tbuckley/cabot-search huggingface dataset:
Functional prokaryotic-like dCTP deaminases and thymidylate synthase in eukaryotic social amoebae: vertical, endosymbiotic or horizontal gene transfer?
Authors: Heng Liang, Jeffrey P Mower, Catherine P Chia
Journal: Molecular Biology and Evolution (2023)

The de novo synthesis of deoxythymidine triphosphate uses several pathways: gram-negative bacteria use deoxycytidine triphosphate deaminase to convert deoxycytidine triphosphate into deoxyuridine triphosphate, whereas eukaryotes and gram-positive bacteria instead use deoxycytidine monophosphate deaminase to transform deoxycytidine monophosphate to deoxyuridine monophosphate. It is then unusual that in addition to deoxycytidine monophosphate deaminases, the eukaryote Dictyostelium discoideum has 2 deoxycytidine triphosphate deaminases (Dcd1Dicty and Dcd2Dicty). Expression of either DcdDicty can fully rescue the slow growth of an Escherichia coli dcd knockout. Both DcdDicty mitigate the hydroxyurea sensitivity of a Schizosaccharomyces pombe deoxycytidine monophosphate deaminase knockout. Phylogenies show that Dcd1Dicty homologs may have entered the common ancestor of the eukaryotic groups of Amoebozoa, Obazoa, Metamonada, and Discoba through an ancient horizontal gene transfer from a prokaryote or an ancient endosymbiotic gene transfer from a mitochondrion, followed by horizontal gene transfer from Amoebozoa to several other unrelated groups of eukaryotes. In contrast, the Dcd2Dicty homologs were a separate horizontal gene transfer from a prokaryote or a virus into either Amoebozoa or Rhizaria, followed by a horizontal gene transfer between them. ThyXDicty, the D. discoideum thymidylate synthase, another enzyme of the deoxythymidine triphosphate biosynthesis pathway, was suggested previously to be acquired from the ancestral mitochondria or by horizontal gene transfer from alpha-proteobacteria. ThyXDicty can fully rescue the E. coli thymidylate synthase knockout, and we establish that it was obtained by the common ancestor of social amoebae not from mitochondria but from a bacterium. We propose horizontal gene transfer and endosymbiotic gene transfer contributed to the enzyme diversity of the deoxythymidine triphosphate synthesis pathway in most social amoebae, many Amoebozoa, and other eukaryotes.
Time to treat the climate and nature crisis as one indivisible global health emergency
Authors: K. Abbasi, P. Ali, V. Barbour, T. Benfield, K. Bibbins-Domingo, S. Hancocks, R. Horton, L. Laybourn-Langton, R. Mash, P. Sahni, W.M. Sharief, P. Yonga, C. Zielinski
Journal: Annals of Oncology (2023)
Open-label, phase II, multicenter study of lasofoxifene plus abemaciclib for treating women with metastatic ER+/HER2− breast cancer and an ESR1 mutation after disease progression on prior therapies: ELAINE 2
Authors: S. Damodaran, C.C. O’Sullivan, A. Elkhanany, I.C. Anderson, M. Barve, S. Blau, M.A. Cherian, J.A. Peguero, M.P. Goetz, P.V. Plourde, D.J. Portman, H.C.F. Moore
Journal: Annals of Oncology (2023)

Acquired ESR1 mutations in estrogen receptor-positive (ER+) metastatic breast cancer (mBC) drive treatment resistance and tumor progression; new treatment strategies are needed. Lasofoxifene, a next-generation, oral, endocrine therapy and tissue-specific ER antagonist, provided preclinical antitumor activity, alone or combined with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) in ESR1-mutated mBC.In the open-label, phase II, ELAINE 2 trial (NCT04432454), women with ESR1-mutated, ER+/human epidermal growth factor receptor 2-negative (HER2-) mBC who progressed on prior therapies (including CDK4/6i) received lasofoxifene 5 mg/day and abemaciclib 150 mg b.i.d until disease progression/toxicity. The primary endpoint was safety/tolerability. Secondary endpoints included progression-free survival (PFS), clinical benefit rate (CBR), and objective response rate (ORR).Twenty-nine women (median age 60 years) participated; all but one were previously treated with a CDK4/6i (median duration 2 years). The lasofoxifene-abemaciclib combination was well tolerated with primarily grade 1/2 treatment-emergent adverse events (TEAEs), most commonly diarrhea, nausea, fatigue, and vomiting. One patient (with no prior CDK4/6i) discontinued treatment due to grade 2 diarrhea. No deaths occurred during the study. Median PFS was 56.0 weeks [95% confidence interval (CI) 31.9 weeks-not estimable; ∼13 months]; PFS rates at 6, 12, and 18 months were 76.1%, 56.1%, and 38.8%, respectively. CBR at 24 weeks was 65.5% (95% CI 47.3% to 80.1%). In 18 patients with measurable lesions, ORR was 55.6% (95% CI 33.7% to 75.4%). ESR1-mutant circulating tumor DNA (ctDNA) allele fraction decreased from baseline to week 4 in 21/26 (80.8%) patients.Lasofoxifene plus abemaciclib had an acceptable safety profile, was well tolerated, and exhibited meaningful antitumor activity in women with ESR1-mutated, ER+/HER2- mBC after disease progression on prior CDK4/6i. Observed decreases in ESR1-mutant ctDNA with lasofoxifene concordant with clinical response suggest target engagement. If the ELAINE 2 findings are confirmed in the initiated, phase III, ELAINE 3 trial, these data could be practice-changing and help address a critical unmet need.
Lasofoxifene versus fulvestrant for ER+/HER2− metastatic breast cancer with an ESR1 mutation: results from the randomized, phase II ELAINE 1 trial
Authors: M.P. Goetz, N.A. Bagegni, G. Batist, A. Brufsky, M.A. Cristofanilli, S. Damodaran, B.R. Daniel, G.F. Fleming, W.J. Gradishar, S.L. Graff, M.T. Grosse Perdekamp, E. Hamilton, S. Lavasani, A. Moreno-Aspitia, T. O’Connor, T.J. Pluard, H.S. Rugo, S.L. Sammons, L.S. Schwartzberg, D.G. Stover, G.A. Vidal, G. Wang, E. Warner, R. Yerushalmi, P.V. Plourde, D.J. Portman, E.N. Gal-Yam
Journal: Annals of Oncology (2023)

Acquired estrogen receptor alpha (ER/ESR1) mutations commonly cause endocrine resistance in ER+ metastatic breast cancer (mBC). Lasofoxifene, a novel selective ER modulator, stabilizes an antagonist conformation of wild-type and ESR1-mutated ER-ligand binding domains, and has antitumor activity in ESR1-mutated xenografts.In this open-label, randomized, phase II, multicenter, ELAINE 1 study (NCT03781063), we randomized women with ESR1-mutated, ER+/human epidermal growth factor receptor 2 negative (HER2-) mBC that had progressed on an aromatase inhibitor (AI) plus a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) to oral lasofoxifene 5 mg daily or IM fulvestrant 500 mg (days 1, 15, and 29, and then every 4 weeks) until disease progression/toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were safety/tolerability.A total of 103 patients received lasofoxifene (n = 52) or fulvestrant (n = 51). The most current efficacy analysis showed that lasofoxifene did not significantly prolong median PFS compared with fulvestrant: 24.2 weeks (∼5.6 months) versus 16.2 weeks (∼3.7 months; P = 0.138); hazard ratio 0.699 (95% confidence interval 0.434-1.125). However, PFS and other clinical endpoints numerically favored lasofoxifene: clinical benefit rate (36.5% versus 21.6%; P = 0.117), objective response rate [13.2% (including a complete response in one lasofoxifene-treated patient) versus 2.9%; P = 0.124], and 6-month (53.4% versus 37.9%) and 12-month (30.7% versus 14.1%) PFS rates. Most common treatment-emergent adverse events with lasofoxifene were nausea, fatigue, arthralgia, and hot flushes. One death occurred in the fulvestrant arm. Circulating tumor DNA ESR1 mutant allele fraction (MAF) decreased from baseline to week 8 in 82.9% of evaluable lasofoxifene-treated versus 61.5% of fulvestrant-treated patients.Lasofoxifene demonstrated encouraging antitumor activity versus fulvestrant and was well tolerated in patients with ESR1-mutated, endocrine-resistant mBC following progression on AI plus CDK4/6i. Consistent with target engagement, lasofoxifene reduced ESR1 MAF, and to a greater extent than fulvestrant. Lasofoxifene may be a promising targeted treatment for patients with ESR1-mutated mBC and warrants further investigation.
Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial
Authors: Lihua E. Budde, Adam J. Olszewski, Sarit Assouline, Izidore S. Lossos, Catherine Diefenbach, Manali Kamdar, Nilanjan Ghosh, Dipenkumar Modi, Waleed Sabry, Seema Naik, Amitkumar Mehta, Shazia K. Nakhoda, Stephen D. Smith, Kathleen Dorritie, Ting Jia, Song Pham, Ling-Yuh Huw, Jing Jing, Hao Wu, Wahib S. Ead, Iris To, Connie Lee Batlevi, Michael C. Wei, Julio C. Chavez
Journal: Nature Medicine (2023)

Abstract Relapsed/refractory aggressive large B cell lymphoma (LBCL) remains an area of unmet need. Here we report the primary analysis of a phase 1b/2 trial of outpatient mosunetuzumab (a CD20xCD3 T-cell-engaging bispecific antibody) plus polatuzumab vedotin (an anti-CD79B antibody–drug conjugate) in relapsed/refractory LBCL. The phase 2 component is a single arm of an ongoing multi-arm trial. The primary endpoint during dose expansion was independent review committee (IRC)-assessed best overall response rate. Secondary endpoints included investigator-assessed overall response rate, complete response, duration of response, progression-free survival and overall survival. At data cutoff, 120 patients were enrolled (22 dose escalation, 98 dose expansion). The primary endpoint was met during dose expansion, with IRC-assessed best overall response rate and complete response rates of 59.2% (58/98; 95% confidence interval (CI): 48.8–69.0) and 45.9% (45/98; 95% CI: 35.8–56.3), respectively (median follow-up, 23.9 months). Median duration of complete was not reached (95% CI: 20.5–not estimable (NE)). Median progression-free survival was 11.4 months (95% CI: 6.2–18.7). Median overall survival was 23.3 months (95% CI: 14.8–NE). Across dose escalation and expansion, the most common grade 3 or higher adverse events were neutropenia (25.0%, 30/120) and fatigue (6.7%, 8/120). Any-grade cytokine release syndrome occurred in 16.7% of patients. These data demonstrate that mosunetuzumab plus polatuzumab vedotin has a favorable safety profile with highly durable responses suitable as second-line therapy in transplant-ineligible relapsed/refractory LBCL. ClinicalTrials.gov identifier: NCT03671018 .
Venetoclax and hypomethylating agent combination therapy in newly diagnosed acute myeloid leukemia: Genotype signatures for response and survival among 301 consecutive patients
Authors: Naseema Gangat, Omer Karrar, Moazah Iftikhar, Kristen McCullough, Isla M. Johnson, Maymona Abdelmagid, Mostafa Abdallah, Aref Al‐Kali, Hassan B. Alkhateeb, Kebede H. Begna, Abhishek Mangaonkar, Antoine N. Saliba, Mehrdad Hefazi Torghabeh, Mark R. Litzow, William Hogan, Mithun Shah, Mrinal M. Patnaik, Animesh Pardanani, Talha Badar, Hemant Murthy, James Foran, Jeanne Palmer, Lisa Sproat, Nandita Khera, Cecilia Arana Yi, Ayalew Tefferi
Journal: American Journal of Hematology (2023)

Abstract Venetoclax + hypomethylating agent (Ven‐HMA) is currently the standard frontline therapy for older/unfit patients with newly diagnosed acute myeloid leukemia (ND‐AML). Our objective in the current retrospective study of 301 adult patients (median age 73 years; 62% de novo) with ND‐AML was to identify molecular predictors of treatment response to Ven‐HMA and survival; European LeukemiaNet (ELN) genetic risk assignment was favorable 15%, intermediate 16%, and adverse 69%. Complete remission, with (CR) or without (CRi), count recovery, was documented in 182 (60%) patients. In multivariable analysis, inclusive of mutations only, “favorable” predictors of CR/CRi were NPM1 (86% vs. 56%), IDH2 (80% vs. 58%), and DDX41 (100% vs. 58%) and “unfavorable” TP53 (40% vs. 67%), FLT3‐ ITD (36% vs. 63%), and RUNX1 (44% vs. 64%) mutations; significance was sustained for each mutation after adjustment for age, karyotype, and therapy‐related qualification. CR/CRi rates ranged from 36%, in the presence of unfavorable and absence of favorable mutation, to 91%, in the presence of favorable and absence of unfavorable mutation. At median follow‐up of 8.5 months, 174 deaths and 41 allogeneic stem cell transplants (ASCT) were recorded. In multivariable analysis, risk factors for inferior survival included failure to achieve CR/CRi (HR 3.4, 95% CI 2.5–4.8), adverse karyotype (1.6, 1.1–2.6), TP53 mutation (1.6, 1.0–2.4), and absence of IDH2 mutation (2.2, 1.0–4.7); these risk factors were subsequently applied to construct an HR‐weighted risk model that performed better than the ELN genetic risk model (AIC 1661 vs. 1750): low ( n = 130; median survival 28.9 months), intermediate ( n = 105; median 9.6 months), and high ( n = 66; median 3.1 months; p &lt; .001); survival in each risk category was significantly upgraded by ASCT. The current study identifies genotype signatures for predicting response and proposes a 3‐tiered, CR/CRi‐based, and genetics‐enhanced survival model for AML patients receiving upfront therapy with Ven‐HMA.
Global burden of vaccine‐associated anaphylaxis and their related vaccines, 1967–2023: A comprehensive analysis of the international pharmacovigilance database
Authors: Kyeonghun Lee, Hayeon Lee, Rosie Kwon, Youn Ho Shin, Seung Geun Yeo, Young Joo Lee, Min Seo Kim, Yong Sung Choi, Nikolaos G. Papadopoulos, Masoud Rahmati, Junyang Jung, Jinseok Lee, Dong Keon Yon
Journal: Allergy (2023)

Abstract Background Vaccine‐associated anaphylaxis is a rare but life‐threatening reaction that occurs within minutes to hours of exposure to allergens. As studies utilizing large‐scale data to investigate this topic are limited, further research is needed to assess its burden, long‐term trends, and associated risk factors so as to gain a comprehensive understanding of vaccine‐associated anaphylaxis globally. Therefore, this study aimed to investigate the global burden of vaccine‐associated anaphylaxis and related vaccines. Method This study utilized the World Health Organization International Pharmacovigilance Database, in which reports of vaccine‐associated anaphylaxis between 1967 and 2023 were obtained (total reports = 131,255,418). We estimated the global reporting counts, reported odds ratio (ROR), and information component (IC) to identify the relationship between 19 vaccines and associated anaphylaxis in 156 countries and territories. Results We identified 31,676 reports of vaccine‐associated anaphylaxis among 363,290 reports of all‐cause anaphylaxis. The cumulative number of reports on vaccine‐associated anaphylaxis has gradually increased over time, with a dramatic increase after 2020, owing to reports of COVID‐19 mRNA vaccine‐associated anaphylaxis. The typhoid vaccines were associated with the most anaphylactic reports (ROR: 4.35; IC 0.25 : 1.86), followed by encephalitis (3.27; 1.45), hepatitis B (2.69; 1.30), cholera (2.65; 0.54), hepatitis A (2.44; 1.12), influenza (2.36; 1.16), inactivated whole‐virus COVID‐19 (2.21; 1.02), and COVID‐19 mRNA vaccines (1.89; 0.79). In terms of age‐ and sex‐specific risks, vaccine‐associated anaphylaxis reports develop more frequently in females and at young ages. The Ad5‐vectored COVID‐19 vaccine anaphylaxis reports were associated with the highest fatality rate (15.0%). Conclusions Although multiple vaccines are associated with various spectra and risks of anaphylaxis, clinicians should recognize the possibility of anaphylaxis occurring with all vaccines, particularly the COVID‐19 mRNA and inactivated whole‐virus COVID‐19 vaccines, and consider the risk factors associated with vaccine anaphylaxis reports. Further studies are warranted to identify better ways of preventing vaccine‐associated anaphylaxis.
Table of Contents
Authors: Seth Wander, I Mcneish, B Monk, A Souza, J King, L Nappi, S Daneshmand, C Nichols, W Lam, Guannan Kang, W Wong, M Franzoi, A Bayle, I Vaz-Luis, S Dogan, P.-H Cournède, E Solary, J.-M Heard, M Aldea, T Conroy, C Robert, F André, D Vasseur, A Italiano, S Nikolaev, K Abbasi, P Ali, V Barbour, T Benfield, K Bibbins-Domingo, S Hancocks, R Horton, L Laybourn-Langton, R Mash, P Sahni, W Sharief, P Yonga, C Zielinski, L Castelo-Branco, A Pellat, D Martins-Branco, A Valachis, J Derksen, K Suijkerbuijk, U Dafni, T Dellaporta, A Vogel, A Prelaj, R Groenwold, H Martins, R Stahel, J Bliss, J Kather, N Ribelles, F Perrone, P Hall, R Dienstmann, C Booth, G Pentheroudakis, S Delaloge, M Koopman
Journal: Annals of Oncology (2023)
Defining interventions and metrics to improve diversity in CNS clinical trial participation: A SNO and RANO effort
Authors: Joshua A Budhu, Ugonma N Chukwueke, Sadhana Jackson, Eudocia Q Lee, J Ricardo McFaline-Figueroa, Nicole Willmarth, Mahalia Dalmage, Ichiro Kawachi, David Arons, Susan M Chang, Evanthia Galanis, Shawn L Hervey-Jumper, Patrick Y Wen, Alyx B Porter
Journal: Neuro-Oncology (2023)

Abstract Despite major strides in cancer research and therapy, these advances have not been equitable across race and ethnicity. Historically marginalized groups (HMG) are more likely to have inadequate preventive screening, increased delays in diagnosis, and poor representation in clinical trials. Notably, Black, Hispanic, and Indigenous people represent 30% of the population but only 9% of oncology clinical trial participants. As a result, HMGs lack equitable access to novel therapies, contradicting the principle of distributive justice, as enshrined in the Belmont report, which demands the equitable selection of subjects in research involving human subjects. The lack of clinical trial diversity also leads to low generalizability and potentially harmful medical practices. Specifically, patients with brain cancer face unique barriers to clinical trial enrollment and completion due to disease-specific neurologic and treatment-induced conditions. Collectively, the intersection of these disease-specific conditions with social determinants of health fosters a lack of diversity in clinical trials. To ameliorate this disparity in neuro-oncology clinical trial participation, we present interventions focused on improving engagement of HMGs. Proposals range from inclusive trial design, decreasing barriers to care, expanding trial eligibility, access to tumor profiling for personalized medical trials, setting reasonable metrics and goals for accrual, working with patient community stakeholders, diversifying the neuro-oncology workforce, and development of tools to overcome biases with options to incentivize equity. The diversification of participation amongst neuro-oncology clinical trials is imperative. Equitable access and inclusion of HMG patients with brain tumors will not only enhance research discoveries but will also improve patient care.
The Risk of Sympathetic Ophthalmia Associated with Open-Globe Injury Management Strategies
Authors: Tim J. Patterson, Adam Kedzierski, David McKinney, Jonathan Ritson, Chris McLean, Weidong Gu, Marcus Colyer, Scott F. McClellan, Sarah C. Miller, Grant A. Justin, Annette K. Hoskin, Kara Cavuoto, James Leong, Andrés Rousselot Ascarza, Fasika A. Woreta, Kyle E. Miller, Matthew C. Caldwell, William G. Gensheimer, Tom Williamson, Felipe Dhawahir-Scala, Peter Shah, Andrew Coombes, Gangadhara Sundar, Robert A. Mazzoli, Malcolm Woodcock, Stephanie L. Watson, Ferenc Kuhn, Sophia Halliday, Renata S.M. Gomes, Rupesh Agrawal, Richard J. Blanch
Journal: Ophthalmology (2023)

Topic Sympathetic ophthalmia (SO) is a sight threatening granulomatous panuveitis caused by a sensitizing event. The use of primary enucleation or primary evisceration, versus primary repair, as a risk management strategy following OGI remains controversial. Clinical relevance This systematic review was conducted to report the incidence of SO after primary repair compared to after primary enucleation or primary evisceration. This enabled the reporting of an estimated number needed to treat (NNT). Methods Five journal databases were searched. This review was registered with PROSPERO: CRD42021262616. Searches were carried out on 29th June 2021 and updated 10th Dec 2022. Prospective or retrospective studies which reported outcomes (including sympathetic ophthalmia or lack of sympathetic ophthalmia) in a patient population who underwent either primary repair and primary enucleation, or primary evisceration, were included. A systematic review and meta-analysis were carried out in accordance with PRISMA guidelines. PROSPERO registration number CRD42021262616. Random effects modelling was used to estimate pooled SO rates and absolute risk reduction (ARR). Results Eight studies reporting SO as an outcome were included in total. The included studies contained 7500 patients and 7635 OGIs. In total 7620 OGIs met the criteria for inclusion in this analysis; 21 developed SO. When all included studies were pooled, the estimated SO rate was 0.12% (95% confidence interval (CI) 0.00% to 0.25%) after OGI. Out of 779 patients who underwent primary enucleation or primary evisceration no SO cases were reported, resulting in pooled SO estimate of 0.05% (95% CI 0.00% – 0.21%). For primary repair, the pooled estimate of SO rate was 0.15% (95% CI 0.00% to 0.33%). The ARR using a random effects model was -0.0010 (in favour of eye removal) (95% CI -0.0031 (in favour of eye removal) to 0.0011 (in favour of primary repair)). GRADE analysis highlighted a low certainty of evidence, as the included studies were observational and there was a risk of bias from missing data. Conclusion Based on the available data, there is no evidence that primary enucleation or primary evisceration reduce the risk of secondary SO.
Hepatic prohibitin 1 and methionine adenosyltransferase α1 defend against primary and secondary liver cancer metastasis
Authors: Wei Fan, DuoYao Cao, Bing Yang, Jiaohong Wang, Xiaomo Li, Diana Kitka, Tony W.H. Li, Sungyong You, Stephen Shiao, Alexandra Gangi, Edwin Posadas, Dolores Di Vizio, Maria Lauda Tomasi, Ekihiro Seki, José M. Mato, Heping Yang, Shelly C. Lu
Journal: Journal of Hepatology (2023)
Skin derived precursors induced Schwann cells mediated tissue engineering-aided neuroregeneration across sciatic nerve defect
Authors: Chengbin Xue, Hui Zhu, Hongkui Wang, Yaxian Wang, Xi Xu, Songlin Zhou, Dong Liu, Yahong Zhao, Tianmei Qian, Qi Guo, Jin He, Kairong Zhang, Yun Gu, Leilei Gong, Jian Yang, Sheng Yi, Bin Yu, Yongjun Wang, Yan Liu, Yumin Yang, Fei Ding, Xiaosong Gu
Journal: Bioactive Materials (2023)

A central question in neural tissue engineering is how the tissue-engineered nerve (TEN) translates detailed transcriptional signals associated with peripheral nerve regeneration into meaningful biological processes. Here, we report a skin-derived precursor-induced Schwann cell (SKP-SC)-mediated chitosan/silk fibroin-fabricated tissue-engineered nerve graft (SKP-SCs-TEN) that can promote sciatic nerve regeneration and functional restoration nearly to the levels achieved by autologous nerve grafts according to behavioral, histological, and electrophysiological evidence. For achieving better effect of neuroregeneration, this is the first time to jointly apply a dynamic perfusion bioreactor and the ascorbic acid to stimulate the SKP-SCs secretion of extracellular matrix (ECM). To overcome the limitation of traditional tissue-engineered nerve grafts, jointly utilizing SKP-SCs and their ECM components were motivated by the thought of prolongating the effect of support cells and their bioactive cues that promote peripheral nerve regeneration. To further explore the regulatory model of gene expression and the related molecular mechanisms involved in tissue engineering-aided peripheral nerve regeneration, we performed a cDNA microarray analysis of gene expression profiling, a comprehensive bioinformatics analysis and a validation study on the grafted segments and dorsal root ganglia tissues. A wealth of transcriptomic and bioinformatics data has revealed complex molecular networks and orchestrated functional regulation that may be responsible for the effects of SKP-SCs-TEN on promoting peripheral nerve regeneration. Our work provides new insights into transcriptomic features and patterns of molecular regulation in nerve functional recovery aided by SKP-SCs-TEN that sheds light on the broader possibilities for novel repair strategies of peripheral nerve injury.