Miracle-dz/UniFAR-FTUs huggingface dataset:
An Orally Active Galectin-3 Antagonist Inhibits Lung Adenocarcinoma Growth and Augments Response to PD-L1 Blockade.

A combination therapy approach is required to improve tumor immune infiltration and patient response to immune checkpoint inhibitors that target negative regulatory receptors. Galectin-3 is a β-galactoside-binding lectin that is highly expressed within the tumor microenvironment of aggressive cancers and whose expression correlates with poor survival particularly in patients with non-small cell lung cancer (NSCLC). To examine the role of galectin-3 inhibition in NSCLC, we tested the effects of galectin-3 depletion using genetic and pharmacologic approaches on syngeneic mouse lung adenocarcinoma and human lung adenocarcinoma xenografts. Galectin-3-/- mice developed significantly smaller and fewer tumors and metastases than syngeneic C57/Bl6 wild-type mice. Macrophage ablation retarded tumor growth, whereas reconstitution with galectin-3-positive bone marrow restored tumor growth in galectin-3-/- mice, indicating that macrophages were a major driver of the antitumor response. Oral administration of a novel small molecule galectin-3 inhibitor GB1107 reduced human and mouse lung adenocarcinoma growth and blocked metastasis in the syngeneic model. Treatment with GB1107 increased tumor M1 macrophage polarization and CD8+ T-cell infiltration. Moreover, GB1107 potentiated the effects of a PD-L1 immune checkpoint inhibitor to increase expression of cytotoxic (IFNγ, granzyme B, perforin-1, Fas ligand) and apoptotic (cleaved caspase-3) effector molecules. In summary, galectin-3 is an important regulator of lung adenocarcinoma progression. The novel galectin-3 inhibitor presented could provide an effective, nontoxic monotherapy or be used in combination with immune checkpoint inhibitors to boost immune infiltration and responses in lung adenocarcinoma and potentially other aggressive cancers. SIGNIFICANCE: A novel and orally active galectin-3 antagonist inhibits lung adenocarcinoma growth and metastasis and augments response to PD-L1 blockade.Graphical Abstract: http://cancerres.aacrjournals. org/content/canres/79/7/1480/F1.large. jpg.
Ribosomal DNA polymorphisms reveal genetic structure and a phylogeographic pattern in the Burgundy truffle Tuber aestivum Vittad.

ABSTRACT Ectomycorrhizal ascomycetes belonging to the genus Tuber produce edible fruiting bodies known as truffles. Tuber aestivum, in particular, is a fungus appreciated worldwide and has a natural distribution throughout Europe. Most of the molecular studies conducted on this species have been focused on the question as to whether or not T. aestivum and the morphologically similar T. uncinatum are conspecific. Conversely, only a handful of studies have assessed the level and distribution of genetic diversity and occurrence of phylogeographic patterns in this species. Here, we analyzed the genetic diversity of T. aestivum over a wide geographic range, performing an extensive sampling of specimens from Turkey, which is novel, to the best of our knowledge. We compared the internal transcribed spacer (ITS) profiles of 45 samples collected in different Turkish areas with those of 144 samples from all over Europe. We identified 63 haplotypes, 32 of which were exclusively present in Turkey. The majority of these haplotyes were also population specific. Haplotype network analysis and statistical tests highlighted the presence of a genetic structure and phylogeographic pattern, with three spatially distinct genetic clusters (northeastern Europe, southern Europe, and Turkey), with Turkey representing a diversity hotspot. Based on these results, we hypothesize the presence of glacial refugia for T. aestivum in Turkey, whereas European populations likely experienced a population bottleneck. The possible occurrence of cryptic species among Turkish T. aestivum samples also emerged. Our results are of practical relevance for the marketing of T. aestivum truffles and mycorrhizal seedlings and the preservation of the biodiversity of this species.
Transjugular Liver Biopsy Versus Percutaneous Liver Biopsy With Tract Embolization in Children With Coagulopathy.

T o the Editor: The article by Tulin-Silver et al made an interesting read where they showed that percutaneous liver biopsy (PLB) with tract embolization could be done in several children with coagulopathy and/or ascites with acceptable complication rates. The authors compared the cohort undergoing PLB with another nonmatched cohort undergoing transjugular liver biopsy (TJLB) and recommended PLB with gelatin tract embolization as procedure of choice in children with coagulopathy (1). There are a few important concerns about the interpretation of the results. First of all, the 2 groups are unmatched with TJLB patients having significantly higher coagulopathy and thrombocytopenia than patients undergoing PLB with tract embolization. In fact, only 11 out of 120 children undergoing PLB had coagulopathy (international normalized ratio [INR] >1.5) and ideally only this cohort should have been compared head-to-head with the TJLB cohort. Secondly, although, in this study, children undergoing TJLB were significantly more coagulopathic and thrombocytopenic; yet, there was no bleeding complication in TJLB group, whereas there were 3 bleeding events requiring blood transfusion in the PLB group. Similarly, in a previously well designed and randomized adult study, bleeding complications were only seen in subjects undergoing PLB and in none undergoing TJLB (2). An important finding was that adequate tissue could be obtained in all but 1 patient undergoing TJLB in this study (1), whereas previous experiences have been to the contrary (3,4). The third issue is that there is no comparison on severity of ascites between the 2 groups as ascites severity often influences the choice between PLB and TJLB as obvious from the adult study (2). Hence, it would not be wise to recommend PLB as procedure of choice in coagulopathy on the basis of a nonrandomized study with a small sample size (n1⁄4 11). We are surprised to learn that PLB was attempted in children with INR as high as 4.7 when the current European Society for Paediatric Gastroenterology Hepatology and Nutrition recommendations advises against it at INR >1.5 (5). PLB with tract embolization may have a role in children with borderline derangement of INR, but robust data need to be generated before it could be advocated in severely coagulopathic patients. Another important finding in this study is that bleeding could not be predicted with current coagulation tests like INR and platelet count (1). In fact, all patients with bleeding had INR <1.7 and platelet count >80,000/mm. Thromboelastogram, although not readily available, may be a good tool to predict bleeding in this setting (3). To conclude, TJLB should be advocated as a feasible and safe method for liver biopsy in coagulopathic children till we have conclusive evidence in form of well designed and randomized trials. PLB with tract embolization may be considered if facility for TJLB is lacking.
Giving Meaning to Alzheimer’s Disease: An Experimental Study Using a Framing Approach

ABSTRACT The prejudices and stereotypes associated with Alzheimer’s disease (AD) are based on contents that highlight the most negative and dramatic aspects of the symptoms of this disease. This is reinforced by the preponderance of negative representations related to AD. In this paper, these representations have been analyzed as frames. The most dominant frame used to represent dementia is “body-mind dualism,” and its alternative is the “body-mind unity” counter-frame. This study aims to define the impact of different messages inspired by the Dualism frame and the Unity counter-frame in the collective representation and meaning given to AD. Posters of simulated health campaigns about AD were designed, combining contents related to the Dualism frame and the Unity counter-frame, and were shown to 85 participants. To analyze the impact of both types of frameworks, a pre-post record of the attitudes of the participants toward AD was conducted using the Attitudes toward Dementia Scale. The assessment of the campaign and the self-report emotions were also registered. Participants’ eye movements were measured during exposure to the posters. Attitudes toward dementia were found to be significantly more positive following exposure to discourses characteristic of the Unity counter-frame. Likewise, the dualism discourse evoked more sadness and anger. Moreover, the posters that used the discourse of the Unity counter-frame were considered more useful. We concluded that attitudes toward dementia are influenced by framing. Designing suitable health campaigns using these frames could help mitigate the attitudes and stigma associated with AD.
The HIV care continuum among resident and non‐resident populations found in venues in East Africa cross‐border areas

HIV care and treatment in cross‐border areas in East Africa face challenges perhaps not seen to the same extent in other geographic areas, particularly for mobile and migrant populations. Here, we estimate the proportion of people with HIV found in these cross‐border areas in each stage of the HIV care and treatment cascade, including the proportion who knows their status, the proportion on treatment and the proportion virally suppressed.
Mitochondrial dysfunction in Alzheimer's disease: Role in pathogenesis and novel therapeutic opportunities

Dysfunction of cell bioenergetics is a common feature of neurodegenerative diseases, the most common of which is Alzheimer's disease (AD). Disrupted energy utilization implicates mitochondria at its nexus. This review summarizes some of the evidence that points to faulty mitochondrial function in AD and highlights past and current therapeutic development efforts. Classical neuropathological hallmarks of disease (β‐amyloid and τ) and sporadic AD risk genes (APOE) may trigger mitochondrial disturbance, yet mitochondrial dysfunction may incite pathology. Preclinical and clinical efforts have overwhelmingly centred on the amyloid pathway, but clinical trials have yet to reveal clear‐cut benefits. AD therapies aimed at mitochondrial dysfunction are few and concentrate on reversing oxidative stress and cell death pathways. Novel research efforts aimed at boosting mitochondrial and bioenergetic function offer an alternative treatment strategy. Enhancing cell bioenergetics in preclinical models may yield widespread favourable effects that could benefit persons with AD.
Reformulating the Worker Identity: Men’s Experiences After Radical Prostatectomy

The number of men in the Canadian workforce who have prostate cancer is increasing. The purpose of the study was to explore the processes involved in men’s return to work post radical prostatectomy and understand how these events are connected to masculinities. Drawing on data collected through individual interviews with 24 participants, constructivist grounded theory method was used to develop the substantive theory of Reformulating the Worker Identity which comprises two processes, recovering after radical prostatectomy and renegotiating work expectations. Recovering after radical prostatectomy revealed how men overcame side effects at home and evaluated their potential for returning to work. Renegotiating work expectations included participant’s strategies for securing graduated return to work accommodations. Study findings revealed that the challenges for fully returning to work post prostatectomy are often underestimated by clinicians and patients. In this context, preempting return to work challenges preoperatively might allay significant anxieties for many men.
The Rationality of Illusory Correlation

When presented with 2 samples (a smaller sample from a Minority population and a larger sample from a Majority population), where some rare or frequent features occur at exactly the same rate in both samples, people reliably associate the rare feature with the Minority population and the frequent feature with the Majority population. This pattern is referred to as “illusory correlation,” reflecting the standard assumption that such associations are fundamentally irrational. In this article we show that this assumption is incorrect, and demonstrate that this pattern of association linking rare features with the Minority and frequent features with the Majority (given a sample where those features occurred at the same proportion in both categories, and no further information) is in fact correct and follows a result in epistemic probability theory known as the “Rule of Succession. ” Building on this result, we present a new computational model of frequency-based illusory correlation, based on the Rule of Succession. We also discuss the implications of the Rule of Succession for our understanding of various other cognitive biases.
The Relation of Psychosocial Distress With Myocardial Perfusion and Stress-Induced Myocardial Ischemia

Objective Mental stress–induced myocardial ischemia is a frequent phenomenon in patients with coronary artery disease (CAD). The link between an integrated measure of chronic psychosocial distress and mental stress–induced myocardial ischemia, and whether it differs by sex, has not been examined before. Methods We used latent class analysis to derive a composite measure of psychosocial distress integrating scales of depression, posttraumatic stress, anxiety, anger, hostility, and perceived stress in 665 individuals with stable CAD. Participants underwent myocardial perfusion imaging with mental stress and perfusion defects were quantified at rest (summed rest score), with mental stress (summed stress score), and their difference (summed difference score), the latter being an index of inducible ischemia. Results The M (SD) age was 63 (9) years, and 185 (28%) were women. Latent class analysis characterized the study sample into four distinct classes of incremental psychosocial distress. In women, class 4 (highest distress) had an adjusted 4.0-point higher summed rest score (95% confidence interval = 0.2–7.7) as compared with class 1 (lowest distress), whereas no difference was observed in men (−0.87 points, 95% confidence interval = −3.74 to 1.99, p = .04 for interaction). There was no association between the psychosocial distress latent variable and summed difference score in either women or men. Conclusions Among patients with CAD, a higher level of psychosocial distress is not associated with mental stress ischemia, but it is associated with more resting (fixed) perfusion abnormalities in women only, as well as with blunted hemodynamic response to mental stress in both men and women.
Six‐year‐old male with a chief complaint of telangiectasias

A 6‐year‐old male with autism and immune thrombocytopenic purpura presented with a chief complaint of telangiectasia, accompanied by his mother. One lesion on his right eyelid was present since birth. Another lesion on his left anterior shin had grown larger and darker over the last 4 months. He also had a 1‐month history of “pinpoint red spots” along the vermilion border of the upper lip. There was no history of epistaxis, other abnormal bleeding, ataxia, or other neurologic symptoms. Physical examination was notable for pinpoint telangiectasias along the upper vermilion border and a telangiectatic mat on the right upper eyelid (Figure 1). Thumbprint‐like macular capillary malformations were scattered on the left forearm and bilateral anterior thighs, all with a surrounding rim of pallor but no background hyperpigmentation on dermoscopy; a similar, larger lesion was noted on the posterior thigh (Figure 2). A large capillary patch with a subcutaneous nontender nodule and no palpable thrill was observed on the left anterior shin. No hypertrophy was noted in the upper or lower extremities. In addition to capillary malformations with surrounding rim of pallor, small splotchy hypopigmented macules consistent with Bier's spots were present on bilateral upper and lower extremities (Figure 3). MRI angiogram of the left anterior shin showed no deep vascular malformations. MRI of the brain and spine showed no definite vascular abnormality or enhancement in the cervical or thoracic cord.
Addressing HPV vaccine myths: practical information for healthcare providers

ABSTRACT Human papillomavirus (HPV) vaccine uptake consistently lags behind that of other adolescent vaccines. In 2017, uptake of a single HPV vaccine dose and HPV vaccine series completion was 66% and 49%, respectively, compared to uptake of tetanus, diphtheria, and acellular pertussis vaccine (89%) and quadrivalent meningococcal conjugate vaccine (85%). Reasons for not vaccinating adolescents again HPV are varied, and in many cases, are rooted in commonly spread myths and misperceptions about the vaccine. In this review, we address five key myths – HPV vaccination is not effective at preventing cancer; Pap smears are sufficient to prevent cervical cancer; HPV vaccination is not safe; HPV vaccination is not needed since most infections are naturally cleared by the immune system; 11–12 years of age is too young to vaccinate. For each myth, we summarize the scientific evidence refuting the myth and provide speaking prompts for healthcare professionals to communicate about HPV vaccination.
Socio-economic status and behavioural and cardiovascular risk factors in Papua New Guinea: A cross-sectional survey

Background Risk factors for cardiovascular disease (CVD) are negatively correlated with socio-economic status (SES) in high-income countries (HIC) but there has been little research on their distribution by household SES within low-and middle-income countries (LMICs). Considering the limited data from LMICs, this paper examines the association between behavioural and cardiovascular risk factors and household SES in Papua New Guinea (PNG). Methods Reported here are results of 671 participants from the 900 randomly selected adults aged 15–65 years. These adults were recruited from three socioeconomically and geographically diverse surveillance sites (peri-urban community, rural Highland and an Island community) in PNG in 2013–2014. We measured their CVD risk factors (behavioural and metabolic) using a modified WHO STEPS risk factor survey and analysis of blood samples. We assessed SES by education, occupation and creating a household wealth index based on household assets. We calculated risk ratios (RR) and their 95% confidence intervals (CI) using a generalized linear model to assess the associations between risks and SES. Findings Elevated CVD risk factors were common in all SES groups but the CVD metabolic risk factors were most prevalent among homemakers, peri-urban and rural highlands, and the highest (4th and 5th) wealth quintile population. Adults in the highest wealth quintile had high risks of obesity, elevated HbA1c and metabolic syndrome (MetS) that were greater than those in the lowest quintile although those in the highest wealth quintiles were less likely to smoke tobacco. Compared to people from the Island community, peri-urban residents had increased risks of increased waist circumference (WC) (RR: 1.67, 95%CI: 1.21–2.31), hypertension (RR: 2∙29, 95%CI: 1∙89–4.56), high cholesterol (RR: 2∙22, 95%CI: 1∙20–4∙10), high triglycerides (RR: 1∙49, 95%CI: 1∙17–1∙91), elevated HbA1c (RR: 5∙54, 95%CI: 1∙36–21∙56), and Metabolic syndrome (MetS) (RR: 2∙04, 95%CI: 1∙25–3∙32). Similarly, Rural Highland residents had increased risk of obesity (Waist Circumference RR: 1∙70, 95%CI: 1∙21–3∙38, Waist-Hip-Ratio RR:1∙48, 95%CI: 1∙28–1∙70), hypertension (RR: 2∙60, 95%CI: 1∙71–3∙95), high triglycerides (RR: 1∙34, 95%CI: 1∙06–1∙70) and MetS (RR: 1∙88, 95%CI: 1∙12–3∙16) compared to those in the rural Island site. Interpretation CVD risk factors are common in PNG adults but their association with SES varies markedly and by location. Our findings show that all community members are at risk of CVD weather they are part of high or low SES groups. These results support the notion that the association between CVD risk factors and SES differ greatly accordingly to the type of SES measure used, risk factors and the population studied. In addition, our findings contribute further to the limited literature in LMIC. Longitudinal studies are needed to monitor changes in rapidly changing societies such as PNG to inform public health policy for control and prevention of NCDs in the country.
Prevalence and Incidence of Rheumatoid Arthritis in Canadian First Nations and Non–First Nations People

In this population-based study, the occurrence of rheumatoid arthritis (RA, incidence, prevalence, age of onset) was examined in the entire population of Manitoba, Canada, which was then divided into First Nations (FN, indigenous to Canada) and non-FN. FN had a higher prevalence and incidence of RA and were younger at disease onset than the non-FN. In addition FN patients had fewer rheumatology visits which probably adds to the burden this disease represents for them. Supplemental digital content is available in the text. Background The aim of this study was to determine the prevalence, incidence, and onset age at rheumatoid arthritis (RA) diagnosis in First Nations (FN) and non-FN populations in Manitoba, Canada. Methods Population-based administrative health records from April 1, 1995, to March 31, 2010, were accessed for all Manitobans. The FN population was identified using the Federal Indian Registry File. Crude and adjusted RA prevalence and incidence rates (adjusted for age, sex, health region of residence) were compared using Poisson regression and reported as relative rates (RRs) with 95% confidence intervals (CIs). Mean (CI) diagnosis age and physician visits were compared with Student t tests. Results Rheumatoid arthritis crude prevalence increased between 2000 and 2010 to 0.65%; adjusted RA prevalence in females was 1.0% and in males was 0.53%. The 2009/2010 adjusted RA prevalence was higher in FN than non-FN (RR, 2.55; CI, 2.08–3.12) particularly for ages 29 to 48 years (RR, 4.52; CI, 2.71–7.56). Between 2000 and 2010, crude RA incidence decreased from 46.7/100,000 to 13.4/100,000. Adjusted RA incidence remained higher in FN than non-FN (2000–2010 RR, 2.1; CI, 1.7–2.6; p < 0.0001) particularly for ages 29 to 48 years (RR, 4.6; CI, 2.8–7.4; p < 0.0001). The FN population was younger at diagnosis than the non-FN population (mean age, 39.6 years [CI, 38.3–40.8 years] vs. 53.3 years [CI, 52.7–53.9 years]; p < 0.0001). The FN population had more physician visits but fewer rheumatology visits than the non-FN population. Conclusions Rheumatoid arthritis prevalence is increasing, and RA incidence is decreasing in Manitoba. The FN population has a greater prevalence and incidence of RA and is younger at diagnosis than the non-FN population. When combined with fewer rheumatology visits, this significant care gap highlights the need to optimize rheumatology care delivery to the FN population.