Miracle-dz/UniFAR-FTUs huggingface dataset:
The Use of IGF-I to Monitor Long-Acting Growth Hormone Therapy—Timing is an Art…

Recombinant growth hormone (GH) is used to treat children and adults with growth hormone deficiency (GHD). Numerous studies confirmed efficacy and safety within approved indications, but it remains an invasive and expensive treatment. Adherence to treatment is important, and might be compromised by the need for daily injections. Long-acting growth-hormone (LAGH) preparations, allowing for less-frequent injections, hold the promise to improve adherence (1). It might be premature to expect that LAGH automatically will result in better adherence to, and, in consequence, better efficacy of GH therapy (2). Some recent studies in adults do not suggest daily injections are the key problem for many patients (3, 4). However, LAGH certainly is a preferred option for individual patients, and might be particularly important in children to improve adherence (3). Concerns were raised that the GH profile following LAGH injection does not mimic the physiologic secretion profile. While the observation certainly is correct, it has been pointed out that the pharmacokinetics following daily GH injection have no similarity to endogenous secretion profiles either (5). Concerns were also raised regarding differences in pharmacodynamic (PD) profiles with daily GH vs LAGH. Indeed, the clinician must be aware of a fundamental difference in this respect: Concentrations of insulin-like growth-factor 1 (IGF-I), the most frequently used PD marker of GH, increase in the beginning of daily GH treatment, but after a steady state on stable dose is reached, fluctuations during the 24 hours following the GH injections are negligible. In contrast, on injection of LAGH, IGF-I concentrations increase over a few days, reach a peak (which can exceed the reference interval), and finally decline to trough concentrations before the next injection. While PD profiles over the injection interval become similar after some LAGH injections, they continue to exhibit much greater excursions compared to daily GH. Therefore, even if the same total GH dose is administered, and assuming the same “total IGF-I exposure” is reached, the temporal pattern of circulating IGF-I concentrations remains hugely different between daily and long-acting GH. Based on available data from clinical studies, this difference seems not to affect efficacy, and no new side effects or risks have been identified for LAGH so far (5). Whether the greater fluctuation of IGF-I, that is, higher peak and lower trough concentrations, might be associated with long-term risks is speculation. Observation periods are still short, and several aspects deserve attention in future studies (1). However, the striking difference in the PD profile causes a very practical problem for physicians used to interpreting IGF-I concentrations during treatment with daily GH: When after LAGH injection should blood samples be drawn? Which time point is best to represent peak or average IGF-I exposure, or to adjust the dose? What to do if a patient’s blood sample cannot be drawn at the ideal time point? Difficult
What happens after graft loss? A large, long‐term, single‐center observation

The number of patients returning to dialysis after graft failure increases. Surprisingly, little is known about the clinical and immunological outcomes of this cohort. We retrospectively analyzed 254 patients after kidney allograft loss between 1997 and 2017 and report clinical outcomes such as mortality, relisting, retransplantations, transplant nephrectomies, and immunization status. Of the 254 patients, 49% had died 5 years after graft loss, while 27% were relisted, 14% were on dialysis and not relisted, and only 11% were retransplanted 5 years after graft loss. In the complete observational period, 111/254 (43.7%) patients were relisted. Of these, 72.1% of patients were under 55 years of age at time of graft loss and only 13.5% of patients were ≥65 years. Age at graft loss was associated with relisting in a logistic regression analysis. In the complete observational period, 42 patients (16.5%) were retransplanted. Only 4 of those (9.5%) were ≥65 years at time of graft loss. Nephrectomy had no impact on survival, relisting, or development of dnDSA. Patients after allograft loss have a high overall mortality. Immunization contributes to long waiting times. Only a very limited number of patients are retransplanted especially when ≥65 years at time of graft loss.
Liquid-Liquid Phase Separation in Supersaturated Lysozyme Solutions and Associated Precipitate Formation/Crystallization

Using cloud point determinations, the phase boundaries (binodals) for metastable liquid–liquid (L–L) separation in supersaturated hen egg white lysozyme solutions with 3%, 5%, and 7% (w/v) NaCl at pH=4.5 and protein concentrations c between 40 and 400 mg/ml were determined. The critical temperature for the binodal increased approximately linearly with salt concentration. The coexisting liquid phases both remained supersaturated but differed widely in protein concentration. No salt repartitioning was observed between the initial and the two separated liquid phases. After the L–L separation, due to the presence of the high protein concentration phase, crystallization occurred much more rapidly than in the initial solution. At high initial protein concentrations, a metastable gel phase formed at temperatures above the liquid binodal. Both crystal nucleation and gel formation were accelerated in samples that had been cycled through the binodal. Solutions in the gel and L–L regions yielded various types of pre.
Assessment of a 4-Week Starch- and Sucrose-Reduced Diet and Its Effects on Gastrointestinal Symptoms and Inflammatory Parameters among Patients with Irritable Bowel Syndrome

Dietary advice constitutes a treatment strategy for irritable bowel syndrome (IBS). We aimed to examine the effect of a starch- and sucrose-reduced diet (SSRD) on gastrointestinal symptoms in IBS patients, in relation to dietary intake and systemic inflammatory parameters. IBS patients (n = 105) were randomized to a 4-week SSRD intervention (n = 80) receiving written and verbal dietary advice focused on starch and sucrose reduction and increased intake of protein, fat and dairy, or control group (n = 25; habitual diet). At baseline and 4 weeks, blood was sampled, and participants filled out IBS-SSS, VAS-IBS, and Rome IV questionnaires and dietary registrations. C-reactive protein and cytokines TNF-α, IFN-γ, IL-6, IL-8, IL-10, and IL-18 were analyzed from plasma. At 4 weeks, the intervention group displayed lower total IBS-SSS, ‘abdominal pain’, ‘bloating/flatulence’ and ‘intestinal symptoms´ influence on daily life’ scores (p ≤ 0.001 for all) compared to controls, and a 74%, responder rate (RR = ΔTotal IBS-SSS ≥ −50; RRcontrols = 24%). Median values of sucrose (5.4 vs. 20 g), disaccharides (16 vs. 28 g), starch (22 vs. 82 g) and carbohydrates (88 vs. 182 g) were lower for the intervention group compared to controls (p ≤ 0.002 for all), and energy percentages (E%) of protein (21 vs. 17 E%, p = 0.006) and fat (47 vs. 38 E%, p = 0.002) were higher. Sugar-, starch- and carbohydrate-reductions correlated weakly-moderately with total IBS-SSS decrease for all participants. Inflammatory parameters were unaffected. IBS patients display high compliance to the SSRD, with improved gastrointestinal symptoms but unaltered inflammatory parameters. In conclusion, the SSRD constitutes a promising dietary treatment for IBS, but needs to be further researched and compared to established dietary treatments before it could be used in a clinical setting.
Neonatal hyperoxia inhibits proliferation and survival of atrial cardiomyocytes by suppressing fatty acid synthesis

Preterm birth increases the risk for pulmonary hypertension and heart failure in adulthood. Oxygen therapy can damage the immature cardiopulmonary system and may be partially responsible for the cardiovascular disease in adults born preterm. We previously showed that exposing newborn mice to hyperoxia causes pulmonary hypertension by 1 year of age that is preceded by a poorly understood loss of pulmonary vein cardiomyocyte proliferation. We now show that hyperoxia also reduces cardiomyocyte proliferation and survival in the left atrium and causes diastolic heart failure by disrupting its filling of the left ventricle. Transcriptomic profiling showed that neonatal hyperoxia permanently suppressed fatty acid synthase (Fasn), stearoyl-CoA desaturase 1 (Scd1), and other fatty acid synthesis genes in the atria of mice, the HL-1 line of mouse atrial cardiomyocytes, and left atrial tissue explanted from human infants. Suppressing Fasn or Scd1 reduced HL-1 cell proliferation and increased cell death, while overexpressing these genes maintained their expansion in hyperoxia, suggesting that oxygen directly inhibits atrial cardiomyocyte proliferation and survival by repressing Fasn and Scd1. Pharmacologic interventions that restore Fasn, Scd1, and other fatty acid synthesis genes in atrial cardiomyocytes may, thus, provide a way of ameliorating the adverse effects of supplemental oxygen on preterm infants.
Food autonomy: decolonial perspectives for Indigenous health and buen vivir

Introduction: Indigenous peoples’ food systems have weakened as a result of pressures exerted by agro-commercial policies and chains, which has led to the dependency and deterioration of their ways of life. It is in this context that the construction of perspectives on food autonomy positions itself as a potential and strategic field of social decolonial mobilization for indigenous peoples’ health and buen vivir. Objective: The aim of this study was to analyze the meanings of food autonomy from the perspectives of a Nasa Indigenous community in Colombia. Method: This was a qualitative study, involving 38 Indigenous people belonging to the Nasa Huila Indigenous community, aged between 18 and 73, with different occupations. The information was obtained by means of discussion groups and processed through content analysis. The project had the consent and ethical endorsement of the indigenous community. Results: According to the study group, food autonomy is related to the Nasa identity, today weakened by territorial conditions, proximity to non-indigenous populations and the external influence of institutional food programs. Food autonomy develops by means of practices aimed at the production, distribution, preparation and consumption of healthy, chemical-free, homegrown food products from the family level, for self-consumption and in resistance to dependence on external commercial chains. Conclusion: Food autonomy positions itself as a community and political strategy that integrates the strengthening of family gardens, the adaptation of a food program menu, education and governance towards the development of autonomous processes from a decolonial perspective, for the promotion of health and buen vivir.
Impact of processing techniques on the glycemic index of rice

Abstract Rice is an important starchy staple food and generally, rice varieties are known to have a higher glycemic index (GI). Over the years, the significance of GI on human health is being better understood and is known to be associated with several lifestyle disorders. Apart from the intrinsic characteristics of rice, different food processing techniques are known to have implications on the GI of rice. This work details the effect of domestic and industrial-level processing techniques on the GI of rice by providing an understanding of the resulting physicochemical changes. An attempt has been made to relate the process-dependent digestion behavior, which in turn reflects on the GI. The role of food constituents is elaborated and the various in vitro and in vivo approaches that have been used to determine the GI of foods are summarized. Considering the broader perspective, the effect of cooking methods and additives is explained. Given the significance of the cereal grain, this work concludes with the challenges and key thrust areas for future research.
T Cell Immunity against Influenza: The Long Way from Animal Models Towards a Real-Life Universal Flu Vaccine

Current flu vaccines rely on the induction of strain-specific neutralizing antibodies, which leaves the population vulnerable to drifted seasonal or newly emerged pandemic strains. Therefore, universal flu vaccine approaches that induce broad immunity against conserved parts of influenza have top priority in research. Cross-reactive T cell responses, especially tissue-resident memory T cells in the respiratory tract, provide efficient heterologous immunity, and must therefore be a key component of universal flu vaccines. Here, we review recent findings about T cell-based flu immunity, with an emphasis on tissue-resident memory T cells in the respiratory tract of humans and different animal models. Furthermore, we provide an update on preclinical and clinical studies evaluating T cell-evoking flu vaccines, and discuss the implementation of T cell immunity in real-life vaccine policies.
Targeted splice sequencing reveals RNA toxicity and therapeutic response in myotonic dystrophy

Abstract Biomarker-driven trials hold promise for therapeutic development in chronic diseases, such as muscular dystrophy. Myotonic dystrophy type 1 (DM1) involves RNA toxicity, where transcripts containing expanded CUG-repeats (CUGexp) accumulate in nuclear foci and sequester splicing factors in the Muscleblind-like (Mbnl) family. Oligonucleotide therapies to mitigate RNA toxicity have emerged but reliable measures of target engagement are needed. Here we examined muscle transcriptomes in mouse models of DM1 and found that CUGexp expression or Mbnl gene deletion cause similar dysregulation of alternative splicing. We selected 35 dysregulated exons for further study by targeted RNA sequencing. Across a spectrum of mouse models, the individual splice events and a composite index derived from all events showed a graded response to decrements of Mbnl or increments of CUGexp. Antisense oligonucleotides caused prompt reduction of CUGexp RNA and parallel correction of the splicing index, followed by subsequent elimination of myotonia. These results suggest that targeted splice sequencing may provide a sensitive and reliable way to assess therapeutic impact in DM1.
Profiling of Phenolic Compounds and Triterpene Acids of Twelve Apple (Malus domestica Borkh.) Cultivars

Apple (Malus domestica Borkh.), a popular and widely cultivated fruit world-wide, contains bioactive compounds responsible for their health benefits. Here we report the amounts of some bioactive compounds: two major triterpenes (oleanolic and ursolic acids) and polyphenols (phenolic acids, flavan-3-ols, flavonoids and t-resveratrol), together with bioactive properties of twelve apple cultivars measured by chromatographic and spectrophotometric methods. Significant variations were found comparing the bioactive potential of the investigated cultivars. High contents of phenolic acids were identified in the Montuan, Golden Delicious and Cretesc cultivars, while the most flavonoid dominant was the Richard cultivar. Starkrimson, Jonatan, Beliy Naliv and Richard cultivars present higher antioxidant capacity. Oleanolic acid ranged from 11 to 83 mg/g apple extract, while ursolic acid ranged from 55 to 436 mg/g apple extract, with higher amounts in Richard and Montuan cultivars. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) allowed the discrimination of apple cultivars depending on polyphenolic and triterpene acids composition. Caffeic acid, gallic acid and epicatechin were identified as the main bioactive compounds in Starkrimson, Jonathan, Beliy Naliv and Richard cultivars, while ursolic and oleanolic acids were identified in high amounts in Richard, Montuan, Golden Delicious, Idared and Beliy Naliv apple cultivars. The results obtained in this study will contribute to the understanding of the bioactive composition of apples as well as the importance of their capitalization to obtain value-added products that promote human health.
PURE mRNA display and cDNA display provide rapid detection of core epitope motif via high‐throughput sequencing

The reconstructed in vitro translation system known as the PURE system has been used in a variety of cell‐free experiments such as the expression of native and de novo proteins as well as various display methods to select for functional polypeptides. We developed a refined PURE‐based display method for the preparation of stable messenger RNA (mRNA) and complementary DNA (cDNA)‐peptide conjugates and validated its utility for in vitro selection. Our conjugate formation efficiency exceeded 40%, followed by gel purification to allow minimum carry‐over of components from the translation system to the downstream assay enabling clean and efficient random peptide sequence screening. We chose the commercially available anti‐FLAG M2 antibody as a target molecule for validation. Starting from approximately 1.7 × 1012 random sequences, a round‐by‐round high‐throughput sequencing showed clear enrichment of the FLAG epitope DYKDDD as well as revealing consensus FLAG epitope motif DYK(D/L/N)(L/Y/D/N/F)D. Enrichment of core FLAG motifs lacking one of the four key residues (DYKxxD) indicates that Tyr (Y) and Lys (K) appear as the two key residues essential for binding. Furthermore, the comparison between mRNA display and cDNA display method resulted in overall similar performance with slightly higher enrichment for mRNA display. We also show that gel purification steps in the refined PURE‐based display method improve conjugate formation efficiency and enhance the enrichment rate of FLAG epitope motifs in later rounds of selection especially for mRNA display. Overall, the generalized procedure and consistent performance of two different display methods achieved by the commercially available PURE system will be useful for future studies to explore the sequence and functional space of diverse polypeptides.
Factors Affecting Slip Reduction in Oblique Lumbar Interbody Fusion With Posterior Fixation for Degenerative Spondylolisthesis

Study Design: Retrospective case series Objectives: Reduction of translational/angular slip is a favorable radiological result in spinal fusion for degenerative spondylolisthesis, although its clinical significance remains controversial. Few studies have investigated slip reduction and associated factors in oblique lumbar interbody fusion (OLIF) for degenerative spondylolisthesis. Methods: This study involved a retrospective analysis of 56 operated levels of 52 consecutive patients who underwent OLIF for degenerative spondylolisthesis and had more than 1-year of regular follow-up. Translational/angular slip, anterior/posterior disc height, and spinopelvic parameters were measured preoperatively, postoperatively at 6-weeks, and at the last follow-up. Demographic, radiological, and surgical parameters were analyzed to determine factors associated with the amount of slip reduction. Result: The mean follow-up duration was 30.4 ± 12.9 months (range, 12 to 61). The mean decrease in translational slip was 5.7 ± 2.1 mm (13.6 ± 5.5%) and the mean increase in angular slip was 7.9 ± 7.1° at the last follow-up (both P < 0.001). The amount of slip reduction was greater in female sex, age < 65 years, use of a 12° cage, cage position from the anterior disc margin of < 7 mm, and cases with posterior decompression (laminectomy with inferior facetectomy). Conclusions: OLIF showed satisfactory translational/angular slip reduction in degenerative spondylolisthesis. Surgical techniques for optimal reduction include the use of a large angle cage, anterior cage placement, and resection of the inferior facet.
Evaluation of Appropriate Hysteresis Model for Nonlinear Dynamic Analysis of Existing Reinforced Concrete Moment Frames

Various seismic analysis methods are being used to predict the response of structures to earthquakes. Although nonlinear dynamic analysis (NDA) is considered an ideal method to represent the most realistic behavior of a structure among these various methods, correct results can be derived only when the analysis model is carefully developed by a knowledgeable person. It is particularly important to properly implement the behavior characteristics depending on the reversed cyclic load in the NDA of a building made of reinforced concrete (RC) moment frames. This study evaluated the hysteresis model suitable for NDA of existing RC moment frames, and 45 analysis models were reviewed, in which the pivot, concrete, and Takeda hysteresis models were applied differently to beams and columns. The pivot model was evaluated as the most reliable hysteresis model for each structural member by comparing and analyzing not only the responses of the entire frame but also the responses of column and beam members focusing on energy dissipation. However, this model can have practical limitations in that the parameters associated with the reinforcement detailing and applied loads need to be defined in detail. The analysis model applying Takeda to the beam, which predicted the average response at a reliable level compared to the reference model, was identified as a practical alternative when it is difficult to apply the pivot model to all frame members.
Deep learning for automatically predicting early haematoma expansion in Chinese patients

Background and purpose Early haematoma expansion is determinative in predicting outcome of intracerebral haemorrhage (ICH) patients. The aims of this study are to develop a novel prediction model for haematoma expansion by applying deep learning model and validate its prediction accuracy. Methods Data of this study were obtained from a prospectively enrolled cohort of patients with primary supratentorial ICH from our centre. We developed a deep learning model to predict haematoma expansion and compared its performance with conventional non-contrast CT (NCCT) markers. To evaluate the predictability of this model, it was also compared with a logistic regression model based on haematoma volume or the BAT score. Results A total of 266 patients were finally included for analysis, and 74 (27.8%) of them experienced early haematoma expansion. The deep learning model exhibited highest C statistic as 0.80, compared with 0.64, 0.65, 0.51, 0.58 and 0.55 for hypodensities, black hole sign, blend sign, fluid level and irregular shape, respectively. While the C statistics for swirl sign (0.70; p=0.211) and heterogenous density (0.70; p=0.141) were not significantly higher than that of the deep learning model. Moreover, the predictive value for the deep learning model was significantly superior to that of the logistic model of haematoma volume (0.62; p=0.042) and the BAT score (0.65; p=0.042). Conclusions Compared with the conventional NCCT markers and BAT predictive model, the deep learning algorithm showed superiority for predicting early haematoma expansion in ICH patients.