Miracle-dz/UniFAR-FTUs huggingface dataset:
Present and Future Research on Anal Squamous Cell Carcinoma

Simple Summary This is an exciting moment in clinical research in the squamous cell carcinoma of the anus (SCCA). Historical barriers regarding this disease are vanishing thanks to the creation of research networks in this rare pathology, gained knowledge in tumor biology and its environment in this human papillomavirus (HPV)-induced disease in more than 90% of patients, and the arrival of taxane-based chemotherapy regimens as well as immunotherapies and its novel combinations. This review sheds light on the present and the future of research on SCCA, new understanding of its rational for ongoing clinical trials, with special focus in locally advanced and metastatic diseases. Abstract Squamous cell carcinoma of the anus is an orphan disease, and after more than three decades of no substantial advances in disease knowledge and treatment, it is finally gaining momentum with the arrival of a taxane-based chemotherapy and immunotherapy. Currently, about 20 combination clinical trials with an anti-PD1/L1 are ongoing in localized and advanced stages, in association with radiotherapy, chemotherapy, tumor vaccines, anti-CTLA4, anti-EGFR, or antiangiogenic molecules. Moreover, a new biomarker with high sensitivity and specificity such as HPV circulating tumor DNA (HPV ctDNA) by liquid biopsy, is improving not only the prognostic measurement but also the treatment strategy guidance for this disease. Finally, better understanding of potential targets is reshaping the present and future clinical research in this unique, HPV genotype-16-related disease in the great majority of patients.
Cardiomyocyte Proliferation as a Source of New Myocyte Development in the Adult Heart

Cardiac diseases such as myocardial infarction (MI) can lead to adverse remodeling and impaired contractility of the heart due to widespread cardiomyocyte death in the damaged area. Current therapies focus on improving heart contractility and minimizing fibrosis with modest cardiac regeneration, but MI patients can still progress to heart failure (HF). There is a dire need for clinical therapies that can replace the lost myocardium, specifically by the induction of new myocyte formation from pre-existing cardiomyocytes. Many studies have shown terminally differentiated myocytes can re-enter the cell cycle and divide through manipulations of the cardiomyocyte cell cycle, signaling pathways, endogenous genes, and environmental factors. However, these approaches result in minimal myocyte renewal or cardiomegaly due to hyperactivation of cardiomyocyte proliferation. Finding the optimal treatment that will replenish cardiomyocyte numbers without causing tumorigenesis is a major challenge in the field. Another controversy is the inability to clearly define cardiomyocyte division versus myocyte DNA synthesis due to limited methods. In this review, we discuss several studies that induced cardiomyocyte cell cycle re-entry after cardiac injury, highlight whether cardiomyocytes completed cytokinesis, and address both limitations and methodological advances made to identify new myocyte formation.
Assessing Health Consequences of Vitamin D Fortification Utilizing a Societal Experiment Design: Methodological Lessons Learned from the D-Tect Project

By utilizing historical changes in Danish legislation related to mandatory vitamin D fortification of margarine, which was implemented in the mid 1930s and abruptly abandoned in June 1985, the studies in the D-tect project investigated the effects of vitamin D on health outcomes in individuals, who during gestation were exposed or unexposed to extra vitamin D from fortified margarine. This paper reviews and narratively summarizes the analytic approaches alongside the results of the societal fortification experiment studies from the D-tect project and addresses the challenges in designing societal experiment studies and evaluating their results. The latter are discussed as lessons learned that may be useful for designers of similar studies, expected to be extensively utilized while researching the health consequences of the COVID-19 pandemic by comparing individuals born before and after the epidemic. In the D-tect project, 16 articles based on the societal fortification experiment were published analyzing 10 different outcomes and using different statistical approaches. Lessons learned included the detail of the analysis of the historical information on the exposure, availability and validity of the outcome data, variety of analytical approaches, and specifics concerning vitamin D effect evaluation, such as consideration of the influence of sunshine or season. In conclusion, the D-tect project clearly demonstrated the cost-effectiveness and research potential of natural- or societal-experiment-based studies.
Hypoxia increases melanoma-associated fibroblasts immunosuppressive potential and inhibitory effect on T cell-mediated cytotoxicity

ABSTRACT Cancer-associated fibroblasts (CAFs) and hypoxia are central players in the complex process of tumor cell-stroma interaction and are involved in the alteration of the anti-tumor immune response by impacting both cancer and immune cell populations. However, even if their independent immunomodulatory properties are now well documented, whether the interaction between these two components of the tumor microenvironment can affect CAFs ability to alter the anti-tumor immune response is still poorly defined. In this study, we provide evidence that hypoxia increases melanoma-associated fibroblasts expression and/or secretion of several immunosuppressive factors (including TGF-β, IL6, IL10, VEGF and PD-L1). Moreover, we demonstrate that hypoxic CAF secretome exerts a more profound effect on T cell-mediated cytotoxicity than its normoxic counterpart. Together, our data suggest that the crosstalk between hypoxia and CAFs is probably an important determinant in the complex immunosuppressive tumor microenvironment.
The Effect of Route Choice in Children’s Exposure to Ultrafine Particles Whilst Walking to School

Children walking to school are at a high risk of exposure to air pollution compared with other modes because of the time they spend in close proximity to traffic during their commute. The aim of this study is to investigate the effect of a walker’s route choice on their exposure to ultrafine particles (UFP) on the walk to school. During morning commutes over a period of three weeks, exposure to UFP was measured along three routes: two routes were alongside both sides of a busy arterial road with significantly higher levels of traffic on one side compared to the other, and the third route passed through quiet streets (the background route). The results indicate that the mean exposure for the pedestrian walking along the background route was half the exposure experienced on the other two routes. Walkers on the trafficked side were exposed to elevated concentrations (>100,000 pt/cc) 2.5 times longer than the low-trafficked side. However, the duration of the elevated exposure for the background route was close to zero. Public health officials and urban planners may use the results of this study to promote healthier walking routes to schools, especially those planned as part of organized commutes.
Muscle Damage Biomarkers in Congestion Weeks in English Premier League Soccer Players: A Prospective Study for Two Consecutive Seasons

The current study was conducted to compare muscle damage biomarkers in single- vs. multi-match weeks in elite soccer players for two consecutive seasons. A secondary objective was to analyze the influence of playing position and exposure time on muscle damage in single- vs. multi-match weeks. This is a prospective cohort study performed in a professional elite soccer club in the English Premier League during the 2018–2019 and 2019–2020 seasons up until the lockdown due to the COVID-19 pandemic. Data were collected in the Medical Department Room of an English Premier League Club before and after the soccer game from a total of 29 elite soccer players (mean ± S.D.; age = 27.59 ± 3.83 years; height = 1.83 ± 0.05 m; body mass = 80.16 ± 7.45 kg) who were enrolled in the club during both seasons. The main outcome measurements were creatine kinase (CK), weight, lean mass, % fat DEXA, high speed running, total distance, density of total distance and high-speed running and wellbeing questionnaires. Significance was set at p < 0.05. Players who completed more than 60 min in the previous game had significantly increased pregame CK levels and fatigue in multi-match weeks. Midfielders had both significantly increased pregame CK and muscle soreness in multi-match weeks. Midfielders and players with an exposure time of at least 60 min showed higher pregame CK values that should play a key role for deciding substitutions.
Mapping Interactions among Green Innovations Barriers in Manufacturing Industry Using Hybrid Methodology: Insights from a Developing Country

Recent years have witnessed continuous rise in adopting green innovations which is considered as an important organizational instrument to achieve profits by reducing environmental deterioration. However, green innovation in developing countries, especially in Pakistan, is surprisingly scant as compared to developed countries. This paper empirically investigated obstacles to green innovations in Pakistani manufacturing firms. Specifically, a novel three phase methodological framework was applied to investigate significant barriers and filtration by integrating Delphi method (DM), interpretive structural modeling (ISM), and cross-impact matrix multiplication applied to classification (MICMAC). Our results highlighted that lack of enforceable laws regarding returned goods and recycled products, lack of rules and regulations for green practices, and lack of collaboration with government and environmental institutions are most critical barriers. However, fear of failure about green innovation is least important barriers to green innovations adoption. This study offers interesting clues to promote green innovation in manufacturing industry.
Helicobacter pylori Infection: Comparison of Knowledge between Health Science and Non-Health Science University Students

Background: Helicobacter pylori (H. pylori), an important human pathogen, is classified as a human carcinogen. It is known to cause dyspepsia, peptic ulcers, and gastric cancer. Awareness regarding H. pylori infections in Saudi Arabia awaits investigation to reduce or even eliminate the infection that would ease the substantial burden of managing H. pylori among both malignant and non-malignant diseases. Aims: The study aims were to (1) assess the knowledge of H. pylori infection, testing, and management among undergraduate students in Saudi Arabia and (2) compare the H. pylori knowledge among health science and non-health science students. Methods: This study involved a cross-sectional online survey among 334 undergraduate students in health science and non-health science colleges at King Saud University, Saudi Arabia, using a valid and reliable author-developed survey. The survey had two sections: the socio-demographic factors and knowledge items regarding H. pylori. Data were collected during the 2019–2020 academic year. Data analysis included descriptive statistics, Chi-square, and Mann–Whitney U test. The knowledge scores were categorized as poor, fair, and good. Results: Less than 10% of the students in both groups had a good knowledge level about H. pylori. The comparison of the overall mean between both groups was non-significant. Moreover, the level of knowledge of the respondents was significantly associated with their university level (p < 0.001), family monthly income (p < 0.007), having heard about H. pylori infection (p < 000.1), and a previous history of H. pylori infection (p < 000.1). Conclusion: The overall knowledge level of Saudi undergraduate students about H. pylori infection was low. Thus, health awareness interventions through educational programs are recommended for improving their knowledge about H. pylori infection and its prevention.
Aflibercept Plus FOLFIRI as Second-Line Treatment for Metastatic Colorectal Cancer: A Single-Institution Real-Life Experience

Simple Summary The continuum of care for mCRC might include anti-angiogenic drug as anti-VEGF/VEGFR moAb and recombinant proteins in combination with fluoropyrimidine-based regimens in first- and second-line treatment, and multikinase inhibitors in refractory patients. The addition of aflibercept to FOLFIRI has been demonstrated to improve survival in patients with metastatic colorectal cancer (mCRC) who progressed after receiving a standard oxaliplatin-based regimen. In this retrospective, single-institution, observational study we collected clinical data from mCRC patients who received aflibercept in combination with FOLFIRI in routine clinical practice to describe feasibility and efficacy of this regimen in a real-world population. Aflibercept-FOLFIRI is a feasible second-line treatment for mCRC in a real-life setting, and PFS in first-line therapy >12 months resulted as the only predictive marker of better survival. Abstract The addition of aflibercept to FOLFIRI has been demonstrated to improve survival in patients with metastatic colorectal cancer (mCRC) who progressed after receiving a standard oxaliplatin-based regimen. In this retrospective, single-institution, observational study we collected clinical data from mCRC patients who received aflibercept in combination with FOLFIRI in routine clinical practice from October 2012 to March 2021 to describe feasibility and efficacy of this regimen in a real-world population. Forty-nine patients receiving aflibercept-FOLFIRI as second-line treatment were identified, 40.8% of whom were aged over 65 years. The majority of patients had multi-organ metastases (73.5%), and had previously received bevacizumab in combination with chemotherapy (CT) as first-line treatment (79.6%). Median overall survival (OS) and progression-free survival (PFS) were 13 and 6 months, respectively; overall response rate (ORR) and disease control rate (DCR) were 12.3% and 49.1%, respectively. Several factors were associated with survival in univariate analysis, including PFS in first-line therapy, number of metastatic sites, bone metastases and others. However, in multivariate analysis, only PFS in first-line CT over 12 months was significantly associated with better OS (HR 0.32; 95% CI 0.13–0.79; p = 0.01). Hypertension was the most commonly reported grade (G) 3–4 adverse event (AE), affecting 18.4% of the overall population. Thromboembolic events were observed in 16.3% of patients, hemorrhagic events in 10.2%, and proteinuria in 8.2%. Neutropenia was the most frequently observed hematological G3–4 AE with an incidence of 10.2%. Aflibercept-FOLFIRI has been confirmed as a feasible second-line treatment for mCRC in a re-al-life setting, and PFS in first-line therapy >12 months resulted as the only predictive marker of better survival.
Gender Differences in the Extended Theory of Planned Behaviour on Smoking Cessation Intention in Young Soldiers

Background: The theory of planned behaviour (TPB) explanation of smoking cessation intentions consists of gender differences. The purpose of this study is to adopt the extended TPB to discuss factors influencing the smoking cessation intentions of young adult volunteer soldiers and to further compare the respective factors for both genders. Methods: This is a cross-sectional study. Data were collected from 139 and 165 male and female volunteer soldiers who smoked, respectively. Research participants completed a self-administered questionnaire that comprised items pertaining to the participants’ demographic characteristics, smoking behaviours, smoking cessation experiences, social environments, and TPB variables. Results: Subjective norms (friends) are a positive key factor for young adult male (β = 0.033, p = 0.012) and female (β = 0.076, p < 0.001) volunteer soldiers’ smoking cessation intentions, and perceived behavioural control is a key factor for male young (β = 0.226, p = 0.040) adult volunteer soldiers’ smoking cessation intention. The extended TPB accounted for 27.9% and 53.2% of the variance in the intention to quit smoking in the male and female volunteer soldiers, respectively. Conclusions: We suggest that smoking cessation strategies can reinforce gender-specific intervention strategies to assist young adult volunteer soldiers in smoking cessation.
Factors That Shape People’s Attitudes towards the COVID-19 Pandemic in Germany—The Influence of MEDIA, Politics and Personal Characteristics

Misinformation that accompanied the current SARS-CoV-2 pandemic led to an impaired risk perception, resulting in the refusal of personal protection measures, as well as a reduced willingness to receive a vaccination. In order to identify factors that might influence people’s attitudes towards COVID-19 policies and engagement in mitigation measures, we carried out a cross-sectional study in Germany. Altogether, n = 808 participants completed our questionnaire concerning items on demographics, media consumption, risk perception, and trust in health authorities, as well as willingness to receive a vaccination. An overwhelming majority of our participants perceived SARS-CoV-2 as a health threat (85.7%), and almost two thirds (63.5%) mentioned they would get vaccinated against SARS-CoV-2 when a vaccination was available. A greater likelihood of vaccination intention was associated with being male (71.5% male vs. 60% female, p < 0.05), left-wing voting, trusting health authorities, using public media as an information source about COVID-19, and, in particular, perceiving COVID-19 as a health threat. A better understanding of factors that contribute to vaccine hesitancy is indispensable in order to eliminate doubts, increase vaccination rates, and create herd immunity, to stop further virus transmission.
Residual characteristics of etofenprox in the processing stages of rice cakes and cookies

The changes in residual amounts of an insecticide (etofenprox) in processed rice cakes and cookies were investigated in this study. Test samples were sprayed with etofenprox during rice cultivation, and brown rice samples were dipped in a pesticide solution to investigate the effects of washing and processing. A multiresidue method for multiclass pesticides was employed for etofenprox analysis using a high-performance liquid chromatography–ultraviolet detector setup. Etofenprox was not detected in polished rice that was processed into rice cakes and cookies. The etofenprox residue levels were 2.13 mg/kg in each processing stage of brown rice products that were dipped in 400 mg/kg etofenprox solutions. The residual amounts of etofenprox in washed/polished rice and rice flour obtained by grinding were 1.25 and 0.77 mg/kg, respectively. The residual levels were 0.38 mg/kg in rice cakes prepared by cooking rice flour in a steamer for 20 min (a decrease of 82.1% compared to that in polished rice), 0.47 mg/kg in rice cookies baked in an oven for 20 min (a decrease of 78.0%), and 0.21 mg/kg in fried rice cookies (a decrease of 90.2%). Overall, the residual levels of etofenprox decreased in a range of 40–100% during the processing of rice cakes and cookies.
COVID-19 Preparedness and Perceived Safety in Nursing Homes in Southern Portugal: A Cross-Sectional Survey-Based Study in the Initial Phases of the Pandemic

(1) Background: Nursing homes’ preparedness in managing a public health emergency has been poor, with effects on safety culture. The objective of this study was to assess nursing homes’ COVID-19 preparedness in southern Portugal, including staff’s work experiences during the pandemic. (2) Methods: We used a COVID-19 preparedness checklist to be completed by management teams, followed by follow-up calls to nursing homes. Thereafter, a survey of staff was applied. Data analysis included descriptive statistics, exploratory factor analysis, and thematic analysis of open-end questions. (3) Results: In total, 71% (138/195) of eligible nursing homes returned the preparedness checklist. We conducted 83 follow-up calls and received 720 replies to the staff survey. On average, 25% of nursing homes did not have an adequate decision-making structure to respond to the pandemic. Outbreak capacity and training were areas for improvement among nursing homes’ contingency plans. We identified teamwork as an area of strength for safety culture, whereas compliance with procedures and nonpunitive response to mistakes need improvement. (4) Conclusions: To strengthen how nursing homes cope with upcoming phases of the COVID-19 pandemic or future public health emergencies, nursing homes’ preparedness and safety culture should be fostered and closely monitored.
Immune Checkpoint Inhibition in Advanced Non-Clear Cell Renal Cell Carcinoma: Leveraging Success from Clear Cell Histology into New Opportunities

Simple Summary Kidney cancer has many forms, which fall under the overall term, renal cell carcinoma. Clear cell renal cell carcinoma is by far the most common type, and all other renal cell carcinomas are categorized as non-clear cell renal cell carcinoma. Patients with non-clear cell renal cell carcinomas unfortunately tend to fare worse and have fewer treatment options. We are now beginning to understand non-clear cell tumors better, including what drives these tumors to grow and spread. With this improved understanding, we can design more effective therapies. The current treatments include drugs that activate the immune system to recognize and destroy cancer cells, which is termed immunotherapy. There are many active clinical trials using immunotherapy either alone or in combination with other drugs to improve the lives of patients with non-clear cell carcinomas. Abstract Renal cell carcinoma (RCC) is a histologically heterogeneous disease with multiple subtypes. Clear cell RCC (ccRCC) represents the most common histology and has thus been easiest to study in clinical trials. Non-clear cell RCC (nccRCC) represents about 25% of RCC tumors, with fewer treatment options available, compared to ccRCC, and with poorer outcomes. Non-clear cell RCC tumors are histologically diverse, with each subtype having distinct molecular and clinical characteristics. Our understanding of nccRCC is evolving, with a gradual shift from treating nccRCC as a single entity to approaching each subtype as its own disease with unique features. Due to the scarcity of patients for study development, trials have predominantly combined all nccRCC subtypes and re-purposed drugs already approved for ccRCC, despite the decreased efficacy. We are now in the early stages of a potential paradigm shift in the treatment of nccRCC, with a rapid development of clinical studies with a focus on this subset of tumors. Investigators have launched trials focused on the molecular drivers of tumorigenesis using targeted therapies. Harboring the immunogenicity of some nccRCC subtypes, and based on promising retrospective studies, clinicians have also devised multiple trials using immune checkpoint inhibitors (ICIs), both alone or in combination with targeted therapies, for nccRCC subtypes. We highlight the promising completed and ongoing studies employing ICIs that will likely continue to improve outcomes in patients with nccRCC and propose future potential immunotherapeutic avenues.