Miracle-dz/UniFAR-FTUs huggingface dataset:
Repopulation of decellularized organ scaffolds with human pluripotent stem cell-derived pancreatic progenitor cells

Diabetes is an emerging global epidemic that affects more that 285 million people worldwide. Engineering of endocrine pancreas tissue holds great promise for the future of diabetes therapy. Here we demonstrate the feasibility of re-engineering decellularized organ scaffolds using regenerative cell source. We differentiated human pluripotent stem cells (hPSC) toward pancreatic progenitor (PP) lineage and repopulated decellularized organ scaffolds with these hPSC-PP cells. We observed that hPSCs cultured and differentiated as aggregates are more suitable for organ repopulation than isolated single cell suspension. However, recellularization with hPSC-PP aggregates require a more extensive vascular support, which was found to be superior in decellularized liver over the decellularized pancreas scaffolds. Upon continued culture for nine days with chemical induction in the bioreactor, the seeded hPSC-PP aggregates demonstrated extensive and uniform cellular repopulation and viability throughout the thickness of the liver scaffolds. Furthermore, the decellularized liver scaffolds was supportive of the endocrine cell fate of the engrafted cells. Our novel strategy to engineer endocrine pancreas construct is expected to find potential applications in preclinical testing, drug discovery and diabetes therapy.
Establishment of predictive nomogram and web-based survival risk calculator for desmoplastic small round cell tumor: A propensity score-adjusted, population-based study

Desmoplastic small round cell tumor (DSRCT) is a rare undifferentiated malignant soft tissue tumor with a poor prognosis and a lack of consensus on treatment. This study’s objective was to build a nomogram based on clinicopathologic factors and an online survival risk calculator to predict patient prognosis and support therapeutic decision-making. A retrospective cohort analysis of the Surveillance, Epidemiology, and End Results (SEER) database was performed for patients diagnosed with DSRCT between 2000 and 2019. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to identify the individual variables related to overall survival (OS) and cancer-specific survival (CSS), as well as to construct online survival risk calculators and nomogram survival models. The nomogram was employed to categorize patients into different risk groups, and the Kaplan–Meier method was utilized to determine the survival rate of each risk category. Propensity score matching (PSM) was used to assess survival with different therapeutic approaches. A total of 374 patients were included, and the median OS and CSS were 25 (interquartile range 21.9–28.1) months and 27 (interquartile range 23.6–30.3) months, respectively. The nomogram models demonstrated high predictive accuracy. PSM found that patients with triple-therapy had better CSS and OS than those who received surgery plus chemotherapy (median survival times: 49 vs 34 months and 49 vs 35 months, respectively). The nomogram successfully predicted the DSRCT patients survival rate. This approach could assist doctors in evaluating prognoses, identifying high-risk populations, and implementing personalized therapy.
Quality of life and factors associated among public university employees retired due to disabilities

Abstract Objective: to analyze quality of life and factors associated among public university employees retired due to disabilities. Method: a cross-sectional study conducted with a sample of public university employees retired due to disabilities. A characterization questionnaire and the World Health Organization Quality of Life - Disabilities instrument were applied via telephone or online contacts from November 2019 to September 2020. The associated factors were verified through multiple linear regression. Results: of the 80 retirees due to disability, 15% were professors and 85% had a technical-administrative career. As for the factors associated with Quality of Life, continuous medication use (βadj: -0.25; p=0.02) and problems in the nervous system (βadj: -0.21; p<0.05) were associated with the Overall domain; continuous medication use (βadj: -0.23; p=0.04), to the Physical domain; smoking (βadj: -0.21; p<0.05) and mental and behavioral disorders (βadj: -0.21; p<0.01), to the Psychological domain; smoking (βadj: -0.46; p<0.01) and respiratory (βadj: -0.21; p=0.03) and circulatory (βadj: -0.21; p=0.03) problems, to the Social domain; smoking (βadj: -0.33; p<0.01) and problems in the nervous system (βadj: -0.22; p=0.04), to the Environmental domain; mental and behavioral disorders, to the Disabilities module (βadj: -0.29; p<0.01) and to the Discrimination domain (βadj: -0.21; p<0.05); and smoking (βadj: -0.32; p<0.01) and problems in the nervous system (βadj: -0.20; p<0.05), to the Inclusion domain. The Autonomy domain did not present any association. Conclusion: the retirees under study presented impaired Quality of Life.
Modified transmission-line method for contact resistance extraction in organic field-effect transistors

A modified transmission-line method (TLM) for organic transistorscontact resistance extraction is proposed. It is shown that the issues of conventional TLM reside in the channel resistance scattering due to parameter variations. These difficulties are overcome in the modified TLM, in which the linear regression slope is directly controlled by the contact resistance rather than by the channel resistance as in conventional TLM. Much smaller transistor-to-transistor dispersion of contact resistance results in a more stable and more reliable extraction method. Moreover, an error study by simulation has been carried out, confirming the greater accuracy of the modified TLM.
Polarized radio outbursts in BL Lacertae. I. Polarized emission from a compact jet. II. The flux and polarization of a piston-driven shock

A second highly polarized burst in BL Lacertae observed in 1983 which has very similar properties to the earlier burst in 1981-82 is described, and it is shown that in both bursts the electric vector of the polarized emission is nearly parallel to the observed extended structure. A weak shock, moving relativistically close to the line of sight, appears to be a very effective means of producing the observed behavior. A simple model is developed to represent the outbursts as due to a piston-driven shock which exhibits polarized emission due to compression of the otherwise random magnetic field of a collimated flow. It is shown that the general features of total flux, polarized flux, and polarization position angle as a function of frequency and time can be understood in terms of such a model. 34 references.
Immunogenicity and reactogenicity of heterologous immunization schedules with COVID-19 vaccines: a systematic review and network meta-analysis

Abstract Background: Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules. Methods: Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model. Results: In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53–24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06–1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16–2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25–2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36–14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08–3.91). No significant difference in the risk for SAEs was found in any comparisons. Conclusions: Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted. Registration: PROSPERO; https://www.crd. york.ac. uk/PROSPERO/; No. CRD42021278149.
CP204L Is a Multifunctional Protein of African Swine Fever Virus That Interacts with the VPS39 Subunit of the Homotypic Fusion and Vacuole Protein Sorting Complex and Promotes Lysosome Clustering

African swine fever virus (ASFV) was first identified over a hundred years ago. Since then, much effort has been made to understand the pathogenesis of ASFV. ABSTRACT Virus replication depends on a complex interplay between viral and host proteins. In the case of African swine fever virus (ASFV), a large DNA virus, only a few virus-host protein-protein interactions have been identified to date. In this study, we demonstrate that the ASFV protein CP204L interacts with the cellular homotypic fusion and protein sorting (HOPS) protein VPS39, blocking its association with the lysosomal HOPS complex, which modulates endolysosomal trafficking and promotes lysosome clustering. Instead, CP204L and VPS39 are targeted to virus factories and localized at the periphery of the virus DNA replication sites. Furthermore, we show that loss of VPS39 reduces the levels of virus proteins synthesized in the early phase of infection and delays ASFV replication but does not completely inhibit it. Collectively, these results identify a novel virus-host protein interaction that modulates host membrane rearrangement during infection and provide evidence that CP204L is a multifunctional protein engaged in distinct steps of the ASFV life cycle. IMPORTANCE African swine fever virus (ASFV) was first identified over a hundred years ago. Since then, much effort has been made to understand the pathogenesis of ASFV. However, the specific roles of many individual ASFV proteins during the infection remain enigmatic. This study provides evidence that CP204L, one of the most abundant ASFV proteins, modulates endosomal trafficking during virus infection. Through protein-protein interaction, CP204L prevents the recruitment of VPS39 to the endosomal and lysosomal membranes, resulting in their accumulation. Consequently, CP204L and VPS39 become sequestered in the ASFV replication and assembly site, known as the virus factory. These results uncover a novel function of viral protein CP204L and extend our understanding of complex interaction between virus and host.
Length measurement using infrared two‐wavelength He–Xe laser interferometer

The results of length measurements made with a 800‐mm‐long gauge block, using an infrared interferometer whose light source is a 3.51– 3.37‐μm simultaneous operation He–Xe laser, are described. The wavelength ratio of the 3.51‐μm line to the 3.37‐μm line is determined to an accuracy of 1.7×10−8 and the absolute length of the gauge block is uniquely determined to an accuracy of 4.9×10−8 by the method of excess fractions. This interferometer has a possibility of measuring lengths up to several meters.
Broadband electrostatic noise due to field-aligned currents

There are observations of broadband electrostatic noise in the plasma sheet boundary layer that are associated with field-aligned currents (electron beams), which often have an upper cutoff frequency above the electron plasma frequency. In this paper, using linear theory and numerical simulations the authors present results from a study of instabilities caused by an electron beam in a thermally mixed plasma. It is shown that two instabilities, the electron acoustic and electron-ion instabilities can combine to form a broadbanded wave spectrum that rapidly destroys the electron beam.
Conducting Goals of Care Conversations: Lessons From the COVID-19 Pandemic

Objective: Internal medicine (IM) residents discuss a patient's goals of care (GOC) as part of their initial consultation. Residents have described inexperience, general discomfort, limited formal teaching, and prognostic uncertainty as barriers to effective GOC conversations. The early COVID-19 pandemic resulted in rapid changes to the healthcare system on the individual, patient, and systemic level that might exacerbate and/or introduce new barriers to IM residents’ GOC conversations. This qualitative study examines how the early COVID-19 pandemic challenged IM residents’ ability to have effective GOC conversations. Methods: Using a constructivist grounded theory approach, participants (n=11) completed a semi-structured interview. Data collection and analysis occurred simultaneously using an open coding, constant comparison process. Interviews were completed until no new themes were identified. Results: Residents self-described their GOC conversations in 5 steps: normalization of the conversation, introduction of expected clinical course, discussion of possible care plans, exploration of the patient's values, and occasionally providing a recommendation. Residents described limited structured teaching around GOC conversations and instead relied on observed role-modelling and self-practice to hone their skillset. Residents described an increased sense of urgency to have GOC conversations due to the uncertainty of clinical course and potential for rapid deterioration of patients with COVID-19. Residents identified restrictive visitor policies as a significant barrier that contributed to feelings of dehumanization. Residents felt that these limitations affected their GOC conversations and potentially resulted in discordant care plans which contributed to moral distress. Conclusion: The early COVID-19 pandemic resulted in several barriers that challenged residents’ ability to conduct effective GOC conversations. This is on the background of previously reported discomfort and limited formal training in conducting GOC conversations. Based on our findings, we present a conceptual model involving teaching validated GOC frameworks, positive role-modelling, and experiential learning to support GOC conversation education in post-graduate medical education.
Theory of the virtual cathode oscillator

A one-dimensional analytical theory is developed to describe the behavior of the virtual cathode oscillator. Theoretical predictions for the microwave frequency and efficiency have been obtained. The results suggested that the feedback of the microwave field to the virtual cathode is very important for the microwave efficiency which, under optimum conditions, can be as high as 30%–40%. In addition, the dependence of the microwave efficiency on the electron-beam energy spread and the electron lifetime was determined. The threshold value of the cavity Q, which is necessary to enhance the microwave field, is also estimated.
Social inequalities in social-emotional problems among preschool children: a population-based study in Sweden

ABSTRACT Background Social-emotional ability is important for overall health and wellbeing in early childhood. Recognizing preschool children in need of extra support, especially those living in unfavourable conditions, can have immediate positive effects on their health and benefit their wellbeing in the long-term. Objectives The aim of this study is to investigate whether there are social inequalities in preschool children’s social-emotional problems, and whether inequalities differ between boys and girls. Method This study utilized repeated measures from cross-sectional population-based surveys of three-year old children (2014–2018). The final study population comprised of 9,099 children which was 61% of all the eligible children in Västerbotten County during the study period. The Ages and Stages Questionnaires: Social-Emotional (ASQ:SE) 36-month interval was used to measure children’s social-emotional ability. Social inequalities were studied with respect to parents’ income, education, and place of birth, for which data was obtained from Statistics Sweden. Multiple logistic and ordered regressions were used. Results Among 3-year-olds, social-emotional problems were more common in the most vulnerable social groups, i.e. parents in the lowest income quintile (OR: 1.45, p < 0.001), parents with education not more than high school (OR: 1.51, p < 0.001), and both parents born outside Sweden (OR: 2.54, p < 0.001). Notably, there was a larger difference in social-emotional problems between the lowest and highest social categories for girls compared to boys. Higher odds of social-emotional problems were associated with boys not living with both parents and girls living in the areas of Skellefteå and Umeå, i.e. more populated geographical areas. Conclusion Already at 3-years of age social-emotional problems were more common in children with parents in the most vulnerable social groups. This does not fulfil the ambition of an equitable start in life for every child and might contribute to reproduction of social inequalities across generations.
Cystatin C proteoforms in chronic kidney disease

Cystatin C, a cysteine protease inhibitor, is used as a biomarker of renal function. It offers several advantages compared to creatinine, and formulas for the estimation of the glomerular filtration rate based on cystatin C have been developed. Recently, several proteoforms of cystatin C have been discovered, including an intact protein with a hydroxylated proline at the N-terminus, and N-terminal truncated forms. There is little knowledge about the biological significance of these proteoforms. Methods: Cross-sectional study of patients with different stages of chronic renal disease (pre-dialysis n = 53; hemodialysis n = 51, renal transplant n = 53). Measurement of cystatin C proteoforms by MALDI-TOF MS, assessment of medicine prescription using the first two levels of the Anatomical Therapeutic chemical system from patients’ records. Results: Patients receiving hemodialysis had the highest cystatin C concentrations, followed by pre-dialysis patients and patients with a renal transplant. In all groups, the most common proteoforms were native cystatin C and CysC 3Pro-OH while the truncated forms made up 28%. The distribution of the different proteoforms was largely independent of renal function and total cystatin C. However, the use of corticosteroids (ATC-L02) and immunosuppressants (ATC-H04) considerably impacted the distribution of proteoforms. Conclusion: The different proteoforms of cystatin C increased proportionally with total cystatin C in patients with chronic kidney disease. Prescription of corticosteroids and immunosuppressants had a significant effect on the distribution of proteoforms. The biological significance of these proteoforms remains to be determined.
Prevalence of and risk factors for chronic kidney disease in ten metropolitan areas of China: a cross-sectional study using three kidney damage markers

Abstract Introduction To estimate the up-to-date prevalence of chronic kidney disease among the health check-up population in economically developed areas of China using estimated glomerular filtration rate, urinary albumin creatinine ratio, and kidney ultrasound. Methods Healthcare data from 38,093 subjects in 10 megalopolises of China who had an annual health check-up in 2021 were used. The overall and stratified prevalence of chronic kidney disease by sex, age, region and comorbidity group was reported. The association between chronic kidney disease and covariates of demographics, and comorbidities were analyzed in the multivariable-adjusted logistic regression model. Results A total of 3837 CKD cases were detected meeting any of the three CKD diagnostic criteria, with a crude prevalence of 10.1% in the study population. Using one criterion of decreased glomerular filtration rate, albuminuria and kidney structural abnormalities alone detected 204 (5.3%), 3289 (85.7%) and 563 (14.7%) cases, respectively. The addition of kidney ultrasound detected 427 (11.1%) structural abnormality cases without decreased GFR and albuminuria. The most common abnormalities were renal masses, hydronephrosis due to obstruction and congenital anomalies of kidney and urinary tract. Female, older age, low city-tier, hypertension, diabetes, obesity, hypertriglyceridemia as well as early disease stages such as pre-hypertension, impaired fasting glucose and overweight were significantly associated with chronic kidney disease. Conclusion Kidney ultrasound helps to amplify the detection of CKD patients, which is a supplement to kidney function and urine protein.
Glucose assimilation rate determines the partition of flux at pyruvate between lactic acid and ethanol in Saccharomyces cerevisiae

Engineered Saccharomyces cerevisiae expressing a lactic acid dehydrogenase can metabolize pyruvate into lactic acid. However, three pyruvate decarboxylase (PDC) isozymes drive most carbon flux toward ethanol rather than lactic acid. Deletion of endogenous PDCs will eliminate ethanol production, but the resulting strain suffers from C2 auxotrophy and struggles to complete a fermentation. Engineered yeast assimilating xylose or cellobiose produce lactic acid rather than ethanol as a major product without the deletion of any PDC genes. We report here that sugar flux, but not sensing, contributes to the partition of flux at the pyruvate branch point in S. cerevisiae expressing the Rhizopus oryzae lactic acid dehydrogenase (LdhA). While the membrane glucose sensors Snf3 and Rgt2 did not play any direct role in the option of predominant product, the sugar assimilation rate was strongly correlated to the partition of flux at pyruvate: fast sugar assimilation favors ethanol production while slow sugar assimilation favors lactic acid. Applying this knowledge, we created an engineered yeast capable of simultaneously converting glucose and xylose into lactic acid, increasing lactic acid production to approximately 17 g L−1 from the 12 g L−1 observed during sequential consumption of sugars. This work elucidates the carbon source‐dependent effects on product selection in engineered yeast.
CircRNP complexes: from nature to design

Supplementary Materials and methods In vitro synthesis of circRNA-based IMP3 sponge Previous work from our lab had revealed an array of IMP3 RNA-binding motifs, based on SELEX analysis (Schneider et al., 2019). A natural high-affinity target, exon 29 of human ANKRD17, which is processed to a circRNA (Schneider et al., 2016), contains this RNAbinding array within 121 nucleotides; this was taken as a comparison to a synthetic, SELEXbased 101-mer RNA (Schneider et al., 2019). In a control sequence, the five elements were mutated to UG-repeats (Figure 1A). Each of these templates was synthesized by T7 transcription, using synthetic double-stranded oligonucleotides (Sigma-Aldrich) and PCRextension for adding the 20-nucleotide stem-loop sequence (Figure 1A) and the T7 promoter. For P-labeling during in vitro transcription, RNA was synthesized with equal amounts of ATP, GTP and CTP (0.5 mM each), 0.04 mM UTP and 10 μCi of [α-P]-UTP. In addition, 10 mM DTT and a 4-fold excess of GMP (2 mM) were used. Following RQ1 DNase treatment, RNA was purified with Mini Quick Spin RNA columns (Roche). Transcripts were ligated with T4 RNA ligase at 16°C overnight, followed by gel extraction (Costar Spin-X centrifuge tube filters; Corning) and ethanol precipitation.