Integrating predictive coding and a user-centric interface for enhanced auditing and quality in cancer registry data.

Data curation for a hospital-based cancer registry heavily relies on the labor-intensive manual abstraction process by cancer registrars to identify cancer-related information from free-text electronic health records. To streamline this process, a natural language processing system incorporating a hybrid of deep learning-based and rule-based approaches for identifying lung cancer registry-related concepts, along with a symbolic expert system that generates registry coding based on weighted rules, was developed. The system is integrated with the hospital information system at a medical center to provide cancer registrars with a patient journey visualization platform. The embedded system offers a comprehensive view of patient reports annotated with significant registry concepts to facilitate the manual coding process and elevate overall quality. Extensive evaluations, including comparisons with state-of-the-art methods, were conducted using a lung cancer dataset comprising 1428 patients from the medical center. The experimental results illustrate the effectiveness of the developed system, consistently achieving F1-scores of 0.85 and 1.00 across 30 coding items. Registrar feedback highlights the system's reliability as a tool for assisting and auditing the abstraction. By presenting key registry items along the timeline of a patient's reports with accurate code predictions, the system improves the quality of registrar outcomes and reduces the labor resources and time required for data abstraction. Our study highlights advancements in cancer registry coding practices, demonstrating that the proposed hybrid weighted neural-symbolic cancer registry system is reliable and efficient for assisting cancer registrars in the coding workflow and contributing to clinical outcomes.

Collagen sponge scaffolds loaded with Trichostatin A pretreated BMSCs-derived exosomes regulate macrophage polarization to promote skin wound healing.

The process of wound healing includes the inflammatory stage, which plays an important role. Macrophages can promote inflammatory response and also promote angiogenesis, wound contraction and tissue remodeling required for wound healing. It is crucial to promote macrophages to polarize from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype at a critical time for the quality of wound healing. Because mesenchymal stem cell-derived exosomes have broad therapeutic prospects in the field of tissue repair and regeneration, in this study, we explored whether trichostatin A pretreated bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (T-Exo) could promote wound healing by binding to biomaterial scaffolds through certain anti-inflammatory effects. In the cell experiment, we established macrophage inflammation model and then treated with T-Exo, and finally detected the expression levels of macrophage polarization proteins CD206, CD86 and TNF-α, iNOS, and Arg-1 by Western Blot and immunofluorescence staining; detected the expression levels of inflammation-related genes TNF-α, iNOS, IL-1ß, IL-10 and anti-inflammatory genes CD206 and Arg-1 by qRT-PCR; explored the promoting ability of T-Exo to promote cell migration and tube formation by cell scratch experiment and angiogenesis experiment. The results showed that T-Exo could promote the polarization of M1 macrophages to M2 macrophages, and promote the migration and angiogenesis of HUVECs. Because TSA pretreatment may bring about changes in the content and function of BMSCs-derived exosomes, proteomic analysis was performed on T-Exo and unpretreated BMSCs-derived exosomes (Exo). The results showed that the differentially expressed proteins in T-Exo were related to some pathways that promote angiogenesis, cell migration, proliferation, and re-epithelialization. Then, exosome/collagen sponge (T-Exo/Col) biological scaffolds were prepared, and the physicochemical properties and biocompatibility of the scaffolds were investigated. Animal skin wound models were established, and the therapeutic effect and anti-inflammatory effect of T-Exo/Col in wound repair were evaluated by small animal in vivo imaging, H&E staining, Masson trichrome staining, immunohistochemical staining, Western Blot, and qRT-PCR. The results showed that T-Exo significantly promoted wound healing by inhibiting inflammation, thereby further promoting angiogenesis and collagen formation in vivo. Moreover, the existence of Col scaffold in T-Exo/Col enabled T-Exo to achieve a certain sustained release effect. Finally, we further explored whether TSA exerts beneficial effects by inhibiting HDAC6 gene of BMSCs, but the results showed that knockdown of HDAC6 gene would cause oxidative stress damage to BMSCs, which means that TSA does not produce these beneficial effects by inhibiting HDAC6 gene. What molecular mechanisms TSA exerts beneficial effects through needs to be further elucidated in the future.

Impact of left ventricular ejection fraction and aortic valve gradient on mortality following transcatheter aortic valve intervention.

BACKGROUND: Data regarding the impact of reduced left ventricular ejection fraction (LVEF) and/or reduced mean aortic valve gradient (AVG) on outcomes following transcatheter aortic valve intervention (TAVI) have been conflicting. We sought to assess the relationship between LVEF, AVG, and 1-year mortality in patients undergoing TAVI. METHODS: We prospectively evaluated 298 consecutive adults undergoing TAVI from 2015 to 2018 at an academic tertiary medical center. Patients were categorized according to LVEF and mean AVG. The primary outcome of interest was all-cause mortality at 1 year. RESULTS: Of 298 adults undergoing TAVI, 66 (22.1%) had baseline LVEF ≤45% while 232 (77.9%) had baseline LVEF >45%; 173 (58.1%) had baseline AVG < 40mmHg while 125 (41.9%) had baseline AVG ≥ 40mmHg. Rates of 1-year all-cause mortality were significantly higher in patients with LVEF ≤45% (28.8% vs 12.1%, p = 0.001) and those with AVG < 40mmHg (19.7% vs 10.4%, p = 0.031) compared to those with LVEF >45% and AVG ≥ 40mmHg respectively. In multivariable analysis, higher AVG (per mmHg) (OR 0.97, 95% CI 0.94-0.99, p = 0.026) was noted to be independently associated with lower rates of 1-year mortality, while LVEF was not (OR 0.98, 95% CI 0.96-1.01). CONCLUSIONS: In this prospective, contemporary registry of adults undergoing TAVI, while 1-year unadjusted mortality rates are significantly higher in patients with reduced LVEF and reduced AVG, risk-adjusted mortality at 1 year is only higher in those with reduced AVG - not in those with reduced LVEF.

Evaluation of 5'-tRF-His-GTG As a Molecular Biomarker in Breast Cancer Diagnoses and Prognosis.

Background: Breast cancer (BC) is the most prevalent cancer among women worldwide. Although advances have been made in the identification of predictive biomarkers, current options for early diagnosis and prognostic analysis are still suboptimal. Recently, transfer-RNA-derived RNA fragments (tRFs) have emerged as a class of small noncoding RNAs that play a role in the cancer progression. The authors aimed to identify a specific class of tRFs as a molecular marker for BC diagnosis and prognosis in clinical management. Methods: The levels of 5'-tRF-His-GTG were quantified in BC tissue (n = 101) and inflammatory normal breast tissue (n = 22) using in situ hybridization. Clinicopathological parameters were obtained, including age, tumor node metastasis stage, hormone receptor status, histopathological grade, lymphovascular invasion, and recurrence. The correlation between the expression of 5'-tRF-His-GTG and these parameters in different BC subtypes was analyzed. Patient death and cancer progression were regarded as clinical endpoints in the survival analysis. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were also performed to predict the involvement in pivotal biological process. Results: The expression of 5'-tRF-His-GTG was significantly downregulated in BC tissues and was in connection with T stage in human epidermal growth factor 2-positive and basal-like BC, as well as N stage and histopathological grade in luminal BC. Patients with low expression of 5'-tRF-His-GTG had a poor overall survival rate. Statistics of GO and KEGG pathway revealed that cation channel activity, protein catabolic process, response to temperature stimulus, cell cycle, focal adhesion, and glycerophospholipid metabolism were significantly enriched. Conclusions: This study suggests that the assessment of 5'-tRF-His-GTG expression could serve as a novel biomarker for individual diagnosis and prognosis in BC.

Quality of life, sleep and anxiety status among patients with rosacea in the Yunnan plateau region: A 2-year retrospective study.

OBJECTIVE: To investigate the life, sleep quality and anxiety of rosacea patients in Yunnan and the improvement of these aspects after treatment. METHODS: A total of 141 patients with rosacea and 123 healthy controls were included in our study. The quality of life, sleep quality and anxiety of patients with rosacea and healthy controls were investigated by the Rosacea Severity Scores (RSSs), the Medical Outcomes Study 36-item short-form health survey (SF-36), the Pittsburgh Sleep Quality Index (PSQI) and Self-rating Anxiety Scale (SAS). The quality of life, sleep quality and anxiety of patients with rosacea were assessed again after treatment. RESULTS: Compared with healthy controls, patients with rosacea had significantly lower physical component scores (PCS) and mental component scores (MCS) but higher PSQI and SAS scores. After treatment, rosacea patients showed significantly higher MCS but lower PSQI and SAS scores. Correlation analysis showed a significant correlation between PCS, MCS, PSQI, SAS and RSSs. CONCLUSIONS: Patients with rosacea have a lower quality of life and sleep quality and tend to be more anxious than healthy controls. In addition, the mental quality of life, sleep quality and anxiety of rosacea patients can be significantly improved after treatment. Therefore, it is important to pay attention to the psychological status of rosacea patients. Psychological counseling and intervention are necessary to better prevent and treat rosacea.

Lactiplantibacillus paraxiangfangensis sp. nov., isolated from traditional Chinese pickle.

Three Gram-stain-positive bacterial strains (designated 231-9T, 142-6 and 463-4) were isolated from traditional Chinese pickle, and were characterized using a polyphasic taxonomic approach. Results of 16S rRNA gene sequence analysis indicated that strains 231-9T, 142-6 and 463-4 were phylogenetically related to the type strains of Lactiplantibacillus xiangfangensis, Lactiplantibacillus garii, Lactiplantibacillus carotarum, Lactiplantibacillus plajomi and Lactiplantibacillus modestisalitolerans, having 98.6-99.9 % 16S rRNA gene sequence similarities. Strains 231-9T, 142-6 and 463-4 were most closely related to the type strain of L. xiangfangensis, having 99.9 % 16S rRNA gene, 95.6 % pheS, 99.4 % rpoA and 98.2 % concatenated pheS and rpoA sequence similarities. Relatively low pheS (95.6 %) sequence similarity indicated that strain 231-9T should be further identified. Strain 231-9T shared 99.7-99.9 % average nucleotide identity (ANI) and 98.8-98.9 % digital DNA-DNA hybridization (dDDH) values with strains 142-6 and 463-4, indicating that they belonged to the same species. The ANI and dDDH values between strain 231-9T and L. xiangfangensis LMG 26013T were 92.4-92.9 and 49.6 %, respectively, less than the threshold for species demarcation (95-96% ANI and 70 % dDDH values, respectively), indicating that strains 231-9T, 142-6 and 463-4 represented a novel species within the genus Lactiplantibacillus. Acid production from d-ribose, d-adonitol, d-galactose and lactose, activity of ß-galactosidase and ß-glucosidase, Voges-Proskauer reaction, hydrolysis of hippurate, resistance to 5 µg ml-1 erythromycin, 100 µg ml-1 tetracycline hydrochloride, 50 µg ml-1 bacitracin, 300 µg ml-1 each of gentamicin sulphate, streptomycin sulphate and neomycin sulphate, tolerance to 6 % NaCl could distinguish strains 231-9T, 142-6 and 463-4 from L. xiangfangensis 3.1.1T. Based upon the data of polyphasic characterization obtained in the present study, a novel species, Lactiplantibacillus paraxiangfangensis sp. nov., is proposed and the type strain is 231-9T (=JCM 36258T=CCTCC AB 2023133T).

Highly Accurate Profiling of Exosome Phenotypes Using Super-resolution Tricolor Fluorescence Co-localization.

Exosomes contain a wealth of proteomic information, presenting promising biomarkers for the noninvasive early diagnosis of diseases, especially cancer. However, it remains a great challenge to accurately and reliably distinguish exosomes secreted from different types of cell lines. Fluorescence immunoassay is frequently used for exosome detection. Nonspecific adsorption in immunoassays is unavoidable and affects the reliability of assay results. Despite the fact that various methods have been proposed to reduce nonspecific adsorption, a more effective method that can eliminate the influence of nonspecific adsorption is still lacking. Here, we report a more convenient way (named SR-TFC) to remove the artifacts caused by nonspecific adsorption, which combines tricolor fluorescence labeling of target exosomes, tricolor super-resolution imaging, and pixel counting. The pixel counting method (named CFPP) is realized by MATLAB and can eliminate nonspecific binding sites at the single-pixel level, which has never been achieved before and could improve the reliability of detection to the maximum extent. Furthermore, as a proof-of-concept, profiling of exosomal membrane proteins and identification of breast cancer subpopulations are demonstrated. To enable multiplex breast cancer phenotypic analysis, three kinds of specific proteins are labeled to obtain the 3D phenotypic information on various exosomes. Breast cancer subtypes can be accurately identified according to the super-resolution images of some clinically relevant exosomal proteins. Worth mentioning is that, by selecting other biomarkers, classification of other cancers could also be realized using SR-TFC. Hence, the present work holds great potential in clinical cancer diagnosis and precision medicine.

Controllable Manipulation of Large-Volume Droplet on Non-Slippery Surfaces Based on Triboelectric Contactless Charge Injection.

Controllable droplet manipulation is crucial in diverse scientific and engineering fields. Traditional electric-based methods usually rely on commercial high-voltage (HV) power sources, which are typically bulky, expensive, and potentially hazardous. The triboelectric nanogenerator (TENG) is a highly studied device that can generate HV output with limited current, showing great potential in droplet manipulation applications. However, current TENG-based approaches usually utilize traditional free-standing TENGs that produce short-pulsed alternating-current signals. This limitation hinders continuous electrostatic forces necessary for precise droplet control, leading to complex circuitry and suboptimal droplet motion control in terms of volume, distance, direction, and momentum. Here, a triboelectric contactless charge injection (TCCI) method employing a novel dual-functional triboelectric nanogenerator (DF-TENG), is proposed. The DF-TENG can produce both high voltage and constant current during unidirectional motion, enabling continuous corona discharges for contactless charge injection into the droplets. Using this method, a large-volume droplet (3000 µL) can be controlled with momentum up to 115.2 g mm s-1 , quintupling the highest value recorded by the traditional methods. Moreover, the TCCI method is adaptable for a variety of non-slippery substrates and droplets of different compositions and viscosities, which makes it an ideal manipulation strategy for droplet transport, chemical reactions, and even driving solids.

Hijacking of nucleotide biosynthesis and deamidation-mediated glycolysis by an oncogenic herpesvirus.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS) and multiple types of B cell malignancies. Emerging evidence demonstrates that KSHV reprograms host-cell central carbon metabolic pathways, which contributes to viral persistence and tumorigenesis. However, the mechanisms underlying KSHV-mediated metabolic reprogramming remain poorly understood. Carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD) is a key enzyme of the de novo pyrimidine synthesis, and was recently identified to deamidate the NF-κB subunit RelA to promote aerobic glycolysis and cell proliferation. Here we report that KSHV infection exploits CAD for nucleotide synthesis and glycolysis. Mechanistically, KSHV vCyclin binds to and hijacks cyclin-dependent kinase CDK6 to phosphorylate Ser-1900 on CAD, thereby activating CAD-mediated pyrimidine synthesis and RelA-deamidation-mediated glycolytic reprogramming. Correspondingly, genetic depletion or pharmacological inhibition of CDK6 and CAD potently impeded KSHV lytic replication and thwarted tumorigenesis of primary effusion lymphoma (PEL) cells in vitro and in vivo. Altogether, our work defines a viral metabolic reprogramming mechanism underpinning KSHV oncogenesis, which may spur the development of new strategies to treat KSHV-associated malignancies and other diseases.

Gemcitabine-based conditioning compared to BEAM/BEAC conditioning prior to autologous stem cell transplantation for non-Hodgkin lymphoma: No difference in outcomes.

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains an effective treatment for non-Hodgkin lymphoma (NHL). The limited availability of carmustine has prompted the exploration of novel alternative conditioning regimens. This study aimed to compare the efficacy and safety profile of GBM/GBC (gemcitabine, busulfan, and melphalan or cyclophosphamide) conditioning compared with the standard BEAM/BEAC regimens (carmustine, etoposide, cytarabine, and melphalan or cyclophosphamide) for ASCT in patients with NHL. METHODS: A retrospective analysis was conducted on 231 NHL patients, who underwent ASCT from October 2010 to October 2021 at the Institute of Hematology & Blood Disease Hospital, including both first-line and salvage settings. This resulted in the inclusion of 112 patients in the GBM/GBC arm and 92 in the BEAM/BEAC arm. Propensity score matching was employed to validate the results. RESULTS: Disease subtype distribution was similar between the GBM/GBC and BEAM/BEAC groups, with diffuse large B-cell lymphoma being the most common (58.9% vs. 58.7%), followed by PTCL (17.0% vs. 18.5%) and MCL (14.3% vs. 14.1%). At 3 months post-ASCT, complete response (CR) rates were comparable (GBM/GBC 93.5% vs. BEAM/BEAC 91.1%; p = 0.607). The 4-year progression-free survival (78.4% vs. 82.3%; p = 0.455) and 4-year overall survival (88.1% vs. 87.7%; p = 0.575) were also similar. Both groups exhibited low non-relapse mortality at 4 years (GBM/GBC 1.8% vs. BEAM/BEAC 3.5%; p = 0.790) with no transplant-related mortalities reported. The GBM/GBC cohort demonstrated a higher incidence of grade 3/4 oral mucositis and hepatic toxicity, whereas the BEAM/BEAC group had more frequent cases of bacteremia or sepsis (13 cases vs. 5 in GBM/GBC). CONCLUSIONS: The GBM/GBC regimen is effective and well-tolerated, offering outcomes that are highly comparable to those in NHL patients conditioned with BEAM/BEAC, as demonstrated in a prognostically matched cohort.

Segmentation of Low-Light Optical Coherence Tomography Angiography Images under the Constraints of Vascular Network Topology.

Optical coherence tomography angiography (OCTA) offers critical insights into the retinal vascular system, yet its full potential is hindered by challenges in precise image segmentation. Current methodologies struggle with imaging artifacts and clarity issues, particularly under low-light conditions and when using various high-speed CMOS sensors. These challenges are particularly pronounced when diagnosing and classifying diseases such as branch vein occlusion (BVO). To address these issues, we have developed a novel network based on topological structure generation, which transitions from superficial to deep retinal layers to enhance OCTA segmentation accuracy. Our approach not only demonstrates improved performance through qualitative visual comparisons and quantitative metric analyses but also effectively mitigates artifacts caused by low-light OCTA, resulting in reduced noise and enhanced clarity of the images. Furthermore, our system introduces a structured methodology for classifying BVO diseases, bridging a critical gap in this field. The primary aim of these advancements is to elevate the quality of OCTA images and bolster the reliability of their segmentation. Initial evaluations suggest that our method holds promise for establishing robust, fine-grained standards in OCTA vascular segmentation and analysis.

The Fanconi anemia pathway repairs colibactin-induced DNA interstrand cross-links.

Colibactin is a secondary metabolite produced by bacteria present in the human gut and is implicated in the progression of colorectal cancer and inflammatory bowel disease. This genotoxin alkylates deoxyadenosines on opposite strands of host cell DNA to produce DNA interstrand cross-links (ICLs) that block DNA replication. While cells have evolved multiple mechanisms to resolve ("unhook") ICLs encountered by the replication machinery, little is known about which of these pathways promote resistance to colibactin-induced ICLs. Here, we use Xenopus egg extracts to investigate replication-coupled repair of plasmids engineered to contain site-specific colibactin-ICLs. We show that replication fork stalling at a colibactin-ICL leads to replisome disassembly and activation of the Fanconi anemia ICL repair pathway, which unhooks the colibactin-ICL through nucleolytic incisions. These incisions generate a DNA double-strand break intermediate in one sister chromatid, which can be repaired by homologous recombination, and a monoadduct ("ICL remnant") in the other. Our data indicate that translesion synthesis past the colibactin-ICL remnant depends on Polη and a Polκ-REV1-Polζ polymerase complex. Although translesion synthesis past colibactin-induced DNA damage is frequently error-free, it can introduce T>N point mutations that partially recapitulate the mutation signature associated with colibactin exposure in vivo. Taken together, our work provides a biochemical framework for understanding how cells tolerate a naturally-occurring and clinically-relevant ICL.

Sequential treatment escalation improves survival in patients with Waldenstrom macroglobulinemia.

Waldenstrom macroglobulinemia (WM) is a type of incurable, indolent B-cell lymphoma that is prone to relapse. Over time, treatment strategies have progressed from cytotoxic drugs to rituximab (R)- or bortezomib (V)-based regimens, and have now entered into an era of Bruton tyrosine kinase inhibitor (BTKi)-based regimens. However, the optimal treatment for the relapsed patients is still unclear. Herein, we analyzed the outcomes of the first- and second-line therapies in 377 patients with WM to illustrate the optimal choices for second-line therapy. After a median follow-up of 45.4 months, 89 patients received second-line therapy, and 53 patients were evaluated for response. The major response rates (MRR) of first- and second-line treatment were 65.1% and 67.9% (P = 0.678). The median progression-free survival (PFS) for the second-line therapy (PFS2) was shorter than that for the first-line therapy (PFS1) (56.3 vs 40.7 months, P = 0.03). However, PFS2 in targeted drugs group (R-/V-/BTKi-based regimens) was comparable to PFS1 (60.7 months vs 44.7 months, respectively, P = 0.21). Regarding second-line therapy, patients who underwent sequential treatment escalation-such as transitioning from cytotoxic drugs to R-/V-/BTKi-based regimens or from R-/V-based to BTKi-based regimens (escalation group) -had higher MRR (80.6% vs 47.1%, respectively, P = 0.023) and longer PFS2 (50.4 vs 23.5 months, respectively, P < 0.001) compared to the non-escalation group. Patients in the escalation group also had longer post-relapse overall survival compared with the non-escalation group (median, 50.4 vs 23.5 months, respectively, P = 0.039). Our findings indicate that sequential treatment escalation may improve the survival of patients with WM.

Preparation and Comprehensive Evaluation of the Efficacy and Safety of Chlorantraniliprole Nanosuspension.

Chlorantraniliprole is a broad-spectrum insecticide that has been widely used to control pests in rice fields. Limited by its low solubility in both water and organic solvents, the development of highly efficient and environmentally friendly chlorantraniliprole formulations remains challenging. In this study, a low-cost and scalable wet media milling technique was successfully employed to prepare a chlorantraniliprole nanosuspension. The average particle size of the extremely stable nanosuspension was 56 nm. Compared to a commercial suspension concentrate (SC), the nanosuspension exhibited superior dispersibility, as well as superior foliar wetting and retention performances, which further enhanced its bioavailability against Cnaphalocrocis medinalis. The nanosuspension dosage could be reduced by about 40% while maintaining a comparable efficacy to that of the SC. In addition, the chlorantraniliprole nanosuspension showed lower residual properties, a lower toxicity to non-target zebrafish, and a smaller effect on rice quality, which is conducive to improving food safety and the ecological safety of pesticide formulations. In this work, a novel pesticide-reduction strategy is proposed, and theoretical and data-based support is provided for the efficient and safe application of nanopesticides.

Research Progress on the Pathogenesis of Aortic Aneurysm and Dissection in Metabolism.

Aortic aneurysm and dissection are complicated diseases having both high prevalence and mortality. It is usually diagnosed at advanced stages and posing diagnostic and therapeutic challenges due to the limitations of current detecting methods for aortic dissection used in clinics. Metabonomics demonstrated its great potential capability in the early diagnosis and personalized treatment of several diseases. Emerging evidence suggests that metabolic disorders including amino acid metabolism, glycometabolism, and lipid metabolism disturbance are involved in the pathogenesis of aortic aneurysm and dissection by affecting multiple functional aortic cells. The purpose of this review is to provide new insights into the metabolism alterations and their related regulatory mechanisms with a focus on recent advances and findings and provide a theoretical basis for the diagnosis, prevention, and drug development for aortic aneurysm and dissection.

Role of a holo-insertase complex in the biogenesis of biophysically diverse ER membrane proteins.

Mammalian membrane proteins perform essential physiologic functions that rely on their accurate insertion and folding at the endoplasmic reticulum (ER). Using forward and arrayed genetic screens, we systematically studied the biogenesis of a panel of membrane proteins, including several G-protein coupled receptors (GPCRs). We observed a central role for the insertase, the ER membrane protein complex (EMC), and developed a dual-guide approach to identify genetic modifiers of the EMC. We found that the back of sec61 (BOS) complex, a component of the 'multipass translocon', was a physical and genetic interactor of the EMC. Functional and structural analysis of the EMC•BOS holocomplex showed that characteristics of a GPCR's soluble domain determine its biogenesis pathway. In contrast to prevailing models, no single insertase handles all substrates. We instead propose a unifying model for coordination between the EMC, multipass translocon, and Sec61 for biogenesis of diverse membrane proteins in human cells.