Spin and charge interactions between nanographene host and ferrocene.

Ferrocene (FeCp2) was introduced as a non-magnetic guest molecule to activated carbon fibers (ACFs) as a nanographene-based host having localized spins originating from zigzag edges of graphene. The introduction of the guest molecule was confirmed by FTIR for ACFs-FeCp2 introduced at 55 (150) °C (FeCp2-ACFs-55(150)). The appearance of satellite Fe2p peaks and the increase in shake-up peak intensity of the C1s in the XPS spectrum proved the emergence of charge-transfer host-guest interaction in FeCp2-ACFs-150, supported by the red-shift of the G-band in the Raman spectrum. The six-times enhancement in the spin concentration in FeCp2-ACFs-150 compared with ACFs indicates the spin magnetism of the non-magnetic guest FeCp2+ molecule induced by a charge-transfer host-guest interaction in the nanographene host. The larger ESR linewidth than that expected from the dipolar interaction estimated by the localized spin concentration suggests the exchange interaction between the nanographene and FeCp2 spins. The narrowing of the ESR linewidth of FeCp2-ACFs-55 upon higher excitation microwave power suggests the inhomogeneity of the environment for FeCp2+ molecules in the nanographene host. The observed induction of spin magnetism by the interfacial interactions between the nanographene host and the guest molecules will be a promising strategy for developing a new class of molecular magnets.

Individual disruption of 12 testis-enriched genes via the CRISPR/Cas9 system does not affect the fertility of male mice.

More than 1200 genes have been shown in the database to be expressed predominantly in the mouse testes. Advances in genome editing technologies such as the CRISPR/Cas9 system have made it possible to create genetically engineered mice more rapidly and efficiently than with conventional methods, which can be utilized to screen genes essential for male fertility by knocking out testis-enriched genes. Finding such genes related to male fertility would not only help us understand the etiology of human infertility but also lead to the development of male contraceptives. In this study, we generated knockout mice for 12 genes (Acrv1, Adgrf3, Atp8b5, Cfap90, Cfap276, Fbxw5, Gm17266, Lrrd1, Mroh7, Nemp1, Spata45, and Trim36) that are expressed predominantly in the testis and examined the appearance and histological morphology of testes, sperm motility, and male fertility. Mating tests revealed that none of these genes is essential for male fertility at least individually. Notably, knockout mice for Gm17266 showed smaller testis size than the wild-type but did not exhibit reduced male fertility. Since 12 genes were not individually essential for male fertilization, it is unlikely that these genes could be the cause of infertility or contraceptive targets. It is better to focus on other essential genes because complementary genes to these 12 genes may exist.

Head impact differences in blind football between Rio 2016 and Tokyo 2020 Paralympic Games: video-based observational study.

OBJECTIVE: In Tokyo 2020 Paralympic Games, there were the rule and goal size changes at the blind football competition. This study aimed to compare the scoring and head impact characteristics during blind football competition between the Rio 2016 and Tokyo 2020 Paralympic Games using the official videos. DESIGN: Video-based observational study. PARTICIPANTS: In total, 36 blind football (men's football 5-a-side) game videos were obtained from the official International Paralympic Committee. PRIMARY AND SECONDARY OUTCOME MEASURES: Head impact was defined as the sudden contact of any object with the head. Videos were analysed to assess the number of scores and head impacts along with their corresponding details (ie, round, playing phase, scoring situation, impact situation, occurrence area, impact object, head impact site, fall and foul). RESULTS: The total number of goals scored at the Tokyo 2020 Paralympic Games was nearly double that at the Rio 2016 Paralympic Games. Regarding head impacts, a total of 2036 cases (Rio 2016, n=1105; Tokyo 2020, n=931) were evaluated. Significant differences were observed in head impact characteristics between the Rio 2016 and Tokyo 2020 Paralympic Games among seven outcomes (round, scoring situation, impact situation, occurrence area, impact object, site of head impact and fall). CONCLUSIONS: Compared with the Rio 2016 Paralympic Games, the Tokyo 2020 Paralympic Games showed an increase in the number of points scored and different head impact characteristics.

Ferroptosis induced by plasma-activated Ringer's lactate solution prevents oral cancer progression.

OBJECTIVE: This study aimed to investigate the effect of plasma-activated Ringer's lactate solution (PAL) on oral squamous cell carcinoma (OSCC) cells and carcinogenic processes with a particular focus on iron and collagenous matrix formation. MATERIALS AND METHODS: We used three OSCC cell lines, one keratinocyte cell line, and two fibroblast lines, and cell viability assays, immunoblotting, flow cytometry, and transmission electron microscopy were performed to evaluate the effect and type of cell death. The effect of PAL treatment on lysyl oxidase (LOX) expression was investigated in vitro and in vivo. Tamoxifen-inducible Mob1a/b double-knockout mice were used for the in vivo experiment. RESULTS: PAL killed OSCC cells more effectively than the control nontumorous cells and suppressed cell migration and invasion. Ferroptosis occurred and the protein level of LOX was downregulated in cancer cells in vitro and in vivo. Additionally, PAL improved the survival rate of mice and suppressed collagenous matrix formation. CONCLUSIONS: We demonstrated that PAL specifically kills OSCC cells and that ferroptosis occurs in vitro and in vivo. Furthermore, PAL can prevent carcinogenesis and improve the survival rate of oral cancer, especially tongue cancer, by changing collagenous matrix formation via LOX suppression.

Oral Microbial Profile Analysis in Patients with Oral and Pharyngeal Cancer Reveals That Tumoral Fusobacterium nucleatum Promotes Oral Cancer Progression by Activating YAP.

The incidence of oral cancer has recently been increasing worldwide, particularly among young individuals and women. The primary risk factors for head and neck cancers, including oral and pharyngeal cancers, are smoking, alcohol consumption, poor oral hygiene, and repeated exposure to mechanical stimuli. However, approximately one-third of the patients with oral and pharyngeal cancers are neither smokers nor drinkers, which points to the existence of other mechanisms. Recently, human microbes have been linked to various diseases, including cancer. Oral pathogens, especially periodontal pathobionts, are reported to play a role in the development of colon and other types of cancer. In this study, we employed a series of bioinformatics analyses to pinpoint Fusobacterium nucleatum as the predominant oral bacterial species in oral and pharyngeal cancer tissue samples. We successfully isolated Fn. polymorphum from the saliva of patients with oral cancer and demonstrated that Fn. polymorphum indeed promoted oral squamous cell carcinoma development by activating YAP in a mouse tongue cancer model. Our research offers scientific evidence for the role of the oral microbiome in oral cancer progression and provides insights that would help in devising preventative strategies against oral cancer, potentially by altering oral bacterial profiles.

Lethal Phenotype-Based Database Screening Identifies Ceramide as a Negative Regulator of Primitive Streak Formation.

In early embryogenesis, the primitive streak (PrS) generates the mesendoderm and is essential for organogenesis. However, because the PrS is a minute and transient tissue, elucidating the mechanism of its formation has been challenging. We performed comprehensive screening of 2 knockout mouse databases based on the fact that failure of PrS formation is lethal. We identified 812 genes involved in various cellular functions and responses that might be linked to PrS formation, with the category of greatest abundance being "Metabolism." In this study, we focused on genes of sphingolipid metabolism and investigated their roles in PrS formation using an in vitro mouse ES cell differentiation system. We show here that elevated intracellular ceramide negatively regulates gene expression essential for PrS formation and instead induces neurogenesis. In addition, sphingosine-1-phosphate (a ceramide derivative) positively regulates neural maturation. Our results indicate that ceramide regulates both PrS formation and the induction of neural differentiation.

A Case of Mesangial Proliferative Nephritis Caused by Slow Cryoglobulin.

The patient was a woman in her 60s. She was found to have proteinuria on a health checkup. She did not have any particular subjective symptoms, and no definitive diagnosis was made, despite serological findings indicative of immune abnormalities. A renal biopsy was performed. Light microscopy of renal tissue section revealed mesangial proliferative nephritis. Electron microscopic findings included electron-dense deposits and fibrillar/tubular structures with a diameter of 20-30 nm. These findings suggested the presence of cryoglobulin (CG), but CG was not detected in qualitative or quantitative hematologic tests. Thus, the serum samples were stored at 37°C for a long period of time and then cooled to 4°C. When the obtained precipitates were examined, CG was successfully detected. CG that precipitates only after a long period of time is referred to as slow cryoglobulin (sCG), and sCG is extremely rare. The present case is the first documented case, to our knowledge, of renal disorders caused by sCG. It should be noted that there are some cases in which it takes much time for CG to precipitate. Thus, when CG cannot be detected, it is necessary to spend much time to determine whether CG precipitates.

Analytical Performance of a Novel Latex Turbidimetric Immunoassay, "Nanopia TARC", for TARC/CCL17 Measurement: A Retrospective Observational Study.

Thymus- and activation-regulated chemokine (TARC, also known as CCL17) is used as a biomarker for atopic dermatitis. The methods currently used for its measurement are complex, time-consuming, and require large machinery, warranting the need for a method that is simple, has a quick turnaround time, and requires less complex machinery. We evaluated the analytical performance of a novel latex turbidimetric immunoassay method, "Nanopia TARC", on 174 residual serum samples from patients with skin or allergic diseases. This evaluation included the assessment of the limit of blank/detection/quantification (LOB/D/Q), precision, accuracy, linearity, interference, and commutability between Nanopia TARC and "HISCL TARC", based on the chemiluminescent enzyme immunoassay (CLEIA) method. The LOB/D/Q values were 13, 57, and 141 pg/mL, respectively. The coefficient of variation of the repeatability was 0.9-3.8%, and that of the intermediate precision was 2.1-5.4%. The total error of the accuracy was 1.9-13.4%. The linearity was 141 and 19,804 pg/mL for TARC. The correlation coefficient between Nanopia TARC and HISCL TARC determined using the Passing-Bablok regression analysis was 0.999. Furthermore, the concordance of diagnostic criteria with AD was 92%. Nanopia TARC was confirmed to have the same analytical performance for TARC measurement as the existing CLEIA method.

Guidelines for the Management of Respiratory Infectious Diseases in Children in Japan 2022.

The members of the Japanese Society for Pediatric Infectious Diseases and the Japanese Society of Pediatric Pulmonology have developed Guidelines for the Management of Respiratory Infectious Diseases in Children with the objective of facilitating appropriate diagnosis, treatment and prevention of respiratory infections in children. The first edition was published in 2004 and the fifth edition was published in 2022. The Guideline 2022 consists of 2 parts, clinical questions and commentary, and includes general respiratory infections and specific infections in children with underlying diseases and severe infections. This executive summary outlines the clinical questions in the Guidelines 2022, with reference to the Japanese Medical Information Distribution Service Manual. All recommendations are supported by a systematic search for relevant evidence and are followed by the strength of the recommendation and the quality of the evidence statements.

Vascular access interventional therapy of early arteriovenous fistula occlusion leading to long-term patency: A case report.

Arteriovenous fistulas (AVFs) are frequently used for hemodialysis access, but approximately 15%-20% of AVFs fail to mature within 3 months of their creation. Vascular access interventional therapy (VAIVT) is typically performed for treating an immature AVF. However, it should be performed 4-6 weeks or later after AVF creation. Here, we present a case in which VAIVT effectively addressed AVF occlusion that occurred only 9 days after its creation. The patient was an 82-year-old woman with chronic kidney disease who underwent surgery to create a left radiocephalic AVF for hemodialysis. Nine days postoperatively, disappearance of the AVF sound prompted an angiography, revealing thrombosis near the AVF anastomosis. VAIVT successfully restored blood flow, resulting in AVF maturation, and with no thrombosis or flow dysfunction at 21 months after VAIVT. To the best of our knowledge, this case presents the earliest successful intervention for an occluded AVF.

Cycle Threshold (Ct) Values of SARS-CoV-2 Detected with the GeneXpert® System and a Mutation Associated with Different Target Gene Failure.

SARS-CoV-2 nucleic acid detection tests enable rapid virus detection; however, it is challenging to identify genotypes to comprehend the local epidemiology and infection routes in real-time qRT-PCR. At the end of June 2022, our hospital experienced an in-hospital cluster of COVID-19. When examined using the GeneXpert® System, the cycle threshold (Ct) value of the N2 region of the nucleocapsid gene of SARS-CoV-2 was approximately 10 cycles higher than that of the envelope gene. Sanger sequencing revealed a G29179T mutation in the primer and probe binding sites. A review of past test results revealed differences in Ct values in 21 of 345 SARS-CoV-2-positive patients, of which 17 cases were cluster-related and 4 were not. Including these 21 cases, 36 cases in total were selected for whole-genome sequencing (WGS). The viral genomes in the cluster-related cases were identified as BA.2.10, and those in the non-cluster cases were closely related and classified as being downstream of BA.2.10 and other lineages. Although WGS can provide comprehensive information, its use is limited in various laboratory settings. A measurement platform reporting and comparing Ct values of different target genes can improve test accuracy, enhance our understanding of infection spread, and be applied to the quality control of reagents.

[Retroperitoneal Dedifferentiated Liposarcoma with No Recurrence after 5 Years of Postoperative Radiation Therapy --A Case Report-].

A 49-year-old woman presented to our hospital with right lower back pain and epigastric pressure. A computed tomographic scan showed a 12×7×20 cm retroperitoneal mass comprising fatty components and contrast areas around the right kidney. Based on the results, a right retroperitoneal liposarcoma was suspected. Thus, right retroperitoneal tumor resection combined with right kidney resection was performed. Instances of tumor adhesion were found in the ascending colon, duodenum, and the iliopsoas muscle, which could be dissected ; therefore, combined resection of the intestinal tract was not performed. The resected tumor was found to be mixed with dedifferentiated and well-differentiated components and was diagnosed as dedifferentiated liposarcoma. Due to the presence of positive margins, the patient received 50 Gy in 25 fractions of radiation therapy to the right side of the retroperitoneum as postoperative adjuvant therapy. During the irradiation period, vomiting and anorexia were observed as adverse events. Five years have passed since the surgery, and no local recurrence or late complications due to radiation have been observed. Although dedifferentiated liposarcoma is a highly malignant histological type with a very high local recurrence rate, no adjuvant therapy has been established. Some reports have suggested that postoperative radiation therapy for retroperitoneal sarcoma is effective in terms of survival and local control. However, there are no reports of prospective clinical trials, and the evidence is expected to widen in the near future.

Distribution-free Phase-I scheme for location, scale and skewness shifts with an application in monitoring customers' waiting time.

Phase-I analysis of historical data from a statistical process is a strategic problem in Statistical Process Monitoring and control. Before the establishment of process stability, it is challenging to model historical data. Consequently, a distribution-free approach is a natural choice in Phase-I monitoring. Existing distribution-free Phase-I control charts are suitable for detecting instability in location and scale parameters only and are often insensitive in complex processes involving skewness or shape parameters. A new Phase-I control chart is proposed to identify more general shifts, including location, scale and skewness. The proposed Phase-I scheme is efficient in such a situation. The proposed Phase-I scheme uses subsamples, and the plotting statistic is based on the omnibus multi-sample linear rank statistic corresponding to the location, scale and skewness shifts. The new scheme can identify subsamples that are not in control, and it can also indicate one or more process parameters where a deviation has occurred. The encouraging performance of the proposed scheme is established with a large-scale numerical study based on Monte-Carlo in detecting shifts of various nature in a comprehensive class of situations. An illustration based on monitoring the waiting time data from a customer service centre is given. Some concluding remarks and some future research problems are also offered.

Nucleolar stress: Molecular mechanisms and related human diseases.

Ribosome biogenesis in the nucleolus is an important process that consumes 80% of a cell's intracellular energy supply. Disruption of this process results in nucleolar stress, triggering the activation of molecular systems that respond to this stress to maintain homeostasis. Although nucleolar stress was originally thought to be caused solely by abnormalities of ribosomal RNA (rRNA) and ribosomal proteins (RPs), an accumulating body of more current evidence suggests that many other factors, including the DNA damage response and oncogenic stress, are also involved in nucleolar stress response signaling. Cells reacting to nucleolar stress undergo cell cycle arrest or programmed death, mainly driven by activation of the tumor suppressor p53. This observation has nominated nucleolar stress as a promising target for cancer therapy. However, paradoxically, some RP mutations have also been implicated in cancer initiation and progression, necessitating caution. In this article, we summarize recent findings on the molecular mechanisms of nucleolar stress and the human ribosomal diseases and cancers that arise in its wake.

Head Impact in Blind Football During the Tokyo Paralympics: Video-Based Observational Study.

ABSTRACT: Head impacts during blind football are common and have high injury rates; however, their characteristics and impact are still underreported. We compared head impact characteristics in blind football players with and without falls on all 18 official blind football match videos from the Tokyo 2020 Paralympic games. The rate of head impacts with falls was significantly higher in the preliminary phase, offense phase, and during dribbling. Significant differences in the region of the head impacted were also observed among the impact subjects/objects. The findings in this study would contribute to the development of injury prevention measures to minimize head injuries from head impact in blind football.

Crystal structure of the motor domain of centromere-associated protein E in complex with a non-hydrolysable ATP analogue.

Centromere-associated protein E (CENP-E) is a kinesin motor protein essential for mitosis and a new target for anticancer agents with less side effects. To rationally design anticancer drug candidates based on structure, it is important to determine the three-dimensional structure of the CENP-E motor domain bound to its inhibitor. Here, we report the first crystal structure of the CENP-E motor domain in complex with a non-hydrolysable ATP analogue, adenylyl-imidodiphosphate (AMPPNP). Furthermore, the structure is compared with the ADP-bound form of the CENP-E motor domain as well as the AMPPNP-bound forms of other kinesins. This study indicates that helix α4 of CENP-E participates in the slow binding of CENP-E to microtubules. These results will contribute to the development of anticancer drugs targeting CENP-E.

Characteristics of Wheelchair Basketball Falls During the Tokyo 2020 Paralympics by Sex and Physical Impairment Classification: A Video-Based Observational Study.

OBJECTIVE: The aim of the study is to evaluate the fall characteristics of wheelchair basketball players by sex and impairment classification using the official videos of the Tokyo 2020 Summer Paralympic Games. DESIGN: This was a video-based observational study. In total, 42 men's and 31 women's wheelchair basketball game videos were obtained from the official International Paralympic Committee. The videos were analyzed to assess the number of falls, playing time of the fall, playing phase, contact, foul judgment, fall location/direction, and the body part that first impacted the floor. RESULTS: A total of 1269 falls (men, n = 944; and women, n = 325) occurred. The analysis of men demonstrated significant differences in rounds, playing phase, location of fall, and body part first impacted. Women demonstrated significant differences in all categories except in rounds. Comparisons by functional impairment showed different trends for men and women. CONCLUSIONS: The detailed observation of videos suggested that men are more likely to have dangerous falls. There is a necessity for discuss the prevention measures based on sex and impairment classification.

Characteristics of Falls Among Men's Wheelchair Rugby Players in the Rio 2016 and Tokyo 2020 Summer Paralympic Games: A Video Analysis.

Wheelchair rugby is a contact sport in which falls are common and injury rates are high, yet the characteristics of the falls are still under-reported. We investigated the fall characteristics of men's wheelchair rugby players by functional classification, using all 36 official match videos from the Rio 2016 and Tokyo 2020 summer Paralympic Games. The videos were analyzed to evaluate the number of falls, playing time when the fall occurred, playing phase (offense or defense), contact with other players, foul judgement, direction of the fall, and the body part first in contact with the floor. All 182 men's wheelchair rugby players (Rio 2016, 94; Tokyo 2020, 88) were classified as low-point players or high-point players depending on their functional classification. A total of 200 falls were detected, 27 (13.5%) for low-point players and 173 (86.5%) for high-point players. Significant differences were noted between low-point players and high-point players in the direction of the fall and body part first in contact with the floor. High-point players had more falls in the forward and left-right directions, whereas low-point players were characterized by a higher percentage of falls in the left-right and backward directions. Additionally, high-point players landed on the floor with their hands with high frequency, whereas low-point players landed with their elbows and shoulders more often. Our findings suggest the significance of devising measures to prevent falls during men's wheelchair rugby games according to their functional classification.

Effects of change in walking speed on time-distance parameters in post-stroke hemiplegic gait.

Objectives: In stroke patients, the assessment of gait ability over time is important. For quantitative gait assessment using measuring devices, the walking speed condition for measurement is generally based on the patient's preferred walking speed or the maximum walking speed at the time of measurement. However, because walking speed often increases during the convalescent stage, understanding the effects of change in walking speed on gait when comparing the course of recovery is necessary. Although several previous studies have reported the effects of change in walking speed on gait in stroke patients, the time-distance parameters described in these reports may not be generalizable because of the small case numbers. Therefore, we measured treadmill gait at the preferred walking speed (PWS) and 1.3 times the PWS (130% PWS) in 43 post-stroke hemiplegic patients and analyzed the effects of change in walking speed on time-distance parameters. Methods: Forty-three patients with hemiplegia after a first stroke, who were able to walk on a treadmill under supervision, were recruited as subjects. Using a three-dimensional motion analysis system, treadmill gait was assessed under two conditions: PWS and 130% PWS. The primary outcome measures were the time-distance parameters, which were compared between the PWS and 130% PWS conditions. Results: Cadence, stride length, and step length of the affected and unaffected lower limbs increased significantly at 130% PWS compared with at PWS. In terms of actual time, single stance time and initial and terminal double stance time in both affected and unaffected limbs decreased significantly at 130% PWS. In terms of relative time (% of the gait cycle), compared with PWS, relative single stance time increased significantly, whereas relative initial and terminal double stance times decreased significantly at 130% PWS in both the affected and unaffected limbs. Conclusions: This study on treadmill gait in patients with hemiplegia after a first stroke confirmed the effects of change in walking speed on time-distance parameters. Our results will help in the interpretation of time-distance parameters measured under different walking speed conditions.