Miracle-dz/UniFAR-FTUs huggingface dataset:
Longer Duration of MAO-B Inhibitor Exposure is Associated with Less Clinical Decline in Parkinson's Disease: An Analysis of NET-PD LS1.

BACKGROUND Monoamine oxidase type B (MAO-B) inhibitors exhibit neuroprotective effects in preclinical models of PD but clinical trials have failed to convincingly demonstrate disease modifying benefits in PD patients. OBJECTIVE To perform a secondary analysis of NET-PD LS1 to determine if longer duration of MAO-B inhibitor exposure was associated with less clinical decline. METHODS The primary outcome measure was the Global Outcome (GO), comprised of 5 measures: change from baseline in the Schwab and England (ADL) scale, the 39-item Parkinson's Disease Questionnaire (PDQ-39), the UPDRS Ambulatory Capacity Scale, the Symbol Digit Modalities Test, and the most recent Modified Rankin Scale. A linear mixed model was used to explore the association between the cumulative duration of MAO-B inhibitor exposure and the GO, adjusting for necessary factors and confounders. Associations between MAO-B inhibitor exposure and each of the five GO components were then studied individually. RESULTS 1616 participants comprised the analytic sample. Mean observation was 4.1 (SD = 1.4) years, and 784 (48.5%) participants received an MAO-B inhibitor. The regression coefficient of cumulative duration of MAO-B inhibitor exposure (in years) on the GO was - 0.0064 (SE = 0.002, p = 0.001). Significant associations between duration of MAO-B inhibitor exposure and less progression were observed for ADL (p < 0.001), Ambulatory Capacity (p < 0.001), and the Rankin (p = 0.002). CONCLUSIONS Our analysis identified a significant association between longer duration of MAO-B inhibitor exposure and less clinical decline. These findings support the possibility that MAO-B inhibitors slow clinical disease progression and suggest that a definitive prospective trial should be considered.
Perceptual inhibition of emotional interference in children

Abstract In daily life, when a bee approaches us while we are sitting in the garden, we must pay attention to that threatening stimulus and give an appropriate response. However, if this bee approaches us while riding a bike, we must inhibit that distractor to avoid an accident. In this case, avoiding the interference of an emotional stimuli and continuing with the task should be preferential. In general, perceptual inhibition is responsible for controlling and suppressing the environmental distractions that interrupt the course of the realization of a goal. In this study, 435 children performed a modified flanker task with entirely irrelevant emotional and neutral stimuli in order to assess perceptual inhibition in contexts with high and low emotional salience. The results showed that entirely irrelevant distractors affected performance, but that there were no significant differences according to whether these distractors were emotionally salient or neutral. These results constitute a first approach to the problem of emotional interference in children considering the multidimensional approach of inhibition.
Anatomical study of presigmoid-retrolabyrinthine approach based on temporal bone high-resolution CT

Abstract Background: The surgical approach of acoustic neuroma includes translabyrinthine, transcranial fossa, suboccipital retrosigmoid sinus, and presigmoid retrolabyrinthine approach. Aims/Objective: To provide the anatomical basis for the surgical selection of presigmoid retrolabyrinthine approach by measuring the anatomical parameters of retrolabyrinthine space of the petrous bone by high-resolution CT. Material and methods: A retrospective study of 208 high-resolution CT (HRCT) images of 104 patients examined in our hospital were analyzed retrospectively. Forty-nine males and 55 females were included in this study. Lines were drawn on the HRCT to measure the morphological data for pre-operational assessment. Result: Morphological data were retracted from HRCT, for preoperational assessment. Conclusion and significance: Using the standard postprocessing images of temporal bone HRCT can predict the size of the retrolabyrinthine space and the degree of exposure to the inner auditory canal, providing an important anatomical index for the choice of presigmoid retrolabyrinthine approach.
Long Non-Coding RNAs in the Regulation of Gene Expression: Physiology and Disease

The identification of RNAs that are not translated into proteins was an important breakthrough, defining the diversity of molecules involved in eukaryotic regulation of gene expression. These non-coding RNAs can be divided into two main classes according to their length: short non-coding RNAs, such as microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). The lncRNAs in association with other molecules can coordinate several physiological processes and their dysfunction may impact in several pathologies, including cancer and infectious diseases. They can control the flux of genetic information, such as chromosome structure modulation, transcription, splicing, messenger RNA (mRNA) stability, mRNA availability, and post-translational modifications. Long non-coding RNAs present interaction domains for DNA, mRNAs, miRNAs, and proteins, depending on both sequence and secondary structure. The advent of new generation sequencing has provided evidences of putative lncRNAs existence; however, the analysis of transcriptomes for their functional characterization remains a challenge. Here, we review some important aspects of lncRNA biology, focusing on their role as regulatory elements in gene expression modulation during physiological and disease processes, with implications in host and pathogens physiology, and their role in immune response modulation.
Spermatogonial stem cells: updates from specification to clinical relevance

Human spermatogonia are target for exploration of adult stem cell characteristics and potential source for the development of therapeutic applications. Almost 50 years ago, Yves Clermont stated with regard to the nature of the true stem cells: 'there is the possibility that other classes of spermatogonia exist beside the three classes (Adark, Apale and type B)…; …we still know too little about the human spermatogonial stem cells'… This review seeks to provide current knowledge, focusing on different aspects of human spermatogonia, and novel information based on species comparisons with regard to the adaptation of their proliferative potential. Moreover, the objective is to provide an update on the state of the art concerning the potential use of human spermatogonia for clinical applications. Germ cell specification mechanisms and epigenetic as well as transcriptional features of primordial germ cells (PGC) and adult spermatogonia at the single-cell level are reviewed. Studies on single-cell analyses have been included as they provide hitherto unequaled resolution of the transcriptional profiles of unselected human testicular cells and, thereby, new insights into the molecular aspects of germ cell differentiation. Datasets on models of spermatogonial expansion were identified and spermatogonial turnover and lifetime sperm production rates in various species were calculated, based exclusively on studies employing the optical dissector approach. Finally, the state of the art concerning causes of impaired spermatogonial function and fertility preservation were comprehensively reviewed. RNA sequencing data from PGC and spermatogonia indicate that transcriptional heterogeneity is a feature of germ cells prior to differentiation. Based on these data as well as lineage-tracing studies it is now debated whether spermatogonia are a rather plastic population of undifferentiated germ cells with the stem cell niche being the regulatory unit for cell fate decisions. Based on our novel calculations we suggest that spermatogonia are adapted to the individual reproductive lifespan and that the life-long sperm output from a spermatogonium is balanced against the duration of a generation. Thereby, the risk of jeopardizing genome integrity is balanced against a maximized sperm output. With reference to Yves Clermont's statement, and based on recent datasets, we suggest that the question that needs to be answered is: 'Is there a true stem cell? ' or better 'Is there a population of various cells with distinct features serving as a stem cell pool? '. This review provides an update including novel views on various aspects of spermatogonial biology (from embryonic to adult stages). We consider this review relevant for all research scientists and clinicians dealing with fertility, spermatogenesis and fertility preservation.
Sex Moderates Relationships Among School Night Sleep Duration, Social Jetlag, and Depressive Symptoms in Adolescents

Social jetlag, a misalignment between sleep timing on the weekend and during the work week, is associated with depressive symptoms among adults across both sexes. A previous study found that later sleep timing was associated with depressive symptoms in women but not men. To date, however, no research has investigated whether the association between social jetlag and depression varies by sex among adolescents. The current study assessed self-reported sleep, depressive symptoms, and demographic information from 3058 adolescents (48% female, mean [SD] age 15.59 [0.77] years) from the age 15 wave of the Fragile Families and Child Wellbeing Study (FFCWS). Social jetlag was calculated as the absolute value of the midpoint of sleep on the weekend minus the midpoint of sleep during the school week. Depressive symptoms were measured through a modified 5-item version of the Center for Epidemiologic Studies Depression Scale (CES-D). We assessed whether the associations among sleep duration on school nights, social jetlag, and depressive symptoms were similar between male and female adolescents using multiple linear regression. In fully adjusted models, sex moderated the association between school night total sleep time and depressive symptoms (p < 0.001) and between social jetlag and depressive symptoms (p = 0.037). In females, but not in males, school night total sleep time was negatively associated with depressive symptoms (p < 0.001), whereas social jetlag (p < 0.001) was positively and independently associated with depressive symptoms. The results indicate the importance of regular sleep timing across the week and adequate sleep duration for the maintenance of optimal emotional health among female adolescents.
Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function Reduces Airway Bacteria and Inflammation in People with Cystic Fibrosis and Chronic Lung Infections

Rationale: Previous work indicates that ivacaftor improves cystic fibrosis transmembrane conductance regulator (CFTR) activity and lung function in people with cystic fibrosis and G551D‐CFTR mutations but does not reduce density of bacteria or markers of inflammation in the airway. These findings raise the possibility that infection and inflammation may progress independently of CFTR activity once cystic fibrosis lung disease is established. Objectives: To better understand the relationship between CFTR activity, airway microbiology and inflammation, and lung function in subjects with cystic fibrosis and chronic airway infections. Methods: We studied 12 subjects with G551D‐CFTR mutations and chronic airway infections before and after ivacaftor. We measured lung function, sputum bacterial content, and inflammation, and obtained chest computed tomography scans. Measurements and Main Results: Ivacaftor produced rapid decreases in sputum Pseudomonas aeruginosa density that began within 48 hours and continued in the first year of treatment. However, no subject eradicated their infecting P. aeruginosa strain, and after the first year P. aeruginosa densities rebounded. Sputum total bacterial concentrations also decreased, but less than P. aeruginosa. Sputum inflammatory measures decreased significantly in the first week of treatment and continued to decline over 2 years. Computed tomography scans obtained before and 1 year after ivacaftor treatment revealed that ivacaftor decreased airway mucous plugging. Conclusions: Ivacaftor caused marked reductions in sputum P. aeruginosa density and airway inflammation and produced modest improvements in radiographic lung disease in subjects with G551D‐CFTR mutations. However, P. aeruginosa airway infection persisted. Thus, measures that control infection may be required to realize the full benefits of CFTR‐targeting treatments.
Changes in Micronutrient Intake and Status, Diet Quality and Glucose Tolerance from Preconception to the Second Trimester of Pregnancy

Data on changes in dietary intake and related blood parameters throughout pregnancy are scarce; moreover, few studies have examined their association with glucose homeostasis. Therefore, we monitored intake of folate, vitamin B6, vitamin B12, vitamin D and iron, their status markers, and diet quality from preconception to the second trimester of pregnancy, and we examined whether these dietary factors were associated with glucose homeostasis during pregnancy. We included 105 women aged 18–40 years with a desire to get pregnancy or who were already <24 weeks pregnant. Women at increased gestational diabetes (GDM) risk were oversampled. Measurements were scheduled at preconception (n = 67), and 12 (n =53) and 24 weeks of pregnancy (n =66), including a fasting venipuncture, 75-grams oral glucose tolerance test, and completion of a validated food frequency questionnaire. Changes in micronutrient intake and status, and associations between dietary factors and glucose homeostasis, were examined using adjusted repeated measures mixed models. Micronutrient intake of folate, vitamin B6 and vitamin D and related status markers significantly changed throughout pregnancy, which was predominantly due to changes in the intake of supplements. Micronutrient intake or status levels were not associated with glucose homeostasis, except for iron intake (FE µg/day) with fasting glucose (β = −0.069 mmol/L, p = 0.013) and HbA1c (β = −0.4843 mmol, p = 0.002). Diet quality was inversely associated with fasting glucose (β = −0.006 mmol/L for each DHD15-index point, p = 0.017). It was shown that micronutrient intakes and their status markers significantly changed during pregnancy. Only iron intake and diet quality were inversely associated with glucose homeostasis.
Deepening trochleoplasty and medial patellofemoral ligament reconstruction normalize patellotrochlear congruence in severe trochlear dysplasia

Aims The aim of this study was to evaluate cartilaginous patellotrochlear congruence and patellofemoral alignment parameters after deepening trochleoplasty in severe trochlear dysplasia. Patients and Methods The study group comprised 20 patients (two male, 18 female; mean age 24 years (16 to 39)) who underwent deepening trochleoplasty and medial patellofemoral ligament (MPFL) reconstruction for the treatment of recurrent lateral patellar dislocation due to severe trochlear dysplasia (Dejour type B to D). Pre‐ and postoperative MRI investigations of the study group were compared with MRI data of 20 age‐ and gender‐matched control patients (two male, 18 female; mean age 27 years (18 to 44)) regarding the patellotrochlear contact ratio, patellotrochlear contact area, posterior patellar edge‐trochlear groove ratio, and patellar tilt. Results Preoperatively, all parameters in the study group indicated significant patellar malalignment, including a reduced patellotrochlear contact ratio (mean 0.38 (0.13 to 0.59) vs mean 0.67 (0.48 to 0.88); p < 0.001), reduced contact area (mean 128 mm2 (87 to 190) vs mean 183 mm2 (155 to 227); p < 0.001), increased patellar lateralization (mean 0.82 (0.55 to 1.0) vs mean 0.99 (0.93 to 1.1); p < 0.001) and increased patellar tilt (mean 25.8° (8.1° to 43.0°) vs mean 9.1° (0.5° to 16.8°); p < 0.001). Postoperatively, all parameters in the study group improved significantly and reached normal values compared with the control group. The patellotrochlear contact ratio increased to a mean of 0.63 (0.38 to 0.85) (p < 0.001), the contact area increased to a mean of 187 mm2 (101 to 255) (p < 0.001), the posterior patellar edge‐trochlear groove ratio improved to a mean of 0.96 (0.83 to 0.91) (p < 0.001), and the patellar tilt decreased to a mean of 13.9° (8.1° to 22.1°) (p < 0.001) postoperatively. Conclusion Deepening trochleoplasty and MPFL reconstruction normalized the patellotrochlear congruence and patellofemoral alignment parameters. Modifying the dysplastic trochlea involves approximating the trochlear morphology to the shape of the patella rather than inducing a patella and trochlea mismatch.
Mouse-Derived Isograft (MDI) In Vivo Tumor Models II. Carcinogen-Induced cMDI Models: Characterization and Cancer Therapeutic Approaches

In this second study, we established syngeneic in vivo models named carcinogen-induced mouse-derived isografts (cMDIs). Carcinogen-induced tumors were obtained during short-term observation (3–9 months) of CBA/J mice treated with various administration routes with 3-methylcholanthrene (MCA) or N-methyl-N-nitrosourea (MNU) as carcinogens. During necropsy, primary tumors and suspicious tissues were assessed macroscopically and re-transplanted (in PDX-like manner) into sex-matched syngeneic animals. Outgrowing tumors were histologically characterized as either spinocellular carcinoma (1/8) or various differentiated sarcomas (7/8). Growth curves of four sarcomas showed striking heterogeneity. These cMDIs were further characterized by flow cytometry, RNA sequencing, or efficacy studies. A variable invasion of immune cells into the tumors, as well as varying expression of tyrosine kinase receptor, IFN-γ signature, or immune cell population marker genes could be observed. Immune checkpoint inhibitor treatment (anti-mPD-1, anti-mCTLA-4, or a combination thereof) showed different responses in the various cMDI models. In general, cMDI models are carcinogen-induced tumors of low passage number that were propagated as tissue pieces in mice without any tissue culturing. Therefore, the tumors contained conserved tumor characteristics and intratumoral immune cell populations. In contrast to the previously described spontaneous MDI, carcinogen induction resulted in a greater number of individual but histologically related tumors, which were preferentially sarcomas.
A Bound for Error-Correcting Codes

This paper gives two new bounds for the code word length n which is required to obtain a binary group code of order 2k with mutual distance d between code words. These bounds are compared with previously known bounds, and are shown to improve upon them for certain ranges of k and d. Values of k and d are given for which one of these bounds can actually be achieved; in such cases, the structure of the resulting codes is shown to satisfy a certain condition.
Corticolimbic fast-tracking: enhanced multimodal integration in functional neurological disorder

Objective Some individuals with functional neurological disorder (FND) exhibit motor and affective disturbances, along with limbic hyper-reactivity and enhanced motor-limbic connectivity. Given that the multimodal integration network (insula, dorsal cingulate, temporoparietal junction (TPJ)) is implicated in convergent sensorimotor, affective and interoceptive processing, we hypothesised that patients with FND would exhibit altered motor and amygdalar resting-state propagation to this network. Patient-reported symptom severity and clinical outcome were also hypothesised to map onto multimodal integration areas. Methods Between-group differences in primary motor and amygdalar nuclei (laterobasal, centromedial) were examined using graph-theory stepwise functional connectivity (SFC) in 30 patients with motor FND compared with 30 healthy controls. Within-group analyses correlated functional propagation profiles with symptom severity and prospectively collected 6-month outcomes as measured by the Screening for Somatoform Symptoms Conversion Disorder subscale and Patient Health Questionnaire-15 composite score. Findings were clusterwise corrected for multiple comparisons. Results Compared with controls, patients with FND exhibited increased SFC from motor regions to the bilateral posterior insula, TPJ, middle cingulate cortex and putamen. From the right laterobasal amygdala, the FND cohort showed enhanced connectivity to the left anterior insula, periaqueductal grey and hypothalamus among other areas. In within-group analyses, symptom severity correlated with enhanced SFC from the left anterior insula to the right anterior insula and TPJ; increased SFC from the left centromedial amygdala to the right anterior insula correlated with clinical improvement. Within-group associations held controlling for depression, anxiety and antidepressant use. Conclusions These neuroimaging findings suggest potential candidate neurocircuit pathways in the pathophysiology of FND.
Astrocytic pyruvate carboxylation: Status after 35 years

The first two publications dealing with the question of the cellular localization of the enzyme pyruvate carboxylase (PC) which in the brain represents the most important metabolic pathway to allow anaplerosis of TCA cycle constituents were published in 1983 and 1985. Hence, 2018 marks the 35th anniversary of the notion based on the results of the publications provided above that PC‐catalyzed anaplerosis in the brain is an astrocytic process. This review will provide the background for investigating this enzymatic pathway as well as a discussion of cataplerosis, the degradation of products from anaplerosis, and the current status of the functional significance of pyruvate carboxylation in brain metabolism.
Renal resistive index: a case of mistaken identity.

Of all the measured parameters in nephrology, none is more misunderstood and misused than the renal resistive index ( RI ). Although it is used widely as a marker of renal pathology based on the assumption that structural changes in the kidney alter renal vascular resistance, the sensitivity and specificity of RI for this purpose are questionable,1 and its clinical use remains uncertain. Both theoretical and experimental analyses of the RI can explain why this is the case. RI is typically measured by Doppler sonography in an intrarenal artery and is the difference between the peak systolic and end-diastolic blood velocities divided by the peak systolic velocity. [Formula][1] (1) It was first introduced in the 1950s and its naming was unfortunate because it is actually a measure of pulsatility. In fact, the closely related index in which the denominator is the mean velocity rather than the peak systolic velocity is termed the pulsatility index. Ironically, renal vascular resistance is the 1 hemodynamic parameter that has the least if any influence on RI . A little mathematics will illustrate this point. Rearranging Equation 1 gives ! [Formula][2] (2) In the simplest analysis, velocity equals flow divided by lumen area ( LA ), and flow equals the difference in blood pressure (Δ P ) divided by vascular resistance ( R ), yielding ! [Formula][3] (3) Equation 2 then becomes ! [Formula][4] (4) Although pressure and lumen area clearly change during systole and diastole, resistance should not. Changes in pressure and flow can alter renal vascular resistance through the myogenic response and flow-mediated vasodilation, respectively, but the time constants for these responses are far greater than the duration of the cardiac cycle.2,3 Thus, renal vascular resistance does not vary between consecutive systoles and diastoles and Equation 4 becomes ! [Formula][5] (5) and RI is independent of vascular resistance. Stated more simply, the proportional effect of resistance on blood flow should … [1]: /embed/graphic-1.gif [2]: /embed/graphic-2.gif [3]: /embed/graphic-3.gif [4]: /embed/graphic-4.gif [5]: /embed/graphic-5.gif