Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple imputation methods for handling incomplete longitudinal and clustered data where the target analysis is a linear mixed effects model

Multiple imputation (MI) is increasingly popular for handling multivariate missing data. Two general approaches are available in standard computer packages: MI based on the posterior distribution of incomplete variables under a multivariate (joint) model, and fully conditional specification (FCS), which imputes missing values using univariate conditional distributions for each incomplete variable given all the others, cycling iteratively through the univariate imputation models. In the context of longitudinal or clustered data, it is not clear whether these approaches result in consistent estimates of regression coefficient and variance component parameters when the analysis model of interest is a linear mixed effects model (LMM) that includes both random intercepts and slopes with either covariates or both covariates and outcome contain missing information. In the current paper, we compared the performance of seven different MI methods for handling missing values in longitudinal and clustered data in the context of fitting LMMs with both random intercepts and slopes. We study the theoretical compatibility between specific imputation models fitted under each of these approaches and the LMM, and also conduct simulation studies in both the longitudinal and clustered data settings. Simulations were motivated by analyses of the association between body mass index (BMI) and quality of life (QoL) in the Longitudinal Study of Australian Children (LSAC). Our findings showed that the relative performance of MI methods vary according to whether the incomplete covariate has fixed or random effects and whether there is missingnesss in the outcome variable. We showed that compatible imputation and analysis models resulted in consistent estimation of both regression parameters and variance components via simulation. We illustrate our findings with the analysis of LSAC data.
Fibrolytic enzymes improve the nutritive value of high-moisture corn for finishing bulls.

Exogenous fibrolytic enzymes (EFE) improve the energy availability of grains for nonruminant animals by reducing encapsulation of the endosperm nutrients within grain cell walls; however, these benefits are unknown in the treatment of corn-based silage for cattle. The objective of the present study was to evaluate the effects of adding EFE at ensiling on the nutritive value of high-moisture corn (HMC) and snaplage (SNAP) for finishing Nellore bulls. The EFE dose was 100 g/Mg fresh matter in both HMC and SNAP. Diets were 1) a SNAP + HMC control (without enzyme addition); 2) SNAP + HMC EFE (with enzymes); 3) a whole-plant corn silage (WPCS) + HMC control (without enzyme addition); and 4) WPCS + HMC EFE (with enzymes). In addition to the silages, the diets were also composed of soybean hulls, soybean meal, and mineral-vitamin supplement. The statistical design was a randomized complete block with a factorial arrangement of treatments, and the experiment lasted 122 d. For in situ and in vitro analyses, two cannulated dry cows were used. There was no interaction between the diets and EFE application (ADG, P = 0.92; DMI, P = 0.77; G:F, P = 0.70), and there was no difference between the SNAP and WPCS diets regarding the DMI (P = 0.53), ADG (P = 0.35) and feed efficiency (ADG:DMI, P = 0.83). Adding EFE to the HMC and SNAP at ensiling did not affect ADG but decreased DMI (P = 0.01), resulting in greater feed efficiency by 5.91% (P = 0.04) than that observed in animals fed diets without the addition of EFE. Addition of EFE to HMC resulted in reduced NDF content and increased in vitro and in situ DM digestibility compared with untreated HMC. No effects were found for the addition of EFE to SNAP. Fecal starch decreased with EFE application (P = 0.05). Therefore, the diet energy content (TDN, NEm, and NEg) calculated from animal performance increased (P = 0.01) with the addition of EFE to HMC. In conclusion, exchanging the NDF from WPCS with that from SNAP did not affect the performance of finishing cattle, whereas the addition of EFE to HMC at ensiling improved animal performance by increasing the energy availability of the grain.
Similar Biomechanical Cross-linking Effect After SMILE and PRK in Human Corneas in an Ex Vivo Model for Postoperative Ectasia.

PURPOSE To evaluate the biomechanical effect of corneal cross-linking (CXL) in paired human corneas following small incision lenticule extraction (SMILE) or photorefractive keratectomy (PRK) in an ex vivo model for postoperative ectasia. METHODS Twenty-six paired human corneas preserved in tissue culture medium were equally divided into two groups: right and left corneas were treated with PRK and SMILE, respectively. Corneal thickness was measured in all eyes before surgery. Corneas were stretched using an extensometer with two cycles of up to 9 N (570 kPA stress), followed by accelerated CXL with irradiance of 9 mW/cm2 for 10 minutes (fluence 5.4 J/cm2) in both groups. The elastic modulus was evaluated using two-dimensional stress-strain extensometry. RESULTS Following accelerated CXL, the ectatic cornea model showed a mean effective elastic modulus of 17.2 ± 5.3 MPa after PRK and 14.1 ± 5.0 MPa after SMILE. Although the elastic modulus in corneas previously subjected to PRK was higher, there was no significant biomechanical difference between the two groups (P = .093). CONCLUSIONS Under similar conditions, both experimental groups (PRK followed by CXL and SMILE followed by CXL) were characterized by similar biomechanical stability as measured experimentally on ex vivo human fellow corneas. The data suggest that, in the event of postoperative ectasia, the biomechanical improvement achieved by CXL may be similar after PRK and SMILE. [J Refract Surg. 2020;36(1):49-54].
Appropriateness of Fluoroquinolone Prescribing in the Long‐Term Care Setting

1970s and 1980s, reaching almost 5% in 1975. While now much less common, it is nevertheless surprising to find “delerium” surviving, not only peer review, editing, and proofreading, but also modern word processor software to make it into publication. One criticism of Google Scholar is that it does not screen out low-quality journals where the quality of peer review and editing may be poor. However, many of the examples we found came from widely respected journals. Although few misspellings were found in geriatric medical journals, the frequency in psychiatric journals was surprisingly high and misspellings seem disproportionately high in anesthetic journals. Phonetic spelling due to the pronunciation of delirium as del-EE-rium may explain some errors. Often with nonspecialist colleagues, one is so pleased to find, given its previous neglect, a diagnosis of delirium being made that it seems churlish to complain about the spelling. For writers, though, misspelling a common term will not impress reviewers or, if published, readers. The most widely studied, and potentially misleading, misspelling of a medical term is use of “pruritis” instead of “pruritus. ” Pruritus is misspelled in almost 5% of articles on the topic in PubMed, even in recent years, with a real risk that significant articles might be missed in literature searches or that “pruritis” might “overrun the correct form. ” “Delerium” is not as significant a problem as “pruritis. ” Nevertheless, our results suggest that, in addition to being sometimes misdiagnosed and mismanaged, delirium is also prone to being misspelled.
The basic helix‐loop‐helix transcription factor TCF4 impacts brain architecture as well as neuronal morphology and differentiation

Germline mutations in the basic helix‐loop‐helix transcription factor 4 (TCF4) cause the Pitt–Hopkins syndrome (PTHS), a developmental disorder with severe intellectual disability. Here, we report findings from a new mouse model with a central nervous system‐specific truncation of Tcf4 leading to severe phenotypic abnormalities. Furthermore, it allows the study of a complete TCF4 knockout in adult mice, circumventing early postnatal lethality of previously published mouse models. Our data suggest that a TCF4 truncation results in an impaired hippocampal architecture affecting both the dentate gyrus as well as the cornu ammonis. In the cerebral cortex, loss of TCF4 generates a severe differentiation delay of neural precursors. Furthermore, neuronal morphology was critically affected with shortened apical dendrites and significantly increased branching of dendrites. Our data provide novel information about the role of Tcf4 in brain development and may help to understand the mechanisms leading to intellectual deficits observed in patients suffering from PTHS.
One-lung ventilation for percutaneous thermal ablation of liver tumors in the hepatic dome

Abstract Purpose To investigate the feasibility, efficacy and safety of one-lung ventilation for percutaneous thermal ablation of liver tumors in the hepatic dome. Materials and methods From 5 January 2017 to 16 April 2019, 64 patients who underwent ultrasound-guided thermal ablation with a total of 75 liver malignant tumors located in the hepatic dome were enrolled in the present study. One-lung ventilation was employed to improve the acoustic window and protect the lung and diaphragm. If the one-lung ventilation was unsuccessful, artificial pleural effusion was added. The technical efficacy was confirmed by contrast-enhanced computed tomography/magnetic resonance imaging (CT/MRI) 1 month later. After that, CT/MRI was performed every 3–6 months. Results Among the enrolled patients, the technical success rate of one lung ventilation was 92.2% (59/64). The visibility scores of tumors were improved significantly after one-lung ventilation compared to those before one-lung ventilation (p < .001). Finally, 78.6% (55/70) of the tumors achieved clinical success of one-lung ventilation to become clearly visible and underwent thermal ablation. Fourteen of the remaining 15 tumors achieved a satisfactory acoustic window after combination of artificial pleural effusion. One lesion remained inconspicuous and partly affected by pulmonary gas. The follow-up period was 8 months (3–30 months). The technical efficacy rate was confirmed to be 100% (75/75). During the follow-up period, local tumor progression occurred in 2 patients (2/75, 2.7%). Major complications occurred in two patients (2/64, 3.1%) receiving one-lung ventilation. Conclusions One-lung ventilation is a promising noninvasive method for the thermal ablation of hepatic dome tumors due to its efficacy and safety.
Conditional switching of KIF2A mutation provides new insights into cortical malformations pathogeny.

By using the Cre-mediated genetic switch technology, we were able to successfully generate a conditional knock-in mouse, bearing the KIF2A p.His321Asp missense point variant, identified in a subject with malformations of cortical development. These mice present with neuroanatomical anomalies and microcephaly associated with behavioral deficiencies and susceptibility to epilepsy, correlating with the described human phenotype. Using the flexibility of this model provides, we investigated RosaCre, NestinCre and NexCre driven expression of the mutation to dissect the pathophysiological mechanisms underlying neurodevelopmental cortical abnormalities. We show that expression of the p.His321Asp pathogenic variant increases apoptosis and causes abnormal multipolar to bipolar transition in newborn neurons, providing therefore insights to better understand cortical organization and brain growth defects that characterize KIF2A-related human disorders. We further demonstrate that the observed cellular phenotypes are likely to be linked to deficiency in the microtubule depolymerizing function of KIF2A.
Orbital seeding of mesenchymal stromal cells increases osteogenic differentiation and bone‐like tissue formation

In bone tissue engineering (TE), an efficient seeding and homogenous distribution of cells is needed to avoid cell loss and damage as well as to facilitate tissue development. Dynamic seeding methods seem to be superior to the static ones because they tend to result in a more homogeneous cell distribution by using kinetic forces. However, most dynamic seeding techniques are elaborate or require special equipment and its influence on the final bone tissue‐engineered construct is not clear. In this study, we applied a simple, dynamic seeding method using an orbital shaker to seed human bone marrow–derived mesenchymal stromal cells (hBMSCs) on silk fibroin scaffolds. Significantly higher cell numbers with a more homogenous cell distribution, increased osteogenic differentiation, and mineral deposition were observed using the dynamic approach both for 4 and 6 hours as compared to the static seeding method. The positive influence of dynamic seeding could be attributed to both cell density and distribution but also nutrient supply during seeding and shear stresses (0.0‐3.0 mPa) as determined by computational simulations. The influence of relevant mechanical stimuli during seeding should be investigated in the future, especially regarding the importance of mechanical cues for bone TE applications. Our results highlight the importance of adequate choice of seeding method and its impact on developing tissue‐engineered constructs. The application of this simple seeding technique is not only recommended for bone TE but can also be used for seeding similar porous scaffolds with hBMSCs in other TE fields.
A promiscuous inflammasome sparks replication of a common tumor virus

Significance Infectious agents, including viruses, activate cellular inflammasomes. Viruses have evolved strategies to parry such host defense mechanisms, and cancer-causing gammaherpesviruses such as Epstein−Barr virus (EBV) are no exception. In distinct contrast, we show that this ubiquitous virus exploits assembly of the NLRP3 inflammasome to kick-start its lytic cascade; this allows EBV to reactivate from quiescence, propagate, and leave the cell when the cell perceives intrinsic or extrinsic threats. This discovery also provides a predictive signature that marks cells in which EBV is poised to enter the lytic phase. Importantly also, with hyperglycemia known to activate the NLRP3 inflammasome, our findings provide a mechanistic basis for recent clinical observations of diabetes as a significant risk factor for EBV-lymphomas in transplant recipients. Viruses activate inflammasomes but then subvert resulting inflammatory responses to avoid elimination. We asked whether viruses could instead use such activated or primed inflammasomes to directly aid their propagation and spread. Since herpesviruses are experts at coopting cellular functions, we investigated whether Epstein−Barr virus (EBV), an oncoherpesvirus, exploits inflammasomes to activate its replicative or lytic phase. Indeed, our experiments reveal that EBV exploits several inflammasome sensors to actually activate its replicative phase from quiescence/latency. In particular, TXNIP, a key inflammasome intermediary, causes assembly of the NLRP3 inflammasome, resulting in caspase-1−mediated depletion of the heterochromatin-inducing epigenetic repressor KAP1/TRIM28 in a subpopulation of cells. As a result, only TXNIPhiKAP1lo cells, that is, in a primed/prolytic state, turn expression of the replication/lytic/reactivation switch protein on to enter the replicative phase. Our findings 1) demonstrate that EBV dovetails its escape strategy to a key cellular danger-sensing mechanism, 2) indicate that transcription may be regulated by KAP1 abundance aside from canonical regulation through its posttranslational modification, 3) mechanistically link diabetes, which frequently activates the NLRP3 inflammasome, to deregulation of a tumor virus, and 4) demonstrate that B lymphocytes from NOMID (neonatal onset multisystem inflammatory disease) patients who have NLRP3 mutations and suffer from hyperactive innate responses are defective in controlling a herpesvirus.
Soluble AXL as a marker of disease progression and survival in melanoma

Receptor tyrosine kinase AXL is a one-pass transmembrane protein upregulated in cancers and associated with lower survival and therapy resistance. AXL can be cleaved by the A Disintegrin and Metalloproteinases (ADAM)10 and ADAM17, yielding a soluble version of the protein. Elevated soluble AXL (sAXL) has been reported to be associated with disease progression in hepatocellular carcinoma, renal cancer, neurofibromatosis type 1 and inflammatory diseases. In the present work, we analyzed sAXL levels in blood from melanoma patients and showed that sAXL increases with disease progression. Additionally, increased sAXL levels were found correlated with shorter two-year survival in stage IV patients treated with ipilimumab. Furthermore, we showed that sAXL levels were related to the percentage of cells expressing AXL in resected melanoma lymph node metastases. This finding was verified in vitro, where sAXL levels in the cell media corresponded to AXL expression in the cells. AXL inhibition using the small-molecular inhibitor BGB324 reduced sAXL levels, while the cellular expression was elevated through increased protein stability. Our findings signify that quantification of sAXL blood levels is a simple and easily assessable method to determine cellular AXL levels and should be further evaluated for its use as a biomarker of disease progression and treatment response.
The presence of the ACA box in archaeal H/ACA guide RNAs promotes atypical pseudouridylation

Archaea and eukaryotes, in addition to protein-only enzymes, also possess ribonucleoproteins containing an H/ACA guide RNA plus four proteins that produce pseudouridine (Ψ). Although typical conditions for these RNA-guided reactions are known, certain variant conditions allow pseudouridylation. We used mutants of the two stem–loops of the Haloferax volcanii sR-h45 RNA that guides three pseudouridylations in 23S rRNA and their target RNAs to characterize modifications under various atypical conditions. The 5′ stem–loop produces Ψ2605 and the 3′ stem–loop produces Ψ1940 and Ψ1942. The latter two modifications require unpaired “UVUN” (V = A, C, or G) in the target and ACA box in the guide. Ψ1942 modification requires the presence of U1940 (or Ψ1940). Ψ1940 is not produced in the Ψ1942-containing substrate, suggesting a sequential modification of the two residues. The ACA box of a single stem–loop guide is not required when typically unpaired “UN” is up to 17 bases from its position in the guide, but is needed when the distance increases to 19 bases or the N is paired. However, ANA of the H box of the double stem–loop guide is needed even for the 5′ typical pseudouridylation. The most 5′ unpaired U in a string of U's is converted to Ψ, and in the absence of an unpaired U, a paired U can also be modified. Certain mutants of the Cbf5 protein affect pseudouridylation by the two stem–loops of sR-h45 differently. This study will help elucidate the conditions for production of nonconstitutive Ψ’s, determine functions for orphan H/ACA RNAs and in target designing.
Pollen morphology of Chinese Pseudostellaria (Caryophyllaceae) and its systematic significance

Using light and scanning electron microscopy, we studied the pollen morphology of six species (one of which are endemic) of Chinese Pseudostellaria. All species were studied for the first time. Results of this study indicated that pollen grains of Pseudostellaria are spheroidal or spheroidal‐polyhedral in shape and small or medium in size and pantoporate. Each pollen grain has 12–16 round pores. These pores are apart from each other by 5.77–7.73 μm and each has 7–13 granules in the operculum region. These features have important taxonomic significance. In addition, their pollen grains have thin exine with microechinate‐punctate‐perforate surface ornamentation. Pollen features do not support the traditional infrageneric classification of Pseudostellaria into two sections, but support that Pseudostellaria is closely related to other species of the Odontostemma clade.
RETRACTED ARTICLE: Litchi Seed Aqueous Extracts play a role in suppression of epithelial-mesenchymal transition, invasion and migration in breast cancer cells

Statement of Retraction We, the Editors and Publisher of the journal Cell Cycle, have retracted the following article: Yanling Ma, Fei Yan, Wujie Wei, Jie Deng, Li Li, Li Liu, and Jianhai Sun. Litchi Seed Aqueous Extracts play a role in suppression of epithelial-mesenchymal transition, invasion and migration in breast cancer cells. Cell Cycle. 2020;18(3):317-325. doi: 10.1080/15384101.2019. 1710912. Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors did not provide their original data or any necessary supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.
The Ability of Baseline Triglycerides and Total Cholesterol Concentrations to Predict Incidence of Type 2 Diabetes Mellitus in Chinese Men and Women: A Longitudinal Study in Qingdao, China.

OBJECTIVE The purpose of this study was to assess the association between triglycerides (TG), total cholesterol (TC) at baseline, and type 2 diabetes mellitus (T2DM) incidence in a general Chinese population. Further, it aimed to evaluate the ability of TG and TC to predict T2DM incidence. METHODS Qingdao Diabetes Prevention Program participants recruited between 2006 and 2009 were followed up in 2012-2015. TG, TC, and T2DM status were measured. Cox proportional hazards models were used to estimate the association between TG, TC, and T2DM incidence. The receiver operating characteristic (ROC) curve was used to evaluate the ability of TG and TC to identify T2DM participants. RESULTS The incidence of T2DM significantly increased with TG in women and TC in both men and women (Ptrend < 0.05). Univariate Cox regression indicated that higher TG {borderline high TG [hazards ratio (HR): 2.05; 95% confidence interval (CI): 1.40, 3.00] and hypertriglyceridemia [HR: 2.64; 95% CI: 1.68, 4.15]} and TC [hypercholesterolemia (HR: 2.05; 95% CI: 1.43, 2.95)] were significantly associated with increased risk of T2DM incidence in women but not in men. Multivariate Cox regression showed that hypertriglyceridemia in women (HR: 1.78, 95% CI: 1.07, 2.97), borderline high TC in men (HR: 1.61, 95% CI: 1.04, 2.48), and hypercholesterolemia in women (HR: 1.68, 95% CI: 1.81, 2.61) had a higher significant risk of T2DM incidence. The optimal cutoff values of TG were > 1.15 and > 1.23 mmol/L in men and women, respectively. For TC, they were > 5.17 and > 5.77 mmol/L in men and women, respectively. The area under the ROCs of TG and TC were 0.54 (0.51-0.57) and 0.55 (0.52-0.58), respectively, in men, and 0.60 (0.58-0.62) and 0.59 (0.56-0.61), respectively, in women. CONCLUSION Elevated TG and TC were risk factors for T2DM incidence. However, no predictive capacity was found for both factors to identify T2DM incidence in Chinese men and women. Hence, TG and TC levels in both Chinese men and women might be used for decreasing the incidence of T2DM but no clinical predictive capacity for T2DM.