Miracle-dz/UniFAR-FTUs huggingface dataset:
Hydraulic Considerations in Declining-Rate Filtration

Flow control through granular filters is an important factors in filter performance in both water and wastewater treament. Declining-rate filtration plants operate without effluent rate control devices on each filter. All the filters in the plant operate at the same water level and the same head loss. Therefore, the cleanest filter operates at the highest filtration rate and the dirtiest filter operates at the lowest rate. The filters decline in rate as each filter is backwashed in succession. Declining-rate filtration plants produce better water quality and require less head loss than constant-rate or constant water level filters. The design of declining-rate plants has been hampered by the absence of rational approaches to several hydraulic questions which are answered in the paper as follows: What total head loss is required? How can excessive filtration rates be prevented without the use of rate controllers? How can the water level variations in the filter be predicted and how are they affected by the number of filters in the plant? How does the plant respond to imposed load variations—
Real-world efficacy of galcanezumab for the treatment of migraine in Korean patients

Background and objective We aimed to provide real-world data on the effectiveness of an anti-calcitonin gene-related peptide monoclonal antibody administered for treating migraine in Korean patients. Methods We prospectively recruited patients with migraine who received galcanezumab treatment at a single university hospital from June 2020 to April 2021. The treatment response was assessed after three consecutive monthly injections. A 50% responder rate was evaluated based on ≥50% reduction in the number of moderate/severe headache days. Results Overall, 87 patients were included in the analysis. Most patients were women (83.9%). They had a mean age of 41.7 ± 12.3 years (range 17–72). Sixty-five patients (74.7%) had chronic migraine, 35 patients (40.2%) had a history of medication-overuse headache, and 32 patients (36.8%) were previously unresponsive to or found intolerable five classes of preventive medication. After three months of treatment, mean changes in numbers of monthly headache days, moderate/severe headache days, crystal clear days, and days of acute medication use were −7.2 ± 8.43, −4.3 ± 9.76, 7.3 ± 8.50, and −4.1 ± 7.93, respectively. The 50% responder rates were 58.3%, 44.2%, and 40.6% for patients with unsuccessful previous use of 0–1, 2–4, and 5 preventive medication classes, respectively. Headache Impact Test-6 and Migraine Disability Assessment Test scores also decreased (−4.4 ± 8.09 and −32.9 ± 77.04, respectively). Conclusion In our cohort, the effectiveness and safety of galcanezumab were comparable with those reported in clinical trials, whereas a higher response rate was observed in the difficult-to-treat patient subset than that reported in trials. We provide real-world evidence of galcanezumab treatment benefits in Asian patients with migraine.
The DADYS-Screen: Development and Evaluation of a Screening Tool for Affective Dysregulation in Children

Affective dysregulation (AD) in children is characterized by persistent irritability and severe temper outbursts. This study developed and evaluated a screening questionnaire for AD in children. The development included the generation of an initial item pool from existing instruments, a Delphi rating of experts, focus groups with experts and parents, and psychometric analyses of clinical and population-based samples. Based on data of a large community-based study, the final screening questionnaire was developed (n = 771; 49.7 % female; age M = 10.02 years; SD = 1.34) and evaluated (n = 8,974; 48.7 % female; age M = 10.00 years; SD = 1.38) with methods from classical test theory and item response theory. The developed DADYS-Screen (Diagnostic Tool for Affective Dysregulation in Children—Screening Questionnaire) includes 12 items with good psychometric properties and scale characteristics including a good fit to a one-factorial model in comparison to the baseline model, although only a “mediocre” fit according to the root mean square error of approximation (RMSEA). Results could be confirmed using a second and larger data set. Overall, the DADYS-Screen is able to identify children with AD, although it needs further investigation using clinical data.
Oral Anticoagulant Treatment and the Risk of Dementia in Patients With Atrial Fibrillation: A Population‐Based Cohort Study

Background We compared the dementia incidence rate between users and nonusers of oral anticoagulants (OACs) in a large cohort of primary care patients with atrial fibrillation. Methods and Results We performed a retrospective study using an Australia‐wide primary care data set, MedicineInsight. Patients aged ≥18 years and newly diagnosed with atrial fibrillation between January 1, 2010, and December 31, 2017, and with no recorded history of dementia or stroke were included and followed until December 31, 2018. We applied a propensity score for 1:1 pair matching of baseline covariates and Cox regression for comparing the dementia incidence rates for OAC users and nonusers. Data were analyzed for 18 813 patients with atrial fibrillation (aged 71.9±12.6 years, 47.1% women); 11 419 had a recorded OAC prescription for at least 80% of their follow‐up time. During the mean follow‐up time of 3.7±2.0 years, 425 patients (2.3%; 95% CI, 2.1%–2.5%) had a documented diagnosis of dementia. After propensity matching, the incidence of dementia was significantly lower in OAC users (hazard ratio [HR], 0.59; 95% CI, 0.44–0.80; P<0.001) compared with nonusers. Direct‐acting oral anticoagulant users had a lower incidence of dementia than non‐OAC users (HR, 0.49; 95% CI, 0.33–0.73; P<0.001) or warfarin users (HR, 0.46; 95% CI, 0.28–0.74; P=0.002). No significant difference was seen between warfarin users and non‐OAC users (HR, 1.08; 95% CI, 0.70–1.70; P=0.723). Conclusions In patients with atrial fibrillation, direct‐acting oral anticoagulant use may result in a lower incidence of dementia compared with treatment with either warfarin or no anticoagulant.
Molecular characterization of KRAS wild type tumors in patients with pancreatic adenocarcinoma.

PURPOSE KRAS mutation (MT) is a major oncogenic driver in PDAC. A small subset of PDACs harbor KRAS-wild-type (WT). We aim to characterize the molecular profiles of KRAS-WT PDAC to uncover new pathogenic drivers and offer targeted treatments. EXPERIMENTAL DESIGN Tumor tissue obtained from surgical or biopsy material was subjected to next-generation DNA/RNA sequencing, microsatellite-instability (MSI) and mismatch-repair (MMR) status determination. RESULTS Of the 2,483 patients (male 53.7%, median-age 66 years) studied, 266 tumors (10.7%) were KRAS-WT. The most frequently mutated gene in KRAS-WT-PDAC was TP53 (44.5%), followed by BRAF (13.0%) . Multiple mutations within the DNA-damage-repair (BRCA2, ATM, BAP1, RAD50, FANCE, PALB2), chromatin-remodeling (ARID1A, PBRM1, ARID2, KMT2D, KMT2C, SMARCA4, SETD2), and cell-cycle-control pathways (CDKN2A, CCND1, CCNE1) were detected frequently. There was no statistically-significant difference in PDL1-expression between KRAS-WT (15.8%) and MT (17%) tumors. However, KRAS-WT-PDAC were more likely to be MSI-high (4.7% vs 0.7%; p<0.05), TMB-high (4.5% vs 1%; p<0.05), and exhibit increased infiltration of CD8+ T-cells, NK-cells and myeloid dendritic cells. KRAS-WT-PDACs exhibited gene fusions of BRAF (6.6%), FGFR2 (5.2%), ALK (2.6%), RET (1.3%) and NRG1 (1.3%), as well as amplification of FGF3 (3%), ERBB2 (2.2%), FGFR3 (1.8%), NTRK (1.8%) and MET (1.3%). Real-world evidence reveals a survival advantage of KRAS-WT patients in overall cohorts as well as in patients treated with gemcitabine/nab-paclitaxel or 5FU/oxaliplatin. CONCLUSIONS KRAS-WT PDAC represents 10.7% of PDAC and is enriched with targetable alterations, including immuno-oncologic markers. Identification of KRAS-WT patients in clinical practice may expand therapeutic options in a clinically meaningful manner.
Long non-coding RNA PTPRG-AS1/microRNA-124-3p regulates radiosensitivity of nasopharyngeal carcinoma via the LIM Homeobox 2-dependent Notch pathway through competitive endogenous RNA mechanism

ABSTRACT Nasopharyngeal carcinoma (NPC) is a malignant tumor in the nasopharyngeal cavity. LncRNA PTPRG-AS1 is essential in NPC radiosensitivity. This study sought to explore the mechanism of PTPRG-AS1 in NPC radiosensitivity by regulating the miR-124-3p/LHX2 axis. First, NPC-related microarray was analyzed to screen differentially expressed lncRNAs. PTPRG-AS1 and miR-124-3p expression patterns in NPC tissues and adjacent tissues of NPC patients and NPC cell lines were detected by RT-qPCR. PTPRG-AS1 was knocked down in CNE2 and 5–8 F cells by transfection. The radiosensitivity, proliferation and apoptosis before and after radiotherapy (0/6 Gy) were detected by cloning formation assay, CCK-8 assay, and flow cytometry. Bioinformatics, Pearson correlation analysis, RNA pull-down, and luciferase reporter assays were performed to explore the regulatory relationship of the lncRNA PTPRG-AS1/miR-124-3/LHX2 axis. The corresponding functions were verified in the complementation test. The levels of LHX2 and Notch pathway-related proteins were detected by Western blot. PTPRG-AS1 was upregulated in NPC cell lines and tissues. PTPRG-AS1 knockdown decreased NPC cell proliferation and promoted radiotherapy-induced apoptosis and cell radiosensitivity. PTPRG-AS1 upregulated LHX2 as a ceRNA of miR-124-3p. miR-124-3p inhibition partially reversed PTPRG-AS1 silencing-induced NPC cell radiosensitivity. miR-124-3p targeted LHX2. LHX2 overexpression attenuated the miR-124-3p overexpression-induced NPC cell radiosensitivity. LHX2 attenuated NPC cell radiosensitivity by activating the Notch pathway. Briefly, lncRNA PTPRG-AS1 reduced NPC cell radiosensitivity by regulating the miR-124-3p/LHX2 axis through the ceRNA mechanism. Graphical abstract
Stellate ganglion block successfully relieved medically unexplained chronic pain: a case report

Medically unexplained symptoms refers to a clinical syndrome characterized by somatic symptoms that cannot be reasonably explained by any organic disease. Chronic pain can be a type of medically unexplained symptom. The current treatment modalities for chronic pain mainly include drugs and psychotherapy. The use of stellate ganglion block for treatment of chronic pain has rarely been reported. Herein, we report a patient whose chronic pain was completely relieved after receiving a stellate ganglion block.
Abnormal High-sensitivity C-reactive Protein is Associated with an Increased Risk of Cardiovascular Disease and Renal Dysfunction among Patients Diagnosed with Type 2 Diabetes Mellitus in Palestine

OBJECTIVE In this study, we aimed to evaluate the prevalence of high sensitivity C-reactive protein (hsCRP) as an inflammatory mediator and its association with renal function and other biochemical markers in patients with type 2 diabetes mellitus. METHODS We carried out a cross-sectional study at private healthcare center. We included 453 patients (48.6% males and 51.4% females) with type 2 diabetes mellitus. We obtained sociodemographic, clinical, and laboratory data from patient medical records. We carried out statistical analysis to ascertain associations between parameters. RESULTS The overall risk of cardiovascular disease (hsCRP > 1 mg/L) among the study participants was 27.2%. Age, gender, body mass index, fasting blood glucose and serum creatinine were significantly associated with risk of cardiovascular disease (hsCRP > 1 mg/L) whereas estimated glomerular filtration rate, vitamin B12, calcium, sodium and metformin users were negatively associated with the hsCRP. CONCLUSIONS We found a significant positive association of elevated level of C-reactive protein with type 2 diabetes mellitus. Moreover, additional to increased cardiovascular disease risk, hsCRP also seems to be a major inflammatory risk marker indicating renal function loss.
Associations Between Dietary Patterns and Incident Type 2 Diabetes: Prospective Cohort Study of 120,343 UK Biobank Participants.

OBJECTIVE To identify dietary patterns (DPs) characterized by a set of nutrients of concern and their association with incident type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS A total of 120,343 participants from the U.K. Biobank study with at least two 24 h dietary assessments were studied. Reduced rank regression was used to derive DPs explaining variability in energy density, free sugars, saturated fat, and fiber intakes. We investigated prospective associations with T2D using Cox proportional hazard models. RESULTS Over 8.4 years of follow-up from the latest dietary assessment, 2,878 participants developed T2D. Two DPs were identified that jointly explained a total of 63% variation in four nutrients. DP1 was characterized by high intakes of chocolate and confectionery, butter, low-fiber bread, and sugars and preserves, and low intakes of fruits and vegetables. DP1 was linearly associated with T2D in multivariable models without BMI adjustment (per z score, hazard ratio [HR] 1.11 [95% CI 1.08-1.14]) and after BMI adjustment (HR 1.09 [95% CI 1.06-1.12]). DP2 was characterized by high intakes of sugar-sweetened beverages, fruit juice, table sugars and preserves, and low intakes of high-fat cheese and butter, but showed no clear association with T2D. There were significant interactions between both DPs and age, with increased risks among younger people in DP1 (HR 1.13 [95% CI 1.09-1.18]) and DP2 (HR 1.10 [95% CI 1.05-1.15]), as well as with DP1 and BMI, with increased risks among people with obesity (HR 1.11 [95% CI 1.07-1.16]). CONCLUSIONS A DP characterized by high intakes of chocolate, confectionery, butter, low-fiber bread, and added sugars, and low in fresh fruits and vegetables intake is associated with a higher incidence of T2D, particularly among younger people and those with obesity.
Induction chemotherapy followed by radical chemoradiotherapy for patients with stage IV non‐metastatic nasopharyngeal carcinoma: 11‐Year Experience in a tertiary centre

T4 nasopharyngeal carcinoma (NPC) with close proximity to critical organs at risk (OARs) is usually underdosed during radiotherapy in order to respect radiation constraints. N3 disease has high risk of distant metastasis. Induction chemotherapy (IC) provides advantages of sparing of OARs during subsequent chemoradiotherapy (CCRT) and early eradication of micrometastasis. However, factors predicting successes of IC in this patient group are not well‐studied.
Copper induces cell death by targeting lipoylated TCA cycle proteins

Copper is an essential cofactor for all organisms, and yet it becomes toxic if concentrations exceed a threshold maintained by evolutionarily conserved homeostatic mechanisms. How excess copper induces cell death, however, is unknown. Here, we show in human cells that copper-dependent, regulated cell death is distinct from known death mechanisms and is dependent on mitochondrial respiration. We show that copper-dependent death occurs by means of direct binding of copper to lipoylated components of the tricarboxylic acid (TCA) cycle. This results in lipoylated protein aggregation and subsequent iron-sulfur cluster protein loss, which leads to proteotoxic stress and ultimately cell death. These findings may explain the need for ancient copper homeostatic mechanisms. Description Copper induces cell death Cell death is an essential, finely tuned process that is critical for the removal of damaged and superfluous cells. Multiple forms of programmed and nonprogrammed cell death have been identified, including apoptosis, ferroptosis, and necroptosis. Tsvetkov et al. investigated whether abnormal copper ion elevations may sensitize cells toward a previously unidentified death pathway (see the Perspective by Kahlson and Dixon). By performing CRISPR/Cas9 screens, several genes were identified that could protect against copper-induced cell killing. Using genetically modified cells and a mouse model of a copper overload disorder, the researchers report that excess copper promotes the aggregation of lipoylated proteins and links mitochondrial metabolism to copper-dependent death. —PNK Lipoylation determines sensitivity to copper-induced cell death.
Helminths get MIFfed by the tuft cell – ILC2 circuit

The gut is a common site for helminth infections. Immunity to helminths relies on a strong type 2 response that is characterized by cytokines such as interleukin (IL)-4, 5 and 13. Intestinal type 2 immunity culminates in a “weep and sweep” response governed by ample mucus production (weep) and an increase in smooth muscle contraction (sweep), which act together to expel helminths. Although some of the characteristics of a type 2 response have been clear for a while, there are still large knowledge gaps in exactly how it is mounted. In a recent study by Varyani et al . , it was found that macrophage migration inhibitory factor (MIF), a cytokine-like factor 1966, essential for the induction of a strong intestinal type 2 immune response 1
Reading and phonological awareness improvement accomplished by transcranial direct current stimulation combined with phonological awareness training: A randomized controlled trial

Abstract Phonological awareness (PA) training is a core intervention in dyslexia. Recently, transcranial direct current stimulation (tDCS) has been probed as a complementary intervention for increasing reading ability in dyslexia, but not for enhancing the efficacy of PA. The aim of the current study was thus to examine whether tDCS combined with a PA intervention improves reading, but also PA abilities as a proxy in children with dyslexia. A randomized, double-blind, sham-controlled clinical trial was performed to assess the effects of tDCS (applied bilaterally over the temporo-parietal junction with the anode placed over the left, and the cathode placed over the right hemisphere) combined with PA training on reading and PA abilities in dyslexic patients. Twenty-eight participants were randomly assigned to active (PA + anodal tDCS) or sham (PA + sham tDCS) groups. Each subject participated in 15 treatment sessions. PA and real/non-word reading were evaluated at baseline before the intervention, at the end of the fifth, tenth, and final intervention sessions, and then 6 weeks after intervention. In the active tDCS group, the mean scores of non-word reading and PA tests were significantly improved during, immediately, and 6 weeks after the treatment, as compared to the sham tDCS group. tDCS is thus a promising complementary intervention if combined with PA training to enhance PA and reading abilities in dyslexia for an extended period after treatment.
Five‐year audit of adherence to an anaesthesia pre‐induction checklist

Although patient safety related to airway management has improved substantially over the last few decades, life‐threatening events still occur. Technical skills, clinical expertise and human factors contribute to successful airway management. Checklists aim to improve safety by providing a structured approach to equipment, personnel and decision‐making. This audit investigates adherence to our institution's airway checklist from 1 June 2016 to 31 May 2021. Inclusion criteria were procedures requiring airway management and we excluded all procedures performed solely under regional anaesthesia, sedation without airway management or paediatric and cardiovascular surgery. The primary outcome was the proportion of wholly performed pre‐induction checklists. Secondary outcomes were the pattern of adherence over the 5 years well as details of airway management, including: airway management difficulties; time and location of induction; anaesthesia teams in operating theatres (including teams for different surgical specialities); non‐operating theatre and emergency procedures; type of anaesthesia (general or combined); and urgency of the procedure. In total, 95,946 procedures were included. In 57.3%, anaesthesia pre‐induction checklists were completed. Over the 5 years after implementation, adherence improved from 48.3% to 66.7% (p < 0.001). Anticipated and unanticipated airway management difficulties (e.g. facemask ventilation, supraglottic airway device or intubation) defined by the handling anaesthetist were encountered in 4.2% of all procedures. Completion of the checklist differed depending on the time of day (61.3% during the day vs. 35.0% during the night, p < 0.001). Completion also differed depending on location (66.8% in operating theatres vs. 41.0% for non‐operating theatre anaesthesia, p < 0.001) and urgency of procedure (65.4% in non‐emergencies vs. 35.4% in emergencies, p < 0.001). A mixed‐effect model indicated that urgency of procedure is a strong predictor for adherence, with emergency cases having lower adherence (OR 0.58, 95%CI 0.49–0.68, p < 0.001). In conclusion, over 5 years, a significant increase in adherence to an anaesthesia pre‐induction checklist was found, and areas for further improvement (e.g. emergencies, non‐operating room procedures, night‐time procedures) were identified.
A label-free biomarkers detection platform relied on a bilayer long-wave infrared metamaterials BioNEMS sensor

A novel approach based on optical Biological-Nano-Electro-Mechanical-Systems (BioNEMS) sensor is presented in this paper to provide highly sensitive and precise detection of biomolecules. The proposed BioNEMS sensor is relied on a bi-layer metamaterials structure, tuned by its wavelength. The presented biosensor consists of a BioNEMS membrane coated by Complementary Split Ring Resonators and an array of Split Ring Resonators cells on the substrate. While the immobilized bioreceptors adsorb the biomarkers (i.e. mRNA or protein), it causes a bending of the suspended membrane. This is due to the differential surface stress which is induced on the Nano-Electro-Mechanical-Systems structure. As a consequence, the coupling strength of two complementary metamaterial layers and thus the electromagnetic response of the biosensor are changed. Furthermore, the proposed device is designed and analyzed by numerical and analytical approaches in order to obtain its functional characteristics as follows: detection sensitivity of 21 967 nm/RIU, figure of merit of 327.8 RIU−1", mechanical sensitivity of 2.6 μm/Nm−1" and resonant frequency of 4.92 kHz. According to the obtained results, the functional characteristics of the proposed label-free biosensor show its high potential for highly sensitive and accurate molecule detections, disease diagnosis as well as drug delivery tests for Lab-On-Chip systems.