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Clostridioides (Clostridium) difficile (C. difficile) infection (CDI), often severe when producing toxin A, toxin B, and CDT, can cause life-threatening fulminant infections, especially in vulnerable patients. This case report discusses a 39-year-old woman with no medical history who developed severe CDI after antibiotic treatment, leading to fatal hypovolemic shock. A rare C. difficile PCR-ribotype 153 strain which is positive for toxin A, toxin B, and CDT was identified. This case emphasizes the need for early CDI diagnosis, cautious antibiotic use, and prompt treatment to prevent severe outcomes like shock and multiorgan failure., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

A 54-year-old man presented with a significant fourth heart sound (S4) and increased intensity of the second heart sound (S2), despite the absence of heart failure symptoms, in the second week of March 2024. Visualized phonocardiograms confirmed these findings, and further interviews revealed that he had suffered lifestyle changes, such as long commutes and sodium overload, while contributing to the response efforts in the 2024 Noto Peninsula Earthquake. Visualized phonocardiograms were also influential in determining the treatment strategy, persuading the patient to undergo a specific therapy, evaluating the therapeutic effects, and suggesting a new model for clinical practice.

Lassa virus (LASV) is an Old World (OW) mammarenavirus that causes Lassa fever, a life-threatening acute febrile disease endemic in West Africa. Lymphocytic choriomeningitis virus (LCMV) is a worldwide-distributed, prototypic OW mammarenavirus of clinical significance that has been largely neglected as a human pathogen. No licensed OW mammarenavirus vaccines are available, and the current therapeutic option is limited to the off-label use of ribavirin, which offers only partial efficacy. This situation underscores the urgent need to develop novel antivirals against human pathogenic mammarenaviruses. Previously, we showed that afatinib, a pan-ErbB tyrosine kinase inhibitor, inhibited multiple steps of the life cycles of OW LASV and LCMV, as well as the New World Junín virus vaccine strain Candid#1. In the present study, we investigated the inhibitory effect of U-73122, a phospholipase C inhibitor that acts downstream of ErbB signalling, on LCMV multiplication. U-73122 inhibited WT recombinant (r) LCMV multiplication in cultured cells. Preincubation of cell-free LCMV virions with U-73122 resulted in impaired virion infectivity. U-73122 also inhibited the infection of rLCMVs expressing heterologous viral glycoproteins, including the vesicular stomatitis Indiana virus (VSIV) glycoprotein, whereas WT VSIV infection was not affected by U-73122 treatment. Our results show the novel bioactivity of U-73122 as an LCMV inhibitor and indicate the presence of a virion-associated molecule that is necessary for virion infectivity and can be exploited as a potential antiviral drug target against human pathogenic mammarenavirus infections.

Biological molecules incorporating trifluoromethyl ketones (TFMKs) have emerged as reversible covalent inhibitors, aiding in the management and treatment of inflammatory diseases, cancer, and respiratory conditions. TFMKs, renowned for their versatile binding properties and adaptability, are pivotal in the rational design of novel drugs for diverse diseases. The photocatalytic insertion of alkenes, abundant feedstocks, into the α-carbon of trifluoromethylacetone represents a highly effective and atom-economical method for synthesizing valuable TFMKs. However, these processes typically necessitate high-energy photoirradiation ( λ > 300 nm, Hg lamp) and stoichiometric oxidants to generate the acetonyl radical from acetone. In our study, we demonstrate the visible-light photocatalytic radical addition into olefins using bromotrifluoroacetone as the trifluoroacetonyl radical precursor under mild conditions. Aliphatic trifluoromethyl ketones or the corresponding bromo-substituted products can be obtained by selecting an appropriate photocatalyst and solvent. Comprehensive experimental investigations, including cyclic voltammetry, Stern-Volmer quenching studies, and kinetic isotope effects, corroborate the synthesis of trifluoroacetonyl radical species from bromotrifluoroacetone under photoredox conditions. Further, we demonstrate the efficient synthesis of an oseltamivir derivative bearing a trifluoromethylketone moiety, which shows promising biological activity. Hence, this methodology will streamline the direct introduction of trifluoromethyl ketone into biological target molecules during drug discovery.

Emphysematous pyelonephritis and emphysematous cystitis are intractable diseases. Eight cases of bilateral emphysematous pyelonephritis and emphysematous cystitis have been reported, but no treatment has been established. An 88-year-old female was admitted with traumatic subarachnoid hemorrhage, and on the fourth day of hospitalization, she developed fever and septic shock. A computed tomography scan revealed bilateral emphysematous pyelonephritis and emphysematous cystitis. The patient was treated with bilateral double-J stents and an indwelling urethral catheter. This is the first report of bilateral emphysematous pyelonephritis and emphysematous cystitis treated conservatively with drainage and an internal stent, which may be a treatment option., Competing Interests: None., (© 2024 The Authors.)

The autologous pericardial aortic valve repair technique developed by Ozaki et al., using glutaraldehyde-treated autologous pericardium, has demonstrated superior durability to bioprosthetic valves. However, this technique has certain limitations, including excessive cusp height and cusp fluttering due to leaflet redunduncy. These limitations can lead to coronary ostium obstruction during transcatheter aortic valve implantation (TAVI) and postoperative infectious endocarditis. Consequently, we used a modified aortic valve repair technique using a Sawazaki's cusp template with a reduced cusp height, approximately 8 mm lower than the original template. This modified template was used in 119 patients between 2012 and 2023, with a maximum follow-up of 11 years. The mean patient age was 74±6.5 years, with 41% being male. The operative mortality rate was 0.8%, with one death attributed to injury of the left main trunk during selective coronary cannulation. Recurrent aortic regurgitation was observed in 4 patients, primarily due to commissural detachment (2 patients) and bottom cusp dehiscence(1 patient). Therefore, the cusp template was enlarged by 1 mm, the bite size was increased, and small 2×2 mm square wings were added at both site of commissures to reinforce the structures. Three patients underwent aortic valve replacement, whereas 1 underwent TAVI. Notably, no cases of infective endocarditis were observed. The mean postoperative pressure gradient was 16.2±7.9 mmHg and the 11-year reoperation-free survival rate was 95.8%. In conclusion, the autologous pericardial aortic valve repair technique using the Sawazaki's porcine cusp template resulted in excellent and favorable long-term outcomes.

Hemophagocytic lymphohistiocytosis (HLH) has been recognized as a rare adverse event following the coronavirus disease 2019 (COVID-19) vaccination. We report a case of neuropsychiatric symptoms and refractory HLH in a woman with systemic lupus erythematosus (SLE) after receiving her COVID-19 vaccine treated with belimumab, later found to have intravascular large B-cell lymphoma (IVLBCL) at autopsy. A 61-year-old woman with SLE was referred to our hospital because of impaired consciousness and fever. One month prior to consulting, she received her second COVID-19 vaccine dose. Afterward, her consciousness level decreased, and she developed a high fever. She tested negative for SARS-CoV-2. Neuropsychiatric SLE was suspected; therefore, glucocorticoid pulse therapy was initiated on day 1 and 8. She had thrombocytopenia, increased serum ferritin levels and hemophagocytosis. The patient was diagnosed with HLH and treated with etoposide, dexamethasone and cyclosporine. Despite treatment, the patient died on day 75; autopsy report findings suggested IVLBCL as the underlying cause of HLH. Differentiating comorbid conditions remains difficult; however, in the case of an atypical clinical presentation, other causes should be considered. Therefore, we speculate that the COVID-19 vaccination and her autoimmune condition may have expedited IVLBCL development.

This study aimed to establish a standard treatment for disseminated extranodal large B-cell lymphoma, including intravascular large B-cell lymphoma (DEN-LBCL/IVL), and to validate the clinical diagnostic criteria we proposed. Between 2006 and 2016, 22 patients were enrolled in a clinical trial conducted by the Hokuriku Hematology Oncology Study Group. The first cycle of chemotherapy consisted of dose-reduced cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with delayed administration of rituximab. From the second to the sixth cycle, patients received conventional rituximab and CHOP therapy. The primary endpoint was overall survival (OS), while the secondary endpoints included the complete response (CR) rate and time to treatment failure (TTF). The results showed a CR rate of 73%, a median OS of 65 months, and a median TTF of 45 months. These findings indicate that patients with DEN-LBCL/IVL were effectively treated with our new chemoimmunotherapy regimen. Our clinical diagnostic criteria are useful for identifying patients who require early intervention., Competing Interests: YM received research grants from Kyowa Kirin Pharma, Astellas Pharma, Eisai Pharma, Asahi Kasei Pharma, Daiichi-Sankyo Pharma, Taisho Pharma, Takeda Pharma, Chugai Pharma, Teijin Pharma, and Japan Blood Product Organization outside the submitted work. The other authors have no conflicts of interest to declare., (2024, National Center for Global Health and Medicine.)

Research Question: Does tailor-made embryo transfer (TmET), timed with respect to embryonic developmental speed, affect pregnancy outcomes in patients with recurrent implantation failure?, Design: Among 741 patients identified as receptive through endometrial receptivity testing, the clinical pregnancy rates and live birth rates were retrospectively compared between those who underwent standard personalized embryo transfer and those who underwent TmET in hormone replacement therapy cycles. Personalized embryo transfer was performed according to endometrial receptivity test results (standard personalized embryo transfer group) or considering embryonic developmental speed (TmET group). For TmET, the expansion grade of warmed blastocysts was estimated based on each patient's previous embryonic developmental pattern. The embryo transfer days were set so that estimated blastocyst grades 3, 4, 5 and 6 were transferred on days P+5, P+5.5, P+6.0 and P+6.5, respectively., Results: In a propensity score matching analysis, the clinical pregnancy rate was significantly higher in the TmET group than the standard personalized embryo transfer group (P = 0.014), whereas the live birth rates were similar between the two groups (P = 0.65). In a subgroup analysis with euploid embryo transfers, the clinical pregnancy rate was significantly higher in the TmET group than the standard personalized embryo transfer group, although there was no difference in live birth rate between the two groups (P = 0.045 and P = 0.057, respectively)., Conclusions: For patients experiencing recurrent implantation failure and identified as receptive through endometrial receptivity testing, subsequent TmET strategies may further enhance pregnancy outcomes., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

A 77-year-old man presented with right inguinal lymphadenopathy and swollen parotid and submandibular glands bilaterally. Histopathology revealed germinal center B-cell type diffuse large B-cell lymphoma (DLBCL) in the inguinal lymph node. Lymphocyte and plasma cell infiltration in the submandibular gland with elevated serum IgG4 levels (13 g/L) prompted a diagnosis of IgG4-related disease (IgG4-RD). Systemic chemotherapy for DLBCL led to shrinkage of the lymph nodes and disappearance of the submandibular gland swelling, as confirmed by fluorodeoxyglucose-positron emission tomography/computed tomography. Although concomitant IgG4-RD and lymphoma have been reported, their simultaneous diagnosis is rare; therefore, a biopsy of all involved organs is crucial in cases with unusual organ involvement.

A 73-year-old man with a history of heterotaxy syndrome and intestinal malrotation developed hemorrhagic shock due to bleeding from a duodenal ulcer. Esophagogastroduodenoscopy failed to achieve hemostasis because of restriction of the view by massive hemorrhage. Transcatheter arterial embolization cannot achieve endovascular hemostasis due to the vascular anatomy. Therefore, surgical hemostasis was achieved. Intestinal malrotation due to heterotaxy syndrome is a risk factor for gastrointestinal bleeding. Severe gastrointestinal bleeding in patients with intestinal malrotation is difficult to control with endoscopy alone. Therefore, combined therapies with endoscopy, interventional radiology, surgical procedures, and intensive care are vital for achieving a better prognosis.

We herein describe a new method for nucleophilic fluorine substitution of alkylbromides using Et 3 N·3HF. The process is characterized by a broad substrate scope, good functional-group compatibility, and mild conditions and provides a variety of alkylfluorides including tertiary alkylfluorides that are versatile and structurally attractive., Competing Interests: There is no conflict of interest to declare., (This journal is © The Royal Society of Chemistry.)

Background: Benzothiazole derivatives have been reported to possess a wide range of biological activities, including antimalarial activity. This systematic review aims to summarize and evaluate the antimalarial activities of benzothiazole analogs., Methods: We conducted an electronic search using nine databases in October 2017 and subsequently updated in September 2022. We included all original in vitro and in vivo studies that documented the antimalarial activities of compounds containing benzothiazole analogs with no restriction. The risk of bias of each included study was assessed by ToxRTool., Results: Twenty-eight articles were included in our study, which are in vitro, in vivo, or both. Of these, 232 substances were identified to have potent antiplasmodial activity against various strains of the malaria parasite. Benzothiazole analogs show different antimalarial mechanisms, including inhibition of Plasmodium falciparum enzymes in in vitro studies and inhibition of blood parasites in in vivo studies., Conclusions: Benzothiazole derivatives are promising substances for treating malaria. The structure-activity relationship studies suggest that the substitution pattern of the benzothiazole scaffold plays a crucial role in determining the antimalarial activity of the analog., (© 2023 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)

Introduction Hypermucoviscous Klebsiella pneumoniae  (hvKP) is related to invasive infections; however, there have been very few comprehensive reports on the clinical features and prognosis of critically ill patients with the infection. Methods We conducted a retrospective case series in a general intensive care unit in Japan. Patients with positive blood cultures for KP between January 1, 2020 and December 31, 2022 were included. hvKP was defined by the positivity in the string test. We analyzed the patient's characteristics at baseline, including comorbidities, abscess formation, Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE) II score, septic shock, duration of hospitalization, 30-day mortality, and infection site. Results A total of 24 patients had a positive blood culture for KP; nine patients (37.5%) were positive for the string test (hvKP) while 15 (62.5%) were negative (non-hvKP). In both groups, the patients were old (mean age, hvKP 80.4 vs. non-hvKP 75.7 years) and more often male (five patients (55.6%) vs. 12 patients (80.0%)). No statistically significant difference was found between the two groups in terms of comorbidities, such as diabetes mellitus, chronic obstructive pulmonary disease, chronic kidney disease, and malignancy. No statistical difference was seen in abscess formation (two patients [22.2%] vs. one patient (6.7%)), SOFA score (5.2±4.8 vs. 4.7±3.4), APACHE II score (19.6 (15.0-20.0) vs. 17.0 (11.2-20.8)), septic shock (five patients (55.6%) vs. four patient (26.7%)), duration of hospitalization (37.2 (12.0-51.0) vs. 32.3 (9.5-21.0)), and 30-day mortality (two patients (22.2%) vs. two patients (13.3%)). Two cases with hvKP died within 24 h. No significant difference was seen in the infection sources; respiratory infection (2 (22.2%) vs. 1 (6.7%)), hepatobiliary infection (2 (22.2%) vs. 7 (46.7%)), and genitourinary infection (1 (11.1%) vs. 5 (33.3%)). Conclusions Critically ill patients with hvKP infection showed characteristics similar to those reported previously. However, the disease could rapidly become severe and have a poor prognostic outcome., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Yomogida et al.)

Research Question: Would the use of the intracytoplasmic sperm injection (ICSI) position detector (IPD) make it possible to identify the optimal puncture position on oolemma during Piezo-ICSI and reduce oocyte degeneration and unintentional membrane rupture (UMR)?, Design: This sibling oocyte study included 917 inseminated oocytes from 113 infertile patients undergoing Piezo-ICSI. Oocytes were randomly divided into two groups: with or without IPD. The rates of UMR, degeneration, fertilization and embryonic development were compared between the two groups. As a secondary analysis, non-IPD oocytes were retrospectively assessed as appropriate or non-appropriate injection sites and analysed alongside prospective 'appropriate' injections., Results: The rates of UMR (7.0% versus 12.9%, P = 0.004) and degeneration (2.4% versus 6.1%, P < 0.01 = 0.008) were significantly lower in the IPD group than in the non-IPD group. No significant differences, however, were observed in the rates of fertilization (two pronuclei, 83.8% versus 78.9%), blastocyst formation (48.5% versus 48.8%) or good-quality blastocysts (22.5% versus 20.5%). Additionally, no significant differences were observed in the rates of pregnancy (29.4% versus 35.1%) or live births (26.5% versus 29.7%) in a single embryo transfer setting with or without IPD. Comparing all 'appropriate' injections with 'non-appropriate' injections also showed a significantly decreased rate of UMR and degeneration (both P ≤ 0.001)., Conclusions: The present study demonstrated that a real-time image analysis during Piezo-ICSI markedly reduced oocyte degeneration by avoiding areas associated with a high risk of UMR. Therefore, IPD may increase the number of embryos available for treatment., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Dimethyl sulfate (DMS) is a drug widely used as a pharmaceutical and synthetic raw material. On the other hand, it is highly toxic and requires management and treatment as a hazardous substance. A mass outbreak of chemical burns resulting from DMS poisoning occurred at a drug factory. All three patients were brought to our hospital, a tertiary emergency medical facility, several hours after exposure. Their vital signs were stable, with only eye pain and a sore throat. However, after admission, two patients required emergency tracheostomy or endotracheal intubation due to laryngeal edema. Improvement was achieved through the administration of steroids, but a severely injured patient required an extended treatment period. DMS poisoning is rare; however, it can be fatal depending on the exposure concentration. Furthermore, even if the initial symptoms are mild, laryngeal edema may develop later, requiring careful monitoring and appropriate airway interventions., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Mizuta et al.)

The function of kidney podocytes is closely associated with actin cytoskeleton regulated by Rho small GTPases. Loss of actin-driven cell adhesions and processes is connected to podocyte dysfunction, proteinuria, and kidney diseases. FilGAP, a GTPase-activating protein for Rho small GTPase Rac1, is abundantly expressed in kidney podocytes, and its gene is linked to diseases in a family with focal segmental glomerulosclerosis. In this study, we have studied the role of FilGAP in podocytes in vitro. Depletion of FilGAP in cultured podocytes induced loss of actin stress fibers and increased Rac1 activity. Conversely, forced expression of FilGAP increased stress fiber formation whereas Rac1 activation significantly reduced its formation. FilGAP localizes at the focal adhesion (FA), an integrin-based protein complex closely associated with stress fibers, that mediates cell-extracellular matrix (ECM) adhesion, and FilGAP depletion decreased FA formation and impaired attachment to the ECM. Moreover, in unique podocyte cell cultures capable of inducing the formation of highly organized processes including major processes and foot process-like projections, FilGAP depletion or Rac1 activation decreased the formation of these processes. The reduction of FAs and process formations in FilGAP-depleted podocyte cells was rescued by inhibition of Rac1 or P21-activated kinase 1 (PAK1), a downstream effector of Rac1, and PAK1 activation inhibited their formations. Thus, FilGAP contributes to both cell-ECM adhesion and process formation of podocytes by suppressing Rac1/PAK1 signaling., (© 2024 Federation of American Societies for Experimental Biology.)

Background: Coexistence of Takotsubo cardiomyopathy and psychogenic nonepileptic seizures has rarely been reported. Herein, we report a case of Takotsubo cardiomyopathy triggered by psychogenic nonepileptic seizures., Case Presentation: A 50-year-old woman with a 22-year history of dissociative and panic disorders and a 7-year history of seizures increasing in frequency was admitted due to cardiogenic shock. Based on the left ventriculography and electroencephalography findings, she was diagnosed with Takotsubo cardiomyopathy and psychogenic nonepileptic seizures. Seizures were controlled using antipsychotic agents, resulting in improved cardiac function, and she was discharged. However, she died of cardiopulmonary arrest 9 days after discharge., Conclusion: Since controlling psychogenic epileptic seizures is difficult, Takotsubo cardiomyopathy triggered by psychogenic nonepileptic seizures may have poor prognosis, requiring careful management and close monitoring., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Introduction: The CD34 + CD38 - population in bone marrow includes hematopoietic stem/progenitor cells. Recently, in acute myeloid leukemia, the focus has shifted to flow cytometry analysis targeting CD34 + CD38 - leukemic cells due to their effectiveness in minimal/measurable residual disease detection and prognosis prediction. Nevertheless, the immunophenotype and cell frequency of these cells in the bone marrow, in the absence of leukemic cells, remains unknown. We aimed to evaluate detailed characteristics of CD34 + CD38 - cells in both normal and leukemic cells by flow cytometry., Methods: We compared the cell frequency and immunophenotype of the CD34 + CD38 - fraction in the following groups: patients with idiopathic thrombocytopenic purpura and malignant lymphoma as controls (n = 17), post-treatment patients without abnormal blasts (n = 35), and patients with myeloid malignancies (n = 86). The comparison was based on the presence or absence of CD45RA expression, a marker commonly used to prospectively isolate lymphoid-primed cell populations within the CD34 + CD38 - fraction., Results: The CD34 + CD38 - CD45RA + cell population exhibited a significant expansion in bone marrow without leukemic cells 1 month after cord blood transplantation and in various type of myeloid malignancies, compared to the control group (p < 0.01). Continuous CD45RA expression and notable expansion of the CD34 + CD38 - CD45RA - population were exclusively observed in myelodysplastic syndrome-related diseases. The CD34 + CD38 - CD45RA + population displayed frequent expression of various markers in both leukemic and non-leukemic cells, in contrast to the CD34 + CD38 - CD45RA - population., Conclusions: The CD34 + CD38 - fraction should be carefully evaluated considering the nature of normal hematopoietic precursor cells, their cell frequency and immunophenotype, including CD45RA expression pattern, for improving the accuracy of myeloid malignancy diagnosis., (© 2023 International Clinical Cytometry Society.)

Measurable residual disease (MRD) status before transplantation has been shown to be a strong prognostic factor in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, the outcomes of unrelated hematopoietic stem cell transplantation based on the MRD status have not been fully investigated. In this retrospective study, we compared the outcomes of 715 consecutive adults with Ph + ALL in complete remission who underwent unrelated cord blood transplantation (UCBT) (single-unit UCBT, n = 232 [4/6, 5/6, and 6/6 HLA match]), HLA-matched unrelated bone marrow transplantation (UBMT; n = 292 [8/8 HLA match]), or HLA-mismatched UBMT (n = 191 [7/8 HLA match]). In the MRD + cohort, adjusted 3-year leukemia-free survival rates were 59.8%, 38.3%, and 55.5% after UCBT, HLA-matched UBMT, and HLA-mismatched UBMT, respectively. In the MRD - cohort, the corresponding rates were 65.3%, 70.4%, and 69.7%, respectively. The MRD + HLA-matched UBMT group had a significantly higher risk of relapse than the MRD + HLA-mismatched UBMT group (hazard ratio [HR] in the MRD + HLA-mismatched UBMT group, 0.33; 95% confidence interval [CI] 0.15-0.74) and the MRD + UCBT group (HR in the MRD + UCBT group, 0.38; 95% CI 0.18-0.83). Furthermore, HLA-matched UBMT had a significant effect of MRD on death (HR 1.87; 95% CI 1.19-2.94), relapse or death (HR 2.24; 95% CI 1.50-3.34), and relapse (HR 3.12; 95% CI 1.75-5.57), while UCBT and HLA-mismatched UBMT did not. In conclusion, our data indicate Ph + ALL patients with positive MRD may benefit from undergoing UCBT or HLA-mismatched UBMT instead of HLA-matched UBMT to reduce leukemic relapse., (© 2023 Wiley Periodicals LLC.)

Cryptococcosis has become a major health problem worldwide and caused morbidity and mortality in immunocompromised patients, especially those infected with human immunodeficiency virus (HIV). Despite the global distribution of cryptococcosis, the number and types of the available antifungals are limited, and the treatment outcomes in HIV patients are generally poor. In this study, we screened a compound library and identified one tetrazole derivative as an efficient inhibitor of Cryptococcus neoformans and Cryptococcus gattii. We further designed and synthesized a series of tetrazole derivatives and determined their structure-activity relationship, demonstrating that tetrazole backbone-containing compounds could be developed as novel antifungal drugs with distinct mechanisms against Cryptococcus spp. Our findings provide a starting point for novel target identification and structural optimization to develop a distinct class of therapeutics for patients with cryptococcosis., (© 2023 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

A 66 year-old male was admitted to our clinic suffering from dyspnea on effort. Cardio thoracic ratio (CTR) was 62%. Electrocardiogram showed atrial fibrillation. Echocardiogram showed severe mitral regurgitation (MR), Barlow like billowing and thickened A2 and A3, and loss of P2 and P3. Operation was performed through median sternotomy and right sided left atrial incision. Left atrial appendage was closed with running suture. Maze operation was done. Triangular resection of A2 and A3 was done. P2 and P3 were adhered to the left ventricular wall. First we cut the adhered posterior leaflet in a shape of inverted T. And the adhered leaflet was dissected from the left ventricle by the scissors. The detached annulus was mattress-sutured with a pledgetted suture. The leaflets were sutured together, then a new posterior leaflet was remade using mitral valve leaflet tissue and the shape became higher and round. Post operatively, MR was none, and posterior leaflet functioned well. Sinus rhythm was recovered. Eleven years later, no MR and sinus rhythm were shown.

We repaired the bicuspid aoric valve( BAV) with aortic regurgitation( AR) by bicuspidization. However, repaired fused cusp does not open full, and shows doming. Between 1997 and 2023 we repaired 30 BAV with AR. Mean Age was 44( 15-79) years old. Male gender was 26/30. Between 1997 and 2017, we repaired by triangular resection and cusp suspension or central plication and the commissural positions remained as it was, in 17 cases. Between 2018 and 2023, we repaired by triangular resection and aortic root remodeling to make the commissure angle 180 degree in 13 cases. One patient died because of compression occlusion of left main trunk by Schaefer's annulplasty suture post-operatively. Postoperative aortic valve pressure gradient was 12.2±5.4 mmHg in natural commissure position group, 14.7±6.8 mmHg in the 180 degree commissure position group( p=0.37). And in the 180 degree commissure position group, the fused cusp did not show doming. In the 180 degree commissure position group, the fused cusp did not show doming. However, trans aortic valve pressure gradient did not decrease. On the other hand, in the natural commissure group, the fused cusp showed doming. However, the valves well functioned up to 25 years without aortic stenosis.

Research and development of personalized cancer vaccines as precision medicine are ongoing. We predicted human leukocyte antigen (HLA)-compatible cancer antigen candidate peptides based on patient-specific cancer genomic profiles and performed a Phase I clinical trial for the safety and tolerability of cancer vaccines with human platelet lysate-induced antigen-presenting cells (HPL-APCs) from peripheral monocytes. Among the five enrolled patients, two patients completed six doses per course (2-3 × 10 7 cells per dose), and an interim analysis was performed based on the immune response. An immune response was detected by enzyme-linked immunosorbent spot (ELISpot) assays to HLA-A*33:03-matched KRAS WT , HLA-DRB1*09:01-compliant KRAS WT or G12D , or HLA-A*31:01-matched SMAD4 WT , and HLA-DRB1*04:01-matched SMAD4 G365D peptides in two completed cases, respectively. Moreover, SMAD4 WT -specific CD8 + effector memory T cells were amplified. However, an attenuation of the acquired immune response was observed 6 months after one course of cancer vaccination as the disease progressed. This study confirmed the safety and tolerability of HPL-APCs in advanced and recurrent cancers refractory to standard therapy and is the first clinical report to demonstrate the immunoinducibility of personalized cancer vaccines using HPL-APCs. Phase II clinical trials to determine immune responses with optimized adjuvant drugs and continued administration are expected to demonstrate efficacy.

We herein report a patient with primary effusion lymphoma-like adult T-cell leukemia/lymphoma (PEL-like ATL) that developed during hemodialysis. A 77-year-old man developed a fever and ascites. Elevated levels of lactate dehydrogenase (LDH), calcium and soluble interleukin-2 receptor (sIL-2R) along with antibodies to human T-cell leukemia virus type 1 (HTLV-1) were seen in his blood. Lymphoma cells in ascites were positive for HTLV-1 proviral DNA, but there were no neoplastic cells in peripheral blood or bone marrow and no lymphadenopathy. He was therefore diagnosed with PEL-like ATL, acute-type. After administration of brentuximab vedotin, his serum LDH, sIL-2R and atypical cells in ascites cytology decreased. The development of novel effective molecular-targeted therapies is warranted.

Aim: To investigate the association between locomotive syndrome and anemia among community-dwelling older adults., Methods: This cross-sectional study was conducted at specific health checkup centers in Japan between 2019 and 2020. We sent a questionnaire to older adults aged ≥65 years who participated in health checkups. A total of 2507 community-dwelling older adults were included in this study (mean age = 72.3 years, 51.4% women). Locomotive syndrome was measured using a 25-question Geriatric Locomotive Function Scale with a score range of 0-100, and was defined as ≥16 points. Anemia was defined using World Health Organization criteria, as a hemoglobin concentration of <13.0 g/dL in men and <12.0 g/dL in women. Logistic regression analyses were performed to investigate the association between locomotive syndrome and anemia, adjusted for age, sex, body mass index, depression symptoms, self-reported comorbidities (cancer, rheumatoid arthritis, knee osteoarthritis, fractures, and spinal disease), hypertension, and renal function., Results: Of all the participants, 11.6% had locomotive syndrome and 12.8% had anemia. Even after adjustment, a relationship between locomotive syndrome and anemia was observed (adjusted odds ratio = 1.9, 95% confidence interval = 1.3-2.7)., Conclusions: Community-dwelling older adults with anemia had a significantly higher prevalence of locomotive syndrome than those without. This finding suggests that older adults with anemia are at risk of locomotive syndrome, and appropriate measures should be taken for prevention. Geriatr Gerontol Int 2023; 23: 426-429., (© 2023 Japan Geriatrics Society.)

Background: Older adults are more likely to experience loneliness than younger people. Moreover, greater loneliness in older adults is associated with poor mental health and increased risk of cardiovascular disease and mortality. Physical activity is an effective intervention for reducing loneliness among older adults. Among physical activities, walking is suitable for older adults, because it is easy and safe to incorporate into daily life. We hypothesized that the association between walking and loneliness depends on the presence of others and the number of people present. The aim of this study is to investigate the association between the context of walking (the number of walkers) and loneliness among community-dwelling older adults., Methods: This cross-sectional study included 173 community-dwelling older adults aged 65 or older. Context of walking was classified as non-walking, walking alone (days of walking alone > days of walking with someone), and walking with someone (days of walking alone ≤ days of walking with someone). Loneliness was measured using the Japanese version of the University of California Los Angeles Loneliness Scale. A linear regression model was used to investigate the relationship between context of walking and loneliness, adjusted for age, sex, living situation, social participation, and physical activity excluding walking., Results: Data from 171 community-dwelling older adults (mean age = 78.0 years, 59.6% women) were analyzed. After adjustment, walking with someone was associated with lower loneliness than non-walking (adjusted β: -0.51, 95% confidence interval: -1.00, -0.01)., Conclusions: The study's findings suggest that walking with a companion may effectively prevent or reduce loneliness among older adults., (© 2023. The Author(s).)

We report the structural functionalization of the terminal amino group of N 1 -(7-chloroquinolin-4-yl) butane-1,4-diamine, leading to a series of 7-chloro-4-aminoquinoline derivatives, and their evaluation as potent anti-malarial and anti-viral agents. Some compounds exhibited promising anti-malarial effects against the Plasmodium falciparum 3D7 (chloroquine-sensitive) and Dd2 (chloroquine-resistant) strains. In addition, these compounds were assayed in vitro against influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Compound 5 h, bearing an N-mesityl thiourea group, displayed pronounced anti-infectious effects against malaria, IAV, and SARS-CoV-2. These results provide new insights into drug discovery for the prevention or treatment of malaria and virus co-infection., (© 2023 Wiley-VCH GmbH.)

Mycobacterium infection gives rise to granulomas predominantly composed of inflammatory M1-like macrophages, with bacteria-permissive M2 macrophages also detected in deep granulomas. Our histological analysis of Mycobacterium bovis bacillus Calmette-Guerin-elicited granulomas in guinea pigs revealed that S100A9-expressing neutrophils bordered a unique M2 niche within the inner circle of concentrically multilayered granulomas. We evaluated the effect of S100A9 on macrophage M2 polarization based on guinea pig studies. S100A9-deficient mouse neutrophils abrogated M2 polarization, which was critically dependent on COX-2 signaling in neutrophils. Mechanistic evidence suggested that nuclear S100A9 interacts with C/EBPβ, which cooperatively activates the Cox-2 promoter and amplifies prostaglandin E2 production, followed by M2 polarization in proximal macrophages. Because the M2 populations in guinea pig granulomas were abolished via treatment with celecoxib, a selective COX-2 inhibitor, we propose the S100A9/Cox-2 axis as a major pathway driving M2 niche formation in granulomas., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Research Question: One of the problems during the intracytoplasmic sperm injection (ICSI) procedure is unintentional membrane rupture (UMR), which often predisposes to subsequent oocyte degeneration. Can the ICSI Position Detector (IPD) be useful in identifying the optimal puncture location to prevent UMR during ICSI?, Design: A total of 709 mature oocytes were included. Conventional ICSI was carried out and images were recorded by IPD; these were analysed retrospectively., Results: Inseminated oocytes were retrospectively grouped according to the IPD, irrespective of whether oolemma was punctured at an area in which UMR is likely (non-appropriate group) or unlikely (appropriate group). In the appropriate group, rates of UMR (5.3% versus 18.2%) and degeneration (2.5% versus 8.7%) were significantly lower than those of the non-appropriate group, whereas rate of fertilization (87.1% versus 69.7%) was significantly higher than those of the non-appropriate group, respectively (P < 0.001). These differences remained even after propensity score matching to adjust for potential differences in characteristics between appropriate and non-appropriate groups., Conclusions: This study demonstrated that the IPD is useful to identify the optimal puncture location to circumvent UMR during the ICSI procedure, resulting in reduced UMR and oocyte degeneration, thereby, generating more embryos available for transfer or cryopreservation., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

TAFRO syndrome was first described in 2010, standing for thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly. Because the lymph node histopathology of TAFRO syndrome mimics idiopathic multicentric Castleman disease (iMCD), some researchers consider TAFRO syndrome to be a subtype of iMCD. However, the clinical features of TAFRO syndrome considerably differ from those of iMCD without TAFRO. The clinical features of patients with TAFRO syndrome with or without iMCD-histopathology are similar, and these patients require an accurate diagnosis and urgent treatment. Although a histological diagnosis, including a differential diagnosis, is important, lymph node involvement in patients with TAFRO syndrome is usually modest or sometimes absent. Furthermore, a bleeding tendency due to thrombocytopenia and severe anasarca hampers performing a biopsy. Nonetheless, patients with various other disorders may manifest TAFRO syndrome-like symptoms, making the differential diagnosis in borderline cases difficult. Therefore, the establishment of precise and specific biomarkers is important.

Assisted reproductive technology (ART) has progressed rapidly, resulting in a great improvement in the clinical pregnancy ratio. When applying the protocol of piezo intracytoplasmic sperm injection (Piezo-ICSI), it is very important to puncture the zona pellucida and the oocyte cytoplasmic membrane without rupturing the oocyte cytoplasmic membrane. Previous studies have shown that the poor extensibility of the oocyte cytoplasmic membrane might be closely related to rupture. However, no consensus has been reached regarding how the quality of the oocyte for extensible ability or rupture possibility affects the surfaces of the oocyte on the microscopic frames. We conducted this study to provide evidence that artificial intelligence (AI) techniques are superior for predicting the tendency of oocyte rupture before puncturing on Piezo-ICSI. To inspect it, we provided a retrospective trial of 38 rupture oocytes and 55 nonruptured oocytes. This study marked the highest accuracy of 91.4% for predicting oocytes rupture using the support-vector machine method of machine learning. We conclude that AI technologies might serve an important role and provide a significant benefit to ART.

Lectins are carbohydrate-binding proteins that possess specific sugar-binding properties and are involved in various biological activities in different organisms. In this study, purification, characterization, and cDNA cloning of a brittle star lectin, designated as Ophioplocus japonicus agglutinin (OJA), were conducted. OJA was isolated from the brittle star O. japonicus by affinity chromatography on a Sephadex G-25 column, followed by ion-exchange chromatography on a Resource Q column. This lectin yielded distinct bands at approximately 176 or 17 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) under non-reducing or reducing conditions, respectively. It also exhibited Ca 2+ -dependent hemagglutination activity, which, however, was not affected by other metal cations, such as Ba 2+ , Co 2+ , Cu 2+ , Zn 2+ , Fe 2+ , Mg 2+ , and Mn 2+ . The OJA activity was strongly inhibited by glucose and xylose among the monosaccharides tested, and by bovine thyroglobulin among the glycoproteins tested. Cloning of the OJA cDNA revealed that its primary structure contained the C-type lectin domain (CTLD). The results of this study showed that OJA is an echinoderm-derived glucose/xylose-specific lectin that belongs to the C-type lectin superfamily., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We compared the outcomes of autologous stem cell transplantation (auto-SCT) with those of allogeneic stem cell transplantation (allo-SCT) from a human leukocyte antigen-matched related donor in patients with Philadelphia chromosome-negative B-lineage acute lymphoblastic leukemia (ALL). Newly diagnosed patients who underwent allo-SCT (n = 486) or auto-SCT (n = 99) after achieving first complete remission (CR) were included. Propensity score matching (PS) and an inverse probability of the treatment weighting (IPTW) analysis were applied to compensate for imbalances in baseline characteristics. The 5 years rates of overall survival (OS) among those in the PS-matched cohorts were 57% [95% confidence interval (CI) 46-67%] for those who received allo-SCT and 44% (95% CI 33-54%) for those who received auto-SCT. Multivariable, propensity score-matched, and IPTW analyses all revealed no statistically significant differences in OS between the two groups [hazard ratios (HR) 0.81, 95% CI 0.53-1.27, p = 0.36; HR 0.84, 95% CI 0.40-1.78, p = 0.65; HR 0.71, 95% CI 0.25-2.02, p = 0.53, respectively]. Prospective trials that include autologous transplantation as a treatment option are needed to examine the potential of autologous transplantation., (© 2022. Japanese Society of Hematology.)

Various systems for predicting the prognosis of patients with myelodysplastic syndromes (MDS) have been developed. However, associations between performance status (PS) and prognosis of MDS require further investigation. To objectively assess the impact of PS on survival, we examined laboratory findings associated with PS, including serum levels of C-reactive protein (CRP), albumin (ALB), and total cholesterol (CHOL). Patients (n = 123; male 86, female 37; median age 74 yrs.) diagnosed with MDS or myelodysplastic/myeloproliferative neoplasms at Kanazawa Medical University Hospital between 2010 and 2020 were enrolled and grouped by cutoff values determined by receiver operating characteristic analysis: 0.44 mg/dL for CRP, 4.0 g/dL for ALB, and 120 mg/dL for CHOL. The median follow-up period was 17.6 months. Kaplan-Meier analysis revealed that overall survival (OS) in the high CRP, low ALB, and low CHOL groups was significantly shorter than in the low CRP, high ALB, and high CHOL groups, respectively. Multivariable analysis revealed that elevated serum CRP was an independent prognostic risk factor independent of gender, bone marrow blast percentage, and cytogenetics., (© 2022. Japanese Society of Hematology.)

Recent advances in chemotherapy have led to the emergence of new types of anticancer agents. With these advances, cases of side effects that have not been witnessed in the past have emerged. The systems of side effect evaluation and their grading have been based on the existing knowledge, such as the CTCAE (Common Terminology Standard for Adverse Events) for evaluating adverse drug reactions in cancer chemotherapy clinical trials. Therefore, new types of side effects may be overlooked or underestimated. Blinatumomab is a bispecific T-cell-engager (BiTE) antibody with specificity for CD19 on B cells and CD3 on T cells. Neurological events, such as neuropathy and encephalopathy, are serious side effects of BiTE antibodies. We encountered a case of a 62-year-old woman who experienced short-term memory impairment and dysgraphia after the first blinatumomab administration for Philadelphia chromosome negative (Ph-) B-cell acute lymphoblastic leukemia (ALL). The CTCAE does not include dysgraphia as a classifier for antibody therapies, such as blinatumomab, and immune effector cell-associated neurotoxicity syndrome, which is defined as a Chimeric antigen receptor T cell therapy-related toxicity; dysgraphia is included in the list of symptoms but is not graded. In this case, the severity of dysgraphia differed depending on the complexity of the letters examined. There is no report that the severity of dysgraphia depends on the letters' complexity, and therefore, it may be overlooked when using simple letters. We have reported the characteristics of dysgraphia in this case and the differences observed when judging different letters.

Chronic myeloid leukemia (CML) blast phase (monocytic lineage) is extremely rare. A 39-year-old Japanese man was diagnosed with CML blast phase (monocytic lineage). T315I mutation was positive, ponatinib was initially started, and then, allogenic hematopoietic stem cell transplantation (allo-HSCT) was performed. Seven days after allo-HSCT, hyper-acute graft-versus-host disease developed, and medial temporal lobe encephalitis emerged 24 days after allo-HSCT. He was alive for over 1 year after allo-HSCT. This is the first case report of HSCT for CML blast phase (monocytic lineage) in tyrosine kinase inhibitor era. Further cases should be documented for effective treatment regimen and analysis of clinical features., Competing Interests: We have no conflicts of interest., (Copyright © 2022 by S. Karger AG, Basel.)

Introduction: GATA1 mutation plays an important role in initiating transient abnormal myelopoiesis (TAM) and in the clonal evolution towards acute megakaryoblastic leukaemia (AMKL) associated with Down syndrome (DS). This study aimed to develop and validate the clinical utility of a complementary DNA (cDNA) analysis in parallel with the conventional genomic DNA (gDNA) Sanger sequencing (Ss), as an initial screening test for GATA1 mutations., Methods: GATA1 mutations were evaluated using both gDNA and cDNA in 14 DS patients using Ss and fragment analysis (FA), respectively., Results: The detection sensitivity of conventional gDNA sequencing was limited in low blast percentage TAM (LBP-TAM); however, cDNA-based Ss readily detected all the pathognomonic GATA1 mutations. The cDNA-based FA readily detected GATA1 frameshift mutation with a reliable sensitivity ranging from 0.005% to 0.01% of clonal cells., Conclusions: GATA1 mutations are heterogeneous; therefore, we would like to propose a dual cDNA and gDNA analysis as a standard diagnostic approach, especially for LBP-TAM. cDNA-based FA promises an excellent sensitivity for detecting frameshift GATA1 mutations in the longitudinal clonal evolution towards AMKL without using a patient specific primer., (© 2021 John Wiley & Sons Ltd.)

The central role of Ebola virus (EBOV) VP40 in nascent virion assembly and budding from infected host cells makes it an important therapeutic target. The mechanism of dimerization, following oligomerization of VP40 leading to the production of virus-like particles (VLP) has never been investigated for the development of therapeutic candidates against Ebola disease. Molecular dynamics-based computational screening targeted VP40 dimer with 40,000,000 compounds selected 374 compounds. A novel in vitro screening assay selected two compounds, NUSU#1 and NUSU#2. Conventional VLP assays consistently showed that both compounds inhibited EBOV VP40-mediated VLP production. Intriguingly, NUSU#1 inhibited the VP40-mediated VLP production in other ebolavirus species and the Marburg virus, but did not inhibit Lassa virus Z-mediated VLP production. These results strongly suggested that the selected compounds are potential lead drug candidates against Filovirus disease via disruption of VP40-mediated particle production., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The emergence of tyrosine kinase inhibitors as part of a front-line treatment has greatly improved the clinical outcome of the patients with Ph + acute lymphoblastic leukemia (ALL). However, a portion of them still become refractory to the therapy mainly through acquiring mutations in the BCR-ABL1 gene, necessitating a novel strategy to treat tyrosine kinase inhibitor (TKI)-resistant Ph + ALL cases. In this report, we show evidence that RUNX1 transcription factor stringently controls the expression of BCR-ABL1, which can strategically be targeted by our novel RUNX inhibitor, Chb-M'. Through a series of in vitro experiments, we identified that RUNX1 binds to the promoter of BCR and directly transactivates BCR-ABL1 expression in Ph + ALL cell lines. These cells showed significantly reduced expression of BCR-ABL1 with suppressed proliferation upon RUNX1 knockdown. Moreover, treatment with Chb-M' consistently downregulated the expression of BCR-ABL1 in these cells and this drug was highly effective even in an imatinib-resistant Ph + ALL cell line. In good agreement with these findings, forced expression of BCR-ABL1 in these cells conferred relative resistance to Chb-M'. In addition, in vivo experiments with the Ph + ALL patient-derived xenograft cells showed similar results. In summary, targeting RUNX1 therapeutically in Ph + ALL cells may lead to overcoming TKI resistance through the transcriptional regulation of BCR-ABL1. Chb-M' could be a novel drug for patients with TKI-resistant refractory Ph + ALL., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Competing Interests: On behalf of all the authors, the corresponding authors states that there are no conflicts of interest to declare. Our sincere thanks go to pediatric oncology team especially, Dr. Atsushi Iwai, Dr. Kuniaki Tanaka and Dr. Ikuya Usami.

Influenza viruses are responsible for contagious respiratory illnesses in humans and cause seasonal epidemics and occasional pandemics worldwide. Previously, we identified a quinolinone derivative PA-49 , which inhibited the influenza virus RNA-dependent RNA polymerase (RdRp) by targeting PA-PB1 interaction. This paper reports the structure optimization of PA-49 , which resulted in the identification of 3-((dibenzylamino)methyl)quinolinone derivatives with more potent anti-influenza virus activity. During the optimization, the hit compound 89 , which was more active than PA-49 , was identified. Further optimization and scaffold hopping of 89 led to the most potent compounds 100 and a 1,8-naphthyridinone derivative 118 , respectively. We conclusively determined that compounds 100 and 118 suppressed the replication of influenza virus and exhibited anti-influenza virus activity against both influenza virus types A and B in the range of 50% effective concentration (EC 50 ) = 0.061-0.226 μM with low toxicity (50% cytotoxic concentration (CC 50 ) >10 μM).

Transient abnormal myelopoiesis (TAM) is a unique neonatal leukemoid reaction caused by a pathognomonic GATA1 mutation in conjunction with the gene dosage effect of trisomy 21, which is either of germline or somatic origin. We encountered a 48,XYY,+21 phenotypically normal neonate with Down syndrome who developed TAM due to cryptic germline mosaicism. Quantification of the mosaic ratio was complicated by an overestimation bias of hyperproliferating TAM within the germline component. To establish a workflow for such a clinical scenario, we analyzed the cytogenetic findings of neonates with TAM associated with somatic or low-level germline mosaicism. We showed that multistep diagnostic procedures (i.e., paired cytogenetic analyses of peripheral blood specimens in culture with or without phytohemagglutinin; serial cytogenetic studies of more than one tissue, such as the buccal membrane; and complementary DNA-based GATA1 mutation screening) can verify the specificity of cytogenetic testing for phenotypically normal neonates with TAM suspected of mosaicism., (© 2023 S. Karger AG, Basel.)

Background: Multi-parametric flow cytometry (MFC) is a helpful tool for detecting neoplastic cells in malignant lymphoma; however, lymphoma cells can be difficult to detect when characteristic immunophenotypic abnormalities are not evident. We evaluated the stainability of VS38, which is used for multiple myeloma, in normal and abnormal B cells using MFC to develop a new strategy for detecting lymphoma cells., Methods: We compared the median fluorescence intensity of VS38 staining in lymphocytes from patients without hematopoietic neoplasms and in B cells from 26 patients with B cell lymphoma (BCL). To evaluate the performance of VS38 gating, we compared VS38-positive B cells with the percentages of BCL cells, and with the mutation ratios of MYD88 L265P measured by droplet digital PCR in patients with lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM)., Results: CD27-positive memory B cells were stained with VS38, whereas normal lymphocytes were faintly stained. Lymphoma cells were stained with VS38 in 11 of 12 patients with LPL/WM, 3 of 3 with chronic lymphocytic leukemia, 3 of 5 with mantle cell lymphoma, 2 of 4 with follicular lymphoma, and 1 of 1 with splenic marginal zone lymphoma. The percentages of VS38-positive B cells in VS38-positive BCL were equivalent to those of lymphoma cells and the mutation ratios of MYD88 L265P in LPL/WM., Conclusions: VS38 identified neoplastic cells in plasma cell disorders and BCL. This might improve the accuracy of BCL diagnosis, especially in patients with LPL/WM., (© 2021 International Clinical Cytometry Society.)

General methods have not been previously developed for the synthesis of sterically hindered α-SCF 3 -substituted carbonyl compounds using nucleophilic trifluoromethylthiolating reagents. Thus, we herein report sp 3 C-SCF 3 bond formation in hindered α-bromoamides containing 3-bromo-oxindoles and linear α-bromoamides using CuSCF 3 or AgSCF 3 under mild conditions to access sterically hindered α-SCF 3 -substituted amides. This transformation is applicable to not only 3-SCF 3 -substituted oxindoles but also primary and secondary amides and reveals a broad functional group tolerance. This method will benefit the fields of medicinal and agricultural chemistry.

Background and Aims: Immunoglobulin 4 (IgG4)-related disease (IgG4-RD) is a lymphoproliferative disorder characterized by elevated serum IgG4 levels and tissue infiltration of IgG4-positive plasma cells. We analyzed the serum proteins, whose levels varied based on the disease state and treatment., Materials and Methods: Serum proteins from patients with IgG4-related disease and healthy subjects were resolved using two-dimensional electrophoresis, silver-stained, and scanned. Alternatively, the proteins were labeled with Cy2, Cy3, and Cy5 before electrophoresis. The proteins, whose expression differed significantly between patients and healthy individuals, and between before and after steroid treatment, were identified and validated using enzyme-linked immunosorbent assays., Results: Pre-treatment sera from patients with IgG4-related disease was characterized by increased levels of immunoglobulins such as IgG1, IgG4; inflammatory factors such as α-1 antitrypsin (A1AT); and proteins associated with immune system regulation such as clusterin and leucine-rich α-2-glycoprotein (LRG-1). The serum levels of A1AT, LRG-1 and clusterin, during treatment with prednisolone for up to 12 months revealed that LRG-1 levels were halved after 1 month of treatment, comparable to those in healthy subjects; LRG-1 levels remained normal until the end of treatment., Conclusion: LRG-1 could serve as a novel biomarker of IgG4-related diseases., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

The optimal treatment for Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR1) has not been established in the high-intensity chemotherapy era. The outcomes of patients with Ph-negative ALL who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched related or unrelated donor in CR1 (HSCT-MRD group and HSCT-MUD group) were obtained from a Japanese registry database. Patients aged 16-24 years and 25-65 years were analyzed separately, and their outcomes were compared to those of patients who continued high-intensity chemotherapy in CR1 in studies (202U group and 202O group) by the Japan Adult Leukemia Study Group (JALSG). In the HSCT-MRD group, patients younger than 25 years had lower overall survival (OS) than the 202U group, presumably due to the higher non-relapse mortality (NRM) in the HSCT-MRD group. Patients 25 years and older had similar OS to the 202O group. The lower relapse rate was counterbalanced by higher NRM in the HSCT-MRD group. In the HSCT-MUD group, patients in both age groups had similar OS to their corresponding groups in the JALSG studies. In conclusion, high-intensity chemotherapy may change the role of HSCT for Ph-negative ALL., (© 2021. Japanese Society of Hematology.)

The Sendai virus vector has received a lot of attention due to its broad tropism for mammalian cells. As a result of efforts for genetic studies based on a mutant virus, we can now express more than 10 genes of up to 13.5 kilo nucleotides in a single vector with high protein expression efficiency. To prove this benefit, we examined the efficacy of the novel ribonucleic acid (RNA) virus vector harboring the human iduronate-2-sulfatase (IDS) gene with 1,653 base pairs, a causative gene for mucopolysaccharidosis type II, also known as a disorder of lysosomal storage disorders. As expected, this novel RNA vector with the human IDS gene exhibited its marked expression as determined by the expression of enhanced green fluorescent protein and IDS enzyme activity. While these cells exhibited a normal growth rate, the BHK-21 transformant cells stably expressing the human IDS gene persistently generated an active human IDS enzyme extracellularly. The human IDS protein produced failed to be incorporated into the lysosome when cells were pretreated with mannose-6-phosphate, demonstrating that this human IDS enzyme has potential for therapeutic use by cross-correction. These results suggest that our novel RNA vector may be applicable for further clinical settings., (© 2021 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)