Miracle-dz/UniFAR-FTUs huggingface dataset:
Characteristics of a Subset of Achalasia With Normal Integrated Relaxation Pressure

Background/Aims Integrated relaxation pressure (IRP) is a critical diagnostic criterion to define achalasia. However, there are some cases with typical symptoms and signs of achalasia but with normal IRP. The aim of this study is to evaluate the clinical characteristics of patients with achalasia with normal IRP and outcomes after peroral endoscopic myotomy (POEM). Methods Patients with achalasia were collected in whom POEM was performed from November 2014 to April 2018 at CHA Bundang Medical Center. Achalasia with normal IRP was defined by findings compatible to achalasia in Eckardt score, endoscopy with endoscopic ultrasound, high-resolution manometry, impedance planimetry (EndoFlip), and timed esophagogram. Results POEM was performed in 89 patients with achalasia; among them, 24 (27%) patients were diagnosed with achalasia with normal IRP. Patients with achalasia with normal IRP were older, had longer duration of symptom, and had a more tortuous esophagus. In EndoFlip, the distensibility index and cross-sectional area were higher in patients with normal IRP. Therapeutic outcomes showed no statistically significant differences. On correlation analysis, IRP had negative correlations with age, disease duration, and distensibility index. Conclusions Patients with achalasia of normal IRP value were older and had longer disease duration and higher distensibility index and cross-sectional area than patients with achalasia with abnormal relaxation of lower esophageal sphincter. Therapeutic outcomes were not different between the 2 groups.
Distribution of functional opioid receptors in human dorsal root ganglion neurons.

Preclinical evidence has highlighted the importance of the μ-opioid peptide (MOP) receptor on primary afferents for both the analgesic actions of MOP receptor agonists, as well as the development of tolerance, if not opioid-induced hyperalgesia. There is also growing interest in targeting other opioid peptide receptor subtypes (δ-opioid peptide (DOP), κ-opioid peptide (KOP), and nociceptin/orphanin-FQ opioid peptide (NOP)) on primary afferents, as alternatives to MOP receptors, that may not be associated with as many deleterious side effects. Nevertheless, results from several recent studies of human sensory neurons indicate that while there are many similarities between rodent and human sensory neurons, there may also be important differences. Thus, the purpose of the present study was to assess the distribution of opioid receptor subtypes among human sensory neurons. A combination of pharmacology, patch-clamp electrophysiology, Ca imaging, and single-cell semi-quantitative polymerase chain reaction (qPCR) were employed. Our results suggest that functional MOP-like receptors are present in approximately 50% of human dorsal root ganglion (DRG) neurons. DOP-like receptors were detected in a subpopulation largely overlapping that with MOP-like receptors. Furthermore, KOP-like and NOP-like receptors are detected in a large proportion (44% and 40%, respectively) human DRG neurons with KOP receptors also overlapping with MOP receptors at a high rate (83%). Our data confirm that all four opioid receptor subtypes are present and functional in human sensory neurons, where the overlap of DOP, KOP, and NOP receptors with MOP receptors suggests that activation of these other opioid receptor subtypes may also have analgesic efficacy.
Two distinct neuroanatomical subtypes of schizophrenia revealed using machine learning.

Neurobiological heterogeneity in schizophrenia is poorly understood and confounds current analyses. We investigated neuroanatomical subtypes in a multi-institutional multi-ethnic cohort, using novel semi-supervised machine learning methods designed to discover patterns associated with disease rather than normal anatomical variation. Structural MRI and clinical measures in established schizophrenia (n = 307) and healthy controls (n = 364) were analysed across three sites of PHENOM (Psychosis Heterogeneity Evaluated via Dimensional Neuroimaging) consortium. Regional volumetric measures of grey matter, white matter, and CSF were used to identify distinct and reproducible neuroanatomical subtypes of schizophrenia. Two distinct neuroanatomical subtypes were found. Subtype 1 showed widespread lower grey matter volumes, most prominent in thalamus, nucleus accumbens, medial temporal, medial prefrontal/frontal and insular cortices. Subtype 2 showed increased volume in the basal ganglia and internal capsule, and otherwise normal brain volumes. Grey matter volume correlated negatively with illness duration in Subtype 1 (r = -0.201, P = 0.016) but not in Subtype 2 (r = -0.045, P = 0.652), potentially indicating different underlying neuropathological processes. The subtypes did not differ in age (t = -1.603, d.f. = 305, P = 0.109), sex (chi-square = 0.013, d.f. = 1, P = 0.910), illness duration (t = -0.167, d.f. = 277, P = 0.868), antipsychotic dose (t = -0.439, d.f. = 210, P = 0.521), age of illness onset (t = -1.355, d.f. = 277, P = 0.177), positive symptoms (t = 0.249, d.f. = 289, P = 0.803), negative symptoms (t = 0.151, d.f. = 289, P = 0.879), or antipsychotic type (chi-square = 6.670, df = 3, P = 0.083). Subtype 1 had lower educational attainment than Subtype 2 (chi-square = 6.389, d.f. = 2, P = 0.041). In conclusion, we discovered two distinct and highly reproducible neuroanatomical subtypes. Subtype 1 displayed widespread volume reduction correlating with illness duration, and worse premorbid functioning. Subtype 2 had normal and stable anatomy, except for larger basal ganglia and internal capsule, not explained by antipsychotic dose. These subtypes challenge the notion that brain volume loss is a general feature of schizophrenia and suggest differential aetiologies. They can facilitate strategies for clinical trial enrichment and stratification, and precision diagnostics.
The Role of PGC-1α and Mitochondrial Biogenesis in Kidney Diseases

Chronic kidney disease (CKD) is one of the fastest growing causes of death worldwide, emphasizing the need to develop novel therapeutic approaches. CKD predisposes to acute kidney injury (AKI) and AKI favors CKD progression. Mitochondrial derangements are common features of both AKI and CKD and mitochondria-targeting therapies are under study as nephroprotective agents. PGC-1α is a master regulator of mitochondrial biogenesis and an attractive therapeutic target. Low PGC-1α levels and decreased transcription of its gene targets have been observed in both preclinical AKI (nephrotoxic, endotoxemia, and ischemia-reperfusion) and in experimental and human CKD, most notably diabetic nephropathy. In mice, PGC-1α deficiency was associated with subclinical CKD and predisposition to AKI while PGC-1α overexpression in tubular cells protected from AKI of diverse causes. Several therapeutic strategies may increase kidney PGC-1α activity and have been successfully tested in animal models. These include AMP-activated protein kinase (AMPK) activators, phosphodiesterase (PDE) inhibitors, and anti-TWEAK antibodies. In conclusion, low PGC-1α activity appears to be a common feature of AKI and CKD and recent characterization of nephroprotective approaches that increase PGC-1α activity may pave the way for nephroprotective strategies potentially effective in both AKI and CKD.
Epidemiology of β-Lactamase-Producing Pathogens

β-Lactam antibiotics have been widely used as therapeutic agents for the past 70 years, resulting in emergence of an abundance of β-lactam-inactivating β-lactamases. Although penicillinases in Staphylococcus aureus challenged the initial uses of penicillin, β-lactamases are most important in Gram-negative bacteria, particularly in enteric and nonfermentative pathogens, where collectively they confer resistance to all β-lactam-containing antibiotics. SUMMARY β-Lactam antibiotics have been widely used as therapeutic agents for the past 70 years, resulting in emergence of an abundance of β-lactam-inactivating β-lactamases. Although penicillinases in Staphylococcus aureus challenged the initial uses of penicillin, β-lactamases are most important in Gram-negative bacteria, particularly in enteric and nonfermentative pathogens, where collectively they confer resistance to all β-lactam-containing antibiotics. Critical β-lactamases are those enzymes whose genes are encoded on mobile elements that are transferable among species. Major β-lactamase families include plasmid-mediated extended-spectrum β-lactamases (ESBLs), AmpC cephalosporinases, and carbapenemases now appearing globally, with geographic preferences for specific variants. CTX-M enzymes include the most common ESBLs that are prevalent in all areas of the world. In contrast, KPC serine carbapenemases are present more frequently in the Americas, the Mediterranean countries, and China, whereas NDM metallo-β-lactamases are more prevalent in the Indian subcontinent and Eastern Europe. As selective pressure from β-lactam use continues, multiple β-lactamases per organism are increasingly common, including pathogens carrying three different carbapenemase genes. These organisms may be spread throughout health care facilities as well as in the community, warranting close attention to increased infection control measures and stewardship of the β-lactam-containing drugs in an effort to control selection of even more deleterious pathogens.
The Clustering of Low Diet Quality, Low Physical Fitness, and Unhealthy Sleep Pattern and Its Association with Changes in Cardiometabolic Risk Factors in Children

The clustering of diet quality, physical activity, and sleep and its association with cardiometabolic risk (CMR) factors remains to be explored. We included 5315 children aged 6–13 years in the analysis. CMR score (CMRS) was computed by summing Z-scores of waist circumference, an average of systolic and diastolic blood pressure, fasting glucose, high-density lipoprotein cholesterol (multiplying by −1), and triglycerides. Low diet quality and low cardiorespiratory fitness (CRF) were more likely to be seen in a pair, but low diet quality was less likely to be clustered with unhealthy sleep patterns. Low diet quality, low CRF, and unhealthy sleep pattern was associated with a 0.63, 0.53, and 0.25 standard deviation (SD) higher increase in CMRS, respectively. Compared to children with no unhealthy factor (−0.79 SD), those with ≥1 unhealthy factor had a higher increase (−0.20 to 0.59 SD) in CMRS. A low diet quality-unhealthy sleep pattern resulted in the highest increase in CMRS, blood pressure, and triglycerides. A low diet quality–low CRF-unhealthy sleep pattern resulted in the highest increase in fatness and fasting glucose. Unhealthy factor cluster patterns are complex; however, their positive associations with changes in CMR factors are consistently significant in children. Some specific patterns are more harmful than others for cardiometabolic health.
Interaction of phenytoin with chloramphenicol or pentobarbital in the dog.

: Two dogs that had been given phenytoin for control of seizures for approximately 1 year developed signs of phenytoin toxicosis (postural ataxia an d a hypermetric gait) when chloramphenicol was added to the therapeutic regimen. The signs of toxicosis disappeared within 24 hours after cessation of chloramphenicol treatment. Oral treatment of laboratory dogs with chloramphenicol (50 mg/kg, TID for 3 days) prior to intravenous injection of phenytoin increased the half-life of phenytoin from 3 hours to 15 hours. Dogs infused with phenytoin during pentobarbital anesthesia had little or no change in serum phenytoin concentration during a 2-hour postinfusion observation period, which was unexpected for the intravenous route of administration.
Game of Stones: feasibility randomised controlled trial of how to engage men with obesity in text message and incentive interventions for weight loss

Objectives To examine the acceptability and feasibility of narrative text messages with or without financial incentives to support weight loss for men. Design Individually randomised three-arm feasibility trial with 12 months’ follow-up. Setting Two sites in Scotland with high levels of disadvantage according to Scottish Index for Multiple Deprivation (SIMD). Participants Men with obesity (n=105) recruited through community outreach and general practitioner registers. Interventions Participants randomised to: (A) narrative text messages plus financial incentive for 12 months (short message service (SMS)+I), (B) narrative text messages for 12 months (SMS only), or (C) waiting list control. Outcomes Acceptability and feasibility of recruitment, retention, intervention components and trial procedures assessed by analysing quantitative and qualitative data at 3, 6 and 12 months. Results 105 men were recruited, 60% from more disadvantaged areas (SIMD quintiles 1 or 2). Retention at 12 months was 74%. Fewer SMS+I participants (64%) completed 12-month assessments compared with SMS only (79%) and control (83%). Narrative texts were acceptable to many men, but some reported negative reactions. No evidence emerged that level of disadvantage was related to acceptability of narrative texts. Eleven SMS+I participants (31%) successfully met or partially met weight loss targets. The cost of the incentive per participant was £81.94 (95% CI £34.59 to £129.30). Incentives were acceptable, but improving health was reported as the key motivator for weight loss. All groups lost weight (SMS+I: −2.51 kg (SD=4.94); SMS only: −1.29 kg (SD=5.03); control: −0.86 kg (SD=5.64) at 12 months). Conclusions This three-arm weight management feasibility trial recruited and retained men from across the socioeconomic spectrum, with the majority from areas of disadvantage, was broadly acceptable to most participants and feasible to deliver. Trial registration number NCT03040518.
Visual field deficits following laser ablation of the hippocampus

Objective To qualify the incidence of and risk factors for visual field deficits (VFD) following laser interstitial thermal ablation (LITT) for mesial temporal lobe epilepsy (MTLE) and to relate this to anterior temporal lobectomy (ATL). Methods Fifty-seven patients underwent LITT of the amygdalo-hippocampal complex (AH) for MTLE. Masks of ablation volumes, laser probe trajectories, and visual radiations (VRs) from individual subject space were transformed into standardized space using nonlinear registration. Voxel-wise statistics were performed to model relationships between VFDs vs ablation volumes, laser trajectories, VRs, and AH asymmetry. A review of VFDs following ATLs was performed. Results The incidence of VFD after LITT is much lower than after ATLs. A total of 37.5% of patients developed a VFD, with the probability of this being much higher after left (50%) vs right hemisphere LITT (10%) (Fisher test, p = 0.05). This laterality effect on VFDs is mirrored but underappreciated in ATL series. The most consistent LITT-VFD occurred in the superior vertical octant. Ablation of Meyer loop as well as the summed probability of VRs within laser trajectories correlated with VFDs (p < 0.05). Left and right hippocampi have significantly distinct orientations in axial and coronal planes, which may be one reason for the variation in VFD probability. Conclusions LITT results in lower rates of and smaller VFDs—typically an octantanopsia. VRs are at greater risk during surgery for left than right MTLE. Anatomical asymmetries in hippocampal anatomy may explain the hemispheric differences in deficits, and should factor into trajectory planning and also into preoperative patient counseling. Overall the incidence and extent of visual deficits following LITT for MTLE is lower than the reported data following anterior temporal lobectomy. VF tractography incorporated into LITT planning may reduce the occurrence of VFDs.
Signal recovery from stimulation artifacts in intracranial recordings with dictionary learning

Objective. Electrical stimulation of the human brain is commonly used for eliciting and inhibiting neural activity for clinical diagnostics, modifying abnormal neural circuit function for therapeutics, and interrogating cortical connectivity. However, recording electrical signals with concurrent stimulation results in dominant electrical artifacts that mask the neural signals of interest. Here we develop a method to reproducibly and robustly recover neural activity during concurrent stimulation. We concentrate on signal recovery across an array of electrodes without channel-wise fine-tuning of the algorithm. Our goal includes signal recovery with trains of stimulation pulses, since repeated, high-frequency pulses are often required to induce desired effects in both therapeutic and research domains. We have made all of our code and data publicly available. Approach. We developed an algorithm that automatically detects templates of artifacts across many channels of recording, creating a dictionary of learned templates using unsupervised clustering. The artifact template that best matches each individual artifact pulse is subtracted to recover the underlying activity. To assess the success of our method, we focus on whether it extracts physiologically interpretable signals from real recordings. Main results. We demonstrate our signal recovery approach on invasive electrophysiologic recordings from human subjects during stimulation. We show the recovery of meaningful neural signatures in both electrocorticographic (ECoG) arrays and deep brain stimulation (DBS) recordings. In addition, we compared cortical responses induced by the stimulation of primary somatosensory (S1) by natural peripheral touch, as well as motor cortex activity with and without concurrent S1 stimulation. Significance. Our work will enable future advances in neural engineering with simultaneous stimulation and recording.
Using computer simulation to model the expansion needs of the ambulatory emergency care unit at Derriford Hospital

ABSTRACT Ambulatory emergency care (AEC) units can treat a wide variety of patients referred from the emergency department (ED) and acute general practitioners, helping to ease ED pressures and reduce unnecessary hospital admissions. We developed a simulation model to assess the potential benefits of expanding the size and opening times of the AEC unit at Derriford Hospital in Plymouth, both separately and in combination. The model predicted that an expanded size of AEC unit could help to improve the effectiveness of the unit, but not as much as extending the opening hours of the unit, which was predicted to result in a significant impact on the number of patients that can be seen and treated in the AEC unit. The hospital used the evidence generated by the model to support a business to case to extend opening hours of the AEC unit, and open the AEC unit at the weekend.
Magnetically Driven Bionic Millirobots with a Low-Delay Automated Actuation System for Bioparticles Manipulation

This paper presents a semi-automatic actuation system which can achieve bio-particles tracking, transportation, and high-precision motion control of robots in a microfluidic chip. This system is mainly applied in magnetically driven robots. An innovative manta ray-like robot was designed to increase stability of robots in a non-contaminated manipulation environment. A multilayer piezo actuator was applied to generate high-frequency vibration to decrease the friction between robots and the glass substrate. We also set up a user-friendly GUI (Graphical User Interface) and realized robot tracking and predetermined trajectory motion through excellent algorithms using Python and C++. In biotechnology, precise transportation of cells is used for the enucleation, microinjection, and investigation of the characteristics of a single cell. Being optimized, the parameters of the robot can effectively reach 10 µm in actuation precision and a maximum actuation speed of 200 mm/s.
In vitro functional characterization and in silico prediction of rare genetic variation in the bile acid and drug transporter, Na+-taurocholate co-transporting polypeptide (NTCP, SLC10A1).

Na+-taurocholate co-transporting polypeptide (NTCP; SLC10A1) is a key hepatic uptake transporter for bile acids and drugs and is the main functional receptor for hepatitis B and D viruses. Next-generation sequencing (NGS) has revealed that a large number of rare SLC10A1 variants exist in the population. Little data exist regarding head-to-head comparison of in silico algorithms to predict functional effects of variants when compared to direct in vitro functional assessment. This study aimed to characterize rare SLC10A1 variants in vitro and to assess the performance of seven in silico algorithms to predict the observed functional impacts. Thirty-five previously uncharacterized, rare, missense SLC10A1 variants were transiently expressed in human embryonic kidney 293 type T (HEK293T) cells. Protein expression as well as uptake of NTCP substrates taurocholic acid (TCA) and rosuvastatin were assessed. Substrate-specific effects were observed for NTCP G191R, with TCA and rosuvastatin transport observed at 89% and 8% of wild type uptake, respectively. Significantly reduced transport of TCA and rosuvastatin was observed for 19 variants (p<0.05), with seven variants displaying decreased protein expression and marked reduction in transport of both substrates (<13% of wild type uptake, p<0.0001). Performance of in silico algorithms to predict in vitro uptake, assessed using area under the receiver operating characteristic curve (AUCROC), ranged from 0.69-0.97 and 0.72-0.84 for TCA and rosuvastatin uptake, respectively. In conclusion, we identified rare variants with significantly reduced NTCP expression and function. We demonstrated that no algorithm performed robustly enough to replace functional study in vitro, particularly given the broad substrate specificity of many pharmacogenes.
Correlations between Sleep Bruxism and Temporomandibular Disorders

The aim of this study was to identify correlations between sleep bruxism (SB) and temporomandibular disorders (TMD) as diagnosed by means of the research diagnostic criteria for temporomandibular disorders (RDC/TMD). Sleep bruxism was diagnosed on the basis of I) validated questionnaires, II) clinical symptoms, and III) electromyographic/electrocardiographic data. A total of 110 subjects were included in the study. Fifty-eight patients were identified as bruxers and 52 as nonbruxers. A psychosocial assessment was also performed. An RDC/TMD group-I diagnosis (myofascial pain) was made for 10 out of 58 bruxers, whereas none of the nonbruxers received a diagnosis of this type. No significant differences were found between bruxers and nonbruxers with regard to RDC/TMD group-II (disc displacement) and group-III (arthralgia, arthritis, arthrosis) diagnoses. Somatization was significantly more common among bruxers than nonbruxers. Multivariate logistic regression analysis revealed that somatization was the only factor significantly correlated with the diagnosis of myofascial pain. The results of this study indicate a correlation between myofascial pain, as diagnosed using the RDC/TMD, and somatization. It seems that somatization is a stronger predictor of an RDC/TMD diagnosis of myofascial pain than sleep bruxism is.
Willow Bark for Sustainable Energy Storage Systems

Willow bark is a byproduct from forestry and is obtained at an industrial scale. We upcycled this byproduct in a two-step procedure into sustainable electrode materials for symmetrical supercapacitors using organic electrolytes. The procedure employed precarbonization followed by carbonization using different types of KOH activation protocols. The obtained electrode materials had a hierarchically organized pore structure and featured a high specific surface area (>2500 m2 g−1) and pore volume (up to 1.48 cm3 g−1). The assembled supercapacitors exhibited capacitances up to 147 F g−1 in organic electrolytes concomitant with excellent cycling performance over 10,000 cycles at 0.6 A g−1 using coin cells. The best materials exhibited a capacity retention of 75% when changing scan rates from 2 to 100 mV s−1.