Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential effects of ELX/TEZ/IVA on organ-specific CFTR function in two patients with the rare CFTR splice mutations c.273+1G>A and c.165-2A>G

Introduction: Evidence for the efficiency of highly-effective triple-CFTR-modulatory therapy with elexacaftor/tezacaftor/ivacaftor (ETI), either demonstrated in clinical trials or by in vitro testing, is lacking for about 10% of people with cystic fibrosis (pwCF) with rare mutations. Comprehensive assessment of CFTR function can provide critical information on the impact of ETI on CFTR function gains for such rare mutations, lending argument of the prescription of ETI. The mutation c.165-2A>G is a rare acceptor splice mutation that has not yet been functionally characterized. We here describe the functional changes induced by ETI in two brothers who are compound heterozygous for the splice mutations c.273+1G>C and c.165-2A>G. Methods: We assessed the effects of ETI on CFTR function by quantitative pilocarpine iontophoresis (QPIT), nasal potential difference measurements (nPD), intestinal current measurements (ICM), β-adrenergic sweat secretion tests (SST) and multiple breath washout (MBW) prior to and 4 months after the initiation of ETI. Results: Functional CFTR analysis prior to ETI showed no CFTR function in the respiratory and intestinal epithelia and in the sweat gland reabsorptive duct in either brother. In contrast, β-adrenergic stimulated, CFTR-mediated sweat secretion was detectable in the CF range. Under ETI, both brothers continued to exhibit high sweat chloride concentration in QPIT, evidence of low residual CFTR function in the respiratory epithelia, but normalized β-adrenergically stimulated production of primary sweat. Discussion: Our results are the first to demonstrate that the c.165-2A>G/c.273+1G>C mutation genotype permits mutant CFTR protein expression. We showed organ-specific differences in the expression of CFTR and consecutive responses to ETI of the c.165-2A>G/c.273+1G>C CFTR mutants that are probably accomplished by non-canonical CFTR mRNA isoforms. This showcase tells us that the individual response of rare CFTR mutations to highly-effective CFTR modulation cannot be predicted from assays in standard cell cultures, but requires the personalized multi-organ assessment by CFTR biomarkers.
Multiple thread ligations versus stapled hemorrhoidopexy on operative outcomes of grade III hemorrhoids: A retrospective cohort study

Object Controversy remains regarding the safety and efficacy of hemorrhoid ligation and stapled hemorrhoidopexy (SH) in the treatment of hemorrhoids. The study was to explore the operative outcomes of patients underwent multiple thread ligations (MTL) with SH for the management of grade III hemorrhoids. Methods This cohort study included patients who underwent MTL (MTL group, 128 cases) or SH (SH group, 141 cases) for grade III hemorrhoids between June 2019 and May 2021. A total of 115 patients in MTL group and 115 patients in SH group were finally included by propensity score matching with a ratio of 1:1. The primary outcome was the recurrence of prolapse within 6 months. Secondary outcomes were operative time, post-operative pain scores, hospital stay, the incidence of complications, Wexner incontinence score, and quality of life of patients with constipation at 6 months post procedure. Results Multiple thread ligations and SH resulted in comparable recurrence within 6 months of follow-up, with five and seven cases of recurrence, respectively, (P = 0.352). The two groups had comparable outcomes in terms of post-operative pain, hospital stay, Wexner incontinence scores, and constipation-related quality of life (all P > 0.05). The median operative time was 16 min (15–18 min) in the MTL group versus 25 min (16–33 min) in the SH group (P < 0.01). Univariate analysis showed that the MTL technique had a lower risk of postoperative bleeding than that with the SH technique (P < 0.05). Conclusion The study indicated that the MTL technique might achieve comparable operative outcomes compared with the SH technique for the management of grade III hemorrhoids, nevertheless, MTL seemed to be associated with less risk of surgical bleeding than SH.
Body roundness index is related to the low estimated glomerular filtration rate in Chinese population: A cross-sectional study

Background Kidney disease is related to visceral obesity. As a new indicator of obesity, body roundness index (BRI) has not been fully revealed with kidney disease. This study’s objective is to assess the relationship between estimated glomerular filtration rate (eGFR) and BRI among the Chinese population. Methods This study enrolled 36,784 members over the age of 40, they were from 7 centers in China by using a random sampling method. BRI was computed using height and waist circumference, eGFR ≤ 90 mL/min/1.73 m2 was considered to indicate low eGFR. To lessen bias, propensity score matching was employed, multiple logistic regression models were utilized to examine the connection between low eGFR and BRI. Results The age, diabetes and coronary heart disease rates, fasting blood glucose, and triglycerides were all greater in participants with low eGFR. The BRI quartile was still positively connected with low eGFR after controlling for confounding variables, according to multivariate logistic regression analysis. (OR [95%CI] Q2:1.052 [1.021-1.091], OR [95%CI] Q3:1.189 [1.062-1.284], OR [95%CI] Q4:1.283 [1.181-1.394], P trend < 0.001). Stratified research revealed that the elders, women, habitual smokers, and those with a history of diabetes or hypertension experienced the connection between BRI level and low eGFR. According to ROC, BRI was able to detect low eGFR more accurately. Conclusion Low eGFR in the Chinese community is positively connected with BRI, which has the potential to be used as an effective indicator for screening kidney disease to identify high-risk groups and take appropriate measures to prevent subsequent complications.
Escherichia coli infection indicates favorable outcomes in patients with infected pancreatic necrosis

Introduction Infected pancreatic necrosis (IPN) is a severe complication of acute necrotizing pancreatitis with increasing morbidity. Escherichia coli is the most frequently cultured microorganism in IPN. However, the implications of Escherichia coli infection on the outcomes of patients with IPN remain unclear. Therefore, this study aimed to evaluate the clinical impacts of Escherichia coli infection on IPN. Methods A prospective database with consecutive patients with IPN between January 2010 and April 2022 at a tertiary hospital was post-hoc analyzed. The clinical and microbiological characteristics, surgical management, and follow-up data of patients with and without Escherichia coli infection were compared. Results A total of 294 IPN patients were enrolled in this cohort. Compared with non-Escherichia coli infection cases (n=80, 27.2%), patients with Escherichia coli infection (n=214, 72.8%) were characterized by more frequent polymicrobial infections (77.5% vs. 65.0%, P=0.04) but a lower occurrence of severe acute pancreatitis (SAP) (42.5% vs. 61.7%, P=0.003). In addition, significantly lower mortality (12.5% vs. 30.4%, p=0.002), fewer step-up surgical interventions (73.8% vs. 85.1%, P=0.025), and a lower rate of multiple organ failure (MOF) (25.0% vs. 40.2%, P=0.016) were also observed in patients with Escherichia coli infection. Multivariate analysis of mortality predictors indicated that MOF (odds ratio [OR], 6.197; 95% confidence interval [CI], 2.373–16.187; P<0.001) and hemorrhage (OR, 3.485; 95% CI, 1.623–7.487; P=0.001) were independent predictors associated with higher mortality in patients with IPN. Escherichia coli infection was significantly associated with a lower mortality (OR, 0.302; 95% CI, 0.121–0.751; P= 0.01). Conclusion Escherichia coli infection indicates a favorable prognosis in patients with IPN, although the mechanism needs further investigation.
Deficits in odor discrimination versus odor identification in patients with schizophrenia and negative correlations with GABAergic and DNA methyltransferase mRNAs in lymphocytes

Introduction People with schizophrenia have been reported to show deficits in tests of olfactory function. DNA methylation and GABAergic input have been implicated in biochemical processes controlling odor in animal studies, but this has not been investigated in human studies. Methods In a study of measures of DNA methylation and GABAergic mRNAs in lymphocytes, we also measured odor identification and discrimination with the Sniffin’ Sticks battery in 58 patients with chronic schizophrenia (CSZ) and 48 controls. mRNAs in lymphocytes were assessed by qPCR using TaqManTM probes. Cognition was assessed by the MATRICS battery (Measurement and Treatment Research to Improve Cognition in Schizophrenia) in CSZ and controls, and symptoms in CSZ were assessed by PANSS scale (Positive and Negative Symptom Scale). The relationships of odor deficits with mRNA, cognition, and symptoms were explored by correlation analysis. Variables which significantly differentiated CSZ from controls were explored by logistic regression. Results Overall, CSZ showed significantly (P≤.001) lower scores on odor discrimination compared to controls, with a moderate effect size, but no difference in odor identification. Deficits in odor discrimination, which has not been standardly assessed in many prior studies, strongly differentiated CSZ from controls. In logistic regression analysis, odor discrimination, but not odor identification, was a significant variable predicting schizophrenia versus control class membership. This is the first study to report relationship between odor deficits and DNA methylation and GABAergic mRNAs in blood cells of human subjects. There were negative correlations of odor identification with DNA methylation enzymes mRNAs and significant negative correlations with odor discrimination and GABAergic mRNAs. Lower odor scores were significantly associated with lower cognitive scores on the MATRICS battery in CSZ but not control subjects. In CSZ, lower odor scores were significantly associated with negative symptom scores, while higher odor identification scores were associated with PANNS Excitement factor. Discussion Odor discrimination was a more powerful variable than odor identification in discriminating CSZ from controls and should be used more regularly as an odor measure in studies of schizophrenia. The substantive meaning of the negative correlations of odor discrimination and GABAergic mRNA variables in peripheral lymphocytes of CSZ needs more investigation and comparison with results in neural tissue.
An essential role of the reversible electron-bifurcating hydrogenase Hnd for ethanol oxidation in Solidesulfovibrio fructosivorans

The tetrameric cytoplasmic FeFe hydrogenase Hnd from Solidesulfovibrio fructosivorans (formely Desulfovibrio fructosovorans) catalyses H2 oxidation and couples the exergonic reduction of NAD+ to the endergonic reduction of a ferredoxin by using a flavin-based electron-bifurcating mechanism. Regarding its implication in the bacterial physiology, we previously showed that Hnd, which is non-essential when bacteria grow fermentatively on pyruvate, is involved in ethanol metabolism. Under these conditions, it consumes H2 to produce reducing equivalents for ethanol production as a fermentative product. In this study, the approach implemented was to compare the two S. fructosivorans WT and the hndD deletion mutant strains when grown on ethanol as the sole carbon and energy source. Based on the determination of bacterial growth, metabolite consumption and production, gene expression followed by RT-q-PCR, and Hnd protein level followed by mass spectrometry, our results confirm the role of Hnd hydrogenase in the ethanol metabolism and furthermore uncover for the first time an essential function for a Desulfovibrio hydrogenase. Hnd is unequivocally required for S. fructosivorans growth on ethanol, and we propose that it produces H2 from NADH and reduced ferredoxin generated by an alcohol dehydrogenase and an aldehyde ferredoxin oxidoreductase catalyzing the conversion of ethanol into acetate. The produced H2 could then be recycled and used for sulfate reduction. Hnd is thus a reversible hydrogenase that operates in H2-consumption by an electron-bifurcating mechanism during pyruvate fermentation and in H2-production by an electron-confurcating mechanism when the bacterium uses ethanol as electron donor.
Study on the influence of scaffold morphology and structure on osteogenic performance

The number of patients with bone defects caused by various bone diseases is increasing yearly in the aging population, and people are paying increasing attention to bone tissue engineering research. Currently, the application of bone tissue engineering mainly focuses on promoting fracture healing by carrying cytokines. However, cytokines implanted into the body easily cause an immune response, and the cost is high; therefore, the clinical treatment effect is not outstanding. In recent years, some scholars have proposed the concept of tissue-induced biomaterials that can induce bone regeneration through a scaffold structure without adding cytokines. By optimizing the scaffold structure, the performance of tissue-engineered bone scaffolds is improved and the osteogenesis effect is promoted, which provides ideas for the design and improvement of tissue-engineered bones in the future. In this study, the current understanding of the bone tissue structure is summarized through the discussion of current bone tissue engineering, and the current research on micro-nano bionic structure scaffolds and their osteogenesis mechanism is analyzed and discussed.
Main social vulnerability indicators in the COVID-19 pandemic in Iran

Background Social factors play the main role in the vulnerability of exposed countries to disasters. The COVID-19 pandemic as a disaster is not an exception to this fact. This study aimed to determine the main social vulnerability indicators in the COVID-19 pandemic in Iran. Methods This study was conducted during the period of 2021–2022 in three phases, including a systematic review, a virtual panel expert, and the Analytical Hierarchy Process. First, the draft of social vulnerability indicators in COVID-19 was extracted through a systematic review. Then, the extracted indicators were finalized and prioritized by the expert panel and the AHP, respectively. Results Initially, the literature review found five domains and 38 indicators of social vulnerability in COVID-19. The outcome of the expert panel increased the related domains to six but decreased the indicators to 31. The three prioritized social vulnerability indicators that were determined by the AHP were population density, accessibility to healthcare facilities, and relevant services and vulnerable groups. Conclusion Measuring social vulnerability with the identified indicators is valuable for addressing high COVID-19 incidence among socially vulnerable hotspot areas. Regarding the result of this study, further research should be conducted to validate the identified indicators.
The association between working memory and mathematical problem solving: A three-level meta-analysis

Although working memory (WM) is an important factor in mathematical problem solving (MPS), it remains unclear how well WM relates to MPS. Thus, we aimed to determine this relationship by using a meta-analysis. We searched electronic databases for studies published between 2000 and 2020 and established operational criteria. We conducted Egger’s regression tests and created funnel plots to test for publication bias. Finally, a three-level meta-analytic model analysis of data from 130 studies involving 43,938 participants and 1,355 effect sizes revealed a moderate relationship between WM and MPS (r = 0.280, 95% CI = [0.263, 0.314]). Moreover, moderator analyses showed that: (1) dressed-up word problems were more strongly tied to WM than to intra-mathematical problems; (2) the central executive function showed the strongest relation with MPS, whereas the phonological loop had the weakest; (3) gender ratio had significant moderating effects; and (4) some of the above-mentioned significant moderating effects were unique after controlling for other factors. Implications for research and practice were also discussed.
What to Look for in Relationships: Development, inter-rater reliability, and initial validity estimates for a young child-caregiver relationship assessment

Introduction Observational assessments are important for understanding a range of behaviors and emotions in the young child-caregiver relationship. This paper provides initial data on a multidimensional assessment for professionals who work with young children and their caregivers, the What to Look for in Relationships (WLR). The WLR was designed to assist providers in evaluating strengths and areas for improvement in five areas of young child-caregiver relationship dimensions. This paper reports on the development, interrater reliability, initial convergent and discriminant validity, and incremental utility of the scales. Methods Data were collected from caregiver-child dyads, who participated in a semi-structured observational caregiver-child interaction session as part of a clinic evaluation for relationship-based therapeutic services for young children in child protection. Recorded interactions were coded using the WLR scales with 146 interactions coded by at least two independent observers for interrater reliability analyses. Results The scales showed adequate internal consistency, good inter-rater reliability, strong convergent associations with a single dimension measure (i.e., the Parent-Infant Relationship Global Assessment Scale; PIR-GAS) and discriminated those in the clinical range from those with adaptive functioning on the PIR-GAS. Discussion This study provides initial support for the usefulness of the WLR scales for assessing dimensions of caregiver-child relationships during early childhood that may be useful targets of intervention.
A robotic arm control system with simultaneous and sequential modes combining eye-tracking with steady-state visual evoked potential in virtual reality environment

At present, single-modal brain-computer interface (BCI) still has limitations in practical application, such as low flexibility, poor autonomy, and easy fatigue for subjects. This study developed an asynchronous robotic arm control system based on steady-state visual evoked potentials (SSVEP) and eye-tracking in virtual reality (VR) environment, including simultaneous and sequential modes. For simultaneous mode, target classification was realized by decision-level fusion of electroencephalography (EEG) and eye-gaze. The stimulus duration for each subject was non-fixed, which was determined by an adjustable window method. Subjects could autonomously control the start and stop of the system using triple blink and eye closure, respectively. For sequential mode, no calibration was conducted before operation. First, subjects’ gaze area was obtained through eye-gaze, and then only few stimulus blocks began to flicker. Next, target classification was determined using EEG. Additionally, subjects could reject false triggering commands using eye closure. In this study, the system effectiveness was verified through offline experiment and online robotic-arm grasping experiment. Twenty subjects participated in offline experiment. For simultaneous mode, average ACC and ITR at the stimulus duration of 0.9 s were 90.50% and 60.02 bits/min, respectively. For sequential mode, average ACC and ITR at the stimulus duration of 1.4 s were 90.47% and 45.38 bits/min, respectively. Fifteen subjects successfully completed the online tasks of grabbing balls in both modes, and most subjects preferred the sequential mode. The proposed hybrid brain-computer interface (h-BCI) system could increase autonomy, reduce visual fatigue, meet individual needs, and improve the efficiency of the system.
Site-directed mutagenesis identified the key active site residues of 2,3-oxidosqualene cyclase HcOSC6 responsible for cucurbitacins biosynthesis in Hemsleya chinensis

Hemsleya chinensis is a Chinese traditional medicinal plant, containing cucurbitacin IIa (CuIIa) and cucurbitacin IIb (CuIIb), both of which have a wide range of pharmacological effects, including antiallergic, anti-inflammatory, and anticancer properties. However, few studies have been explored on the key enzymes that are involved in cucurbitacins biosynthesis in H. chinensis. Oxidosqualene cyclase (OSC) is a vital enzyme for cyclizing 2,3-oxidosqualene and its analogues. Here, a gene encoding the oxidosqualene cyclase of H. chinensis (HcOSC6), catalyzing to produce cucurbitadienol, was used as a template of mutagenesis. With the assistance of AlphaFold2 and molecular docking, we have proposed for the first time to our knowledge the 3D structure of HcOSC6 and its binding features to 2,3-oxidosqualene. Mutagenesis experiments on HcOSC6 generated seventeen different single-point mutants, showing that single-residue changes could affect its activity. Three key amino acid residues of HcOSC6, E246, M261 and D490, were identified as a prominent role in controlling cyclization ability. Our findings not only comprehensively characterize three key residues that are potentially useful for producing cucurbitacins, but also provide insights into the significant role they could play in metabolic engineering.
A surveillance procedure for random walks based on local linear estimation

We study the problem of detecting a change in the trend of time series whose stochastic part behaves as a random walk. Interesting applications in finance and engineering come to mind. Local linear estimation provides a well established approach to estimating level and derivative of an underlying trend function, provided the time instants where observations are available become dense asymptotically. Here we study the local linear estimation principle for the classic time series setting where the distance between time points is fixed. It turns out that local linear estimation is applicable to the detection problem, and we identify the underlying (asymptotic) parameters. Assuming that observations arrive sequentially, we propose surveillance procedures and establish the relevant asymptotic theory, particularly, an invariance principle for the sequential empirical local linear process. A simulation study illustrates the remarkable accuracy of the approximations obtained by our asymptotics even in small samples as well as the excellent detection performance of the proposed surveillance procedure.
Falling and heaviness: Heaviness judgment for a visual object which users lift up is influenced by the presentation of the object's falling or staying still

When lifting and subsequently releasing a visual object on a screen using a computer mouse, users tend to judge the object to be heavier when the motion speed of the object during lifting is smaller. However it was unclear how the presentation of an object falling after its release influenced the judgment of heaviness. Users generally believe mistakenly that heavier objects fall faster. Based on the previous report of this misbelief, we briefly explored how the falling speed of a visual object after release by a user influenced the judgment of heaviness. The falling speed of the object was systematically modulated by changing gravity in the simulation of the natural falling of the object. Participants judged the object's heaviness after they lifted and subsequently released it. As a result, the participants judged the object to be lighter when the falling speed was zero. However, no significant differences were observed among the conditions with a falling speed greater than zero. It is suggested that for the judgment of heaviness, a vital aspect in the presentation of a falling object after releasing is whether the object falls or not.