New treatment for antibody-mediated rejection: interleukin-6 inhibitors.

Following kidney transplantation, antibody-mediated rejection (AMR) occurs when the antibodies of the immune system attack the transplanted organ, leading to damage of the kidney tissue. De novo human leukocyte antigen donor-specific antibodies (HLA-DSAs) play a key role in AMR. Current therapeutic approaches include intravenous immunoglobulin, anti-CD20 antibodies, and plasmapheresis. In cases resistant to treatment, proteasome inhibitors and C5 inhibitors may be employed. Nevertheless, a pressing need exists for new medications to improve transplant survival and reduce complications. In the context of AMR, interleukin (IL)-6 is instrumental in the development and maturation of B cells into plasma cells, which then produce HLA-DSAs targeting the allograft. IL-6 inhibitors are currently under investigation and show promise due to the essential role of IL-6 in the immune response; however, additional research is necessary.

Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

Grb7 Ablation in Mice Improved Glycemic Control, Enhanced Insulin Signaling, and Increased Abdominal fat Mass in Females.

OBJECTIVES: Growth factor receptor bound protein 7 (GRB7) is a multidomain signaling adaptor. Members of the Grb7/10/14 family, specifically Gbrb10/14, have important roles in metabolism. We ablated the Grb7 gene in mice to examine its metabolic function. METHODS: Global ablation of Grb7 in FVB/NJ mice was generated. Growth, organ weight, food intake, and glucose homeostasis were measured. Insulin signaling was examined by Western blotting. Fat and lean body mass was measured by nuclear magnetic resonance, and body composition after fasting or high-fat diet was assessed. Energy expenditure was measured by indirect calorimetry. Expression of adiposity and lipid metabolism genes was measured by quantitative PCR. RESULTS: Grb7-null mice were viable, fertile, and without obvious phenotype. Grb7 ablation improved glycemic control and displayed sensitization to insulin signaling in the liver. Grb7-null females but not males had increased gonadal white adipose tissue mass. Following a 12-week high-fat diet, Grb7-null female mice gained fat body mass and developed relative insulin resistance. With fasting, there was less decrease in fat body mass in Grb7-null female mice. Female mice with Grb7 ablation had increased baseline food intake, less energy expenditure, and displayed a decrease in the expression of lipolysis and adipose browning genes in gonadal white adipose tissue by transcript and protein analysis. CONCLUSION: Our study suggests that Grb7 is a negative regulator of glycemic control. Our results reveal a role for Grb7 in female mice in the regulation of the visceral adipose tissue mass, a powerful predictor of metabolic dysfunction in obesity.

Mechanistic Evidence for Hg Removal from Wastewater by Biologically Produced Sulfur.

A significant quantity of biologically produced sulfur (BPS) is generated as a by-product of chemical and biological desulfurization processes applied to landfill gas treatment. The beneficial upcycling of BPS has seen limited use in the environmental context. The effectiveness and underlying mechanism of BPS as an adsorbent for removing Hg2+ from both solution and wastewater were elucidated based on experiments encompassing surface characterization, adsorption isotherms, kinetics, and thermodynamics. The BPS exhibited remarkable efficacy in removing Hg2+ from solution, with the Langmuir model accurately describing the adsorption process and showing a maximum adsorption capacity of 244 mg g-1. Surface analysis through X-ray photoelectron spectroscopy and scanning electron microscopy revealed that Hg2+ complexed with sulfide on BPS surfaces, forming stable HgS. The adsorbed Hg was strongly retained in BPS, with less than 0.2% of the adsorbed Hg desorbed by strong acids. Adsorption kinetics followed the double-exponential first-order model, showing an initial rapid adsorption phase wherein 75% of the initial Hg2+ was removed within 5 min, followed by a slower adsorption rate. The thermodynamic parameters suggested that adsorption of Hg2+ by BPS was a spontaneous and endothermic process. Additionally, BPS effectively removed Hg2+ from wastewater, showing preference for Hg over other co-existing metals. These findings underscore the potential of BPS as an effective adsorbent for Hg2+ removal from wastewater.

Re-order parameter of interacting thermodynamic magnets.

Phase diagrams of materials are typically based on a static order parameter, but it faces challenges when distinguishing subtle phase changes, such as re-ordering. Here, we report a dynamic nonequilibrium order parameter termed re-order parameter to determine subtle phases and their transitions in interacting magnets. The dynamical precession of magnetization, so-called magnon, premises as a reliable re-order parameter of strong spin-orbit coupled magnets. We employ orthoferrites YFeO3 and its Mn-doped variations, where diverse magnetic phases, including canted antiferromagnetic (Γ4) and collinear antiferromagnetic (Γ1) states, have been well-established. Low-energy magnon uncovers the spin-orbit coupling-induced subtle magnetic structures, resulting in distinct terahertz emissions. The temporal and spectral parameters of magnon emission exhibit characteristics akin to BCS-type order parameters, constructing the magnetic phase diagram of Mn-doped YFeO3. This approach further reveals a concealed ferrimagnetic phase within the Γ1 state, underscoring its potential to search for hidden phases of materials, completing their phase diagrams.

Plastic Wound Protector vs Surgical Gauze for Surgical Site Infection Reduction in Open GI Surgery: A Randomized Clinical Trial.

Importance: Surgical site infections (SSIs) are prevalent hospital-acquired infections with significant patient impacts and global health care burdens. The World Health Organization recommends using wound protector devices in abdominal surgery as a preventive measure to lower the risk of SSIs despite limited evidence. Objective: To examine the efficacy of a dual-ring, plastic wound protector in lowering the SSI rate in open gastrointestinal (GI) surgery irrespective of intra-abdominal contamination levels. Design, Setting, and Participants: This multicenter, patient-blinded, parallel-arm randomized clinical trial was conducted from August 2017 to October 2022 at 13 hospitals in an academic setting. Patients undergoing open abdominal bowel surgery (eg, for bowel perforation) were eligible for inclusion. Intervention: Patients were randomized 1:1 to a dual-ring, plastic wound protector to protect the incision site of the abdominal wall (experimental group) or a conventional surgical gauze (control group). Main Outcomes and Measures: The primary end point was the rate of SSI within 30 days of open GI surgery. Results: A total of 458 patients were randomized; after 1 was excluded from the control group, 457 were included in the intention-to-treat analysis (mean [SD] age, 58.4 [12.1] years; 256 [56.0%] male; 341 [74.6%] with a clean-contaminated wound): 229 in the wound protector group and 228 in the surgical gauze group. The overall SSI rate in the intention-to-treat analysis was 15.7% (72 of 458 patients). The SSI rate for the wound protector was 10.9% (25 of 229 patients) compared with 20.5% (47 of 229 patients) with surgical gauze. The wound protector significantly reduced the risk of SSI, with a relative risk reduction (RRR) of 46.81% (95% CI, 16.64%-66.06%). The wound protector significantly decreased the SSI rate for clean-contaminated wounds (RRR, 43.75%; 95% CI, 3.75%-67.13%), particularly for superficial SSIs (RRR, 42.50%; 95% CI, 7.16%-64.39%). Length of hospital stay was similar in both groups (mean [SD], 15.2 [10.5] vs 15.3 [10.2] days), as were the overall postoperative complication rates (20.1% vs 18.8%). Conclusions and Relevance: This randomized clinical trial found a significant reduction in SSI rates when a plastic wound protector was used during open GI surgery compared with surgical gaze, supporting the World Health Organization recommendation for use of wound protector devices in abdominal surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT03170843.

Diagnostic performance of a deep-learning model using 18F-FDG PET/CT for evaluating recurrence after radiation therapy in patients with lung cancer.

OBJECTIVE: We developed a deep learning model for distinguishing radiation therapy (RT)-related changes and tumour recurrence in patients with lung cancer who underwent RT, and evaluated its performance. METHODS: We retrospectively recruited 308 patients with lung cancer with RT-related changes observed on 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) performed after RT. Patients were labelled as positive or negative for tumour recurrence through histologic diagnosis or clinical follow-up after 18F-FDG PET/CT. A two-dimensional (2D) slice-based convolutional neural network (CNN) model was created with a total of 3329 slices as input, and performance was evaluated with five independent test sets. RESULTS: For the five independent test sets, the area under the curve (AUC) of the receiver operating characteristic curve, sensitivity, and specificity were in the range of 0.98-0.99, 95-98%, and 87-95%, respectively. The region determined by the model was confirmed as an actual recurred tumour through the explainable artificial intelligence (AI) using gradient-weighted class activation mapping (Grad-CAM). CONCLUSION: The 2D slice-based CNN model using 18F-FDG PET imaging was able to distinguish well between RT-related changes and tumour recurrence in patients with lung cancer.

Vitamin C Supplementation Among Pregnant Smokers and Airway Function Trajectory in Offspring: A Secondary Analysis of a Randomized Clinical Trial.

This secondary analysis of a randomized clinical trial analyzes the association of vitamin C supplementation in women who smoked during pregnancy with airway function trajectory in their offspring at 4 to 6 years of age.

Psychiatric adverse events associated with the COVID-19 vaccines approved in the Republic of Korea: a systematic review.

This systematic review evaluated psychiatric adverse events (AEs) following vaccination against coronavirus disease 2019 (COVID-19). We included studies that reported or investigated psychiatric AEs in individuals who had received an approved COVID-19 vaccine in the Republic of Korea. Systematic electronic searches of Ovid-Medline, Embase, CENTRAL, and KoreaMed databases were conducted on March 22, 2023. Risk of bias was assessed using the Risk of Bias Assessment Tool for Non-randomized Studies 2.0. The study protocol was registered in the International Prospective Register of Systematic Reviews (CRD42023449422). Of the 301 articles initially selected, 7 were included in the final analysis. All studies reported on sleep disturbances, and 2 highlighted anxiety-related AEs. Sleep disorders like insomnia and narcolepsy were the most prevalent AEs, while depression was not reported. Our review suggests that these AEs may have been influenced by biological mechanisms as well as the broader psychosocial context of the COVID-19 pandemic. Although this study had limitations, such as a primary focus on the BNT162b2 vaccine and an observational study design, it offered a systematic, multi-vaccine analysis that fills a critical gap in the existing literature. This review underscores the need for continued surveillance of psychiatric AEs and guides future research to investigate underlying mechanisms, identify risk factors, and inform clinical management.

The COVID-19 Vaccine Safety Research Center: a cornerstone for strengthening safety evidence for COVID-19 vaccination in the Republic of Korea.

The COVID-19 Vaccine Safety Research Committee (CoVaSC) was established in November 2021 to address the growing need for independent, in-depth scientific evidence on adverse events (AEs) following coronavirus disease 2019 (COVID-19) vaccination. This initiative was requested by the Korea Disease Control and Prevention Agency and led by the National Academy of Medicine of Korea. In September 2022, the COVID-19 Vaccine Safety Research Center was established, strengthening CoVaSC's initiatives. The center has conducted various studies on the safety of COVID-19 vaccines. During CoVaSC's second research year, from September 29, 2022 to July 19, 2023, the center was restructured into 4 departments: Epidemiological Research, Clinical Research, Communication & Education, and International Cooperation & Policy Research. Its main activities include (1) managing CoVaSC and the COVID-19 Vaccine Safety Research Center, (2) surveying domestic and international trends in AE causality investigation, (3) assessing AEs following COVID-19 vaccination, (4) fostering international collaboration and policy research, and (5) organizing regular fora and training sessions for the public and clinicians. Causality assessments have been conducted for 27 diseases, and independent research has been conducted after organizing ad hoc committees comprising both epidemiologists and clinical experts on each AE of interest. The research process included protocol development, data analysis, interpretation of results, and causality assessment. These research outcomes have been shared transparently with the public and healthcare experts through various fora. The COVID-19 Vaccine Safety Research Center plans to continue strengthening and expanding its research activities to provide reliable, high-quality safety information to the public.

Interaction between p21-activated kinase 4 and ß-catenin as a novel pathway for PTH-dependent osteoblast activation.

Parathyroid hormone (PTH) serves dual roles in bone metabolism, exhibiting both anabolic and catabolic effects. The anabolic properties of PTH have been utilized in the treatment of osteoporosis with proven efficacy in preventing fractures. Despite these benefits, PTH can be administered therapeutically for up to 2 years, and its use in patients with underlying malignancies remains a subject of ongoing debate. These considerations underscore the need for a more comprehensive understanding of the underlying mechanisms. p21-activated kinase 4 (PAK4) is involved in bone resorption and cancer-associated osteolysis; however, its role in osteoblast function and PTH action remains unknown. Therefore, in this study, we aimed to clarify the role of PAK4 in osteoblast function and its effects on PTH-induced anabolic activity. PAK4 enhanced MC3T3-E1 osteoblast viability and proliferation and upregulated cyclin D1 expression. PAK4 also augmented osteoblast differentiation, as indicated by increased mineralization found by alkaline phosphatase and Alizarin Red staining. Treatment with PTH (1-34), an active PTH fragment, stimulated PAK4 expression and phosphorylation in a protein kinase A-dependent manner. In addition, bone morphogenetic protein-2 (which is known to promote bone formation) increased phosphorylated PAK4 (p-PAK4) and PAK4 levels. PAK4 regulated the expression of both phosphorylated and total ß-catenin, which are critical for osteoblast proliferation and differentiation. Moreover, p-PAK4 directly interacted with ß-catenin, and disruption of ß-catenin's binding to T-cell factor impaired PAK4- and PTH-induced osteoblast differentiation. Our findings elucidate the effect of PAK4 on enhancing bone formation in osteoblasts and its pivotal role in the anabolic activity of PTH mediated through its interaction with ß-catenin. These insights improve the understanding of the mechanisms underlying PTH activity and should inform the development of more effective and safer osteoporosis treatments.

Towards high performance wood composites through interface customization with cellulose-based adhesive.

How to efficiently produce high performance plywood is of particular interest, while its sensitivity to moisture is overcome. This paper presents a simple and scalable strategy for the preparation of high-performance plywood based on the chemical bonding theory; a wood interfacial functionalized platform (WIFP) based on (3-aminopropyl) triethoxysilane (APTES) was established. Interestingly, the APTES-enhanced dialdehyde cellulose-based adhesive (DAC-APTES) was able to effectively establish chemically active adhesive interfaces; the dry/wet shear strength of WIFP/DAC-APTES adhesive was 3.15/1.31 MPa, which was much higher than 0.7 MPa (GB/T 9846-2015). The prepared plywood showed excellent wood-polymer interface adhesion, which exceeded the force that the wood itself could withstand. In addition, the DAC-APTES adhesive exhibits moisture evaporation-induced curing behavior at room temperature and can easily support the weight of an adult weighing 65.7 Kg. This research provides a novel approach for functionalized interface design of wood products, an effective means to prepare high-performance plywood.

Current use of antithymoglobulin as induction regimen in kidney transplantation: A review.

Currently, various immunosuppressive drugs are used in organ transplantation. In particular, antithymoglobulin is a widely used drug in kidney transplantation in Korea, accounting for 20% of all induction therapy. According to existing studies, antithymoglobulin induction therapy has several advantages and disadvantages compared with other immunotherapies depending on the kidney transplant situation (dead donor, living donor, low-risk recipient, and high-risk recipient) or antithymoglobulin dose. In this review, we summarize the research conducted so far on antithymoglobulin and hope that antithymoglobulin research on kidney transplantation will be actively conducted in the future.

Amination and crosslinking of acetone-fractionated hardwood kraft lignin using different amines and aldehydes for sustainable bio-based wood adhesives.

Hardwood kraft lignin from the pulping industry is burned or discarded. Its valorization was conducted by subjecting fractionation, amination with ethylenediamine, diethylenetriamine, and monoethanolamine, and crosslinking with formaldehyde or glyoxal to obtain bio-based wood adhesives. Acetone-soluble and insoluble hardwood kraft lignin were prepared and subjected to amination and then crosslinking. Fourier transform infrared, 13C NMR, 15N NMR, and X-ray photoelectron spectroscopy results revealed successful amination with amide, imine, and ether bonds and crosslinking of all samples. Hardwood kraft lignin aminated with diethylenetriamine/ethylenediamine and crosslinked using glyoxal exhibited excellent results in comparison with samples crosslinked using formaldehyde. Acetone-insoluble hardwood kraft lignin aminated and crosslinked using diethylenetriamine and formaldehyde, respectively, exhibited excellent adhesion strength with plywood, satisfying the requirements of the Korean standards. The amination and crosslinking of industrial waste hardwood kraft lignin constitute a beneficial valorization method.

A framework for inferring and analyzing pharmacotherapy treatment patterns.

BACKGROUND: To discover pharmacotherapy prescription patterns and their statistical associations with outcomes through a clinical pathway inference framework applied to real-world data. METHODS: We apply machine learning steps in our framework using a 2006 to 2020 cohort of veterans with major depressive disorder (MDD). Outpatient antidepressant pharmacy fills, dispensed inpatient antidepressant medications, emergency department visits, self-harm, and all-cause mortality data were extracted from the Department of Veterans Affairs Corporate Data Warehouse. RESULTS: Our MDD cohort consisted of 252,179 individuals. During the study period there were 98,417 emergency department visits, 1,016 cases of self-harm, and 1,507 deaths from all causes. The top ten prescription patterns accounted for 69.3% of the data for individuals starting antidepressants at the fluoxetine equivalent of 20-39 mg. Additionally, we found associations between outcomes and dosage change. CONCLUSIONS: For 252,179 Veterans who served in Iraq and Afghanistan with subsequent MDD noted in their electronic medical records, we documented and described the major pharmacotherapy prescription patterns implemented by Veterans Health Administration providers. Ten patterns accounted for almost 70% of the data. Associations between antidepressant usage and outcomes in observational data may be confounded. The low numbers of adverse events, especially those associated with all-cause mortality, make our calculations imprecise. Furthermore, our outcomes are also indications for both disease and treatment. Despite these limitations, we demonstrate the usefulness of our framework in providing operational insight into clinical practice, and our results underscore the need for increased monitoring during critical points of treatment.

Intraoperative Brainstem Auditory Evoked Potentials and Postoperative Nausea and Vomiting After Microvascular Decompression.

BACKGROUND: We performed this study to investigate the effect of intraoperative brainstem auditory evoked potential (IBAEP) changes on the development of postoperative nausea and vomiting (PONV) after microvascular decompression (MVD) for neurovascular cross compression. METHODS: A total of 373 consecutive cases were treated with MVD. The use of rescue antiemetics after surgery was used as an objective indicator of PONV. IBAEP monitoring was routinely performed in all. RESULTS: The use of rescue antiemetics was significantly associated with female sex (OR = 3.427; 95% CI, 2.077-5.654; P < 0.001), PCA use (OR = 3.333; 95% CI, 1.861-5.104; P < 0.001), and operation time (OR = 1.017; 95% CI, 1.008-1.026; P < 0.001). A Wave V peak delay of more than 1.0 milliseconds showed a significant relation with the use of rescue antiemetics (OR = 1.787; 95% CI, 1.114-2.867; P = 0.016) and a strong significant relation with the use of rescue antiemetics more than 5 times (OR = 2.426; 95% CI, 1.372-4.290; P = 0.002). CONCLUSIONS: A wave V peak delay of more than 1.0 milliseconds might have value as a predictor of PONV after MVD. More detailed neurophysiological studies will identify the exact pathophysiology underlying PONV after MVD.

Improvements in lung function following vitamin C supplementation to pregnant smokers are associated with buccal DNA methylation at 5 years of age.

BACKGROUND: We previously reported in the "Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function" randomized clinical trial (RCT) that vitamin C (500 mg/day) supplementation to pregnant smokers is associated with improved respiratory outcomes that persist through 5 years of age. The objective of this study was to assess whether buccal cell DNA methylation (DNAm), as a surrogate for airway epithelium, is associated with vitamin C supplementation, improved lung function, and decreased occurrence of wheeze. METHODS: We conducted epigenome-wide association studies (EWAS) using Infinium MethylationEPIC arrays and buccal DNAm from 158 subjects (80 placebo; 78 vitamin C) with pulmonary function testing (PFT) performed at the 5-year visit. EWAS were performed on (1) vitamin C treatment, (2) forced expiratory flow between 25 and 75% of expired volume (FEF25-75), and (3) offspring wheeze. Models were adjusted for sex, race, study site, gestational age at randomization (≤ OR > 18 weeks), proportion of epithelial cells, and latent covariates in addition to child length at PFT in EWAS for FEF25-75. We considered FDR p < 0.05 as genome-wide significant and nominal p < 0.001 as candidates for downstream analyses. Buccal DNAm measured in a subset of subjects at birth and near 1 year of age was used to determine whether DNAm signatures originated in utero, or emerged with age. RESULTS: Vitamin C treatment was associated with 457 FDR significant (q < 0.05) differentially methylated CpGs (DMCs; 236 hypermethylated; 221 hypomethylated) and 53 differentially methylated regions (DMRs; 26 hyper; 27 hypo) at 5 years of age. FEF25-75 was associated with one FDR significant DMC (cg05814800), 1,468 candidate DMCs (p < 0.001), and 44 DMRs. Current wheeze was associated with 0 FDR-DMCs, 782 candidate DMCs, and 19 DMRs (p < 0.001). In 365/457 vitamin C FDR significant DMCs at 5 years of age, there was no significant interaction between time and treatment. CONCLUSIONS: Vitamin C supplementation to pregnant smokers is associated with buccal DNA methylation in offspring at 5 years of age, and most methylation signatures appear to be persistent from the prenatal period. Buccal methylation at 5 years was also associated with current lung function and occurrence of wheeze, and these functionally associated loci are enriched for vitamin C associated loci. Clinical trial registration ClinicalTrials.gov, NCT01723696 and NCT03203603.

Strong intramolecular charge-transfer effect strengthening naphthoquinone-based chemosensor: Experimental and theoretical evaluation.

An aminophenol-linked naphthoquinone-based fluorometric and colorimetric chemosensor 2-chloro-3-((3-hydroxyphenyl) amino) naphthalene-1,4-dione (2CAN-Dione) was synthesized for selective detection of Sn2+ ion in aqueous solution. The amine and conversion of carbonyl into carboxyl groups play a vital role in the sensing mechanism when Sn2+ is added to 2CAN-Dione. Comprehensive characterization of the sensor was carried out using standard spectral and analytical approaches. Because of the intramolecular charge transfer (ICT) effect and the turn-on sensing mode, the strong fluorometric emission towards Sn2+ was observed at about 435 nm. The chemosensor exhibited good selectivity for Sn2+ in the presence of coexisting metal ions. An improved linear connection was established with a low limit of detection (0.167 µM). FT-IR, 1H NMR, 13C NMR, and quantum chemistry methods were performed to verify the binding coordination mechanism. The chemosensing probe 2CAN-Dione was successfully employed in bioimaging investigations, demonstrating that it is a reliable fluorescent marker for Sn2+ in human cancer cells.

The development of anin vitrohuman hair follicle organoid with a complexity similar to thatin vivo.

In vitrohair follicle (HF) models are currently limited toex vivoHF organ cultures (HFOCs) or 2D models that are of low availability and do not reproduce the architecture or behavior of the hair, leading to poor screening systems. To resolve this issue, we developed a technology for the construction of a humanin vitrohair construct based on the assemblage of different types of cells present in the hair organ. First, we demonstrated that epithelial cells, when isolatedin vitro, have similar genetic signatures regardless of their dissection site, and their trichogenic potential is dependent on the culture conditions. Then, using cell aggregation techniques, 3D spheres of dermal papilla (DP) were constructed, and subsequently, epithelial cells were added, enabling the production and organization of keratins in hair, similar to what is seenin vivo. These reconstructed tissues resulted in the following hair compartments: K71 (inner root-sheath), K85 (matrix region), K75 (companion layer), and vimentin (DP). Furthermore, the new hair model was able to elongate similarly toex vivoHFOC, resulting in a shaft-like shape several hundred micrometers in length. As expected, when the model was exposed to hair growth enhancers, such as ginseng extract, or inhibitors, such as TGF-B-1, significant effects similar to thosein vivowere observed. Moreover, when transplanted into skin biopsies, the new constructs showed signs of integration and hair bud generation. Owing to its simplicity and scalability, this model fully enables high throughput screening of molecules, which allows understanding of the mechanism by which new actives treat hair loss, finding optimal concentrations, and determining the synergy and antagonism among different raw materials. Therefore, this model could be a starting point for applying regenerative medicine approaches to treat hair loss.