Miracle-dz/UniFAR-FTUs huggingface dataset:
Alcohol and cigarette consumption predict mortality in patients with head and neck cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium

Abstract Background This study evaluated whether demographics, pre-diagnosis lifestyle habits and clinical data are associated with the overall survival (OS) and head and neck cancer (HNC)-specific survival in patients with HNC. Patients and methods We conducted a pooled analysis, including 4759 HNC patients from five studies within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Cox proportional hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated including terms reported significantly associated with the survival in the univariate analysis. Results Five-year OS was 51.4% for all HNC sites combined: 50.3% for oral cavity, 41.1% for oropharynx, 35.0% for hypopharynx and 63.9% for larynx. When we considered HNC-specific survival, 5-year survival rates were 57.4% for all HNC combined: 54.6% for oral cavity, 45.4% for oropharynx, 37.1% for hypopharynx and 72.3% for larynx. Older ages at diagnosis and advanced tumour staging were unfavourable predictors of OS and HNC-specific survival. In laryngeal cancer, low educational level was an unfavourable prognostic factor for OS (HR = 2.54, 95% CI 1.01–6.38, for high school or lower versus college graduate), and status and intensity of alcohol drinking were prognostic factors both of the OS (current drinkers HR = 1.73, 95% CI 1.16–2.58) and HNC-specific survival (current drinkers HR = 2.11, 95% CI 1.22–3.66). In oropharyngeal cancer, smoking status was an independent prognostic factors for OS. Smoking intensity (>20 cigarettes/day HR = 1.41, 95% CI 1.03–1.92) was also an independent prognostic factor for OS in patients with cancer of the oral cavity. Conclusions OS and HNC-specific survival differ among HNC sites. Pre-diagnosis cigarette smoking is a prognostic factor of the OS for patients with cancer of the oral cavity and oropharynx, whereas pre-diagnosis alcohol drinking is a prognostic factor of OS and HNC-specific survival for patients with cancer of the larynx. Low educational level is an unfavourable prognostic factor for OS in laryngeal cancer patients.
Risk factors for food poisoning among self-catering university students

ABSTRACT Limited research has investigated self-catering university students’ food hygiene practices that may increase their vulnerability to food poisoning. This study assessed the practice-related risk factors for food poisoning among 600 self-catering university students. A validated questionnaire was self-administered to collect data about their food hygiene practices in the previous 12 months. Factors associated with the prevalence of food poisoning were determined using logistic regression methods. Analyses showed significant associations of the use of wooden chopping boards and the consumption of unwashed fruits, with the prevalence of food poisoning (p < 0.05). However, the strongest association was for thawing of meat at room temperature (odds ratio for thawing at room temperature versus inside refrigerator, 6.07, 95% CI 3.98–9.25). Findings highlight the need for risk-based food hygiene training to inculcate safe food handling practices among self-catering university students.
Risky decision making and cognitive flexibility among online sports bettors in Nigeria

Online sports betting is a popular recreational activity in Nigeria. Like other forms of gambling, risk of pathological progression exists for gamblers who continue betting despite severe financial and psychosocial consequences. In the present study, we examined whether this population of gamblers shows deficits in decision making and cognitive flexibility that have been documented in Western gambling populations. Thirty‐six online sports bettors and 42 non‐gambling participants completed a version of the Iowa gambling task (IGT) and an established set‐shifting task for the assessment of cognitive flexibility. The two groups did not differ significantly in the selection of disadvantageous decks on the IGT. In contrast, sports bettors committed significantly more errors on the set‐shifting task than non‐gambling control participants. As this performance deficit was not specific to trials requiring a set shift, it most likely resulted from gambling‐related changes in general cognitive or motivational abilities that are required to successfully complete challenging mental tasks. While our results illustrate that findings from Western populations cannot automatically be generalised to other contexts, it should be noted that we focused on only one particular type of gambling and included mostly participants with mild gambling‐related problems.
Combining microenvironment normalization strategies to improve cancer immunotherapy

Significance Immunotherapy has changed the standard of care in cancer treatment, but an estimated 87% of patients currently do not derive long-term benefit from immune checkpoint blocker monotherapy. Therefore, new therapeutic strategies are needed to improve the response rates in patients who are resistant to immune checkpoint inhibition. We have developed a mathematical framework to determine how tumor microenvironment normalization strategies—specifically, vascular and stroma normalization—might improve immunotherapy efficacy. By incorporating complex interactions among various types of cancer cells, immune cells, stromal cells, and the vasculature, as well as physical mechanisms, we provide guidelines for designing effective combinatorial therapeutic strategies and point out areas for future investigation. Advances in immunotherapy have revolutionized the treatment of multiple cancers. Unfortunately, tumors usually have impaired blood perfusion, which limits the delivery of therapeutics and cytotoxic immune cells to tumors and also results in hypoxia—a hallmark of the abnormal tumor microenvironment (TME)—that causes immunosuppression. We proposed that normalization of TME using antiangiogenic drugs and/or mechanotherapeutics can overcome these challenges. Recently, immunotherapy with checkpoint blockers was shown to effectively induce vascular normalization in some types of cancer. Although these therapeutic approaches have been used in combination in preclinical and clinical studies, their combined effects on TME are not fully understood. To identify strategies for improved immunotherapy, we have developed a mathematical framework that incorporates complex interactions among various types of cancer cells, immune cells, stroma, angiogenic molecules, and the vasculature. Model predictions were compared with the data from five previously reported experimental studies. We found that low doses of antiangiogenic treatment improve immunotherapy when the two treatments are administered sequentially, but that high doses are less efficacious because of excessive vessel pruning and hypoxia. Stroma normalization can further increase the efficacy of immunotherapy, and the benefit is additive when combined with vascular normalization. We conclude that vessel functionality dictates the efficacy of immunotherapy, and thus increased tumor perfusion should be investigated as a predictive biomarker of response to immunotherapy.
The Roles of the NLRP3 Inflammasome in Neurodegenerative and Metabolic Diseases and in Relevant Advanced Therapeutic Interventions

Inflammasomes are intracellular multiprotein complexes in the cytoplasm that regulate inflammation activation in the innate immune system in response to pathogens and to host self-derived molecules. Recent advances greatly improved our understanding of the activation of nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasomes at the molecular level. The NLRP3 belongs to the subfamily of NLRP which activates caspase 1, thus causing the production of proinflammatory cytokines (interleukin 1β and interleukin 18) and pyroptosis. This inflammasome is involved in multiple neurodegenerative and metabolic disorders including Alzheimer’s disease, multiple sclerosis, type 2 diabetes mellitus, and gout. Therefore, therapeutic targeting to the NLRP3 inflammasome complex is a promising way to treat these diseases. Recent research advances paved the way toward drug research and development using a variety of machine learning-based and artificial intelligence-based approaches. These state-of-the-art approaches will lead to the discovery of better drugs after the training of such a system.
Ecological drivers of bacterial community assembly in synthetic phycospheres

Significance The regions surrounding living marine phytoplankton cells harbor communities of heterotrophic bacteria that play roles in carbon and energy flux in the microbial ocean and have global-scale carbon cycle implications. Yet, the drivers underlying bacterial community assembly remain unclear. In synthetic systems designed to mimic the chemistry and turnover time of natural phycospheres, bacterial community assembly could be predicted as a simple sum of assemblages supported by each individual metabolite. For host phytoplankton cells in the ocean, this implies control over bacterial associates through excreted metabolites, a condition that could favor the evolution of marine microbial interactions and influence heterotrophic carbon processing in the surface ocean. In the nutrient-rich region surrounding marine phytoplankton cells, heterotrophic bacterioplankton transform a major fraction of recently fixed carbon through the uptake and catabolism of phytoplankton metabolites. We sought to understand the rules by which marine bacterial communities assemble in these nutrient-enhanced phycospheres, specifically addressing the role of host resources in driving community coalescence. Synthetic systems with varying combinations of known exometabolites of marine phytoplankton were inoculated with seawater bacterial assemblages, and communities were transferred daily to mimic the average duration of natural phycospheres. We found that bacterial community assembly was predictable from linear combinations of the taxa maintained on each individual metabolite in the mixture, weighted for the growth each supported. Deviations from this simple additive resource model were observed but also attributed to resource-based factors via enhanced bacterial growth when host metabolites were available concurrently. The ability of photosynthetic hosts to shape bacterial associates through excreted metabolites represents a mechanism by which microbiomes with beneficial effects on host growth could be recruited. In the surface ocean, resource-based assembly of host-associated communities may underpin the evolution and maintenance of microbial interactions and determine the fate of a substantial portion of Earth’s primary production.
The complex of outer-arm dynein light chain-1 and the microtubule-binding domain of the γ heavy chain shows how axonemal dynein tunes ciliary beating

Axonemal dynein is a microtubule-based molecular motor that drives ciliary/flagellar beating in eukaryotes. In axonemal dynein, the outer-arm dynein (OAD) complex, which comprises three heavy chains (α, β, and γ), produces the main driving force for ciliary/flagellar motility. It has recently been shown that axonemal dynein light chain-1 (LC1) binds to the microtubule-binding domain (MTBD) of OADγ, leading to a decrease in its microtubule-binding affinity. However, it remains unclear how LC1 interacts with the MTBD and controls the microtubule-binding affinity of OADγ. Here, we have used X-ray crystallography and pulldown assays to examine the interaction between LC1 and the MTBD, identifying two important sites of interaction in the MTBD. Solving the LC1-MTBD complex from Chlamydomonas reinhardtii at 1.7 Å resolution, we observed that one site is located in the H5 helix and that the other is located in the flap region that is unique to some axonemal dynein MTBDs. Mutational analysis of key residues in these sites indicated that the H5 helix is the main LC1-binding site. We modeled the ternary structure of the LC1-MTBD complex bound to microtubules based on the known dynein-microtubule complex. This enabled us to propose a structural basis for both formations of the ternary LC1-MTBD-microtubule complex and LC1-mediated tuning of MTBD binding to the microtubule, suggesting a molecular model for how axonemal dynein senses the curvature of the axoneme and tunes ciliary/flagellar beating.
Beyond LDL-C levels, does remnant cholesterol estimation matter?

Clinical evidence suggests that the residual cardiovascular (CV) risk observed in patients with well-controlled low-density lipoprotein cholesterol (LDL-C) levels can be, in part, explained by residual lipid risk factors, among which the cholesterol content of remnants of triglyceride (TG)-rich lipoproteins (TRLs) appears to play a key role. 1 Observational and genetic studies have shown that remnant cholesterol (RC) is a causal risk factor for ischemic heart disease, 2 and more recently it has been associated also with an increased risk of ischemic stroke. 3 Indeed, several studies have shown that non-high-density lipoprotein cholesterol (non-HDL-C) levels, which recapitulate the cholesterol content of all atherogenic apolipopro-tein B (apoB)-containing lipoproteins including remnants, are a better predictor of CV risk than LDL-C levels alone. 4,5 In agreement with these observations, Mendelian randomization studies have suggested that the clinical beneﬁt of lowering LDL-C may be better explained by the absolute reduction in apoB-containing lipoproteins. 6,7
Caring for the Transgender Patient

The term transgender refers to persons whose gender identity is different from that recorded at birth. Similar to other marginalized populations, transgender patients commonly experience discrimination in the health care setting, and they may not have access to medical professionals who can provide competent care. In addition to primary medical and preventive health care, transgender patients need access to gender-affirming interventions, including hormone therapy and surgeries. In 2017, the Endocrine Society updated its clinical practice guideline for the care of transgender persons on the basis of the best available evidence from systematic reviews and individual studies. Among its general requirements for adolescents and recommendations for adults were the following: Involvement of a mental health professional who is knowledgeable about the diagnostic criteria for gender dysphoria and criteria for gender-affirming treatment, has training and experience in assessing psychopathology, and is willing to participate in ongoing care. Hormone therapy should be offered to transgender adult patients, with levels maintained within the normal range for gender identity and treatment appropriately monitored. Clinicians involved in the care of transgender adult patients should be knowledgeable about diagnostic criteria for gender dysphoria/gender incongruence, the use of medical and surgical gender-affirming interventions, and appropriate monitoring for reproductive organ cancer risk. Here, 2 clinicians with expertise in this area debate whether psychological evaluation is warranted in a transgender patient requesting gender-affirming hormones or surgery, the potential risks and benefits of estrogen therapy, and the role of the primary care practitioner in the care of transgender persons.
Outcomes of Peptide Vaccine GV1001 Treatment in a Murine Model of Acute Noise-Induced Hearing Loss

Noise-induced hearing loss (NIHL) is primarily caused by damage to cochlear hair cells, associated with synaptopathy. The novel cell-penetrating peptide GV1001, an antitumor agent, also has antioxidant and anti-inflammatory effects, and is otoprotective in a murine model of kanamycin-induced ototoxicity. Here, we explored whether GV1001 attenuated NIHL, and the underlying mechanism at play. We established an NIHL model by exposing 4- to 6-week-old C57/BL6 mice to white noise at 120 dB SPL for 2 h, resulting in a significant permanent threshold shift (PTS). We then subcutaneously injected saline (control), GV1001, or dexamethasone immediately after cessation of PTS-noise exposure and evaluated the threshold shifts, structural damages to outer hair cells (OHCs), and ribbon synapses. We also verified whether GV1001 attenuates oxidative stress at the level of lipid peroxidation or protein nitration in OHCs 1 h after exposure to white noise at 120 dB SPL. GV1001-treated mice exhibited significantly less hearing threshold shifts over 2 weeks and preserved OHCs and ribbon synapses compared with controls. Similarly, dexamethasone-treated mice showed comparable protection against NIHL. Importantly, GV1001 markedly attenuated oxidative stress in OHCs. Our findings suggest that GV1001 may protect against NIHL by lowering oxidative stress and may serve as preventive or adjuvant treatment.
US toddler milk sales and associations with marketing practices

Abstract Objective: Extensive marketing of ‘toddler milks’ (sugar-sweetened milk-based drinks for toddlers) promotes unsubstantiated product benefits and raises concerns about consumption by young children. The present study documents trends in US toddler milk sales and assesses relationships with brand and category marketing. Design: We report annual US toddler milk and infant formula sales and marketing from 2006 to 2015. Sales response models estimate associations between marketing (television advertising spending, product price, number of retail displays) and volume sales of toddler milks by brand and category. Setting: US Nielsen retail scanner sales and advertising spending data from 2006 to 2015. Participants: Researchers analysed all Universal Product Codes (n 117·4 million) sold by seven infant formula and eight toddler milk brands from 2006 to 2015. Results: Advertising spending on toddler milks increased fourfold during this 10-year period and volume sales increased 2·6 times. In contrast, advertising spending and volume sales of infant formulas declined. Toddler milk volume sales were positively associated with television advertising and retail displays, and negatively associated with price, at both the brand and category levels. Conclusions: Aggressive marketing of toddler milks has likely contributed to rapid sales increases in the USA. However, these sugar-sweetened drinks are not recommended for toddler consumption. Health-care providers, professional organizations and public health campaigns should provide clear guidance and educate parents to reduce toddler milk consumption and address misperceptions about their benefits. These findings also support the need to regulate marketing of toddler milks in countries that prohibit infant formula marketing to consumers.
Preclinical Imaging Using Single Track Location Shear Wave Elastography: Monitoring the Progression of Murine Pancreatic Tumor Liver Metastasis In Vivo

Recently, researchers have discovered the direct impact of the tumor mechanical environment on the growth, drug uptake and prognosis of tumors. While estimating the mechanical parameters (solid stress, fluid pressure, stiffness) can aid in the treatment planning and monitoring, most of these parameters cannot be quantified noninvasively. Shear wave elastography (SWE) has shown promise as a means of noninvasively measuring the stiffness of soft tissue. However, stiffness is still not a recognized imaging biomarker. While SWE has been shown to be capable of measuring tumor stiffness in humans, much important research is done in small animal preclinical models, where tumors are often too small for the resolution of traditional SWE tools. Single-track location SWE (STL-SWE) has previously been shown to overcome the fundamental resolution limit of SWE imposed by ultrasound speckle, which may make it suitable for preclinical imaging. Using STL-SWE, in this work, we demonstrate, for the first time, that the stiffness changes occurring inside metastatic murine pancreatic tumors can be monitored over long time scales (up to 9 weeks). To prevent the respiration motion from degrading the STL-SWE estimates, we developed a real-time software-based respiration gating scheme that we implemented on a Verasonics ultrasound imaging system. By imaging the liver of three healthy mice and performing correlation analysis, we confirmed that the respiration-gated STL-SWE data was free from motion corruption. By performing coregistered power-doppler imaging, we found that the local variability in liver shear wave speed (SWS) measurements increased from 5.4% to 9.9% due to blood flow. We performed a longitudinal study using a murine model of pancreatic cancer liver metastasis to assess the temporal changes (over nine weeks) in SWS in two groups: a controlled group receiving no treatment (n=8), and an experimental group (n=6) treated with Gemcitabine, a chemotherapy agent. We independently evaluated tumor burden using bioluminescence imaging (BLI). The initial and endpoint SWS measurements were statistically different (p<0.05). Additionally, when the liver SWS exceeded 2.5 ± 0.3 and 2.73 ± 0.34 m/s in untreated and treated mice, respectively, the death of the mice was imminent within approximately 10 days. The time taken for the SWS to exceed the thresholds was 17 days (on average) longer in Gemcitabine treated mice compared to the untreated ones. The survival statistics corroborated the effectiveness of Gemcitabine. Spearman correlation analysis revealed a monotonic relationship between SWE measurements (SWS) and BLI measurements (radiance) for tumors whose radiance exceeded $1\times 10^{7}$ photons/s/cm2/sr. Longitudinal measurements on the liver of four healthy mice revealed a maximum coefficient of variation of 11.4%. The results of this investigation demonstrate that with appropriate gating, researchers can use STL-SWE for small animal imaging and perform longitudinal studies using preclinical cancer models.
Evaluation of Sperm Mitochondrial Function: A Key Organelle for Sperm Motility

Introduction: The role of nutraceuticals in the treatment of male infertility, especially in the “idiopathic form”, remains the subject of significant debate. Many antioxidants improve sperm motility but the exact mechanism by which they act is still unclear. Although several studies have shown a correlation between sperm motility and mitochondrial function, the effects of antioxidant therapy on mitochondrial membrane potential (MMP) are poorly studied. The first aim of this review was to evaluate the efficacy of antioxidants on mitochondrial function and, consequently, on sperm motility in male infertile patients. Material and Methods: we performed a systematic search of all randomized controlled and uncontrolled studies available in the literature that reported sperm motility and MMP at baseline and after antioxidant administration in-vivo and in-vitro in patients with idiopathic asthenozoospermia. Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar and Scopus databases were used. Results: Unexpectedly, among 353 articles retrieved, only one study met our inclusion criteria and showed a significant effect of myoinositol on both MMP and sperm motility. We then summarized the main knowledge on anatomy and metabolism of sperm mitochondria, techniques allowing to assess sperm mitochondria function and its relationships with low sperm motility. Finally, we paid special attention to the effect of antioxidant/prokinetic molecules for the treatment of asthenozoospermia. Conclusions: This is the first systematic review that has attempted to evaluate the effects of antioxidants on MMP and sperm motility. Although results are not conclusive due to the dearth of studies, the close relationship between mitochondria and sperm motility is clear. The investigation of this correlation could provide valuable information to be exploited in clinical practice for the treatment of male infertility.