Conserved regulatory switches for the transition from natal down to juvenile feather in birds.

The transition from natal downs for heat conservation to juvenile feathers for simple flight is a remarkable environmental adaptation process in avian evolution. However, the underlying epigenetic mechanism for this primary feather transition is mostly unknown. Here we conducted time-ordered gene co-expression network construction, epigenetic analysis, and functional perturbations in developing feather follicles to elucidate four downy-juvenile feather transition events. We report that extracellular matrix reorganization leads to peripheral pulp formation, which mediates epithelial-mesenchymal interactions for branching morphogenesis. α-SMA (ACTA2) compartmentalizes dermal papilla stem cells for feather renewal cycling. LEF1 works as a key hub of Wnt signaling to build rachis and converts radial downy to bilateral symmetry. Novel usage of scale keratins strengthens feather sheath with SOX14 as the epigenetic regulator. We show that this primary feather transition is largely conserved in chicken (precocial) and zebra finch (altricial) and discuss the possibility that this evolutionary adaptation process started in feathered dinosaurs.

Melanoma biology and treatment: a review of novel regulated cell death-based approaches.

The incidence of melanoma, the most lethal form of skin cancer, has increased due to ultraviolet exposure. The treatment of advanced melanoma, particularly metastatic cases, remains challenging with poor outcomes. Targeted therapies involving BRAF/MEK inhibitors and immunotherapy based on anti-PD1/anti-CTLA4 antibodies have achieved long-term survival rates of approximately 50% for patients with advanced melanoma. However, therapy resistance and inadequate treatment response continue to hinder further breakthroughs in treatments that increase survival rates. This review provides an introduction to the molecular-level pathogenesis of melanoma and offers an overview of current treatment options and their limitations. Cells can die by either accidental or regulated cell death (RCD). RCD is an orderly cell death controlled by a variety of macromolecules to maintain the stability of the internal environment. Since the uncontrolled proliferation of tumor cells requires evasion of RCD programs, inducing the RCD of melanoma cells may be a treatment strategy. This review summarizes studies on various types of nonapoptotic RCDs, such as autophagy-dependent cell death, necroptosis, ferroptosis, pyroptosis, and the recently discovered cuproptosis, in the context of melanoma. The relationships between these RCDs and melanoma are examined, and the interplay between these RCDs and immunotherapy or targeted therapy in patients with melanoma is discussed. Given the findings demonstrating melanoma cell death in response to different stimuli associated with these RCDs, the induction of RCD shows promise as an integral component of treatment strategies for melanoma.

Nutritional deficiencies in alcohol use disorder/alcohol-associated liver disease.

PURPOSE OF REVIEW: To delineate common and uncommon dietary and nutritional deficiencies in individuals with chronic heavy alcohol use and alcohol use disorder and to highlight important advances in the nutrition field in patients ranging from those with alcohol use disorder (AUD) and no liver disease to those with decompensated alcohol-associated liver disease (ALD). RECENT FINDINGS: Patients with AUD may have nutritional deficiencies, especially isolated nutrient deficiencies, such as thiamine or zinc deficiencies. This should not be surprising, as alcohol is a major source of "empty calories." It is devoid of critical macronutrients, such as protein, and micronutrients including important vitamins and minerals. Patients with AUD frequently drink much more than often appreciated (10-20 drinks a day). Patients with AUD and early ALD often begin to develop more apparent nutritional deficiencies. Healthcare providers need to be aware of the presenting features of individual nutrient deficiencies, such as thiamine deficiency, and to provide prompt treatment. In patients with more advanced liver disease, malnutrition correlates with severity of liver disease. It is important to understand the value of nutritional support throughout the spectrum of AUD. SUMMARY: We review nutritional deficiencies in the spectrum of patients with AUD and ALD and highlight new information and recommendations.

Congenital staphylococcal scalded skin syndrome in a preterm infant.

Staphylococcal scalded skin syndrome (SSSS) is a rare condition in premature infants. We report a case of SSSS in a preterm neonate who displayed all clinical manifestations at birth, leading to a fatal outcome from Candida parapsilosis fungemia. The clinical presentation was challenging to differential diagnosis. SSSS diagnosis was confirmed by skin biopsy. This case emphasizes the significance of early recognition and diagnosis of SSSS promptly for clinicians. Congenital SSSS in premature infants can be fatal, but with early recognition and appropriate supportive and antimicrobial therapy, outcomes can be improved and lives can be saved.

Transition from natal downs to juvenile feathers: conserved regulatory switches in Neoaves.

The transition from natal downs for heat conservation to juvenile feathers for simple flight is a remarkable environmental adaptation process in avian evolution. However, the underlying epigenetic mechanism for this primary feather transition is mostly unknown. Here we conducted time-ordered gene co-expression network construction, epigenetic analysis, and functional perturbations in developing feather follicles to elucidate four downy-juvenile feather transition events. We discovered that LEF1 works as a key hub of Wnt signaling to build rachis and converts radial downy to bilateral symmetry. Extracellular matrix reorganization leads to peripheral pulp formation, which mediates epithelial -mesenchymal interactions for branching morphogenesis. ACTA2 compartments dermal papilla stem cells for feather cycling. Novel usage of scale keratins strengthens feather sheath with SOX14 as the epigenetic regulator. We found this primary feather transition largely conserved in chicken (precocious) and zebra finch (altricial) and discussed the possibility that this evolutionary adaptation process started in feathered dinosaurs.

Molecular and Cellular Characterization of Avian Reticulate Scales Implies the Evo-Devo Novelty of Skin Appendages in Foot Sole.

Among amniotic skin appendages, avian feathers and mammalian hairs protect their stem cells in specialized niches, located in the collar bulge and hair bulge, respectively. In chickens and alligators, label retaining cells (LRCs), which are putative stem cells, are distributed in the hinge regions of both avian scutate scales and reptilian overlapping scales. These LRCs take part in scale regeneration. However, it is unknown whether other types of scales, for example, symmetrically shaped reticulate scales, have a similar way of preserving their stem cells. In particular, the foot sole represents a special interface between animal feet and external environments, with heavy mechanical loading. This is different from scutate-scale-covered metatarsal feet that function as protection. Avian reticulate scales on foot soles display specialized characteristics in development. They do not have a placode stage and lack ß-keratin expression. Here, we explore the molecular and cellular characteristics of avian reticulate scales. RNAscope analysis reveals different molecular profiles during surface and hinge determination compared with scutate scales. Furthermore, reticulate scales express Keratin 15 (K15) sporadically in both surface- and hinge-region basal layer cells, and LRCs are not localized. Upon wounding, the reticulate scale region undergoes repair but does not regenerate. Our results suggest that successful skin appendage regeneration requires localized stem cell niches to guide regeneration.

Histopathological Study on Collagen in Full-Thickness Wound Healing in Fraser's Dolphins (Lagenodelphis hosei).

Fraser's dolphins (Lagenodelphis hosei) possess great healing abilities. Their skin composition can be restored after wounding, including collagen spacing, orientation, and bundle thickness. However, it remains unclear how collagens are involved in the wound-healing process and eventually regain normality in Fraser's dolphins. Learned from the other two scarless healing animals, changes in type III/I collagen composition are believed to modulate the wound healing process and influence the scarring or scarless fate determination in human fetal skin and spiny mouse skin. In the current study, Herovici's, trichrome, and immunofluorescence staining were used on normal and wounded skin samples in Fraser's dolphins. The results suggested that type I collagens were the main type of collagens in the normal skin of Fraser's dolphins, while type III collagens were barely seen. During the wound healing process, type III collagens showed at early wound healing stages, and type I collagen increased in the mature healed wound. In an early healed wound, collagens were organized in a parallel manner, showing a transient hypertrophic-like scar, and eventually restored to normal collagen configuration and adipocyte distribution in the mature healed wound. The remarkable ability to remove excessive collagens merits further investigation to provide new insights into clinical wound management.

Upper-Arm Photoplethysmographic Sensor with One-Time Calibration for Long-Term Blood Pressure Monitoring.

Wearable cuffless photoplethysmographic blood pressure monitors have garnered widespread attention in recent years; however, the long-term performance values of these devices are questionable. Most cuffless blood pressure monitors require initial baseline calibration and regular recalibrations with a cuffed blood pressure monitor to ensure accurate blood pressure estimation, and their estimation accuracy may vary over time if left uncalibrated. Therefore, this study assessed the accuracy and long-term performance of an upper-arm, cuffless photoplethysmographic blood pressure monitor according to the ISO 81060-2 standard. This device was based on a nonlinear machine-learning model architecture with a fine-tuning optimized method. The blood pressure measurement protocol followed a validation procedure according to the standard, with an additional four weekly blood pressure measurements over a 1-month period, to assess the long-term performance values of the upper-arm, cuffless photoplethysmographic blood pressure monitor. The results showed that the photoplethysmographic signals obtained from the upper arm had better qualities when compared with those measured from the wrist. When compared with the cuffed blood pressure monitor, the means ± standard deviations of the difference in BP at week 1 (baseline) were -1.36 ± 7.24 and -2.11 ± 5.71 mmHg for systolic and diastolic blood pressure, respectively, which met the first criterion of ≤5 ± ≤8.0 mmHg and met the second criterion of a systolic blood pressure ≤ 6.89 mmHg and a diastolic blood pressure ≤ 6.84 mmHg. The differences in the uncalibrated blood pressure values between the test and reference blood pressure monitors measured from week 2 to week 5 remained stable and met both criteria 1 and 2 of the ISO 81060-2 standard. The upper-arm, cuffless photoplethysmographic blood pressure monitor in this study generated high-quality photoplethysmographic signals with satisfactory accuracy at both initial calibration and 1-month follow-ups. This device could be a convenient and practical tool to continuously measure blood pressure over long periods of time.

Risk Factors of Language Delay at Two Years of Corrected Age among Very-Low-Birth-Weight Preterm Infants: A Population-Based Study.

Language delays are often underestimated in very-low-birth-weight (VLBW) preterm infants. We aimed to identify the risk factors of language delay at two years of corrected age in this vulnerable population. VLBW infants, who were assessed at two years of corrected age using the Bayley Scale of Infant Development, third edition, were included using a population-based cohort database. Language delay was defined as mild to moderate if the composite score was between 70 and 85 and severe if the score was < 70. Multivariable logistic regression analysis was used to identify the perinatal risk factors associated with language delay. The study comprised 3797 VLBW preterm infants; 678 (18%) had a mild to moderate delay and 235 (6%) had a severe delay. After adjusting for confounding factors, low maternal education level, low maternal socioeconomic status, extremely low birth weight, male sex, and severe intraventricular hemorrhage (IVH) and/or cystic periventricular leukomalacia (PVL) were found to be significantly associated with both mild to moderate and severe delays. Resuscitation at delivery, necrotizing enterocolitis, and patent ductus arteriosus requiring ligation showed significant associations with severe delay. The strongest factors predicting both mild to moderate and severe language delays were the male sex and severe IVH and/or cystic PVL; thus, early targeted intervention is warranted in these populations.

Successful Repigmentation of Full-Thickness Wound Healing in Fraser's Dolphins (Lagenodelphis hosei).

Fraser's dolphins (Lagenodelphis hosei) exhibit the capability to restore nearly normal pigmentation after full-thickness wounding. However, the association among melanocytes, melanin and skin pigmentation during wound healing in cetaceans has yet to be addressed. Here, the number of melanocytes and the distribution of melanocytes and melanin in different-colored skin and different wound-healing stages in Fraser's dolphins were analyzed by using Fontana-Masson staining, immunofluorescence staining and immunohistochemical staining. It was noticed that there was the highest number of melanocytes in dark skin and the lowest number of melanocytes in white skin. The appearance of functional melanocytes and full-melanized neoepidermis was observed in the early stage of wound healing in Fraser's dolphins. Furthermore, the melanocyte number and skin pigmentation and pattern in healed wounds recovered to a similar condition of unwounded skin. This study provides fundamental knowledge of skin repigmentation in cetaceans for further research, and it will be warranted to elucidate the mechanisms of the replenishment of melanocytes and the regulation of melanocyte activity that contribute to the successful repigmentation in cetacean skin wounds.

A Rare Case of Esophagitis Dissecans Superficialis Occurring with Barrett's Esophagus.

Esophagitis dissecans superficialis (EDS) is a rare but benign disease of the esophagus often identified endoscopically by sloughing of the superficial esophageal mucosa. We present an asymptomatic 66-year-old patient found to have EDS in the setting of Barrett's esophagus. The association of EDS with Barrett's esophagus has not been previously reported. He was initiated on proton pump inhibitor therapy with rapid and complete resolution of the endoscopic abnormality. This case illustrates the importance of identification of EDS as prognosis relies on prompt diagnosis and treatment.

Verbal Training Induces Enhanced Functional Connectivity in Japanese Healthy Elderly Population.

This study employs fMRI to examine the neural substrates of response to cognitive training in healthy old adults. Twenty Japanese healthy elders participated in a 4-week program and practiced a verbal articulation task on a daily basis. Functional connectivity analysis revealed that in comparison to age- and education-matched controls, elders who received the cognitive training demonstrated increased connectivity in the frontotemporal regions related with language and memory functions and showed significant correlations between the behavioral change in a linguistic task and connectivity in regions for goal-oriented persistence and lexical processing. The increased hippocampal connectivity was consistent with previous research showing efficacious memory improvement and change in hippocampal functioning. Moreover, the increased intra-network connectivity following cognitive training suggested an improved neural differentiation, in contrast to the inter-network activation pattern typical in the aging brain. This research not only validates the relationship of functional change in the frontal and temporal lobes to age-associated cognitive decline but also shows promise in turning neural change toward the right direction by cognitive training.

Defining Wound Healing Progression in Cetacean Skin: Characteristics of Full-Thickness Wound Healing in Fraser's Dolphins (Lagenodelphis hosei).

Cetaceans are tight-skinned mammals that exhibit an extraordinary capacity to heal deep soft tissue injuries. However, essential information of large full-thickness wound healing in cetaceans is still lacking. Here, the stages of full-thickness wound healing were characterized in Fraser's dolphins (Lagenodelphis hosei). The skin samples were collected from normal skin and full-thickness cookiecutter shark (Isistius brasiliensis)-bite wounds of stranded carcasses. We defined five stages of wound healing according to macroscopic and histopathological examinations. Wounds in Stage 1 and 2 were characterized by intercellular and intracellular edema in the epidermal cells near the wound edge, mixed inflammatory cell infiltration, and degradation of collagen fibers. In Stage 3 wounds, melanocytes, melanin granules, rete and dermal ridges were noticed in the neo-epidermis, and the adipose tissue in adjacent blubber was replaced by cells and fibers. Wounds in Stage 4 and 5 were characterized by gradual restoration of the normal skin architecture including rete and dermal ridges, collagen bundles, and adipose tissue. These phenomena were quite different from previous studies in terrestrial tight-skinned mammals, and therefore, further in-depth research into the mechanisms of dolphin wound healing would be needed to gain new insights into veterinary and human regenerative medicine.

The Effect of Feeding Restriction on the Microbiota and Metabolome Response in Late-Phase Laying Hens.

This study investigated cecal bacterial community profile, cecal and serum metabolites, and its biosynthesis pathway in late-phase laying hens during 6 weeks feeding restriction (FR), using 16S rDNA as gene sequencing and non-targeted LC-MS/MS as metabolomics approach. We used three groups (ad libitum, FR20, and FR40). FR can reduce excessive fat in late-phase laying hens, while egg production rate is not affected, except for the FR40 group. In phylum level, FR20 had more population of Bacteriodetes and Firmicutes amongst groups. The same result is at genus level, FR20 were higher of the predominant genus (Bacteroides and Rikenellaceae_RC9_gut_group). Both of FR20 and FR40 reduced Proteobacteria as potential pathogenic bacteria. Non-targeted metabolomic analysis revealed that FR20 modified 20 metabolites in cecal and 10 metabolites in serum of laying hens, whereas 48 cecal metabolites and 31 serum metabolites has revealed in FR40. KEGG assay showed FR20 and FR40 upregulated lipid, carbohydrate, amino acid, nucleic acid pathway, and FR40 modified steroid metabolism in cecal analysis. In serum, only FR40 modified lipid, amino acid pathway, and carbohydrate biosynthesis were shown. This study showed that FR during late-phase laying hens altered the microbiome composition, modified metabolites profile and biosynthesis of the cecal as well as serum.

Exploring Dielectric Constant and Dissipation Factor of LTCC Using Machine Learning.

Low-temperature co-fired ceramics (LTCCs) have been attracting attention due to rapid advances in wireless telecommunications. Low-dielectric-constant (Dk) and low-dissipation-factor (Df) LTCCs enable a low propagation delay and high signal quality. However, the wide ranges of glass, ceramic filler compositions, and processing features in fabricating LTCC make property modulating difficult via experimental trial-and-error approaches. In this study, we explored Dk and Df values of LTCCs using a machine learning method with a Gaussian kernel ridge regression model. A principal component analysis and k-means methods were initially performed to visually analyze data clustering and to reduce the dimension complexity. Model assessments, by using a five-fold cross-validation, residual analysis, and randomized test, suggest that the proposed Dk and Df models had some predictive ability, that the model selection was appropriate, and that the fittings were not just numerical due to a rather small data set. A cross-plot analysis and property contour plot were performed for the purpose of exploring potential LTCCs for real applications with Dk and Df values less than 10 and 2 × 10-3, respectively, at an operating frequency of 1 GHz. The proposed machine learning models can potentially be utilized to accelerate the design of technology-related LTCC systems.

NPO at Midnight: Reassessing Unnecessary Pre-Endoscopy Fasting.

INTRODUCTION: Endoscopy with sedation is a common inpatient procedure. "NPO after midnight" remains the prevailing fasting practice despite ASA guidelines indicating specific fasting times. This quality improvement project aims to assess patient discomfort with the "NPO after midnight" order versus implementation of specific NPO times. METHODS: Patients in the inpatient wards scheduled for endoscopy after 1 pm the following day were recruited. The gastroenterology services designated specific NPO times per ASA guidelines for the post-intervention group. Each participant completed a survey qualifying hunger, thirst, and discomfort levels. Pearson's chi-squared analysis was performed. RESULTS: NPO duration was reduced in the post-intervention group with significant improvement in thirst, hunger, and discomfort levels. A shortened preoperative fasting period did not lead to increase in procedural complications. CONCLUSION: Despite ASA guidelines, the practice of keeping patients NPO after midnight remains pervasive, resulting in unnecessarily prolonged fasting and patient discomfort. Implementing specific diet recommendations reduces duration of NPO and improves patient comfort and overall satisfaction.

Determinants Impacting User Behavior towards Emergency Use Intentions of m-Health Services in Taiwan.

Emergency usage intention and behavior are crucial to business service success for m-Health providers and patient healthcare service. This study aimed to identify the factors that influence m-Health acceptance and the effect of emergency use intentions on usage behavior among Taiwanese m-Health users by adopting and extending the Unified Theory of Acceptance and Use of Technology (UTAUT). This study also examines the moderating role of gender and age in the effects of the independent variables on satisfaction with m-Health services. An online questionnaire was used to collect data from 371 participants. The results revealed that performance expectancy, facilitating conditions, and trust had positive effects on user satisfaction. Additionally, m-Health knowledge and user satisfaction had positive effects on emergency use intentions. However, social influence and effort expectancy did not have a significant effect on satisfaction. Moreover, age and gender significantly moderated the effects of some predictors.

Effects of Dietary Inclusion of Dry Hydrastis canadensis on Laying Performance, Egg Quality, Serum Biochemical Parameters and Cecal Microbiota in Laying Hens.

Alternative growth promoters are able to not only effectively replace the traditional use of antibiotics but also provide additional health benefits for livestock and reduce food safety concerns. This study investigated the effects of dry Hydrastis canadensis on the laying performance and fecal microbial community of laying hens. Twenty-four Lohmann (LSL, white layer strain) hens were reared from 40 to 48 weeks of age and randomly allotted to four dietary treatments (six birds/treatment). The dietary treatments comprised a basal diet with no treatment as control, a basal diet plus 0.6% powder of dry Hydrastis canadensis roots (R) or leaves (L), and a basal diet plus 0.6% powder of a mixture of dry Hydrastis canadensis roots and leaves (1:1, LR). No mortality was observed in the whole experimental period. The results indicated that albumen height in the LR group was significantly greater than that in the control group. The diet supplemented with Hydrastis canadensis had no significant effects on egg production rate, egg weight, eggshell strength, eggshell thickness, Haugh unit, or yolk height during the whole experimental phase. However, principal coordinate analysis, comparative heat map analysis, and cluster dendrogram analysis of cecal microbiota showed distinct clusters among the groups treated with Hydrastis canadensis and the control group. Regarding blood biochemical parameters, serum cholesterol levels were significantly lower in all Hydrastis canadensis-treated groups compared with those in the control group. Moreover, serum low-density lipoprotein levels were lower in hens supplemented with the leaf of Hydrastis canadensis. The abundances of the phyla Fusobacteria and Kiritimatiellaeota were increased (p < 0.05) in laying hens fed with 0.6% Hydrastis canadensis leaves, whereas the abundance of the phylum Firmicutes in cecum digesta decreased in response to treatment with Hydrastis canadensis roots and leaves. The relative abundance of the Fusobacterium genus was higher in the LR group compared with that in the control. On the contrary, we found a different trend in the Synergistes genus. The potential influences of these microbiota on the performance of laying hens were discussed. The results demonstrate that Hydrastis canadensis can improve the egg albumen height and modulate the cecum digesta microbiota composition of laying hens.