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Detailed γ-ray spectroscopy of the exotic neon isotope 28Ne has been performed for the first time using the one-neutron removal reaction from 29Ne on a liquid hydrogen target at 240 MeV/nucleon. Based on an analysis of parallel momentum distributions, a level scheme with spin-parity assignments has been constructed for 28Ne and the negative-parity states are identified for the first time. The measured partial cross sections and momentum distributions reveal a significant intruder p-wave strength providing evidence of the breakdown of the N=20 and N=28 shell gaps. Only a weak, possible f-wave strength was observed to bound final states. Large-scale shell-model calculations with different effective interactions do not reproduce the large p-wave and small f-wave strength observed experimentally, indicating an ongoing challenge for a complete theoretical description of the transition into the island of inversion along the Ne isotopic chain.

The nucleus Ne29 is situated at the border of the island of inversion. Despite significant efforts, no bound low-lying intruder f7/2 state, which would place Ne29 firmly inside the island of inversion, has yet been observed. Here, the first investigation of unbound states of Ne29 is reported. The states were populated in Ne30(p,pn) and Na30(p,2p) reactions at a beam energy of around 230 MeV/nucleon, and analyzed in terms of their resonance properties, partial cross sections, and momentum distributions. The momentum distributions are compared to calculations using the eikonal, direct reaction model, allowing ℓ assignments for the observed states. The lowest-lying resonance at an excitation energy of 1.48(4) MeV shows clear signs of a significant ℓ=3 component, giving first evidence for f7/2 single particle strength in Ne29. The excitation energies and strengths of the observed states are compared to shell-model calculations using the sdpf-u-mix interaction.

Hyocheong Chae,1,2,&ast; Hongmin Chu,1,3,&ast; Junghun Lee,1 Hagdong Kim,1 Dongha Kim,1 Sebong Park,1 Kwanghwan Lim,1 Minsu Jeong,1 Kyungho Kang,1 Gyeongchan Kim,1 Joo Hyun Lee,1 Sehun Jung,1 Jaehyo Kim,4 Yongjoo Kim,5 Myungseok Ryu1,6 On behalf of Korean Medical Society of Acupotomology KM Doctors Group1Departmental Research Committee, Korean Medical Society of Acupotomology, Seoul, Republic of Korea; 2Sunyujae Korean Medicine Clinic, Yongin, Republic of Korea; 3Department of Korean Internal Medicine, College of Korean Medicine, Wonkwang University, Iksan, Republic of Korea; 4Department of Meridian & Acupoint, College of Korean Medicine, Wonkwang University, Iksan, Republic of Korea; 5College of Korean Medicine, Sangji University, Wonju, Republic of Korea; 6Clinic Department, Daemyeong Korean Medicine Clinic, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Myungseok Ryu, Clinic Department of Daemyung Korean Medicine Clinic, Wonwoo b/d 3rd fl, Yangpyeong-ro, Yeongdeungpo-gu, Seoul, 07208, Republic of Korea, Tel +82-2-2671-7191, Fax +82-2-2676-1297, Email yeonbu16@gmail.comObjective: Shoulder pain is a common complaint in outpatient clinics and can result in an inability to work or perform household activities, leading to significant socioeconomic burden. Acupotomy, as one kind acupuncture that has flat knife-shaped tip, has been widely used for treating shoulder pain. However, despite the widespread use of acupotomy in primary medical institutions, large sample size clinical trials have not sufficiently been performed. In this respect, this multi-center retrospective study aimed to investigate the effectiveness and safety of acupotomy in reducing shoulder pain and disability using data from multi-center primary care clinics.Methods: This study was conducted in 25 Korean medicine clinics affiliated with the Korean Medical Society of Acupotomology, Republic of Korea, from August 2021 to December 2021. The medical records of patients who visited the clinics complaining of shoulder pain were gathered, and among them were those of patients who underwent acupotomy treatment and those who received acupuncture combined therapy. The Numeric Rating Scale (NRS), SPADI (Shoulder Pain and Disability Index), Range of Motion (ROM) and adverse event were evaluated at each visit. A linear mixed-effects models and paired t-test were used to identify the effectiveness of the treatment.Results: Overall analysis showed that the NRS score of patients decreased from 4.95 ± 1.97 before treatment to 3.78 ± 2.03 after treatment (n = 332, difference in NRS score, 1.17; 95% CI: 0.96– 1.38, t = 10.89 p < 0.001). SPADI score decreased from 19.05 ± 20.44 at baseline before treatment to 12.12 ± 17.26 after the last visit, which was statistically significant (n = 332, mean difference in SPADI score, 6.93; 95% CI: 4.71– 9.15, t = 6.150, p < 0.001). No serious adverse event was reported in both groups.Conclusion: This study showed the effectiveness of acupotomy therapy for shoulder pain, and as the treatment sessions increased, the effect of pain reduction and shoulder function improvement were also increased.Keywords: acupotomy, shoulder pain, retrospective study, multicenter study

Dong-Hoe Koo,1,&ast; Keun Seok Lee,2,&ast; Sung Hoon Sim,2 Heejung Chae,2 Eun-Gyeong Lee,2 Jai Hong Han,2 So-Youn Jung,2 Seeyoun Lee,2 Han-Sung Kang,2 Eun Sook Lee,2 Cheol-Young Park,1,&ast; Sang Woo Oh3,&ast; 1Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 2Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea; 3Department of Family Medicine, Center for Obesity, Metabolism, and Nutrition, Dongguk University Ilsan Hospital, Goyang-si, Gyeonggi-do, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Cheol-Young Park, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul, 03181, Republic of Korea, Tel +82-2-2001-1869, Fax +82-2-2001-1588, Email cydoctor@chol.com Sang Woo Oh, Center for Obesity, Nutrition, and Metabolism, Department of Family Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, 27 Donggung-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea, Tel +82-31-961-7000, Email osw6021@gmail.comBackground: We have reported that serum progranulin (PGRN) levels are clinically significant in predicting recurrence in patients with HR-positive breast cancer. The aim of the present study was to examine whether PGRN levels might be associated with breast cancer mortality.Methods: This was a cohort study of 695 newly diagnosed breast cancer patients who underwent curative surgery between 2001 and 2004. The relationship between breast cancer mortality and pre-operative serum PGRN levels in these patients with a median follow-up of 12.7 years was evaluated until May 2020.Results: A total of 118 (17%) deaths were identified in the cohort. According to the HR status, (10, 15, and 20)-year overall survival (OS) rates were (91.4, 81.1, and 75.9) % for HR-positive patients, and (76.5, 74.2, and 69.8) % for HR-negative patients, respectively (p = 0.003). Higher levels of PGRN were significantly associated with poor OS in the HR-positive group (p for trend = 0.001). In particular, hazard ratios for PGRN quartiles suggested a dose–response relationship, with the highest quartile having the worst OS in the HR-positive group (highest vs lowest: 15-year OS, (68.3 vs 90.0) %; 20-year OS, (62.3 vs 84.8) %, even after adjusting for age, tumor stage, and metabolic confounders.Conclusion: Pre-operative serum PGRN levels had clinical significance for predicting cancer mortality in breast cancer patients independent of tumor stage and metabolic parameters, especially in HR-positive tumors.Keywords: breast cancer, progranulin, mortality, long-term follow-up

Detailed spectroscopy of the neutron-unbound nucleus ^{28}F has been performed for the first time following proton/neutron removal from ^{29}Ne/^{29}F beams at energies around 230  MeV/nucleon. The invariant-mass spectra were reconstructed for both the ^{27}F^{(*)}+n and ^{26}F^{(*)}+2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the ^{28}F ground state, with S_{n}(^{28}F)=-199(6)  keV, while analysis of the 2n decay channel allowed a considerably improved S_{n}(^{27}F)=1620(60)  keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of ^{28}F. Importantly, in the case of the ground state, the reconstructed ^{27}F+n momentum distribution following neutron removal from ^{29}F indicates that it arises mainly from the 1p_{3/2} neutron intruder configuration. This demonstrates that the island of inversion around N=20 includes ^{28}F, and most probably ^{29}F, and suggests that ^{28}O is not doubly magic.

Detailed spectroscopy of the neutron-unbound nucleus ^{28}F has been performed for the first time following proton/neutron removal from ^{29}Ne/^{29}F beams at energies around 230  MeV/nucleon. The invariant-mass spectra were reconstructed for both the ^{27}F^{(*)}+n and ^{26}F^{(*)}+2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the ^{28}F ground state, with S_{n}(^{28}F)=-199(6)  keV, while analysis of the 2n decay channel allowed a considerably improved S_{n}(^{27}F)=1620(60)  keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of ^{28}F. Importantly, in the case of the ground state, the reconstructed ^{27}F+n momentum distribution following neutron removal from ^{29}F indicates that it arises mainly from the 1p_{3/2} neutron intruder configuration. This demonstrates that the island of inversion around N=20 includes ^{28}F, and most probably ^{29}F, and suggests that ^{28}O is not doubly magic.

The transcription factor CREB (cAMP Response-Element Binding Protein) is overexpressed in the majority of acute myeloid leukemia (AML) patients, and this is associated with a worse prognosis. Previous work revealed that CREB overexpression augmented AML cell growth, while CREB knockdown disrupted key AML cell functions in vitro. In contrast, CREB knockdown had no effect on long-term hematopoietic stem cell activity in mouse transduction/transplantation assays. Together, these studies position CREB as a promising drug target for AML. To test this concept, a small molecule inhibitor of CREB, XX-650-23, was developed. This molecule blocks a critical interaction between CREB and its required co-activator CBP (CREB Binding Protein), leading to disruption of CREB-driven gene expression. Inhibition of CBP-CREB interaction induced apoptosis and cell-cycle arrest in AML cells, and prolonged survival in vivo in mice injected with human AML cells. XX-650-23 had little toxicity on normal human hematopoietic cells and tissues in mice. To understand the mechanism of XX-650-23, we performed RNA-seq, ChIP-seq and Cytometry Time of Flight with human AML cells. Our results demonstrate that small molecule inhibition of CBP-CREB interaction mostly affects apoptotic, cell-cycle and survival pathways, which may represent a novel approach for AML therapy.

Histone deacetylase 9 (HDAC9) is expressed in B cells, and its overexpression has been observed in B-lymphoproliferative disorders, including B-cell non-Hodgkin lymphoma (B-NHL). We examined HDAC9 protein expression and copy number alterations in primary B-NHL samples, identifying high HDAC9 expression among various lymphoma entities and HDAC9 copy number gains in 50% of diffuse large B-cell lymphoma (DLBCL). To study the role of HDAC9 in lymphomagenesis, we generated a genetically engineered mouse (GEM) model that constitutively expressed an HDAC9 transgene throughout B-cell development under the control of the immunoglobulin heavy chain (IgH) enhancer (Eμ). Here, we report that the Eμ-HDAC9 GEM model develops splenic marginal zone lymphoma and lymphoproliferative disease (LPD) with progression towards aggressive DLBCL, with gene expression profiling supporting a germinal center cell origin, as is also seen in human B-NHL tumors. Analysis of Eμ-HDAC9 tumors suggested that HDAC9 might contribute to lymphomagenesis by altering pathways involved in growth and survival, as well as modulating BCL6 activity and p53 tumor suppressor function. Epigenetic modifications play an important role in the germinal center response, and deregulation of the B-cell epigenome as a consequence of mutations and other genomic aberrations are being increasingly recognized as important steps in the pathogenesis of a variety of B-cell lymphomas. A thorough mechanistic understanding of these alterations will inform the use of targeted therapies for these malignancies. These findings strongly suggest a role for HDAC9 in B-NHL and establish a novel GEM model for the study of lymphomagenesis and, potentially, preclinical testing of therapeutic approaches based on histone deacetylase inhibitors.

Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Z ratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10−21 s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z = 8 and N = 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called ‘doubly magic’ nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N = 20 shell structure.Observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively, is reported, with the 28O nucleus being of particular interest owing to proton and neutron magic numbers and its extremely asymmetric neutron-to-proton ratio. [ABSTRACT FROM AUTHOR]