Miracle-dz/UniFAR-FTUs huggingface dataset:
Multimaterial bioprinting and combination of processing techniques towards the fabrication of biomimetic tissues and organs

Tissue reconstruction requires the utilization of multiple biomaterials and cell types to replicate the delicate and complex structure of native tissues. Various three-dimensional (3D) bioprinting techniques have been developed to fabricate customized tissue structures; however, there are still significant challenges, such as vascularization, mechanical stability of printed constructs, and fabrication of gradient structures to be addressed for the creation of biomimetic and complex tissue constructs. One approach to address these challenges is to develop multimaterial 3D bioprinting techniques that can integrate various types of biomaterials and bioprinting capabilities towards the fabrication of more complex structures. Notable examples include multi-nozzle, coaxial, and microfluidics-assisted multimaterial 3D bioprinting techniques. More advanced multimaterial 3D printing techniques are emerging, and new areas in this niche technology are rapidly evolving. In this review, we briefly introduce the basics of individual 3D bioprinting techniques and then discuss the multimaterial 3D printing techniques that can be developed based on combination of these techniques for the engineering of complex and biomimetic tissue constructs. We also discuss the perspectives and future directions to develop state-of-the-art multimaterial 3D bioprinting techniques for engineering tissues and organs.
Gynogenetic diploids, tetraploids, or octoploids, and a path to polyploidy in Anuran Amphibians.

Unreduced gametes have been implicated in the evolution of polyploid species of plants and animals and are normally produced by female anuran amphibians. Such eggs may initiate the evolution of polyploid species that have independently arisen in several anuran families. Polyploid females could also produce unreduced eggs that might lead to species with higher ploidy levels or their eggs may develop gynogenetically to reduce the ploidy level. Diploid Hyla chrysoscelis (2n=24) and tetraploid H. versicolor (4n=48) are sibling cryptic species of North American Grey Treefrogs. Artificial crosses using H. versicolor females and genetically distant diploid males were performed to produce haploid H. versicolor and to assess the production of unreduced eggs in this tetraploid species. Gynogenetic diploid (haploid H. versicolor), allotriploid, gynogenetic tetraploid, allopentaploid, autohexaploid, and gynogenetic octoploid tadpoles were confirmed using chromosome counts from tadpole tail tip squashes. Transformation and survival of the different ploidies varied. Gynogenetic diploids transformed but expressed aspects of the haploid syndrome and died before or shortly after transformation.
MACF1 alleviates aging‐related osteoporosis via HES1

Ageing‐related osteoporosis is becoming an emerging threat to human health along with the ageing of human population. The decreased rate of osteogenic differentiation and bone formation is the major cause of ageing‐related osteoporosis. Microtubule actin cross‐linking factor 1 (MACF1) is an important cytoskeletal factor that promotes osteogenic differentiation and bone formation. However, the relationship between MACF1 expression and ageing‐related osteoporosis remains unclear. This study has investigated the expression pattern of MACF1 in bone tissues of ageing‐related osteoporosis patients and ageing mice. The study has further elucidated the mechanism of MACF1 promoting bone formation by inhibiting HES1 expression and activity. Moreover, the therapeutic effect of MACF1 on ageing‐related osteoporosis and post‐menopausal osteoporosis was evaluated through in situ injection of the MACF1 overexpression plasmid. The study supplemented the molecular mechanisms between ageing and bone formation, and provided novel targets and potential therapeutic strategy for ageing‐related osteoporosis.
Investigating the origin of the fetal gut and placenta microbiome in twins

Abstract Objective It is widely accepted that the microbiota is critical for human well-being; however, the origin of microbiota in the newborn is not well understood. In this study, we hypothesized that within a maternal-twin dyad (MTD) the meconium microbiome will be similar to the placenta microbiome and the meconium microbiome of within MTD will be similar to one another. Methods Prospectively, meconium (proxy for fetal gut), placenta and maternal buccal, skin, vaginal, stool samples were collected from a cohort of MTDs at time of delivery hospitalization. We performed gene sequencing using the V4 region of 16S rRNA with rigorous negative controls. Alpha and beta diversity indices were computed to characterize the microbial community of MTD samples. A p value of <. 05 was considered significant. Results From 17 MTD, 87/132 samples were successfully sequenced. The alpha diversity of the microbiome collected from all the body sites were different (p ≤ .001). The meconium samples when compared to other samples in the MTD microbial community were different (p = .009) and the Bray–Curtis dissimilarity was greater than 0.95 for all of the comparisons (beta diversity). The MTD within-twin placenta microbiome samples were also different, confirmed by Bray–Curtis pairwise dissimilarity distance, 0.83. Conclusion The fetal gut microbiome is different from placenta and maternal buccal, skin, vaginal and stool microbiome. We clearly identified a distinct placenta microbiome. Furthermore, placentas in the same MTD have distinct microbiomes, suggesting that fetal gut and placenta origin is complex and remains unclear.
Walnut intake, cognitive outcomes and risk factors: a systematic review and meta-analysis

Abstract Background Walnuts contain nutrients that are associated with improved cognitive health. To our knowledge, no review has systematically examined the effects of walnuts on cognitive function and risk for cognitive decline. Objective To conduct a systematic review and meta-analysis evaluating the effects of walnut intake on cognition-related outcomes and risk-factors for cognitive decline in adults. Methods Medline®, Commonwealth Agricultural Bureau, and Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) and observational studies published until April 2020 on walnut intake, cognition (e.g. cognitive function, stroke, and mood), and selected risk factors for cognitive decline (e.g. glucose homeostasis and inflammation). Risk-of-bias and strength-of-evidence assessments were conducted using standard validated tools. Random-effects meta-analyses were conducted when ≥3 studies reported quantitative data for each outcome. Results 32 RCT and 7 observational study publications were included. Meta-analysis of cognition-related outcomes could not be conducted due to heterogeneity of tests. None of the 5 cognition RCTs found significant effects of walnuts on overall cognition, although 3 studies found improvements on subdomains and/or subgroups. All 7 observational studies found significant associations and a dose-response relationship between walnut intake and cognition-related outcomes. Meta-analyses of 27 RCTs reporting glucose homeostasis and inflammation outcomes, selected risk factors for cognitive decline, did not show significant effects of walnut intake. Conclusions Due to the non-uniformity of tests for cognition-related outcomes, definitive conclusions regarding the effect of walnut consumption on cognition could not be reached. Additionally, evidence does not show associations between walnut intake and glucose homeostasis or inflammation, cognitive decline risk-factors. High-quality studies with standardized measures are needed to clarify the role of walnuts in cognitive health. KEY MESSAGES This is a systematic review and meta-analysis of 5 randomized clinical trials and 7 observational study articles of the impact of walnut intake on cognition decline and 27 randomized clinical trials of the effect of walnut intake on risk factors for cognitive decline including glucose homeostasis and inflammation. The non-uniformity of tests performed to measure cognitive function in the various studies did not allow for a meta-analysis of these studies. A definitive conclusion could therefore not be reached regarding the effect of walnut intake on cognitive decline. The evidence available does not show an association between walnut intake and glucose homeostasis or inflammation.
Photometric Evaluation of Adult Patients With Bilateral Cleft Lip and Palate Treated With Nasoalveolar Molding and Primary Columella Lengthening

A short columella and a flattened nasal tip are the characteristic stigmata of patients with complete bilateral cleft lip and palate (BCLP). Objective: The aim of this study was to assess the nasal shape of young adults with BCLP treated with primary surgical columella lengthening and nasoalveolar molding (NAM). Setting and Patients: A group of 28 young adult patients with BCLP (mean age: 19.1±1.4 years) was compared through normalized photogrammetry to a control of 28 age- and sex-matched noncleft young adults. Results: Nasal protrusion and length of the columella were not different from noncleft young adults. On the other hand, nasolabial angle, columellar width, interalar, and nasal tip width were significantly wider than the noncleft controls. Thus, 27% of the patients have requested at this time secondary correction of the excessive nasal width. Conclusions: Both NAM and primary rhinoplasty in patients with BCLP resulted in a near normal length of the columella and nasal projection until young adulthood. Nevertheless, width of all nasal features was significantly wider than the noncleft population and required secondary nasal correction in one-third of the sample.
Development and psychometric properties of the Nursing Student Academic Resilience Inventory (NSARI): A mixed-method study

Introduction Resilience has been proposed as a suitable solution to better deal with nursing students in cases of challenges but the complex and multidimensional nature of resilience has made its measurement challenging. This study aimed to develop and validate a new inventory theory-driven labeled Nursing Student Academic Resilience Inventory. Methods This study was performed with an exploratory sequential mixed-method design. In the qualitative phase of the study, individual interviews were conducted by including 15 participants to elicit the concept of resilience through purposive sampling. In the quantitative phase, psychometric analysis of the extracted items was performed using face, content, and construct validities (exploratory and confirmatory factor analyses) on a sample size of 405 nursing students. Besides, reliability has been tested using internal consistency and test-retest methods. According to the COSMIN standards, beside two important indicators of validity and reliability, responsiveness and interpretability were also considered. Results A 6-factor structure (optimism, communication, self-esteem/evaluation, self-awareness, trustworthiness, and self-regulation) with 24 items were extracted in terms of the derived categories from the qualitative phase. In confirmatory factor analysis, the χ2/df ratio was calculated as 2.11 for the NSARI six-factor structure. Suitable values were obtained for the goodness of fit indices (CFI = 0.904, AGFI = 0.885, IFI = 0.906, PCFI = 0.767, and RMSEA = 0.053). In the second-order factor analysis, AVE = 0.70 indicated the existence of both convergent and divergent validities. The Cronbach’s alpha and omega coefficients were investigated as (0.66–0.78) and (0.66–0.80), respectively. The AIC was between 0.33 and 0.45 for all factors, which is an acceptable rate. Additionally, an intraclass correlation coefficient (ICC) was obtained as . 903 for the whole instrument (CI .846- .946, P <0.0001). Conclusion Multidimensional nature of resilience was supported through exploring its 6-factor structures in the nursing students’ field. This tool also showed an acceptable validity and reliability for measuring resilience in the population of nursing students.
Periodic Manual Algorithm Updates and Generalizability: A Developer’s Response. Comment on “Evaluation of Four Artificial Intelligence–Assisted Self-Diagnosis Apps on Three Diagnoses: Two-Year Follow-Up Study”

We have several comments on the recent publication of Ćirković [1], in which repeated testing of four symptom assessment applications with clinical vignettes was carried out to look for “hints of ‘non-locked learning algorithms’. ” As the developer of one of the symptom assessment applications studied by Ćirković [1], we are supportive of studies evaluating app performance; however, there are important limitations in the methodology of this study.
FDA Approval Summary: Selinexor for Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

In June 2020, the FDA granted accelerated approval to selinexor for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Approval was based on SADAL, a multicenter trial of selinexor monotherapy in patients with DLBCL after 2 to 5 systemic regimens. Efficacy was based on independent review committee-assessed objective response rate (ORR) and duration of response using Lugano criteria. In 134 patients treated with the approved dosage (60 mg orally on Days 1 and 3 of each week), the ORR was 29% (95% CI, 22-38), with complete response in 13% and 38% of responses lasting at least 6 months. Gastrointestinal toxicity developed in 80% of patients, hyponatremia in 61%, central neurological toxicity (such as dizziness and mental status changes) in 25%, and ocular toxicity in 18%. New or worsening Grade 3 or 4 thrombocytopenia, lymphopenia, neutropenia, anemia, or hyponatremia developed in ≥15%. Adverse reactions led to selinexor dose interruption in 61% of patients, dose reduction in 49%, and permanent discontinuation in 17%, with thrombocytopenia being the leading cause of dose modifications. Post-marketing studies will evaluate reduced dosages of selinexor and further evaluate clinical benefit in patients with relapsed or refractory DLBCL. IMPLICATIONS FOR PRACTICE: Selinexor is a new potential option for adults with relapsed or refractory DLBCL NOS in the third-line setting or beyond. Toxicities are typically manageable, but can be difficult to tolerate and necessitate close monitoring and supportive care.
Comparing Two Commercially Available Diabetes Apps to Explore Challenges in User Engagement: Randomized Controlled Feasibility Study

Background Diabetes apps represent a promising addition to face-to-face self-management interventions, which can be time and resource intensive. However, few randomized controlled trials have evaluated the efficacy of diabetes apps, in particular as a stand-alone intervention without additional clinical support. Objective We used a feasibility randomized trial design to investigate differences in user engagement between 2 commercially available apps (free versions of Glucose Buddy and mySugr) over 2 weeks in adults with type 2 diabetes. Feasibility was assessed based on recruitment uptake, adherence to the diabetes apps, and follow-up rates. We also hypothesized that the diabetes app mySugr would demonstrate higher user engagement at follow-up due to its use of gamification. We also predicted higher user engagement would be associated with improved self-care behaviors and illness beliefs. Methods Adults with type 2 diabetes attending outpatient diabetes clinics in Auckland were recruited and randomized (1:1 without blinding) to use either the Glucose Buddy or mySugr diabetes apps. User engagement, self-care behaviors, and illness beliefs were measured 2 weeks after baseline. Spearman rank correlations, Mann-Whitney tests, and Wilcoxon signed-rank tests were used to explore associations between the outcome measures and to investigate possible changes between and within groups. Six participants were interviewed to further explore acceptability and usability. Results In total, 58 participants (29 per group) completed the 2-week follow-up, of whom only 38 reported using the apps (Glucose Buddy: n=20; mySugr: n=18). Both groups reported low engagement (Glucose Buddy: median 4 days; mySugr: median 6.5 days; P=.06; use for both groups: median 10 minutes). No changes were observed in self-care or illness beliefs in either group. Out of the self-care behaviors, only blood glucose testing was significantly associated with minutes of app use (P=.02). The interviews suggested that although both apps were deemed acceptable, they were generally viewed as time-consuming and too complicated to use. Conclusions Low engagement with both Glucose Buddy and mySugr reflect the challenges associated with engaging users with diabetes apps. Due to low engagement and loss to follow-up, the changes in outcome measures should be interpreted with caution. The results highlight the need for more clinical support as well as involvement from end users and behavior change specialists in order to incorporate evidence-based behavior change techniques to motivate and provide value to users. Trial Registration Australia New Zealand Clinical Trials Registry ACTRN12618000424202; https://www.anzctr. org.au/Trial/Registration/TrialReview.aspx? id=374671
Heart rate variability and chronotype – a systematic review

ABSTRACT There is a scarcity of evidence on the association between heart rate variability (HRV) and chronotype, i.e., morningness and eveningness. The aim of this systematic review was to examine the association between chronotype, HRV, mood and stress response. We searched PubMed, Web of Science, Scopus, Cinahl, PsycINFO and Google Scholar for peer-reviewed articles published in English between January 2000 and June 2020. A total of 11 articles met the inclusion criteria and were on study population, assessment of HRV and chronotype, main results and study limitations. Seven of the included studies were experimental and four were crossovers. The sample size varied from 9 to 221 participants, and both females and males were included. HRV was assessed using mostly time-domain and frequency-domain parameters; nonlinear parameters were used in only one study. The most used assessments for measuring chronotype were the Horne-Östberg Morningness-Eveningness Questionnaire (MEQ) and the Munich Chronotype Questionnaire (MCTQ). The results showed that chronotype was associated with HRV, but the study designs were situation-specific, focusing, for example, on the effects of shiftwork, stressful situations, exercise, or sleep deprivation on HRV. In addition, some studies showed that evening types (E-type) performed better during evening or nighttime tasks, whereas morning types (M-type) performed better during morning activities. Specifically, E-types showed decreased HRV and HRV recovery in relation to tasks performed during morning or daytime when compared to M-types. As the findings are somewhat contradictory and include some methodological limitations (e.g., small sample sizes, age groups), it is important for future studies to evaluate the association between chronotype and HRV in a longitudinal setting. In addition, further research is needed to determine how chronotype can be optimally and individually utilized to increase the health and well-being of M-type and E-type individuals.
Pharmacogenetics‐Guided Advances in Antipsychotic Treatment

Pharmacogenetics (PGx) research over the past 2 decades has produced extensive evidence for the influence of genetic factors on the efficacy and tolerability of antipsychotic treatment. However, the application of these findings to optimize treatment outcomes for patients in clinical practice has been limited. This paper presents a meta‐review of key PGx findings related to antipsychotic response and common adverse effects, including antipsychotic‐induced weight gain, tardive dyskinesia (TD), and clozapine‐induced agranulocytosis (CIAG), and highlights advances and challenges in clinical implementation. Most robust findings from candidate gene and genomewide association studies were reported for associations between polymorphisms in CYP2D6 and exposure and response to specific antipsychotics. As a result, product labels and guidelines from various PGx expert groups have provided selection and dosing recommendations based on CYP2D6 metabolizer phenotypes for commonly prescribed antipsychotics. Other interesting genetic targets include DRD2 for antipsychotic response, SLC18A2 for TD, and the human leukocyte antigen (HLA) genes, HLA‐DQB1 and HLA‐B, for CIAG. Well‐designed studies using large, well‐characterized samples that leverages international collaborations are needed to validate previous findings, as well as discover new genetic variants involved in antipsychotic response and adverse effects.
Integrin β7 Inhibits Colorectal Cancer Pathogenesis via Maintaining Antitumor Immunity

ITGB7 (integrin β7) inhibits tumorigenesis and progression of colorectal cancer (CRC) by maintaining sufficient tumor infiltration of various immune cell subsets essential for cancer cell recognition and killing. The data highlight an immune-supportive role of ITGB7 in CRC. Immune cell infiltration is important for predicting the clinical outcomes of colorectal cancer. Integrin β7 (ITGB7), which is expressed on the surface of leukocytes, plays an essential role in the homing of immune cells to gut-associated lymphoid tissue and facilitating the retention of lymphocytes in gut epithelium; however, its role in colorectal cancer pathogenesis is poorly explored. Here, we found that the number of β7+ cells decreased significantly in tumor tissue compared with adjacent normal tissue. β7 expression decreased in tumor-derived compared with normal tissue–derived CD8+ T cells. With bulk RNA expression data from public platforms, we demonstrated that higher ITGB7 expression correlated with longer patient survival, higher cytotoxic immune cell infiltration, lower somatic copy-number alterations, decreased mutation frequency of APC and TP53, and better response to immunotherapy. The possible cell–cell interactions mediated by ITGB7 and its ligands MAdCAM-1, VCAM-1, and CDH1 were investigated using public single-cell RNA sequencing data. ITGB7 deficiency led to exaggerated tumorigenesis and progression in both Apcmin/+ spontaneous and MC38 orthotopic models of colorectal cancer, which could be due to a reduced infiltration of activated CD8+ T cells, effector memory CD8+ T cells, IFNγ+ CD8+ T cells, IFNγ+ natural killer cells, CD103+ dendritic cells, and other immune cell subsets that are essential players in antitumor immunity. In conclusion, our data revealed that ITGB7 could inhibit the tumorigenesis and progression of colorectal cancer by maintaining antitumor immunity.
Clinical use of zinc in viral warts: a systematic review of the clinical trials

Abstract Background Zinc has shown promise in the treatment of patients with viral warts in several clinical trials, but there is no consensus on its effectiveness. Objective To investigate the efficacy of various formulations of zinc on cutaneous warts. Data sources We searched the Cochrane Central Register of Controlled Trials, EMBASE, PUBMED, and Web of Science without publishing-time restriction. Trials examining zinc in the treatment of warts were collected. Results Out of 265 articles, a total of 16 met inclusion criteria. Six clinical trials investigated the clinical effectiveness of oral zinc supplementation alone in treating viral warts, two trials evaluated the efficacy of oral zinc in combination with other therapy, five trials investigated the efficacy of intralesional zinc sulfate, and three trials investigated topical zinc treatment efficacy. Zinc therapy was found to be beneficial in 13 of 16 studies evaluating its effects on warts. Conclusions The use of zinc is a simple, safe, and cost-effective treatment in viral warts based on some preliminary evidence. However, more well-designed studies need to be performed to further evaluate the effect of zinc on warts.