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Sarcomas are rare malignancies with over 100 distinct histological subtypes. Their rarity and heterogeneity pose significant challenges to identifying effective therapies, and approved regimens show varied responses. Novel, personalized approaches to therapy are needed to improve patient outcomes. Patient-derived tumor organoids (PDTOs) model tumor behavior across an array of malignancies. We leverage PDTOs to characterize the landscape of drug resistance and sensitivity in sarcoma, collecting 194 specimens from 126 patients spanning 24 distinct sarcoma subtypes. Our high-throughput organoid screening pipeline tested single agents and combinations, with results available within a week from surgery. Drug sensitivity correlated with clinical features such as tumor subtype, treatment history, and disease trajectory. PDTO screening can facilitate optimal drug selection and mirror patient outcomes in sarcoma. We could identify at least one FDA-approved or NCCN-recommended effective regimen for 59% of the specimens, demonstrating the potential of our pipeline to provide actionable treatment information., Competing Interests: Declaration of interests A.S., J.Y., P.C.B., and N.C.F. are founders and owners of Icona BioDx. A.S. is a founder and owner of MiRiO., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Salvage radical prostatectomy is a postradiation treatment for patients with localized prostate cancer. In 2016, Ozu et al. (Ozu C, Aoki K, Nakamura K, Yagi Y, Muro Y, Nishiyama T, et al. The initial case report: salvage robotic assisted radical prostatectomy after heavy ion radiotherapy. Urol Case Rep 2016; 7 :45-7) first reported salvage robotic-assisted radical prostatectomy (sRARP) after heavy-ion radiotherapy (HIRT). Thereafter, sRARP has been performed in >100 cases. However, it is currently avoided owing to some difficulties. Herein, we report about sRARP in a 67-year-old man who received two sessions of HIRT despite some expected challenges. He was initially treated with HIRT for prostate cancer in 2009 and received the second HIRT as salvage treatment for local recurrence in 2016. In 2019, he had biochemical recurrence and underwent sRARP. There were no significant peri- or postoperative complications. Subsequently, 12 months after sRARP, hormonal therapy was introduced after the diagnosis of biochemical recurrence. The patient's prostate-specific antigen level is currently undetectable., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Background: Palliative care, including symptom alleviation and advance-care planning, is relevant for patients with heart failure (HF). The Supportive and Palliative Care Indicator Tool (SPICT) is a tool for identifying patients who may benefit from palliative-care assistance but has not been validated in patients hospitalized due to HF., Methods and Results: Clinical backgrounds, symptom burdens and outcomes were evaluated using the SPICT as assessed on admission in consecutive hospitalized patients with HF. SPICT-positive was defined when 2 or more general indicators and a New York Heart Association class ≥ III were present. Of 601 patients hospitalized due to HF (mean age: 79 ± 12 years; male, 314 [52%]; and mean left ventricular ejection fraction: 44 ± 18%), 100 (17%) patients were SPICT-positive. SPICT-positive patients were older (85 ± 9 vs 78 ± 12 years; P < 0.001) and had higher clinical frailty scales (6 ± 1 vs 4 ± 1 points; P < 0.001), whereas symptom burdens assessed by the Integrated Palliative care Outcome Scale were not different (17 [13, 28] vs 20 [11, 26] points; P = 0.97) when compared with patients who were SPICT-negative. During the median follow-up period of 518 days, 178 patients (30%) died. Being SPICT-positive was independently associated with higher all-cause mortality (hazard ratio: 3.49, 95% confidence interval: 2.41-5.05; P < 0.001) after adjusting for age, sex, New York Heart Association class IV, Get-With-The-Guideline risk score, N-terminal pro B-type natriuretic peptide levels, and left ventricular ejection fractions., Conclusions: In patients admitted for HF, being SPICT-positive was significantly associated with higher all-cause mortality rates, suggesting the utility of the SPICT as an indicator to initiate advance-care planning for end-of-life care among patients hospitalized due to HF., Competing Interests: Disclosures None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A 70-year-old woman with acute kidney injury, a high serum Creatinine (Cr) level (3.91 mg/dL), and proteinuria (protein/Cr ratio 1.59 g/gCr) was admitted. Serum IgG λ-type and urinary λ-type M proteins were observed. A bone marrow examination indicated monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy showed distended proximal tubular cells, and immunofluorescence identified tissue positive for proximal tubular cell λ light chains. Electron microscopy identified fibril-like structures in the lysosomes. The patient was diagnosed with light chain proximal tubulopathy without crystals in IgG λ-type MGUS and treated with bortezomib and dexamethasone therapy, which improved her renal function.

Purpose: Upfront dual checkpoint blockade with immune checkpoint inhibitors (ICI) has demonstrated efficacy for treating melanoma brain metastases (MBM) in asymptomatic patients. Whether the combination of stereotactic radiosurgery (SRS) with dual checkpoint blockade improves outcomes over dual-checkpoint blockade alone is unknown. We evaluated clinical outcomes of patients with MBM receiving ICI with nivolumab and ipilimumab, with and without SRS., Methods: 49 patients with 158 MBM receiving nivolumab and ipilimumab for untreated MBM between 2015 and 2022 were identified at our institution. Patient and tumor characteristics including age, Karnofsky Performance Status (KPS), presence of symptoms, cancer history, MBM burden, and therapy course were recorded. Outcomes measured from initiation of MBM-directed therapy included overall survival (OS), local control (LC), and distant intracranial control (DIC). Time-to-event analysis was conducted with the Kaplan-Meier method., Results: 25 patients with 74 MBM received ICI alone, and 24 patients with 84 MBM received concurrent SRS. Median follow-up was 24 months. No differences in age (p = 0.96), KPS (p = 0.85), presence of symptoms (p = 0.79), prior MBM (p = 0.68), prior MBM-directed surgery (p = 0.96) or SRS (p = 0.68), MBM size (p = 0.67), or MBM number (p = 0.94) were seen. There was a higher rate of nivolumab and ipilimumab course completion in the SRS group (54% vs. 24%; p = 0.029). The SRS group received prior immunotherapy more often than the ICI alone group (54% vs. 8.0%; p < 0.001). There was no significant difference in 1-year OS (72% vs. 71%, p = 0.20) and DIC (63% v 51%, p = 0.26) between groups. The SRS group had higher 1-year LC (92% vs. 64%; p = 0.002). On multivariate analysis, LC was improved with combination therapy (AHR 0.38, p = 0.01)., Conclusion: In our analysis, patients who received SRS with nivolumab and ipilimumab had superior LC without increased risk of toxicity or compromised immunotherapy treatment completion despite the SRS cohort having higher rates of prior immunotherapy. Further prospective study of combination nivolumab and ipilimumab with SRS is warranted., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Culturally appropriate communication training programs for a wide range of professions that can be used during infection epidemics are crucial for advance care planning implementation. Starting in 2018, the Japanese Ministry of Health, Labour and Welfare made a major policy change, and doctors, nurses, and social workers, and care managers were identified in the guidelines as the professions that promote advance care planning. Motivated by the lack of online programs for Japanese care managers, we proposed a new one-day program., Objectives: This study aimed to determine the changes in the positive attitude of care managers toward dying patients compared to that of nurses, which has been used in past literature as an outcome of advance care planning educational interventions, after administering the program in Japan., Design: Before-after comparison study., Methods: Care managers were recruited through our website, ACP-Piece, http://plaza.umin.ac.jp/~acp-piece/piece.html. A questionnaire survey concerning positive attitudes toward dying patients was administered before and after the program on 28 August 2021. Sixty-six subjects participated in the training and 60 participants, including 14 care managers, consented to the study and completed the questionnaire surveys before and after the program., Results: The Frommelt attitude toward care of the dying scores for care managers increased after the program ( p -values, confidence intervals, and effect sizes: p  < 0.001, -11.90 to -4.388, -1.252). After training, care managers had a significantly higher maximum score occurrence than nurses. Older care managers with advance care planning experience may have had a higher maximum score occurrence compared to younger, inexperienced participants., Conclusion: To our knowledge, this is the first to demonstrate the increased positive attitude scores toward dying patients after online communication training for Japanese care managers. The limitations of this study include the lack of evidence regarding reasons for score changes, long-term score changes, and effectiveness for patients and their families., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

A large and diverse library of glycan-directed monoclonal antibodies (mAbs) was used to determine if plant cell walls are modified by low-gravity conditions encountered during spaceflight. This method called glycome profiling (glycomics) revealed global differences in non-cellulosic cell wall epitopes in Arabidopsis thaliana root extracts recovered from RNA purification columns between seedlings grown on the International Space Station-based Vegetable Production System and paired ground (1-g) controls. Immunohistochemistry on 11-day-old seedling primary root sections showed that ten of twenty-two mAbs that exhibited spaceflight-induced increases in binding through glycomics, labeled space-grown roots more intensely than those from the ground. The ten mAbs recognized xyloglucan, xylan, and arabinogalactan epitopes. Notably, three xylem-enriched unsubstituted xylan backbone epitopes were more intensely labeled in space-grown roots than in ground-grown roots, suggesting that the spaceflight environment accelerated root secondary cell wall formation. This study highlights the feasibility of glycomics for high-throughput evaluation of cell wall glycans using only root high alkaline extracts from RNA purification columns, and subsequent validation of these results by immunohistochemistry. This approach will benefit plant space biological studies because it extends the analyses possible from the limited amounts of samples returned from spaceflight and help uncover microgravity-induced tissue-specific changes in plant cell walls., (© 2023. Springer Nature Limited.)

Background: Genomic profiling cannot solely predict the complexity of how tumor cells behave in their in vivo microenvironment and their susceptibility to therapies. The aim of the study was to establish a functional drug prediction model utilizing patient-derived GBM tumor samples for in vitro testing of drug efficacy followed by in vivo validation to overcome the disadvantages of a strict pharmacogenomics approach., Methods: High-throughput in vitro pharmacologic testing of patient-derived GBM tumors cultured as 3D organoids offered a cost-effective, clinically and phenotypically relevant model, inclusive of tumor plasticity and stroma. RNAseq analysis supplemented this 128-compound screening to predict more efficacious and patient-specific drug combinations with additional tumor stemness evaluated using flow cytometry. In vivo PDX mouse models rapidly validated (50 days) and determined mutational influence alongside of drug efficacy. We present a representative GBM case of three tumors resected at initial presentation, at first recurrence without any treatment, and at a second recurrence following radiation and chemotherapy, all from the same patient., Results: Molecular and in vitro screening helped identify effective drug targets against several pathways as well as synergistic drug combinations of cobimetinib and vemurafenib for this patient, supported in part by in vivo tumor growth assessment. Each tumor iteration showed significantly varying stemness and drug resistance., Conclusions: Our integrative model utilizing molecular, in vitro, and in vivo approaches provides direct evidence of a patient's tumor response drifting with treatment and time, as demonstrated by dynamic changes in their tumor profile, which may affect how one would address that drift pharmacologically.

There has been insufficient research on gender, race, and ethnic differences in unmet needs of homeless populations. This study analyzed 5 years of data collected by Project Community Homelessness Assessment, Local Education, and Networking Groups (CHALENG) surveys from 2012 to 2016 to examine gender, race, and ethnic differences in "literally homeless" veterans (i.e., veterans living in the streets, shelters, vehicles, or any other place not meant for habitation). Of 7,040 participants, there were 6,335 male and 705 female literally homeless veterans from 4 self-identified racial/ethnic categories (White, Black, Hispanic, and Other). The results showed that homeless female veterans were significantly more likely to report unmet needs related to emergency shelter, transitional housing, and dental care than male veterans. Among men, White veterans reported greater unmet needs in housing, healthcare, basic needs, and specialized needs than racial/ethnic minority veterans. Among women, veterans who were racial/ethnic minorities reported greater unmet needs than their White counterparts. These findings suggest programmatic attention to gender, race, and ethnicity is important in addressing diverse needs of homeless veterans and specialized services may be needed to address their specific and consistent unmet needs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Fusion-positive rhabdomyosarcoma (FP-RMS) is driven by a translocation that creates the chimeric transcription factor PAX3-FOXO1 (P3F), which assembles de novo super enhancers to drive high levels of transcription of other core regulatory transcription factors (CRTFs). P3F recruits co-regulatory factors to super enhancers such as BRD4, which recognizes acetylated lysines via BET bromodomains. In this study, we demonstrate that inhibition or degradation of BRD4 leads to global decreases in transcription, and selective downregulation of CRTFs. We also show that the BRD4 degrader ARV-771 halts transcription while preserving RNA Polymerase II (Pol2) loops between super enhancers and their target genes, and causes the removal of Pol2 only past the transcriptional end site of CRTF genes, suggesting a novel effect of BRD4 on Pol2 looping. We finally test the most potent molecule, inhibitor BMS-986158, in an orthotopic PDX mouse model of FP-RMS with additional high-risk mutations, and find that it is well tolerated in vivo and leads to an average decrease in tumor size. This effort represents a partnership with an FP-RMS patient and family advocates to make preclinical data rapidly accessible to the family, and to generate data to inform future patients who develop this disease.

Background: For prostate cancer, accurate prediction of the pathological stage before surgery is very important. Therefore, the aim of the present study was establishing the prostate-specific antigen (PSA) threshold nomogram to predict pathologically advanced prostate cancer using the novel method of area under the receiver operating characteristic curve boosting (AUCBoost)., Methods: The medical records of patients with clinically localized prostate cancer who underwent robot-assisted radical prostatectomy were retrospectively reviewed. Multivariate logistic regression analysis was performed to identify clinical covariates significantly associated with pathological tumor stage ≥3a. The best combination of the variables was determined by validated values of the area under the curve (AUC). The optimal individualized PSA threshold values were developed using AUCBoost., Results: In the multivariate logistic regression analysis, PSA, prostate volume, clinical tumor stage, Gleason Grade Group, the number of positive cores, and the percentage of positive cores were independent predictive factors for pathological tumor stage ≥3a. A combination model comprising PSA, prostate volume, clinical tumor stage, percent positive core, and Gleason Grade Group produced the highest AUC for predicting pathological tumor stage ≥3a (AUC = 0.777). The PSA threshold values for detecting pathological tumor stage ≥3a were calculated and a table of individualized PSA threshold nomogram was developed using AUCBoost., Conclusions: We developed a nomogram of the PSA threshold values for predicting adverse pathological tumor stages of prostate cancer using a novel statistical method. Further validation is necessary; however, the individualized PSA threshold nomogram may be useful in determining treatment strategies before surgery., Competing Interests: Conflicts of interest and Financial disclosures The authors have no conflicts of interest directly relevant to the content of this article. The corresponding author (T.H.) was supported by JSPS KAKENHI Grant Number 18K09209. The second author (O.K.) was supported by JSPS KAKENHI Grant Number 18K11190., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The histological diagnosis of type 1 autoimmune pancreatitis (AIP) based on the findings obtained by an endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is feasible, but the diagnostic consistency of this method has not been confirmed. We determined the interobserver agreement among 20 pathologists regarding the diagnosis of type 1 AIP, including the distinction from pancreatic ductal adenocarcinoma (PDAC) using large tissue samples obtained by EUS-FNB. After guidance for diagnosing AIP with biopsy tissues was provided, a round 2 was performed. The median sensitivity and specificity for diagnosing PDAC vs. non-neoplastic diseases were 95.2% and 100%, respectively. In groups of specialists (n = 7) and the generalists (n = 13), Fleiss' к-values increased from 0.886 to 0.958 and from 0.750 to 0.816 in round 2. The concordance was fair or moderate for obliterative phlebitis and storiform fibrosis but slight for ductal lesion of type 1 AIP. Discordant results were due to ambiguous findings and biopsy tissue limitations. Among the specialists, the ratio of cases with perfect agreement regarding the presence of storiform fibrosis increased in round 2, but agreement regarding obliterative phlebitis or ductal lesions was not improved. Although the histological definite diagnosis of type 1 AIP was achieved by most observers in > 60% of the cases, the confidence levels varied. Because some ambiguities exist, the histological diagnostic levels based on the diagnostic criteria of type 1 AIP should not be taken for granted. Guidance is effective for improving accurate PDAC diagnoses (notably by recognizing acinar-ductal metaplasia) and for evaluating storiform fibrosis., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Microscopy is an important tool used for biological research and has played a crucial role toward understanding of cellular mechanisms and protein function. However, specific steps in processing of biological samples for microscopy warrant improvements to consistently generate data that can more reliably help in explaining mechanisms underlying complex biological phenomenon. Due to their small and fragile nature, some biological specimens such as Arabidopsis thaliana roots are vulnerable to damage during long sample preparation steps. Moreover, when specimens with a small diameter (typically less than 100 μm) are embedded in conventional silicone mold or capsule embedding, it is not only difficult to locate their orientation inside the capsule, but also a challenge to obtain good median longitudinal sections. Specimen orientation in particular is crucial because understanding certain plant biological processes such as gravitropism rely on precisely knowing spatial information of cells and tissues of the plant organ being studied. Here, we present a simple embedding technique to properly orient small plant organs such as roots so that the desired sectioning plane is achieved. This method is inexpensive and can be accomplished with minimal equipment and supplies., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: During computed tomography (CT) examinations, it may be necessary to assist the patient to maintain an appropriate body position. However, there is little protective equipment available for caregivers who approach the gantry. This study aimed to evaluate the effectiveness of novel radiation protective curtains in reducing radiation exposure to caregivers while assisting patients, especially during CT examinations of the head., Method: The absorbed dose in air around the gantry during CT examinations of the head was measured using glass dosimeters. The measurement points from the center of the gantry were 40 to 120 cm in the front, 0 to 100 cm for each side in the right and left, and 60 to 180 cm from the floor. Measurements were performed at each 20-cm interval, and all points were accumulated 10 times. The absorbed dose in air in a CT room was compared with and without the protective curtains. Next, we assumed the height of the caregiver to be 170 cm, and measured the points for the crystalline lens, chest, and abdomen. Also, using the protective glasses and the protective apron, we measured the absorbed dose in air for the caregivers behind the protective curtains., Result: The absorbed exposure dose in air toward the crystalline lenses, chest, and abdomen was reduced more than 90% by using the protective curtains and more than 95% by using the protective apron and protective glasses in addition to them., Conclusion: This study showed the usefulness of protective curtains in reducing the absorbed exposure dose in air to caregivers.

Objective The standard treatment for chronic myeloid leukemia (CML) is the continuous use of tyrosine kinase inhibitors (TKIs), which results in a favorable prognosis for the majority of patients. Recent studies have identified cardiovascular diseases (CVDs) as late adverse events (AEs) related to TKIs. In this study, we evaluated the long-term efficacy and AEs of TKIs, focusing on CVDs. Methods We performed a retrospective survey of CML patients (diagnosed from 2001 to 2016) treated with TKIs in Nagasaki Prefecture. Clinical data were obtained from their medical records. We analyzed the survival, estimated cumulative incidence of CVDs, and risk factors for CVD among CML patients treated with TKIs. Results The overall survival rate of 264 CML patients treated with TKIs (median age 58 years old) was 89.6% [95% confidence interval (CI), 84.9-92.9%], and 80.5% (95% CI, 73.4-85.9%) at 5 and 10 years after the CML diagnosis, respectively. CVD events occurred in 26 patients (9.8%, median age 67.5 years old) with a median 65.5 months of TKI treatment. The cumulative incidences at 2 and 5 years was 2.4% (95% CI, 1.0-4.8%) and 5.2% (95% CI, 2.8-8.6%), respectively. Hypertension and a high SCORE chart risk at the diagnosis of CML were associated with CVD events during TKI treatment. Conclusion TKI treatment contributed to the long-term survival of CML patients in Nagasaki Prefecture in a "real-world" setting, but the incidence of CVDs seemed to be increased in these patients. A proper approach to managing risk factors for CVD is warranted to reduce CVD events during TKI treatment.

Background: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) is a life-threatening progressive disease. Recent studies have shown that the detection of transthyretin (TTR) amyloid in tenosynovial tissue may play an important role in the diagnosis of cardiac amyloidosis. The aim of this study was to determine the prevalence of TTR amyloid deposits in surgical tissue of patients undergoing carpal tunnel surgery and to clarify the clinical significance of concomitant cardiac examination with 99 m Tc-labeled pyrophosphate ( 99 m Tc-PYP) scintigraphy in those patients with TTR deposition. Methods and Results: We evaluated 79 consecutive patients undergoing carpal tunnel release surgery and biopsy of tenosynovial tissue. The mean (±SD) age of the patients at surgery was 71.6±12.5 years (range 30-95 years); 32 patients (41%) were male. TTR amyloid deposition in tenosynovial tissue was observed in 27 patients (34%). Sixteen of those 27 patients underwent 99 m Tc-PYP scintigraphy. Of those 16 patients, 3 (19%) had Grade 2 uptake on 99 m Tc-PYP scintigraphy. None of the 3 patients with a diagnosis of ATTRwt-CA had apparent cardiac symptoms and left ventricular wall thickness >13 mm. Conclusions: Concomitant cardiac examination with 99 m Tc-PYP scintigraphy in patients who had TTR amyloid deposition in tenosynovial tissue resulted in the identification of 19% of patients with a diagnosis of ATTRwt-CA. This diagnostic approach seems to be useful for the early diagnosis of the disease., Competing Interests: T.K. and H. Kitaoka have received remuneration from Pfizer. H. Kitaoka is a member of Circulation Reports’ Editorial Team. The remaining authors have no conflicts of interest to declare., (Copyright © 2021, THE JAPANESE CIRCULATION SOCIETY.)

Objective Classic Hodgkin lymphoma (CHL) has been regarded as a curable disease when treated appropriately, especially in younger patients, and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) has been regarded as the standard regimen. However, a relatively poor prognosis has been reported in older patients with CHL, and the efficacy and tolerability of the ABVD regimen has not been fully elucidated. We retrospectively investigated the outcomes in patients with CHL treated with ABVD at our institute. Methods Twenty-five patients were evaluated; 14 were ≤60 years of age, and 11 were >60 years of age (older group). Results The ABVD doses were reduced in all patients in the older group; the median average relative dose intensity was 0.58. In the older group, the 5-year overall survival (OS) and median OS were 100% and not reached, respectively, for patients with early-stage CHL and 66.7% and not reached, respectively, for those with advanced-stage CHL. No patients died of CHL, and only one treatment-related death was observed in the older group. Conclusion ABVD with dose attenuation may represent a feasible and effective strategy for the treatment of older patients with CHL in clinical practice, particularly in those with early-stage disease, although the optimal degree of attenuation remains unclear.

Many plant-encoded E3 ligases are known to be involved in plant defense. Here, we report a novel role of E3 ligase SALT- AND DROUGHT-INDUCED RING FINGER1 (SDIR1) in plant immunity. Even though SDIR1 is reasonably well-characterized, its role in biotic stress response is not known. The silencing of SDIR1 in Nicotiana benthamiana reduced the multiplication of the virulent bacterial pathogen Pseudomonas syringae pv. tabaci . The Arabidopsis sdir1 mutant is resistant to virulent pathogens, whereas SDIR1 overexpression lines are susceptible to both host and nonhost hemibiotrophic bacterial pathogens. However, sdir1 mutant and SDIR1 overexpression lines showed hypersusceptibility and resistance, respectively, against the necrotrophic pathogen Erwinia carotovora . The mutant of SDIR1 target protein, i.e., SDIR-interacting protein 1 (SDIR1P1), also showed resistance to host and nonhost pathogens. In SDIR1 overexpression plants, transcripts of NAC transcription factors were less accumulated and the levels of jasmonic acid (JA) and abscisic acid were increased. In the sdir1 mutant, JA signaling genes JAZ7 and JAZ8 were downregulated. These data suggest that SDIR1 is a susceptibility factor and its activation or overexpression enhances disease caused by P. syringae pv. tomato DC3000 in Arabidopsis . Our results show a novel role of SDIR1 in modulating plant defense gene expression and plant immunity.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Alfalfa (Medicago sativa L.) is one of the most important forage crops throughout the world. Maximizing leaf retention during the haymaking process is critical for achieving superior hay quality and maintaining biomass yield. Leaf abscission process affects leaf retention. Previous studies have largely focused on the molecular mechanisms of floral organ, pedicel and seed abscission but scarcely touched on leaf and petiole abscission. This study focuses on leaf and petiole abscission in the model legume Medicago truncatula and its closely related commercial species alfalfa. By analysing the petiolule-like pulvinus (plp) mutant in M. truncatula at phenotypic level (breakstrength and shaking assays), microscopic level (scanning electron microscopy and cross-sectional analyses) and molecular level (expression level and expression pattern analyses), we discovered that the loss of function of PLP leads to an absence of abscission zone (AZ) formation and PLP plays an important role in leaflet and petiole AZ differentiation. Microarray analysis indicated that PLP affects abscission process through modulating genes involved in hormonal homeostasis, cell wall remodelling and degradation. Detailed analyses led us to propose a functional model of PLP in regulating leaflet and petiole abscission. Furthermore, we cloned the PLP gene (MsPLP) from alfalfa and produced RNAi transgenic alfalfa plants to down-regulate the endogenous MsPLP. Down-regulation of MsPLP results in altered pulvinus structure with increased leaflet breakstrength, thus offering a new approach to decrease leaf loss during alfalfa haymaking process., (© 2020 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)