Miracle-dz/UniFAR-FTUs huggingface dataset:
Maternal and Fetal Outcomes in Pheochromocytoma and Pregnancy: a multi-center retrospective cohort study and systematic review of literature

Background: Concurrent pheochromocytoma and/or paraganglioma (PPGL) in pregnant women can lead to severe complications and death due to associated catecholamine excess. We aimed to identify factors associated with maternal and fetal outcomes in women with PPGL during pregnancy. Methods: We performed a multi-center retrospective study of patients with PPGL and pregnancy between 1980 and 2019 and a systematic review of literature conducted on studies published between 2005 and 2019 containing at least 5 cases. Outcomes of interest were maternal/fetal death and maternal severe cardiovascular complications of catecholamine excess. Findings: We identified 232 eligible patients who had a total of 249 pregnancies while harboring a PPGL. Diagnosis was made before, during pregnancy, or after delivery in 37 (15%), 134 (54%), and 78 (31%) cases, respectively. Of 144 patients evaluated for genetic predisposition for pheochromocytoma, 95 (66%) were positive. Unrecognized PPGL during pregnancy (OR of 27.0; 95%CI 3.5-3128.0), abdominal/pelvic tumor location (OR of 11.3; 95%CI 1.5-1441.0), and catecholamine level ≥10 times the upper limit of reference range (OR of 4.7; 95%CI 1.8-13.8) were associated with adverse outcomes. For patients diagnosed antepartum, alpha-adrenergic blockade therapy prevented adverse outcomes (OR 3.6; 95%CI 1.1-13.2), while antepartum surgery was not associated with better outcomes (no surgery vs surgery: OR 0.9; 95%CI 0.3-3.9). Interpretation: Unrecognized and untreated PPGL was associated with a 27-times higher risk of either maternal or fetal complications. Appropriate case detection and counseling performed in premenopausal women at risk for PPGL may prevent adverse pregnancy-related outcomes. Funding: National Institutes of Health, Maryland, USA. PPGL disorder. Alpha-adrenergic blockade therapy alone can be considered in women diagnosed with PPGL during pregnancy.
Activation and Inhibition of Skeletal RyR Channels by a Part of the Skeletal DHPR II-III Loop: Effects of DHPR Ser 687 and FKBP12

Peptides, corresponding to sequences in the N-terminal region of the skeletal muscle dihydropyridine receptor (DHPR) II-III loop, have been tested on sarcoplasmic reticulum (SR) Ca 2 1 release and ryanodine receptor (RyR) activity. The peptides were: A1, Thr 671 -Leu 690 ; A2, Thr 671 -Leu 690 with Ser 687 Ala substitution; NB, Gly 689 -Lys 708 and A1S, scrambled A1 sequence. The relative rates of peptide-induced Ca 2 1 release from normal (FKBP12 1 ) SR were A2 . A1 . A1S . NB. Removal of FKBP12 reduced the rate of A1-induced Ca 2 1 release by ; 30%. A1 and A2 (but not NB or A1S), in the cytoplasmic ( cis ) solution, either activated or inhibited single FKBP12 1 RyRs. Maximum activation was seen at 2 40 mV, with 10 m M A1 or 50 nM A2. The greatest A1-induced increase in mean current (sixfold) was seen with 100 nM cis Ca 2 1 . Inhibition by A1 was greatest at 1 40 mV (or when permeant ions flowed from cytoplasm to SR lumen) with 100 m M cis Ca 2 1 , where channel activity was almost fully inhibited. A1 did not activate FKBP12-stripped RyRs, although peptide-induced inhibition remained. The results show that peptide A activation of RyRs does not require DHPR Ser 687 , but required FKBP12 binding to RyRs. Peptide A must interact with different sites to activate or inhibit RyRs, because current direction-, voltage-, cis [Ca 2 1 ]-, and FKBP12-dependence of activation and inhibition differ. Details of production electrophoresis, and Western are given in Ahern et
Acute Alcohol Intoxication Impairs Sonic Hedgehog-Gli1 Signaling and Activation of Primitive Hematopoietic Precursor Cells in the Early Stage of Host Response to Bacteremia

Background: Activation of hematopoietic stem cells [HSCs, lineage(lin) − stem cell growth factor receptor (c-kit) + stem cell antigen-1(Sca-1) + , or LKS cells in mice] is critical for initiating the granulopoietic response. This study determined the effect of alcohol exposure on sonic hedgehog (SHH) signaling in the regulation of HSC activation during bacteremia. Methods: Acute alcohol intoxication was induced in mice by intraperitoneal (i.p.) injection of 20% alcohol (5 g alcohol/kg body weight). Control mice received i.p. saline. Thirty minutes later, mice were intravenously (i.v.) injected with Escherichia coli (E. coli, 1 to 5 × 10 7 CFUs/mouse) or saline. Results: SHH expression by lineage-negative bone marrow cells (BMCs) was significantly increased 24 hours after E. coli infection. Extracellular signal-regulated kinase 1/2 (ERK1/2)-specificity protein 1 (Sp1) signaling promotes SHH expression. ERK1/2 was markedly activated in BMCs 8 hours following E. coli infection. Alcohol suppressed both the activation of ERK1/2 and up-regulation of SHH expression following E. coli infection. E. coli infection up-regulated GLI family zinc finger 1 (Gli1) gene expression by BMCs and increased Gli1 protein content in LKS cells. The extent of Gli1 expression was correlated with the activity of proliferation in LKS cells. Alcohol inhibited up-regulation of Gli1 expression and activation of LKS cells in response to E. coli infection. Alcohol also interrupted the granulopoietic response to bacteremia. Conclusion: These data show that alcohol disrupts SHH-Gli1 signaling and HSC activation in the early stage of the granulopoietic response, which may serve as an important mechanism underlying the impairment of immune defense against bacterial infection in host excessively consuming alcohol.
Preliminary Data on Help-Seeking Intentions and Behaviors of Individuals Completing a Widely Available Online Screen for Eating Disorders in the U.S.

Objective: Scaling an online screen that provides referrals may be key in closing the treatment gap for eating disorders (EDs), but we need to understand respondents’ help-seeking intentions and behaviors after receiving screen results. This study reported on these constructs among respondents to the National Eating Disorders Association (NEDA) online screen who screened positive or at high risk for an ED. Method: Respondents completed the screen over 18 months (2/9/18–8/28/19). Those screening positive or at high risk for an ED (n=343,072) had the option to provide data on help-seeking intentions (after screen completion) and behaviors (2-month follow-up). Results: Of eligible respondents, 4.8% (n=16,396) provided data on help-seeking intentions, with only 33.7% of those reporting they would seek help. Only 7.6% of eligible respondents opted in to the 2-month follow-up, with 10.6% of those completing it (n=2,765). Overall, 8.9% of respondents to the follow-up reported being in treatment when they took the screen, 15.5% subsequently initiated treatment, and 75.5% did not initiate/were not already in treatment. The data that the findings of this study available from the upon reasonable Discussion: Preliminary results suggest that among the small minority who provided data, only one-third expressed help-seeking intentions and 16% initiated treatment. Online screening should consider ways to increase respondents’ motivation for and follow-through with care.
Multiple Sleep Latency Test: when are 4 naps enough?

Study Objectives: The Multiple Sleep Latency Test (MSLT)is central to the diagnosis of narcolepsy and idiopathic hypersomnia. This study is the ﬁ rst to assess the impact of a 5-nap protocol on meeting MSLT-derived diagnostic criteria in a general cohort referred for MSLT, without selection bias. Methods: Dataforall MSLTsperformedat2tertiarysleepunitsin Australia betweenMay2012andMay2018wereretrospectively assessedfortheimpactofthe ﬁ fth nap on mean sleep latency (MSL) and sleep onset rapid eye movement periods. Results: There were 122 MSLTs included. The MSL was 8.7 ± 5.1 minutes after 4 naps, compared with 9.2 ± 5.2 minutes for 5 naps ( P <.0001). In 8 cases, inclusion of the ﬁ fth nap changed the MSL to a value above the diagnostic threshold of 8 minutes. There were no instances in which the MSL moved to ≤ 8 minutes based on ﬁ fth nap data. A sleep onset rapid eye movement period occurred in the ﬁ fth nap in 9 patients and altered the interpretation in 2 cases. Conclusions: The ﬁ fth nap in an MSLT is associated with an increased MSL, although this difference is rarely clinically signi ﬁ cant. In patients with borderline MSL or 1sleeponsetrapideyemovementperiodafter4naps,a ﬁ fthnapcanaltertheoutcomeandshouldbeperformed.However,formanycases,a4-napMSLTprotocolwillsuf ﬁ ce, potentiallyallowingresourcesavingswithoutcompromisingdiagnosticaccuracy.Weproposetheadoptionofaconditional4-napor5-napprotocolbasedonspeci ﬁ ccriteria. Current Knowledge/Study Rationale: There is institutional variation in performance of a 4-nap or 5-nap protocol for the Multiple Sleep Latency Test, a key measurement used in the assessment of disorders of hypersomnolence. This study is the ﬁ rst to speci ﬁ cally assess the impact of a 5-nap protocol on Multiple Sleep Latency Test-derived diagnostic criteria in a general cohort with routine performance of a ﬁ fth nap. Study Impact: In our cohort referred for Multiple Sleep Latency Test, the ﬁ fth nap data did not alter the overall interpretation of the test for a signi ﬁ cant number (60%) of cases. We propose a conditional 4-nap or 5-nap protocol based on criteria for mean sleep latency and sleep onset rapid eye movement periods obtained after 4 naps.
Arkadia ampli ® es TGF-b superfamily signalling through degradation of Smad 7

Arkadia was originally identiﬁed as a protein that enhances signalling activity of Nodal and induces mammalian nodes during early embryogenesis; how-ever, the mechanisms by which Arkadia affects transforming growth factor- b (TGF- b ) superfamily signalling have not been determined. Here we show that Arkadia is widely expressed in mammalian tissues, and that it enhances both TGF- b and bone morphogenetic protein (BMP) signalling. Arkadia physically interacts with inhibitory Smad, Smad7, and induces its poly-ubiquitination and degradation. In contrast to Smurf1, which interacts with TGF- b receptor complexes through Smad7 and degrades them, Arkadia fails to associate with TGF- b receptors. In contrast to Smad7, expression of Arkadia is down-regulated by TGF- b . Silencing of the Arkadia gene resulted in repression of transcriptional activities induced by TGF- b and BMP, and accumulation of the Smad7 protein. Arkadia may thus play an important role as an ampliﬁer of TGF- b superfamily signalling under both physiological and pathological conditions.
The eﬀect of mechanical and chemical polishing techniques on the surface roughness of denture base acrylic resins The Saudi Dental

Smooth polished surface of dental prostheses is important to prevent bacterial colonization and plaque accumulation. The acrylic base of prosthodontic appliances needs to be adjusted by grinding which often alters the surface of the denture base. It is therefore important to know how different polishing techniques affect surface roughness of acrylic resin. Objective: The aim of this study was to evaluate the effect of mechanical polishing (MP) and chemical polishing (CP) on the surface roughness of heat cured (HC) and auto cured (AC) denture base acrylic resins. Materials and methods: Sixty acrylic resin specimens (30 · 15 · 3 mm) were made for each of the two types of acrylic resins. Thirty HC specimens received mechanical conventional lathe polishing using cone with pumice slurry and soft brush with chalk powder. The other thirty HC specimens received chemical polishing by immersing in methyl-methacrylate monomer heated to 75 (cid:2) C ± 1 (cid:2) C for 10 s. The sixty AC specimens received mechanical and chemical polishing in the same manner. Surface roughness was measured using surface analyzing instrument in microns. The data were statistically analyzed by two-way analysis of variance (ANOVA) followed by post hoc Tukey’s test ( a = 0.05). Results: The surface roughness mean in microns in order of decreasing values were: CP-HC: 1.4132 l m; CP-AC: 1.3494 l m; MP-AC: 0.7364 l m and MP-HC: 0.6333 l m. Two-way ANOVA revealed that the MP-HC was signiﬁcantly different from CP-HC and CP-AC ( P < 0.05). The MP-AC is also signiﬁcantly different from CP-HC and CP-AC ( P < 0.05). There was no signiﬁcant difference between MP and CP of HC and AC acrylic resin groups. Conclusion: It can be concluded that smoother than CP. The surface roughness obtained by MP was not inﬂuenced by acrylic resin type where as this was not true for CP.
Reduced fractional anisotropy of genu of corpus callosum as a predictor of longitudinal cognition in MCI

Our goal was to evaluate the utility of diffusion tensor imaging (DTI) for predicting future cognitive decline in mild cognitive impairment (MCI) in conjunction with AD biomarkers (amyloid PET and AD signature neurodegeneration) in 132 MCI individuals ≥60 years old with structural MRI, DTI, amyloid PET, and at least one clinical follow-up. We used mixed effect models to evaluate the prognostic ability of fractional anisotropy of genu of the corpus callosum (FA-Genu), as a cerebrovascular disease (CVD) marker, for predicting cognitive decline along with AD biomarkers. We contrasted the value of white matter hyperintensities, a traditional CVD marker as well as FA in the hippocampal cingulum bundle (FA-HCB) with the FA-Genu models. FA-Genu significantly predicted cognitive decline even after accounting for AD biomarkers. WMH was not associated with cognitive decline in the model with WMH and FA-Genu. DTI specifically FA-Genu provides unique complementary information to AD biomarkers and has significant utility for prediction of cognitive decline in MCI.
Sexual Minority Bariatric Patients: Examination of Eating Behaviors, Anxiety, and Depression

Background: Disparities in obesity care and bariatric surgery persist among patients of diverse identities. However, little is known about sexual minority (SM) bariatric patients. Objectives: This study sought to describe, in a preliminary fashion, sexual orientation variables of outness, self-esteem, and perceived discrimination among a sample of SM patients pursuing bariatric surgery. The study also sought to compare SM and heterosexual bariatric candidates on measures of eating behaviors, anxiety, and depression. Setting: Academic medical center in the United States. Methods: Data were collected as part of a standard psychological evaluation for surgical clearance between May 1 st , 2018 and December 31 st , 2019. Data included demographics, sexual orientation variables, eating behaviors, anxiety, and depression. Descriptive statistics were included to present findings among SM patients. One-way analyses of covariance (ANCOVAs) were conducted to assess differences between SM and heterosexual patients. Results: A total of 633 patients were evaluated (38 SM and 595 heterosexual). SM patients had high outness scores with high self-esteem and minimal perceived discrimination. SM patients endorsed lower cognitive restraint, higher disinhibition and increased hunger compared to heterosexual patients (p < 0.05). SM patients also reported significantly more symptoms of anxiety and depression compared to heterosexual patients (p < 0.05). Conclusions: Findings provide preliminary evidence toward the importance of assessing for sexual orientation among bariatric patients. Future research is warranted to assess the unique role of sexual orientation, as well as explore causal links between sexual orientation, eating behaviors, and mental health among bariatric patients pre- and post-surgery.
Using Neuropsychological Process Scores to Identify Subtle Cognitive Decline and Predict Progression to MCI

Background: We previously operationally-defined subtle cognitive decline (SCD) in preclinical Alzheimer’s disease (AD) using total scores on neuropsychological (NP) tests. NP process scores (i.e., provide information about how a total NP score was achieved) may be a useful tool for identifying early cognitive inefficiencies prior to objective impairment seen in mild cognitive impairment (MCI) and dementia. Objective: We aimed to integrate process scores into the SCD definition to identify stages of SCD and improve early detection of those at risk for decline. Methods: Cognitively “normal” participants from the Alzheimer’s Disease Neuroimaging Initiative were classified as “early” SCD (E-SCD; >1 SD below mean on 2 process scores or on 1 process score plus 1 NP total score), “late” SCD (L-SCD; existing SCD criteria of >1 SD below norm-adjusted mean on 2 NP total scores in different domains), or “no SCD” (NC). Process scores considered in the SCD criteria were word-list intrusion errors, retroactive interference, and learning slope. Cerebrospinal fluid AD biomarkers were used to examine pathologic burden across groups. Results: E-SCD and L-SCD progressed to MCI 2.5-3.4 times faster than the NC group. Survival curves for E-SCD and L-SCD converged at 7-8 years after baseline. The combined (E-SCD+L-SCD) group had improved sensitivity Conclusions: Process scores can be integrated into the SCD criteria to allow for increased sensitivity and earlier identification of cognitively normal older adults at risk for decline prior to frank impairment on NP total scores.
INTEGRATED Supplementing calcium salts of soybean oil to beef steers early in life to enhance carcass development and quality 1

This study evaluated the effects of supplementing Ca salts of soybean oil ( CSSO ) to beef steers at 2 mo of age via creep-feeding, and/or during a 40-d preconditioning period on performance and carcass development responses. A total of 64 steers were enrolled in this study over 2 yr (32 steers per year), with 4 periods each year: creep-feeding ( CF ; day 0 to 60), preweaning No treatment differences were detected for ( P ≥ 0.18) performance or carcass traits, including marbling and backfat thickness. Results from this study suggest that supplementing CSSO to suckled beef steers via creep-feeding upregulated mRNA expression of the adipogenic genes investigated herein later in life. These outcomes, however, were not translated into improved carcass quality.
fﬁ d f h Efﬁ cacy and toxicity of the antisense oligonucleotide aprinocarsen directed against protein kinase C- (cid:1) delivered as a 21-day continuous intravenous infusion in patients with recurrent high-grade astrocytomas 1,2

Protein kinase C alpha (PKC- (cid:1) ) is a cytoplasmic serine threonine kinase involved in regulating cell differentiation and proliferation. Aprinocarsen is an antisense oligonucleotide against PKC- (cid:1) that reduces PKC- (cid:1) in human cell lines and inhibits a human glioblastoma tumor cell line in athymic mice. In this phase 2 study, aprinocarsen was administered to patients with recurrent high-grade glio-mas by continuous intravenous infusion (2.0 mg/kg/day
Distribution of Three a-Chain 13-Hexosaminidase A Mutations Among Tay-Sachs Carriers

Summary DNA from 176 carriers of the Tay-Sachs gene was tested for the presence of the three mutations most commonly found among Ashkenazi Jews: the so-called insertion, splice junction, and adult mutations. Among 148 Ashkenazi Jews tested, 108 had the insertion mutation, 26 had the splice junction mutation, five had the adult mutation, and nine had none of the three. Among 28 non-Jewish carriers tested, most of whom were obligate carriers, four had the insertion mutation, one had the adult mutation, and the remaining 23 had none of the three.
The multifaceted role of ischemia/reperfusion in sickle cell anemia

and/or leukocytes 15). Sickle cell anemia is a unique disease dominated by hemolytic anemia and vaso-occlusive events. The latter trigger a version of ischemia/reperfusion (I/R) pathobiology that is singular in its origin, cyclicity, complexity, instability, perpetuity, and breadth of clinical consequences. Specific clinical features are probably attributable to local I/R injury (e.g., stroke syndromes) or remote organ injury (e.g., acute chest syndrome) or the systematization of inflammation (e.g., multifocal arteriopathy). Indeed, by fashioning an underlying template of endothelial dysfunction and vulnerability, the robust inflammatory systematization no doubt contributes to all sickle pathology. In this Review, we highlight I/R–targeting therapeutics shown to improve microvascular blood flow in sickle transgenic mice undergoing I/R, and we suggest how such insights might be translated into human therapeutic strategies.
TBS in Mexican American Women with Type 2 diabetes

Dual energy x-ray absorptiometry (DXA) acquired bone mineral density (BMD) remains the gold standard for diagnosing osteoporosis and assessing risk of fragility fractures (1). However, a paradoxical presence of fragility fractures with high or normal (nonosteoporotic) BMD in patients with type 2 diabetes (T2D) suggests that DXA may not be reliable for assessing fracture risk in subjects with T2D. (2). An altered state of bone quality caused by underlying metabolic changes of T2D has been hypothesized to cause reduced strength and bone turnover leading to increased fracture risk in T2D patients (2–3).
Exploiting pre-existing CD4 + T cell help from BCG vaccination to improve anti-viral antibody responses

The continuing emergence of viral pathogens and their rapid spread into heavily populated areas around the world underscore the urgency for development of highly effective vaccines to generate protective anti-viral antibody responses. Many established and newly emerging viral pathogens, including HIV and Ebola viruses, are most prevalent in regions of the world in which Mycobacterium tuberculosis infection remains endemic and vaccination at birth with M. bovis bacille Calmette-Guérin (BCG) is widely used. We have investigated the potential for using CD4 + T cells arising in response to BCG as a source of help for driving antibody responses against viral vaccines. To test this approach, we designed vaccines comprised of protein immunogens fused to an immunodominant CD4 + T cell epitope of the secreted Antigen 85B protein of BCG. Proof of concept experiments showed that the presence of BCG-specific T helper cells in previously BCG vaccinated mice had a dose sparing effect for subsequent vaccination with fusion proteins containing the Antigen 85B epitope, and consistently induced isotype switching to the IgG2c subclass. Studies using an Ebola virus glycoprotein fused to the Antigen 85B epitope showed that prior BCG vaccination promoted high affinity IgG1 responses that neutralized viral infection. The design of fusion protein vaccines with the ability to recruit BCG-specific CD4 + helper T cells may be a useful and broadly applicable approach to generating improved vaccines against Here we show that with BCG developed BCG-specific cell such drive BCG-specific Th cells were induced by BCG vaccination in neonatal mice, and their contribution to antibody responses in persisted in Our analysis showed that antibodies facilitated by BCG-specific Th cells had enhanced capacity for neutralizing entry into host cells, which correlated with increased antibody affinity in the IgG1 subclass. Antibodies that were class switched to IgG2c were also consistently detected, suggesting the potential for other relevant effector functions such as ADCC. Overall, our findings provide an initial proof-of-concept for a practical approach to improving anti-viral vaccines by designing immunogens that can use pre-existing BCG-specific Th cells to promote protective antibody responses.