Miracle-dz/UniFAR-FTUs huggingface dataset:
The shield of self-compassion: A buffer against disordered eating risk from physical appearance perfectionism

General perfectionistic tendencies as well as perfectionism focussed specifically on one’s physical appearance have been implicated as risk factors for disordered eating. This study extends previous research on protective factors by investigating self-compassion as a moderator of the relationship between both general and physical-appearance-perfectionism and disordered eating. A cross-sectional online survey assessed general perfectionism, physical-appearance-perfectionism, disordered eating symptoms, self-compassion and negative affect in female UK university students (N = 421). Results showed physical-appearance-perfectionism explained variance (15%) in disordered eating symptoms above general perfectionism and negative affect. Both perfectionistic concerns about and strivings for appearance perfection were significant unique predictors of disordered eating. Self-compassion moderated the relationship between both perfectionistic concerns and strivings of physical-appearance-perfectionism, but not general perfectionism, and disordered eating. This study suggests both perfectionistic concerns about and strivings for appearance perfection represent potential risk factors for disordered eating among female university students and that self-compassion may reduce their impact.
Continuous Glucose Monitoring Devices: Past, Present, and Future Focus on the History and Evolution of Technological Innovation

The concept of implantable glucose sensors has been promulgated for more than 40 years. It is now accepted that continuous glucose monitoring (CGM) increases quality of life by allowing informed diabetes management decisions as a result of more optimized glucose control. The focus of this article is to provide a brief overview of the CGM market history, emerging technologies, and the foreseeable challenges for the next CGM generations as well as proposing possible solutions in an effort to advance the next generation of implantable sensor.
Common misconceptions, hidden biases and modern challenges of dMRI tractography

The human brain is a complex and organized network, where the connection between regions is not achieved with single axons crisscrossing each other but rather millions of densely packed and well-ordered axons. Reconstruction from diffusion MRI tractography is only an attempt to capture the full complexity of this network, at the macroscale. This review provides an overview of the misconceptions, biases and pitfalls present in structural white matter bundle and connectome reconstruction using tractography. The goal is not to discourage readers, but rather to inform them of the limitations present in the methods used by researchers in the field in order to focus on what they can do and promote proper interpretations of their results. It also provides a list of open problems that could be solved in future research projects for the next generation of PhD students.
Time estimation exposure modifies cognitive aspects and cortical activity of attention deficit hyperactivity disorder adults

Abstract Aim This study investigated whether time-estimation task exposure influences the severity of Attention Deficit Hyperactivity Disorder (ADHD), as well as theta band activity in the dorsolateral prefrontal cortex and ventrolateral prefrontal cortex. Material and methods Twenty-two patients with ADHD participated in a crossover experiment with a visual time-estimation task under control conditions (without exposure to time estimation tasks) and experimental (thirty days exposure to time-estimation tasks) in association with electroencephalographic analysis of theta band. Results ADHD patients with thirty days of time-estimation task exposure presented a worse performance of the time-estimation task, as revealed by the measurements of the absolute error and relative error (p ≤ 0.05). However, our findings show the improvement of self-reported symptoms of attention, impulsivity, and emotional control in patients after the time-estimation task exposure (p = 0.0001). Moreover, the theta band oscillations in the right dorsolateral prefrontal cortex and in the ventrolateral prefrontal increased with thirty days of time-estimation task exposure (p ≤ 0.05). Conclusion We propose that the decrease in EEG theta power may indicate an efficient accumulation of temporal pulses, which could be responsible for the improvement in the patient cognitive aspects as demonstrated by the current study. Time-estimation task improves ADHD cognitive symptoms, with a substantial increase in cortical areas activity related to attention and memory, suggesting its use as a tool for cognitive timing function management and non-invasive therapeutic aid in ADHD.
Osseointegrated prostheses for the rehabilitation of amputees (OPRA): results and clinical perspective

ABSTRACT Introduction: Patients who undergo extremity amputation have historically used socket prosthetics to ambulate and perform daily functions; however, these prosthetics can be limited by poor terminal control and wear issues. In patients who have difficulty wearing their prostheses or with upper extremity amputations, osseointegrated implants may offer better function and quality of life. The Osseointegrated Prostheses for the Rehabilitation of Amputees (OPRA) was the first such device to become commercially available. Clinical trials have demonstrated benefit in patient gait, prosthetic use, and overall well-being, and new implants may be applied for various amputation levels. Areas covered: The OPRA, the most studied osseointegrated prosthetic stem, is reviewed, presenting indications, surgical procedure, complications, and results of clinical studies. Expert commentary: Osseointegration for amputees is an expanding field that has the potential to enhance rehabilitative potential. The OPRA implant is an effective device with a long life-span and low complication profile.
Suppressor of fused controls cerebellum granule cell proliferation by suppressing Fgf8 and spatially regulating Gli proteins

ABSTRACT Cerebellar granule cell (GC) development relies on precise regulation of sonic hedgehog (Shh)-Gli signalling activity, failure of which is associated with motor disorders and medulloblastoma. Mutations in the pathway regulator suppressor of fused (Sufu), which modulates Gli activators and repressors, are linked to cerebellar dysfunction and tumourigenesis. The mechanism by which Sufu calibrates Shh signalling in GCs is unknown. Math1-Cre-mediated deletion of Sufu in mouse GC progenitors (GCPs) demonstrated that Sufu restricts GCP proliferation and promotes cell cycle exit, by promoting expression of Gli3R and suppressing Gli2 levels. Sufu is also required to promote a high threshold of pathway activity in GCPs. Remarkably, central cerebellar lobules are more deleteriously impacted by Sufu deletion, but are less sensitive to downstream genetic manipulations to reduce Gli2 expression or overexpress a Gli3R mimic, compared with anterior lobules. Transcriptome sequencing uncovered new Sufu targets, especially Fgf8, which is upregulated in Sufu-mutant GCPs. We demonstrate that Fgf8 is necessary and sufficient to drive Sufu-mutant GCP proliferation. This study reveals new insights into the spatial and temporal regulation of cerebellar Shh-Gli signalling, while uncovering new targets, such as Fgf8. Summary: Granule neuron proliferation is regulated at distinct rates in different cerebellar regions through spatially defined interactions of Sufu with Gli activator and repressor proteins, and through the repression of Fgf8 signalling.
Modulation of ABCG2 surface expression by Rab5 and Rab21 to overcome multidrug resistance in cancer cells

Abstract Human ABCG2 is a half transporter implicated in drug efflux and development of multidrug resistance (MDR) in cancer cells. Here we present the regulatory effects of early endocytic Rab GTPases, Rab5A and Rab21 on ABCG2. ABCG2 was stably expressed in MCF-7 cells (MCF-7/G2). Rab5A and Rab21 were manipulated in MCF-7/G2 cells by co-expression or siRNA knockdown and their effect on ABCG2-mediated drug efflux was quantified using fluorescence microscopy. The ectopically expressed ABCG2 was predominantly confined to the plasma membrane and was capable of drug efflux. Expression of constitutively active Rab5A-Q79L mutant in MCF-7/G2 cells decreased the cell surface expression of ABCG2, resulting in the reduction of ABCG2-mediated drug efflux. In contrast, expression of inactive Rab5A-S34N mutant enhanced cell surface expression of ABCG2 and drug efflux. Moreover, reduction in endogenous Rab21 levels in MCF-7/G2 cells by siRNA knockdown, increased the surface localisation of ABCG2. Consequently, efflux ability of cells increased and intracellular retention of doxorubicin and Hoechst 33342; substrates of ABCG2, decreased significantly. These findings suggest that Rab5A and Rab21 play important roles in regulating ABCG2 surface localisation and turnover and can be exploited as a potential strategy to overcome MDR in cancer cells.
Effects of soybean hulls and lignocellulose on performance, nutrient digestibility, microbial metabolites and immune response in piglets

ABSTRACT A feeding trial with 96 piglets was performed to investigate the effect of added soluble (SDF) and insoluble dietary fibre (IDF) sources on performance, apparent total tract digestibility (ATTD), concentration of microbial metabolites and pro-inflammatory marker genes as indicators for immune response. Piglets were allotted to four treatments (T): T1 control, T2 with soybean hulls (IDF/SDF: 8.35) and T3 and T4 with two different kinds of lignocellulose (IDF/SDF: >70). Diets were isofibrous for their value of total dietary fibre to underline the particular physicochemical properties of fibre sources. No differences were observed regarding average daily feed intake, average daily gain (ADG), feed conversion ratio and body weight, while T2 expressed higher ADG in the grower phase (day 14-54) vs. T3. Soybean hulls (T2) resulted in higher ATTD of dry matter and organic matter vs. T4; ether extract vs. T1 and neutral detergent fibre vs. T1, T2 and T3. The concentration of short chain fatty acids did not differ among treatments. Ileal digesta in T2 generated higher amounts of cadaverine vs. T3 and T4, likewise T1 vs. T4. Finally, no impact on immune response was detected. In conclusion, soybean hulls affected ATTD positively and lignocellulose prevented the formation of cadaverine, no overall direct response of SDF nor of IDF for the inclusion level were observed.
Prevalence of Iron Deficiency (ID) without anemia in the general population presenting to primary care clinics: a cross-sectional study

ABSTRACT Objectives There are no evidence-based recommendations to screen for iron deficiency in non-anemic patients, even though symptoms may be present. The aim of this study is to measure the prevalence of iron deficiency (ID) without anemia in the general population aged 18–50 presenting to primary care along with the incidence and time to develop anemia in the iron-deficient population. Methods A single-center retrospective chart review of patients who presented to family medicine clinics between June 2010 and March 2018 at the American University of Beirut Medical Center (AUBMC). Adults 18–50 years old, who had a CBC and ferritin levels ordered with the proximity of maximum four weeks, with an absence of current or previously documented anemia (back to 2007) defined as MCV less than 80 or hemoglobin (Hb) less than 12 in females and 13 in males were included. ID was defined as serum ferritin level below 30 ng/mL. Results A total of 1,784 adults aged 18–50 years were included. The prevalence of iron deficiency without anemia was 57.5% [95% confidence interval, 55.08% to 59.92%] among females and 7.6% [95% confidence interval, 3.77% to 11.43%] among males. Iron deficiency without anemia was significantly associated with the level of hemoglobin (Hb) among females (Chi-square, p < 0.001). Overt iron deficiency anemia developed within the 5 years follow up in 14% of females and 0.5% of males. There was a statistically significant association between iron deficiency and menorrhagia (Chi-square, P-value = 0.004), dizziness (Chi-square, P-value = 0.018), dyspnea/shortness of breath (Chi-square, P-value = 0.020), polycystic ovarian syndrome (Chi-square, P-value = 0.0256) and rheumatoid arthritis (Chi-square, P-value = 0.00278). Conclusion Iron deficiency without anemia in childbearing females is common but only one-seventh of females developed anemia within 5 years. Guidelines should consider incorporating ferritin levels with CBC in the workup of patients presenting with symptoms suggestive of iron deficiency or anemia.
Allosteric inhibitors of Mycobacterium tuberculosis tryptophan synthase

Global dispersion of multidrug resistant bacteria is very common and evolution of antibiotic‐resistance is occurring at an alarming rate, presenting a formidable challenge for humanity. The development of new therapeuthics with novel molecular targets is urgently needed. Current drugs primarily affect protein, nucleic acid, and cell wall synthesis. Metabolic pathways, including those involved in amino acid biosynthesis, have recently sparked interest in the drug discovery community as potential reservoirs of such novel targets. Tryptophan biosynthesis, utilized by bacteria but absent in humans, represents one of the currently studied processes with a therapeutic focus. It has been shown that tryptophan synthase (TrpAB) is required for survival of Mycobacterium tuberculosis in macrophages and for evading host defense, and therefore is a promising drug target. Here we present crystal structures of TrpAB with two allosteric inhibitors of M. tuberculosis tryptophan synthase that belong to sulfolane and indole‐5‐sulfonamide chemical scaffolds. We compare our results with previously reported structural and biochemical studies of another, azetidine‐containing M. tuberculosis tryptophan synthase inhibitor. This work shows how structurally distinct ligands can occupy the same allosteric site and make specific interactions. It also highlights the potential benefit of targeting more variable allosteric sites of important metabolic enzymes.
Genetic Basis of De Novo Appearance of Carotenoid Ornamentation in Bare-Parts of Canaries

Unlike wild and domestic canaries (Serinus canaria), or any of the three dozen species of finches in genus Serinus, the domestic urucum breed of canaries exhibits bright red bills and legs. This novel bare-part coloration offers a unique opportunity to understand how leg and bill coloration evolve in birds. To identify the causative locus, we resequenced the genome of urucum canaries and performed a range of analyses to search for genotype-to-phenotype associations across the genome. We identified a nonsynonymous mutation in the gene BCO2 (beta-carotene oxygenase 2, also known as BCDO2), an enzyme involved in the cleavage and breakdown of full-length carotenoids into short apocarotenoids. Protein structural models and in vitro functional assays indicate that the urucum mutation abrogates the carotenoid cleavage activity of BCO2. Consistent with the predicted loss of carotenoid cleavage activity, urucum canaries had increased levels of full-length carotenoid pigments in bill tissue and a significant reduction in levels of carotenoid cleavage products (apocarotenoids) in retinal tissue compared to other breeds of canaries. We hypothesize that carotenoid-based bare-part coloration might be readily gained, modified, or lost through simple switches in the enzymatic activity or regulation of BCO2 and this gene may be an important mediator in the evolution of bare-part coloration among bird species.
Powerful Tools for Caregivers: Improving Self-Care and Self-Efficacy of Family Caregivers

Americans provide care to persons aged 65 and older whoneed help with everyday activities.A 1997 report by theNational Alliance for Caregivers and AARP estimates that22.4 million households are involved in caring for personsaged 50 and older, including more than 5 million house-holds caring for someone with dementia.
Attenuating apoptosis in Chinese hamster ovary cells for improved biopharmaceutical production

Chinese hamster ovary (CHO) cells are the predominant host cell line for the production of biopharmaceuticals, a growing industry currently worth more than $188 billion USD in global sales. CHO cells undergo programmed cell death (apoptosis) following different stresses encountered in cell culture, such as substrate limitation, accumulation of toxic by‐products, and mechanical shear, hindering production. Genetic engineering strategies to reduce apoptosis in CHO cells have been investigated with mixed results. In this review, a contemporary understanding of the real complexity of apoptotic mechanisms and signaling pathways is described; followed by an overview of antiapoptotic cell line engineering strategies tested so far in CHO cells.
From Paris to Montreal: disease regression is common during long term follow-up of paediatric Crohn’s disease

Abstract Introduction: Paediatric Crohn’s disease (PCD) often presents with extensive and a frequent pan-enteric phenotype at onset. However, its long term evolution into adulthood, especially since the widespread use of biological agents, is not well characterised. We conducted a single centre cohort study of all PCD patients transitioned to adult care to assess the long term disease evolution in the era of biologic therapy. Methods: We conducted a retrospective observational, study of all PCD patients who were subsequently transferred to the care of an adult gastroenterology unit and had a minimum follow up of 2 years. We examined the case notes for evolution of disease location and behaviour. Disease location and behaviour was characterised using Paris classification at diagnosis and Montreal classification at last follow-up. In addition, we examined variables associated with complicated disease behaviour and the need for CD related intestinal resection. Results: In total, 132 patients were included with a median age at diagnosis of 13 (IQR 11–14) and a median follow up of 11 years (range 4–14). At diagnosis, 23 (17.4%), 39 (29.6%) and 70 (53%) patients had ileal, colonic and ileocolonic disease respectively. In addition, 31 (23.5%) patients had L4a or L4b disease at diagnosis (proximal or distal to the ligament of treitz respectively) and 13 patients (9.8%) had both whilst 27 (20.4%) patients had perianal disease. At diagnosis, 27 (20.4%) patients had complicated disease behaviour but 83 (62.9)% of patients had an extensive ‘pan-enteric’ phenotype. Of these patients only 55 (66.3%) retained the pan-enteric phenotype at last follow-up (p = .0002). Disease extension was noted in 25 (18.9%) of patients and regression was noted in 47 (35.6%) of patients, whereas upper GI disease was noted in significantly fewer patients at last follow-up (21, 15.9%) (p = .0001). More patients had complicated disease behaviour (46 patients, 34.9%, p = .0018) at last follow-up. There was a high exposure to both thiopurines 121 (91.7%) and biologics 84 (63.6%). The cumulative probability (95% CI) of surgery was 0.05 (0.02, 0.11) at 1 year, 0.17 (0.11, 0.24) at 3 years and 0.22 (0.15, 0.30) at 5 years. Neither disease location nor behaviour were associated with the need for intestinal resectional surgery. Conclusions: Over the course of an extended follow-up period, there appeared to be changes in both disease location and behaviour in PCD. Interestingly, a significant proportion of patients had disease involution which may be related to a high rate of exposure to thiopurines and biologics. We were unable to identify any variables associated with complicated disease course or the need for intestinal surgery.
Tubulin polyglutamylation is a general traffic-control mechanism in hippocampal neurons

ABSTRACT Neurons are highly complex cells that heavily rely on intracellular transport to distribute a range of functionally essential cargoes within the cell. Post-translational modifications of tubulin are emerging as mechanisms for regulating microtubule functions, but their impact on neuronal transport is only marginally understood. Here, we have systematically studied the impact of post-translational polyglutamylation on axonal transport. In cultured hippocampal neurons, deletion of a single deglutamylase, CCP1 (also known as AGTPBP1), is sufficient to induce abnormal accumulation of polyglutamylation, i.e. hyperglutamylation. We next investigated how hyperglutamylation affects axonal transport of a range of functionally different neuronal cargoes: mitochondria, lysosomes, LAMP1 endosomes and BDNF vesicles. Strikingly, we found a reduced motility for all these cargoes, suggesting that polyglutamylation could act as a regulator of cargo transport in neurons. This, together with the recent discovery that hyperglutamylation induces neurodegeneration, makes it likely that perturbed neuronal trafficking could be one of the central molecular causes underlying this novel type of degeneration. This article has an associated First Person interview with the first author of the paper. Summary: The tubulin modification polyglutamylation regulates the overall motility of different types of transport cargoes in axons of hippocampal neurons, and is thus likely to act as a general transport control mechanism in neurons.
Screening for obstructive lung disease in hospitalized psychiatric patients

Abstract Objective: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of mortality worldwide and it remains under-diagnosed. Unrecognized somatic disease contributes significantly to the observed increased mortality rate in patients with psychiatric diseases. Aims: To investigate whether screening with spirometry and simple questions on respiratory symptoms were efficacious in identifying previously unknown cases of COPD and/or asthma in patients admitted to psychiatric wards. Methods: In this observational cohort study, we included hospitalized psychiatric patients in2013. All were assessed with handheld spirometry, medical history and completion of a simple, short questionnaire on respiratory symptoms, the COPD assessment test (CAT questionnaire). Results: In total, 106 patients were screened and 45 patients (age: median 45, range 19–75, 43% female gender) were included whereas 61 patients (age: median 42, range 19–73) 34% female gender) were excluded. Prior to screening three patients (6.5%) reported having a diagnosis of COPD whereas eight patients (17%) reported having a diagnosis of asthma. Six new cases were diagnosed with COPD and four new cases with asthma. The number needed to screen to find one new case was 3.4 (total cohort 4.5). Conclusion: We present a simple study where the patients are screened for obstructive lung disease with a handheld spirometry and a questionnaire on respiratory symptoms. Number needed to screen is low at 3.4–4.5. In all, 10 new cases of obstructive lung disease were diagnosed. This study illustrates that screening for COPD and asthma is feasible even in a psychiatric population.