Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple‐ascending doses of ACT‐1014‐6470, an oral complement factor 5a receptor 1 (C5a1 receptor) antagonist: Tolerability, pharmacokinetics and target engagement

Targeting the complement factor 5a receptor 1 (C5a1 receptor) offers potential to treat various autoimmune diseases. The C5a1 receptor antagonist ACT‐1014‐6470 was well tolerated in a single‐ascending dose study in healthy subjects. This double‐blind, randomized, placebo‐controlled study aimed to investigate the safety, tolerability, pharmacokinetics (PK) and target engagement of multiple‐ascending doses of ACT‐1014‐6470.
Minimal water exchange by the air–water valve versus left colon water exchange in unsedated colonoscopy: a randomized controlled trial

BACKGROUND AND OBJECTIVE Water exchange colonoscopy is the least painful method for unsedated colonoscopies. Simplified left water exchange (LWE) reduced the cecal intubation time, but it was difficult to avoid the use of an additional pump. Minimal water exchange (MWE) is an improved novel method that eliminates the need for pumps, but it is not clear whether MWE has the same efficiency as LWE. METHODS This was a prospective, randomized controlled, non-inferiority trial conducted in a tertiary hospital. Enrolled patients were randomized 1:1 to the LWE group and MWE group. The primary outcome was recalled insertion pain measured by a 4-point verbal rating scale, and the secondary outcomes mainly included adenoma detection rate (ADR), cecal intubation time, the volume of water used, and the willingness to undergo unsedated colonoscopy. RESULTS A total of 226 patients were included (LWE, n = 113 and MWE, n = 113). The MWE showed non-inferior moderate/severe pain rates compared with the LWE (10.6% vs. 9.7%), with a difference of 0.9% (99% confidence interval [CI], [-9.5, 11.3]; threshold, 15%). ADR, cecal intubation time and willingness were not significantly different between the two groups, but the mean water used (volume) in the MWE was significantly less than in the other (163.7 ml vs. 407.2 ml, 99% CI [-298.28, -188.69]). CONCLUSION Compared to LWE, MWE demonstrated a non-inferior outcome for insertion pain, and comparable cecal intubation time and ADR, but reduced the volume of water used and eliminated the need for a water pump.
Bronchodilator reversibility in the GAN severe asthma cohort.

BACKGROUND AND OBJECTIVE Positive bronchodilator reversibility (BDR) is a diagnostic criterion for asthma. However, patients with asthma may exhibit negative BDR test.To describe frequency of positive and negative BDR in patients with severe asthma and associations with phenotypic characteristics. METHODS Positive BDR was defined as FEV1 increase > 200 ml AND > 12% upon testing with a short-acting beta-agonist (SABA). RESULTS Out of 2013 patients included in the German Asthma Net (GAN) severe asthma registry, 793 had data on BDR. Hereof, 250 (31.5%) had a positive and 543 (68.5%) had a negative BDR test. Comorbidities significantly associated with negative BDR were gastro-esophageal reflux (GERD) (28.0% vs 40.0%, p<0.01) and EGPA (0.4% vs 3.0%; p<0.05), while smoking history (active: 2.8% vs 2.2%; ex: 40.0% vs 41.7%) and COPD comorbidity (5.2% vs 7.2%) were similar in both groups. Patients with positive BDR had worse asthma control (median ACQ-5 3.4 vs 3.0, p<0.05), reported dyspnea at rest (26.8% vs 16.4%, p<0.001) and chest tightness (36.4% vs 26.2%, p<0.001) more frequently, had more severe airway obstruction at baseline (FEV1% pred: 56 vs 64, p<0.001) and higher FeNO levels (41 vs 33 ppb, p<0.05), while diffusion capacity did not differ (DLCO-SB % pred. 70% vs 71%). Multivariate linear regression analysis identified association of lower baseline FEV1% (p<0.001) and chest tightness (p<0.05) with positive, and GERD (p<0.05) with negative BDR. CONCLUSION In this real-life setting the majority of patients with severe asthma exhibited negative BDR. Interestingly, this was not associated with smoking history or COPD, but with lower FeNO and presence of GERD.
Tactile Sensation Assisted Motor Imagery Training for Enhanced BCI Performance: A Randomized Controlled Study

<italic>Objective:</italic> Independent of conventional neurofeedback training, in this study, we propose a tactile sensation assisted motor imagery training (SA-MI Training) approach to improve the performance of MI-based BCI. <italic>Methods:</italic> Twenty-six subjects were recruited and randomly divided into a Training-Group and a Control-Group. All subjects were required to perform three blocks of MI tasks. In the Training-Group, during the second block (SA-MI Training block), tactile stimulation was applied to the left or right wrist while the subjects were performing the left or right-hand MI task, while during the first block (Pre-Training block) and the third block (Post-Training block), subjects performed pure MI tasks without the tactile sensation assistance. In contrast, in the Control-Group, subjects performed the left and right-hand MI tasks in all three blocks. <italic>Results:</italic> The performance of the Post-Training block (83.2 <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math></inline-formula> 11.4%) was significantly (<italic>p</italic> = 0.0014) higher than that of the Pre-Training block (73.2 <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math></inline-formula> 16.3%). By contrast, in the Control-Group, no significant difference was found among the three blocks. Moreover, after the SA-MI Training, the motor-related cortex activation (i.e., ERD/ERS) and the R<inline-formula><tex-math notation="LaTeX">$^{2}$</tex-math></inline-formula> coefficient in the alpha-beta band were enhanced, while no training effect was found in the Control-Group. <italic>Conclusion:</italic> The proposed SA-MI Training approach can significantly improve the performance of MI, which provides a novel training framework for MI-based BCI. <italic>Significance:</italic> It may be especially beneficial to those who are with difficulty in convention neurofeedback training or performing pure MI mental tasks to gain BCI control.
The influence of methylphenidate on sustained attention in paediatric acquired brain injury: a meta-analytical review

ABSTRACT Impairment in sustained attention is a common consequence of childhood Acquired Brain Injury (ABI). Whilst methylphenidate provides promise in enhancing “attention” as a unitary construct, little work has explored its effectiveness upon individual attentional domains. The current systematic review and meta-analysis evaluates the utility of methylphenidate on sustained attentional performance across childhood ABI groups. Five databases (PsycINFO, MEDLINE, Embase, Scopus & Cochrane Library) were searched for relevant articles from their inception to March 2022. A purpose-developed evaluation tool was used to assess each study’s research quality (QuEST:MAP). Nine of the 1600 identified articles were included within this review (n = 259). Meta-analytical findings reported an overall significant benefit of methylphenidate on sustained attention in childhood ABI (g = −0.33, 95% CI: −0.62 to −0.04). Associated summary effect sizes were relatively small, particularly when adjusting for outlier cases. Subgroup analyses identified a significantly greater benefit of methylphenidate in clinical subgroups with comorbid ADHD diagnoses (p < .01). The current evidence base is characterized by small-scale clinical trials with variable research quality and low generalizability. Further robust research is needed to quantify methylphenidate utility upon individual attentional domains in larger and more representative ABI samples.
Aberrant RNA processing contributes to the pathogenesis of mitochondrial diseases in trans-mitochondrial mouse model carrying mitochondrial tRNALeu(UUR) with a pathogenic A2748G mutation

Abstract Mitochondrial tRNAs are indispensable for the intra-mitochondrial translation of genes related to respiratory subunits, and mutations in mitochondrial tRNA genes have been identified in various disease patients. However, the molecular mechanism underlying pathogenesis remains unclear due to the lack of animal models. Here, we established a mouse model, designated ‘mito-mice tRNALeu(UUR)2748’, that carries a pathogenic A2748G mutation in the tRNALeu(UUR) gene of mitochondrial DNA (mtDNA). The A2748G mutation is orthologous to the human A3302G mutation found in patients with mitochondrial diseases and diabetes. A2748G mtDNA was maternally inherited, equally distributed among tissues in individual mice, and its abundance did not change with age. At the molecular level, A2748G mutation is associated with aberrant processing of precursor mRNA containing tRNALeu(UUR) and mt-ND1, leading to a marked decrease in the steady-levels of ND1 protein and Complex I activity in tissues. Mito-mice tRNALeu(UUR)2748 with ≥50% A2748G mtDNA exhibited age-dependent metabolic defects including hyperglycemia, insulin insensitivity, and hepatic steatosis, resembling symptoms of patients carrying the A3302G mutation. This work demonstrates a valuable mouse model with an inheritable pathological A2748G mutation in mt-tRNALeu(UUR) that shows metabolic syndrome-like phenotypes at high heteroplasmy level. Furthermore, our findings provide molecular basis for understanding A3302G mutation-mediated mitochondrial disorders.
The Impact of Group Feedback on Self-Perceptions Following Videotape Exposure in CBT for Social Anxiety Disorder

Video feedback following social anxiety exposures improves self-perceptions. Clinical studies have not examined whether feedback from group members has incremental benefit beyond that of viewing the tape itself. Sixty-seven individuals with social anxiety disorder completed videotaped exposure during group based cognitive behavior therapy (CBT). After participants viewed their taped exposure, group members and therapists gave feedback. Participants completed ratings of anxiety and performance before and after taping their exposure, after viewing the video themselves, and after receiving group feedback. Appraisal of social concerns were assessed after taping, viewing, and group feedback. There were significant improvements in anxiety, performance, and decreased social concerns across time points. Comparing only the time points of after viewing and after receiving group feedback, the same pattern emerged for anxiety, performance, and appraisal of social concerns, with moderate to large effect sizes. Group feedback led to ratings that exceeded their own initial evaluation of their video. Video feedback in group CBT that also includes feedback from others may improve clinical outcomes.
The Complexity of Impulsivity Dimensions among Abstinent Individuals with Substance Use Disorders

ABSTRACT Impulsivity is a complex construct that has been operationalized considering personality dimensions (e.g., negative urgency [NU], lack of perseverance [LPe], lack of premeditation [LPr], positive urgency [PU]), and neuropsychological processes (i.e., cognitive disinhibition, motor disinhibition, impulsive decision-making). Empirical research suggested that they could represent core features of substance use disorders (SUDs). However, there are no studies that have comprehensively assessed them among patients with SUDs. Furthermore, the quality of relationships among such domains remains unclear. The current case–control study included 59 abstinent patients with SUDs and 56 healthy controls (HCs). There were two independent assessment phases: i) the administration of UPPS-P impulsive behavior scale; ii) a computerized neuropsychological battery (i.e., Attentional Network Test, Go/No-Go task, Iowa Gambling task). Patients with SUDs reported higher levels of NU and PU than HCs. NU, LPe, and LPr were associated to the co-occurrence of multiple SUDs. Motor disinhibition was the core dimension of SUDs. Cognitive disinhibition and Impulsive decision-making were also associated to SUDs. Self-report and neuropsychological dimensions of impulsivity were not correlated within the clinical group. HCs showed significant associations among these domains of impulsivity. Impulsivity should be viewed as a complex system of personality traits and neuropsychological processes among individuals with SUDs.
PRIOR: Prior-Regularized Iterative Optimization Reconstruction For 4D CBCT

4D cone-beam computed tomography (CBCT) is an important imaging modality in image-guided radiation therapy to address the motion-induced artifacts caused by organ movements during the respiratory process. However, due to the extremely sparse projection data for each temporal phase, 4D CBCT reconstructions will suffer from severe streaking artifacts. Therefore, to tackle the streak artifacts and provide high-quality images, we proposed a framework termed Prior-Regularized Iterative Optimization Reconstruction (PRIOR) for 4D CBCT. The PRIOR framework combines the physics-based model and data-driven method simultaneously, with powerful feature extracting capacity, significantly promoting the image quality compared to single model-based or deep learning-based methods. Besides, we designed a specialized deep learning model named PRIOR-Net, which can effectively excavate the static information in the prior image reconstructed from the fully-sampled projections at the encoding stage to improve the reconstruction performance for individual phase-resolved images. Both the simulated and clinical 4D CBCT datasets were performed to evaluate the performance of the PRIOR-Net and the PRIOR framework. Compared with the advanced 4D CBCT reconstruction methods, the proposed methods achieve promising results quantitatively and qualitatively in streak artifact suppression, soft tissue restoration, and tiny detail preservation.
Effect of LncRNA OIP5-AS1/microRNA-186-5p on isoflurane-induced cognitive dysfunction in aged rats

Background Post-operative recognition dysfunction (POCD) is a kind of central nervous system complication that appears after operative anesthesia. Recent studies on the mechanism of long non-coding RNA (lncRNA) in neurodegenerative diseases are abundant. Aims The study aimed to explore the expression pattern and role of lncRNA OIP5-AS1 in POCD and to investigate its underlying mechanism in old rats. Methods The old rats were exposed to isoflurane to mimic the POCD in the elderly, and their cognitive function was tested via Morris water maze (MWM) test. Enzyme linked immunosorbent assay was applied for the concentration detection of inflammation and oxidative stress-related factors. Luciferase reporter assay was done for the target gene analysis. Results Downregulation of OIP5-AS1 was accompanied by isoflurane treatment in rats, overexpression of OIP5-AS1 induced the rats to spend more time in the target quadrant, and shorten escape latency time. OIP5-AS1 inhibited the release of TNF-α, IL-6 and IL-1β, GSH and superoxide dismutase, decreased the activation of caspase-3, but promoted malondialdehyde release. miR-186-5p was a target miRNA of OIP5-AS1, and exhibited high expression in rats after isoflurane exposure. miR-186-5p can abolish the beneficial role of OIP5-AS1 against cognitive impairment, inflammatory response, oxidative stress and neuron apoptosis. Conclusion OIP5-AS1 plays a neuroprotective role in elderly POCD rats through sponging miR-186-5p, and it is related to OIP5-AS1/miR-186-5p mediated inflammatory response, oxidative stress and neuron apoptosis.
Tuberculosis at a university hospital, Thailand: A surprising incidence of TB among a new generation of highly exposed health care workers who may be asymptomatic

Objectives There are a few reports of TB disease among healthcare workers (HCWs) in Thailand. The authors assessed the demographic data and incidence of overall TB disease including specific profession among HCWs in order to reduce the incidence rate. Methods This was a descriptive, cross-sectional study of 195 HCWs at King Chulalongkorn Memorial Hospital (KCMH), Bangkok, Thailand, who had TB disease from 2003–2020. Results The average incidence of TB disease in HCWs at KCMH was 164 per 100,000 HCWs with 95% confidential interval [CI], 107 to 220; (94.4% had pulmonary TB). Most of the HCWs were from a young age group (43.08% were 20–29 years old) and the duration of work was short (58.82% had worked at KCMH for less than 5 years). Radiological technicians had the highest incidence of TB, followed by supportive teams, scientists, and physicians (429, 241, 205, and 193 per 100,000 HCWs according to their profession, respectively). Seventy five percent of TB disease was found in physicians who worked at KCMH within 2 years. TB incidence was highest among residents (688 per 100,000 residents) in a subgroup of physicians. Conclusions The incidence of TB disease in HCWs was close to the general population of Thailand (153 per 100,000 population with 95% CI, 116 to 195). A higher incidence was observed in the profession that had contact with TB patients and their specimens. A high proportion of asymptomatic HCWs also had TB disease and TB incidence was found in a new generation of HCWs who have worked for less than 5 years. More rigorous epidemiology investigations are needed to establish a definitive relation to subsequently developing TB after working in a hospital. The authors suggest active surveillance in all new incoming HCWs and TB preventive therapy should also be provided to recent converters.
Deep learning: applications in retinal and optic nerve diseases

ABSTRACT Deep learning (DL) represents a paradigm-shifting, burgeoning field of research with emerging clinical applications in optometry. Unlike traditional programming, which relies on human-set specific rules, DL works by exposing the algorithm to a large amount of annotated data and allowing the software to develop its own set of rules (i.e. learn) by adjusting the parameters inside the model (network) during a training process in order to complete the task on its own. One major limitation of traditional programming is that, with complex tasks, it may require an extensive set of rules to accurately complete the assignment. Additionally, traditional programming can be susceptible to human bias from programmer experience. With the dramatic increase in the amount and the complexity of clinical data, DL has been utilised to automate data analysis and thus to assist clinicians in patient management. This review will present the latest advances in DL, for managing posterior eye diseases as well as DL-based solutions for patients with vision loss.
Pediatric Headache Experience During the COVID-19 Pandemic

Objective Headache disorders are exceedingly common in children and adolescents. The association between headaches, emotional stress, and disruptions in daily routines are well established. The goal of this study is to compare the experiences of patients with a preexisting diagnosis of a primary headache disorder in terms of headache frequency and severity, lifestyle techniques for headache prevention, screen use, and mood from before and after the onset of the COVID-19 pandemic. Methods Patients evaluated by the Headache Clinic at Children’s National Hospital between Summer 2020 and Winter 2021 were enrolled in a patient registry. Patients completed a questionnaire examining changes in headache characteristics and lifestyle factors since the onset of the COVID-19 pandemic. Results A total of 107 patients completed the survey. Since the pandemic’s onset, patients reported decreased physical activity (n = 59, 55%), increased frequency of chronic headaches from 40% (N = 42) to 50% (N = 54), and increased constant daily headaches from 22% (n = 24) to 36% (n = 38). Patients reported worsened anxiety (n = 58, 54%), mood (n = 50, 47%), and workload (n = 49, 46%). Sixty-one percent (n = 65) of patients reported using screens for school for more than 6 hours per day. The majority (n = 67, 63%) of patients indicated that they would prefer attending in-person school, with 14% (n = 15) responding that they preferred online school. Conclusion Since the COVID-19 pandemic’s onset, pediatric headache patients have experienced increasing headache frequency, worsening anxiety and mood, decreased physical activity, and increased screen usage. Although this study is limited by sample size and observational design, future population-based studies will further elucidate the impact of this pandemic on pediatric headache.
Modeling Spinal Muscular Atrophy in Drosophila article Please share how this access benefits you. Your story matters

Spinal Muscular Atrophy (SMA), a recessive hereditary neurodegenerative disease in humans, has been linked to mutations in the survival motor neuron ( SMN ) gene. SMA patients display early onset lethality coupled with motor neuron loss and skeletal muscle atrophy. We used Drosophila , which encodes a single SMN ortholog, survival motor neuron ( Smn ), to model SMA, since reduction of Smn function leads to defects that mimic the SMA pathology in humans. Here we show that a normal neuromuscular junction (NMJ) structure depends on SMN expression and that SMN concentrates in the post- synaptic NMJ regions. We conducted a screen for genetic modifiers of an Smn phenotype using the Exelixis collection of transposon-induced mutations, which affects approximately 50% of the Drosophila genome. This screen resulted in the recovery of 27 modifiers, thereby expanding the genetic circuitry of Smn to include several genes not previously known to be associated with this locus. Among the identified modifiers was wishful thinking (wit) , a type II BMP receptor, which was shown to alter the Smn NMJ phenotype. Further characterization of two additional members of the BMP signaling pathway, Mothers against dpp ( Mad ) and Daughters against dpp ( Dad ), also modify the Smn NMJ phenotype. The NMJ defects caused by loss of Smn function can be ameliorated by increasing BMP signals, suggesting that increased BMP activity in SMA patients may help to alleviate symptoms of the disease. These results confirm that our genetic approach is likely to identify bona fide modulators of SMN activity, especially regarding its role at the neuromuscular junction, and as a consequence, may identify putative SMA therapeutic targets. also viable. In addition, a small deficiency uncovering the entire Smn transcript was generated (Df(3L) Smn X7 ). We crossed all three Smn alleles to Df(3L) Smn X7 and found that both Smn 73Ao /Df(3L) Smn X7 and Smn f05960 /Df(3L) Smn X7 heterozygotes die between the 2 nd and 3 rd instar larval stages, while , 60% of Smn f01109 /Df(3L) Smn X7 are viable. Therefore, using lethality as a criterion, all three alleles behave as loss-of-function mutations with Smn f01109 displaying the weakest phenotype of the three. No obvious maternal or paternal effect is observed for the different alleles. individuals were examined for each genotype.
Beery-Buktenica visual Motor integration test Validity Evidence Examination

This exploratory study examined the validity of the results obtained from the administration of the Beery VMI to a sample of Puerto Rican children. The process included translation of test instructions, interviews with four professionals that use the test in their clinical practice, and the administration of the test to 50 Kindergarten students from two schools in San Juan, Puerto Rico. Quantitative and qualitative data was collected as established by the Standards for Educational and Psychological Testing (1999): test content, response process, internal structure, relation to other variables, and test consequences. Information regarding test content, response process, and test consequences supported the validity of the results. However, more research is needed to reach a definitive conclusion.