Research square最新文献

{"title":"Associations of Health Insurance with Guideline-Concordant Treatment and Overall Survival Among Women with Breast Cancer.","authors":"Tu C Le, Ruixiao R Wang, Candice A M Sauder, Qian Li, Mahnoor Wani, Ana I Jacinto, Theresa H M Keegan","doi":"10.21203/rs.3.rs-10989233/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-10989233/v1","url":null,"abstract":"<p><p>Purpose Inadequate health insurance is a barrier to timely, appropriate breast cancer treatment. This study examined the association of insurance with receipt of guideline-concordant therapy and overall survival. Methods Women aged ≥ 18 years when diagnosed with invasive breast cancer between 2014-2022 were identified through the California Cancer Registry (n = 200,080). Guideline-concordant treatment was defined by three Commission on Cancer quality measures: breast-conserving surgery (BCS) or mastectomy for American Joint Commission on Cancer (AJCC) stages I or II cancers (Q1); radiation within one year of diagnosis for women < 70 who received BCS (Q2); and radiation within one year of diagnosis for patients with ≥ 4 positive regional lymph nodes following mastectomy (Q3). Multivariable logistic regression and Cox proportional hazards models assessed receipt of each measure and overall survival, respectively, stratified by age group. Results Adherence was highest for Q1 (95-96%), followed by Q2 (76%) and Q3 (50-56%). Women 18-64 years with Medicaid or Medicare (vs. private) insurance were less likely to receive all quality measures [adjusted odds ratio (aORs): 0.52-0.68]. Women ≥ 65 years with Medicaid or Medicare were less likely to receive Q1 or Q2 (ORs: 0.54-0.88), although Q2 adherence with Medicare plus supplemental was similar to private insurance. Non-adherence was associated with worse overall survival across all quality measures. Conclusion Insurance-related disparities in care and survival persisted after ACA implementation, particularly among younger, publicly insured patients. While Medicare has improved access to care for older adults, disparities remain, highlighting the need to address these disparities to ensure equitable cancer care for all patients.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Δ4-p63 Enhances Epithelial Stem Cell Clonogenicity and Cooperates with Oncogenic KRAS to Promote Squamous Dysplasia.","authors":"Keshia Pitt, Filipa Pinto, Thabet AlHousami, Yoshiyuki Mochida, Makoto Senoo","doi":"10.21203/rs.3.rs-11038772/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11038772/v1","url":null,"abstract":"<p><p>p63 is a critical transcription factor for the development and maintenance of stratified epithelia and is essential for the proliferative capacity of epithelial stem cells. Here, we investigated the biological significance of a Δ4-p63 isoform generated by deletion of exon 4 of the <i>p63</i> gene. Although Δ4-p63 is undetectable in normal epithelia, its expression is positively associated with human squamous cell carcinoma (SCC). Mice heterozygous for the p63 exon 4 deletion developed normally, whereas homozygous mutants were neonatal lethal. Although no overt histological abnormalities were detected in the skin of heterozygous mice, epithelial cells isolated from these animals exhibited markedly enhanced clonogenic potential compared with cells from wild-type (WT) mice. This phenotype persisted during prolonged culture and serial passage, suggesting an intrinsic increase in epithelial stem cell proliferative or self-renewal capacity rather than transient expansion associated with differentiation. Furthermore, heterozygosity for the p63 exon 4 deletion markedly enhanced epithelial dysplasia in mice expressing oncogenic Kras ^G12D , revealing a genetic interaction between p63 exon 4 deficiency and oncogenic KRAS signaling. ChIP-seq analysis demonstrated that p63 in WT mice and the p63/Δ4-p63 complex in heterozygous mice retain highly similar genome-wide DNA-binding profiles, indicating that exon 4 deletion does not abolish p63 chromatin occupancy. However, p63 and p63/Δ4-p63 showed preferential association with distinct subsets of regulatory regions. p63 in WT mice preferentially occupied regions associated with epithelial transcriptional regulators, whereas p63/Δ4-p63 in heterozygous mice preferentially associated with regulatory regions linked to Klf14, Elk4, Npas/Bmal1, Arnt, and Ar. Together, these findings suggest that Δ4-p63 is not simply a loss-of-function isoform, but instead alters the p63-dependent transcriptional landscape and epithelial stem cell state, creating a cellular context that cooperates with oncogenic KRAS to promote squamous epithelial dysplasia.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Exome to Optical Mapping: Resolving a Complex 17q12 Rearrangement Underlying a Severe Neurodevelopmental Disorder.","authors":"Zain Dardas, Haowei Du, Daniel G Calame, Davut Pehlivan, Elif Yilmaz Gulec, Ahmed K Saad, P J Hastings, Jennifer E Posey, Richard A Gibbs, Christopher M Grochowski, James R Lupski","doi":"10.21203/rs.3.rs-11055592/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11055592/v1","url":null,"abstract":"<p><p>Background Complex genomic rearrangements (CGRs) are significant contributors to neurodevelopmental disorders, yet their full structural architecture often eludes conventional diagnostic methods. We investigated the genetic basis of a 7-year-old boy presenting with severe intellectual and growth delay, immune deficiency, and multiple congenital anomalies. Methods We combined exome sequencing, array comparative genomic hybridization, short-read and long-read genome sequencing, droplet digital PCR, and optical genome mapping to characterize a chromosomal rearrangement identified in the proband and to assess segregation within the family trio. Results This integrated approach reconstructed the architecture of a highly complex duplication-triplication-quadruplication rearrangement on chromosome 17q12, encompassing the developmental and immune-regulatory genes <i>DUSP14</i> , <i>SYNRG</i> , <i>DDX52</i> , and <i>HNF1B</i> , consistent with the proband's phenotypic spectrum. Breakpoint mapping revealed microhomologies and inverted repeats, implicating a replication-based mechanism, such as microhomology-mediated break-induced replication, in the rearrangement's formation. Droplet digital PCR further uncovered low-level mosaicism in the asymptomatic father, indicating a potential germline transmission pathway relevant to familial recurrence risk. Conclusions Integrating multiple sequencing and optical mapping technologies can resolve complex structural variation, uncover parental mosaicism, and implicate candidate genes that conventional methods alone would miss. This approach improves molecular diagnosis and advances understanding of the mutational mechanisms underlying complex disease-associated rearrangements.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MTHFR*677C&gt;T produces distinct prodromal disease signatures in a mouse model of late-onset Alzheimer's disease.","authors":"Kevin P Kotredes, Ravi S Pandey, Alaina M Reagan, Zeynep Sarica, Rita O'Rourke, Sarah Herrick, Avery Davis, Dylan Garceau, Michael Sasner, Gregory W Carter, Gareth R Howell","doi":"10.21203/rs.3.rs-11166891/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11166891/v1","url":null,"abstract":"<p><p><b>Background</b> Late-onset Alzheimer's disease (LOAD) comprises more than 95% of all AD cases. Transgenic, overexpression animal models have off-target side effects, do not effectively produce the heterogeneity observed clinically in LOAD patients, and are therefore not best suited for preclinical therapeutic development. The Model Organism Development and Evaluation for Late-onset Alzheimer's Disease (MODEL-AD) Consortium was established to develop novel mouse strains to model human-relevant genetic and environmental risk factors for LOAD. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme in the folate/methionine pathway. Variants in the <i>MTHFR</i> gene, notably <i>677C > T</i> , are associated with ADRD, and we have previously shown the <i>Mthfr</i> ^{<i>677C>T</i>} mouse model phenocopies humans carrying the variant and develops cerebrovascular deficits. <b>Methods</b> To examine the contributions of <i>Mthfr</i> ^{<i>677C>T</i>} in the context of late-onset Alzheimer's disease (LOAD), MODEL-AD created a novel mouse strain on the C57BL/6J (B6) background that was homozygous for <i>Mthfr</i> ^{<i>677C>T</i>} , in combination with humanized <i>Aβ</i> , <i>APOEe4</i> , and <i>Trem2*R47H</i> ( <i>referred to as LOAD2.Mthfr</i> ^{<i>677C>T</i>} <i>)</i> . Mice were assessed over multiple ages for disease-relevant phenotypes. Regular behavior measurements and biometric samples were collected longitudinally to 24 months of age. Blood and brain tissue were collected for transcriptomics, proteomics, human disease correlation, and neuropathology. <b>Results</b> Despite lacking hallmark pathologies such as amyloid deposition and significant neuroinflammation, compared to LOAD2 controls, <i>LOAD2.Mthfr</i> ^{<i>677C>T</i>} mice showed transcriptional and proteomic signatures in the brain that relate to the cerebrovasculature, myelination, and synaptic biology, similar to those seen in human LOAD patients. <b>Conclusions</b> These data further support the use of the LOAD2.Mthfr ^{<i>677C>T</i>} mouse model to study aspects of ADRD such as cerebrovascular compromise.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Food noise among U.S. adults: Psychometric evaluation and prevalence estimates from a nationally representative sample.","authors":"Branislav Jovanovic, Nickolas Jones, Fengqing Zhang, Alison Holman, Michael Lowe","doi":"10.21203/rs.3.rs-10997388/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-10997388/v1","url":null,"abstract":"<p><p><b>Background:</b> Widespread use of GLP-1 medications has revealed not only their effectiveness in reducing food intake and body mass, but also the clinical relevance of a seemingly underrecognized cognitive-affective process, food noise, that may be highly distressing for some individuals. Although the concept has gained increasing attention in public discourse, empirical research on food noise remains quite limited. We aimed to provide an initial epidemiologic characterization of food noise among U.S. adults. <b>Methods:</b> Our study utilized data from a nationally representative sample of U.S. adults ( <i>N</i> =3 646) conducted in Fall 2025. Survey-weighted exploratory and confirmatory factor analyses were used to evaluate the structure of the Food Noise Questionnaire (FNQ; ref. 1). Food noise endorsement was estimated using three operational definitions. Survey-weighted linear regression was used to examine associations between food noise and sociodemographic and weight-related subgroups. <b>Results:</b> Exploratory factor analysis supported a strongly loaded one-factor solution explaining approximately 80% of the variance. Confirmatory factor analysis supported the one-factor structure, with factor loadings and model fit broadly consistent with the original FNQ validation study. Depending on the operational definition, approximately 4% to 9.5% of U.S. adults met criteria for food noise endorsement. Among adults with obesity, prevalence ranged from approximately 6% to 14%. Food noise scores were higher among women than men ( <i>B</i> =0.18, 95%CI[0.09, 0.26], <i>p</i> <.001), higher among younger adults, and progressively increased across weight categories, from overweight ( <i>B</i> =0.23, 95%CI[0.13, 0.32], <i>p</i> <.001) to class III obesity ( <i>B</i> =0.61, 95%CI[0.46, 0.76], <i>p</i> <.001), relative to normal weight. <b>Conclusions:</b> These findings provide an initial indication of the potential scope and public health relevance of food noise, suggesting that its occurrence is not negligible but is far from ubiquitous among adults with obesity. Further research is needed to establish clinically meaningful thresholds, determine the overlap of food noise with related constructs, and examine its underlying mechanisms.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Movement and sociodemographic predictors of zoonotic and human hookworm infection in rural Madagascar.","authors":"Georgia Titcomb, Kayla Kauffman, Tyler Barrett, Randall Kramer, Peter Mucha, Michelle Pender, Jean Yves Rabezara, Prisca Rahary, Toky Randriamoria, Voahangy Soarimalala, Charles L Nunn","doi":"10.21203/rs.3.rs-11295240/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11295240/v1","url":null,"abstract":"<p><p>Hookworms infect half a billion people worldwide, disproportionately impacting those living in poverty. Previous research has focused on sociodemographic predictors of infection, while less is known about how human land use influences infection. Moreover, recent molecular research has revealed that humans are frequently infected by multiple hookworm species that likely differ in their transmission patterns. In this study, we combined DNA metabarcoding of human and domesticated animal parasites with fine-scale GPS movement data to investigate how hookworm infection relates to people's land use and sociodemographic characteristics in three villages in rural Madagascar. We found high hookworm infection prevalence (52% in women and 69% in men; n = 881). <i>Necator americanus</i> predominated (53% prevalence), but the zoonotic hookworm <i>Ancylostoma ceylanicum</i> was also common (20% prevalence). Domesticated animals hosted several parasite species typically absent in humans. However, the zoonotic hookworm <i>A. ceylanicum</i> was highly prevalent in dogs (67-88% across villages). Consistent with previous findings, men had double the odds of <i>Necator americanus</i> infection than women, and prevalence was higher in those with lower material wealth (64% prevalence in the bottom quartile versus 47% prevalence in the top quartile). Zoonotic hookworm infections were more common in men than women (OR = 1.54), those with less formal education, and those reporting close contact with dogs (OR = 1.61). Regarding land use by people, we found that larger home ranges and greater use of vegetated areas outside villages was linked with increased <i>N. americanus</i> , but not <i>A. ceylanicum,</i> infection risk. Network analyses revealed that infected individuals were more strongly connected to each other than to uninfected individuals on networks of shared vegetated patches outside of the village. However, in one village with low levels of vegetation cover, we found significant spatial associations between people's dwellings and human hookworm infections, illustrating the importance of ecological context for hookworm transmission. These findings underscore the importance of integrating fine-scale land use patterns with sociodemographic risk factors to better understand and mitigate human and zoonotic hookworm transmission.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct subtypes of the negative hemodynamic response function across cortical distance and depth in human visual cortex.","authors":"Artemy Vinogradov, Nooshin J Fesharaki, Junseok Park, Eunyoung Lee, Huimahn A Choi, Jung Hwan Kim","doi":"10.21203/rs.3.rs-11088189/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11088189/v1","url":null,"abstract":"<p><p>The negative blood-oxygenation-level-dependent (BOLD) response (NBR) and its origins have been investigated for over a decade. However, the temporal characteristics and spatial organization of the NBR are not fully understood. Previous studies by our group and others have shown that the negative HRF (nHRF)-the NBR evoked by a brief stimulus-exhibits substantial spatial variability. To investigate this spatial variability in greater detail, we used a unilateral parafoveal visual stimulus and examine nHRF temporal dynamics as a function of cortical distance from the stimulus representation (SR) and throughout cortical depth in both the contralateral and ipsilateral visual cortex. We identified two temporally distinct patterns of nHRF dynamics and defined the corresponding subtypes: 1) a transient nHRF (T-nHRF), characterized by a weak but significant initial negative response (INR) followed by a prominent positive peak, and 2) a fully developed nHRF (FD-nHRF), characterized by a delayed and strong INR followed by a weak or absent positive peak. We observed that the two subtypes coexisted throughout visual cortex in regionally varying proportions. T-nHRFs predominated near the SR while FD-nHRFs predominated in more peripheral contralateral regions and homologous ipsilateral regions. Response magnitudes increased toward the superficial gray matter, with pronounced depth dependence in the positive peak for T-nHRFs and in the INR for FD-nHRFs. For each subtype, depth dependence was most consistent in regions where that subtype predominated. The regional distributions and depth-dependent response profiles of two nHRF subtypes showed systematic nHRF organization with respect to cortical distance from the SR and cortical depth. This organization suggests that distinct NBR mechanisms may contribute to the two subtypes, with their relative contributions varying cortical locations.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Immunopeptidomics by Characterizing Immunopeptides Against HLAs, TCRs, and Antibodies.","authors":"Hongyi Liu, Effram Wei, Yingwei Hu, Yuefan Wang, Zhenyu Sun, Hui Zhang","doi":"10.21203/rs.3.rs-11040221/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11040221/v1","url":null,"abstract":"<p><p>Target-directed immunotherapies, including TCR-T cell therapies, targeted antibody therapy, and therapeutic vaccines, rely on the identification of tumor-specific antigens (TSAs). However, classical immunopeptidomics is severely constrained by an inability to distinguish passively presented self-ligands of HLAs from functionally recognized by T cells. To resolve these challenges, we developed immunopeptidomics for receptor-associated antigens, a platform capable of sequentially isolating immunopeptidome and their functions with immune cell receptors from a single clinical tissue specimen. Applied to a cohort of 30 renal cell carcinoma (RCC) specimens (18 primary tumors and 12 paired normal adjacent tissues), this approach generated expansive presentation maps encompassing 38,848 unique HLA-I and 26,961 unique HLA-II peptides. Functional receptor captures (IgG- and TCR-bound) achieved up to 5.3-fold higher tumor-specific peptide (TSP) purity ratios compared to direct baseline HLA isolation. Furthermore, cross-fractional co-identification validated recurrent, high-priority unmutated targets (NNMT, TMBIM6, RPL3, VIM, and ENPP3) alongside tumor-specific phosphopeptide hubs and macrophage-restricted N-glycopeptides (CD68). Integrating companion global proteomics uncovered a fundamental regulatory divergence between MHC classes: HLA-I presentation throughput scales linearly (R = 0.883) via a STAT1-orchestrated transcriptional program driving the antigen presentation machinery (APM), whereas HLA-II presentation is uncoupled from parental protein abundance (R = 0.302) due to asynchronous downstream endolysosomal processing and proteolytic over-cleavage kinetics. Together, this platform establishes a micro-input framework that unifies physical presentation with native functional characterization and microenvironmental regulation to accelerate target discovery in low-TMB human cancers.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-Technical Skills for Surgery in African Perioperative Curricula: A Scoping Review.","authors":"Shaliz Barzani, Marie Merci Cyuzuzo, Wendy Williams, Egide Abahuje, Robert Riviello, Barnabas Tobi Alayande","doi":"10.21203/rs.3.rs-11125425/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11125425/v1","url":null,"abstract":"<p><p><b>Introduction</b> : Non-technical skills (NTS) such as situation-awareness, decision-making, communication, and leadership among surgical healthcare providers are vital to safe surgical care. Studies have associated poor NTS with errors in the operating room. The extent to which African training curricula address NTS is unclear. We mapped the presence and absence of NTS content in surgery, obstetrics and gynecology, anesthesia, and nursing/midwifery training curricula across Africa. <b>Methods</b> : Using the Arksey and O'Malley methodological framework, we conducted a scoping review on PubMed, AJOL, and Google Scholar databases, followed by a grey literature search to identify published perioperative training curricula from African institutions. Data on NTS were abstracted and were categorized as explicitly teaching, explicitly mentioning, implicitly mentioning, or making no mention of NTS. <b>Results</b> : From 55 screened documents, 31 specialty curricula from 18 institutions across 11 countries met inclusion criteria. West Africa was represented at 45.2%, followed by East Africa at 29.0%, and North and South Africa at 6.5% each. Curricula from the College of Surgeons of East, Central and Southern Africa, the College of Anesthesiologists of East, Central and Southern Africa, the East, Central and Southern African College of Obstetrics and Gynecology, and the WHO Africa Prototype Competency-Based Curriculum accounted for 12.9%. No single-country NTS curriculum was identified from Central Africa. NTS were mentioned implicitly (38.7%), explicitly (48.4%), both implicitly and explicitly (6.5%), or not at all (6.5%). Most curricula (93.5%) mentioned at least one NTS. Among NTS domains, leadership was most frequently mentioned (67.7%), followed by teamwork (61.3%), communication (45.2%), professionalism (35.5%), decision-making (32.3%), and problem-solving (29.0%). Critical thinking and situation awareness (6.5%) were the least represented domains. <b>Conclusion</b> : While several African perioperative curricula mention NTS, gaps exist in the incorporation of formalized NTS training in existing courses and assessments, especially in Central Africa. Targeted curriculum reform is needed to transition NTS from implicit expectations to explicitly taught and assessed competencies in African perioperative training. Structured coursework, such as the Non-Technical Skills for Surgeons in Variable Resource Contexts (NOTSS-VRC) may help fill these gaps.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An in vitro platform for the rapid and scalable biocatalysis of complex polyketides.","authors":"Adrian Keatinge-Clay, Jie Zhang","doi":"10.21203/rs.3.rs-10935154/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-10935154/v1","url":null,"abstract":"<p><p>Modular polyketide synthases (PKSs) are enzymatic assembly lines that naturally produce complex, bioactive compounds challenging to obtain through traditional synthesis or fermentation. Early attempts to harness these molecular factories outside the cell indicated they make poor biocatalysts. However, we observe that a refactored pikromycin synthase optimized for in vitro performance operates as rapidly as iterative fatty acid synthases, two orders of magnitude faster than measured for the equivalently-sized erythromycin synthase. The activities of four engineered variants of the pikromycin synthase were also enhanced through relocating histidine tags, swapping enzymatic/docking domains, and tuning polypeptide stoichiometry. To enable the economic conversion of feedstock chemicals malonate and methylmalonate by these and other synthases into scalable quantities of complex polyketides, we developed the Extender unit to PolyKetide (EPK) platform, which incorporates extender unit and NADPH regeneration systems. In a 10-mL, 2-hour, room-temperature reaction, 1 μM of a refactored pikromycin synthase converts malonate and methylmalonte into 2.8 mM (1 mg/mL) narbonolide with a total turnover number (TTON) of 2800. All five stereocomplex products were readily obtained in pure form at the milligram scale and structurally characterized, demonstrating the advantages of accessing complex polyketide through in vitro biocatalysis as well as the potential to access combinatorial polyketide libraries for medicinal chemistry.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}