Miracle-dz/UniFAR-FTUs huggingface dataset:
New insights into Early Celtic consumption practices: Organic residue analyses of local and imported pottery from Vix-Mont Lassois

The rich Mediterranean imports found in Early Celtic princely sites (7th-5th cent. BC) in Southwestern Germany, Switzerland and Eastern France have long been the focus of archaeological and public interest. Consumption practices, particularly in the context of feasting, played a major role in Early Celtic life and imported ceramic vessels have consequently been interpreted as an attempt by the elite to imitate Mediterranean wine feasting. Here we present the first scientific study carried out to elucidate the use of Mediterranean imports in Early Celtic Central Europe and their local ceramic counterparts through organic residue analyses of 99 vessels from Vix-Mont Lassois, a key Early Celtic site. In the Mediterranean imports we identified imported plant oils and grape wine, and evidence points towards appropriation of these foreign vessels. Both Greek and local wares served for drinking grape wine and other plant-based fermented beverage(s). A wide variety of animal and plant by-products (e.g. fats, oils, waxes, resin) were also identified. Using an integrative approach, we show the importance of beehive products, millet and bacteriohopanoid beverage(s) in Early Celtic drinking practices. We highlight activities related to biomaterial transformation and show intra-site and status-related differences in consumption practices and/or beverage processing.
Exercise training intensity determination in cardiovascular rehabilitation: Should the guidelines be reconsidered?

Aims In the rehabilitation of cardiovascular disease patients a correct determination of the endurance-type exercise intensity is important to generate health benefits and preserve medical safety. It remains to be assessed whether the guideline-based exercise intensity domains are internally consistent and agree with physiological responses to exercise in cardiovascular disease patients. Methods A total of 272 cardiovascular disease patients without pacemaker executed a maximal cardiopulmonary exercise test on bike (peak respiratory gas exchange ratio >1.09), to assess peak heart rate (HRpeak), oxygen uptake (VO2peak) and cycling power output (Wpeak). The first and second ventilatory threshold (VT1 and VT2, respectively) was determined and extrapolated to %VO2peak, %HRpeak, %heart rate reserve (%HRR) and %Wpeak for comparison with guideline-based exercise intensity domains. Results VT1 was noted at 62 ± 10% VO2peak, 75 ± 10% HRpeak, 42 ± 14% HRR and 47 ± 11% Wpeak, corresponding to the high intensity exercise domain (for %VO2peak and %HRpeak) or low intensity exercise domain (for %Wpeak and %HRR). VT2 was noted at 84 ± 9% VO2peak, 88 ± 8% HRpeak, 74 ± 15% HRR and 76 ± 11% Wpeak, corresponding to the high intensity exercise domain (for %HRR and %Wpeak) or very hard exercise domain (for %HRpeak and %VO2peak). At best (when using %Wpeak) in only 63% and 72% of all patients VT1 and VT2, respectively, corresponded to the same guideline-based exercise intensity domain, but this dropped to about 48% and 52% at worst (when using %HRR and %HRpeak, respectively). In particular, the patient’s VO2peak related to differently elicited guideline-based exercise intensity domains (P < 0.05). Conclusion The guideline-based exercise intensity domains for cardiovascular disease patients seem inconsistent, thus reiterating the need for adjustment.
Betel Nut (areca) and Smokeless Tobacco Use in Myanmar

Abstract Background: Betel nut (areca) is the world’s fourth most commonly used addictive substance. Arecoline, a muscarinic agonist in areca, is also a partial agonist for the addiction-related high-affinity brain nicotine receptors. In many countries, smokeless tobacco is commonly mixed with areca. Objective: We sought to evaluate the knowledge of self-harm, and addiction associated betel quid use in an unban population. Methods: We conducted a survey study of 200 betel quid users in Yangon, Myanmar, and a survey of betel quid vendors to determine the relative amounts of areca and tobacco in the available quids. Results: The data determined that a large majority of the survey subjects (84%) used tobacco with their areca. Users had a general awareness that betel chewing was “a bad habit” (85%) and 80% were aware of the cancer risks. Understanding areca addiction remains a challenge since, aside from the strong muscarinic activity of arecoline stimulating salivation, overt neurologic effects are difficult for even the users to identify. Fifty eight percent of the respondents indicated that chewing betel quid had effects like drinking coffee, and 55.5% indicated that it had effects like drinking alcohol. Data obtained from the quid vendors indicated that 75% added tobacco in equal amounts to areca. Conclusion: The concomitant use of nicotine and areca indicates that betel quid addiction includes a significant component of nicotine dependence. However, the additional activities of areca, including the muscarinic effects of arecoline, indicate that potential cessation therapies should optimally address other factors as well.
A novel histone H4 variant H4G regulates rDNA transcription in breast cancer

Abstract Histone variants, present in various cell types and tissues, are known to exhibit different functions. For example, histone H3.3 and H2A.Z are both involved in gene expression regulation, whereas H2A.X is a specific variant that responds to DNA double-strand breaks. In this study, we characterized H4G, a novel hominidae-specific histone H4 variant. We found that H4G is expressed in a variety of human cell lines and exhibit tumor-stage dependent overexpression in tissues from breast cancer patients. We found that H4G localized primarily to the nucleoli of the cell nucleus. This localization was controlled by the interaction of the alpha-helix 3 of the histone fold motif with a histone chaperone, nucleophosmin 1. In addition, we found that modulating H4G expression affects rRNA expression levels, protein synthesis rates and cell-cycle progression. Our data suggest that H4G expression alters nucleolar chromatin in a way that enhances rDNA transcription in breast cancer tissues.
A Post hoc analysis on rhythm and high intensity interval training in cardiac resynchronization therapy

Abstract Objectives. Evaluate the effects of a 6-month High Intensity Interval Training (HIIT) program on (1) functional capacity and health-related quality of life, (2) multiple blood biomarkers, (3) echocardiographic parameters, and (4) exercise performance, in patients in cardiac resynchronization therapy (CRT) stratified by the presence of atrial fibrillation (AF), targeting the following questions: (1) Does CRT provide similar benefits in patients in AF and sinus rhythm (SR)? ; and (2) Does HIIT provides similar benefits in patients in AF and SR? Design. Estimates were available at baseline and 6 months after CRT implantation in 37 patients with heart failure. Patients were randomized after CRT to a 24-week HIIT group or to a usual care group (CON). In this sub-analysis, HIIT (AF = 7; SR = 11) and CON (AF = 9; SR = 10) were stratified by the presence of AF. Results. Patients in AF benefitted to a lesser degree from CRT in functional status than patients in SR (23.8–46.0%). However, HIIT induced superior improvements in patients in AF compared to CON (23.9–61.0%). Decreases in TNF-α (8.5–42.9%), BNP (15.3–34.6%) and left ventricular mass (9.6–26.2%) were only observed in patients in SR, whereas increases in peak oxygen uptake were only observed in patients in AF (19.5–23.2%). HIIT improved exercise capacity (8.8–59.4%) in patients in SR. Conclusions. Patients in AF or SR undergoing CRT demonstrated distinct benefits from device implantation and from HIIT as an adjunctive therapeutic strategy. This suggests that both mainstay and adjunctive therapeutics may need to be managed differently in patients in AF and SR.
Postoperative opioid‐prescribing practices in otolaryngology: A multiphasic study

In otolaryngology, postoperative pain management lacks evidence‐based guidelines. We designed a prospective, multiphasic study aimed to develop evidence‐based guidelines for postoperative pain management within our institution. In this first phase of our project, we investigated opioid prescription and consumption as well as pain trends for common otolaryngologic procedures.
Molecular and phenotypic spectrum of Noonan syndrome in Chinese patients

Noonan syndrome (NS) is a common autosomal dominant/recessive disorder. No large‐scale study has been conducted on NS in China, which is the most populous country in the world. Next‐generation sequencing (NGS) was used to identify pathogenic variants in patients that exhibited NS‐related phenotypes. We assessed the facial features and clinical manifestations of patients with pathogenic or likely pathogenic variants in the RAS‐MAPK signaling pathway. Gene‐related Chinese NS facial features were described using artificial intelligence (AI). NGS identified pathogenic variants in 103 Chinese patients in eight NS‐related genes: PTPN11 (48.5%), SOS1 (12.6%), SHOC2 (11.7%), KRAS (9.71%), RAF1 (7.77%), RIT1 (6.8%), CBL (0.97%), NRAS (0.97%), and LZTR1 (0.97%). Gene‐related facial representations showed that each gene was associated with different facial details. Eight novel pathogenic variants were detected and clinical features because of specific genetic variants were reported, including hearing loss, cancer risk due to a PTPN11 pathogenic variant, and ubiquitous abnormal intracranial structure due to SHOC2 pathogenic variants. NGS facilitates the diagnosis of NS, especially for patients with mild/moderate and atypical symptoms. Our study describes the genotypic and phenotypic spectra of NS in China, providing new insights into distinctive clinical features due to specific pathogenic variants.
Time Spent in Sedentary Activity Is Related to Gross Motor Ability During the Second Year of Life

Sedentary activity occupies a substantial amount of time during early childhood, with these habits influenced by changing trends in screen time for very young children. Among school-aged children, motor ability is inversely related to sedentary activity. However, the concept of sedentary activity is rarely investigated in toddlers, and thus little is known concerning its relationship with motor development during this rapidly changing and early period of life. Among two groups of toddlers, aged 18 months (N = 26) and aged 24 months (N = 16), this study investigated cross-sectional correlations of motor development (Bayley Scales of Infant Development—III) with daily sedentary activity (accelerometers). In both groups, gross motor ability, but not fine motor ability, was inversely correlated with time spent in sedentary activity. At 18 months, gross motor raw scores inversely correlated significantly with time in sedentary activity (r = −.533, p < .001) but fine motor raw scores did not (r = .182, p = .441). Also, at 24 months, gross motor raw scores inversely correlated with time in sedentary activity (r = −.563, p = .029), while fine motor raw scores did not (r = −.112, p = .425). These findings add important missing knowledge to the empirical literature regarding sedentary activity in toddlers and its relationship to emerging motor development. Future work might investigate best practices for measuring sedentary activity in this age-group and mechanisms behind its relationship with gross motor skills.
What Causes the Onset of Psychosis in Individuals at Clinical High Risk? A Meta-analysis of Risk and Protective Factors

Abstract Twenty percent of individuals at clinical high risk for psychosis (CHR-P) develop the disorder within 2 years. Extensive research has explored the factors that differentiate those who develop psychosis and those who do not, but the results are conflicting. The current systematic review and meta-analysis comprehensively addresses the consistency and magnitude of evidence for non-purely genetic risk and protective factors associated with the risk of developing psychosis in CHR-P individuals. Random effects meta-analyses, standardized mean difference (SMD) and odds ratio (OR) were used, in combination with an established stratification of evidence that assesses the association of each factor and the onset of psychotic disorders (from class I, convincing evidence to class IV weak evidence), while controlling for several types of biases. A total of 128 original controlled studies relating to 26 factors were retrieved. No factors showed class I-convincing evidence. Two further factors were associated with class II-highly suggestive evidence: attenuated positive psychotic symptoms (SMD = 0.348, 95% CI: 0.280, 0.415) and global functioning (SMD = −0.291, 95% CI: −0.370, −0.211). There was class III-suggestive evidence for negative psychotic symptoms (SMD = 0.393, 95% CI: 0.317, 0.469). There was either class IV-weak or no evidence for all other factors. Our findings suggest that despite the large number of putative risk factors investigated in the literature, only attenuated positive psychotic symptoms, global functioning, and negative psychotic symptoms show suggestive evidence or greater for association with transition to psychosis. The current findings may inform the refinement of clinical prediction models and precision medicine in this field.
Ethnic Disparities in EPA and DHA Intake in US Adults: Results from the NHANES 2011-2014 (P04-107-19).

Objectives Recent studies suggest a large percentage of US adults are not meeting recommended dietary intakes for omega-3 polyunsaturated fatty acids (n-3 PUFA), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Meanwhile, the Institute of Medicine has yet to establish Dietary Reference Intakes for either EPA or DHA and some US populations may be particularly vulnerable. Therefore, we investigated dietary consumption and main food sources of EPA and DHA across racial and ethnic group potentially at-risk. We hypothesized differences in mean dietary intakes of EPA and DHA (P < 0.05) may exist across targeted groups due to differences in ethnocentric dietary patterns. Methods For these investigations, data from the NHANES 2011-2014 was analyzed. Group mean daily EPA and DHA intake in grams (g), along with 95% confidence intervals (CI), were computed from up to two 24-hour recall measurements in Hispanics, non-Hispanics whites and others (NHW), non-Hispanic blacks (NHB), and non-Hispanic Asians (NHA). For major food sources across race/ethnic group, the fractions of total intake (and corresponding 95% CIs) from each food item were calculated from the first day's 24-hour recall. Results A total of 9848 individuals were included in this analysis, representing 21% Hispanics, 44% NHW, 23% NHB, and 12% NHA. As expected, significant differences (P < 0.0001 for all tests) in mean intake were observed across racial and ethnic groups for energy, total/saturated/monounsaturated/PUFA fat, cholesterol, EPA, and DHA. NHB reported highest total PUFA intake (Mean: 19.60 g; 95% CI: 18.99-20.22) and NHA reported the lowest (Mean: 16.57 g; 95% CI: 15.86-17.27). However, NHA reported an intake 3x higher of EPA (Mean: 0.07 g; 95% CI: 0.06-0.07) and 2x higher of DHA (Mean: 0.12 g; 95% CI: 0.11-0.14) than other ethnic groups. For NHA, oily fish, which are food sources higher in EPA and DHA, were the largest total EPA and DHA contributors. On the other hand, main contributors to EPA and DHA in Hispanics were food sources lower in EPA and DHA. Conclusions In summary, we observed EPA and DHA mean daily intakes differ significantly across racial/ethnic groups. Further studies assessing dietary n-3 PUFA intakes in the US population should include differences in ethnocentric dietary patterns. Funding Sources This project was funded by the NCI Introduction to Cancer Research Careers.
Rational reprogramming of cellular states by combinatorial perturbation

Ectopic expression of transcription factors (TFs) can reprogram cell state. However, due to the large combinatorial space of possible TF cocktails, it remains difficult to identify TFs that reprogram specific cell types. Here, we develop Reprogram-Seq to experimentally screen thousands of TF cocktails for reprogramming performance. Reprogram-Seq leverages organ-specific cell atlas data with single-cell perturbation and computational analysis to predict, evaluate, and optimize TF combinations that reprogram a cell type of interest. Focusing on the cardiac system, we perform Reprogram-Seq on MEFs using an undirected library of 48 cardiac factors and separately on a directed library of 10 epicardial-related TFs. We identify a novel combination of 3 TFs which efficiently reprogram MEFs to epicardial-like cells that are transcriptionally, molecularly, morphologically, and functionally similar to primary epicardial cells. Reprogram-Seq holds promise to accelerate the generation of specific cell types for regenerative medicine.
Patient experiences of ART adherence clubs in Khayelitsha and Gugulethu, Cape Town, South Africa: A qualitative study

Background Globally, 37 million people are in need of lifelong antiretroviral treatment (ART). With the continual increase in the number of people living with HIV starting ART and the need for life-long retention and adherence, increasing attention is being paid to differentiated service delivery (DSD), such as adherence clubs. Adherence clubs are groups of 25–30 stable ART patients who meet five times per year at their clinic or a community location and are facilitated by a lay health-care worker who distributes pre-packed ART. This qualitative study explores patient experiences of clubs in two sites in Cape Town, South Africa. Methods A total of 144 participants took part in 11 focus group discussions (FGDs) and 56 in-depth interviews in the informal settlements of Khayelitsha and Gugulethu in Cape Town, South Africa. Participants included current club members, stable patients who had never joined a club and club members referred back to clinician-led facility-based standard care. FGDs and interviews were conducted in isiXhosa, translated and transcribed into English, entered into NVivo, coded and thematically analysed. Results The main themes were 1) understanding and knowledge of clubs; 2) understanding of and barriers to enrolment; 3) perceived benefits and 4) perceived disadvantages of the clubs. Participants viewed membership as an achievement and considered returning to clinician-led care a ‘failure’. Moving between clubs and the clinic created frustration and broke down trust in the health-care system. Conclusions Adherence clubs were appreciated by patients, particularly time-saving in relation to flexible ART collection. Improved patient understanding of enrolment processes, eligibility and referral criteria and the role of clinical oversight is essential for building relationships with health-care workers and trust in the health-care system.
Blood Pressure Variability Predicts Poor In-Hospital Outcome in Spontaneous Intracerebral Hemorrhage.

Background and Purpose- There is increasing evidence that higher systolic blood pressure variability (SBPV) may be associated with poor outcome in patients with intracerebral hemorrhage (ICH). We explored the association between SBPV and in-hospital ICH outcome. Methods- We collected 10-years of consecutive data of spontaneous ICH patients at 2 healthcare systems. Demographics, medical history, laboratory tests, computed tomography scan data, in-hospital treatments, and neurological and functional assessments were recorded. Blood pressure recordings were extracted up to 24 hours postadmission. SBPV was measured using SD, coefficient of variation, successive variation (SV), range and 1 novel index termed functional SV. The effects of SBPV on the functional outcome at discharge were evaluated by multivariate logistic and ordinal regression analyses for dichotomous and trichotomous modified Rankin Scale categorizations, respectively. In secondary analyses, associations between SBPV, history of hypertension, and hematoma expansion were explored. Results- The analysis included 762 subjects. All 5 SBPV indices were significantly associated with the probability of unfavorable outcome (modified Rankin Scale, 4-6) in logistic models. In ordinal models, SD, coefficient of variation, range, and functional SV were found to have a significant effect on the probabilities of poor (modified Rankin Scale, 3-4) and severe/death (modified Rankin Scale, 5-6) outcomes. Normotensive patients had significantly lower mean SBPV compared with the untreated-hypertension cohort for all SBPV indices and compared with treated-hypertension patients for 3 out of 5 SBPV indices. Lower mean SBPV of treated-hypertension subjects compared with untreated-hypertension subjects was only detected in the SV and functional SV indices ( P=0.045). None of the SBPV indices were significantly associated with the probability of hematoma expansion. Conclusions- Higher SBPV in the first 24 hours of admission was associated with unfavorable in-hospital outcome among ICH patients. Further prospective studies are warranted to understand any cause-effect relationship and whether controlling for SBPV may improve the ICH outcome.
Fluoxetine‐related mania in an adolescent girl diagnosed with selective mutism: A case report

Selective mutism (SM) is a member of the anxiety disorders (ADs), in which while a child is able to speak with individuals to whom he is closely related, he refuses to speak with most people who he perceives as authority figures in foreign settings (American Psychiatric Association., 2013). SM can have a severe impact on a child's social life, adversely affect school performance, and even make it difficult to remain in education. While significant and gradual improvement in the clinical manifestation of SM has been reported even if cases are not treated, other ADs, and particularly social phobia (SP), are observed more frequently (Steinhausen, Wachter, Laimböck, & Metzke, 2006). Treatment in the early period is therefore highly important. Cognitive behavioral therapy (CBT) and pharmacological therapies have been described as particularly effective for SM ( stergaard, 2018). The most commonly used drug in the treatment of SM is fluoxetine, and successful results have been achieved in various studies (Standart & Couter, 2003). However, pharmacological agents used to treat mental or nonmental diseases have also been shown to cause manic or hypomanialike attacks in individuals with no history of mood disorder (Krauthammer & Klerman, 1978; Wehr & Goodwin, 1987). Prepubertal manic attacks are more frequent in countries in which childhood use of antidepressants and stimulants is more common (Reichart & Nolen, 2004), and children and adolescents receiving antidepressant therapy are at greater risk of developing mania and hypomania than adults (Martin et al., 2004). One study performed in a young population reported a manichypomanic symptom rate of 5.4% (Martin et al., 2004). In another study, while the highest incidence of fluoxetine-induced manic symptoms in pediatric patients was found to be 6%, the incidence with placebos was 0% to 2% (Cheung, Emslie, & Mayes, 2005). This case report describes a manic attack developing in an adolescent girl using fluoxetine for SM.