Miracle-dz/UniFAR-FTUs huggingface dataset:
An independent, replicable, functional and significant risk variant block at intron 3 of CACNA1C for schizophrenia

Objectives: Genome-wide association studies have identified a significant risk gene, CACNA1C, for schizophrenia. In this study, we comprehensively investigated a large set of CACNA1C single-nucleotide polymorphisms (SNPs) to identify the replicable risk alleles for schizophrenia and explore their biological functions. Methods: One Jewish (1044 cases vs 2052 controls), one European (1350 cases vs 1378 controls) and one exploratory African American samples (98 cases vs 20 controls) were analyzed to identify replicable single-nucleotide polymorphism–schizophrenia associations. The regulatory effects of risk alleles on CACNA1C messenger RNA expression were examined. The most robust risk tagSNP (rs1006737) was meta-analyzed on 17 studies (74,122 cases vs 109,062 controls), and associated with the gray matter volumes of seven subcortical structures in 38,258 Europeans, and the surface areas and thickness of 34 cortical regions in 33,992 Europeans and 2944 non-Europeans. Results: Forty-seven replicable risk single-nucleotide polymorphisms, including a 20-single-nucleotide polymorphism haplotype block, were identified in our samples (1.8 × 10−4 ⩽ p ⩽ 0.049). This variant block was consistently associated with schizophrenia across four independent Psychiatric Genomics Consortium cohorts (79,645 cases vs 109,590 controls; 2.5 × 10–17 ⩽ p ⩽ 0.017). This block showed significant expression quantitative trait loci in three independent European brain cohorts (5.1 × 10–12 ⩽ p ⩽ 8.3 × 10–3) and could be tagged by the most significant risk single-nucleotide polymorphism rs1006737. The minor allele A of rs1006737 significantly increased risk for schizophrenia across the Jewish and European samples (p = 0.029 and 0.004, respectively), and this association was highly significant in the meta-analysis (p = 1.62 × 10–42). This allele also significantly altered the CACNA1C messenger RNA expression in five brain regions (5.1 × 10–12 ⩽ p ⩽ 0.05), decreased the gray matter volume of thalamus (p = 0.010), the surface area of isthmus cingulate cortex (p = 0.013) and the thickness of transverse temporal and superior temporal sulcus cortexes (0.005 ⩽ p ⩽ 0.043). Conclusion: We identified an independent, replicable, functional, and significant risk variant block at CACNA1C for schizophrenia, which could be tagged by the most robust risk marker rs1006737, suggesting an important role of CACNA1C in the pathogenesis of schizophrenia.
Analysis of the prognostic factors determining the oncological outcomes in patients with high-risk early-stage cervical cancer

Abstract We aimed to evaluate clinicopathological data in high-risk early-stage cervical cancer and to define the prognostic factors determining the oncological outcomes. This retrospective study included 158 patients with stage IB–IIA cervical cancer who underwent radical hysterectomy plus lymph node dissection. Each patient had at least one high-risk factor. The median tumour diameter of the study group was 30 mm (range, 6–80). Seventy-five (47.5%) patients had parametrial invasion, 32 (20.3%) had positive surgical margins, and 108 (68.4%) had lymph node metastasis. The median duration of follow-up was 42 months (range, 1–228). During this period, 28 patients developed recurrence, and the recurrent disease occurred in a distant area in 18 patients. Five-year disease-free survival was 77.5%, and five-year disease-specific survival was 85%. In multivariate analysis, adjuvant radiotherapy was identified as an independent prognostic factor for recurrence and death. The recurrence (Odds ratio: 10.139, 95% CI: 1.477–69.590, p = .018) and mortality rates (Odds ratio: 16.485, 95% CI: 2.484–109.408, p =.004) were higher in patients who did not receive adjuvant therapy. IMPACT STATEMENT What is already known on this subject? The decision to proceed with adjuvant therapy in the patients with early-stage disease treated with surgery depends on the presence of risk factors in pathological examination. Various prognostic factors have been identified in cervical cancer (CC). However, there is a limited number of studies describing the prognostic factors in early-stage CC with high-risk factors. What do the results of this study add? In current study, the recurrence and mortality rates were higher in patients who did not receive adjuvant therapy. No relationship was found between the survival outcomes and the number of high-risk factors. Most of the patients who developed recurrence had the recurrence in the distant localisation. This result questioned the adequacy of adjuvant therapy. What are the implications of these findings for clinical practice and/or further research? There is still a debate over the prognostic factors and the adjuvant treatment options in the patients with early-stage cervical cancer who possess high-risk factors. Adjuvant RT or adjuvant concomitant chemoradiotherapy must definitely be used in this patients. However, adjuvant therapy fails approximately 14–32%, thus multimodal treatment modalities must be developed to improve the recurrence rates and the survival.
Fractional amplitude of low-frequency fluctuation in patients with neovascular glaucoma: a resting-state functional magnetic resonance imaging study.

Background Neovascular glaucoma (NVG) is a secondary refractory disease with a poor prognosis, and there are few advanced studies on its pathogenesis and treatment. In this research, the fractional amplitude of low-frequency fluctuation (fALFF) technology was used in resting-state functional magnetic resonance imaging (rsfMRI) to investigate intrinsic neuron activity in the patient's brain with NVG. Methods Sixteen patients with NVG (eight males and eight females) and 16 healthy controls (HCs) of similar age and sex were included. All patients and controls received rsfMRI scans, and the differences between the two groups in fALFF values were compared by independent sample t-test. Receiver operating characteristic (ROC) curves were used to compare fALFF values in the brain regions of NVG patients and HCs and assess accuracy. Finally, Pearson linear correlation analysis assessed the correlation between fALFF signals in brain regions and the clinical evaluation indicators of patients with NVG. Results In patients with NVG, fALFF signal values in the right Rolandic operculum, left anterior cingulate and paracingulate gyri, and right caudate were significantly decreased. In contrast, fALFF signal values in the left precuneus were significantly higher than those recorded in the HCs. Analysis of the ROC curve for each brain region showed that the area under the ROC curve of NVG patients was large (close to 1), and the accuracy was good. In the NVG group, the hospital anxiety and depression scale (r=-0.952, P<0.001) and left best-corrected visual acuity (r=-0.802, P<0.001) had a negative linear correlation with the fALFF signal value of the right Rolandic operculum. The hospital anxiety and depression scale had a negative linear correlation with the fALFF signal value of the right caudate (r=-0.948, P<0.001). Conclusions NVG patients showed dysfunction in several brain regions. These findings may assist in revealing the underlying neural mechanism of brain activity associated with NVG.
A meta-synthesis exploring caregiver experiences of home enteral tube feeding.

BACKGROUND It is estimated that 18,232 people received home enteral tube feeding (HETF) in the UK in 2013 and often HETF requires reliance on a caregiver. Caregivers are an essential resource, so research is needed to explore their perspectives to inform how best to support them. Therefore, this meta-synthesis aimed to explore caregiver experiences of HETF. METHODS A systematic search and meta-synthesis of literature relating to caregiver experiences of HETF was undertaken. Ethical approval was obtained from Coventry University Ethics. A comprehensive search of CINAHL, MEDLINE, Academic Search Complete, and SCOPUS databases was conducted, followed by a reference list search of included studies. Studies were screened for eligibility using a priori inclusion criteria. Included studies used qualitative methodology, were in English, and explored caregivers' experiences of supporting an adult or child receiving HETF for at least one month. The meta-synthesis was conducted using a thematic-synthesis method. Included studies were assessed for quality, and rigour was ensured via transparent reporting of methodology, peer review, and reflexivity. RESULTS In total 328 records were screened, with ten studies included and a total of 97 caregivers' experiences were reported. Four analytical themes were developed: loss of a normal life, psychological impact, practical challenges, and becoming the 'expert'. Overall quality of the included studies was assessed as good. CONCLUSION This meta-synthesis highlighted the challenges experienced by caregivers, and revealed the need for improved HETF training for caregivers and psychological support from HCPs, in order to provide personalised advice and regimes as part of holistic care.
The role of distinct executive functions on adaptive behavior in children and adolescents with Down syndrome

ABSTRACT Difficulties in executive function are a relatively well-characterized feature of the neuropsychological profile in Down syndrome (DS), yet the impact of these challenges on aspects of daily functioning remain poorly understood. We examined the role of specific executive functions on domains of adaptive behavior in children and adolescents with DS. Participants included 68 children and adolescents with DS between 6–17 years old (mean chronological age = 12.56 years; SD = 3.22) and their caregivers. Parent reported executive function skills were measured using the BRIEF-2 and adaptive behavior was measured using the Vineland Adaptive Behavior Scales-III. Results identified working memory as a significant predictor of Communication, Daily Living, and Socialization skills, and Shifting significantly predicted Daily Living and Socialization. Findings demonstrate the relation between executive functions and adaptive behavior and highlight the effects of working memory on aspects of daily functioning for individuals with DS.
Impact of Infant Milk-Type and Childhood Eating Behaviors on Functional Constipation in Preschool Children

ABSTRACT Objective: To investigate the association between functional constipation, infant feeding in early infancy and eating behavior in preschool children. Methodology: A cross-sectional study was undertaken in public and private schools in the state of Sergipe (Northeast of Brazil). The sample calculation was based on a 25% estimate of constipation prevalence in Brazilian children, resulting in a sample size of 1051 children. Functional constipation was assessed using Rome IV criteria. Eating behavior was assessed using the Children's Eating Behavior Questionnaire. Adjusted odds ratios were estimated using a multivariate model. Results: The prevalence of functional constipation was 23%. After adjusting for water intake, children with food fussiness were >6 times likely to have constipation (odds ratio [OR] = 6.65; 95% confidence interval [CI] 5.19–8.52). Children who were fed with cow's milk in the first 6 months of age were up to 15.2 times more likely to have functional constipation. Bottle feeding at 0–6 months of age increased the risk of functional constipation at preschool age (whole cow's milk: OR = 17.02; 95% CI 7.33–39.51, infant formula: OR = 6.35; 95% CI 3.42–11.79, mixed breastfeeding: OR = 10.83; 95% CI 4.57–25.69). Conclusion: Food fussiness and the use of cow's milk-based feeding bottles at 0–6 months of age were associated with functional constipation in preschool children.
It's the therapist and the treatment: The structure of common therapeutic relationship factors

Abstract Objective: Prior research has established that common therapeutic relationship factors are potent predictors of change in psychotherapy, but such factors are typically studied one at a time and their underlying structure when studied simultaneously is not clear. We assembled empirically validated relationship factors (e.g., therapist empathy; patient expectations; agreement about goals) into a single instrument and subjected it to factor analysis. Method: The instrument was applied to patients (N = 332) undergoing intensive psychotherapy of different types for depressive disorders, anxiety disorders, eating disorders, and childhood trauma in an inpatient specialized mental health setting. In order to examine the psychometric properties of the scale, we used half the sample (N=164) to conduct exploratory factor analysis (EFA) and parallel analysis before we tested the solution using exploratory structural equation modeling (ESEM) on the second half of the sample (N=168). Measurement invariance analysis was conducted to examine the stability of the factor structure. Results: The analysis yielded two factors, which were termed 1. “Confidence in the therapist” and 2. “Confidence in the treatment. ” Discussion: When assessed simultaneously, patients differentiate between their evaluation of the therapist and of the treatment. The results indicate that there is substantial overlap among previously established relationship factors. Trial registration: ClinicalTrials.gov identifier: NCT03503981.
In-hospital Complications Are More Likely to Occur After Reverse Shoulder Arthroplasty Than After Locked Plating for Proximal Humeral Fractures

Abstract Background Currently, there seems to be a paradigm change in the surgical treatment of proximal humeral fractures in patients aged 65 years and older, with a considerable increase in the use of reverse total shoulder arthroplasty (RTSA) compared with angular stable internal fixation (locking plate fixation). However, even among shoulder specialists there is controversy regarding the best treatment strategy. Questions/purposes To evaluate for (1) a greater risk of in-hospital major adverse events, (2) a greater risk for in-hospital surgical complications, and (3) a greater risk of 30-day mortality, locking plate fixation and RTSA were compared for the treatment of proximal humerus fractures of patients aged 65 years and older after controlling for potentially confounding variables in a large-database analysis. Methods Health claims data of the largest German insurance company including approximately one-third of the population (26.5 million policyholders) between 2010 and 2018 were analyzed. This database was chosen because of its size, nationwide distribution, and high quality/completeness. In total, 55,070 patients (≥ 65 years of age) treated with locking plate fixation (75% [41,216]) or RTSA (25% [13,854]) for proximal humeral fracture were compared. As primary endpoints, major adverse events (including acute myocardial infarction, stroke, organ failure, resuscitation, and death) and surgical complications (infection, hematoma, loss of reduction, dislocation, and revision surgery) were analyzed. The risk of all endpoints was analyzed with multivariable logistic regression models in the context of comorbidities to address existing group differences. Results After controlling for potentially confounding variables such as age, sex, and risk profile, RTSA was associated with a higher risk for major adverse events (OR 1.40 [95% CI 1.29 to 1.53]; p < 0.001) and surgical complications (OR 1.13 [95% CI 1.05 to 1.21]; p < 0.01) compared with locking plate fixation. There was no evidence for an increase in mortality (OR 0.98 [95% CI 0.86 to 1.12]; p = 0.81). Conclusion The increased in-hospital risk for major adverse events and surgical complications may moderate the enthusiasm associated with RTSA for proximal humeral fractures in patients 65 years and older. Treatment decisions should be based on individual risk estimation to avoid potential harmful events. Future studies must include long-term outcomes and quality of life to enlighten these findings in a broader context. Level of Evidence Level III, therapeutic study.
Kluyveromyces marxianus: a potential biocatalyst of renewable chemicals and lignocellulosic ethanol production

Abstract Kluyveromyces marxianus is an ascomycetous yeast which has shown promising results in cellulosic ethanol and renewable chemicals production. It can survive on a variety of carbon sources under industrially favorable conditions due to its fast growth rate, thermotolerance, and acid tolerance. K. marxianus, is generally regarded as a safe (GRAS) microorganism, is widely recognized as a powerhouse for the production of heterologous proteins and is accepted by the US Food and Drug Administration (USFDA) for its pharmaceutical and food applications. Since lignocellulosic hydrolysates are comprised of diverse monomeric sugars, oligosaccharides and potential metabolism inhibiting compounds, this microorganism can play a pivotal role as it can grow on lignocellulosic hydrolysates coping with vegetal cell wall derived inhibitors. Furthermore, advancements in synthetic biology, for example CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats with Cas9)-mediated genome editing, will enable development of an engineered yeast for the production of biochemicals and biopharmaceuticals having a myriad of industrial applications. Genetic engineering companies such as Cargill, Ginkgo Bioworks, DuPont, Global Yeast, Genomatica, and several others are actively working to develop designer yeasts. Given the important traits and properties of K. marxianus, these companies may find it to be a suitable biocatalyst for renewable chemicals and fuel production on the large scale. This paper reviews the recent progress made with K. marxianus biotechnology for sustainable production of ethanol, and other products utilizing lignocellulosic sugars.
Preoperative medication use and development of postoperative delirium and cognitive dysfunction

Postoperative delirium (POD) and postoperative (neuro‐)cognitive disorder (POCD) are frequent and serious complications after operations. We aim to investigate the association between pre‐operative polypharmacy and potentially inappropriate medications and the development of POD/POCD in elderly patients. This investigation is part of the European BioCog project (www.biocog.eu), a prospective multicenter observational study with elderly surgical patients. Patients with a Mini‐Mental State Examination score less than or equal to 23 points were excluded. POD was assessed up to 7 days after surgery using the Nursing Delirium Screening Scale, Confusion Assessment Method (for the intensive care unit [ICU]), and a patient chart review. POCD was assessed 3 months after surgery with a neuropsychological test battery. Pre‐operative long‐term medication was evaluated in terms of polypharmacy (≥5 agents) and potentially inappropriate medication (defined by the PRISCUS and European list of potentially inappropriate medications [EU(7)‐PIM] lists), and associations with POD and POCD were analyzed using logistic regression analysis. Eight hundred thirty‐seven participants were included for analysis of POD and 562 participants for POCD. Of these, 165 patients (19.7%) fulfilled the criteria of POD and 60 (10.7%) for POCD. After adjusting for confounders, pre‐operative polypharmacy and intake of potentially inappropriate medications could not be shown to be associated with the development of POD nor POCD. We found no associations between pre‐operative polypharmacy and potentially inappropriate medications and development of POD and POCD. Future studies should focus on the evaluation of drug interactions to determine whether patients benefit from a pre‐operative adjustment.
Evaluating outcomes of conservation with multidimensional indicators of well‐being

Many conservation interventions are hypothesized to be beneficial for both the environment and people's well‐being, but this has rarely been tested rigorously. We examined the effects of adoption or nonadoption of a conservation intervention on 3 dimensions of people's well‐being (material, relational, and subjective) over time. We focused on a fisheries bycatch management initiative intended to reduce environmental externalities associated with resource extraction. We collected panel data from fishers (n = 250) in villages with (adopters and nonadopters) and without (control) the conservation intervention 3 times over 2 years. We found no evidence that adoption reduced any of the 3 dimensions of well‐being in the local populations affected by the intervention. There were modest improvements in material (t = –1.58) and subjective livelihood well‐being (p = 0.04) for adopters relative to nonadopters over time. The variations in well‐being experiences (in terms of magnitude of change) among adopters, nonadopters, and controls across the different domains over time affirmed the dynamic and social nature of well‐being.
Establishment and verification of a prediction model based on clinical characteristics and positron emission tomography/computed tomography (PET/CT) parameters for distinguishing malignant from benign ground-glass nodules.

Background To develop and verify a prediction model for distinguishing malignant from benign ground-glass nodules (GGNs) combined with clinical characteristics and 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) parameters. Methods We retrospectively analyzed 170 patients (56 males and 114 females) with GGNs who underwent PET/CT and high-resolution CT examination in our hospital from November 2011 to December 2019. The clinical and imaging data of all patients were collected, and the nodules were randomly divided into a derivation set and a validation set. For the derivation set, we used multivariate logistic regression to develop a prediction model for distinguishing benign from malignant GGNs. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of the model, and the data in the validation set were used to verify the prediction model. Results Among the 170 patients, 197 GGNs were confirmed via postoperative pathological examination or clinical follow-up. There were 21 patients with 27 GGNs in the benign group and 149 patients with 170 GGNs in the adenocarcinoma group. A total of five parameters, including the patient's sex, nodule location, margin, pleural indentation, and standardized uptake value (SUV) index (the ratio of nodule SUVmax to liver SUVmean), were selected to develop a prediction model for distinguishing benign from malignant GGNs. The area under the curve (AUC) of the model was 0.875 in the derivation set, with a sensitivity of 0.702 and a specificity of 0.923. The positive likelihood ratio was 9.131, and the negative likelihood ratio was 0.322. In the validation set, the AUC of the model was 0.874, which was not significantly different from the derivation set (P=0.989). Conclusions This study developed and validated a prediction model based on 18F-FDG PET/CT imaging and clinical characteristics for distinguishing malignant from benign GGNs. The model showed good diagnostic efficacy and high specificity, which can improve the preoperative diagnosis of high-risk GGNs.