Miracle-dz/UniFAR-FTUs huggingface dataset:
Association Between Clinically Meaningful Posttraumatic Stress Disorder Improvement and Risk of Type 2 Diabetes.

Importance Posttraumatic stress disorder (PTSD) is associated with increased risk of type 2 diabetes (T2D). Improvement in PTSD has been associated with improved self-reported physical health and hypertension; however, there is no literature, to our knowledge, on whether PTSD improvement is associated with T2D risk. Objective To examine whether clinically meaningful PTSD symptom reduction is associated with lower risk of T2D. Design, Setting, and Participants This retrospective cohort study examined Veterans Health Affairs medical record data from 5916 patients who received PTSD specialty care between fiscal years 2008 and 2012 and were followed up through fiscal year 2015. Eligible patients had 1 or more PTSD Checklist (PCL) scores of 50 or higher between fiscal years 2008 and 2012 and a second PCL score within the following 12 months and at least 8 weeks after the first PCL score of 50 or higher. The index date was 12 months after the first PCL score. Patients were free of T2D diagnosis or an antidiabetic medication use for 12 months before the index date and had at least 1 visit after the index date. Data analyses were completed during January 2019. Exposures Reduction in PCL scores during a 12-month period was used to define patients as those with a clinically meaningful improvement (≥20-point PCL score decrease) and patients with less or no improvement (<20-point PCL score decrease). Main Outcomes and Measures Incident T2D diagnosed during a 2- to 6-year follow-up. Results Medical records from a total of 1598 patients (mean [SD] age, 42.1 [13.4] years; 1347 [84.3%] male; 1060 [66.3%] white) were studied. The age-adjusted cumulative incidence of T2D was 2.6% among patients with a clinically meaningful PCL score decrease and 5.9% among patients without a clinically meaningful PCL score decrease (P = .003). After control for confounding, patients with a clinically meaningful PCL score decrease were significantly less likely to develop T2DM compared with those without a clinically meaningful decrease (hazard ratio, 0.51; 95% CI, 0.26-0.98). Conclusions and Relevance The findings suggest that clinically meaningful reductions in PTSD symptoms are associated with a lower risk of T2D. A decrease in PCL score, whether through treatment or spontaneous improvement, may help mitigate the greater risk of T2D in patients with PTSD.
Synaptonemal Complex Central Region Proteins Promote Localization of Pro-crossover Factors to Recombination Events During Caenorhabditis elegans Meiosis

Errors during meiosis are the leading cause of birth defects and miscarriages in humans. Thus, the coordinated control of meiotic events is critical for the faithful inheritance of the genome with each generation. Crossovers (COs) between homologous chromosomes are critical for meiotic chromosome segregation and form in the context of the synaptonemal complex (SC), a meiosis-specific structure that assembles between aligned homologs. During Caenorhabditis elegans meiosis, central region components of the SC (SYP proteins) are essential to repair double-strand DNA breaks (DSBs) as COs. Here, we investigate the relationships between the SYP proteins and conserved pro-CO factors by examining the immunolocalization of these proteins in meiotic mutants where SYP proteins are absent, reduced, or mislocalized. Although COs do not form in syp null mutants, pro-CO factors COSA-1, MSH-5, and ZHP-3 nevertheless colocalize at DSB-dependent sites during late prophase, reflecting an inherent affinity of these factors for DSB repair sites. In contrast, in mutants where SYP proteins are present but form aggregates or display abnormal synapsis, pro-CO factors consistently track with SYP-1 localization. Further, pro-CO factors usually localize to a single site per SYP-1 structure, even in SYP aggregates or in mutants where the SC forms between sister chromatids, suggesting that CO regulation occurs within these aberrant SC structures. Moreover, we find that the meiotic cohesin REC-8 is required to ensure that SC formation occurs between homologs and not sister chromatids. Taken together, our findings support a model in which SYP proteins promote CO formation by promoting the localization of pro-CO factors to recombination events within an SC compartment, thereby ensuring that pro-CO factors identify a recombination event within an SC structure and that CO maturation occurs only between properly aligned homologous chromosomes.
Oral and dental health status in patients with eating disorders in Madrid, Spain

Background The aim of the present study was to describe and compare the oral and dental health status of two groups, one diagnosed with eating disorders (EDs), and another group without this pathology, assessing the following oral manifestations: dental alterations, periodontal disorders, soft tissue disorders, non-stimulated salivary flow, and oral pH. Material and Methods This comparative transversal epidemiological study included 179 participants, of whom 59 were diagnosed with EDs (Eating Disorder Group: EDG) and 120 had no antecedents of EDs (No Eating Disorder Group: NEDG). All patients fulfilled the following inclusion criteria: women aged over 18 years, diagnosed with an ED by a specialist, patients who had undergone at least 1 year monitoring by the Clinical Nutrition Unit, and had not received any periodontal treatment during the previous 6 months. Both groups were homogeneous in terms of sex, age, education, and socioeconomic level. Oral exploration was performed, registering clinical variables, as well as sociodemographic and socioeconomic data, oral hygiene habits, and smoking. Statistical significance was established as p<0.05 (confidence level > 95%). Results The dental erosion (DE) was the most significative feature of dental alterations. The degree of DE was significantly greater in the EDG (p<0.001). A significant association between soft tissue lesions and EDs was found (p<0.001) A notable difference in non-stimulated salivary flow was found between the groups (p<0.001). No significant differences between the groups were found for periodontal status, dental caries, or oral hygiene practices. Conclusions On the basis of the results obtained, it is necessary to carry out oral/dental examination as soon as an ED is diagnosed with regular check-ups thereafter. Key words:Eating disorders, anorexia nervosa, bulimia nervosa, oral health, dental erosion.
Concussion Guidelines Step 2: Evidence for Subtype Classification

Abstract BACKGROUND Concussion is a heterogeneous mild traumatic brain injury (mTBI) characterized by a variety of symptoms, clinical presentations, and recovery trajectories. By thematically classifying the most common concussive clinical presentations into concussion subtypes (cognitive, ocular-motor, headache/migraine, vestibular, and anxiety/mood) and associated conditions (cervical strain and sleep disturbance), we derive useful definitions amenable to future targeted treatments. OBJECTIVE To use evidence-based methodology to characterize the 5 concussion subtypes and 2 associated conditions and report their prevalence in acute concussion patients as compared to baseline or controls within 3 d of injury. METHODS A multidisciplinary expert workgroup was established to define the most common concussion subtypes and their associated conditions and select clinical questions related to prevalence and recovery. A literature search was conducted from January 1, 1990 to November 1, 2017. Two experts abstracted study characteristics and results independently for each article selected for inclusion. A third expert adjudicated disagreements. Separate meta-analyses were conducted to do the following: 1) examine the prevalence of each subtype/associated condition in concussion patients using a proportion, 2) assess subtype/associated conditions in concussion compared to baseline/uninjured controls using a prevalence ratio, and 3) compare the differences in symptom scores between concussion subtypes and uninjured/baseline controls using a standardized mean difference (SMD). RESULTS The most prevalent concussion subtypes for pediatric and adult populations were headache/migraine (0.52; 95% CI = 0.37, 0.67) and cognitive (0.40; 95% CI = 0.25, 0.55), respectively. In pediatric patients, the prevalence of the vestibular subtype was also high (0.50; 95% CI = 0.40, 0.60). Adult patients were 4.4, 2.9, and 1.7 times more likely to demonstrate cognitive, vestibular, and anxiety/mood subtypes, respectively, as compared with their controls (P < .05). Children and adults with concussion showed significantly more cognitive symptoms than their respective controls (SMD = 0.66 and 0.24; P < .001). Furthermore, ocular-motor in adult patients (SMD = 0.72; P < .001) and vestibular symptoms in both pediatric and adult patients (SMD = 0.18 and 0.36; P < .05) were significantly worse in concussion patients than in controls. CONCLUSION Five concussion subtypes with varying prevalence within 3 d following injury are commonly seen clinically and identifiable upon systematic literature review. Sleep disturbance, a concussion-associated condition, is also common. There was insufficient information available for analysis of cervical strain. A comprehensive acute concussion assessment defines and characterizes the injury and, therefore, should incorporate evaluations of all 5 subtypes and associated conditions.
Ultrasound Assessment of Lung Aeration in Subjects Supported by Venovenous Extracorporeal Membrane Oxygenation

BACKGROUND: The value of ultrasound in assessing lung aeration of patients with ARDS who require venovenous extracorporeal membrane oxygenation (ECMO) has, to our knowledge, never been studied. The objective of the study was to evaluate by using ultrasound lung aeration at ECMO initiation and withdrawal in subjects with severe ARDS supported by venovenous ECMO. METHODS: Fifty subjects were included in this pilot retrospective study. The lung ultrasound aeration score (LUS) and respiratory variables were collected at ECMO initiation (T0) and ECMO withdrawal (T1). The LUS at T0 between the subjects who survived to ICU discharge and those who died in ICU was compared. The relationship between changes in LUS and changes in PaO2/FIO2 from T0 to T1 was assessed. RESULTS: The ICU mortality was 34%. The LUS at T0 did not differ between survivors and non-survivors (median 22 [interquartile range] {IQR} 19–26 vs median 24 [IQR, 19–28]; P = .60). From T0 to T1, the LUS decreased significantly in survivors (median 22 [IQR, 19–26] vs median 16 [IQR, 13–19]; P < .001), it decreased moderately in non-survivors who were weaned off ECMO (median 26 [24–29]) vs median 22 (IQR, 17–24), P = . 031), and remained stable in those who died during ECMO (median 25 [IQR, 19–29] vs median 25 [IQR, 23–31]; P = .22). Changes in PaO2/FIO2 were not related to changes in the LUS between T0 and T1. CONCLUSIONS: At the time of ECMO placement, the subjects who survived ARDS had aeration loss close to that observed in the subjects who did not survive. At the time of ECMO withdrawal, there was a significant improvement in lung aeration in the survivors, whereas a severe loss of lung aeration persisted in the non-survivors, although some were weaned off ECMO. Lung ultrasound provided a valuable tool for bedside assessment of lung aeration in subjects supported by ECMO.
Performance of laboratory tests used to measure blood phenylalanine for the monitoring of patients with phenylketonuria

Analysis of blood phenylalanine is central to the monitoring of patients with phenylketonuria (PKU) and age‐related phenylalanine target treatment‐ranges (0‐12 years; 120‐360 μmol/L, and >12 years; 120‐600 μmol/L) are recommended in order to prevent adverse neurological outcomes. These target treatment‐ranges are based upon plasma phenylalanine concentrations. However, patients are routinely monitored using dried bloodspot (DBS) specimens due to the convenience of collection. Significant differences exist between phenylalanine concentrations in plasma and DBS, with phenylalanine concentrations in DBS specimens analyzed by flow‐injection analysis tandem mass spectrometry reported to be 18% to 28% lower than paired plasma concentrations analyzed using ion‐exchange chromatography. DBS specimens with phenylalanine concentrations of 360 and 600 μmol/L, at the critical upper‐target treatment‐range thresholds would be plasma equivalents of 461 and 768 μmol/L, respectively, when a reported difference of 28% is taken into account. Furthermore, analytical test imprecision and bias in conjunction with pre‐analytical factors such as volume and quality of blood applied to filter paper collection devices to produce DBS specimens affect the final test results. Reporting of inaccurate patient results when comparing DBS results to target treatment‐ranges based on plasma concentrations, together with inter‐laboratory imprecision could have a significant impact on patient management resulting in inappropriate dietary change and potentially adverse patient outcomes. This review is intended to provide perspective on the issues related to the measurement of phenylalanine in blood specimens and to provide direction for the future needs of PKU patients to ensure reliable monitoring of metabolic control using the target treatment‐ranges.
Stem Cells from a Female Rat Model of Type 2 Diabetes/Obesity and Stress Urinary Incontinence Are Damaged by In Vitro Exposure to its Dyslipidemic Serum, Predicting Inadequate Repair Capacity In Vivo

Female stress urinary incontinence (FSUI) is prevalent in women with type 2 diabetes/obesity (T2D/O), and treatment is not optimal. Autograph stem cell therapy surprisingly has poor efficacy. In the male rat model of T2D/O, it was demonstrated that epigenetic changes, triggered by long-term exposure to the dyslipidemic milieu, led to abnormal global transcriptional signatures (GTS) of genes and microRNAs (miR), and impaired the repair capacity of muscle-derived stem cells (MDSC). This was mimicked in vitro by treatment of MDSC with dyslipidemic serum or lipid factors. The current study aimed to predict whether these changes also occur in stem cells from female 12 weeks old T2D/O rats, a model of FSUI. MDSCs from T2D/O (ZF4-SC) and normal female rats (ZL4-SC) were treated in vitro with either dyslipidemic serum (ZFS) from late T2D/O 24 weeks old female Zucker fatty (ZF) rats, or normal serum (ZLS) from 24 weeks old female Zucker lean (ZL) rats, for 4 days and subjected to assays for fat deposition, apoptosis, scratch closing, myostatin, interleukin-6, and miR-GTS. The dyslipidemic ZFS affected both female stem cells more severely than in the male MDSC, with some gender-specific differences in miR-GTS. The changes in miR-GTS and myostatin/interleukin-6 balance may predict in vivo noxious effects of the T2D/O milieu that might impair autograft stem cell (SC) therapy for FSUI, but this requires future studies.
The Moderation of Obesity Penalty on Job Market Outcomes by Employment Efforts

The current study explores the moderation of the relationship between obesity and labor market outcomes by direct employment efforts such as job hunting and job training of young adults. The study used data provided by the Korean Education and Employment Panel, a longitudinal data survey comprising middle and high school students from 2004 to 2015. Two dependent variables were assessed in this study: employment status and wage. The individual-level fixed effects were controlled. Despite having more direct employment efforts of either or both experience in job hunting and job training, compared to normal-weight counterparts, underweight men and overweight and obese women were reported to have a disadvantage in both dependent variables. Underweight men with job training experience were 12.02% less likely to be employed, while overweight and obese men had 6.80 times higher monthly wages when job training experience was accompanied compared to no such experience. For overweight and obese women, compared to that of their normal-weight counterparts, employment probability decreased by 4.78% per week-increase in job hunting, by 2.81% if any experience in job hunting. For underweight women, compared to that of their normal-weight counterparts, employment probability increased by 4.56 times per week-increase in job hunting and by 5.59 times if experience in job hunting, and by 6.96% if experience in job training. The results indicate that employment efforts do not fully moderate the presence of obesity penalty for labor market outcomes on those early in their careers.
Case of Smith-Magenis Syndrome.

with adequate therapeutic levels and good antiepileptic control. Extensive workup was pursued to rule out/in medical causation of this behavioral decompensation but was entirely unrevealing. Functional behavioral assessment failed to track any environmental trigger either. The patient has already been through multiple psychotropic trials with mediocre response at best; sleep has improved (5 hours), psychomotor activity a little bit lessened, but both aggressivity and self-injurious behaviors remained the same throughout, as reported by parents. He failed sequential trials on risperidone (2 mg/d) for 8 weeks and aripiprazole (7.5 mg/d) for 6 weeks with resultant hyperprolantinemia, tremors, and weight gain. Clonidine (300 μg/d), naltrexone (12.5 mg/d), and sertraline (20 mg/d) were all prematurely aborted, after 2 weeks, for presyncopy, transaminitis, and paradoxical agitation, respectively. Clonazepam (1.5 mg/d), for 3 weeks, helped with sleep but at the expense of sialorrhea. Given the sluggish clinical response and adverse effects, we opted to embark on a time-bound trial of tianeptine. Parents' consent was obtained beforehand. The outcome was remarkable spanning different target symptoms as depicted in Table 1. This has been achievedwith great tolerability andwell sustained over 30 weeks at the time of writing this report. No change of epileptic control was noted throughout the trial. Definitely, large well-conducted studies are needed to replicate this finding to define the real place of tianeptine in the ASD niche of psychopharmacology. Tianeptine remains a viable therapeutic option to deploy especially in the prepubertal ASD population only after exhausting other pharmacologic agents with stronger evidence base.
Molecular defects in thyroid dysgenesis

Congenital hypothyroidism (CH) is a neonatal endocrine disorder that might occur as itself or be associated to congenital extra‐thyroidal defects. About 85% of affected subjects experience thyroid dysgenesis (TD), characterized by defect in thyroid gland development. In vivo experiments on null mice paved the way for the identification of genes involved thyroid morphogenesis and development, whose mutation has been strongly associated to TD. Most of them are thyroid‐specific transcription factors expressed during early thyroid development. Despite the arduous effort in unraveling the genetics of TD in animal models, up to now these data have been discontinuously confirmed in humans and only 5% of TD have associated with known null mice‐related mutations (mainly PAX8 and TSHR). Notwithstanding, the advance in genetic testing represented by the next‐generation sequencing (NGS) approach is steadily increasing the list of genes whose highly penetrant mutation predisposes to TD. In this review we intend to outline the molecular bases of TD, summarizing the current knowledge on thyroid development in both mice and humans and delineating the genetic features of its monogenetic forms. We will also highlight current strategies to enhance the insight into the non‐Mendelian mechanisms of abnormal thyroid development.
Targeting heterotopic ossification by inhibiting activin receptor-like kinase 2 function

Heterotopic ossification (HO) refers to the appearance of osteoblasts in soft tissues under pathological conditions, such as trauma or infection. HO arises in an unpredictable way without any recognizable initiation. Activin receptor-like kinase-2 (ALK2) is a type I cell surface receptor for bone morphogenetic proteins (BMPs). The dysregulation of ALK2 signaling is associated with a variety of diseases, including cancer and HO. At present, the prevention and treatment of HO in the clinic predominantly includes nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates and other drug treatments, low-dose local radiation therapy and surgical resection, rehabilitation treatment and physical therapy. However, most of these therapies have adverse effects. These methods do not prevent the occurrence of HO. The pathogenesis of HO is not being specifically targeted; the current treatment strategies target the symptoms, not the disease. These treatments also cannot solve the fundamental problem of the occurrence of HO. Therefore, scholars have been working to develop targeted therapies based on the pathogenesis of HO. The present review focuses on advances in the understanding of the underlying mechanisms of HO, and possible options for the prevention and treatment of HO. In addition, the role of ALK2 in the process of HO is introduced and the progress made towards the targeted inhibition of ALK2 is discussed. The present study aims to offer a platform for further research on possible targets for the prevention and treatment of HO.
RETRACTED ARTICLE: Silencing of long noncoding RNA SBF2-AS1 inhibits proliferation, migration and invasion and contributes to apoptosis in osteosarcoma cells by upregulating microRNA-30a to suppress FOXA1 expression

Statement of Retraction We, the Editors and Publisher of the journal Cell Cycle, have retracted the following article: Jiang-Hua Dai, Wen-Zhou Huang, Chen Li, Jun Deng, Si-Jian Lin and Jun Luo. Silencing of long noncoding RNA SBF2-AS1 inhibits proliferation, migration and invasion and contributes to apoptosis in osteosarcoma cells by upregulating microRNA-30a to suppress FOXA1 expression. Cell Cycle. 2019;18(20):2727-2741. doi: 10.1080/15384101.2019. 1656478 Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors checked their data and confirmed there are fundamental errors present. Therefore, they have agreed to the retraction of this article. The authors apologise for this oversight. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.
Transplantation in adults with relapsed/refractory acute lymphoblastic leukemia who are treated with blinatumomab from a phase 3 study

Blinatumomab, a bispecific T‐cell‐engaging (BiTE®) immuno‐oncology therapy, demonstrated superior overall survival versus standard‐of‐care chemotherapy (SOC) in adults with relapsed/refractory B‐cell precursor acute lymphoblastic leukemia (R/R ALL) in the phase 3 TOWER study. Herein, the authors reported clinical features and outcomes for those patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after treatment with blinatumomab.