Miracle-dz/UniFAR-FTUs huggingface dataset:
Islet1 and Brn3 Expression Pattern Study in Human Retina and hiPSC-Derived Retinal Organoid

This study was conducted to determine the dynamic Islet1 and Brn3 (POU4F) expression pattern in the human fetal retina and human-induced pluripotent stem cell- (hiPSC-) derived retinal organoid. Human fetal eyes from 8 to 27 fetal weeks (Fwks), human adult retina, hiPSC-derived retinal organoid from 7 to 31 differentiation weeks (Dwks), and rhesus adult retina were collected for cyrosectioning. Immunofluorescence analysis showed that Islet1 was expressed in retinal ganglion cells in the fetal retina, human adult retina, and retinal organoids. Unexpectedly, after Fwk 20, Brn3 expression gradually decreased in the fetal retina. In the midstage of development, Islet1 was detected in bipolar and developing horizontal cells. As the photoreceptor developed, the Islet1-positive cone precursors gradually became Islet1-negative/S-opsin-positive cones. This study highlights the distinguishing characteristics of Islet1 dynamic expression in human fetal retina development and proposes more concerns which should be taken regarding Brn3 as a cell-identifying marker in mature primate retina.
Editorial

Abstract:Extending a nascent line of Asian philosophical research in music education, we mine Indian philosophies of music and education. Three key questions guide our project: What are Vedic philosophies of music? What are Vedic philosophies of education? Taken together, what insights can we draw for contemporary music education writ large? To address our questions, we analyze key passages from the Upanishads and synthesize ideas from these texts. A quartet of inter-related ideas emerge from our analysis: the guru, the shishya, vidya, and moksha. In brief, the guru (teacher) is revered as one would god, for it is the teacher who leads the shishya (student) toward vidya (knowledge) and through that toward moksha (liberation of the soul), which can also be attained via making music, such as the singing of Om (the absolute sound). In addition to proffering insights for contemporary music education, particularly in terms of how the ancient Vedic guru-shishya parampara adds nuance to contemporary discussions on the master-apprentice model of music education, we imagine how music education philosophy might look like if it were to be sung.
Activity Limitations and Depressive Symptoms Among Older Couples: The Moderating Role of Spousal Care.

OBJECTIVES Limitations in performing basic daily activities, as well as spousal caregiving that arises from activity limitations, are important factors that have ramifications for mental health among couples. The objective of this study was to investigate the interplay of these factors by focusing on whether the associations between activity limitations and depressive symptoms among coupled-individuals were moderated by receipt and provision of spousal care. METHODS Longitudinal household data from the Health and Retirement Study (2004-2014; dyad N=6,614) were analyzed to estimate within-person associations between one's own and spousal activity limitations, receipt and provision of spousal care, and depressive symptoms. RESULTS Findings showed a consistent link between one's own activity limitations and depressive symptoms for both spouses, whereas spousal activity limitations were associated with depressive symptoms for wives only. We also found moderating effects of spousal care in the link between one's own and spousal activity limitations and depressive symptoms. DISCUSSION Receipt and provision of ADL-related assistance may contextualize the association between activity limitations and depressive symptoms among older coupled-individuals in a direction that could alleviate or aggravate the risk of depression.
Hashimoto encephalopathy in the 21st century

Objective To report the presenting syndromes and to determine whether pretreatment criteria of Hashimoto encephalopathy (HE) predict response to steroids. Methods We assessed symptoms and steroid responsiveness in 24 patients with pretreatment criteria of HE, including (1) subacute onset of cognitive impairment, psychiatric symptoms, or seizures; (2) euthyroid status or mild hypothyroidism; (3) serum thyroid peroxidase antibodies (TPOAb) >200 IU/mL; (4) absent neuronal antibodies in serum/CSF; and (5) no other etiologies. Additional studies included determination of TPOAb (>200 IU/mL) in 74 patients with criteria of possible autoimmune encephalitis (AE) without neuronal antibodies and 205 patients with different neuroimmunologic diseases, psychosis, or new-onset refractory status epilepticus (NORSE). Serum antibodies to the amino (ΝΗ2)-terminal of α-enolase (NH2-α-enolaseAb) were examined in the indicated 24 patients and 13 controls. Results The 24 patients (14 women) with suspected HE had a median age of 48 years (range 8–79 years). Four syndromes were identified: psychiatric (7, 29%), encephalopathy (7, 29%), NORSE-like (6, 25%), and limbic encephalitis (4, 17%). Only 6 of 19 (31.6%) patients completely responded to steroids. The frequency of TPOAb in the 74 patients with possible AE (6 of 74, 8.1%) was similar to that of the 205 controls (17 of 205, 8.2%; p = 0.84). NH2-α-enolaseAb were identified in 1 of 24 suspected HE cases and 1 of 13 controls. Conclusion Current pretreatment criteria of HE do not predict steroid responsiveness. The detection of TPOAb across all control groups reveals their poor disease-specificity. NH2-α-enolaseAb did not help in the diagnosis of HE. These findings imply a redefinition of HE that requires a systematic exclusion of antibody-mediated encephalitis.
Contribution of Non-Saccharomyces Yeasts to Wine Freshness. A Review

Freshness, although it is a concept difficult to define in wines, can be understood as a combination of different circumstances. Organolepticwise, bluish red, floral and fruity, more acidic and full-bodied wines, are perceived as younger and fresher by consumers. In traditional winemaking processes, these attributes are hard to boost if no other technology or biotechnology is involved. In this regard, the right selection of yeast strains plays an important role in meeting these parameters and obtaining wines with fresher profiles. Another approach in getting fresh wines is through the use of novel non-thermal technologies during winemaking. Herein, the contributions of non-Saccharomyces yeasts and emerging technologies to these parameters are reviewed and discussed.
Ketoprofen-Based Ionic Liquids: Synthesis and Interactions with Bovine Serum Albumin

The development of ionic liquids based on active pharmaceutical ingredients (API-ILs) is a possible solution to some of the problems of solid and/or hydrophobic drugs such as low solubility and bioavailability, polymorphism and an alternative route of administration could be suggested as compared to the classical drug. Here, we report for the first time the synthesis and detailed characterization of a series of ILs containing a cation amino acid esters and anion ketoprofen (KETO-ILs). The affinity and the binding mode of the KETO-ILs to bovine serum albumin (BSA) were assessed using fluorescence spectroscopy. All compounds bind in a distance not longer than 6.14 nm to the BSA fluorophores. The estimated binding constants (KA) are in order of 105 L mol−1, which is indicative of strong drug or IL-BSA interactions. With respect to the ketoprofen-BSA system, a stronger affinity of the ILs containing l-LeuOEt, l-ValOBu, and l-ValOEt cation towards BSA is clearly seen. Fourier transformed infrared spectroscopy experiments have shown that all studied compounds induced a rearrangement of the protein molecule upon binding, which is consistent with the suggested static mechanism of BSA fluorescence quenching and formation of complexes between BSA and the drugs. All tested compounds were safe for macrophages.
Physicochemical Properties and Protein Denaturation of Pork Longissimus Dorsi Muscle Subjected to Six Microwave-Based Thawing Methods

Physicochemical changes and protein denaturation were evaluated for pork longissimus dorsi muscle subjected to different thawing methods. Fresh pork longissimus dorsi muscle served as a control. Microwave (MT), microwave combined with ultrasonic (MUT), microwave combined with 35 °C water immersion (MIT), microwave combined with 4 °C refrigeration (MRT), microwave combined with air convection (MAT), and microwave combined with running water (MWT) were applied. All microwave-based methods excepted for MT avoided localized overheating. The changes in the water holding capacity (WHC), color, TBARS, and protein solubility were lowest with MAT. Differential scanning calorimetry (DSC) and dynamic rheological property measurements indicated, that the MAT samples changed only slightly and presented with complete peaks and high G′ values compared with the other treatments. Thus, MAT may reduce protein denaturation associated with meat thawing. The results of this study indicated that MAT effectively shortens thawing time, preserves meat quality and uniformity, and could benefit the meat industry and those who consume its products.
Character displacement drives floral variation in Pelargonium (Geraniaceae) communities

Interactions between plant community members are an underexplored driver of angiosperm floral variation. We investigate character displacement as a potential contributor to floral variation in Pelargonium communities. Pelargoniums all place pollen on the ventral sides of their pollinators, potentially leading to interspecific pollen transfer (IPT) in sympatry. We show that the positions of pollen placement and receipt are determined by anther and style exsertion lengths. Using field experiments, we demonstrate that heterospecific species experience higher IPT if they have similar style lengths than when they have greater style length differences. Using crosses, we show that IPT has negative consequences on seed set. In combination, these results suggest that character displacement in style length is likely to reduce IPT and increase female fitness in sympatry. Patterns of style length variation across 29 different Pelargonium communities suggest that character displacement has occurred in multiple communities. Furthermore, analyses using a wide‐ranging species pair show that style lengths are more different between sympatric populations than they are between allopatric populations. In addition to pollinators as agents of floral divergence, this study suggests that variation in Pelargonium community structure has driven style length variation through character displacement.
A European multicentre evaluation of detection and typing methods for human enteroviruses and parechoviruses using RNA transcripts

Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in‐house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV‐A71, echovirus 30, coxsackie A virus 21, and EV‐D68), HPeV3, and specificity controls. Reported results from 48 in‐house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 µL) transcripts. In‐house assays showed significantly greater detection frequencies of the low copy (10 copies/5 µL) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 × 10−5). EV‐specific PCRs showed low cross‐reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in‐house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point‐of‐care tests.
Antiviral Inflammation during Early Pregnancy Reduces Placental and Fetal Growth Trajectories

Key Points dsRNA induces an intrauterine antiviral response in early pregnancy. The antiviral response reduces imprinted gene expression and fetal–placental size. Type I IFNs inhibit trophoblast stem cell developmental potential. Visual Abstract Many viruses are detrimental to pregnancy and negatively affect fetal growth and development. What is not well understood is how virus-induced inflammation impacts fetal–placental growth and developmental trajectories, particularly when inflammation occurs in early pregnancy during nascent placental and embryo development. To address this issue, we simulated a systemic virus exposure in early pregnant rats (gestational day 8.5) by administering the viral dsRNA mimic polyinosinic:polycytidylic acid (PolyI:C). Maternal exposure to PolyI:C induced a potent antiviral response and hypoxia in the early pregnant uterus, containing the primordial placenta and embryo. Maternal PolyI:C exposure was associated with decreased expression of the maternally imprinted genes Mest, Sfrp2, and Dlk1, which encode proteins critical for placental growth. Exposure of pregnant dams to PolyI:C during early pregnancy reduced fetal growth trajectories throughout gestation, concomitant with smaller placentas, and altered placental structure at midgestation. No detectable changes in placental hemodynamics were observed, as determined by ultrasound biomicroscopy. An antiviral response was not evident in rat trophoblast stem (TS) cells following exposure to PolyI:C, or to certain PolyI:C-induced cytokines including IL-6. However, TS cells expressed high levels of type I IFNR subunits (Ifnar1 and Ifnar2) and responded to IFN-⍺ by increasing expression of IFN-stimulated genes and decreasing expression of genes associated with the TS stem state, including Mest. IFN-⍺ also impaired the differentiation capacity of TS cells. These results suggest that an antiviral inflammatory response in the conceptus during early pregnancy impacts TS cell developmental potential and causes latent placental development and reduced fetal growth.
Comparability of size measurements of the pancreas in magnetic resonance imaging and transabdominal ultrasound

Transabdominal ultrasound (US) and magnetic resonance imaging (MRI) are commonly used for the examination of the pancreas in clinical routine. We therefore were interested in the concordance of these two imaging methods for the size measurement of the pancreas and how age, gender, and body mass index (BMI) affect the organ size.
The sigmoidea ima artery: A player in colonic ischemia?

Abstract Introduction The sigmoidea ima artery is defined as the lowest sigmoid artery, which forms the distal end of the marginal artery by linking with the superior rectal artery. It supplies the rectosigmoid junction, which is a critical area for ischemia. The aim of the present study was to delineate the area supplied by the inferior mesenteric artery with special consideration of the sigmoidea ima artery. Materials and Methods The inferior mesenteric artery was dissected from its origin to the bifurcation of the superior rectal artery in 30 cadavers (15 male, 15 female). Vessel length and distance to the promontory were measured for each branch. Results There were two manifestations of the sigmoidea ima artery, irrespective of the branching pattern of the inferior mesenteric artery. It originated below the promontory in 25 cases (83.3%) and above it in three (10%). It did not derive from the superior rectal artery in two cases (6.7%). In these 16.7%, the marginal artery was absent near the rectosigmoid junction. Conclusions We suggest the terms “arteria sigmoidea ima pelvina” and “arteria sigmoidea ima abdominalis” for the two variants. The terms “arteria marginalis pelvina” and “arteria marginalis abdominalis” could be applied in clinical practice. An abdominal marginal artery could be considered a risk factor for colonic ischemia in colorectal resections and abdominal aortic aneurysm repair. Both variants should be considered when pre‐ and intra‐operative perfusion measurements are interpreted.
Serum creatinine is a biomarker of progressive denervation in spinal muscular atrophy

Objective Identifying simple biomarkers that can predict or track disease progression in patients with spinal muscular atrophy (SMA) remains an unmet clinical need. To test the hypothesis that serum creatinine (Crn) could be a prognostic biomarker for monitoring progression of denervation in patients with SMA, we determined whether serum Crn concentration correlates with disease severity in patients with SMA. Methods We examined a cohort of 238 patients with SMA with 1,130 Crn observations between 2000 and 2016. Analyses were corrected for age, and 156 patients with SMA had dual-energy x-ray absorptiometry data available for correction for lean mass. We investigated the relationship between Crn and SMA type, survival motor neuron 2 (SMN2) copies, and Hammersmith Functional Motor Scale (HFMS) score as primary outcomes. In addition, we tested for associations between Crn and maximum ulnar compound muscle action potential amplitude (CMAP) and motor unit number estimation (MUNE). Results Patients with SMA type 3 had 2.2-fold (95% confidence interval [CI] 1.93–2.49; p < 0.0001) higher Crn levels compared to those with SMA type 1 and 1.7-fold (95% CI 1.52–1.82; p < 0.0001) higher Crn levels compared to patients with SMA type 2. Patients with SMA type 2 had 1.4-fold (95% CI 1.31–1.58; p < 0.0001) higher Crn levels than patients with SMA type 1. Patients with SMA with 4 SMN2 copies had 1.8-fold (95% CI 1.57–2.11; p < 0.0001) higher Crn levels compared to patients with SMA with 2 SMN2 copies and 1.4-fold (95% CI 1.24–1.58; p < 0.0001) higher Crn levels compared to patients with SMA with 3 SMN2 copies. Patients with SMA with 3 SMN2 copies had 1.4-fold (95% CI 1.21–1.56; p < 0.0001) higher Crn levels than patients with SMA with 2 SMN2 copies. Mixed-effect model revealed significant differences in Crn levels among walkers, sitters, and nonsitters (p < 0.0001) and positive associations between Crn and maximum CMAP (p < 0.0001) and between Crn and MUNE (p < 0.0001). After correction for lean mass, there were still significant associations between Crn and SMA type, SMN2 copies, HFMS, CMAP, and MUNE. Conclusions These findings indicate that decreased Crn levels reflect disease severity, suggesting that Crn is a candidate biomarker for SMA progression. We conclude that Crn measurements should be included in the routine analysis of all patients with SMA. In future studies, it will be important to determine whether Crn levels respond to molecular and gene therapies.
Phase III trials of anamorelin in patients with advanced non-small cell lung cancer (NSCLC) and cachexia (ROMANA 1 and 2)

9500 Background: Patients with advanced cancers frequently experience anorexia and cachexia, which is associated with decreased functional status and poor tolerance of chemotherapy. ROMANA 1 and 2 were two randomized, double blind trials evaluating the effect of anamorelin, a ghrelin receptor agonist, on cachexia in patients with advanced NSCLC. Methods: We randomly assigned 484 patients (ROMANA 1) and 495 patients (ROMANA 2) with inoperable stage III or stage IV NSCLC and cachexia ( ≥ 5% weight loss within prior 6 months or BMI < 20 kg/m2) to placebo or anamorelin 100 mg orally once daily. Co-primary efficacy endpoints were the change in lean body mass and handgrip strength from baseline over 12 weeks. Secondary endpoints included change in body weight and symptom burden over 12 weeks and pooled survival from ROMANA 1 and ROMANA 2. Exploratory analyses evaluated change in total body mass and fat mass from baseline to 12 weeks. Results: Patients assigned to anamorelin experienced an increase in lean body .
Thermoregulatory and cardiovasculareffects of capsaicin application on human skin during dynamic exercise to temperate and warm conditions

Thermoregulatory and cardiovascular responses during cycling in temperate and warm environments without and with application of capsaicin on the skin were investigated. We hypothesized that regardless of environmental temperature, capsaicin application would activate heat loss mechanisms attenuating exercise‐induced rectal temperature (Tre) and blood pressure increase. Eight males cycled at 55% of their maximal aerobic power so long as to reach 38.2°C Tre at 20.8 ± 1.0°C and at 30.6 ± 1.1°C ambient temperatures twice: without (NCA) and with (CA) application of capsaicin patches (12 × 18 cm, 4.8 mg). Patches were applied on pectoralis major, trapezius and vastus lateralis muscles. Thermoregulatory (Tre, proximal‐distal skin temperature gradient, sweating rate), cardiovascular variables and oxygen uptake were continuously recorded. In both ambient conditions, during the first 14 min of exercise, the local vasoconstrictive tone as a function of the relative change in Tre was lower in CA than NCA (p < .05, d = 0.84–1.15). Further, sweating rate was higher and occurred at a lower Tre increase in CA compared to NCA (p = .03, d = 0.6) resulting in extended time to reach 38.2°C Tre (p = .03, d = 0.9). Moreover, oxygen consumption was higher in CA than in NCA (p < .001, d = 0.8). Mean arterial pressure was lower during cycling in warm compared to temperate environment, but was unaffected by capsaicin. We conclude that activation of thermal sensors by capsaicin results in lower Tre rise during exercise, which is mediated through greater skin vasodilation along with higher rate and earlier onset of sweating. Nonetheless, capsaicin application has no extra effect on exercise cardiovascular responses.
A Cross-sectional Study Examining the Risk Factors Associated with Lymphedema and its Prevalence in Breast Cancer Patients after Level 3 Axillary Lymph Node Dissection

Objective: To determine the prevalance of lymphedema after breast cancer treatment with level 3 axillary lymph node dissection (ALND) and to evaluate the risk factors which underlie this condition. Material and Methods: A total of 190 women >18-years-old who underwent breast cancer treatment with level 3 ALND >6 months ago were included in this cross-sectional study. The sociodemographic and clinical characteristics of all of the patients were recorded, and all patients were evaluated for lymphedema of the upper extremity by a circumferential measurement method. Results: On examination, 79 (41.5%) women had lymphedema with a mean development time of 12.7±26.62 months. After univariate analysis, the patients’ age, body mass index (BMI), and number of metastatic lymph nodes (LNs) were found to increase the development of lymphedema. In addition, chemotherapy, breast or chest wall radiotherapy, and axillary radiotherapy also played a role. In the multivariate model, BMI (OR=5.491; 95% CI: 1.382-21.82), metastatic LNs (OR=0.314; 95% CI: 0.118-0.839), axillary radiotherapy (OR=15.34; 95% CI: 5.526-42.581), chemotherapy (OR=5.325; 95% CI: 1.48-19.153), and age (OR=1.044; 95% CI: 1.007-1.083) were significantly associated with an increased risk of lymphedema. Conclusion: This study demonstrated that there was a higher lymphedema prevalence ratio of 41.5% in breast cancer patients who underwent level 3 ALND and found that the risk factors for lymphedema development were axillary radiotherapy, chemotherapy, number of metastatic LNs, age, and BMI.