Benefit of axicabtagene ciloleucel versus chemoimmunotherapy in older patients and/or patients with poor ECOG performance status with relapsed or refractory large B-cell lymphoma after 2 or more lines of prior therapy.

Axicabtagene ciloleucel (axi-cel) in trials has demonstrated favorable efficacy compared with historical controls after ≥2 lines of therapy for the treatment of relapsed or refractory (R/R) large B cell lymphoma (LBCL). Herein, we compared the real-world effectiveness of axi-cel with efficacy and effectiveness of chemoimmunotherapy (CIT) in patients aged ≥65 years and patients with Eastern Cooperative Oncology Group performance status (ECOG PS) of 2. A total of 1146 patients treated with commercial axi-cel for R/R LBCL with ≥2 lines of prior therapy were included from the Center for International Blood and Marrow Transplantation Research prospective observational study, and 469 patients treated with CIT for R/R LBCL after ≥2 lines of prior therapy were included from SCHOLAR-1 (an international, multicohort, retrospective study). After propensity score matching, at a median follow-up of 24 months for patients receiving axi-cel and 60 months for patients receiving CIT, 12-month overall survival rates were 62% and 28%, respectively (hazard ratio, 0.30 [95% CI, 0.24-0.37]). Objective response rate (ORR) was 76% (complete response [CR] rate 58%) in patients receiving axi-cel versus 28% (CR rate 16%) for those receiving CIT. A 57% difference in ORR (55% difference in CR rate) favoring axi-cel over CIT was observed among patients aged ≥65 years. Increased magnitude of benefit in response rates for axi-cel versus CIT was also observed among patients with ECOG PS = 2. These findings further support the broader use of axi-cel in older patients and patients with ECOG PS = 2 with R/R LBCL.

Computer-Vision Based Gesture-Metasurface Interaction System for Beam Manipulation and Wireless Communication.

Hand gesture plays an important role in many circumstances, which is one of the most common interactive methods in daily life, especially for disabled people. Human-machine interaction is another popular research topic to realize direct and efficient control, making machines intelligent and maneuverable. Here, a special human-machine interaction system is proposed and namedas computer-vision (CV) based gesture-metasurface interaction (GMI) system, which can be used for both direct beam manipulations and real-time wireless communications. The GMI system first needs to select its working mode according to the gesture command to determine whether to perform beam manipulations or wireless communications, and then validate the permission for further operation by recognizing unlocking gesture to ensure security. Both beam manipulation and wireless communication functions are validated experimentally, which show that the GMI system can not only realize real-time switching and remote control of different beams through gesture command, but also communicate with a remote computer in real time by translating the gesture language to text message. The proposed non-contact GMI system has the advantages of good interactivity, high flexibility, and multiple functions, which can find potential applications in community security, gesture-command smart home, barrier-free communications, and so on.

N6-methyl-2'-deoxyadenosine promotes self-renewal of BFU-E progenitor in erythropoiesis.

Red blood cells supply the oxygen required for all human cells and are in demand for emerging blood-loss therapy. Here we identified N6-methyl-2'-deoxyadenosine (6mdA) as an agonist that promotes the hyperproliferation of burst-forming unit erythroid (BFU-E) progenitor cells. In addition, 6mdA represses the apoptosis of erythroid progenitor cells (EPCs). Combined use of with SCF and EPO enabled cultures of isolated BFU-E to be expanded up to 5,000-fold. Transcriptome analysis showed that 6mdA upregulates the expression of the EPC-associated factors c-Kit, Myb, and Gata2 and downregulates that of the erythroid maturation-related transcription factors Gata1, Spi1, and Klf1. Mechanistic studies suggested that 6mdA enhances and prolongs the activation of erythropoiesis-associated master gene c-Kit and its downstream signaling, leading to expansion and accumulation of EPCs. Collectively, we demonstrate that 6mdA can efficiently stimulate the EPC hyperproliferation and provide a new regenerative medicine recipe to improve ex vivo generation of red blood cells.

m6 A promotes planarian regeneration.

Regeneration is the regrowth of damaged tissues or organs, a vital process in response to damages from primitive organisms to higher mammals. Planarian possesses active whole-body regenerative capability owing to its vast reservoir of adult stem cells, neoblasts, providing an ideal model to delineate the underlying mechanisms for regeneration. RNA N6 -methyladenosine (m6 A) modification participates in many biological processes, including stem cell self-renewal and differentiation, in particular the regeneration of haematopoietic stem cells and axons. However, how m6 A controls regeneration at the whole-organism level remains largely unknown. Here, we demonstrate that the depletion of m6 A methyltransferase regulatory subunit wtap abolishes planarian regeneration, potentially through regulating genes related to cell-cell communication and cell cycle. Single-cell RNA-seq (scRNA-seq) analysis unveils that the wtap knockdown induces a unique type of neural progenitor-like cells (NP-like cells), characterized by specific expression of the cell-cell communication ligand grn. Intriguingly, the depletion of m6 A-modified transcripts grn, cdk9 or cdk7 partially rescues the defective regeneration of planarian caused by wtap knockdown. Overall, our study reveals an indispensable role of m6 A modification in regulating whole-organism regeneration.

[Factors Influencing and Adverse Reactions of Voriconazole Clearance in Patients with Hematological Diseases].

OBJECTIVE: To monitor the changes of voriconazole minimum concentration(Cmin) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole. METHODS: 136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole Cmin were analyzed, and the changes of voriconazole Cmin after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole. RESULTS: Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole Cmin and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole Cmin was negatively correlated with albumin level (r=-2.673). Voriconazole Cmin in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole Cmin showed that compared with voriconazole Cmin 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole Cmin> 5.0 mg/L group was increased (χ2=4.318, P=0.038). CONCLUSION: The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole Cmin, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole Cmin of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.

[Factors Affecting the Surgical Level of Major Amputations in Patients with Severe Diabetic Foot].

Objective: To investigate the main factors affecting the surgical level of major amputations in patients with severe diabetic foot. Methods: A case-control study was conducted to analyze the clinical data of severe diabetic foot patients who had major amputations and were admitted to the Intensive Care Unit (ICU), Air Force Hospital of PLA Eastern Theater Command between July 2020 and July 2022. According to their surgical level of amputation, patients were divided into transtibial amputation (TT) group and transfemoral amputation (TF) group. Correlation analysis was performed with the clinical data of the patients, and multivariate logistic regression was performed to screen for relevant factors affecting the surgical level of major amputation. Results: The data of 48 patients with major amputations were collected, including 15 patients in the TT group and 33 patients in the TF group. The proportion of patients who had cardiovascular and cerebrovascular complications in the TT group was lower than that in the TF group (26.67% [4/15] vs. 57.58% [19/33], P<0.05), the proportion of patients who had lower extremity arterial intervention history was higher in the TT group than that in the TF group (40% [6/15] vs. 9.09% [3/33], P<0.05), and the proportion of patients who had elevated creatinine level was lower in the TT group than that in the TF group (70.31±22.98 vs. 127.98±108.38, P<0.05). Moreover, the history of lower extremity arterial intervention may be an independent protective factor for determining the surgical level of major amputations (odds ratio [ OR]=0.15, 95% confidence interval [ CI]: 0.03-0.72, P=0.018). Conclusion: History of cardiovascular and cerebrovascular diseases, serum creatinine level and history of lower extremity arterial intervention are the main factors affecting the surgical level of major amputations in patients with severe diabetic foot, and the history of lower extremity arterial intervention may be an independent protective factor.

A Polarization-Modulated Information Metasurface for Encryption Wireless Communications.

Programmable and information metasurfaces have shown great potentials in wireless communications, but there are few reports on encrypted communications. In this paper, a programmable polarization-modulated (PoM) information metasurface is proposed, which can not only customize arbitrarily linearly polarized reflected waves, but also modulate their amplitudes in real time. Based on this feature, a physical-level wireless communication encryption scheme is presented and experimentally demonstrated by introducing a meta-key, which can be encrypted and sent by the programmable PoM information metasurface. To be specific, the key is encoded and concealed into different linear polarization channels, and then modulated and transmitted by the information metasurface at the transmitting end. At the receiving end, the modulated signal can be received and decoded by using a pair of polarization discrimination antennas. A wireless transceiver system is established to verify the feasibility of the scheme. It is shown that, once the meta-key is obtained, the corresponding encrypted target information that has been sent to the user in advance can be recovered.

A narrative review of research progress on the role of NLRP3 inflammasome in acne vulgaris.

Background and Objective: Acne vulgaris is a common skin disease around the world which affects the appearance of patients, as well as their physical and mental health. Cutibacterium acnes plays a vital role in the occurrence and development of acne vulgaris. Pattern recognition receptors (PRRs) are the first line of defense against external pathogens. The nucleotide oligomerization domain (NOD)-like receptor family pyrin containing 3 (NLRP3) inflammasome has recently been shown to contribute to the pathogenesis of acne vulgaris. The purpose of this review is to clarify the underlying mechanisms of NLRP3 inflammasome in the pathogenesis of acne vulgaris, and its potential as a therapeutic target for the condition. Methods: The PubMed database was searched for relevant articles published in English between January 2003 to December 2021 using keywords "acne vulgaris", "NLRP3 inflammasome", and "Cutibacterium acnes". The reference lists of retrieved articles were also reviewed to identify relevant articles. Key Content and Findings: Cutibacterium acnes infection can lead to a series of inflammatory reactions and the production of inflammatory factors such as interleukin (IL)-1ß. In vitro and in vivo studies demonstrated that the NLRP3 inflammasome plays essential roles in acne vulgaris. Further, innate immunity and adaptive immunity pervade the entire pathogenesis of acne vulgaris. Conclusions: The NLRP3 inflammasome may be a potential therapeutic target for acne vulgaris. Future studies are needed to investigate the potential therapeutic effects of NLRP3 inhibitors on acne vulgaris.

Broadband and Programmable Amplitude-Phase-Joint-Coding Information Metasurface.

Information metasurfaces have attracted much attention in recent years due to the capability to link the physical world and information science. However, most of the current information metasurfaces are either phase-only coding or amplitude-only coding, limiting their functions and applications. Here, a broadband and programmable amplitude-phase-joint-coding (APJC) information metasurface is proposed and experimentally demonstrated, from which the phase and amplitude of reflected electromagnetic waves can be independently controlled by adjusting the bias voltage of PIN diode integrated in the meta-atom. In particular, the reflection amplitude can be continuously controlled from 0.1 to 0.9, and the reflection phase can be switched between two states with about 180° phase difference. Thus, the proposed metasurface is capable of realizing independent 1-bit or multibit amplitude coding and 1-bit phase coding, and both of them can be reprogrammed in real time in broad band from 8 to 13 GHz. The abilities of the programmable APJC information metasurface in manipulating the electromagnetic waves are demonstrated by both numerical simulations and experiments, including to suppress the sidelobes of scattering beam, generate the diffractive waves with arbitrary magnitudes, and so on. These results show unique advantages of APJC information metasurface in real-time independent controls of energy allocation and wavefront tailoring of the electromagnetic waves in a wide frequency band.

Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia.

The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLA-matched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P ≤ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P ≤ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (≤18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.

A SAS macro for estimating direct adjusted survival functions for time-to-event data with or without left truncation.

There are several statistical programmes to compute direct adjusted survival estimates from results of the Cox proportional hazards model. However, when used to analyze observational databases with large sample sizes or highly stratified treatment groups such as in registry-related datasets, these programmes are inefficient or unable to generate confidence bands and simultaneous p values. Also, these programmes do not consider potential left-truncation in retrospectively collected data. To address these deficiencies we developed a new SAS macro %adjsurvlt() able to produce direct adjusted survival estimates based on a stratified Cox model. The macro has improved computational performance and is able to handle left-truncated and right-censored time-to-event data. Several mechanisms were implemented to improve computational efficiency including choosing matrix operations over do-loops and reducing dimensions of co-variate matrices. Compared to the latest SAS macro, %adjsurvlt() used < 0.1% computational time to process a dataset with 100 treatment cohorts and a sample size of 20,000 and showed similar computational efficiency when analyzing left-truncated and right-censored data. We illustrate use of %adjsurvlt() to compare retrospectively collected survival data of 2 transplant cohorts.

Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML.

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.

[Emission Characteristics and Environment Impacts of VOCs from Typical Rubber Manufacture].

The emission characteristics of VOCs from three typical rubber manufacture industries were studied by GC-MS/FID. Maximum incremental reactivity(MIR) and fractional aerosol coefficient(FAC) were employed to evaluate the ozone formation potential(OFP) and secondary organic aerosol(SOA) formation potential. The results show that the VOC types emitted from the manufacturing of rubber products mainly include alkanes, ketones, aldehydes, alcohols, and benzene series. For traditional rubber products manufactured through rubber mixing and vulcanization, the main pollutants are ketones and alcohols, whereas for production processes involving gluing and painting, the main pollutants belong to the benzene series. In terms of ozone impact, the traditional processes contribute to ozone formation mainly through oxygenated hydrocarbons. In industries that utilize adhesives and paints, the extensive use of these organic solvents lead to a significantly higher contribution of the benzene series than other VOC species to ozone formation; the benzene series account for 82.9% of the total contribution. In terms of SOA impact, the benzene series are the main contributor to SOA, whereas the contribution of VOCs from traditional processes is small; hence, SOA primarily originates from the gluing and painting processes. Therefore, in traditional production of rubber products through rubber mixing and vulcanization, the emission of oxygenated hydrocarbons should be preferentially controlled, whereas for rubber industries utilizing gluing and painting processes, the emission of benzene series should be preferentially controlled.

Allogeneic Transplantation to Treat Therapy-Related Myelodysplastic Syndrome and Acute Myelogenous Leukemia in Adults.

Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myelogenous leukemia (t-AML), have a poor prognosis. An earlier Center for International Blood and Marrow Transplant Research (CIBMTR) analysis of 868 allogeneic hematopoietic cell transplantations (allo-HCTs) performed between 1990 and 2004 showed a 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%, respectively. Modern supportive care, graft-versus-host disease prophylaxis, and reduced-intensity conditioning (RIC) regimens have led to improved outcomes. Therefore, the CIBMTR analyzed 1531 allo-HCTs performed in adults with t-MDS (n = 759) or t-AML (n = 772) between and 2000 and 2014. The median age was 59 years (range, 18 to 74 years) for the patients with t-MDS and 52 years (range, 18 to 77 years) for those with t-AML. Twenty-four percent of patients with t-MDS and 11% of those with t-AML had undergone a previous autologous (auto-) HCT. A myeloablative conditioning (MAC) regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Nonrelapse mortality at 5 years was 34% (95% confidence interval [CI], 30% to 37%) for patients with t-MDS and 34% (95% CI, 30% to 37%) for those with t-AML. Relapse rates at 5 years in the 2 groups were 46% (95% CI, 43% to 50%) and 43% (95% CI, 40% to 47%). Five-year OS and DFS were 27% (95% CI, 23% to 31%) and 19% (95% CI, 16% to 23%), respectively, for patients with t-MDS and 25% (95% CI, 22% to 28%) and 23% (95% CI, 20% to 26%), respectively, for those with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low-risk t-MDS and those with t-AML undergoing HCT with MAC while in first complete remission, but worse for those with previous auto-HCT, higher-risk cytogenetics or Revised International Prognostic Scoring System score, and a partially matched unrelated donor. Relapse remains the major cause of treatment failure, with little improvement seen over the past 2 decades. These data mandate caution when recommending allo-HCT in these conditions and indicate the need for more effective antineoplastic approaches before and after allo-HCT.

Mode of action and efficacy of quinolinic acid for the control of Ceratocystis fimbriata on sweet potato.

BACKGROUND: Ceratocystis fimbriata is a hazardous fungal pathogen able to cause black rot disease on sweet potato. The management of C. fimbriata strongly relies on the use of toxic fungicides, and there is a lack of efficient alternative strategies. RESULTS: The antifungal properties of quinolinic acid (QA) were studied for the first time, indicating that QA shows selective antifungal activity against C. fimbriata. QA inhibited completely the mycelial growth of C. fimbriata at less than 0.8 mg mL-1 concentration (pH 4), and was able to produce alterations in the fungal cell wall, and to impede spore agglutination and mycelium formation. QA significantly reduced the concentration of ergosterol, and was able to associate to iron (II), suggesting that QA may be a lanosterol 14-α demethylase inhibitor. In preventive applications, QA reduced the disease incidence of C. fimbriata on sweet potato by 75%, achieving higher control efficacy in comparison with commercial fungicides prochloraz and carbendazim. CONCLUSIONS: The first selective antifungal agent against C. fimbriata was discovered in this work, and showed suitable antifungal properties for the management of black rot disease. © 2021 Society of Chemical Industry.

Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation.

Acute myeloid leukemia (AML) patients often undergo allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR). We examined the effect of depth of clinical response, including incomplete count recovery (CRi) and/or measurable residual disease (MRD), in patients from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry. We identified 2492 adult patients (1799 CR and 693 CRi) who underwent alloHCT between January 1, 2007 and December 31, 2015. The primary outcome was overall survival (OS). Multivariable analysis was performed to adjust for patient-, disease-, and transplant-related factors. Baseline characteristics were similar. Patients in CRi compared to those in CR had an increased likelihood of death (HR: 1.27; 95% confidence interval: 1.13-1.43). Compared to CR, CRi was significantly associated with increased non-relapse mortality (NRM), shorter disease-free survival (DFS), and a trend toward increased relapse. Detectable MRD was associated with shorter OS, shorter DFS, higher NRM, and increased relapse compared to absence of MRD. The deleterious effects of CRi and MRD were independent. In this large CIBMTR cohort, survival outcomes differ among AML patients based on depth of CR and presence of MRD at the time of alloHCT. Further studies should focus on optimizing post-alloHCT outcomes for patients with responses less than CR.