Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic strategies for social anxiety disorder: where are we now?

ABSTRACT Introduction: Classical well-established treatments of social anxiety disorder (SAD) are now complemented by more recent therapeutic strategies. This review aims to summarize available therapies for SAD and discuss recent evidence-based findings on the management of this disorder. Areas covered: Recent guidelines recommend psychotherapy, particularly cognitive-behavioral therapy (CBT), and pharmacotherapy, as first-line treatments of patients with SAD, without a clear superiority of one option over the other. CBT includes classical approaches such as in vivo exposure to social situations and cognitive therapy, but new modalities and techniques have been recently developed: third-wave approaches, internet-delivered therapy, virtual reality exposure, and cognitive bias modification. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors have been also extensively studied and shown to be effective in SAD. Two alternative strategies have been developed to treat SAD with disappointing results: cognitive bias modification, and pharmacological augmentation of psychotherapy using D-cycloserine during exposure sessions. Expert opinion: Personalized treatments for SAD patients are now available. Innovative strategies such as online psychotherapy and virtual reality exposure are useful alternatives to CBT and SSRIs. Future developments and optimization of attention bias modification and of pharmacological augmentation of psychotherapy can be promising.
Longitudinal emotional process among adolescent soccer player in intensive training centre

ABSTRACT Grounded in Lazarus’s (1999) cognitive motivational relational theory of emotions, this study aimed to explore longitudinal relationships between appraisals, everyday emotions related to the competitive environment and emotional regulation strategies during a competitive season. Forty adolescent soccer players (Mage = 15.8) involved in an intensive training centre from a professional club voluntarily participated to the study. A series of hierarchical linear modelling analyses were conducted upon the 9 measurement times to: (a) examine the relationships between appraisals (threat, challenge, loss), pleasant (happiness, excitement) and unpleasant (anxiety, dejection, anger) emotions, and emotional regulation strategies (adaptive and less adaptive); and (b) ascertain whether the relationships between appraisals and emotions were mediated by emotion regulation strategies. The results of the random coefficient regression models showed: (a) positive relationships between challenge appraisal, adaptive emotion regulation, and pleasant emotions as well as between threat and loss appraisals, less adaptive emotion regulation and unpleasant emotions; and (b) mediating effects of emotional regulation strategies in the appraisals – emotions relationships. As a whole, this study furthered knowledge base about the competitive environment in showing that appraisals, emotion regulation and emotions are intertwined psychological constructs in a dynamic relationship allowing athletes to continuously adjust to their constantly changing everyday demands.
Perceptual Consequences of Early-Onset Hereditary Hearing Loss in the Belgian Waterslager Canary (Serinus Canarius)

Title of Document: PERCEPTUAL CONSEQUENCES OF EARLY-ONSET HEREDITARY HEARING LOSS IN THE BELGIAN WATERSLAGER CANARY (SERINUS CANARIUS) Amanda M. Lauer, Doctor of Philosophy, 2006 Directed By: Professor Robert J. Dooling, Department of Psychology Belgian Waterslager canaries (BWS) are bred for a distinctive low-pitched song that includes sounds that are thought to resemble water. This strain of canary has been used in multiple neurobiological and behavioral studies of song learning. These birds have a permanent hereditary hearing loss associated with missing and abnormal hair cells. The hearing deficit develops after hatch, but is present when the birds learn their song. The manner in which these birds process complex sounds indisputably affects the content of their vocalizations; however, no studies have looked at BWS canaries’ ability to detect and discriminate sounds other than detection of pure tones in quiet. Thus, the BWS canary provides a unique opportunity to investigate the relationship between the form and function of an auditory system involved in vocal learning. Here I describe a series of psychoacoustic experiments that investigate differences in masking, discrimination, temporal processing, and perception of song elements in BWS canaries and normal-hearing non-BWS canary strains. Spectral and temporal studies of masking showed that frequency resolution and the phase response of the basilar papilla are impaired in BWS canaries. Frequency discrimination was superb at low frequencies, but worse than normal at high frequencies in BWS canaries. Duration and intensity discrimination was not adversely affected by the hearing loss. Temporal resolution was normal or better than normal under some conditions in BWS canaries. Despite the hearing loss, BWS canaries are able to accurately discriminate among strain-specific song syllables as well as syllables of other canary strains. In fact, BWS canaries are actually better than non-BWS canaries at discriminating among BWS canary syllables. These perceptual predispositions in BWS canaries are presumably related to the structural abnormalities of the inner ear, and are likely to play a role in song learning and song maintanence by enhancing the birds’ ability to attend to important acoustic features that are characteristic of BWS vocalizations. PERCEPTUAL CONSEQUENCES OF EARLY-ONSET HEREDITARY HEARING LOSS IN THE BELGIAN WATERSLAGER CANARY (SERINUS CANARIUS)
Isolation of five Enterobacteriaceae species harbouring blaNDM-1 and mcr-1 plasmids from a single paediatric patient

In Argentina, NDM metallo-β-lactamase was first reported in 2013. By now, it has disseminated throughout the country in diverse Gram negative bacteria. Here, we report the case of a paediatric patient that underwent a 1-year hospitalisation due to erythrodermic psoriasis in 2014 and received multiple antimicrobial treatments. During his stay, five isolates were obtained from rectal swabs (rs) or blood culture (bc) suspicious of carbapenemase production: a K. quasipneumoniae subsp. quasipneumoniae (rs), Citrobacter freundii (rs), Escherichia coli (bc), Enterobacter cloacae (rs), and a Serratia marcescens (bc). The isolates were studied with broth microdilution, biparental conjugation and plasmid and whole genome sequencing (Illumina). All isolates harboured an 138,998-bp type 1 IncC plasmid that carried blaNDM-1, bleMBL, blaCMY-6, rmtC, aac(6’)-Ib, and sul1 resistance genes. Additionally, the blaNDM-plasmids contained ISKpn8 an insertion sequence previously described as associated only to blaKPC. One isolate, a colistin-resistant E. coli, also carried a mcr-1-containing an IncI2 plasmid, which did not harbour additional resistance. The whole genome of K. quasipneumoniae subsp. quasipneumoniae isolate was fully sequenced. This isolate harboured, additionally to blaNDM, three plasmid-mediated quinolone resistance genes: qnrB4, qnrB52 and aac(6’)-Ib-cr1. The E. cloacae isolate also harboured qnrA1. These findings alert to the underestimated horizontal dissemination of multidrug-resistant plasmids limiting treatment options with last resort antimicrobials.
Multiple Cycle-in-Cycle Generative Adversarial Networks for Unsupervised Image Super-Resolution

With the help of convolutional neural networks (CNN), the single image super-resolution problem has been widely studied. Most of these CNN based methods focus on learning a model to map a low-resolution (LR) image to a high-resolution (HR) image, where the LR image is downsampled from the HR image with a known model. However, in a more general case when the process of the down-sampling is unknown and the LR input is degraded by noises and blurring, it is difficult to acquire the LR and HR image pairs for traditional supervised learning. Inspired by the recent unsupervised image-style translation applications using unpaired data, we propose a multiple Cycle-in-Cycle network structure to deal with the more general case using multiple generative adversarial networks (GAN) as the basis components. The first network cycle aims at mapping the noisy and blurry LR input to a noise-free LR space, then a new cycle with a well-trained <inline-formula> <tex-math notation="LaTeX">$\times 2$ </tex-math></inline-formula> network model is orderly introduced to super-resolve the intermediate output of the former cycle. The number of total cycles depends on the different up-sampling factors (<inline-formula> <tex-math notation="LaTeX">$\times 2$ </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">$\times 4$ </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">$\times 8$ </tex-math></inline-formula>). Finally, all modules are trained in an end-to-end manner to get the desired HR output. Quantitative indexes and qualitative results show that our proposed method achieves comparable performance with the state-of-the-art supervised models.
Long non‐coding subgenomic flavivirus RNAs have extended 3D structures and are flexible in solution

Most mosquito‐borne flaviviruses, including Zika virus (ZIKV), Dengue virus (DENV), and West Nile virus (WNV), produce long non‐coding subgenomic RNAs (sfRNAs) in infected cells that link to pathogenicity and immune evasion. Until now, the structural characterization of these lncRNAs remains limited. Here, we studied the 3D structures of individual and combined subdomains of sfRNAs, and visualized the accessible 3D conformational spaces of complete sfRNAs from DENV2, ZIKV, and WNV by small angle X‐ray scattering (SAXS) and computational modeling. The individual xrRNA1s and xrRNA2s adopt similar structures in solution as the crystal structure of ZIKV xrRNA1, and all xrRNA1‐2s form compact structures with reduced flexibility. While the DB12 of DENV2 is extended, the DB12s of ZIKV and WNV are compact due to the formation of intertwined double pseudoknots. All 3′ stem‐loops (3′SLs) share similar rod‐like structures. Complete sfRNAs are extended and sample a large conformational space in solution. Our work not only provides structural insight into the function of flavivirus sfRNAs, but also highlights strategies of visualizing other lncRNAs in solution by SAXS and computational methods.
Transcriptome dynamics of long noncoding RNAs and transcription factors demarcate human neonatal, adult, and human mesenchymal stem cell‐derived engineered cartilage

The engineering of a native‐like articular cartilage (AC) is a long‐standing objective that could serve the clinical needs of millions of patients suffering from osteoarthritis and cartilage injury. An incomplete understanding of the developmental stages of AC has contributed to limited success in this endeavor. Using next generation RNA sequencing, we have transcriptionally characterized two critical stages of AC development in humans—that is, immature neonatal and mature adult, as well as tissue‐engineered cartilage derived from culture expanded human mesenchymal stem cells. We identified key transcription factors (TFs) and long noncoding RNAs (lncRNAs) as candidate drivers of the distinct phenotypes of these tissues. AGTR2, SCGB3A1, TFCP2L1, RORC, and TBX4 stand out as key TFs, whose expression may be capable of reprogramming engineered cartilage into a more expandable and neonatal‐like cartilage primed for maturation into biomechanically competent cartilage. We also identified that the transcriptional profiles of many annotated but poorly studied lncRNAs were dramatically different between these cartilages, indicating that lncRNAs may also be playing significant roles in cartilage biology. Key neonatal‐specific lncRNAs identified include AC092818.1, AC099560.1, and KC877982. Collectively, our results suggest that tissue‐engineered cartilage can be optimized for future clinical applications by the specific expression of TFs and lncRNAs.
The Impact of HIV/AIDS on Children: Lights and Shadows in the "Successful Case" of Uganda*

This chapter analyses the socio-economic impacts of HIV/AIDS on children in Uganda, with specific focus on their health, education and social welfare, and on the current and future policy/program responses in the field of prevention, treatment and mitigation. Ever since the first HIV/AIDS case was diagnosed in Uganda in 1982, over 2.2 million people have been infected and about 838,000 have died, leaving behind close to 1.7 million AIDS orphans. HIV/AIDS has unleashed severe impacts on children and the country as a whole, notably, the straining of the health system, socio-economic disruptions, reductions in productive capacity, increase in AIDS orphans, with related problems such as street children and child abuse, and it has also exacerbated poverty at household and community levels. Trends show a general decline in infections but these are no cause for relaxation in the fight. Uganda was one of the first countries to suffer the brunt of the scourge. Fortunately, deliberate measures have been taken at the political, medical and civil levels to deal with the crisis in a coherent manner. The study clearly finds that there has been good attempt to provide a working policy framework for the HIV/AIDS control but there are shortcomings in design of response particularly for the case of children. However, Uganda still faces the challenges of inadequate information and fact pertaining to the prevalence of HIV/AIDS infection as well as determining the effectiveness of alternative strategies in interrupting or completely stopping the further spread of HIV/AIDS.
Results of Surgical Treatment of Leg Shaft Mal-Union in Adults at CHU-Brazzaville. A Five Case Retrospective Observation

Objective: To assess the anatomical and functional results after surgical management of leg shaft mal-union in African environment. Methodology: This was a retrospective study of patients operated for leg mal-union at Brazzaville University Hospital between January 2014 and December 2018. The studied parameters were epidemiological and therapeutic. The anatomical evaluation was based on the quality of the leg’s relaxation and bone healing, which was indicated on standard X-rays. The functional evaluation was based on Thorensen’s criteria. Results: Five patients were selected for this study. There were 3 men and 2 women with an average age of 39 years with extremes of 27 and 59 years. Three patients were treated with locked intramedullary nail and 2 patients with screwed plate. At an average follow-up of 9 months, bone consolidation was achieved in all our patients. The average consolidation time was 4 months (range 3 to 7 months). We noted 1 case of residual mal-union in valgus (5°) on screwed plate and 1 case of valgus angulation (5°) on locked intramedullary nail. Walking was considered normal in 3 patients. The wearing of a 2 cm heel was indicated in 2 patients. According to Thorensen’s criteria, the overall results were considered good in 3 patients and average in 2 patients. Conclusion: Leg shaft mal-union are likely to cause serious functional issues. Their treatment is strictly surgical and osteotomy is the only management option to restore the anatomy of the deformed limb.
Long‐term follow‐up of two randomized trials comparing laparoscopic Nissen 360° with anterior 90° partial fundoplication

The side‐effects of Nissen fundoplication have led to modifications, including partial fundoplications such as an anterior 90° wrap. Five‐year follow‐up of two randomized trials suggested fewer side‐effects following anterior 90° partial fundoplication, but better reflux control after Nissen fundoplication. However, longer‐term outcomes have not been reported. This study combined data from previous trials to determine 10‐year outcomes.
Anthracyclines Suppress Both NADPH Oxidase- Dependent and -Independent NETosis in Human Neutrophils

Neutrophil extracellular traps (NETs) are cytotoxic DNA-protein complexes that play positive and negative roles in combating infection, inflammation, organ damage, autoimmunity, sepsis and cancer. However, NETosis regulatory effects of most of the clinically used drugs are not clearly established. Several recent studies highlight the relevance of NETs in promoting both cancer cell death and metastasis. Here, we screened the NETosis regulatory ability of 126 compounds belonging to 39 classes of drugs commonly used for treating cancer, blood cell disorders and other diseases. Our studies show that anthracyclines (e.g., epirubicin, daunorubicin, doxorubicin, and idarubicin) consistently suppress both NADPH oxidase-dependent and -independent types of NETosis in human neutrophils, ex vivo. The intercalating property of anthracycline may be enough to alter the transcription initiation and lead NETosis inhibition. Notably, the inhibitory doses of anthracyclines neither suppress the production of reactive oxygen species that are necessary for antimicrobial functions nor induce apoptotic cell death in neutrophils. Therefore, anthracyclines are a major class of drug that suppresses NETosis. The dexrazoxane, a cardioprotective agent, used for limiting the side effects of anthracyclines, neither affect NETosis nor alter the ability of anthracyclines to suppress NETosis. Hence, at correct doses, anthracyclines together with dexrazoxane could be considered as a therapeutic candidate drug for suppressing unwanted NETosis in NET-related diseases.
Association Between First-Trimester Subchorionic Hematomas and Adverse Pregnancy Outcomes After 20 Weeks of Gestation in Singleton Pregnancies.

OBJECTIVE To assess the association of first-trimester subchorionic hematomas with pregnancy outcomes after 20 weeks of gestation in women with singleton pregnancies. METHODS We conducted a retrospective cohort study of all women with singleton pregnancies presenting for prenatal care before 14 weeks of gestation over a 3-year period at a single obstetric practice. All patients underwent routine first-trimester ultrasound examinations. We compared rates of adverse pregnancy outcomes at more than 20 weeks of gestation in women with and without a subchorionic hematoma on the initial ultrasound examination, excluding women with pregnancy loss before 20 weeks of gestation. RESULTS From January 2015 to December 2017, a total of 2,172 women met the inclusion criteria for the study, 389 (17.9%) of whom had a subchorionic hematoma (mean largest diameter 2.1±1.4 cm). Women with subchorionic hematomas had their first ultrasound examination at earlier gestational ages (8 5/7 vs 9 6/7 weeks, P<.001) and were more likely to have vaginal bleeding at the time of the ultrasound examination (31.9% vs 7.9%, P<.001). Maternal age, race, use of in vitro fertilization, body mass index, and medical comorbidities did not differ between the groups. On univariable analysis, subchorionic hematoma was not associated with any pregnancy outcomes at more than 20 weeks of gestation, including gestational age at delivery, preterm birth, birth weight, birth weight less than the 10th percentile for gestational age, gestational hypertension, preeclampsia, placental abruption, intrauterine fetal death at more than 20 weeks of gestation, cesarean delivery, blood transfusion, and antepartum admissions. On regression analysis including subchorionic hematoma, vaginal bleeding, and gestational age at ultrasound examination, vaginal bleeding was independently associated with preterm birth at less than 37 weeks of gestation and birth weight less than the 10th percentile. Subchorionic hematoma was not independently associated with pregnancy outcomes. This study had 80% power to detect a 5% absolute difference in the frequency of preterm birth; that is, from 10% to 15%. CONCLUSION In singleton pregnancies, a first-trimester subchorionic hematoma is not associated with adverse pregnancy outcomes at more than 20 weeks of gestation.
Biallelic mutations in neurofascin cause neurodevelopmental impairment and peripheral demyelination

See Karakaya and Wirth (doi:10.1093/brain/awz273) for a scientific commentary on this article. Neurofascin (NFASC) isoforms are immunoglobulin cell adhesion molecules involved in node of Ranvier assembly. Efthymiou et al. identify biallelic NFASC variants in ten unrelated patients with a neurodevelopmental disorder characterized by variable degrees of central and peripheral involvement. Abnormal expression of Nfasc155 is accompanied by severe loss of myelinated fibres.
Outpatient and Caregiver Understanding of Auxiliary Instructions on Medication Labels at Ongkharak Hospital, Nakhon Nayok

Objective: To investigate the understanding of common auxiliary instructions among outpatients and caregivers at Ongkharak Hospital, Nakhon Nayok, Thailand.Material and Methods: This cross-sectional descriptive study was conducted from March to April 2017 at Ongkharak Hospital. The convenience sampling subjects were directly interviewed in order to assess their understanding of auxiliary instructions on five medication labels: Ibuprofen, Amoxicillin, Cetirizine, Ferrous fumarate and Insulin.Results: Three hundred and eighty-five subjects participated in this study (212 patients and 173 caregivers). Most were female (66.0%) with an average age of 48.95±17.02 years, secondary school graduates (44.7%), and employees (29.6%). Concerning their experience, most of them (>90.0%) had seen and read the auxiliary instructions. All of the instructions were explicit. Pharmacists explained the instructions to them. Most of them received the auxiliary instructions of Ibuprofen, Amoxicillin and Cetirizine. Concerning their understanding of auxiliary instructions, they correctly understood the indication of Ibuprofen (62.3%), Cetirizine (58.4%), Ferrous fumarate (19.2%) and Amoxicillin (12.5%). They could comprehend how to administer Insulin (78.2%), Ibuprofen (74.8%) and Amoxicillin (61.3%). A few of them truly interpreted the side effects of Cetirizine (9.4%), Ferrous fumarate (8.8%) and Insulin storage (4.9%). Conclusion: Some of the auxiliary instructions used at Ongkharak Hospital should be revised in order to be more concise and pertinent. Moreover, pharmacists should explain auxiliary labels every time to enhance outpatient and caregiver understanding of medication uses.
RNA-seq Based Transcriptome Analysis of the Anti-Obesity Effect of Green Tea Extract Using Zebrafish Obesity Models

Green tea is a popular beverage that is rich in polyphenolic compounds such as catechins. Its major content, (-)-epigallocatechin-3-gallate, has been shown to have beneficial effects on several diseases including cancer, metabolic syndrome, cardiovascular diseases, and neurodegenerative diseases. The aim of this study was to assess the anti-obesity effects and the underlying molecular mechanisms of green tea extract (GTE) using zebrafish larva and adult obesity models. We administered 100 μg/mL GTE to zebrafish larvae and performed a short-term obesogenic test. GTE significantly decreased the visceral adipose tissue volume induced by a high-fat diet. Oral administration (250 µg/g body weight/day) of GTE to adult diet-induced obese zebrafish also significantly reduced their visceral adipose tissue volume, with a reduction of plasma triglyceride and total cholesterol levels. To investigate the molecular mechanism underlying the GTE effects, we conducted RNA sequencing using liver tissues of adult zebrafish and found that GTE may ameliorate the obese phenotypes via the activation of Wnt/β-catenin and adenosine monophosphate-activated protein kinase (AMPK) pathway signaling. In addition, the comparative transcriptome analysis revealed that zebrafish and mammals may share a common molecular response to GTE. Our findings suggest that daily consumption of green tea may be beneficial for the prevention and treatment of obesity.