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Background/aim: The aim of the study was to develop a novel predictive scoring system based on the dynamics of serum inflammatory indicators in immune checkpoint inhibitor (ICI) treatment on non-small-cell lung cancer (NSCLC) with bone metastases., Patients and Methods: Sixty patients with NSCLC and bone metastases treated with ICIs between January 2016 and March 2021 were included in the development cohort. Serum neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels were assessed before (pre-value) and 6 weeks after (post-value) ICI treatment, and a novel predictive score was developed: pre-value ≥ post-value, 0 points; pre-value < post-value, 1 point; total score: 0-2 points. The associations of these dynamics and the score with clinical outcomes, including overall survival (OS), progression-free survival (PFS), response rate (RR) of bone metastases, and disease control rate (DCR), were evaluated. Furthermore, cross-validation was performed with 23 patients after April 2021 using the same inclusion criteria., Results: The patients with decreased serum inflammation levels had significantly better OS, PFS, and RR than those with increased levels. Applying the developed score to the development cohort, the patients with 0 points had significantly better OS, PFS, and RR than others. In multivariable analysis, the score independently predicted treatment response to ICI for bone metastasis and prognosis. Cross-validation showed that OS, PFS, and RR were significantly better in the patients in the 0-point group., Conclusion: The early NLR and CRP dynamics were associated with therapeutic responses to ICIs in NSCLC with bone metastases. Our novel scoring system based on these dynamics is simple and has a high predictive accuracy., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Myxoid pleomorphic liposarcoma (MPLS) is an extremely rare tumor listed in the fifth edition of the WHO classification (2020). Histologically, it mainly comprises a mixture of myxoid and pleomorphic liposarcoma-like components. Genetically, it lacks FUS/EWSR1::DDIT3 fusion and MDM2 amplification. Herein, we describe an example of MPLS with rhabdoid cells in a 10-year-old girl who presented with a growing mass in the right inguinal region. The specimen from the wide excision measured 68 mm × 55 mm × 43 mm, and a circumscribed and lobulated mass was observed in the subcutaneous tissue. Histologically, oval-to-short, spindle-shaped, proliferating tumor cells with moderate nuclear atypia and mesh-like capillaries against a myxoid background were noted. Adipocytes were observed focally, while rhabdoid cells were observed multifocally. Immunohistochemically, the tumor showed inconsistent reactivity for desmin but was negative for MYOD1, myogenin, MDM2, and CDK4. Fluorescence in situ hybridization revealed no DDIT3 rearrangement. Despite adjuvant chemotherapy, the tumor metastasized to the thoracic cavity 24 months after excision. The metastatic lesions contained abundant lipoblasts rather than rhabdoid cells, and we concluded this tumor was a MPLS. The presence of rhabdoid cells could be a diagnostic pitfall, and recognizing such a variation in histology would help improve diagnostic accuracy., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Interleukin-17 (IL-17) is elevated in human inflammatory and autoimmune diseases. The polymorphism in the promoter region of the IL-17 A gene is associated with susceptibility to several inflammatory diseases, including acute graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation from adult donors. However, the impacts of IL-17 A polymorphism on cord blood transplantation (CBT) outcomes remain unclear., Objective: The objective of this study was to assess the impact of IL-17 A polymorphism rs2275913 on GVHD, survival, relapse, non-relapse mortality (NRM), and hematopoietic recovery after CBT., Study Design: We conducted a retrospective analysis of data from adult patients who underwent single-unit CBT at our institution from January 2005 to March 2023 for whose recipient or donor DNA samples were available. IL-17 A genotyping was performed using real-time polymerase chain reaction with the TaqMan® SNP genotyping assay for rs2275913., Results: A total of 158 recipients and 136 donors were evaluated in this study. Multivariate analysis showed that rs2275913 GA or AA recipients were associated with increased risk of grades II to IV acute GVHD compared to GG recipients (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.00-2.13; P = 0.047). Serum IL-17 A levels at eight weeks were significantly higher in rs2275913 GA or AA recipients compared to GG. The rs2275913 polymorphism did not affect survival, relapse, NRM, or hematopoietic recovery after single-unit CBT., Conclusion: Our data showed recipient IL-17 A polymorphism rs2275913 was associated with the risk of grade II to IV acute GVHD in adults undergoing single-unit CBT. However, the rs2275913 polymorphism in recipients and donors did not affect survival or relapse. Thus, the polymorphism of IL-17 A rs2275913 in recipients might predict the risk of acute GVHD after single-unit CBT., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Hypomethylating agent treatment for myeloid leukemia associated with Down syndrome (ML-DS) has been scarcely reported. Herein, we collected information on azacitidine treatment for ML-DS in Japan. Forty-eight cycles of azacitidine treatment were performed for 12 patients, including 11 relapsed or refractory (R/R) patients. In 40 cycles, azacitidine was used as monotherapy. No azacitidine-related death was observed. One cycle concurrently administered with methotrexate-based intrathecal therapy was discontinued due to toxicities. Only 4 of the 19 cycles given in non-remission achieved complete or partial remission. In conclusion, although most toxicities were acceptable, azacitidine monotherapy might be insufficient for R/R ML-DS cases., (© 2024 Wiley Periodicals LLC.)

Physical parameters such as tissue interplay forces, luminal pressure, fluid flow, temperature, and electric fields are crucial regulators of embryonic morphogenesis. While significant attention has been given to cellular and molecular responses to these physical parameters, their roles in morphogenesis are not yet fully elucidated. This is largely due to a shortage of methods for spatiotemporal modulation and direct quantitative perturbation of physical parameters in embryos. Recent advancements addressing these challenges include microscopes equipped with devices to apply and adjust forces, direct perturbation of luminal pressure, and the application of micro-forces to targeted cells and cilia in vivo. These methods are critical for unveiling morphogenesis mechanisms, highlighting the importance of integrating molecular and physical approaches for a comprehensive understanding of morphogenesis., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The flexibility to adjust actions and attitudes in response to varying social situations is a fundamental aspect of adaptive social behavior. Adaptive social behaviors influence an individual's vulnerability to social stress. While oxytocin has been proposed to facilitate active coping behaviors during social stress, the exact mechanisms remain unknown., Methods: By using a social defeat stress paradigm in male mice, we identified the distribution of oxytocin receptor (OXTR)-expressing neurons in the ventrolateral part of the ventromedial hypothalamus (vlVMH) that are activated during stress by detection of c-Fos protein expression. We then investigated the role of vlVMH OXTR-expressing neurons in social defeat stress responses by chemogenetic methods or deletion of local OXTRs. The social defeat posture was measured for quantification of adaptive social behavior during repeated social stress., Results: Social defeat stress activated OXTR-expressing neurons rather than estrogen type 1-expressing neurons in the rostral vlVMH. OXTR-expressing neurons in the vlVMH were glutamatergic. Chemogenetic activation of vlVMH OXTR-expressing neurons facilitated exhibition of the social defeat posture during exposure to social stress, while local OXTR deletion suppressed it. In contrast, over-activation of vlVMH-OXTR neurons induced generalized social avoidance after exposure to chronic social defeat stress. Neural circuits for the social defeat posture centered on OXTR-expressing neurons were identified by viral tracers and c-Fos mapping., Conclusions: VlVMH OXTR-expressing neurons are a functionally unique population of neurons that promote an active coping behavior during social stress, but their excessive and repetitive activation under chronic social stress impairs subsequent social behavior., (Copyright © 2024. Published by Elsevier Inc.)

This study explores the challenge of differentiating autism spectrum (AS) from non-AS conditions in adolescents and adults, particularly considering the heterogeneity of AS and the limitations ofssss diagnostic tools like the ADOS-2. In response, we advocate a multidimensional approach and highlight lexicogrammatical analysis as a key component to improve diagnostic accuracy. From a corpus of spoken language we developed, interviews and story-recounting texts were extracted for 64 individuals diagnosed with AS and 71 non-AS individuals, all aged 14 and above. Utilizing machine learning techniques, we analyzed the lexicogrammatical choices in both interviews and story-recounting tasks. Our approach led to the formulation of two diagnostic models: the first based on annotated linguistic tags, and the second combining these tags with textual analysis. The combined model demonstrated high diagnostic effectiveness, achieving an accuracy of 80%, precision of 82%, sensitivity of 73%, and specificity of 87%. Notably, our analysis revealed that interview-based texts were more diagnostically effective than story-recounting texts. This underscores the altered social language use in individuals with AS, a csrucial aspect in distinguishing AS from non-AS conditions. Our findings demonstrate that lexicogrammatical analysis is a promising addition to traditional AS diagnostic methods. This approach suggests the possibility of using natural language processing to detect distinctive linguistic patterns in AS, aiming to enhance diagnostic accuracy for differentiating AS from non-AS in adolescents and adults., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kato et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background Context: Growing evidence suggests that obesity is implicated in the progression of heterotopic ossification of the posterior longitudinal ligament of the spine (OPLL), a major cause of myelopathy in Asians. However, it remains unclear whether dysregulation of adipokine production due to fat accumulation contributes to OPLL progression., Purpose: To determine whether adipose-derived biochemical signals are associated with OPLL development or severity., Study Design/setting: A nationwide, multicenter, case-control study., Patient Sample: Patients with symptomatic thoracic OPLL (T-OPLL) who received treatment between June 2017 and March 2021 and 111 controls without OPLL., Outcome Measures: OPLL severity index based on whole-spine computed tomography., Methods: Serum concentrations of adipokines, including leptin (Lep), tumor necrosis factor α (TNFα), and adiponectin (Adpn), as well as the Adpn/Lep ratio-an indicator of adipokine production dysregulation-were compared between the multiple-region OPLL and the single-region OPLL groups. Regression analysis was performed to examine the correlation between adipokine concentrations and OPLL severity index, which was calculated using whole-spine computed tomography images of 77 patients with T-OPLL within 3 years of onset. Using propensity score matching, the adipokine profiles of 59 patients with T-OPLL were compared with those of 59 non-OPLL controls., Results: Patients with multiple-region OPLL exhibited a higher body mass index (BMI), lower serum Adpn/Lep ratio, and higher serum concentration of osteocalcin (OCN) than those with single-region OPLL. The OPLL severity index exhibited a weak positive correlation with BMI and serum Lep levels and a weak negative correlation with the Adpn/Lep ratio. Serum TNFα and OCN concentrations were significantly higher in patients with T-OPLL than in controls with similar age, sex, and BMI., Conclusions: Patients with diffuse OPLL over the entire spine are often metabolically obese with low Adpn/Lep ratios. In patients with OPLL, TNFα and OCN serum concentrations were essentially elevated regardless of obesity, suggesting a potential association with OPLL development. Considering the absence of therapeutic drugs for OPLL, the findings presented herein offer valuable insights that can aid in identifying therapeutic targets and formulating strategies to impede its progression., 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 Inc.)

The growing interest in high-efficiency solar energy technologies has driven research on multijunction solar cells to flourish over the last several years. This study sheds light on the optical, structural, and morphological aspects of the (CH 3 NH 3 ) 3 Bi 2 I 9 ((MA) 3 Bi 2 I 9 ) film by fabricating and analyzing it experimentally. This thorough investigation lays the groundwork for more research into the film's possible uses in solar cell technology. We performed simulations to enhance the efficiency of two-terminal (2T) perovskite/perovskite double junction and perovskite/perovskite/c-Si triple-junction solar cells (TJSC) by using the MA 3 Bi 2 I 9 material. The power conversion efficiency was greatly increased by using 2T triple-junction solar cells; the increase was around 116.59% from single junction (13.80-29.89%) and 31.91% from double junction (22.66-29.89%). As far as we know, this is the first investigation of the efficacy of MA 3 Bi 2 I 9 as a top layer in multijunction tandem configurations. This revolutionary approach allows both academics and industry experts to produce cost-effective and efficient tandem solar cells, thereby enhancing earth-based solar energy development.

A novel bacterium, designated as strain LOR1-02 T and isolated from a lichen sample collected from Kham Riang Subdistrict, Kantharawichai District, Maha Sarakham Province, Thailand, underwent thorough investigation utilizing a polyphasic taxonomic approach. Strain LOR1-02 T demonstrated growth within a temperature range of 20-42 °C (optimal at 30 °C), pH range of 5.0-7.5 (optimal at pH 7.0), and tolerance to 4.0% (w/v) NaCl. Phylogenetic analysis revealed its close relation to Paracraurococcus ruber JCM 9931 T , with a 16S rRNA gene sequence similarity of 97.16%, placing it within the genus Paracraurococcus. The approximate genome size of strain LOR1-02 T was determined to be 8.6 Mb, with a G + C content of 70.9 mol%. Additionally, ANIb, ANIm, and AAI values between the whole genomes of strain LOR1-02 T and type strains were calculated as 82.6-83.4%, 86.1-86.8%, and 81.4-82.2%, respectively, while the dDDH value was determined to be 26.3-28.5% (C.I. 24.0-31.0%). The predominant fatty acids detected were C 18:1 ω7c and/or C 18:1 ω6c, C 16:0 , and C 18:1 2OH. The major ubiquinone identified was Q-10, and the polar lipids included phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, diphosphatidylglycerol, along with unidentified phosphoaminolipid, lipids, and an amino lipid. Based on comprehensive phenotypic, chemotaxonomic, and genotypic characterization, it is concluded that strain LOR1-02 T represents a novel species within the genus Paracraurococcus, for which the name Paracraurococcus lichenis sp. nov. is proposed. The type strain designation is LOR1-02 T (= JCM 33121 T  = NBRC 112776 T = TISTR 2503 T )., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The roasting process of sesame oil is expected to alter its internal composition and stability under oxidation condition. Presumably, the effect of roasting may differ with oxidation conditions (i.e., thermal and photo-oxidation), but such studies have not been undertaken. To further evaluate this notion, several type of sesame oils (raw and refined as unroasted oil, and roasted oil) and rapeseed oils as comparison were subjected to thermal oxidation (120℃) and photo-oxidation (50,000 lx) for 5 and 10 hours. The result revealed that the roasting sesame oil exhibited good stability under thermal oxidation, possibly due to the change on antioxidant agents such as sesamol and Maillard products during the roasting process. In contrast, the refined sesame oil (unroasted) demonstrated high stability under photo-oxidation, indicating that the refining process has a more significant impact on the oxidative stability in sesame oil compared to the alterations in its components caused by the roasting process. Taken together, this study is the first to show that the roasting and refining processes of sesame oil alter its internal composition and show different variations in sesame oils' oxidative stability under thermal and photo-oxidation, which holds significance considering its global consumption.

We recently reported a method for recovering and quantifying residual proteins bound to surfaces of various medical instruments via thermal coagulation under neutral pH and room temperature. The method effectively recovered and solubilised coagulated proteins at high temperatures in dry and humid conditions, with a protein recovery rate of > 90%. This study validated the previous method by comparing residual protein recovery from test samples using a conventional extraction solution (1% SDS, [pH 11.0]) and proposed solution (1% SDS, 10 mM TCEP, and 10 mM HEPES [pH 7.0]). To mimic soiled medical equipment, pseudo-blood-contaminated stainless steel plates were prepared. Residual protein was recovered using conventional and proposed solutions under varying temperature and humidity conditions. Quantitative protein recovery limits were determined at nine facilities. Compared with the conventional solution, the proposed solution recovered proteins more effectively from samples processed at temperatures > 60 °C. However, low recovery rates were observed for samples processed at 95 °C, possibly owing to differences in protein adhesion due to sample and plate-surface properties. Our findings present a method for quantifying residual proteins on medical instruments exposed to high temperatures during use or disinfection. Further studies should standardise test soiling conditions, materials, and solutions to evaluate cleaning methods., (© 2024. The Author(s).)

Members of the kingdom Nanobdellati , previously known as DPANN archaea, are characterized by ultrasmall cell sizes and reduced genomes. They primarily thrive through ectosymbiotic interactions with specific hosts in diverse environments. Recent successful cultivations have emphasized the importance of adhesion to host cells for understanding the ecophysiology of Nanobdellati . Cell adhesion is often mediated by cell surface carbohydrates, and in archaea, this may be facilitated by the glycosylated S-layer protein that typically coats their cell surface. In this study, we conducted glycoproteomic analyses on two co-cultures of Nanobdellati with their host archaea, as well as on pure cultures of both host and non-host archaea. Nanobdellati exhibited various glycoproteins, including archaellins and hypothetical proteins, with glycans that were structurally distinct from those of their hosts. This indicated that Nanobdellati autonomously synthesize their glycans for protein modifications probably using host-derived substrates, despite the high energy cost. Glycan modifications on Nanobdellati proteins consistently occurred on asparagine residues within the N-X-S/T sequon, consistent with patterns observed across archaea, bacteria, and eukaryotes. In both host and non-host archaea, S-layer proteins were commonly modified with hexose, N -acetylhexosamine, and sulfonated deoxyhexose. However, the N -glycan structures of host archaea, characterized by distinct sugars such as deoxyhexose, nonulosonate sugar, and pentose at the nonreducing ends, were implicated in enabling Nanobdellati to differentiate between host and non-host cells. Interestingly, the specific sugar, xylose, was eliminated from the N -glycan in a host archaeon when co-cultured with Nanobdella . These findings enhance our understanding of the role of protein glycosylation in archaeal interactions.IMPORTANCE Nanobdellati archaea, formerly known as DPANN, are phylogenetically diverse, widely distributed, and obligately ectosymbiotic. The molecular mechanisms by which Nanobdellati recognize and adhere to their specific hosts remain largely unexplored. Protein glycosylation, a fundamental biological mechanism observed across all domains of life, is often crucial for various cell-cell interactions. This study provides the first insights into the glycoproteome of Nanobdellati and their host and non-host archaea. We discovered that Nanobdellati autonomously synthesize glycans for protein modifications, probably utilizing substrates derived from their hosts. Additionally, we identified distinctive glycosylation patterns that suggest mechanisms through which Nanobdellati differentiate between host and non-host cells. This research significantly advances our understanding of the molecular basis of microbial interactions in extreme environments., Competing Interests: The authors declare no conflict of interest.

In vivo imaging of bacterial infection models enables noninvasive and temporal analysis of individuals, enhancing our understanding of infectious disease pathogenesis. Conventional in vivo imaging methods for bacterial infection models involve the insertion of the bacterial luciferase LuxCDABE into the bacterial genome, followed by imaging using an expensive ultrasensitive charge-coupled device (CCD) camera. However, issues such as limited light penetration into the body and lack of versatility have been encountered. We focused on near-infrared (NIR) light, which penetrates the body effectively, and attempted to establish an in vivo imaging method to evaluate the number of lung-colonizing bacteria during the course of bacterial pneumonia. This was achieved by employing a novel versatile system that combines plasmid-expressing firefly luciferase bacteria, NIR substrate, and an inexpensive, scientific complementary metal-oxide semiconductor (sCMOS) camera. The D-luciferin derivative "TokeOni," capable of emitting NIR bioluminescence, was utilized in a mouse lung infection model of Acinetobacter baumannii , an opportunistic pathogen that causes pneumonia and is a concern due to drug resistance. TokeOni exhibited the highest sensitivity in detecting bacteria colonizing the mouse lungs compared with other detection systems such as LuxCDABE, enabling the monitoring of changes in bacterial numbers over time and the assessment of antimicrobial agent efficacy. Additionally, it was effective in detecting A. baumannii clinical isolates and Klebsiella pneumoniae . The results of this study are expected to be used in the analysis of animal models of infectious diseases for assessing the efficacy of therapeutic agents and understanding disease pathogenesis., Importance: Conventional animal models of infectious diseases have traditionally relied upon average assessments involving numerous individuals, meaning they do not directly reflect changes in the pathology of an individual. Moreover, in recent years, ethical concerns have resulted in the demand to reduce the number of animals used in such models. Although in vivo imaging offers an effective approach for longitudinally evaluating the pathogenesis of infectious diseases in individual animals, a standardized method has not yet been established. To our knowledge, this study is the first to develop a highly versatile in vivo pulmonary bacterial quantification system utilizing near-infrared luminescence, plasmid-mediated expression of firefly luciferase in bacteria, and a scientific complementary metal-oxide semiconductor camera. Our research holds promise as a useful tool for assessing the efficacy of therapeutic drugs and pathogenesis of infectious diseases.

Background: Although involvement of toddlers in swimming activities has increased recently, information regarding the impact of swimming during toddlerhood on subsequent child motor competence development is scarce. This study aimed to determine how swimming experience, particularly the timing of initiation and the continuity of swimming activities up to the age of 3 years, affects motor competence development., Methods: This prospective cohort study included data on children aged 1.5 and 3 years (100,286 mother-child pairs) from the Japan Environment and Children's Study. The outcomes measured were gross and fine motor function, using the Japanese version of the Ages and Stages Questionnaire (Third edition). We assessed how these functions correlated with the continuous pattern of swimming pool use frequency from age 1 up to 3 years., Results: The group that used a swimming pool once a month or more from age 1-1.5 years but stopped from age 2-3 years showed consistently significant negative associations with gross motor development delay (minimum adjusted odds ratio [aOR]: 0.66, 95% confidence interval [CI]: 0.60-0.73) and fine motor development delay (minimum aOR: 0.66, 95% CI: 0.58-0.76). The group that continued swimming once a month or more from age 1-3 years showed consistently significant negative associations with gross motor development delay (minimum aOR: 0.64, 95% CI: 0.54-0.75) and fine motor development delay (minimum aOR: 0.42, 95% CI: 0.31-0.55)., Conclusions: These results suggest that swimming experience starting around age 1 year is positively associated with gross and fine motor function development. The beneficial impact on gross motor function persisted from age 1-3 years. In contrast, the effects on fine motor function were not evident until age ≥ 2.5 years after starting swimming at approximately age 1 year. These findings underscore the potential benefits of early swimming experiences in enhancing overall motor skills development during early childhood., (© 2024. The Author(s).)

Mobocertinib (formerly known as TAK-788) is a targeted covalent tyrosine kinase inhibitor of epidermal growth factor receptor with exon 20 insertion mutations. This article describes the metabolism and excretion of mobocertinib in healthy male subjects after a single oral administration of [ 14 C]mobocertinib. Mobocertinib-related materials were highly covalently bound to plasma proteins such as human serum albumin. The mean extraction recovery of total radioactivity was only 3.9% for six individual Hamilton pooled plasma samples. After extraction, mobocertinib was the most abundant component accounting for 7.7% of total extracted circulating radioactivity (TECRA) in the supernatant. Each of identified metabolites accounted for <10% of TECRA. Mobocertinib underwent extensive first-pass metabolism with the fraction of the dose absorbed estimated to be approximately 91.7%. Fecal excretion of mobocertinib metabolites was the major elimination route. Mobocertinib was mainly eliminated via oxidative metabolism with a fraction of approximately 88% metabolized by CYP3A4/5. The other minor elimination pathways included cysteine conjugation, metabolism by other cytochrome P450s, and renal excretion of unchanged mobocertinib. SIGNIFICANCE STATEMENT: This article describes the metabolism and excretion of a targeted covalent inhibitor mobocertinib in humans after a single oral administration of [ 14 C]mobocertinib. Mobocertinib was highly covalently bound to human plasma proteins. No metabolite accounted for >10% of total extracted circulating radioactivity in human plasma. Mobocertinib was mainly eliminated via CYP3A4/5 mediated oxidative metabolism followed by fecal excretion after approximately 91.7% of the dose was absorbed., (Copyright © 2024 by The Author(s).)

Background: The standard treatment for patients in good general condition with limited-disease small cell lung cancer (LD-SCLC) is concurrent platinum/etoposide chemotherapy and thoracic radiotherapy (TRT). However, the efficacy and safety of chemoradiotherapy (CRT) in older patients with LD-SCLC has not been fully explored; moreover, the optimal treatment for this patient group remains unclear. This study aimed to investigate the feasibility and efficacy of CRT in older patients with LD-SCLC., Patients and Methods: From April 2007 to June 2021, consecutive older patients (aged ≥ 75 years) with stage I to III SCLC who received concurrent or sequential CRT at two institutions were retrospectively evaluated for efficacy and toxicity of CRT., Results: A total of 32 older patients underwent concurrent (n = 19) or sequential (n = 13) CRT for LD-SCLC. The median ages of the patients in the concurrent and sequential CRT groups were 77 (range: 75-81) years and 79 (range: 76-92) years, respectively. The median number of chemotherapeutic treatment cycles was four (range, 1-5), and the response rate was 96.9% in all patients (94.7% in concurrent and 100% in sequential CRT groups). The median progression-free survival (PFS) and median overall survival (OS) for all patients were 11.9 and 21.1 months, respectively. The median PFS was 13.0 and 9.0 months in the concurrent CRT and sequential CRT groups, respectively, with no statistically significant difference ( p = 0.67). The median OS from the initiation of CRT was 19.2 and 23.5 months in the concurrent and sequential CRT groups, respectively ( p = 0.46). The frequencies of Grade ≥ 3 hematological adverse events were as follows: decreased white blood cell count, 20/32 (62.5%); decreased neutrophil count, 23/32 (71.9%); anemia, 6/32 (18.8%); decreased platelet count, 7/32 (21.9%); and febrile neutropenia, 3/32 (9.4%). Treatment-related deaths occurred in one patient from each group., Conclusions: Although hematological toxicities, particularly reduced neutrophil count, were severe, CRT showed favorable efficacy in both concurrent and sequential CRT groups. However, concurrent CRT may not be feasible for all older patients with LD-SCLC; accordingly, sequential CRT may be considered as a treatment of choice for these patients. Further prospective trials are warranted to identify optimal treatment strategies for this patient group., (© 2024 Ayako Shiono et al., published by Sciendo.)

Cord blood transplantation (CBT) presents unique challenges related to inflammation during neutropenia, such as mucosal damage, infections, and the potential development of pre-engraftment syndrome or pre-engraftment immune reaction. These factors can contribute to significant inflammation and infection shortly after CBT. However, the effect of severe inflammation during neutropenia, specifically elevated C-reactive protein (CRP) level and body temperature, on post-transplant outcomes after CBT remains unclear. This retrospective study aimed to investigate the association between maximum CRP level, maximum body temperature during neutropenia, and post-transplantation outcomes in adult patients undergoing single-unit CBT. We retrospectively evaluated the impact of maximum CRP level and maximum body temperature during neutropenia on post-transplantation outcomes in adults who underwent single-unit unrelated CBT between 1998 and 2023 at our institution. A total of 336 adult patients were included in this study. The median maximum CRP level before neutrophil recovery was 7.75 mg/dL (interquartile range [IQR], 4.70 to 12.05 mg/dL) at a median of 14 d (IQR, 8 to 16 d). The median maximum body temperature before neutrophil recovery was 39.5°C (IQR, 39.0 to 40.0°C) at a median of 15 d (IQR, 12 to 17 d). In the multivariate analysis, a maximum CRP level≥20 mg/dL was significantly associated with lower neutrophil recovery (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.23 to 0.59; P < .001), lower platelet recovery (HR, 0.28; 95% CI, 0.16 to 0.48; P < .001), and a higher incidence of veno-occlusive disease/sinusoidal obstruction syndrome (HR, 16.42; 95% CI, 4.11 to 65.54; P < .001), which resulted in higher non-relapse mortality (NRM) (HR, 5.16; 95% CI, 2.62 to 10.15; P < .001) and worse overall survival (HR, 2.81; 95% CI, 1.66 to 4.78; P < .001). Similarly, a maximum body temperature≥40.5°C was significantly associated with lower neutrophil recovery (HR, 0.51; 95% CI, 0.33 to 0.79; P = .002), lower platelet recovery (HR, 0.55; 95% CI, 0.38 to 0.79; P = .001), higher incidence of grades III to IV acute GVHD (HR, 2.93; 95% CI, 1.24 to 6.88; P = .013), and extensive chronic GVHD (HR, 2.47; 95% CI, 1.22 to 4.97; P = .011), which resulted in higher NRM (HR, 3.43; 95% CI, 1.53 to 7.67; P = .002). Maximum CRP level and maximum body temperature during neutropenia were significantly associated with lower hematopoietic recovery and higher NRM following single-unit CBT in adults. Further studies are warranted to explore early intervention strategies aimed at preventing severe inflammation and improving post-transplant outcomes in single-unit CBT., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Mutations of KRAS, CDKN2A, TP53, and SMAD4 are the four major driver genes for pancreatic ductal adenocarcinoma (PDAC), of which mutations of KRAS and TP53 are the most frequently recognized. However, molecular-targeted therapies for mutations of KRAS and TP53 have not yet been developed. To identify novel molecular targets, we newly established organoids with the Kras mutation (Kras mu OR) and Trp53 loss of function using Cre transduction and CRISPR/Cas9 (Kras mu /p53 mu OR) from murine epithelia of the pancreatic duct in Kras LSL-G12D mice, and then analyzed the proteomic and metabolomic profiles in both organoids by mass spectrometry. Hyperfunction of the glycolysis pathway was recognized in Kras mu /p53 mu OR compared with Kras mu OR. Loss of function of triosephosphate isomerase (TPI1), which is involved in glycolysis, induced a reduction of cell proliferation in human PDAC cell lines with the TP53 mutation, but not in PDAC or in human fibroblasts without TP53 mutation. The TP53 mutation is clinically recognized in 70% of patients with PDAC. In the present study, protein expression of TPI1 and nuclear accumulation of p53 were recognized in the same patients with PDAC. TPI1 is a potential candidate therapeutic target for PDAC with the TP53 mutation., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Pulmonary high-grade neuroendocrine carcinomas (HGNECs) have poor prognoses and require multimodal treatment, and interstitial lung disease (ILD) restricts sufficient treatment of patients with lung cancer. We aimed to clarify ILD's prognostic impact on pulmonary HGNEC, which has previously gone unreported. We retrospectively analyzed 53 patients with HGNEC who underwent resections at our department between 2006 and 2021 and evaluated the clinicopathological prognostic features, including ILD. The patients' mean age was 70 years; 46 (87%) were male, and all were smokers. Large-cell neuroendocrine and small-cell lung carcinomas were diagnosed in 36 (68%) and 17 (32%) patients, respectively. The pathological stages were stage I, II, and III in 31 (58%), 11 (21%), and 11 (21%) patients, respectively. Nine patients (17%) had ILD, which was a significant overall survival prognostic factor in a multivariate Cox proportional hazards regression analysis (p = 0.048), along with lymph node metastasis (p = 0.004) and non-administration of platinum-based adjuvant chemotherapy (p = 0.003). The 5 year survival rate of the ILD patients was 0%, significantly worse than that of patients without ILD (58.7%; p = 0.003). Patients with HGNEC and ILD had a poor prognosis owing to adjuvant therapy's limited availability for recurrence and the development of acute exacerbations associated with ILD., (© 2024. The Author(s).)

Previously, we successfully introduced laeA gene into a fungal strain in order to significantly increase the production of a bioactive compound, allowing use to discover novel biological activity. To demonstrate the universal applicability of the laeA gene introduction strategy for taping the potential of fungal secondary metabolism, in this present study, we created a library of microorganisms which we had the laeA gene inserted, and from that library we aimed to isolate compounds which are produced at significantly greater quantities compared to the respective wild type strains. From this investigation, we were able to isolate sclerotinin A (1) from Pochonia sp. KTF-0504 strain. We revealed that 1 showed anti-malarial activity against Plasmodium falciparum parasite strains. On the other hands, 1 showed no anti-fungal activity against multidrug-sensitive budding yeast. Our study implies that the utilization of the laeA gene in fungi is a versatile method for the discovery of drug candidates., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Y.A., T.T., and K.I. are employees of Kikkoman Corporation. Kitasato University received research funding from Kikkoman Corporation., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Not available.

Background: Heated tobacco products (HTPs) have gained global popularity, but their health risks remain unclear. Therefore, the current study aimed to identify plasma metabolites associated with smoking and HTP use in a large Japanese population to improve health risk assessment., Methods: Metabolomics data from 9,922 baseline participants of the Tsuruoka Metabolomics Cohort Study (TMCS) were analyzed to determine the association between smoking habits and plasma metabolites. Moreover, alterations in smoking-related metabolites among HTP users were examined based on data obtained from 3,334 participants involved from April 2018 to June 2019 in a follow-up survey., Results: Our study revealed that cigarette smokers had metabolomics profiles distinct from never smokers, with 22 polar metabolites identified as candidate biomarkers for smoking. These biomarker profiles of HTP users were closer to those of cigarette smokers than those of never smokers. The concentration of glutamate was higher in cigarette smokers, and biomarkers involved in glutamate metabolism were also associated with cigarette smoking and HTP use. Network pathway analysis showed that smoking was associated with the glutamate pathway, which could lead to endothelial dysfunction and atherosclerosis of the vessels., Conclusion: Our study showed that the glutamate pathway is affected by habitual smoking. These changes in the glutamate pathway may partly explain the mechanism by which cigarette smoking causes cardiovascular disease. HTP use was also associated with glutamate metabolism, indicating that HTP use may contribute to the development of cardiovascular disease through mechanisms similar to those in cigarette use.

Background/aim: Transanal endoscopic local excision requires fine operation in a very narrow space in the rectum. We report a case in which the use of surgical instruments with a multi-jointed structure allowed safe resection of a lesion with a stable field of view, resulting in preservation of postoperative function., Case Report: The patient was a 49-year-old man who had a rectal neuroendocrine tumor (NET) (G1) with erosive changes in the lower rectum. Preoperative imaging showed no evidence of surrounding lymph node or distant metastasis; thus, we performed a transanal endoscopic local excision of the tumor. After positioning the patient under general anesthesia and securing the field of view in the intra-rectal cavity, the flexion of the surgical instruments with a multi-jointed structure was used to secure the operating space to not interfere with the camera and the surgeon's right hand. The operating field was developed, and the tumor was incised by stable traction. After the excision, the needle was advanced in the direction of the intestinal axis using the multi-jointed holder, and continuous suturing was performed. The patient has no recurrence without any defecation disorder., Conclusion: The use of multi-jointed surgical instruments in transanal endoscopic excision of rectal tumors can provide a stable operative field and preserve postoperative function. The advanced flexibility of these instruments allows precise manipulation in the narrow rectal space, resulting in successful tumor resection with minimal invasiveness and no postoperative complications. These findings suggest that multi-jointed instruments are valuable for enhancing the safety and efficacy of minimally invasive rectal surgery., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A prospective multicenter observational study of organ response was conducted in patients with chronic GVHD diagnosed by the NIH criteria. When response was assessed at 12 months (12 M) in 118 patients, 74.6% were classified as responders and 25.4% as non-responders. The skin and oral cavity were the most frequent organs used as the basis for determining overall response. The lungs, liver, and eyes were also used in 20% of patients. Non-response decisions at 12 M were most frequent in the lungs. A significantly higher percentage of responders than non-responders completed systemic treatment (24.3% vs. 3.3%, P = 0.02). Global scoring showed significant changes, with improvement in responders and worsening in non-responders throughout the observation period. Two-year transplant-related mortality, using the 12 M assessment as the landmark, was significantly worse in non-responders (28.5% vs. 2,7%, P = 0.0001), while the 2-year recurrence rate was equivalent (5.4% vs. 4.8%, P = 0.78). Consequently, the 2-year overall survival rate from the 12 M assessment was significantly better in responders than non-responders (95% vs. 65.3%, P = 0.0001). Our data suggests that patients who do not achieve a response within the first year should be candidates for clinical studies on chronic GVHD., (© 2024. Japanese Society of Hematology.)

SATB2 has been reported to be highly specific for lower gastrointestinal tract tumors. On the basis of its ileum-colon conversion effects, which involve the activation of colonic genes in cooperation with CDX2 and HNF4A, we hypothesized that SATB2 and CDX2 might define the characteristics of colorectal cancers (CRCs). In the present study, the clinicopathologic and immunohistochemical characteristics of 269 CRCs were analyzed according to SATB2 and CDX2 expression. CRCs with SATB2- and/or CDX2- phenotypes showed associations with poorly differentiated histotypes ( P <0.00001), mucus production ( P =0.0019), and mismatch repair-deficient phenotypes ( P <0.00001). SATB2-/CDX2- CRCs were significantly associated with CK20-negativity, with or without CK7 expression ( P <0.00001), as well as with MUC5AC-positivity ( P <0.00001), and CD10-negativity ( P =0.00047). Negativity for SATB2 or CDX2 was associated with the expression of PD-L1 in both all CRC ( P <0.00001) and mismatch repair-proficient CRC ( P =0.000091). Multivariate Cox hazard regression analysis identified negativity for SATB2 and/or CDX2 as potential independent risk factors for patients with CRC. Regarding the diagnostic utility of SATB2, all of the 44 CRC metastases could be diagnosed as colorectal in origin if the immunohistochemical phenotypes (including CK7, CK20, and p53) of the primary lesions and patient history were considered. Among the other 684 tumors, we were unable to distinguish a case of CK7-/CK20+/CDX2+/SATB2+ ovarian mucinous cystadenocarcinoma from metastatic CRC without the patient history and clinical information., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Hematopoietic stem cell transplants for inherited metabolic disorders performed at Tokai University Hospital between June 5, 1986, and May 28, 2021, were analyzed and compared between the period before 2007 and the period from 2007 onward based on availability of medical resources. Transplants were performed for 38 patients with mucopolysaccharidosis, 33 with adrenoleukodystrophy, and 16 with another disorder. Before 2007, oral busulfan-based regimens were mainly used. From 2007 onward, intravenous busulfan-based regimens or 4 Gy of thoracoabdominal irradiation (TAI), fludarabine, and melphalan (Mel)/treosulfan were adopted. Between 2002 and 2010, adrenoleukodystrophy was treated with 12 Gy of TAI and Mel. HLA-identical sibling bone marrow was used in 43% of cases before 2007 and 15% from 2007 onward, while alternative donors were selected for other transplants. Overall survival and event-free survival (EFS) before 2007 and from 2007 onward were 76% and 62%, and 97% and 85%, respectively (P = 0.006 and 0.017). Transplant era predicted superior overall survival and EFS, while myeloablative conditioning also predicted EFS. The incidence of primary graft failure decreased from 2007 onward, especially in cord blood transplant when 4 Gy of TAI with 150 mg/m 2 fludarabine and 180 mg/m 2 Mel or 42 g/m 2 treosulfan were used as conditioning., (© 2024. Japanese Society of Hematology.)

Immune checkpoint inhibitors have changed the treatment landscape for various malignancies; however, their benefit is limited to a subset of patients. The immune machinery includes both mediators of suppression/immune evasion, such as PD-1, PD-L1, CTLA-4, and LAG-3, all of which can be inhibited by specific antibodies, and immune-stimulatory molecules, such as T-cell co-stimulatory receptors that belong to the tumor necrosis factor receptor superfamily (TNFRSF), including OX40 receptor (CD134; TNFRSF4), 4-1BB (CD137; TNFRSF9), and glucocorticoid-induced TNFR-related (GITR) protein (CD357; TNFRSF18). In particular, OX40 and its binding ligand OX40L (CD134L; TNFSF4; CD252) are critical for immunoregulation. When OX40 on activated T cells binds OX40L on antigen-presenting cells, T-cell activation and immune stimulation are initiated via enhanced T-cell survival, proliferation and cytotoxicity, memory T-cell formation, and abrogation of regulatory T cell (Treg) immunosuppressive functions. OX40 agonists are in clinical trials both as monotherapy and in combination with other immunotherapy agents, in particular specific checkpoint inhibitors, for cancer treatment. To date, however, only a minority of patients respond. Transcriptomic profiling reveals that OX40 and OX40L expression vary between and within tumor types, and that only ~ 17% of cancer patients have high OX40 and low OX40L, one of the expression patterns that might be theoretically amenable to OX40 agonist enhancement. Taken together, the data suggest that the OX40/OX40L machinery is a critical part of the immune stimulatory system and that understanding endogenous expression patterns of these molecules and co-existing checkpoints merits further investigation in the context of a precision immunotherapy strategy for cancer therapy., (© 2024. The Author(s).)

Background: In shoulder surgery, low-virulence bacteria such as Cutibacterium acnes and coagulase-negative staphylococci can cause postoperative infection. However, the degree of sterility during surgery after disinfection is not known, and the efficacy of double skin preparation for such bacteria is unclear. This study aimed to evaluate chronological changes in the surgical field contamination rate in the shoulder joint and to compare single and double skin preparation., Methods: In total, 126 shoulders in 121 patients undergoing shoulder surgery (64 men, 62 women; mean age 64 years) were enrolled. Patients were divided into two groups: single skin preparation, where the site was painted with 10% povidone iodine, and double skin preparation, where the site was treated with 1% chlorhexidine gluconate/83% isopropyl alcohol and painted 10% povidone iodine. Swab samples from the axillary and proximal areas in the surgical field were collected chronologically before starting surgery and at 30, 60, and 120 min after starting surgery (MAS). The contamination rate of each sample was compared and detected species were evaluated., Results: The contamination rate for the axillary area was 48.4%, 85.9%, 95.3%, and 97.1% in the single-preparation group and 32.3%, 72.6%, 87.1%, and 91.2% in the double-preparation group before starting surgery and 30, 60, and 120 MAS, respectively, and that the proximal area was 12.5%, 26.6%, 29.7%, and 35.3% in the single-preparation group and 16.1%, 19.4%, 27.4%, and 38.2% in the double-preparation group, respectively. Significant differences were not seen between the groups by area or time point. Most detected species were Cutibacterium acnes and coagulase-negative staphylococci., Conclusions: The incidence of surgical field contamination in shoulder joint was high from immediately after starting surgery. In the axillary area, the contamination rates exceeded 70% from 30 MAS in both groups. Measures against infection should be instituted considering these findings when performing shoulder surgery., Competing Interests: Declaration of competing interest The authors declare no conflict of interest associated with this manuscript., (Copyright © 2023. Published by Elsevier B.V.)

Background: ChatGPT is an AI platform whose relevance in the peer review of scientific articles is steadily growing. Nonetheless, it has sparked debates over its potential biases and inaccuracies. This study aims to assess ChatGPT's ability to qualitatively emulate human reviewers in scientific research., Methods: We included the first submitted version of the latest twenty original research articles published by the 3rd of July 2023, in a high-profile medical journal. Each article underwent evaluation by a minimum of three human reviewers during the initial review stage. Subsequently, three researchers with medical backgrounds and expertise in manuscript revision, independently and qualitatively assessed the agreement between the peer reviews generated by ChatGPT version GPT-4 and the comments provided by human reviewers for these articles. The level of agreement was categorized into complete, partial, none, or contradictory., Results: 720 human reviewers' comments were assessed. There was a good agreement between the three assessors (Overall kappa >0.6). ChatGPT's comments demonstrated complete agreement in terms of quality and substance with 48 (6.7 %) human reviewers' comments, partially agreed with 92 (12.8 %), identifying issues necessitating further elaboration or recommending supplementary steps to address concerns, had no agreement with a significant 565 (78.5 %), and contradicted 15 (2.1 %). ChatGPT comments on methods had the lowest proportion of complete agreement (13 comments, 3.6 %), while general comments on the manuscript displayed the highest proportion of complete agreement (17 comments, 22.1 %)., Conclusion: ChatGPT version GPT-4 has a limited ability to emulate human reviewers within the peer review process of scientific research., Competing Interests: Declaration of competing interest Maximilian S. Schaefer received funding for investigator-initiated studies from Merck & Co., which do not pertain to this manuscript. He is an associate editor for BMC Anesthesiology. He received honoraria for presentations from Fisher & Paykel Healthcare and Mindray Medical International Limited and an unrestricted philantropic grant from Jeffrey and Judith Buzen. All other authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The fibrosis-4 (FIB-4) index is a noninvasive marker of liver fibrosis. The FIB-4 index predicts poor outcomes in patients with hepatic and non-hepatic diseases. However, the association of the FIB-4 index with mortality and liver-related clinical outcomes following cord blood transplantation (CBT) is unclear., Methods: We retrospectively evaluated the impact of the pretransplant FIB-4 index on outcomes in 336 adults following single-unit unrelated CBT at our institution., Results: In multivariate analyses, when the FIB-4 index &lt;1.3 group was used as the reference, non-relapse mortality was significantly higher in the FIB-4 index 1.3-2.67 (hazard ratio [HR], 2.51; 95% confidence interval [CI], 1.19-5.30) and FIB-4 index &gt;2.67 (HR, 2.34; 95% CI, 1.12-4.90) groups. Overall mortality was significantly higher in the FIB-4 index &gt;2.67 group (HR, 1.66; 95% CI, 1.00-2.73), but with only marginal significance in the FIB-4 index 1.3-2.67 group (HR, 1.59; 95% CI, 0.96-2.64). Hematopoietic recovery, acute and chronic graft-versus-host disease of the liver, and veno-occlusive disease/sinusoidal obstruction syndrome were not associated with the pretransplant FIB-4 index., Conclusion: The pretransplant FIB-4 index is accurate and useful in predicting mortality in adult patients undergoing single-unit unrelated CBT., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background and Aims: Urbanization-induced environmental changes affect the geographical distribution of natural plant species. This study focused on how polyploidization, a dynamic genome change, influences the survival and distribution of Commelina communis L. (Cc) and its subspecies, C. communis f. ciliata (Masam.) Murata (Ccfc) which have different chromosome numbers (e.g. Cc: 2n = 88, Ccfc: 2n = 46). The aim is to investigate polyploidization effects on natural plant distribution in urban environments., Methods: The geographical distribution across urban-rural gradients was investigated at a total of 218 sites in Japan. Stomata size and density were measured and compared between Cc and Ccfc. Flow cytometry determined genome size and polyploidy. Chromosome karyotyping was performed using genomic in situ hybridization (GISH) method., Key Results: Urban areas were exclusively dominated by Cc, while Cc and Ccfc coexisted in rural areas. Cc had larger and fewer stomata and more than twice the genome size than Ccfc. GISH results indicated that Cc possesses Ccfc and another unknown genome, suggesting allopolyploidy., Conclusions: Our results show that the ploidy difference affects the geographical distribution, the stomata traits, and genome size between two distinct taxa in the genus Commelina, C. communis as a neo-tetraploid and C. communis f. ciliata, the diploid. Cc is an allopolyploid, therefore, not only polyploidy but also an additional genome with new sets of genes and alleles contributes to Cc having enhance survival potentials in urban environments compared to Ccfc. This is the first investigation to clarify the distribution difference related to urban environments, the difference in stomata traits and genome size, and to conduct chromosome composition in Commelina species., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: This prospective multicenter study assessed the prevalence of myocardial injury in patients with COVID-19 using cardiac magnetic resonance imaging (CMR)., Methods and Results: We prospectively screened 505 patients with moderate to severe COVID-19 disease from 7 hospitals in Japan. Of these patients, 31 (mean [±SD] age 63.5±10.4 years, 23 [74%] male) suspected of myocardial injury, based on elevated serum troponin or B-type natriuretic peptide concentrations either upon admission or 3 months after discharge, underwent CMR 3 months after discharge. The primary endpoint was the presence of myocardial injury, defined by any of the following: (1) contrast enhancement in the left or right ventricle myocardium on late gadolinium enhancement CMR; (2) left or right ventricular dysfunction (defined as <50% and <45%, respectively); and (3) pericardial thickening on contrast enhancement. The mean (±SD) duration between diagnosis and CMR was 117±16 days. The primary endpoint was observed in 13 of 31 individuals (42%), with 8 (26%) satisfying the modified Lake Louise Criteria for the diagnosis of acute myocarditis., Conclusions: This study revealed a high incidence of myocardial injury identified by CMR in patients with moderate to severe COVID-19 and abnormal findings for cardiac biomarkers.

Postoperative complications related to anastomosis, including postoperative anastomotic bleeding and anastomotic leakage, remain a serious issue. The effect of anastomotic devices on suture complications during intestinal anastomosis remains unclear. The present study examined the utility of automated anastomotic devices for reducing anastomotic complication risks. A retrospective cohort study of colorectal cancer surgeries in which an anastomosis device was used at Osaka University Hospital (Suita, Japan) between January 2018 and December 2022 was conducted. Cases of emergency surgery, inflammatory bowel disease and simultaneous surgery for other cancers were excluded. Experienced gastrointestinal surgeons performed manual anastomosis using the ETHICON Circular Stapler CDH or EEA Circular Stapler, and automatic anastomosis using the ECHELON CIRCULAR Powered Stapler, with no observed operator bias. Additionally, a meta-analysis that included other study results was performed. The outcomes included postoperative complications, mainly anastomotic leakage. The study included 414 patients: 183 in the manual circular stapler group and 231 in the powered circular stapler (PCS) group. Although this retrospective study found no statistically significant association between the anastomotic device used and anastomotic complications, an increased risk ratio was observed in the manual group compared with the automatic group when restricted to elderly patients. Similarly, a meta-analysis found a significantly higher anastomotic complication risk in the manual group compared with the automatic group (random-effects model; odds ratio, 0.376; 95% confidence interval, 0.232-0.610; P<0.0001). The findings of the present study suggested that a PCS is useful for reducing the anastomotic complication risk in patients undergoing colorectal cancer surgery., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Mizumoto et al.)

Background: Anterior knee pain due to patellar maltracking following total knee arthroplasty (TKA) reduces patients' satisfaction. This study aimed to determine the patellofemoral pressure (PFP) in patients with favorable patellar tracking (FT) and impaired patellar tracking (IT) following TKA, the factors causing patellar maltracking, and the effect of lateral retinacular release (LRR) on patients with IT., Methods: Forty-four patients with varus knee osteoarthritis undergoing cruciate-retaining TKA were enrolled. After component implantation, patients with a separation of ≥ 2 mm of the patellar medial facet from the medial femoral trochlea throughout knee range of motion were classified into the IT group; meanwhile, the others were classified into the FT group. PFP was measured intraoperatively in three phases: (1) with the resurfaced patella (RP); (2) with the resurfaced patella and knee (RPK); and (3) when LRR was performed in IT (post-LRR). The PFPs at 0°, 90°, 120°, and 135° knee flexion were compared between FT and IT using the Mann-Whitney U test. Pairwise comparison of the PFP in IT between RPK and post-LRR was performed using the Wilcoxon signed-rank test. Correlations between PFP and pre- and postoperative radiographic parameters, such as hip-knee-ankle angle, lateral distal femoral angle, medial proximal tibial angle, anterior femoral offset, Insall-Salvati ratio (ISR), patellar tilt, and patellar resection angle (PRA), were evaluated using Spearman's rank correlation coefficients., Results: High lateral PFP in the knee flexion position led to patellar maltracking. Patients with IT (n = 24) had higher lateral and lower medial PFP than did patients with FT (n = 20) at 90°, 120°, and 135° knee flexion in RP and RPK. LRR in IT reduced the lateral PFP in the knee flexion position. PRA and ISR were correlated with the lateral PFP at no less than 90° in RP and RPK., Conclusions: This study demonstrated that internal rotational patellar resection, which resulted in a thick medial patellar remnant and a thin lateral counterpart, and patella alta were the causative factors of high lateral PFP, which induced patellar maltracking after TKA. Surgeons should avoid internal rotational patellar resection to achieve FT and perform LRR in patients with patellar maltracking., (© 2024. The Author(s).)

The vitamin D receptor (VDR) plays a critical role in the regulation of mineral and bone homeostasis. Upon binding of 1α,25-dihydroxyvitamin D 3 to the VDR, the activation function 2 (AF2) domain repositions and recruits coactivators for the assembly of the transcriptional machinery required for gene transcription. In contrast to coactivator-induced transcriptional activation, the functional effects of coactivator-independent VDR signaling remain unclear. In humans, mutations in the AF2 domain are associated with hereditary vitamin D-resistant rickets, a genetic disorder characterized by impaired bone mineralization and growth. In the present study, we used mice with a systemic or conditional deletion of the VDR-AF2 domain (Vdr ΔAF2 ) to study coactivator-independent VDR signaling. We confirm that ligand-induced transcriptional activation was disabled because the mutant VDR ΔAF2 protein was unable to interact with coactivators. Systemic Vdr ΔAF2 mice developed short, undermineralized bones with dysmorphic growth plates, a bone phenotype that was more pronounced than that of systemic Vdr knockout (Vdr -/- ) mice. Interestingly, a rescue diet that is high in calcium, phosphate, and lactose, normalized this phenotype in Vdr -/- , but not in Vdr ΔAF2 mice. However, osteoblast- and osteoclast-specific Vdr ΔAF2 mice did not recapitulate this bone phenotype indicating coactivator-independent VDR effects are more important in other organs. In addition, RNA-sequencing analysis of duodenum and kidney revealed a decreased expression of VDR target genes in systemic Vdr ΔAF2 mice, which was not observed in Vdr -/- mice. These genes could provide new insights in the compensatory (re)absorption of minerals that are crucial for bone homeostasis. In summary, coactivator-independent VDR effects contribute to mineral and bone homeostasis., (© 2024. The Author(s).)

Purpose: As long-term survival improves after allogeneic hematopoietic stem cell transplantation (HSCT), the risk for secondary solid cancers, including colon cancer, also increases. However, the pathogenesis of secondary solid cancers in post-HSCT patients remains unclear. This study aimed to investigate the involvement of local immunity in colon carcinogenesis in post-HSCT patients by assessing the infiltrating T cells in colon adenomas as premalignant lesions of colon cancer in adenoma-carcinoma sequence., Methods: Colon adenoma samples obtained from 19 post-HSCT patients and 57 non-HSCT participants were analyzed via immunohistochemistry. Double staining of CD4/T-bet, CD4/GATA3, and CD4/FoxP3 was performed for evaluation of helper T-cell lineages (Th1, Th2, and regulatory T cells, respectively) and CD8 staining for CD8 + T cells., Results: There were no significant between-group differences in the number of infiltrating CD4 + T cells and CD8 + T cells in adenomas. However, the number of both CD4 + /T-bet + and CD4 + /GATA3 + T cells was significantly lower in the post-HSCT adenomas than in the non-HSCT adenomas (P = 0.0171 and 0.0009, respectively), whereas no significant differences were found in the number of CD4 + /FoxP3 + cells., Conclusion: Although the number of infiltrating CD4 + and CD8 + T cells, and even Treg cell counts, is sufficiently recovered post-HSCT, CD4 + T-cell dysfunction due to suppressed activation and differentiation in colon adenomas might be involved in colon carcinogenesis in post-HSCT patients. Elucidating the pathogenesis will contribute to the development of effective screening and prevention programs for secondary colon cancer in post-HSCT patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The usefulness of monitoring treatment effect of tafamidis using magnetic resonance imaging (MRI) extracellular volume fraction (ECV) has been reported., Objective: we conducted a meta-analysis to evaluate the usefulness of this method., Methods: Data from 246 ATTR-CMs from six studies were extracted and included in the analysis. An inverse variance meta-analysis using a random effects model was performed to evaluate the change in MRI-ECV before and after tafamidis treatment. The analysis was also performed by classifying the patients into ATTR-CM types (wild-type or hereditary)., Results: ECV change before and after tafamidis treatment was 0.33% (95% CI: -1.83-2.49, I 2 = 0%, p = 0.76 for heterogeneity) in the treatment group and 4.23% (95% CI: 0.44-8.02, I 2 = 0%, p = 0.18 for heterogeneity) in the non-treatment group. The change in ECV before and after treatment was not significant in the treated group (p = 0.76), but there was a significant increase in the non-treated group (p = 0.03). There was no difference in the change in ECV between wild-type (95% CI: -2.65-3.40) and hereditary-type (95% CI: -9.28-4.28) (p = 0.45)., Conclusions: The results of this meta-analysis suggest that MRI-ECV measurement is a useful imaging method for noninvasively evaluating the efficacy of tafamidis treatment for ATTR-CM.

Heliorhodopsin (HeR) is a new rhodopsin family discovered in 2018 through functional metagenomic analysis. Similar to microbial rhodopsins, HeR has an all-trans retinal chromophore, and its photoisomerization to the 13-cis form triggers a relatively slow photocycle with sequential intermediate states (K, M, and O intermediates). The O intermediate has a relatively long lifetime and is a putative active state for transferring signals or regulating enzymatic reactions. Although the first discovered HeR, 48C12, was found in bacteria and the second HeR (TaHeR) was found in archaea, their key amino acid residues and molecular architectures have been recognized to be well conserved. Nevertheless, the rise and decay kinetics of the O intermediate are faster in 48C12 than in TaHeR. Here, using a new infrared spectroscopic technique with quantum cascade lasers, we clarified that the hydrogen bond between transmembrane helices (TM) 3 and 4 is essential for the altered O kinetics (Ser112 and Asn138 in 48C12). Interconverting mutants of 48C12 and TaHeR clearly revealed that the hydrogen bond is important for regulating the dynamics of the O intermediate. Overall, our study sheds light on the importance of the hydrogen bond between TM3 and TM4 in heliorhodopsins, similar to the DC gate in channelrhodopsins., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cervical radiculopathy might affect finger movement and dexterity. Postoperative features and clinical outcomes comparing C8 radiculopathies with other radiculopathies are unknown. This prospective multicenter study analyzed 359 patients undergoing single-level surgery for pure cervical radiculopathy (C5, 48; C6, 132; C7, 149; C8, 30). Background data and pre- and 1-year postoperative neck disability index (NDI) and numerical rating scale (NRS) scores were collected. The C5-7 and C8 radiculopathy groups were compared after propensity score matching, with clinical significance determined by minimal clinically important differences (MCID). Postoperative arm numbness was significantly higher than upper back or neck numbness, and arm pain was reduced the most (3.4 points) after surgery among the C5-8 radiculopathy groups. The C8 radiculopathy group had worse postoperative NDI scores (p = 0.026), upper back pain (p = 0.042), change in arm pain NRS scores (p = 0.021), and upper back numbness (p = 0.028) than the C5-7 group. NDI achieved MCID in both groups, but neck and arm pain NRS did not achieve MCID in the C8 group. In conclusion, although arm numbness persisted, arm pain was relieved after surgery for cervical radiculopathy. Patients with C8 radiculopathy exhibited worse NDI and change in NRS arm pain score than those with C5-7 radiculopathy., (© 2024. The Author(s).)

Introduction: Primary small bowel carcinoma in pregnant women is extremely rare. Small bowel cancer is difficult to diagnose because of its rarity, lack of specific clinical symptoms, and particular anatomical features. We experienced a case of primary small bowel adenocarcinoma with ovarian metastasis during pregnancy. This is the first reported case of a patient with small bowel adenocarcinoma whose pregnancy continued to term and ended in delivery., Case Presentation: A 32-year-old pregnant woman developed abdominal pain, and imaging examination revealed an ovarian tumor at 29 weeks of gestation. We performed laparotomy and resected the ovarian tumor, which was initially suspected to be primary ovarian cancer. The patient continued the pregnancy to term. A detailed examination of the abdominal cavity during cesarean delivery at 37 weeks revealed that the primary lesion was located in the small bowel., Conclusion: It is important to recognize that the small bowel may be the primary site of metastatic ovarian cancer. Detailed and careful examination is necessary to diagnose small bowel cancer during pregnancy., Competing Interests: The authors declare that they have no conflicts of interest to disclose., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Advanced glycation end-products (AGEs) formation increases with metabolic disorders, leading to higher serum AGE levels in patients with progressive vascular complications. Measuring AGE levels in biological samples requires multiple pre-analytical processing steps, rendering analysis of multiple samples challenging. This study evaluated the progression of diabetic complications by analyzing AGE levels using a pre-analytical processing strategy based on a fully automated solid phase-extraction system. Serum samples from patients with diabetes, with or without macrovascular complications (Mac or non-Mac) or microvascular complications (Mic or non-Mic), were processed with the established methods. Free and total AGE levels in sera were measured using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). In patients with diabetes, both free and total AGE levels were elevated in those with complications compared to those without complications. In Mac and Mic groups, free and total AGE levels and z-scores (the sum of normalized AGE levels) also increased. AGE z-scores were markedly higher than those of single AGE levels in distinguishing each complication. Our study demonstrated that the free AGE z-score, measured using a new analytical method without hydrolysis, correlated with the presence of vascular complications and may serve as a marker of disease complications., (© 2024. The Author(s).)

Objective: This study aimed to elucidate postoperative outcomes in patients with spinal metastases of prostate cancer, with a focus on patient-oriented assessments., Methods: This was a prospective multicenter registry study involving 35 centers. A total of 413 patients enrolled in the Japanese Association for Spine Surgery and Oncology Multicenter Prospective Study of Surgery for Metastatic Spinal Tumors were evaluated for inclusion. The eligible patients were followed for at least 1 year after surgery. The Frankel Classification, Eastern Cooperative Oncology Group Performance Status, visual analog scale for pain, face scale, Barthel Index, vitality index, indications for oral pain medication, and the EQ-5D-5L questionnaire were used for evaluating functional status, activities of daily living, and patient motivation., Results: Of the 413 eligible patients, 41 with primary prostate cancer were included in the study. The patient-oriented assessments indicated that the patients experienced postoperative improvements in quality of life and motivation in most items, with the improvements extending for up to 6 months. More than half of the patients with Frankel classifications B or C showed improved neurological function at 1 month after surgery, and most patients presented maintained or improved their classification at 6 months., Conclusion: Surgical intervention for spinal metastases of prostate cancer significantly improved neurological function, quality of life, and motivation of the patients. Consequently, our results support the validity of surgical intervention for improving the neurological function and overall well-being of patients with spinal metastases of prostate cancer., Competing Interests: Declaration of competing interest The Authors declare that there is no conflict of interest., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

We report the existence of a working memory system in the nematode C. elegans that is employed for deferred action in a sensory-guided decision-making process. We find that the turn direction of discrete reorientations during navigation is under sensory-guided control and relies on a working memory that can persist over an intervening behavioral sequence. This memory system is implemented by the phasic interaction of two distributed oscillatory dynamical components. The interaction of oscillatory neural ensembles may be a conserved primitive of cognition across the animal kingdom.

Background: Some genomic alterations in non-small cell lung cancer (NSCLC) are known to differ according to race, sex, or age. These studies have been limited in sample size and thus they cannot detect the differences precisely and comprehensively., Methods: Tissue-based comprehensive genomic profiling was performed on 75,362 patients with NSCLC from the United States during routine clinical care. Additionally, we examined data of a Japanese NSCLC cohort with 1,019 patients. In the US cohort, 296 genes were examined for pathogenic alterations. Predominant genetic ancestry was inferred using a SNP-based approach, and patients were categorized into European (EUR), African (AFR), East Asian (EAS), Admixed American (AMR), and South Asian (SAS) ancestry groups. Patients were additionally stratified by histologic type, age (<40/≥40 years, <75/≥75 years), and sex. The prevalence of high tumor mutational burden (TMB-High) and microsatellite instability status was also calculated., Results: Stratified by ancestry, EGFR alterations were significantly enriched in EAS versus other ancestry groups. The prevalence of ALK was significantly higher in the AMR, EAS, and SAS patients than in AFR and EUR patients. KRAS and STK11 were enriched in EUR and AFR patients versus other groups. TMB-High was significantly enriched in AFR patients versus all other groups. An analysis based on sex revealed differences in prevalence of alterations in 80 genes and TMB-High status. For example, EGFR, ALK, BRAF, and KRAS alterations were significantly enriched in females, whereas TP53, STK11, KEAP1, and TMB-High were significantly enriched in males. With respect to age, the prevalence of alterations in 41 genes, including ALK, RET, MET, EGFR, STK11, KEAP1, BRAF, and KRAS, as well as TMB-High, were significantly different between patients aged <40 years and those aged ≥40 years., Conclusions: Comprehensive analysis from a large real-world dataset revealed ancestry-associated differences in genomic alterations in NSCLC. Age- and sex-related differences in prevalence of genomic alterations and TMB-High status were also observed.

When a neuroendocrine tumor with abundant blood flow is located in the pancreatic tail, it is difficult to distinguish it from accessory spleen. The patient was a 71-year-old woman who was admitted with impaired consciousness and hypoglycemia, raising suspicion of insulinoma. The selective arterial calcium injection test suggested a lesion in the pancreatic tail. Contrast-enhanced computed tomography and magnetic resonance imaging (MRI) showed a mass in the splenic hilum; however, its continuity with the pancreas was unclear. Contrast-enhanced MRI using super paramagnetic iron oxide (SPIO) showed no SPIO uptake in the splenic hilar mass. SPIO contrast-enhanced MRI is considered useful for differentiating pancreatic endocrine tumors from paraspleen tumors.