Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical information and management status of de novo stage IV breast cancer patients: a Chinese multicenter investigation (CSBrS-002)

Supplemental Digital Content is available in the text Abstract Background: Although de novo stage IV breast cancer is so far incurable, it has entered an era of individualized treatment and chronic disease management. Based on systemic treatment, whether the surgical resection of primary or metastatic foci of de novo stage IV breast cancer can bring survival benefits is currently controversial. We aimed to explore the clinicopathological factors and current status of the management of de novo stage IV breast cancer in China to provide a reference for clinical decisions. Methods: Based on the assistance of Chinese Society of Breast Surgery, a retrospective study was conducted to analyze the clinical data of patients with de novo stage IV breast cancer in 33 centers from January 2017 to December 2018. The relationship between basic characteristic (age, menstrual status, family history, reproductive history, pathological type, estrogen receptor [ER] status, progesterone receptor [PR] status, human epidermal growth factor receptor 2 [HER2] status, Ki-67 percentage, and molecular subtype), and metastasis sites (lung metastasis, liver metastasis, and bone metastasis) was examined by Pearson Chi-square tests. Results: A total of 468 patients with de novo stage IV breast cancer were enrolled. The median age of the enrolled patients was 51.5 years. The most common pathological type of primary lesion was invasive carcinoma (97.1%). Luminal A, luminal B, HER2 overexpressing, and triple-negative subtypes accounted for 14.3%, 51.8%, 22.1%, and 11.8% of all cases, respectively. Age, PR status, and HER2 status were correlated with lung metastasis (χ2 = 6.576, 4.117, and 8.643 and P = 0.037, 0.043, and 0.003, respectively). Pathological type, ER status, PR status, and molecular subtype were correlated with bone metastasis (χ2 = 5.117, 37.511, 5.224, and 11.603 and P = 0.024, <0.001, 0.022, and 0.009, respectively). Age, PR status, HER2 status, Ki-67 percentage, and molecular subtype were correlated with liver metastasis (χ2 = 11.153, 13.378, 10.692, 21.206, and 17.684 and P = 0.004, <0.001, 0.001, <0.001, and 0.001, respectively). Combined treatment with paclitaxel and anthracycline was the most common first-line chemotherapy regimen for patients with de novo stage IV breast cancer (51.7%). Overall, 91.5% of patients used paclitaxel-containing regimens. Moreover, 59.3% of hormone receptor-positive patients underwent endocrine therapy. Conclusions: In 2018, 1.07% of patients from all studied centers were diagnosed with de novo stage IV breast cancer. This study indicated that 95.1% of patients received systemic therapy and 54.2% of patients underwent surgical removal of the primary lesion in China.
Three-component access to 2-pyrrolin-5-ones and their use in target-oriented and diversity-oriented synthesis

The Hantzsch-type microwave-assisted, solvent-free sequential three-component reaction between primary amines, β-dicarbonyl compounds and α-bromoesters in the presence of indium trichloride afforded 2-pyrrolin-5-ones, which are difficult to access by alternative methods. Ready access to these compounds allowed their use as synthetic building blocks in a target-oriented project aimed at the synthesis of a compound that had previously been postulated as a candidate for HIV integrase inhibition on the basis of computational studies. The versatility of 2-pyrrolin-5-ones was further verified by their use in a diversity-oriented synthesis context, leading to a library of highly functionalized bispiro compounds. The overall process leading to these compounds involved the generation of six bonds and two cycles over three steps, two of which are multicomponent, and the fully controlled generation of up to four stereocenters, including two quaternary ones.
Perspectives of older adults with chronic disease on the use of wearable technology and video games for physical activity

Background There is increasing interest in technology to deliver physical rehabilitation and allow clinicians to monitor progress. Examples include wearable activity trackers and active video games (AVGs), where physical activity is required to play the game. However, few studies have explored what may influence the effectiveness of these as technology-based physical activity interventions in older adults with chronic diseases. Objective This study aimed to explore: 1) perceptions about wearable physical activity trackers; 2) perceptions about using technology to share physical activity information with clinicians; 3) barriers and motivators to playing games, including AVGs for rehabilitation. Methods Qualitative study based on semi-structured interviews with older adults (n = 19) with chronic obstructive pulmonary disease (COPD). Results Wearable activity trackers were perceived as useful to quantify activity, facilitate goal-setting, visualize long-term improvements and provide reminders. Participants generally wished to share data with their clinicians to gain greater accountability, receive useful feedback and improve the quality of clinical care. Participants were motivated to play games (including AVGs) by seeking fun, social interaction and health benefits. Some felt that AVGs were of no benefit or were too difficult. Competition was both a motivator and a barrier. Conclusions The findings of the present study seek to inform the design of technology to encourage physical activity in older adults with chronic diseases.
Neosartorya hiratsukae: Environmental isolation from intensive care units in an Italian hospital

To the Editor — Fungi are opportunistic pathogens, ubiquitously distributed. Fungal colonization acquired from the environment might evolve into an invasive infection during hospitalization due to immunosuppressive treatments to which patients are exposed. Environmental surveillance in hospital settings requires special attention to prevent fungal and non-fungal infections. the hiratsukae, of the section Fumigati, is a rare for the first time in from air and from pasteurized aloe
Environmental drivers of sexual dimorphism in a lizard with alternative mating strategies

Understanding the relative importance of sexual and natural selection in shaping morphological traits is a long‐standing goal of evolutionary ecology. Male‐biased sexual size dimorphism (SSD) is typically associated with male–male competition. Similarly, male polymorphisms are considered a consequence of competitive social interactions. This classic paradigm overlooks the fact that environmental factors mediate social interactions and can lead to ecological adaptations. Common side‐blotched lizards, Uta stansburiana, are a model system for this paradigm due to well‐known rock‐paper‐scissors social dynamics between male morphs. SSD in this species has been considered primarily a consequence of social interactions, with male size resulting from the number of morphs in each population and female size being constrained through fecundity benefits. We test if the environment explains intraspecific variation in SSD and number of male morphs in U. stansburiana. By compiling data from 49 populations, we show that environmental variables are stronger predictors of SSD than the number of male morphs. Similarly, we show that the environment mediates SSD and potentially contributes to morph loss in colder environments. We propose that the environment favours smaller males in areas of high seasonality. Our results demonstrate the importance of the environment as a mediator of SSD.
FTO (Fat-Mass and Obesity-Associated Protein) Participates in Hemorrhage-Induced Thalamic Pain by Stabilizing Toll-Like Receptor 4 Expression in Thalamic Neurons

Supplemental Digital Content is available in the text. Background and Purpose: Hemorrhage-caused gene changes in the thalamus likely contribute to thalamic pain genesis. RNA N6-methyladenosine modification is an additional layer of gene regulation. Whether FTO (fat-mass and obesity-associated protein), an N6-methyladenosine demethylase, participates in hemorrhage-induced thalamic pain is unknown. Methods: Expression of Fto mRNA and protein was assessed in mouse thalamus after hemorrhage caused by microinjection of Coll IV (type IV collagenase) into unilateral thalamus. Effect of intraperitoneal administration of meclofenamic acid (a FTO inhibitor) or microinjection of adeno-associated virus 5 (AAV5) expressing Cre into the thalamus of Ftofl/fl mice on the Coll IV microinjection–induced TLR4 (Toll-like receptor 4) upregulation and nociceptive hypersensitivity was examined. Effect of thalamic microinjection of AAV5 expressing Fto (AAV5-Fto) on basal thalamic TLR4 expression and nociceptive thresholds was also analyzed. Additionally, level of N6-methyladenosine in Tlr4 mRNA and its binding to FTO or YTHDF2 (YTH N6-methyladenosine RNA binding protein 2) were observed. Results: FTO was detected in neuronal nuclei of thalamus. Level of FTO protein, but not mRNA, was time-dependently increased in the ipsilateral thalamus on days 1 to 14 after Coll IV microinjection. Intraperitoneal injection of meclofenamic acid or adeno-associated virus-5 expressing Cre microinjection into Ftofl/fl mouse thalamus attenuated the Coll IV microinjection–induced TLR4 upregulation and tissue damage in the ipsilateral thalamus and development and maintenance of nociceptive hypersensitivities on the contralateral side. Thalamic microinjection of AAV5-Fto increased TLR4 expression and elicited hypersensitivities to mechanical, heat and cold stimuli. Mechanistically, Coll IV microinjection produced an increase in FTO binding to Tlr4 mRNA, an FTO-dependent loss of N6-methyladenosine sites in Tlr4 mRNA and a reduction in the binding of YTHDF2 to Tlr4 mRNA in the ipsilateral thalamus. Conclusions: Our findings suggest that FTO participates in hemorrhage-induced thalamic pain by stabilizing TLR4 upregulation in thalamic neurons. FTO may be a potential target for the treatment of this disorder.
Low educational level increases functional disability risk subsequent to heart failure in Japan: On behalf of the Iwate KENCO study group

Objectives The risk factors that contribute to future functional disability after heart failure (HF) are poorly understood. The aim of this study was to determine potential risk factors to future functional disability after HF in the general older adult population in Japan. Methods The subjects who were community-dwelling older adults aged 65 or older without a history of cardiovascular diseases and functional disability were followed in this prospective study for 11 years. Two case groups were determined from the 4,644 subjects: no long-term care insurance (LTCI) after HF (n = 52) and LTCI after HF (n = 44). We selected the controls by randomly matching each case of HF with three of the remaining 4,548 subjects who were event-free during the period: those with no LTCI and no HF with age +/-1 years and of the same sex, control for the no LTCI after HF group (n = 156), and control for the LTCI after HF group (n = 132). HF was diagnosed according to the Framingham diagnostic criteria. Individuals with a functional disability were those who had been newly certified by the LTCI during the observation period. Objective data including blood samples and several socioeconomic items in the baseline survey were assessed using a self-reported questionnaire. Results Significantly associated risk factors were lower educational levels (odds ratio (OR) [95% confidence interval (CI)]: 3.72 [1.63–8.48]) in the LTCI after HF group and hypertension (2.20 [1.10–4.43]) in no LTCI after HF group. Regular alcohol consumption and unmarried status were marginally significantly associated with LTCI after HF (OR [95% CI]; drinker = 2.69 [0.95–7.66]; P = 0.063; unmarried status = 2.54 [0.91–7.15]; P = 0.076). Conclusion Preventive measures must be taken to protect older adults with unfavorable social factors from disability after HF via a multidisciplinary approach.
Why do some patients with stage 1A and 1B endometrial endometrioid carcinoma experience recurrence? A retrospective study in search of prognostic factors.

OBJECTIVES Endometrial endometrioid carcinoma (EEC) is the most encountered subtype of endometrial cancer (EC). Our study aimed to investigate the factors affecting recurrence in patients with stage 1A and 1B EEC. MATERIAL AND METHODS Our study included 284 patients diagnosed with the International Federation of Gynecology and Obstetrics stage 1A/1B EEC in our center from 2010 to 2018. The clinicopathological characteristics of the patients were obtained retrospectively from their electronic files. RESULTS The median age of the patients was 60 years (range 31-89). The median follow-up time of the patients was 63.6 months (range 3.3-185.6). Twenty-two (7.74%) patients relapsed during follow-up. Among the relapsed patients, 59.1% were at stage 1A ECC, and 40.9% were at stage 1B. In our study, the one-, three-, and five-year recurrence-free survival (RFS) rates were 98.9%, 95.4%, and 92.9%, respectively. In the multivariate analysis, grade and tumor size were found to be independent parameters of RFS in all stage 1 EEC patients. Furthermore, the Ki-67 index was found to affect RFS in stage 1A EEC patients, and tumor grade affected RFS in stage 1B EEC patients. In the time-dependent receiver operating characteristic curve analysis, the statistically significant cut-off values were determined for tumor size and Ki-67 index in stage 1 EEC patients. CONCLUSIONS Stage 1-EEC patients in the higher risk group in terms of tumor size, Ki-67, and grade should be closely monitored for recurrence. Defining the prognostic factors for recurrence in stage 1 EEC patients may lead to changes in follow-up algorithms.
Let’s Talk About Each Other: Neural Responses to Dissenting Personality Evaluations Based on Real Dyadic Interactions

Dyadic interactions are associated with the exchange of personality-related messages, which can be congruent or incongruent with one’s self-view. In the current preregistered study (N = 52), we investigated event-related potentials (ERPs) toward real social evaluations in order to uncover the neural mechanisms underlying the processing of congruent and incongruent evaluative feedback. Participants interacted first, and then during an electroencephalogram (EEG) session, they received evaluations from their interaction partner that were either congruent or incongruent with their own ratings. Findings show potentiated processing of self-related incongruent negative evaluations at early time points (N1) followed by increased processing of both incongruent negative and positive evaluations at midlatency time windows (early posterior negativity) and a prioritized processing of self-related incongruent positive evaluations at late time points (feedback-related P3, late positive potential). These findings reveal that, after real social interactions, evaluative feedback about oneself that violates one’s self-view modulates all processing stages with an early negativity and a late positivity bias.
Immunoadjunctive Therapy against Bacterial Infections Using Herbal Medicines Based on Th17 Cell-mediated Protective Immunity.

One of the major health concerns in the world is the global increase in intractable bacterial infectious diseases due to the emergence of multi- and extensively drug-resistant bacterial pathogens as well as an increase in compromised hosts around the world. Particularly, in the case of mycobacteriosis, the high incidence of tuberculosis in developing countries, resurgence of tuberculosis in industrialized countries, and increase in the prevalence of Mycobacterium avium complex infections are important worldwide health concerns. However, the development of novel antimycobacterial drugs is currently making slow progress. Therefore, it is considered that devising improved administration protocols for clinical treatment against refractory mycobacteriosis using existing chemotherapeutics is more practical than awaiting the development of new antimycobacterial drugs. The regulation of host immune responses using immunoadjunctive agents may increase the efficacy of antimicrobial treatment against mycobacteriosis. The same situations also exist in cases of intractable infectious diseases due to common bacteria other than mycobacteria. The mild and long-term up-regulation of host immune reactions in hosts with intractable chronic bacterial infections, using herbal medicines and medicinal plants, may be beneficial for such immunoadjunctive therapy. This review describes the current status regarding basic and clinical studies on therapeutic regimens using herbal medicines, useful for the clinical treatment of patients with intractable bacterial infections. In particular, we focus on immunoadjunctive effects of herbal medicines on the establishment and manifestation of host antibacterial immunity related to the immunological roles of Th17 cell lineages.
Cortical processing of speaker politeness: Tracking the dynamic effects of voice tone and politeness markers

ABSTRACT Information in the tone of voice alters social impressions and underlying brain activity as listeners evaluate the interpersonal relevance of utterances. Here, we presented requests that expressed politeness distinctions through the voice (polite/rude) and explicit linguistic markers (half of the requests began with Please). Thirty participants performed a social perception task (rating friendliness) while their electroencephalogram was recorded. Behaviorally, vocal politeness strategies had a much stronger influence on the perceived friendliness than the linguistic marker. Event-related potentials revealed rapid effects of (im)polite voices on cortical activity prior to ~300 ms; P200 amplitudes increased for polite versus rude voices, suggesting that the speaker’s polite stance was registered as more salient in our task. At later stages, politeness distinctions encoded by the speaker’s voice and their use of Please interacted, modulating activity in the N400 (300–500 ms) and late positivity (600–800 ms) time windows. Patterns of results suggest that initial attention deployment to politeness cues is rapidly influenced by the motivational significance of a speaker’s voice. At later stages, processes for integrating vocal and lexical information resulted in increased cognitive effort to reevaluate utterances with ambiguous/contradictory cues. The potential influence of social anxiety on the P200 effect is also discussed.
Food insecurity partially mediates the association between drug use and depressive symptoms among men who have sex with men in Los Angeles, California

Abstract Objective: To understand the relationship between drug use, food insecurity (FI) and mental health among men who have sex with men (MSM). Design: Cohort study (2014–2019) with at least one follow-up. Setting: Visits at 6-month intervals included self-assessment for FI and depressive symptoms. Urine testing results confirmed drug use. Factors associated with FI were assessed using multiple logistic regression with random effects for repeated measures. General structural equation modelling tested whether FI mediates the relationship between drug use and depressive symptoms. Participants: Data were from HIV-positive and high-risk HIV-negative MSM in Los Angeles, CA (n 431; 1192 visits). Results: At baseline, FI was reported by 50·8 % of participants, depressive symptoms in 36·7 % and 52·7 % of urine screening tests were positive for drugs (i.e. marijuana, opioids, methamphetamine, cocaine and ecstasy). A positive drug test was associated with a 96 % increase in the odds of being food insecure (95 % CI 1·26, 3·07). Compared to those with high food security, individuals with very low food security have a nearly sevenfold increase in the odds of reporting depressive symptoms (95 % CI 3·71, 11·92). Findings showed 14·9 % of the association between drug use (exposure) and depressive symptoms (outcome) can be explained by FI (mediator). Conclusion: The prevalence of FI among this cohort of HIV-positive and high-risk HIV-negative MSM was high; the association between drug use and depressive symptoms was partially mediated by FI. Findings suggest that enhancing access to food and nutrition may improve mood in the context of drug use, especially among MSM at risk for HIV transmission.
Long-Term Changes in Post-Stroke Depression, Emotional Incontinence, and Anger

Background and Purpose Long-term changes in post-stroke depression (PSD), post-stroke emotional incontinence (PSEI), and post-stroke anger (PSA) have rarely been studied. Methods This is a sub-study of EMOTION, a randomized, placebo-controlled trial, that examined the efficacy of escitalopram on PSD, PSEI, and PSA in patients with stroke. We interviewed patients at the long-term period (LTP) using predefined questionnaires: Montgomery-Åsberg depression rating scale (MADRS) for PSD, modified Kim’s criteria for PSEI, and Spielberger trait anger scale for PSA. Additionally, the ENRICHD Social Support Instrument (ESSI) for the social support state and the modified Rankin Scale (mRS) were measured. We investigated the changes in and factors behind PSD, PSEI, and PSA at LTP. Results A total of 222 patients were included, and the median follow-up duration was 59.5 months (interquartile range, 50 to 70). Compared to the data at 6 months post-stroke, the prevalence of PSEI (11.7% at 6 months, 6.3% at LTP; P=0.05) and mean anger score (21.62, 16.24; P<0.01) decreased, while the prevalence of PSD (35.6%, 44.6%; P=0.03) and mean MADRS (6.16, 8.67; P<0.01) increased at LTP. ESSI was associated with PSD and PSA, but not with PSEI. The effect of the baseline National Institutes of Health Stroke Scale score on PSD decreased over time. The effect of low social support on PSD was greater than that of mRS at LTP. Conclusions The prevalence and degree of PSD significantly increased, while those of PSEI and PSA decreased at LTP. PSD in this stage appeared to be more closely associated with a lack of social support than patients' physical disabilities.
Adjuvant Aromatase Inhibitors or Tamoxifen Following Chemotherapy for Perimenopausal Breast Cancer Patients

Abstract Background The benefit of adjuvant aromatase inhibitors (AI) vs tamoxifen has been investigated in randomized clinical trials for premenopausal and postmenopausal patients with early, estrogen receptor–positive (ER+) breast cancer. The optimal endocrine treatment for chemotherapy-treated perimenopausal women, who generally develop chemotherapy-induced amenorrhea, is uncertain. Methods All Dutch women who received adjuvant chemotherapy and endocrine treatment for stage I-III, ER+ (>10% positive cells), invasive breast cancer diagnosed between 2004 and 2007 were identified through the Netherlands Cancer Registry. Included women were considered perimenopausal based on an age at diagnosis of 45 to 50 years (n = 2295). For each patient, AI treatment duration relative to total endocrine treatment duration was calculated. Predominantly tamoxifen-treated patients (AI < 25%) were compared with those receiving AI and tamoxifen for a similar duration (AI 25%-75%) and those mostly using AI (AI > 75%). Adjusted hazard ratios (HRs) for recurrence-free survival (RFS) and overall survival were calculated using time-dependent Cox regression. Results After an average follow-up of 7.6 years, 377 RFS events occurred. Women mostly receiving AI (AI > 75%) had the best RFS (adjusted HR = 0.63, 95% confidence interval = 0.46 to 0.86) followed by those receiving AI 25% to 75% (adjusted HR = 0.85, 95% confidence interval = 0.65 to 1.12) compared with predominantly tamoxifen-treated women. Trend analyses showed that every 10% increase in AI-endocrine treatment ratio reduced RFS event risk by 5% (2-sided Ptrend = .002). In total, 236 deaths occurred; hazard ratios for overall survival showed similar trends. Conclusions These results suggest that the best adjuvant endocrine treatment for chemotherapy-treated, ER+ breast cancer patients diagnosed aged 45-50 years consists of mainly AI followed by a switch strategy and mainly tamoxifen.