Miracle-dz/UniFAR-FTUs huggingface dataset:
MRI Tumor Regression Grade and Circulating Tumor DNA as Complementary Tools to Assess Response and Guide Therapy Adaptation in Rectal Cancer

Purpose: Response to preoperative chemo-radiotherapy (CRT) varies. We assessed whether circulating tumor DNA (ctDNA) might be an early indicator of tumor response or progression to guide therapy adaptation in rectal cancer. Experimental Design: A total of 243 serial plasma samples were analyzed from 47 patients with localized rectal cancer undergoing CRT. Up to three somatic variants were tracked in plasma using droplet digital PCR. RECIST and MRI tumor regression grade (mrTRG) evaluated response. Survival analyses applied Kaplan–Meier method and Cox regression. Results: ctDNA detection rates were: 74% (n = 35/47) pretreatment, 21% (n = 10/47) mid CRT, 21% (n = 10/47) after completing CRT, and 13% (n = 3/23) after surgery. ctDNA status after CRT was associated with primary tumor response by mrTRG (P = 0.03). With a median follow-up of 26.4 months, metastases-free survival was shorter in patients with detectable ctDNA after completing CRT [HR 7.1; 95% confidence interval (CI), 2.4–21.5; P < 0.001], persistently detectable ctDNA pre and mid CRT (HR 3.8; 95% CI, 1.2–11.7; P = 0.02), and pre, mid, and after CRT (HR 11.5; 95% CI, 3.3–40.4; P < 0.001) compared with patients with undetectable or nonpersistent ctDNA. In patients with detectable ctDNA, a fractional abundance threshold of ≥0.07% mid CRT or ≥0.13% after completing CRT predicted for metastases with 100% sensitivity and 83.3% specificity for mid CRT and 66.7% for CRT completion. All 3 patients with detectable ctDNA post-surgery relapsed compared with none of the 20 patients with undetectable ctDNA (P = 0.001). Conclusions: ctDNA identified patients at risk of developing metastases during the neoadjuvant period and post-surgery, and could be used to tailor treatment.
[Secondary Aerosol Formation in Urban Shanghai: Insights into the Roles of Photochemical Oxidation and Aqueous-Phase Reaction].

Secondary species are one of the most important components of PM1 particles. To investigate the contributions as well as the factors that affect the formation of the secondary aerosols, a high-resolution time-of-flight aerosol mass spectrometer (HR-TOF-AMS, AMS) was employed to characterize sub-micron particles (PM1) during spring and summer in urban Shanghai. Organics were dominant in PM1 particles and comprised around 55% of the total PM1 mass concentration, followed by sulfate (24%) and nitrate (10%). Positive matrix factorization was further applied to explore the sources of the organics. It was found that primary and secondary organic aerosols accounted for around 34% and 66% of the total organics, respectively. Three episodes were observed during the measurements, where secondary species increased substantially. Increases of secondary species were represented by increases of sulfate and LV-OOA1 in spring, especially during the noontime, thus indicating that their formation is promoted by photochemical oxidation; yet in summer, photochemical and aqueous chemistry together accelerate the formation of secondary species, as indicated by the good correlations between nitrate and aerosol liquid water as well as between SOA and Ox. Overall, we found that contributions from secondary organic and inorganic aerosols to total PM1 particles were 35.5% and 43%, respectively. This study highlights that the influence of photochemical and aqueous chemistry is significant in the promotion of secondary species formation in Shanghai.
A descriptive, historical, and thematic analysis of Acta Dermatovenerologica Alpina, Pannonica et Adriatica.

INTRODUCTION Journal bibliometric indicators are useful tools in assessing the characteristics, development history, and future trending of a particular medical journal. Moreover, they can help potential authors when deciding which journal to submit their work to in order to achieve the highest visibility. METHODS A single journal study of the medical journal Acta Dermatovenerologica Alpina, Pannonica et Adriatica (ADAPA) from January 1994 to July 2019 was performed. The corpus was harvested from the bibliographical database Scopus (Elsevier, Netherlands) for the period between 1994 and 2019 (inclusive), and the bibliometric analysis was performed using Scopus built-in services and MS Excel (Microsoft, USA). The historical, cooperation, and hot topic analysis was performed on scientific landscapes induced by VOSviewer software (Leiden University, Netherlands). RESULTS From 1994 to 2019, a total of 759 publications were published in ADAPA. The trend in the number of publications has varied; it increased somewhat until 2009, then decreased until 2015, when the number of articles began to rise again, reaching a peak in 2018 (46 articles annually). A small decline in source normalized impact per paper (SNIP) was observed from 1.2 in 2010 to 0.46 in 2018. Slovenia ranked first (n = 210) in the number of publications among 55 countries. Authors from 44 out of 55 countries published their articles through co-authorships. CONCLUSIONS Whereas it was initially considered a primarily regional journal, ADAPA's influence has gradually broadened and the journal has become truly international. The number of articles published increased significantly during the last few years, with ADAPA strongly supporting international collaboration, resulting in a high proportion of international co-authorships.
How youth cognitive and sociodemographic factors relate to the development of overweight and obesity in the UK and the USA: a prospective cross-cohort study of the National Child Development Study and National Longitudinal Study of Youth 1979

Objectives We investigated how youth cognitive and sociodemographic factors are associated with the aetiology of overweight and obesity. We examined both onset (who is at early risk for overweight and obesity) and development (who gains weight and when). Design Prospective cohort study. Setting We used data from the US National Longitudinal Study of Youth 1979 (NLSY) and the UK National Child Development Study (NCDS); most of both studies completed a cognitive function test in youth. Participants 12 686 and 18 558 members of the NLSY and NCDS, respectively, with data on validated measures of youth cognitive function, youth socioeconomic disadvantage (eg, parental occupational class and time spent in school) and educational attainment. Height, weight and income data were available from across adulthood, from individuals’ 20s into their 50s. Primary and secondary outcome measures Body mass index (BMI) for four time points in adulthood. We modelled gain in BMI using latent growth curve models to capture linear and quadratic components of change in BMI over time. Results Across cohorts, higher cognitive function was associated with lower overall BMI. In the UK, 1 SD higher score in cognitive function was associated with lower BMI (β=−0.20, 95% CI −0.33 to −0.06 kg/m²). In America, this was true only for women (β=−0.53, 95% CI −0.90 to −0.15 kg/m²), for whom higher cognitive function was associated with lower BMI. In British participants only, we found limited evidence for negative and positive associations, respectively, between education (β=−0.15, 95% CI −0.26 to −0.04 kg/m²) and socioeconomic disadvantage (β=0.33, 95% CI 0.23 to 0.43 kg/m²) and higher BMI. Overall, no cognitive or socioeconomic factors in youth were associated with longitudinal changes in BMI. Conclusions While sociodemographic and particularly cognitive factors can explain some patterns in individuals’ overall weight levels, differences in who gains weight in adulthood could not be explained by any of these factors.
A meta-analysis

Background: Several studies have explored the associations between interleukin-6 (IL-6) gene polymorphisms and the susceptibility to liver diseases, however, results remain ambiguous. The goal of this study was to conduct a meta-analysis to provide more credible evidence. Methods:Studies identified in the PubMed, Cochrane Library, and EMBASE databases were used to perform a meta-analysis via the STATA software. Pooled odds ratios (OR) were calculated under fixedand random-effects models to estimate the potential genetic associations. Results: Twenty-five case-control studies involving 5813 cases and 5298 controls were included in this meta-analysis. Overall, the pooled results suggested that rs1800795 polymorphism was significantly associated with the risk of liver diseases in heterozygote (GC vs CC; OR=1.57) and dominant (GG+GC vs CC: OR=1.47) models; rs1800796 polymorphism was significantly associated with the susceptibility to liver diseases in heterozygote (GG vs GC; OR=0.58) and recessive (GG vs GC+CC: OR=0.68) models; rs1800797 polymorphism was significantly associated with genetic predisposition to liver diseases in homozygote (GG vs AA: OR= 1.63), heterozygote (GA vs AA; OR=1.53) and dominant (GG + GA vs AA: OR=1.61) models. A similar conclusion was found in the HBV, HCV, HCC, NASH and alcoholic liver disease of all ethnic populations for rs1800795; HBV and Asian subgroups for rs1800796; HCV and non-Asian subgroups for rs1800797. However, IL-6 rs2069837 and rs2066992 polymorphisms did not exhibit significant associations with the risk of liver diseases under any genetic models. Conclusion: This meta-analysis suggests that patients carrying G (rs1800795), C (rs1800796) or G (rs1800797) allele or genotypes of IL-6 may be more likely to suffer from liver diseases, which was ethnic-dependent. Abbreviations: CI= confidence interval, HBV= hepatitis B virus, HC= healthy, HCC= hepatocellular carcinoma, HCV= hepatitis C virus, HIV = human immunodeficiency virus-type 1, IF = infection resolved, IL-6 = interleukin-6, LC = liver cirrhosis, NASH = nonalcoholic steatohepatitis, NOS = New-castle–Ottawa Scale, OR = odds ratio, PRISMA = Preferred Reporting Items for Systematic Review and Meta-analysis, SNP = single nucleotide polymorphism, STAT3 = signal transducer and activator of transcription 3.
Changes in cellular processes occurring in mucopolysaccharidoses as underestimated pathomechanisms of these diseases

Mucopolysaccharidoses (MPS) are a group of genetic disorders belonging to lysosomal storage diseases. They are caused by genetic defects leading to a lack or severe deficiency of activity of one of lysosomal hydrolases involved in degradation of glycosaminoglycans (GAGs). Partially degraded GAGs accumulate in lysosomes, which results in dysfunctions of cells, tissues, and organs. Until recently, it was assumed that GAG accumulation in cells is the major, if not the only, mechanism of pathogenesis in MPS, as GAGs may be a physical ballast for lysosomes causing inefficiency of cells due to a large amount of a stored material. However, recent reports suggest that in MPS cells there are changes in many different processes, which might be even more important for pathogenesis than lysosomal accumulation of GAGs per se. Moreover, there are many recently published results indicating that lysosomes not only are responsible for degradation of various macromolecules, but also play crucial roles in the regulation of cellular metabolism. Therefore, it appears plausible that previous failures in treatment of MPS (i.e., possibility to correct only some symptoms and slowing down of the disease rather than fully effective management of MPS) might be caused by underestimation of changes in cellular processes and concentration solely on decreasing GAG levels in cells.
Psychological well-being and happiness among Middle-aged women: A cross-sectional study

Abstract Biological, physical, and psychosocial changes that occur during the aging process can negatively impact women's mental health and happiness at midlife. In this cross-sectional study, we aimed to determine the level of psychological well-being and happiness among middle-aged women in Tabriz. Data were collected from December 2017 to February 2018 by face-to-face interviews, using structured questionnaires of happiness and psychological well-being. The participants were 40-60-year-old middle-aged women (n = 300) selected by clustered random sampling allocation. A total of 167 (55.7%) out of all the women had decreased levels of psychological well-being. Psychological well-being was found to be significantly lower among the women with low levels of happiness (B: 24.43, CI (18.57 to 30.29), p < 0.001). Health care centers should implement more comprehensive mental health promotion programs for middle-aged women, including free of charge recreational opportunities (e.g., walking, swimming, dancing) to improve psychological health and well-being.
A “vision” for fast snaring: please take your time

cers result from either missed or incompletely resected lesions during previous examinations. Additionally, a very small proportion may be attributed to de novo cancers. In this context, a number of different techniques, technologies, and devices have so far been studied with the aim of improving colonoscopy outcomes, with varying results [1]. Among these, the Endocuff device (Arc Medical Design, Leeds, UK) and its descendant the Endocuff vision device (EVD; Norgine Pharmaceuticals Ltd, Uxbridge, UK) – devices mounted on the tip of the scope with flexible projections that aim to flatten the mucosal folds and facilitate inspection – have been extensively studied. Two studies have shown that compared with standard colonoscopy, Endocuff use is associated with a lower adenoma miss rate [2], and the most recent meta-analysis revealed a significant, albeit small, benefit in terms of the adenoma detection rate (ADR) with Endocuff-assisted colonoscopy; this benefit was restricted to endoscopists with an ADR lower than 35% [3]. “. given the faster insertion and polypectomy times owing to the hypothesized ease of snare positioning, one would expect to see higher levels of endoscopist satisfaction in the EVD arm, but this was not detected. ”
Syphilis among adult males with a history of male-to-male sexual contact living with diagnosed HIV in New York State (excluding New York City): The challenge of intersecting epidemics

Since 2009, syphilis has been increasing in New York State (NYS) excluding New York City (NYC) among men with a history of male-to-male sexual contact (MSM). Because MSM make up a disproportionate number of new HIV infections, this study aims to: 1) establish yearly rates of early syphilis diagnosis, 2) assess factors associated with early syphilis diagnosis, and 3) describe missed opportunities for earlier diagnosis of syphilis among MSM living with diagnosed HIV(MSMLWDH) in NYS, excluding NYC. A cohort of adult MSMLWDH alive in 2013 were followed through 2016 to identify individuals with at least one early syphilis diagnosis between July 2014 and December 2016. Early syphilis diagnosis rates were calculated for 2015 and 2016. Crude relative risks and 95% confidence intervals were calculated to determine associations between available covariates and both syphilis diagnosis and missed opportunities. Missed opportunities were defined as reports of an HIV-related laboratory test within a given window corresponding to syphilis staging where syphilis testing was not performed at the same time. Of 7,512 MSMLWDH, 50.0% were non-Hispanic white, 85.4% aged ≥35, and 320(4.3%) had an early syphilis diagnosis. Yearly rates were: 1,838/100,000, and 1,681/100,000 in 2015 and 2016, respectively. Persons who were non-Hispanic black, living with diagnosed HIV for less than three years, aged <45, and were always virally suppressed or always in HIV care were significantly more likely to have a syphilis diagnosis. Over half of individuals had evidence of a missed opportunity for earlier syphilis diagnosis. Syphilis stage at diagnosis, older age, and syphilis diagnosis not concurrent with an HIV-related laboratory test were associated with a higher likelihood of having a missed opportunity. This study supports high interrelatedness of the syphilis and HIV epidemics among MSM. Since syphilis can impact HIV viral load suppression status, efforts to end the HIV epidemic need to be coupled with syphilis elimination efforts.
Population pharmacokinetic modelling of busulfan and the influence of body composition in paediatric Fanconi anaemia patients

Fanconi anaemia (FA) is a rare disorder characterized by progressive bone marrow failure that requires haematopoietic cell transplantation (HCT). Busulfan is used in conditioning regimens prior to HCT. Doses used in non‐FA patients cause life‐threatening toxicities in FA patients and data on busulfan pharmacokinetics (PK) in this population are limited. This study characterized busulfan PK in paediatric FA patients using population PK modelling and evaluated the effect of body composition on steady‐state concentrations (Css).
Prognostic Awareness, Disease and Palliative Understanding Among Caregivers of Patients With Dementia

Background: Persons with dementia (PwD) often have significant cognitive deficits and functional limitations, requiring substantial caregiver assistance. Given the high symptom burden and terminal nature of dementia, good prognostic awareness and integration of palliative care (PC) is needed. Objective: To evaluate prognostic awareness, disease, and PC understanding among caregivers of PwD and to assess for improvements in routine care. Design: A cross-sectional study of 2 cohorts at a single-academic medical center. Surveys were mailed to 200 caregivers of PwD in 2012 (cohort 1). Surveys were sent to new subset of caregivers of PwD (n = 80) in 2018 (cohort 2) to assess trends over time. Results: A total of 154 of caregivers completed the survey (response rate 55%). Compared to 2012, a higher proportion of caregivers in 2018 reported having conversations about prognosis with PwD’s physicians (25% in 2012 vs 45% in 2018; P = .027). However, a large percentage (43% in 2012 and 40% in 2018) of caregivers reported no understanding of the PwD’s prognosis. Despite most stating dementia was not curable, only 39% in 2012 and 52% in 2018 (P = .015) understood that dementia was a terminal disease. In addition, only 32% in 2012 and 40% in 2018 (P = .39) felt that they were knowledgeable about PC. Conclusions: Prognostic discussions between caregivers of PwD and the PwD’s physicians may be occurring more often; however, a high percentage of caregivers report a poor understanding about the terminal nature of dementia and the role of PC.
Trial of Anifrolumab in Active Systemic Lupus Erythematosus.

BACKGROUND Anifrolumab, a human monoclonal antibody to type I interferon receptor subunit 1 investigated for the treatment of systemic lupus erythematosus (SLE), did not have a significant effect on the primary end point in a previous phase 3 trial. The current phase 3 trial used a secondary end point from that trial as the primary end point. METHODS We randomly assigned patients in a 1:1 ratio to receive intravenous anifrolumab (300 mg) or placebo every 4 weeks for 48 weeks. The primary end point of this trial was a response at week 52 defined with the use of the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA). A BICLA response requires reduction in any moderate-to-severe baseline disease activity and no worsening in any of nine organ systems in the BILAG index, no worsening on the Systemic Lupus Erythematosus Disease Activity Index, no increase of 0.3 points or more in the score on the Physician Global Assessment of disease activity (on a scale from 0 [no disease activity] to 3 [severe disease]), no discontinuation of the trial intervention, and no use of medications restricted by the protocol. Secondary end points included a BICLA response in patients with a high interferon gene signature at baseline; reductions in the glucocorticoid dose, in the severity of skin disease, and in counts of swollen and tender joints; and the annualized flare rate. RESULTS A total of 362 patients received the randomized intervention: 180 received anifrolumab and 182 received placebo. The percentage of patients who had a BICLA response was 47.8% in the anifrolumab group and 31.5% in the placebo group (difference, 16.3 percentage points; 95% confidence interval, 6.3 to 26.3; P = 0.001). Among patients with a high interferon gene signature, the percentage with a response was 48.0% in the anifrolumab group and 30.7% in the placebo group; among patients with a low interferon gene signature, the percentage was 46.7% and 35.5%, respectively. Secondary end points with respect to the glucocorticoid dose and the severity of skin disease, but not counts of swollen and tender joints and the annualized flare rate, also showed a significant benefit with anifrolumab. Herpes zoster and bronchitis occurred in 7.2% and 12.2% of the patients, respectively, who received anifrolumab. There was one death from pneumonia in the anifrolumab group. CONCLUSIONS Monthly administration of anifrolumab resulted in a higher percentage of patients with a response (as defined by a composite end point) at week 52 than did placebo, in contrast to the findings of a similar phase 3 trial involving patients with SLE that had a different primary end point. The frequency of herpes zoster was higher with anifrolumab than with placebo. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT02446899.).
Molecular Basis of the Mechanisms Controlling MASTL*

MASTL is a unique kinase because of a non-conserved insertion of 550 residues within its activation loop. Using different constructs of MASTL, we show that the NCMR is essential for target discrimination and the regulation of kinase activity. We also show that truncations of MASTL containing a cryptic C-lobe in the NCMR are active and can be found in cancer cell lines containing mutations in one of the MASTL alleles, suggesting an intriguing role for these short forms of the kinase in cancer. Graphical Abstract Highlights NCMR is crucial for substrate recognition and activity regulation. MASTL conserves a cryptic C-Lobe in the non-conserved middle region. MASTL450 containing the cryptic C-lobe is observed in cancer cell lines. Key phosphorylation sites for MASTL provide an activation model. The human MASTL (Microtubule-associated serine/threonine kinase-like) gene encodes an essential protein in the cell cycle. MASTL is a key factor preventing early dephosphorylation of M-phase targets of Cdk1/CycB. Little is known about the mechanism of MASTL activation and regulation. MASTL contains a non-conserved insertion of 550 residues within its activation loop, splitting the kinase domain, and making it unique. Here, we show that this non-conserved middle region (NCMR) of the protein is crucial for target specificity and activity. We performed a phosphoproteomic assay with different MASTL constructs identifying key phosphorylation sites for its activation and determining whether they arise from autophosphorylation or exogenous kinases, thus generating an activation model. Hydrogen/deuterium exchange data complements this analysis revealing that the C-lobe in full-length MASTL forms a stable structure, whereas the N-lobe is dynamic and the NCMR and C-tail contain few localized regions with higher-order structure. Our results indicate that truncated versions of MASTL conserving a cryptic C-Lobe in the NCMR, display catalytic activity and different targets, thus establishing a possible link with truncated mutations observed in cancer-related databases.