Miracle-dz/UniFAR-FTUs huggingface dataset:
Associations of plasma, RBCs, and hair carbon and nitrogen isotope ratios with fish, meat, and sugar-sweetened beverage intake in a 12-wk inpatient feeding study.

BACKGROUND Naturally occurring carbon and nitrogen stable isotope ratios [13C/12C (CIR) and 15N/14N (NIR)] are promising dietary biomarkers. As these candidate biomarkers have long tissue residence times, long-term feeding studies are needed for their evaluation. OBJECTIVE Our aim was to evaluate plasma, RBCs, and hair CIR and NIR as biomarkers of fish, meat, and sugar-sweetened beverage (SSB) intake in a 12-wk dietary intervention. METHODS Thirty-two men (aged 46.2 ± 10.5 y; BMI: 27.2 ± 4.0 kg/m2) underwent a 12-wk inpatient dietary intervention at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in Phoenix, Arizona. The effects of fish, meat, and SSB intake on CIR and NIR were evaluated using a balanced factorial design, with each intake factor at 2 levels (present/absent) in a common, background diet (50% carbohydrate, 30% fat, 20% protein). Fasting blood samples were taken biweekly from baseline, and hair samples were collected at baseline and postintervention. Data were analyzed using multivariable regression. RESULTS The postintervention CIR of plasma was elevated when diets included meat (β = 0.89, 95% CI: 0.73,1.05) and SSBs (β = 0.48, 95% CI: 0.32, 0.64). The postintervention NIR of plasma was elevated when diets included fish (β = 0.85, 95% CI: 0.64, 1.05) and meat (β = 0.61, 95% CI: 0.42, 0.8). Results were similar for RBCs and hair. Postintervention RBC CIR and NIR had strong associations with baseline, suggesting that turnover to the intervention diets was incomplete after 12 wk. Estimates of isotopic turnover rate further confirmed incomplete turnover of RBCs. CONCLUSIONS CIR was associated with meat and SSBs, and more strongly with meat. NIR was associated with fish and meat, and more strongly with fish. Overall, CIR and NIR discriminated between dietary fish and meat, and to a lesser extent SSBs, indicating their potential utility as biomarkers of intake in US diets. Approaches to make these biomarkers more specific are needed. This trial was registered at clinicaltrials.gov as NCT01237093.
Psychological Barriers to Digital Living in Older Adults: Computer Anxiety as Predictive Mechanism for Technophobia

This study aimed to investigate the emotional impact of technology use in an Italian adult population and to detect technophobia. This cross-sectional study was conducted with 117 Italian participants (age range of 50–67 years). Measured variables were computer anxiety and technology use ability. The results revealed technophobia features in the Italian adult population related to inadequate management of technology. One-way analysis of variance and Bonferroni’s post-hoc analysis showed that non-autonomous (p < 0.01), low-frequency (p < 0.01), and feeling-a-need-for-help users (p < 0.01) had higher levels of computer anxiety. Based on our data, although lifelong learning is a powerful digital need, a considerable proportion of the adult population is not digitally skilled, enlarging the gap between young (native digital) and adult (digital and non-digital adults and seniors) populations. Adult inclusivity in digital living is inadequate and likely affects their quality of life. Thus, our findings highlight technophobia as a possible new risk factor for Italian adults because it can affect their daily life through low adherence to digital living; rather than aging successfully, they could develop fragile aging.
Larger brains spur species diversification in birds

Evidence is accumulating that species traits can spur their evolutionary diversification by influencing niche shifts, range expansions, and extinction risk. Previous work has shown that larger brains (relative to body size) facilitate niche shifts and range expansions by enhancing behavioral plasticity but whether larger brains also promote evolutionary diversification is currently backed by insufficient evidence. We addressed this gap by combining a brain size dataset for >1900 avian species worldwide with estimates of diversification rates based on two conceptually different phylogenetic‐based approaches. We found consistent evidence that lineages with larger brains (relative to body size) have diversified faster than lineages with relatively smaller brains. The best supported trait‐dependent model suggests that brain size primarily affects diversification rates by increasing speciation rather than decreasing extinction rates. In addition, we found that the effect of relatively brain size on species‐level diversification rate is additive to the effect of other intrinsic and extrinsic factors. Altogether, our results highlight the importance of brain size as an important factor in evolution and reinforce the view that intrinsic features of species have the potential to influence the pace of evolution.
Evaluation of Blood Transfusion Services in Public and Private Blood Bank Centers, Sana’a Capital, Yemen

The aim of this study was to evaluate blood transfusion services (BTS) at the main blood banks (BBs) of the Sana’a Capital. The 4 main BBs at Sana’a Capital were evaluated according to the safe World Health Organization BTS standards. Qualitative and quantitative data were collected using semi-structured questionnaires covering 6 components: activities, quality assurance system (QAS) and training, donation, grouping and compatibility testing, components, and screening for transfusion-transmitted infections (TTIs). An overall mean percent score for BTS was calculated where <60% is considered unsatisfactory, 60% to 79.9% satisfactory, and ≥80% highly satisfactory. The 4 BBs screen for HIV, hepatitis B, and hepatitis C and perform all functions except therapeutic transfusion. While 75% of the staff in BBs had received training in biosafety and half of the staff had received training in Standard Operating Procedures (SOPs), no QAS in place at any of the 4 BBs. The 4 BBs depended on 71% of their transfusions on family donors. Two BBs do not perform reverse grouping and do not keep patient/donor samples for the required minimum 5 days. Only one BB achieved an overall high satisfactory score and one achieved a satisfactory score. Findings highlight the increasing challenges facing BTS in Sana’a Capital especially the lack of therapeutic transfusion, poor QAS, and predominant dependence on the family donors. Therefore, there is a need to develop and train staff on QAS and to increase awareness among public on importance of voluntary donation. A wider scale evaluation of BTS in Sana’a is recommended.
Developing a Typology of HIV/STI Testing Patterns Among Gay, Bisexual, and Queer Men: A Framework to Guide Interventions

Although factors associated with HIV/sexually transmitted infection (STI) testing among gay, bisexual, and queer (GBQ) men are well-established in the literature, few studies have attempted to delineate the processes underlying different patterns of testing. We conducted a qualitative study involving 35 semistructured interviews with a purposive sample of GBQ men in Singapore from October 2017 to July 2018. Topics explored included formative sexual experiences, relationships, and experiences of HIV/STI testing. Interviews were audio-recorded, transcribed, coded, and analyzed through inductive thematic analysis. A typology comprising four distinct HIV/STI testing patterns was identified from the data, categorized based on the regularity of testing, relative to internal or external factors that motivate testing behaviors. These include triggered episodic testing, influenced episodic testing, institutionalized regular testing, and value-based regular testing. The typology highlights the preconditions that underlie different testing patterns and provides a framework for developing interventions that promote HIV/STI testing among GBQ men.
Common Themes, Different Perspectives: A Systematic Analysis of Employer-Employee Experiences of Occupational Rehabilitation.

Workers with injuries and their employers were interviewed using a semistructured protocol to elicit their perceptions about their own and each others behavior and that of other stakeholders in the process of occupational rehabilitation. Four common themes emerged from the interviews. Whereas workers with injuries focused on the perceived failure of the system to provide adequate care, employers were concerned with issues of cost containment and productivity. A process of triangulation of stakeholders occurs that results in polarization of the primary employer-employee dyad. Changes to the current system are recommended, including specifi c educational campaigns targeting employers and the training and accreditation of rehabilitation coordinators.
Periodontal disease and oral health-related quality of life : smoking cessation adventures in primary dental care

Much of the workload of primary dental care teams in remote-rural Scotland consists of treating periodontal disease, an inflammatory condition for which smoking is a proven risk factor. This thesis sought to ascertain the effectiveness of a smoking cessation intervention applied in a primary care dental setting and employed a narrative literature review to explore periodontal disease, smoking and smoking cessation interventions. This literature review informed the design of a randomised controlled trial which failed due to lack of recruitment. The Medical Research Council Framework for the Development and Evaluation of Complex Interventions was employed to provide structure to the modelling of a feasibility trial likely to succeed in evaluating the benefit of smoking cessation provision in rural dental settings. A systematic literature review was undertaken to evaluate evidence regarding prevalence of periodontal disease, tobacco use and the effectiveness of tobacco cessation interventions applied in remote-rural areas. This identified a dearth of robust evidence particularly in relation to smoked tobacco. In order to model a feasibility study better adapted to the current study population, a prevalence study exploring the smoking attitudes and behaviours, the oral health-related quality of life and periodontal status of 398 dental patients was undertaken at the two study locations.
Evaluation of IH-1000 for Automated ABO-Rh Typing and Irregular Antibody Screening

3 samples showed positive in IH-1000 and negative in manual method. 1 anti-E Ab was identified and revealed false negative of manual method 2 cases were false-positive reactions of IH-1000 system. :1 hemolytic specimen from patient with newly diagnosed acute leukemia with WBC 110,000/μl. :1 hyperglycemic specimen with HbA1c 10.4%, ESR 120mm/h, WBC 34,700/μl. 1 samples showed negative in IH-1000, positive in manual method, 1 anti-E Ab was identified, revealed false negative results in IH-1000 system. : It was diluted specimen from a patient tranfused 2 pack of PRC.
Preclinical disposition of MGS0274 besylate, a prodrug of a potent group II metabotropic glutamate receptor agonist MGS0008 for the treatment of schizophrenia

MGS0274 besylate is an ester‐based lipophilic prodrug of a metabotropic glutamate (mGlu) 2 and mGlu3 receptor agonist MGS0008 and being developed for the treatment of schizophrenia. We investigated the disposition of these compounds in rats and monkeys and in vitro metabolism in humans to evaluate whether MGS0274 besylate could be useful as a prodrug in humans. After the oral administration of MGS0274 besylate to monkeys (2.89 mg/kg), MGS0008 was immediately found in plasma, reached a maximum concentration at 4 hours postdose, and decreased with a terminal half‐life of 16.7 hours; MGS0274 was barely detectable. The oral bioavailability as MGS0008 was 83.7%, which was approximately 20‐fold greater than that after oral dosing of MGS0008 (3.8%). In rats, MGS0008 penetrated the cerebrospinal fluid and was eliminated slower than from plasma. The in vitro metabolism study indicated that MGS0274 was rapidly hydrolyzed to MGS0008, which was not further metabolized. After the intravenous administration of MGS0008 to rats and monkeys, almost all the dose was excreted unchanged in urine. These results suggested that MGS0274 was, as expected, presystemically hydrolyzed to MGS0008 after gastrointestinal absorption and that MGS0008 was distributed throughout the body without further metabolism and ultimately excreted in urine in the animals. Furthermore, the hydrolytic activity against MGS0274 in the human liver S9 fraction was comparable to that in monkeys, suggesting the possibility of the rapid presystemic hydrolysis of MGS0274 to MGS0008 in humans, as it is in monkeys. Consequently, MGS0274 besylate is expected to function as a preferable prodrug in humans.
Single-molecule analysis reveals rotational substeps and chemo-mechanical coupling scheme of Enterococcus hirae V1-ATPase

V1-ATPase (V1), the catalytic domain of an ion-pumping V-ATPase, is a molecular motor that converts ATP hydrolysis–derived chemical energy into rotation. Here, using a gold nanoparticle probe, we directly observed rotation of V1 from the pathogen Enterococcus hirae (EhV1). We found that 120° steps in each ATP hydrolysis event are divided into 40 and 80° substeps. In the main pause before the 40° substep and at low ATP concentration ([ATP]), the time constant was inversely proportional to [ATP], indicating that ATP binds during the main pause with a rate constant of 1.0 × 107 m−1 s−1. At high [ATP], we observed two [ATP]-independent time constants (0.5 and 0.7 ms). One of two time constants was prolonged (144 ms) in a rotation driven by slowly hydrolyzable ATPγS, indicating that ATP is cleaved during the main pause. In another subpause before the 80° substep, we noted an [ATP]-independent time constant (2.5 ms). Furthermore, in an ATP-driven rotation of an arginine-finger mutant in the presence of ADP, −80 and −40° backward steps were observed. The time constants of the pauses before −80° backward and +40° recovery steps were inversely proportional to [ADP] and [ATP], respectively, indicating that ADP- and ATP-binding events trigger these steps. Assuming that backward steps are reverse reactions, we conclude that 40 and 80° substeps are triggered by ATP binding and ADP release, respectively, and that the remaining time constant in the main pause represents phosphate release. We propose a chemo-mechanical coupling scheme of EhV1, including substeps largely different from those of F1-ATPases.
Reward Boosts Neural Coding of Task Rules to Optimize Cognitive Flexibility

Cognitive flexibility is critical for intelligent behavior. However, its execution is effortful and often suboptimal. Recent work indicates that flexible behavior can be improved by the prospect of reward, which suggests that rewards optimize flexible control processes. Here we investigated how different reward prospects influence neural encoding of task rule information to optimize cognitive flexibility. We applied representational similarity analysis to human electroencephalograms, recorded while female and male participants performed a rule-guided decision-making task. During the task, the prospect of reward varied from trial to trial. Participants made faster, more accurate judgements on high-reward trials. Critically, high reward boosted neural coding of the active task rule, and the extent of this increase was associated with improvements in task performance. Additionally, the effect of high reward on task rule coding was most pronounced on switch trials, where rules were updated relative to the previous trial. These results suggest that reward prospect can promote cognitive performance by strengthening neural coding of task rule information, helping to improve cognitive flexibility during complex behavior. SIGNIFICANCE STATEMENT The importance of motivation is evident in the ubiquity with which reward prospect guides adaptive behavior and the striking number of neurological conditions associated with motivational impairments. In this study, we investigated how dynamic changes in motivation, as manipulated through reward, shape neural coding for task rules during a flexible decision-making task. The results of this work suggest that motivation to obtain reward modulates the encoding of task rules needed for flexible behavior. The extent to which reward increased task rule coding also tracked improvements in behavioral performance under high-reward conditions. These findings help to inform how motivation shapes neural processing in the healthy human brain.
Applicability of biological fertility indicators for effective birth control after orthotopic liver transplantation

a Cátedra Gianna Barretta para Estudios de Bioética, Sexualidad y Reconocimiento de la Fertilidad. Universidad Alfonso X el Sabio-Fundación COF Getafe, Boadilla del Monte, Madrid, Spain; b Departamento de enfermería. Facultad de las Ciencias de la Salud. Universidad Católica de Ávila c Consulta de alto riesgo obstétrico. Servicio de Ginecología y Obstetricia. Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain. d Unidad de trasplante hepático. Servicio de Medicina Interna. Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain.
The human cytomegalovirus-encoded G protein–coupled receptor UL33 exhibits oncomodulatory properties

Herpesviruses can rewire cellular signaling in host cells by expressing viral G protein–coupled receptors (GPCRs). These viral receptors exhibit homology to human chemokine receptors, but some display constitutive activity and promiscuous G protein coupling. Human cytomegalovirus (HCMV) has been detected in multiple cancers, including glioblastoma, and its genome encodes four GPCRs. One of these receptors, US28, is expressed in glioblastoma and possesses constitutive activity and oncomodulatory properties. UL33, another HCMV-encoded GPCR, also displays constitutive signaling via Gαq, Gαi, and Gαs proteins. However, little is known about the nature and functional effects of UL33-driven signaling. Here, we assessed UL33's signaling repertoire and oncomodulatory potential. UL33 activated multiple proliferative, angiogenic, and inflammatory signaling pathways in HEK293T and U251 glioblastoma cells. Notably, upon infection, UL33 contributed to HCMV-mediated STAT3 activation. Moreover, UL33 increased spheroid growth in vitro and accelerated tumor growth in different in vivo tumor models, including an orthotopic glioblastoma xenograft model. UL33-mediated signaling was similar to that stimulated by US28; however, UL33-induced tumor growth was delayed. Additionally, the spatiotemporal expression of the two receptors only partially overlapped in HCMV-infected glioblastoma cells. In conclusion, our results unveil that UL33 has broad signaling capacity and provide mechanistic insight into its functional effects. UL33, like US28, exhibits oncomodulatory properties, elicited via constitutive activation of multiple signaling pathways. UL33 and US28 might contribute to HCMV's oncomodulatory effects through complementing and converging cellular signaling, and hence UL33 may represent a promising drug target in HCMV-associated malignancies.
Epstein-Barr virus subverts mevalonate and fatty acid pathways to promote infected B-cell proliferation and survival

Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with multiple human malignancies. EBV drives B-cell proliferation, which contributes to the pathogenesis of multiple lymphomas. Yet, knowledge of how EBV subverts host biosynthetic pathways to transform resting lymphocytes into activated lymphoblasts remains incomplete. Using a temporal proteomic dataset of EBV primary human B-cell infection, we identified that cholesterol and fatty acid biosynthetic pathways were amongst the most highly EBV induced. Epstein-Barr nuclear antigen 2 (EBNA2), sterol response element binding protein (SREBP) and MYC each had important roles in cholesterol and fatty acid pathway induction. Unexpectedly, HMG-CoA reductase inhibitor chemical epistasis experiments revealed that mevalonate pathway production of geranylgeranyl pyrophosphate (GGPP), rather than cholesterol, was necessary for EBV-driven B-cell outgrowth, perhaps because EBV upregulated the low-density lipoprotein receptor in newly infected cells for cholesterol uptake. Chemical and CRISPR genetic analyses highlighted downstream GGPP roles in EBV-infected cell small G protein Rab activation. Rab13 was highly EBV-induced in an EBNA3-dependent manner and served as a chaperone critical for latent membrane protein (LMP) 1 and 2A trafficking and target gene activation in newly infected and in lymphoblastoid B-cells. Collectively, these studies identify highlight multiple potential therapeutic targets for prevention of EBV-transformed B-cell growth and survival.
Proteomic mapping by rapamycin-dependent targeting of APEX2 identifies binding partners of VAPB at the inner nuclear membrane

Vesicle-associated membrane protein–associated protein B (VAPB) is a tail-anchored protein that is present at several contact sites of the endoplasmic reticulum (ER). We now show by immunoelectron microscopy that VAPB also localizes to the inner nuclear membrane (INM). Using a modified enhanced ascorbate peroxidase 2 (APEX2) approach with rapamycin-dependent targeting of the peroxidase to a protein of interest, we searched for proteins that are in close proximity to VAPB, particularly at the INM. In combination with stable isotope labeling with amino acids in cell culture (SILAC), we confirmed many well-known interaction partners at the level of the ER with a clear distinction between specific and nonspecific hits. Furthermore, we identified emerin, TMEM43, and ELYS as potential interaction partners of VAPB at the INM and the nuclear pore complex, respectively.
Clinical applications, accuracy, and limitations of Guided Endodontics: a systematic review.

BACKGROUND The novel concept of guided endodontics has been reported as an effective method to obtain safe and reliable results in endodontic treatment. AIM To evaluate by means of a systematic review the clinical applications, accuracy and limitations of guided endodontic treatment. DATA SOURCES A search of the literature was performed on PubMed, EMBASE, Web of Science and Cochrane Library databases, until April 25th , 2019. No language or year restrictions were applied. STUDY ELIGIBILITY CRITERIA Articles that answered the research question, including case reports, in vitro and ex vivo studies were included. Data extraction was performed independently by two reviewers. STUDY APPRAISAL Quality assessment was done with STROBE, CARE and Modified CONSORT guidelines for observational, case reports and preclinical studies, respectively. RESULTS A total of 22 articles including fifteen case reports, six pre-clinical studies (in vitro and ex vivo studies), and one observational study, were included. LIMITATIONS AND CONCLUSIONS Even though the level of evidence is low, and the methodology described among studies heterogeneous, all articles describe guided access cavity preparation and guided surgery as being highly accurate and successful techniques when comparing the drilled path to the planned treatment. More studies with a larger number of patients are necessary to obtain significant conclusions.