Miracle-dz/UniFAR-FTUs huggingface dataset:
Bio-fabrication of stem-cell-incorporated corneal epithelial and stromal equivalents from silk fibroin and gelatin-based biomaterial for canine corneal regeneration

Corneal grafts are the imperative clinical treatment for canine corneal blindness. To serve the growing demand, this study aimed to generate tissue-engineered canine cornea in part of the corneal epithelium and underlying stroma based on canine limbal epithelial stem cells (cLESCs) seeded silk fibroin/gelatin (SF/G) film and canine corneal stromal stem cells (cCSSCs) seeded SF/G scaffold, respectively. Both cell types were successfully isolated by collagenase I. SF/G corneal films and stromal scaffolds served as the prospective substrates for cLESCs and cCSSCs by promoting cell adhesion, cell viability, and cell proliferation. The results revealed the upregulation of tumor protein P63 (P63) and ATP-binding cassette super-family G member 2 (Abcg2) of cLESCs as well as Keratocan (Kera), Lumican (Lum), aldehyde dehydrogenase 3 family member A1 (Aldh3a1) and Aquaporin 1 (Aqp1) of differentiated keratocytes. Moreover, immunohistochemistry illustrated the positive staining of tumor protein P63 (P63), aldehyde dehydrogenase 3 family member A1 (Aldh3a1), lumican (Lum) and collagen I (Col-I), which are considerable for native cornea. This study manifested a feasible platform to construct tissue-engineered canine cornea for functional grafts and positively contributed to the body of knowledge related to canine corneal stem cells.
Developing the Breast Utility Instrument, a preference-based instrument to measure health-related quality of life in women with breast cancer: Confirmatory factor analysis of the EORTC QLQ-C30 and BR45 to establish dimensions

Objectives Breast cancer (BrC) and its treatments impair health-related quality of life (HRQoL). Utility is a measure of HRQoL that includes preferences for health outcomes, used in treatment decision-making. Generic preference-based instruments lack BrC-specific concerns, indicating the need for a BrC-specific preference-based instrument. Our objective was to determine dimensions of the European Organisation for Research and Treatment of Cancer (EORTC) general cancer (QLQ-C30) and breast module (BR45) instruments, the first step in our development of the novel Breast Utility Instrument (BUI). Methods Patients (n = 408) attending outpatient BrC clinics at an urban cancer centre, and representing a spectrum of BrC health states, completed the QLQ-C30 and BR45. We performed confirmatory factor analysis of the combined QLQ-C30 and BR45 using mean-and variance-adjusted unweighted least squares estimation. The hypothesized factor model was based on clinical relevance, item distributions, missing data, item-importance, and internal reliability of dimensions. Models were evaluated based on global and item fit, local areas of strain, and likelihood ratio tests of nested models. Results Our final model had 10 dimensions: physical and role functioning, emotional functioning, social functioning, body image, pain, fatigue, systemic therapy side effects, sexual functioning and enjoyment, arm and breast symptoms, and endocrine therapy symptoms. Good overall model fit was achieved: χ2/df: 1.45, Tucker-Lewis index: 0.946, comparative fit index: 0.951, standardized root-mean-square residual: 0.069, root-mean-square error of approximation: 0.033 (0.030–0.037). All items had salient factor loadings (λ>0.4, p<0.001). Conclusions We identified important BrC HRQoL dimensions to develop the BUI, a BrC-specific preference-based instrument.
Reduced Plasmacytoid Dendritic Cell Output Is Associated With High Risk in Low-grade Myelodysplastic Syndrome

1Department of Pathology and Laboratory Medicine, Hematopathology Service, Memorial Sloan Kettering Cancer Center, New York, USA 2Department of Pathology and Laboratory Medicine, Diagnostic Molecular Service, Memorial Sloan Kettering Cancer Center, New York, USA 3Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA 4Department of Pathology and Laboratory Medicine, Cytogenetics Laboratory, Memorial Sloan Kettering Cancer Center, New York, USA 5Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, USA Supplemental digital content is available for this article. Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercialShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. HemaSphere (2022) 6:2(e685). http://dx.doi. org/10.1097/HS9.0000000000000685. Received: 30 September 2021 / Accepted: 9 January 2022 Reduced Plasmacytoid Dendritic Cell Output Is Associated With High Risk in Low-grade Myelodysplastic Syndrome
Predicting the Hydraulic Conductivity of Metallic Iron Filters: Modeling Gone Astray

Since its introduction about 25 years ago, metallic iron (Fe0) has shown its potential as the key component of reactive filtration systems for contaminant removal in polluted waters. Technical applications of such systems can be enhanced by numerical simulation of a filter design to improve, e.g., the service time or the minimum permeability of a prospected system to warrant the required output water quality. This communication discusses the relevant input quantities into such a simulation model, illustrates the possible simplifications and identifies the lack of relevant thermodynamic and kinetic data. As a result, necessary steps are outlined that may improve the numerical simulation and, consequently, the technical design of Fe0 filters. Following a general overview on the key reactions in a Fe0 system, the importance of iron corrosion kinetics is illustrated. Iron corrosion kinetics, expressed as a rate constant kiron, determines both the removal rate of contaminants and the average permeability loss of the filter system. While the relevance of a reasonable estimate of kiron is thus obvious, information is scarce. As a conclusion, systematic experiments for the determination of kiron values are suggested to improve the database of this key input parameter to Fe0 filters.
Multiregion sequencing of sarcomatoid renal cell carcinoma arising from autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited cystic kidney disease associated with a spectrum of various renal and extrarenal manifestations, including increased risk of kidney cancers. Here, we present the initial molecular description of sarcomatoid renal cell carcinoma (sRCC) arising in the setting of ADPKD.
The Role of Stimulus‐Specific Perceptual Fluency in Statistical Learning

Abstract Humans have the ability to learn surprisingly complicated statistical information in a variety of modalities and situations, often based on relatively little input. These statistical learning (SL) skills appear to underlie many kinds of learning, but despite their ubiquity, we still do not fully understand precisely what SL is and what individual differences on SL tasks reflect. Here, we present experimental work suggesting that at least some individual differences arise from stimulus‐specific variation in perceptual fluency: the ability to rapidly or efficiently code and remember the stimuli that SL occurs over. Experiment 1 demonstrates that participants show improved SL when the stimuli are simple and familiar; Experiment 2 shows that this improvement is not evident for simple but unfamiliar stimuli; and Experiment 3 shows that for the same stimuli (Chinese characters), SL is higher for people who are familiar with them (Chinese speakers) than those who are not (English speakers matched on age and education level). Overall, our findings indicate that performance on a standard SL task varies substantially within the same (visual) modality as a function of whether the stimuli involved are familiar or not, independent of stimulus complexity. Moreover, test–retest correlations of performance in an SL task using stimuli of the same level of familiarity (but distinct items) are stronger than correlations across the same task with stimuli of different levels of familiarity. Finally, we demonstrate that SL performance is predicted by an independent measure of stimulus‐specific perceptual fluency that contains no SL component at all. Our results suggest that a key component of SL performance may be related to stimulus‐specific processing and familiarity.
Effect of Oral Vitamin D3 Supplementation in Exclusively Breastfed Newborns: Prospective, Randomized, Double‐Blind, Placebo‐Controlled Trial

Exclusively breastfed infants are at a high risk of vitamin D deficiency. Few studies have evaluated the effects of vitamin D supplementation. Hence, we conducted a prospective randomized controlled trial investigating the effects of oral vitamin D3 400 IU/d supplementation in exclusively breastfed newborns. Serum 25‐hydroxy‐vitamin D (25[OH]D) levels in pregnant women and their newborns were evaluated. Breastfed newborns were randomized to one of two regimens at age 10 days. One group received vitamin D3 supplementation at a dose of 400 IU/d (vD‐400 group), whereas the placebo group received a liquid product without vitamin D3. Outcomes were assessed at 4 months of age. A total of 92 pregnant women and their infants were enrolled, and the data of 72 infants (37 in the vD‐400 group and 35 in the placebo group) who completed the study at 4 months of age were assessed. The results showed severe vitamin D deficiency in 15.2% of mothers before delivery, while 54.3% had vitamin D deficiency. Moreover, 15.2% of newborns presented with severe vitamin D deficiency at birth, while 52.2% had vitamin D deficiency. Maternal vitamin D levels were significantly correlated with infant vitamin D levels at birth (r = 0.816, p < 0.001). At 4 months of age, weight, head circumference, serum 25(OH)D, phosphorus, and intact parathyroid hormone levels significantly differed between the vD‐400 and placebo groups. However, the body length and bone mineral density of the two groups did not differ significantly. Regardless of vitamin D supplementation, participants with severe vitamin D deficiency had significantly higher intact parathyroid hormone levels and lower bone mineral content. In conclusion, among exclusively breastfed infants, oral supplementation with vitamin D3 at a dose of 400 IU/d from age 10 days increased 25(OH)D concentrations at 4 months of age, but it did not affect bone mineralization. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
A Mixed-Methods Examination of the Impact of the Partnerships to Improve Community Health Produce Prescription Initiative in Northeastern North Carolina

Objective: To conduct a mixed-methods examination of the impact of the Partnerships to Improve Community Health produce prescription initiative in northeastern North Carolina. Design: Quantitative surveys were conducted among participants before and after the distribution of produce prescription vouchers. Univariate statistics were used to describe the participant population, and paired t tests were used to examine change in fruit and vegetable intake. Qualitative, in-depth telephone interviews were conducted among participants, health educators, and food retailers and coded for themes. Setting: Eight health promotion programs, 2 food pantries, and 11 food retailers. Participants: In each health promotion program or food pantry, between 6 and 97 participants were enrolled. Intervention: Produce prescription vouchers were distributed to participants and redeemed at local food retailers. Main Outcome Measure (s): An increase in local fruit and vegetable purchasing and consumption. Results: Of the produce prescription participants who completed the baseline survey (n = 93), 86% were female, 64% were African American, and 68% were food insecure. The voucher redemption rate was 18%. The majority of participants indicated that they visit farmers' markets more now than before the produce prescription initiative, that shopping at the farmers' market made it easy to include more fresh produce in their family's diet, and that they tried a new farmers' market because of the produce prescription initiative. All health educators and food retailers who participated felt that the initiative benefited their program or operation and were willing to partner with the program again. Conclusions: While redemption rates were lower than anticipated, the produce prescription initiative had positive impacts on participants' local fruit and vegetable purchasing and consumption. Because of COVID-19, the initiative was not implemented until late in the North Carolina produce season. Moving forward, the program will start earlier and work with local food retailers to connect with their communities to increase redemption rates.
A dominant negative variant of RAB5B disrupts maturation of surfactant protein B and surfactant protein C

Significance The Rab5 GTPase functions in early endosome (EE) fusion in the endocytic pathway. Here, we propose that RAB5B also has a noncanonical vesicular fusion function in the regulated secretion pathway that produces mature surfactant proteins SP-B and SP-C in the lung. This function was revealed from investigation of a proband with interstitial lung disease suggestive of a surfactant dysfunction disorder who carried a de novo Asp136His variant in the RAB5B gene. Our modeling in C. elegans provided information on the genetic and cell biological mechanism, and analyses of proband and normal lung biopsies suggested a function for RAB5B and EEs in surfactant protein processing/trafficking. This work indicates that RAB5B p.Asp136His causes a surfactant dysfunction disorder. Pathogenic variants in surfactant proteins SP-B and SP-C cause surfactant deficiency and interstitial lung disease. Surfactant proteins are synthesized as precursors (proSP-B, proSP-C), trafficked, and processed via a vesicular-regulated secretion pathway; however, control of vesicular trafficking events is not fully understood. Through the Undiagnosed Diseases Network, we evaluated a child with interstitial lung disease suggestive of surfactant deficiency. Variants in known surfactant dysfunction disorder genes were not found in trio exome sequencing. Instead, a de novo heterozygous variant in RAB5B was identified in the Ras/Rab GTPases family nucleotide binding domain, p.Asp136His. Functional studies were performed in Caenorhabditis elegans by knocking the proband variant into the conserved position (Asp135) of the ortholog, rab-5. Genetic analysis demonstrated that rab-5[Asp135His] is damaging, producing a strong dominant negative gene product. rab-5[Asp135His] heterozygotes were also defective in endocytosis and early endosome (EE) fusion. Immunostaining studies of the proband’s lung biopsy revealed that RAB5B and EE marker EEA1 were significantly reduced in alveolar type II cells and that mature SP-B and SP-C were significantly reduced, while proSP-B and proSP-C were normal. Furthermore, staining normal lung showed colocalization of RAB5B and EEA1 with proSP-B and proSP-C. These findings indicate that dominant negative–acting RAB5B Asp136His and EE dysfunction cause a defect in processing/trafficking to produce mature SP-B and SP-C, resulting in interstitial lung disease, and that RAB5B and EEs normally function in the surfactant secretion pathway. Together, the data suggest a noncanonical function for RAB5B and identify RAB5B p.Asp136His as a genetic mechanism for a surfactant dysfunction disorder.
The economic burden of influenza among adults aged 18 to 64: A systematic literature review

While the economic burden of influenza infection is well described among adults aged 65 and older, less is known about younger adults. A systematic literature review was conducted to describe the economic burden of seasonal influenza in adults aged 18 to 64 years, to identify the main determinants of direct and indirect costs, and to highlight any gaps in the existing published evidence. MEDLINE and Embase were searched from 2007 to February 7, 2020, for studies reporting primary influenza‐related cost data (direct or indirect) or absenteeism data. Of the 2613 publications screened, 51 studies were included in this review. Half of them were conducted in the United States, and 71% of them described patients with influenza‐like illness rather than laboratory‐confirmed disease. Only 12 studies reported cost data specifically for at‐risk populations. Extracted data highlighted that within the 18‐ to 64‐year‐old group, up to 88% of the economic burden of influenza was attributable to indirect costs, and up to 75% of overall direct costs were attributable to hospitalizations. Furthermore, within the 18‐ to 64‐year‐old group, influenza‐related costs increased with age and underlying medical conditions. The reported cost of influenza‐related hospitalizations was found to be up to 2.5 times higher among at‐risk populations compared with not‐at‐risk populations. This review documents the considerable economic impact of influenza among adults aged 18 to 64. In this age group, most of the influenza costs are indirect, which are generally not recognized by decision makers. Future studies should focus on at‐risk subgroups, lab‐confirmed cases, and European countries.
A 12-Month Randomized Clinical Trial of 38% SDF vs. Restorative Treatment

Purpose: The aim of this 2-arm, parallel-group, 12-mo randomized clinical trial was to compare the effectiveness of semiannual application of 38% silver diamine fluoride (SDF) versus restorative treatment (RT) to manage cavitated caries lesions in primary teeth in a diverse population of children in Michigan. Methods: Children aged 2 to 10 y with at least 1 soft cavitated lesion (International Caries Detection and Assessment System 5 or 6) with no pain or signs/symptoms of irreversible pulpitis were recruited and randomly assigned to 2 intervention groups. One random lesion per child received 38% SDF (twice, at a 6-mo interval) or RT. All interventions and assessments were done by calibrated dentists. Primary outcome measures were clinical failure rates: minor (e.g., reversible pulpitis, active/soft lesion or progression, restoration loss or need for replacement/repair, secondary caries) and major (e.g., irreversible pulpitis, abscess, extraction). Parent, child, and provider acceptability was also assessed. Results: Ninety-eight children were enrolled and randomized, with a mean (SD) age of 4.8 y (1.8); 46% were female and their mean dmft + DMFT was 6.3 (3.9). Sixty-nine children were assessed at 12 mo (sample was within the planned 30% attrition rate). There were significantly more teeth with minor failures (SDF = 65%, RT = 23%, P ≤ 0.001) and major failures (SDF = 13%, RT = 3%, P ≤ 0.001) in the SDF group than the RT group; 74% of SDF-treated lesions were hard at 12 mo vs. 57% at 6 mo. Providers stated that SDF was easier, faster, and more preferable than RT (P ≤ 0.001). No significant differences were found in parental satisfaction and acceptability. At 12 mo, children in the RT arm felt significantly (P < 0.05) happier with their tooth appearance and stated that their visit to the dentist hurt less. Conclusion: At 12 mo, SDF-treated lesions had significantly more minor and major failures than RT, suggesting that SDF-treated teeth need to be closely monitored in a population at high caries risk (ClinicalTrials.gov NCT02601833). Knowledge of Transfer Statement: The results of this study can be used by clinicians when deciding whether to restore or apply silver diamine fluoride to cavitated lesions in primary teeth. Information on treatment outcomes and parent, child, and provider acceptability can help guide appropriate treatment decisions and need for monitoring.
Demographics and significance of porotic hyperostosis as assessed by surface microscopy

Examination of parietal surface anatomy has been limited because standard techniques have insufficient resolution to identify and characterize the structures of interest. Perspectives derived thereof have not clarified their nature. Surface microscopy is pursued as a nondestructive technique to assess the character and implications of porotic pores (referred to as porotic hyperostosis), which have been subject of much speculation.
Small-Scale Cyber Security Competitions

Cyber security competitions are becoming more common and more complex, and faculty interested in hosting a small scale event may be intimidated into thinking that they necessarily require significant investments of time and resources. In this paper, we describe how we a single faculty member has been able to run a number of small scale competitions in a variety of formats, ranging from class and club level up to competitions with five different participating schools.
Incidence of potentially disruptive medical and social events in older adults with and without dementia

Potentially disruptive medical, surgical, and social events—such as pneumonia, hip fracture, and widowhood—may accelerate the trajectory of decline and impact caregiving needs in older adults, especially among people with dementia (PWD). Prior research has focused primarily on nursing home residents with dementia. We sought to assess the incidence of potentially disruptive events in community‐dwelling people with and without dementia.
IKKα-deficient lung adenocarcinomas generate an immunosuppressive microenvironment by overproducing Treg-inducing cytokines

Significance This study reveals that impaired IKKα expression or activity in lung cancer enhances differentiation of protumorigenic Treg cells through a TNF/TNFR2/NF-κB signaling pathway in both human and mouse lung ADC. Depletion of one of the molecules that are required for Treg cell induction represses lung ADC development. Thus, the components that interfere with this particular Treg differentiation provide targets for the generation of TME-modifying therapies. The tumor microenvironment (TME) provides potential targets for cancer therapy. However, how signals originating in cancer cells affect tumor-directed immunity is largely unknown. Deletions in the CHUK locus, coding for IκB kinase α (IKKα), correlate with reduced lung adenocarcinoma (ADC) patient survival and promote KrasG12D-initiated ADC development in mice, but it is unknown how reduced IKKα expression affects the TME. Here, we report that low IKKα expression in human and mouse lung ADC cells correlates with increased monocyte-derived macrophage and regulatory T cell (Treg) scores and elevated transcription of genes coding for macrophage-recruiting and Treg-inducing cytokines (CSF1, CCL22, TNF, and IL-23A). By stimulating recruitment of monocyte-derived macrophages from the bone marrow and enforcing a TNF/TNFR2/c-Rel signaling cascade that stimulates Treg generation, these cytokines promote lung ADC progression. Depletion of TNFR2, c-Rel, or TNF in CD4+ T cells or monocyte-derived macrophages dampens Treg generation and lung tumorigenesis. Treg depletion also attenuates carcinogenesis. In conclusion, reduced cancer cell IKKα activity enhances formation of a protumorigenic TME through a pathway whose constituents may serve as therapeutic targets for KRAS-initiated lung ADC.