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Previous studies have shown how adipocytes can modulate the activity of hair follicle stem cells. However, the role of adipocytes in the pathogenesis of androgenetic alopecia (AGA) remains unknown. We aimed to determine signaling pathways related to the adipose tissue changes in the human scalp with AGA through RNA-seq analysis. RNA was isolated from the adipose tissues derived from the bald (frontal) and normal (occipital) scalps of male patients with AGA (n = 4). The pooled RNA extracts from these samples were subjected to RNA sequencing, followed by differential gene expression and pathway analysis. Our gene expression analysis identified 1,060 differentially expressed genes, including 522 upregulated and 538 downregulated genes in the bald AGA scalp. Biological pathways pertaining to either adipose tissue metabolism or the hair cycle were generated in our pathway analysis. Downregulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway was noted to be significant in the bald scalp. Expression of adipogenic markers (e.g., PPARG, FABP4, PLN1, and ADIPOQ) was also decreased in the bald site. These findings imply that adipogenesis becomes downregulated in AGA, specifically within the bald scalp adipose. Our results lead to the hypothesis that PPARγ-mediated adipogenesis in the scalp adipose, via crosstalk with signaling pathways involved in hair cycling, might play a role in AGA.

Rubinstein–Taybi Syndrome (RSTS) is a rare congenital disease with distinctive facial features, broadening of the thumbs and halluces, and developmental delay. RSTS is caused by de novo genetic alterations in CREBBP and the homologous EP300 genes. In this study, we established a genetic diagnostic protocol by integrating multiplex ligation-dependent probe amplification (MLPA) and whole-exome sequencing (WES). Five patients clinically diagnosed with RSTS were enrolled for genetic testing. Germline DNA was extracted from the peripheral blood of the patients and their families. One patient (case 1) was identified as harboring a large heterozygous deletion in the 16p13.3 region, spanning the CREBBP gene. Three patients (Cases 2–4) harbored different CREBBP variants (c.2608C>T:p.Gln870Ter,c.4404_4405del:p.Thr1468fs,c.3649C>T:p.Gln1217Ter). No causative variants were identified for the fifth RSTS patient (case 5). Here, we propose a molecular diagnostic protocol that identified causative genetic alterations in 4/5 of the patients, yielding a molecular diagnostic rate of 80%. Given the rarity of RSTS, more research is needed to explore its pathogenesis and mechanism.

O SEXTO PROBLEMA DE HILBERT: QUANDO O FIM SE TORNOU O MÉTODO

Farmer perspectives are relevant for understanding agricultural issues and formulating policies. In this study, we conducted a cross-sectional survey on 70 Filipino farmers (i.e., 35 organic and 35 biotech) to understand farmers’ perspectives regarding coexisting farming methods. Internal response variables were tested to verify the type of decision-making processes being undertaken by biotech and organic farmers. Our results showed that a non-linear decision-making process, similar to the Stimulus–Organism–Response Model, was present for both farmer groups. The study also found that biotech farmers were more influenced by internal factors (e.g., consumer resources) than organic farmers, who rely more on external influences (e.g., culture and social interactions), in connection to their coexistence perspective. The presence of “maverick executives” within the organic farmers gives traction to the notion that coexistence can help empower farmers in choosing what farming method is most suitable to their needs. Our data can also provide insights to policymakers in terms of surveying farmer perspectives to balance farmer needs, primarily in yield and income security, with the national agricultural agenda centered on environmental conservation. Thus, farmer perspectives should be considered alongside ongoing studies and debates on coexistence.

Ecological modeling has been used as a tool to estimate potential impacts caused by aquaculture to the surrounding environment. In this work, a mathematical model was applied to estimate the maximum amount of pink shrimp (Farfantepenaeus paulensis) culture units (3,100m2 pen enclosures) that could be installed at two shallow estuarine bays of Patos Lagoon (known as Coreia and Porto do Rei) with no significant effects on either water quality or viability of the culture system. To calibrate the model, information about the culture of Litopenaeus vannamei and F. paulensis as well as field data (influence of netting material, water current speed and nitrogen concentrations) were used. Under a bad scenario (water current velocity of 0.01m s–1 and a mesh clogging effect of 40%), it would be possible to install up to 29 pens at the Coreia bay, and 39 pens at the Porto do Rei bay. Results indicate that the model was useful in determining the maximum number of culture units that could be installed at these bays, and thus have the potential to become an important tool in the definition of environmental management strategies in relation to aquaculture development.

The information contained in this article is suitable for clinicians practicing in the United States desiring a general overview of the assessment and management of spinal cord injury (SCI), focusing on initial care, assessment, acute management, complications, prognostication, and future research directions. SCI presents significant challenges, affecting patients physically, emotionally, and financially, with variable recovery outcomes ranging from full functionality to lifelong dependence on caregivers. Initial care aims to minimize secondary injury through thorough neurological evaluations and imaging studies to assess the severity of the injury. Acute management prioritizes stabilizing respiratory and cardiovascular functions and maintaining proper spinal cord perfusion. Patients with unstable or progressive neurological decline benefit from timely surgical intervention to optimize neurological recovery. Subacute management focuses on addressing common complications affecting the respiratory, gastrointestinal, and genitourinary systems, emphasizing a holistic, multidisciplinary approach. Prognostication is currently based on neurological assessments and imaging findings, but emerging biomarkers offer the potential to refine outcome predictions further. Additionally, novel therapeutic interventions, such as hypothermia therapy and neuroprotective medications are being explored to mitigate secondary damage and enhance recovery. This paper serves as a high-yield refresher for clinicians for the assessment and management of acute spinal cord injury during index admission. [ABSTRACT FROM AUTHOR]

Background Dominant dystrophic epidermolysis bullosa (DDEB) is characterized by trauma-induced blisters and, in some individuals, intense pruritus. Precisely what causes itch in DDEB and optimal ways to reduce it have not been fully determined. Objectives To characterize DDEB skin transcriptomes to identify therapeutic targets to reduce pruritus in patients. Methods Using bulk RNA sequencing, we evaluated affected and unaffected skin biopsy samples from six patients with DDEB (all with the very itchy pruriginosa subtype) and four healthy individuals. Single-cell transcriptomes of affected (n = 2) and unaffected (n = 1) DDEB skin and healthy skin (n = 2) were obtained. Dupilumab treatment was provided for three patients. Results The skin bulk transcriptome showed significant enrichment of T helper (Th)1/2 and Th17 pathways in affected DDEB skin compared with nonlesional DDEB skin and healthy skin. Single-cell transcriptomics showed an association of glycolytically active GATA3 + Th2 cells in affected DDEB skin. Treatment with dupilumab in three people with DDEB led to significantly reduced visual analogue scale (VAS) itch scores after 12 weeks (mean VAS 3.83) compared with pretreatment (mean VAS 7.83). Bulk RNAseq and quantitative polymerase chain reaction showed that healthy skin and dupilumab-treated epidermolysis bullosa (EB) pruriginosa skin have similar transcriptomic profiles and reduced Th1/Th2 and Th17 pathway enrichment. Conclusions Single-cell RNAseq helps define an enhanced DDEB-associated Th2 profile and rationalizes drug repurposing of anti-Th2 drugs in treating DDEB pruritus. [ABSTRACT FROM AUTHOR]

Autosomal recessive congenital ichthyosis (ARCI) is a genetically heterogeneous disorder with aberrant skin scaling and increased transepidermal water loss (TEWL). Current treatments for ARCI are limited and suboptimal. We present the case of a 27-year-old man with ARCI resulting from a homozygous missense variant in TGM1. RNA-sequencing of lesional skin revealed aberrant Janus kinase–signal transducer and activator of transcription signalling, providing a rationale for innovative treatment with a Janus kinase inhibitor. We prescribed oral tofacitinib (11 mg daily) for 26 weeks. Rapid improvements in erythema and fissuring occurred within the first month. Sustained reductions in 5-D itch scale and Dermatology Life Quality Index scores were also observed. TEWL decreased for the first 10 weeks but increased thereafter. Tofacitinib downregulated inflammatory genes and pathways, while enhancing skin barrier markers. Moreover, transglutaminase 1 distribution was normalized although enzymatic activity remained deficient. This study suggests that oral tofacitinib may be a useful therapy to consider for patients with ARCI. [ABSTRACT FROM AUTHOR]

Recent developments in biomimetic hydrogel research have expanded the scope of biomedical technologies that can be used to model, diagnose, and treat a wide range of medical conditions. Cancer presents one of the most intractable challenges in this arena due to the surreptitious mechanisms that it employs to evade detection and treatment. In order to address these challenges, biomimetic design principles can be adapted to beat cancer at its own game. Biomimetic design strategies are inspired by natural biological systems and offer promising opportunities for developing life-changing methods to model, detect, diagnose, treat, and cure various types of static and metastatic cancers. In particular, focusing on the cellular and subcellular phenomena that serve as fundamental drivers for the peculiar behavioral traits of cancer can provide rich insights into eradicating cancer in all of its manifestations. This review highlights promising developments in biomimetic nanocomposite hydrogels that contribute to cancer therapies via enhanced drug delivery strategies and modeling cancer mechanobiology phenomena in relation to metastasis and synergistic sensing systems. Creative efforts to amplify biomimetic design research to advance the development of more effective cancer therapies will be discussed in alignment with international collaborative goals to cure cancer. [ABSTRACT FROM AUTHOR]