elevate the expression of PBX3, thereby activating the epithelial-to-mesenchymal transition (EMT) pathway and facilitating tumor progression in HCC.

Conclusions

Our findings indicate that EIF4A3-induced circTOLLIP promotes the progression of HCC through the circTOLLIP/miR-516a-5p/PBX3/EMT axis.
Characteristics of the level of psychomotor abilities of female handball players
Authors: Śliż Maciej , Przednowek Karolina H. , Kapuściński Paweł , Dziadek Bartosz , Godek Łukasz , Warchoł Krzysztof , Zieliński Janusz , Przednowek Krzysztof
Published: May 2022

Background

Handball is a high-intensity game, during which players run, change directions with or without the ball, interact with the opponent and make different decisions in both offensive and defensive actions. Players‘ performance may depend on a number of factors, including explosive force, power, speed and agility. Players‘ results may be significantly influenced by their, psychomotor abilities. This article presents an analysis of selected psychomotor abilities of female handball players at different level of competition.

Methods

Test2Drive computer tests were used. The following four tests were used to measure psychomotor abilities: the Simple Reaction Time Test (SIRT), the Choice Reaction Time Test (CHORT), the Hand-Eye Coordination Test and the Spatial Anticipation Test (SPANT). The study covered a group of 118 female handball players (average age 19.6 ± 3.16), playing in the PGNiG Polish Women’s Superliga, the Polish 1st Handball League and 2nd the Polish 2nd Handball League, in the playing positions: goalkeepers, centre players, pivot players and wing players. The study also included analyses of the players‘ body composition and aerobic capacity through the use of the multistage 20-m shuttle run test. In addition, the players‘ psychomotor abilities were analysed depending on the level of competition and playing position.

Results

The analysis of the reaction time and movement time showed statistically significant differences between the results obtained by the female handball players on different levels of competition. Moreover the female players from the Polish Women’s Superliga exhibited the fastest reaction times according to the SIRT, the CHORT and the SPANT. Additionally, on the basis of the linear Pearson correlation coefficient, a statistically significant relationship was determined between the players‘ psychomotor abilities (movement time in the SIRT, the CHORT and the SPANT) and elements of their body composition or aerobic capacity.

Conclusions

The analysis showed that the higher the level of competition (leagues), the shorter the female handball players‘ reaction times. The study also revealed that the players‘ body mass index and percentage of fat content reassociated with movement times, while their aerobic capacity (measured in the multistage 20-m shuttle run test) had a significant influence on their reaction times. This study shows that reaction time it’s one of ability which should be consider to develop in training of female handball players.
Mending a broken heart with novel cardiogenic small molecules
Authors: Powers Nevan , Huang Guo N.
Published: May 2022

Adult mammalian cardiomyocytes are unable to proliferate to regenerate lost tissue after heart injury. Du et al., reporting inCell Stem Cell, employ a FUCCI- and MADM-based system to screen for small molecules combinations that produced a collaborative effect on cardiomyocyte cycling and cytokinesis. The authors generate a cocktail of five small molecules that increase cardiomyocyte proliferation and regeneration in vitro and in vivo with high efficiency, and explore its potential in cardiac regenerative repair after myocardial infarction through a new potential pathway for cardiomyocyte cell-cycle re-entry.
Can parliament govern the transport transition? How the German Bundestag scrutinizes rail projects
Authors: Koch Felix Julian , Rademann Jenny , Fink Simon
Published: May 2022

Background

The paper aims to elucidate to what extent the German Parliament exerts control over rail planning. Parliament has the budgetary right, but information asymmetries vis-à-vis the railway company Deutsche Bahn and the Ministry of Transport make parliamentary control difficult.

Methods

Recently, Germany has instituted a parliamentary review process that allows the Parliament to take up concerns by the public affected by rail projects. We use the principal-agent theory to model this new institution. Parliament delegates rail planning to the Deutsche Bahn, while the Federal Railway Authority serves as a budget watchdog, and parliament uses input from public participation as a deck-stacking procedure. The paper first situates the institutional innovations—the new parliamentary oversight procedure—against the former logic of railway planning. Second, based on the documentation of parliamentary oversight, we analyze for which demands by the affected public the Parliament uses its power to change rail projects.

Results

The paper showed that public participation matters. The German Parliament introduced expensive changes to rail projects. In particular, demands that had been voiced in well-institutionalized public participation (that is, when municipalities, regional associations, etc., were engaged in long-term institutionalized dialogues with the Deutsche Bahn) were more likely to be addressed. An Extra budget was then allocated to, for example, noise-regulating measures.

Conclusions

To sum up, the German Parliament uses information gained in public participation in combination with its budget rights to exert control over railway planning for conflictual projects. Thus, Parliament takes a more active role in railway planning. Whether this also leads to more acceptance for rail projects, is an open question.
Weight over-reporting is associated with low muscle mass among community-dwelling Japanese adults aged 40 years and older: a cross sectional study
Authors: Nakagata Takashi , Yoshida Tsukasa , Watanabe Daiki , Arishima-Hashii Yukako , Yamada Yosuke , Sawada Naomi , Shimada Hidekazu , Nishi Nobuo , Miyachi Motohiko
Published: May 2022

Background

Weight misperception adversely affects health-related quality of life (HRQol); however, few studies have evaluated the relationship between weight misperception and muscle mass. This study aimed to examine the relationship of weight misperception with low muscle mass using skeletal muscle index (SMI) estimated by multifrequency bioelectrical impedance analysis (MF-BIA) among community-dwelling Japanese.

Methods

Participants were 525 Japanese individuals aged 40–91 years old (male 89, female 436). Misperception was calculated by subtracting measured value from self-reported weight, presented as a percentage and categorized into tertiles based on sex (under-reporters, acceptable reporters, and over-reporters). Appendicular lean mass was estimated using MF-BIA, and low muscle mass was defined using SMI values of 7.0 and 5.7 kg/m2 for males and females, respectively, based on the Asian Working Group for Sarcopenia 2019 consensus. We evaluated the association between prevalence of low muscle mass and weight misperception (under-reporters and over-reporters) using multivariate logistic regression including covariate.

Results

In total, 9.3% (49/525) of participants had low muscle mass. After adjusting for covariates, prevalence of low muscle mass was higher among over-reporters than acceptable-reporters (odds ratio [OR]; 2.37, 95% confidence interval [CI]; 1.03–5.44). Additionally, sensitivity analysis was performed on females, which confirmed that the prevalence of low muscle mass was higher in over-reporters than in acceptable-reporters (OR, 3.27; 95% CI, 1.18–9.12).

Conclusion

Weight misperception was significantly correlated with low muscle mass, especially in over-reporters.
Mental health status of adolescents in-home quarantine: a multi-region, cross-sectional study during COVID-19 pandemic in Bangladesh
Authors: Afrin Sadia , Nasrullah Sarker Mohammad , Dalal Koustuv , Tasnim Zarrin , Benzadid Md. Shadly , Humayra Farhin , Saif-Ur-Rahman K. M. , Hawlader Mohammad Delwer Hossain
Published: May 2022

Background

The population's mental and physical health worldwide are currently at risk due to the coronavirus pandemic. We evaluated the mental health status of the adolescents trapped indoors because of the precautionary restrictions and prolonged closure of the educational institutions.

Method

A cross-sectional study was conducted on adolescents from multiple urban and semi-urban areas of Bangladesh from 22 January to 3 February 2021. A self-reported online questionnaire containing questions regarding sociodemographic factors, home quarantine-related factors and mental health symptoms was distributed to collect data. Descriptive analysis, bivariate and multivariable logistic regressions were performed to measure the association of the variables. Cronbach's alpha was estimated to present the internal consistency of the scales.

Results

A total of 322 adolescents (aged 12–19) with a mean age of 16.00 years (SD = 1.84) responded to the invitation. 54.97% (n = 177) of them were male, and the participants were predominantly urban residents (87.27%, n = 281). We observed varying degrees of depression in 67.08%, anxiety in 49.38% and stress in 40.68% of the participants according to DASS-21. Age, sex, education, mother's occupation, total monthly income, playing sports, doing household chores, going out of home, watching television, using the internet, attending online classes, changing food habits, and communicating with friends had a positive significant association with mental health burdens.

Conclusion

Home quarantine has a noticeable adverse impact on the mental health of teenagers. Psychological evaluations and counselling via online and offline programs are essential to improve adolescents' declining mental health conditions.
Erratic and random noise attenuation using adaptive local orthogonalization
Authors: Oboué Yapo Abolé Serge Innocent , Chen Yunfeng , Bai Min , Chen Wei , Chen Yangkang
Published: May 2022

The local orthogonalization (LO) approach has been broadly applied to attenuate random noise and deal with the signal-leakage problem induced using the traditional denoising schemes. First, this approach removes noise and applies the LO weight (LOW) operator to the originally estimated signal. Then, the signal leakage is predicted and subsequently recovered from the original noise component. Finally, the original denoised component and the recovered signal are mixed to output the denoised seismic signal. However, this approach has limits when the seismic data include random and erratic noise. We find that this shortcoming is mainly caused by the weakness of the traditional denoising operators (e.g., curvelet and f- x deconvolution methods), which are insufficient to adapt themselves to the originally denoised signal and noise sections for the LOW process. Therefore, we aim to attenuate random and erratic noise using an adaptive LO method. By mixing the hard thresholding (HT) operator and the exponential moving-average (EMA) filter, we have developed a novel operator, which we call the HTEMA operator. Then, by introducing this novel operator into the curvelet method framework, we adapt the initially denoised signal and noise sections for the LOW process. The proposed operator is applied to the frequency domain curvelet coefficients provided by the inverse transform. Then, we use the LOW operator to compensate for the damage of useful signals. The proposed approach is not limited to the curvelet method but can be applied to other traditional denoising methods. We estimate the noise attenuation performance by the visual inspections, local similarity maps, and the signal-to-noise ratio. Synthetic and field data examples indicate the effectiveness of the proposed method in applications to erratic and random noise attenuation compared with the curvelet, f- x deconvolution, and the LO methods.
Enhancing Healthcare Workers’ Capacity in Cancer and Other Non-Communicable Diseases (NCDs) Care in Sub-Saharan Africa (SSA) Through e-Health Innovations: A Case of International Cancer Institute (ICI), Eldoret, Kenya
Authors: Kitur Gloria , Achieng Emmah , Chemweno Carolyne , Asirwa Chite
Published: May 2022

PURPOSE

Sub-Saharan Africa (SSA) hosts 11% of the world’s population yet bears 24% of the global disease burden with only 3% of the world’s health workforce at the frontline. The new threat of NCDs is worsened by the challenge of infrastructure, access to care and health workforce capacity. E-health bridges the gap of formal education and training through telemedicine and virtual e-learning platforms.

METHODS

International Cancer Institute (ICI) leveraged on telemedicine to build capacity of Health Care Providers (HCPs) in the COVID era. Through bi-weekly virtual multi-disciplinary tumour boards, on-line preceptorship training programs and tele-consultations between healthcare providers across Kenya and SSA, access to quality and timely cancer care was evaluated.

RESULTS

Between May 2020 and April 2021, ICI conducted 95 virtual multi-disciplinary tumour boards which were attended by 7,483 health care workers from 21 countries across the world, 16 from countries in SSA. ICI also conducted 27 virtual unique training programs in cancer and other NCDs care which attracted 578 participants from across the globe, 95% of which were from SSA. The training participants distribution included 77% clinical healthcare providers; 17% non-clinical health care workers and 6% allied healthcare workers. The online training platform provided the opportunity for HCPs to be trained from their locality thus bridging the gap of cost and distance to advance their training. The innovative e-learning platform has made it possible to reach more healthcare workers across SSA without the limitation of restricted classroom sessions.

CONCLUSION

Capacity building of HCPs in SSA in cancer and other NCDs care and control goes beyond formal training. On-going peer to peer mentorship and on-job skills training have proved to be effective in building HCP capacity in improved standard of care across the cancer and other NCDs care. Use of a multi-disciplinary approach to care while leveraging on e-health solutions contributes to positive patient outcomes in resource limited settings.
Addressing the Barrier of Physical Access to Oncology Care in Sub-Saharan Africa (SSA) Through Establishment of Short-Stay Homes for Cancer Patients: A Case of International Cancer Institute, Child and Family Wellness Center in Eldoret, Kenya
Authors: Kitur Gloria , Mbandar Florence , Muyodi David , Asirwa Chite
Published: May 2022

PURPOSE

Geographical distance to access services and lack of decentralized diagnostic and treatment facilities have been identified as barriers to positive treatment outcomes among cancer patients in Sub-Saharan Africa who have to undergo financial and logistical challenges. Potential approaches to reducing this barrier include providing transport/travel allowance to patients from far flung regions, decentralizing cancer care services or providing patient housing close to cancer treatment facilities.

METHODS

The International Cancer Institute Child and Family Wellness Center was established in June 2020 as a half-way home for patients undergoing treatment at the ICI Cancer Care and Research Clinic (ICI_CRC). The center aims to provide safe accommodation for patients having challenges to travel to and from their homes for diagnostic work-up and treatment.

RESULTS

Between June 2020 and October 2021, a total of 101 admissions were made to the ICI Child and Family Wellness Center, of these 76% were female while 24% were male patients. A majority of the patients were first time admissions while 22% of them were admitted more than once; 69% of them were accompanied by a caregiver. The longest duration of stay was 18 days while the shortest was 1 day depending on the reason for admission; the most common being treatment sessions ending late in the day or treatment sessions taking more than one day. The patients admitted were drawn from 15 different counties in Kenya.

CONCLUSION

Physical inaccessibility to cancer care services in SSA greatly affects patient compliance with treatment and follow-up. Patients who live far from specialist care hospitals are more likely to have an advanced disease at diagnosis, inappropriate treatment, a worse prognosis and poorer quality of life compared to those living closer to hospitals. In addition to decentralization of cancer care, provision of accommodation for cancer patients close to hospitals can greatly improve compliance to treatment resulting in positive treatment outcomes.
Effective Innovative Models of Health Care Delivery in the Era of the COVID-19 Pandemic to Reduce Disparities in Cancer Care and for Cancer Control in Low-Middle Income Countries—South African Experience of the Cancer ECHO Model
Authors: Osei-Fofie Daniel
Published: May 2022

PURPOSE

The Northern Cape province is the largest province in South Africa. However, it has the least resources for cancer care. Patients have to travel very long distances to access cancer care. Cancers are diagnosed in late stages due to lack of resources including trained health care personnel. There was the need for an innovative model for training health care personnel, mentorship and empowerment to enable provision of cancer care in the rural areas of the province.

METHODS

In 2017, the Northern Cape Health Department had a collaboration with the Project ECHO Institute, University of New Mexico. An Immersion training in ECHO was provided in Albuquerque under the sponsorship of Bristol Myers Squibb Foundation and the Project ECHO Institute. An ECHO Hub was established at the tertiary cancer center with spoke sites in two district hospitals. The first cancer ECHO in Africa was launched at Kimberley Hospital in July 2018 to provide training and mentorship in Lung cancer and Mesothelioma care. In 2020, during the COVID-19 pandemic, the ECHO clinics were used on a more regular basis for patients' management.

RESULTS

Doctors, nurses and community healthcare workers have been trained using the ECHO model to provide cancer care in all the district hospitals. The ECHO clinics have now been expanded to cover other cancers. Palliative care ECHO has also been launched to improve provision of palliative care services. There has been retention of staff in the rural areas to provide cancer care due to mentorship and empowerment using the ECHO model.

CONCLUSION

ECHO is an effective innovative model to democratize knowledge and help reduce disparities and inequities in cancer care and for cancer control in low-middle income countries. In the era of the COVID-19 pandemic, ECHO clinics can assist with effective patient care.
How Did the Covid-19 Pandemic Impact Cancer Prevention and Treatment? Examining Nationally Representative Survey Data
Authors: Semprini Jason
Published: May 2022

PURPOSE

In March 2020, policymakers, healthcare providers, and public health professionals shifted their resources toward covid-19 prevention and mitigation. This reallocation came at the expense of other essential healthcare services, including cancer prevention and treatment. Delaying cancer services will increase the burden and cost of cancer treatment in the coming years, but the extent of these delays is unknown. As the country continues to move forward, a better understanding of how cancer services were impacted will help policymakers prioritize strategies to mitigate the adverse effects of delayed cancer prevention and treatment.

METHODS

This study is among the first to use the newly released 2020 Behavioral Risk Factor Surveillance System (BRFSS) questionnaire. BRFSS is a phone-based survey and is representative of the U.S population. The BRFSS questionnaire asks about cancer screening, vaccination, and treatment services within the past year. I compared the total weighted responses in Q1, 2020 with the total weighted responses in Q4, 2020. With the latter group being exposed to six months of the covid-19 pandemic, these results serve as a baseline or “floor” estimate of how much cancer prevention and detection service patterns changed in the United States.

RESULTS

Mammographies declined 4.7% (Q1 = 21,407,433 v Q4 = 20,403,265), pap smears declined 1.3% (Q1 = 19,464,724 v Q4 = 19,211,238), colorectal cancer screenings declined 9.9% (Q1 = 8,534,587 v Q4 = 7,693,484). While there was no estimated change in adults diagnosed with cancer, the number of adults currently receiving cancer treatment declined by 5.3% (Q1 = 485,425 v Q4 = 459,620).

CONCLUSION

The covid-19 pandemic forced Americans to delay critical cancer prevention and treatment services. Fewer breast cancer, cervical, colorectal cancer screenings in 2020 will undoubtedly lead to more cancer diagnoses in the coming years, likely at more advanced and aggressive stages. Meanwhile cancer patients seemed to have delayed cancer treatment, but such delays cannot be sustained. Policymakers can mitigate the potential strain on cancer control systems by advancing cancer screening initiatives.
Immortalized B Cells Transfected With mRNA of Antigen Fused to MITD (IBMAM): An Effective Immunological Tool for In-Vitro Immune-Monitoring of Antigen-specific T Cells
Authors: Zhang Tiantian , Wang Zhe , Cha Soung-Chul , Liu Jingwei , Dong Zhenyuan , Szymura Szymon , Anderson Aaron , Kuang Benjamin , Neelapu Sattva , Kwak Larry
Published: May 2022

PURPOSE

To overcome technical limitations of detecting low frequencies of antigen-specific-T cells in human patients, we sought to establish a highly sensitive platform for antigen-specific-T cell detection and activation using IBMAM (immortalized B cells transfected with mRNA of antigen fused to MHC-class-I-trafficking-domain [MITD]).

METHODS

We first established immortalized B cells in-vitro as antigen-presenting cells. B cells were isolated from CMV-seropositive normal healthy donors (NHDs), stimulated, and transduced with retrovirus containing BCL-6 and BCL-XL. Purified CD4+ T lymphocytes obtained from the NHDs PBMC were co-cultured in-vitro with autologous immortalized B cells transfected with CMVpp65 mRNA fused to MITD (IBMAM) as a model antigen and then measured for activation using IFN-g ELISA. We developed two pathways for IBMAM mediated antigen-specific T cell activation and detection. For the first pathway, if IFN-g is detected, T cells are isolated again from NHDs PBMC and expanded using rapid expansion procedures (REP). After the first REP, antigen-specific T cells are detected using IBMAM, sorted, and a second REP is performed. However, for the second pathway, if IFN-g is not detected, NHDs PBMC is stimulated twice using IBMAM and subsequently antigen-specific T cells are detected using IBMAM again.

RESULTS

B cells were successfully immortalized by transfecting at least 5*105 cells with retrovirus (1MOI) and co-cultured with CD40L-IL21 expressing human fibroblasts. We observed a significantly increased activation of antigen-specific CD4+ T cells when using IBMAM in comparison to controls transfected with CMVpp65 mRNA lacking the MITD fusion or a known CMVpp65 peptide pool. For pathway 1 and 2 of our platform, successful detection, activation, and expansion of CMVpp65-specific T cells were observed from low frequency NHDs samples using IBMAM.

CONCLUSION

We have thus established a highly sensitive method of immuno-monitoring that can be used for the detection of antigen-specific T cells in patient samples with low frequencies of antigen-specific-T cells, such as human cancer antigens.
Formative Research to Design SMS Messages to Increase Breast Cancer Screening Uptake in Argentina
Authors: Antelo Victoria Sanchez , Paolino Melisa , Frejdkes Paula , Correa Silvina , Furia Anabel , Lopez de Degani Graciela , Arrossi Silvina
Published: May 2022

PURPOSE

There is a need for interventions to promote breast cancer screening among high-risk population. This formative research is part of a pragmatic randomized trial being conducted in Santa Fe, Argentina, in which we are evaluating whether SMS messages sent to women aged 50-69 increases breast cancer screening uptake. Here, we describe the formative results used to design the content of the SMS messages to be tested in the trial.

METHODS

We conducted four on-line focus groups with women aged 50+ (n = 14). Participatory techniques were used to debate the advantages and disadvantages of different options for the five structural elements -i.e., greeting, recipient, sender, message's topic, and closing line-of the SMS message. We openly coded the discussions for agreements and preferences regarding the SMS message content.

RESULTS

SMS messages as reminders to increase breast cancer screening were highly accepted. Women argued that the greeting line should provide clear information about the topic of the SMS message (eg, Health information). SMS messages should also include the woman's name, because this inclusion would be an indicator that it was a personal SMS message. Most women considered that the sender of the SMS messages should be a health institution as this would legitimize the content. Regarding the topic of the message, women preferred an imperative tone and they mentioned that the SMS message should include information about how to get a mammogram (eg, “Women aged 50-69 should have a mammogram done every two years. Do you have an appointment? WhatsApp to xxxxx”). The closing line should encourage women to get a mammogram (eg, “Ask for your appointment now! It is important!”).

CONCLUSION

Our findings have some implications for the design of mHealth interventions targeted at improving breast cancer screening. A personalized SMS could be a good way of inviting women, although its content must be carefully designed to provide clear information about how to get a mammogram.
Modulation of Metastasis and Stemness-Associated Genes by Heme Oxygenase 1 (HO-1) in Prostate Cancer
Authors: Sabater Agustina , Toro Ayelen , Sanchis Pablo , Pascual Gaston , Seniuk Rocio , Vazquez Elba , Cotignola Javier , Gueron Geraldine , Bizzotto Juan , Lage-Vickers Sofia
Published: May 2022

PURPOSE

Prostate cancer stem cells enhance the tumor's capacity to proliferate, metastasize, and to resist therapies. Thus, stemness represents a therapeutic challenge in prostate cancer (PCa). We have previously reported a strong anti-tumoral effect of heme oxygenase 1 (HO-1) in prostate carcinogenesis in vivo and in vitro. However, its association with metastasis-stemness is still poorly elucidated. Thus, we aimed at describing the effects of HO-1 overexpression on metastasis/stemness processes in PCa, by also identifying key HO-1-modulated genes.

METHODS

We performed clonogenic assays to evaluate the effect of HO-1 pharmacological induction on the stem properties of PC3-cells. We carried out an RNA-seq analysis to assess the transcriptional differences of 144 metastasis/stemness/STAT3-signature genes after HO-1 induction. The clinical significance of HO-1-modulated genes was assessed by comprehensive bioinformatics analyses using public data repositories with gene expression and survival data of PCa patients (Oncomine, n = 1,128; TCGA-PRAD, n = 565). RNA-seq results were validated by RT-qPCR.

RESULTS

Clonogenic assays results showed a significant reduction in colony formation efficiency after HO-1 pharmacological induction with hemin ( P ≤ .01). Transcriptomics profiling by RNA-seq evidenced a significant modulation of 32 key markers related to metastasis/stemness/STAT3-signature under HO-1 induction. Further, 15 HO-1-modulated genes were differentially expressed in PCa vs. normal prostate gland (Oncomine) and HO-1 induction reverted the expression profile observed for these genes. We next used the TCGA-PRAD dataset which revealed that ADAM15, BCL2L1, LTBR, MBNL2 and SPINT1 had the same expression profile as in Oncomine. Additionally, PCa patients with high MBNL2 expression showed a longer disease progression-free survival, which is interesting as it is upregulated in PC3-cells overexpressing HO-1, as validated by RT-qPCR.

CONCLUSION

Here, we propose a potential mechanism by which HO-1 could inhibit metastasis/stemness by modulating relevant genes in PCa progression. This study may cast a new light on PCa treatment, highlighting HO-1 modulation of cell plasticity, supporting it as a potential therapeutic target for the disease.
Breast Cancer Among Indigenous and Non-Indigenous Women at the Mexican Teachers' Cohort
Authors: Gómez-Flores-Ramos Liliana , Cortés-Valencia Adrian , Stern Dalia , Brochier Marion , Sánchez-Blas Hugo Rodrigo , Erazo-Valle-Solís Aura , Chávez-Cárdenas Mildred Yazmin , Miranda Pabel , Lajous Martín
Published: May 2022

PURPOSE

Hispanics and Indigenous women are underrepresented in cancer research. We aimed to estimate the incidence of breast cancer (BC) among indigenous and non-indigenous women and describe reproductive and lifestyle risk factors.

METHODS

The baseline questionnaire was completed by 115,307 women (2006-2008). Indigenous ancestry was defined by self-adscription and/or speaking an indigenous language. Incident BC-cases were confirmed using self-reports, administrative and clinical databases, cancer registries, and death certificates. We calculated person-years from the baseline questionnaire to the date of diagnosis, death, or the end of follow-up (December 31, 2019). We age-standardized reproductive and lifestyle information.

RESULTS

After a median follow-up of 10.8 years, we confirmed 1,212 BC-cases. The crude incidence rate per 100,000 person-years was 55 for indigenous and 95 for non-indigenous women; the mean age at diagnosis was 48.2 and 50.8, respectively. In indigenous BC-cases, early menarche (11.9 v 26.7%), first pregnancy > 25 years (36.8% v 51.7%), and nulliparity (11.7% v 14.1%) were less frequent compared to non-indigenous. The number of children (3.0 v 2.6) and breastfeeding > 12 months (71.6% v 45.2%) were higher among indigenous. Indigenous had earlier menopause (44.8 v 47.5 years) and more premenopausal-BC (27.8% v 25.1%). Oral contraceptives use (42.6% v 48.0%), hormone-replacement therapy (12.4% v 24.6%), family history of BC (11.9% v 15.1%) and benign breast-disease (17.8% v 23.0%) were less frequent in indigenous cases. Physical activity (> 150 min/week) was higher in indigenous women (34.3% v 27.8%). Smoking (6.6% v 11.2%) and alcohol consumption (47.9% v 61.3%) were lower in indigenous women; however, they had more diabetes (14.6% v 6.0%) and were at the highest tertile of the dietary glycemic index (40.2% v 35.0%).

CONCLUSION

In the MTC, BC-incidence in indigenous women is lower than in non-indigenous; this might be explained by a lower prevalence of hormonal and reproductive risk factors and higher physical activity among indigenous women.
Dental Health Utilization in the Republic of Palau: A Survey to Determine Feasibility of an Oral Cancer Screening Program
Authors: Rieth Katherine , Dye Timothy , Ikerdu Edolem , McIntosh Scott , Sy Angela
Published: May 2022

PURPOSE

Oral cancer is the 5th most common cancer in Palau. Betel nut use is a highly prevalent cultural tradition in Palau and also a carcinogen, whose effect may be synergistic with the addition of smokeless tobacco in betel quid in the development of oral cancer. Prognosis can be improved with early detection. The purpose of this study is to assess the feasibility of an oral cancer screening program using existing dental health infrastructure with mixed methods assessment of utilization of dental health resources by adults in Palau.

METHODS

An Internet-based survey was used. Both quantitative and qualitative assessments of dental health care utilization were explored. Quantitative analyses of survey responses were done using descriptive and analytical statistical functions. Open-ended survey questions were coded and analyzed for emergent themes to develop recommendations for the proposed intervention.

RESULTS

The survey was available (Facebook Ads) for 9 days. There were 223 completed surveys, age range was 18-75 (mean = 42.7 years), 177 (80.1%) identified as female, 60.4% reside on Koror, and 60.4% have some university/college level education. Dental care was seen to be important (mean score 82.27). Most felt there were no major barriers to seeing a dentist (n = 164, 72.5%). Themes pertaining to barriers to access focused on lack of availability of appointments and cost. Themes pertaining to facilitators included multilevel resources and services provided by dental clinics.

CONCLUSION

Dental care is important to Palauans, and most would prefer to have this occur in a clinic setting. The themes generated suggest that while there are important facilitators that are in place to promote seeking and obtaining dental care, the existing infrastructure and access to dental care currently do not support an oral cancer screening program. However, these data do provide important areas to address the delays associated with dental care that can improve access and support the implementation of oral cancer screening in the future.
A Prebiotic Hydrogel to Prevent Cervical Cancer by Optimizing the Vaginal Ecology and Reducing Oncogenic Biological Risk Factors in Women Across Global Health Care Access
Authors: Ellington Joanna , Clifton G. Dennis , Ellington-Lawrence Rayne D. , De la Fuente Vega Zamora , Fichorova Raina
Published: May 2022

PURPOSE

Persistent oncogenic, high-risk human papillomavirus (hrHPV) is a leading cause of cervical cancer and driven by vaginal dysbiosis and mucosal irritation. There is a high need for a product to optimize vaginal ecology and decrease biological risk factors of hrHPV persistence and cervical cancer.

METHODS

A prebiotic hydrogel (PreBioGyn) was designed for cervical cancer prevention to support the cervicovaginal ecology and anti-viral function. PreBioGyn was compared to over-the-counter (OTC) acidifying vaginal gels RepHresh and Trimosan for impact on: (1) in-vitro growth of L. crispatus—a Lactobacillus essential for the healthy vaginal biome; (2) inhibition of P. bivia—a pathobiont characteristic of vaginal dysbiosis and directly linked to hrHPV reactivation and cervical cancer spread; (3) mucosal irritation potential measured as daily mucus production by slugs (Arion lusitanicus) after 5-day intermittent product exposure; and (4) osmolality and mucoadhesion essential for compatibility with the cervicovaginal mucosal barrier (ability of gel to interdigitate with mucins in vivo).

RESULTS

Exposure to PreBioGyn for 24 hours completely suppressed P. bivia while sustaining L. crispatus growth which was recovered at 100 ± 1%. Trimosan was bactericidal to L. crispatus within 4 hours incubation and RepHresh within 24 hours of incubation. The mucosal irritation potential of PreBioGyn equaled negative controls, whereas the OTC acidifying-gels resulted in greater irritation potential with > 2-fold mucus production versus the control ( P < .05). The PreBioGyn formula was iso-osmotic to the human vagina (280 mOsmo/kg), while RepHresh was hyper- (1,400 mOsmo/kg) and Trimosan - hypoosmotic (81 mOsmo/kg). The mucoadhesion index of PreBioGyn (10 ± 2.0) was higher ( P < .05) than that of RepHresh (1 ± 0.2) and Trimosan (1 ± 0.3).

CONCLUSION

Our results provide preclinical evidence for the biocompatibility and safety of the Pre-BioGyn gel. The prebiotic PreBioGyn vaginal gel improved microbiota parameters essential for cervical cancer prevention, compared to leading OTC acidifying-gels. PreBioGyn may offer a simple, affordable user-directed cervical cancer prevention intervention.
Findings of a Nationwide Mixed-Methods Assessment of Cancer Care and Prevention Needs in Botswana
Authors: Sharma Kirthana , Lebelonyane Refeletswe , Ralefela Tlotlo , Vuylsteke Peter , Antony Reena , Legwaila Morongwa , Leselwa Tapologo , Masupe Tiny , Gaolathe Tendani , Marlink Richard
Published: May 2022

PURPOSE

High-level investment in cancer prevention and control in low- and middle-income countries is urgently needed to address the predicted surge in cancer incidence, yet few assessments of health systems have systematically identified gaps in infrastructure, training, and patient care in sub-Saharan Africa. In Botswana, we evaluated the current state of cancer care and prevention, to understand the strengths, weaknesses, and needs regarding the provision of comprehensive cancer services.

METHODS

The study evaluated four regional hospitals designated as cancer sites by the Botswana Ministry of Health and Wellness to decentralize cancer services. A multi-site, cross-sectional evaluation using qualitative and quantitative methods was conducted. Focus Group Discussions with cancer patients, cancer survivors, caregivers, the general population, and healthcare workers were analyzed for emergent themes. Quantitative surveys assessed knowledge, attitudes and practices of health workers and hospital management staff, and cancer service gaps at health facilities.

RESULTS

Knowledge gaps included low awareness of cancer signs and symptoms among the general population, poor knowledge of early detection and treatment among health workers, and caregivers lacked skills to support cancer patients. Cancer screening services, other than cervical screening, were limited in all sites. Diagnosis and treatment barriers included lack of specialized personnel, equipment, timely pathology services, and drug stockouts. There were low levels of confidence in cancer management, including chemotherapy, without support from oncologists. Providers reported low patient screening uptake due lack of access and patients reported fear of diagnosis. Health facilities did not routinely notify cancers to the national registry. Radiotherapy was limited to one private hospital in the capital.

CONCLUSION

Decentralization of cancer services to regions will require substantial capacity building at district hospitals to strengthen fragmented screening, early diagnosis and treatment services. Health provider training needs and infrastructure gaps were substantial, with low public awareness of cancer signs, symptoms and causes.
Neoadjuvant Therapy Effects on Invasive Mammary Carcinomas: Comparative Study of Pre- and Post-Therapy Cases and Assessment of Overall Survival Time
Authors: Gomes Virginia , De Castro Carolina , Balabram Debora , Santos Barbara Dos , Nunes Cristiana
Published: May 2022

PURPOSE

To evaluate the pathological effects of neoadjuvant therapy (NT) on prognostic and predictive factors of invasive mammary carcinomas (IMC) and the impact of these changes on overall survival time.

METHODS

Sixty-eight IMC diagnosed, treated with NT (2008-2016), with surgical excision at Hospital das Clínicas of UFMG showing pathological partial response. All samples were revised by an experienced breast pathologist, classified and graduated according to the WHO criteria. The histological tumor types were divided into three groups (no special type, lobular type and others). Estrogen and Progesterone receptors (ER and PR), HER2 and Ki67 status were evaluated through IHC. Statistical analysis was performed using the SPSS statistical program.

RESULTS

Nineteen of 55 tumors (34.5%) showed changes in histological type ( P = .024). Although not significant, 26/55 tumors had changes in histological grade, such as higher (27.3%) or lower grade (10.9%). Seven percent showed an increase in the percentage of inflammatory infiltrate ( P = .004) and 35% had a decrease. Twenty-two of 55 (40%) of tumors showed ER changes and 20/55 (36,4%) showed PR changes. 96.4% of cases kept the same HER2 expression. 34.5% of tumors showed changes in the Ki67 expression. Ki67 distribution was different in post-therapy samples (non-normal distribution), diverting from expected ( P = .014). There was an increase in Luminal A-like type (from 18.2% on pre-NT to 25.5% on post-NT samples) and Triple Negative type (from 34.5% on pre-NT to 45.5% on post-NT samples). These pathological changes found in post-neoadjuvant therapy samples did not affect the overall survival time of patients (median time of 44 months).

CONCLUSION

Prognostic and predictive factors of IMC can change after neoadjuvant therapy. Reclassifying and retesting the residual samples is important to reevaluate treatment. There was no impact on overall survival of patients.
Exploiting Interdata Relationships in Prostate Cancer Proteomes: Clinical Significance of HO-1, HSPB1, DDB1 and 14-3-3ζ/δ Interaction
Authors: Lage-Vickers Sofia , Sanchis Pablo , Bizzotto Juan , Toro Ayelen , Valacco Maria P. , Cotignola Javier , Vazquez Elba , Gueron Geraldine
Published: May 2022

PURPOSE

Prostate cancer (PCa) is the second most common type of cancer in men and the sixth leading cause of cancer-related death in men worldwide. The discovery of new therapeutic avenues in PCa, and the development of effective drugs in the era of personalized medicine, would greatly benefit from the field of proteomics. We have previously shown the anti-tumoral role of Heme oxygenase 1 (HO-1) in PCa.

METHODS

In this work, we undertook a mass spectrometry-based proteomics study to assess whether in PCa cells and under oxidative stress conditions, HO-1 could interact with proteins previously documented to have nuclear localization.

RESULTS

Among the HO-1 interactors, we identified 11 proteins with nuclear localization. Significant and positive correlation between HMOX1 and six of those genes was observed, using the GSE70770 dataset. Alternatively, HMOX1 and YWHAZ showed negative correlation. High expression of HNRNPA2B1, HSPB1, NPM1, DDB1, HMGA1, ZC3HAV1, and HMOX1 was associated with an increased relapse-free survival (RFS) in PCa patients through univariable analyses. Further, PCa patients with high HSPB1/HMOX1, DDB1/HMOX1, and YWHAZ/HMOX1 showed a worse RFS compared with patients with lower ratios. Moreover, by using a prognostic risk score model, a decrease in RFS for patients with higher scores of this signature was observed. However, the only factor significantly associated with a higher risk of relapse was high YWHAZ. HSPB1, DDB1 and YWHAZ independence from PCa clinic-pathological parameters was confirmed through multivariable analyses. Moreover, co-immunoprecipitation analysis in PCa cells ascertained HO-1/14-3-3ζ/δ (YWHAZ encoding gene) interaction.

CONCLUSION

Herein, we report novel interactions between HO-1 and HSPB1, DDB1 and 14-3-3ζ/δ, highlighting their clinical relevance in PCa.
The Cost Implication of Trastuzumab in Patients With HER2-Positive Breast Cancer at Moi Teaching and Referal Hospital, Eldoret, Kenya
Authors: Wabende Lucy Najala , Bhatia Manisha , Kiptoo Stephen , Kisilu Nicholas , Kiboss Caroline , Kibiwot Silvanus , Jepkirui Sally , Awuor Dorice Adhiambo , Busakhala Naftali , Hunter-Squires Joanna
Published: May 2022

PURPOSE

A year course of trastuzumab revolutionized treatment for human epidermal growth factor receptor (HER2)-positive breast cancer by increasing survival rates. However, trastuzumab treatment is cost-prohibitive, and data on abbreviated courses is lacking in advanced disease. At Moi Teaching and Referral Hospital (MTRH), one of two national referral hospitals in Kenya, HER2-positive breast cancer accounts for 20% and 95% of patients present with Stage III/IV disease. The national health insurance fund (NHIF) covers four of the recommended 18 cycles. In this study, we aimed to understand varying trastuzumab treatment plans and patient adherence.

METHODS

This is a retrospective chart review for breast cancer patients seen at the MTRH oncology clinic from January to December 2020. Immunohistochemistry results were reviewed and those with HER2+ by immunohistochemistry were included. Data was analyzed via NVivo with multivariate analysis.

RESULTS

Ninety-five patients were included with an average age of 48.7 years. 33.59% (n = 31) completed 18 cycles of trastuzumab. However, 53.3% (n = 16) of those who completed the treatment were inconsistent in treatment schedule. Nearly half, 45.26% (n = 43), received only the four cycles being covered by NHIF. More concerning, 23.15% (n = 22) did not begin trastuzumab. For MTRH patients, the cost of trastuzumab is 111,244 Kenyan Shillings (990 USD), 9 times the average monthly income per family in western Kenya.

CONCLUSION

Although trastuzumab is lifesaving, < 33% of patients with HER2-positive breast cancer complete treatment in the public sector in western Kenya. Of these patients, half experience treatment delays that may be attributable to secondary costs related to travel and absence from employment. External charity funding has improved patient access but is unsustainable. The Kenyan Ministry of Health can reduce the cost burden for patients by negotiating with pharmaceutical companies to offer subsidies or adjusting NHIF policies to promote drug access. Further studies into shorter course trastuzumab are merited.