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Diatoms are one of the most prominent oceanic primary producers and are now recognized to be distributed throughout the world. They maintain their population despite predators, infections, and unfavourable environmental conditions. One of the smallest diatoms, Chaetoceros tenuissimus , can coexist with infectious viruses during blooms. To further understand this relationship, we sequenced the C. tenuissimus strain NIES-3715 genome. A gene fragment of a replication-associated gene from the infectious ssDNA virus (designated endogenous virus-like fragment, EVLF) was found to be integrated into each 41 Mb of haploid assembly. In addition, the EVLF was transcriptionally active and conserved in nine other C. tenuissimus strains from different geographical areas, although the primary structures of their proteins varied. The phylogenetic tree further suggested that the EVLF was acquired by the ancestor of C. tenuissimus . Additionally, retrotransposon genes possessing a reverse transcriptase function were more abundant in C. tenuissimus than in Thalassiosira pseudonana and Phaeodactylum tricornutum . Moreover, a target site duplication, a hallmark for long interspersed nuclear element retrotransposons, flanked the EVLF. Therefore, the EVLF was likely integrated by a retrotransposon during viral infection. The present study provides further insights into the diatom-virus evolutionary relationship.

Relapsed and refractory aggressive lymphoma have a poor prognosis. High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is effective in chemosensitive patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is among the few options for non-chemosensitive patients. 18Fluoro-2-deoxy-d-glucose positron emission tomography–computed tomography (18FDG-PET/CT) is the standard tool for evaluating response to chemotherapy and residual tumor volume. However, accurate assessment of residual tumor volume is not currently being achieved in clinical practice, and its value in prognostic and therapeutic stratification remains unclear. To answer this question, we investigated the efficacy of quantitative indicators, including total metabolic tumor volume (TMTV), in predicting prognosis after auto-HSCT and allo-HSCT. We retrospectively analyzed 39 patients who received auto-HSCT and 28 who received allo-HSCT. In the auto-HSCT group, patients with a higher TMTV had a poor prognosis due to greater risk of relapse. In the allo-HSCT group, patients with a higher TMTV had a lower progression-free survival rate and a significantly higher relapse rate. Neither Deauville score nor other clinical parameters were associated with prognosis in either group. Therefore, pre-transplant TMTV on PET is effective for prognostic prediction and therapeutic decision-making for relapsed or refractory aggressive lymphoma.

Background Additional surgical treatment after non-curative endoscopic resection for superficial esophageal cancer should be considered unless the tumor is pathologically proven to be categorized within the absolute indication of endoscopic resection. However, the significance of this treatment strategy has been poorly evaluated until now. Methods Additional esophagectomy with lymph node dissection was carried out for a total of 34 patients with esophageal cancer pathologically diagnosed as in contact with or invading the muscularis mucosa (pT1a-MM) or submucosa (pSM) and/or accompanying vascular permeation after endoscopic resection. The surgical results, pathological diagnosis after esophagectomy, and outcomes were analyzed. Results The pathological diagnosis after endoscopic resection revealed pT1a-MM in 7 patients, pSM in 27 patients, and vessel permeation in 24 patients. The approach to esophagectomy was via right and left thoracotomy in 26 patients and 2 patients, respectively, and was transhiatal in 6 patients. Three-field lymph node dissection was performed in 12 patients, and the mean number of dissected lymph nodes was 72 (range 31–132). Pathological lymph node metastasis was noted in 10 patients. Postoperative complications developed in 10 patients, and death due to pulmonary complications was observed in one patient. No postoperative recurrence was observed during the follow-up period (1–87 months). Conclusions Esophagectomy after endoscopic resection provides favorable disease control for esophageal cancer with pT1a-MM/pSM and/or vessel permeation, while strict consideration is required to determine the indication and procedure for surgery because of its invasiveness.

Background Yokukansan, a traditional Japanese medicine (Kampo), has been widely used to treat neurosis, dementia, and chronic pain. Previous in vitro studies have suggested that Yokukansan acts as a partial agonist of the 5-HT 1A receptor, resulting in amelioration of chronic pain through inhibition of nociceptive neuronal activity. However, its effectiveness for treating postoperative pain remains unknown, although its analgesic mechanism of action has been suggested to involve serotonin and glutamatergic neurotransmission. This study aimed to investigate the effect of Yokukansan on postoperative pain in an animal model. Methods A mouse model of postoperative pain was created by plantar incision, and Yokukansan was administered orally the day after paw incision. Pain thresholds for mechanical and heat stimuli were examined in a behavioral experiment. In addition, to clarify the involvement of the serotonergic nervous system, we examined the analgesic effects of Yokukansan in mice that were serotonin-depleted by para -chlorophenylalanine (PCPA) treatment and intrathecal administration of NAN-190, 5-HT 1A receptor antagonist. Results Orally administered Yokukansan increased the pain threshold dose-dependent in postoperative pain model mice. Pretreatment of para -chlorophenylalanine dramatically suppressed serotonin immunoreactivity in the spinal dorsal horn without changing the pain threshold after the paw incision. The analgesic effect of Yokukansan tended to be attenuated by para -chlorophenylalanine pretreatment and significantly attenuated by intrathecal administration of 2.5 µg of NAN-190 compared to that in postoperative pain model mice without para -chlorophenylalanine treatment and NAN-190 administration. Conclusion This study demonstrated that oral administration of Yokukansan has acute analgesic effects in postoperative pain model mice. Behavioral experiments using serotonin-depleted mice and mice intrathecally administered with a 5-HT 1A receptor antagonist suggested that Yokukansan acts as an agonist at the 5-HT 1A receptor, one of the serotonin receptors, to produce analgesia.

Background This study aimed to investigate survival outcomes, the efficacy of lymph node (LN) dissection, and recurrence patterns in patients who underwent salvage surgery (SALV) for esophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy (dCRT). Methods We retrospectively reviewed 69 patients with clinical stage I–IV thoracic ESCC who underwent SALV. Recurrence patterns and the distribution of LN metastases were analyzed according to the primary tumor location. Results The 90‐day mortality rate was 2.9%, and the 3‐year overall survival (OS) rate of the 69 patients was 47.1%. OS curves were significantly stratified by the presence of abdominal LN metastases (p = 0.007). Among six patients whose clinically positive LNs were not dissected because their swelling disappeared after dCRT (cN+/CRT‐cN0 cases), two (33.3%) developed locoregional recurrence. In contrast, among 25 patients whose clinically positive LNs were dissected regardless of CRT‐cN status, the incidence of locoregional recurrence alone was 4.0%. Patients with lower thoracic (Lt) tumors had a higher incidence of distant metastases than those with middle (Mt) or upper thoracic (Ut) tumors (61.5% vs. 36.8%/33.3%). Mediastinal LN metastases were rare (7.7%) in Lt tumors, whereas LN metastases were widely distributed within the regional zones in Mt/Ut tumors. Patients with Lt tumors and pathological LN metastases had extremely poor OS (3‐year OS: 0%). Conclusions Abdominal LN metastases had a negative impact on survival in ESCC patients who underwent SALV. Clinically positive LNs should be dissected, provided it is technically feasible. The tumor location might influence the distribution and prognostic impact of pathological LN metastases. This study aimed to investigate survival outcomes, the efficacy of lymph node (LN) dissection, and recurrence patterns in 69 patients who underwent R0 salvage surgery for esophageal squamous cell carcinoma. Of note, abdominal LN metastases had a negative impact on survival in our series. Tumor location significantly influenced the distribution and survival impact of pathological LN metastases.

Objective: The aim of this study was to investigate the influence of chemoradiotherapy (CRT) on nutritional status and the association between changes in nutritional status and clinical outcomes (treatment completion, adverse events, perioperative complications, and relapse-free survival [RFS]) in patients with locally advanced rectal cancer (LARC). Methods: In this multicenter, phase II study, 41 patients with LARC underwent CRT for 5 wk, followed by a 6- to 8-wk interval before surgery. Body weight, body mass index (BMI), lean body mass, serum albumin, and prealbumin levels were measured before (pre-), during, and after CRT, and before surgery. Changes in these data and scores on the Malnutrition Universal Screening Tool (MUST) were calculated based on pre-CRT status. Results: Twelve patients (29.3%) experienced body weight loss (BWL) ≥5% (defined as malnutrition) after CRT (P < 0.001) and before surgery (P = 0.035). Significant changes were seen in serum albumin levels and BMI during and after CRT (P < 0.001), and in MUST scores after CRT (P = 0.003) and before surgery (P = 0.035). Treatment completion was significantly associated with BWL (P = 0.028), MUST score (P = 0.013), and decreased serum albumin level (P = 0.001) after CRT. Regarding adverse events, MUST score before surgery (P = 0.009) and serum albumin level after CRT (P = 0.002) were significantly associated with diarrhea severity. Serum albumin level during CRT was associated with the onset of neutropenia (P = 0.005). No association was found between BWL and RFS. Conclusions: These findings suggest that malnutrition and changes in nutritional status are not only commonly observed after CRT, but also associated with treatment completion and adverse events. •This is a prospective study regarding chemoradiotherapy for rectal cancer.•Malnutrition is a common side effect of chemoradiotherapy for rectal cancer.•Malnutrition is associated with treatment completion and adverse events.

PurposeAlthough sleep bruxism (SB) is one of the most important clinical problems in dental practice, there is no definitive method for controlling it. This pilot study evaluated the effects of contingent vibratory feedback stimuli using an occlusal splint for inhibition of sleep bruxism.MethodsThirteen subjects with clinically diagnosed SB participated after providing an informed consent. Portable polysomnographic recordings were conducted in the subjects’ home environment to make a definitive SB diagnosis and to evaluate the effects of the vibratory stimuli on SB. A force-based bruxism detection system, which used a pressure-sensitive piezoelectric film embedded in the occlusal splint, was utilized to trigger vibration feedback stimuli, which was scheduled to be applied intermittently for 30 min, at 30-min intervals.ResultsThe number of SB episodes (times/hour), the total SB duration (seconds/hour), the mean duration of SB episodes (seconds/episode), and the micro-arousal index (times/hour) were scored for each time period (with and without vibration). The effects of the vibration on these scores were tested (paired t test; p < 0.05). The number of SB episodes tended to decrease with the vibration stimuli, and the decrease in the total SB duration was statistically significant (14.3 ± 9.5 vs. 26.0 ± 20.0, p = 0.03). No substantial change was found in terms of the micro-arousal index.ConclusionsThese study results suggested that the SB inhibitory system employing a vibratory stimulus might be able to suppress the total SB duration without disturbing sleep.

RationalCorticosteroid therapy plays a key role in the treatment of COVID-19 patients with respiratory failure. However, a rebound phenomenon after steroid cessation rarely occurs. Here, we investigated the clinical features of patients with rebound after steroid therapy.MethodsIn total, 84 patients with COVID-19 treated with corticosteroids were enrolled and analysed retrospectively. A rebound was defined as when a patient’s respiratory status deteriorated after the cessation of corticosteroid therapy, without secondary bacterial infection.ResultsSubjects in the rebound group were more likely to having severe respiratory failure than those in the non-rebound group. While the duration of steroid therapy was longer in the rebound group (8 days vs 10 days, p=0.0009), the dosage of steroid and the timing of the start or termination of steroid therapy did not show any differences between the two groups (p=0.17 and 0.68, respectively). The values of soluble interleukin-2 receptor (sIL-2R) at the baseline and the values of C reactive protein (CRP) or lactate dehydrogenase (LDH) at the end of steroid therapy were significantly higher in the rebound group (937 vs 1336 U/mL; p=0.002, 0.63 vs 3.96 mg/dL; p=0.01 and 278 vs 451 IU/mL; p=0.01, respectively). No patient in the rebound group suffered from thromboses, and the causes of death were exacerbation of COVID-19, ventilator-associated pneumonia or sepsis. The prediction model using baseline features for the rebound phenomenon included four variables of age >68 years, required supplemental oxygen >5 L/min, lymphocyte counts <792 /µL and sIL-2R >1146 U/mL. The discrimination ability of this model was 0.906 (0.755–0.968).ConclusionThese findings suggest that severe respiratory failure has a higher risk for the rebound phenomenon after the cessation of corticosteroids, and the values of sIL-2R, LDH and CRP are useful to assess the probability of developing rebound. A multivariate model was developed to predict rebound risk, which showed acceptable discrimination ability.

Background To investigate the association between each clinical diagnosis criterion for sleep bruxism (SB) and the frequency of jaw motor events during sleep. Methods Video-polysomnography was performed on 17 healthy adult subjects (mean age, 26.7 ± 2.8 years), with at least one of the following clinical signs and symptoms of SB: (1) a report of frequent tooth grinding, (2) tooth attrition with dentine exposure through at least three occlusal surfaces, (3) morning masticatory muscle symptoms, and (4) masseter muscle hypertrophy. Episodes of rhythmic masticatory muscle activity (RMMA) and isolated tonic activity were scored visually. These variables were compared with regards to the presence or absence of each clinical sign and symptom. Results In 17 subjects, 4.0 ± 2.5/h (0.1–10.2) RMMA and 1.0 ± 0.8/h (0–2.4) isolated tonic episodes were observed (total episodes: 5.0 ± 2.4/h (1.2–11.6)). Subjects with self-reported grinding sounds ( n  = 7) exhibited significantly higher numbers of RMMA episodes (5.7 ± 2.3/h) than those without ( n  = 10; 2.8 ± 1.8/h) ( p  = 0.011). Similarly, subjects with tooth attrition ( n  = 6) showed significantly higher number of RMMA episodes (5.6 ± 3.1/h) than those without ( n  = 11; 3.2 ± 1.6/h) ( p  = 0.049). The occurrence of RMMA did not differ between the presence and absence of morning masticatory muscle symptoms or muscle hypertrophy. Conclusions Clinical signs and symptoms frequently used for diagnosing SB can represent different clinical and physiological aspects of jaw motor activity during sleep.