Sex Differences in Strength During Development: Implications for Inclusivity and Fairness in Sport.

OBJECTIVES: Males, on average, are bigger and stronger than females. Hormonal differences during puberty are one reason given for this performance advantage. However, not all evidence supports that thesis. Our aim was to further this discussion by measuring early life changes between sexes (when hormones would be similar) in components of muscle function. METHODS: Fifty-one children (29 boys, 22 girls) completed this study. Forearm muscle size and strength were assessed three times with each time point being separated by approximately a year (2021-2023). RESULTS: There was no sex*time interaction for handgrip strength (p = 0.637). There was, however, a time (p < 0.001) and sex (p < 0.001) effect. Strength increased each year and boys were stronger than girls (difference of 1.5 [95% 0.7, 2.3] kg). There was no sex*time interaction for ulnar muscle thickness (p = 0.714) but there was a time (p < 0.001) effect. Muscle size increased each year but there was no evidence of a sex effect (p = 0.12; difference of 0.81 [95% -0.21, 1.8] mm). A strong positive within-participant correlation between muscle size and strength (r = 0.803 95% CI: [0.72, 0.86], p < 0.0001) was found across time. CONCLUSION: Muscle size and strength increased together but this increase did not differ based on sex and boys were stronger than girls. Future work is needed to determine the reason for this difference in maximal strength. Any effect was seemingly present at the initial measurement (at the age of 4 years), since muscle size and strength did not change differently between boys and girls over time.

Skeletal muscle mass in competitive physique-based athletes (bodybuilding, 212 bodybuilding, bikini, and physique divisions): A case series.

OBJECTIVES: (1) To examine the muscle thickness of various muscle groups of the body to estimate the absolute and relative skeletal muscle mass (SM) in competitive physique-based athletes (Bodybuilding, 212 Bodybuilding, Bikini, and Physique divisions) and (2) to compare values across various divisions of competition and to resistance trained and non-resistance trained individuals. METHODS: Eight competitive physique-based athletes (2 M and 6 F), two recreationally resistance trained (1 M and 1 F) and two non-resistance trained (1 M and 1 F) participants had muscle thickness measured by ultrasound at nine sites on the anterior and posterior aspects of the body. SM was estimated from an ultrasound-derived prediction equation and SM index was used to adjust for the influence of standing height (i.e., divided by height squared). RESULTS: SM values ranged from 19.6 to 60.4 kg in the eight competitive physique-based athletes and 16.1 to 32.6 kg in the four recreationally resistance trained and non-resistance trained participants. SM index ranged from 7.2 to 17.9 kg/m2 in the eight competitive physique-based athletes and 5.8 to 9.3 kg/m2 in the four recreationally resistance trained and non-resistance trained participants. CONCLUSION: Overall, varying magnitudes of SM and SM index were present across competitors and their respective divisions of bodybuilding. The Men's Open Bodybuilder in the present study had greater values of total SM and SM index compared to previously published values in the literature. Our data provides insight into the extent of SM present in this population and further extends the discussion regarding SM accumulation in humans.

Tracking handgrip strength in Kendo athletes from university to middle and older adulthood.

OBJECTIVE: This study aimed to compare the current handgrip strength (HGS) of Kendo athletes with their HGS when they were in university (up to 50 years). METHODS: Eighty male graduates who were Kendo club members during their university days performed anthropometric and HGS measurements, and these HGS were compared with those measured during their university days (mean age of 19.5 years old). RESULTS: There was no evidence of a statistical difference in HGS between the current measurement and the measurement taken during university [-0.64 (-1.9, 0.67) kg, p = .336]. There was, however, evidence that the difference in HGS depended upon the current age of the individual (t = -6.43, p < .001). When probing the interaction, there were statistical differences between the ages of 24.6 and 38.2 years and between the ages of 47.4 and 69.9 years. Strength increased across time in the younger participants and decreased for those who were older. Between the ages of 38.9 and 46.1 years, there was no evidence of a statistical difference indicating a maintenance of strength. CONCLUSION: The HGS of Kendo club graduates, which they acquired during their formative years, continued to increase even after they graduated from university and entered their 30s. However, their HGS decreased from age 50, even though they practiced Kendo.

Blood eosinophil count correlates with alveolar damage in emphysema-predominant COPD.

BACKGROUND: Although blood eosinophil count is recognized as a useful biomarker for the management of chronic obstructive pulmonary disease (COPD), the impact of eosinophils in COPD has not been fully elucidated. Here we aimed to investigate the relationships between the blood eosinophil count and various clinical parameters including lung structural changes. METHODS: Ninety-three COPD patients without concomitant asthma were prospectively enrolled in this study. Blood eosinophil count, serum IgE level, serum periostin level, and chest computed tomography (CT) scans were evaluated. Eosinophilic COPD was defined as COPD with a blood eosinophil count ≧ 300/µL. We examined the correlation between the blood eosinophil count and structural changes graded by chest CT, focusing specifically on thin airway wall (WT thin) and thick airway wall (WT thick) groups. In a separate cohort, the number of eosinophils in the peripheral lungs of COPD patients with low attenuation area (LAA) on chest CT was assessed using lung resection specimens. RESULTS: The mean blood eosinophil count was 212.1/µL, and 18 patients (19.3%) were categorized as having eosinophilic COPD. In the whole group analysis, the blood eosinophil count correlated only with blood white blood cells, blood basophils, C-reactive protein level, and sputum eosinophils. However, the blood eosinophil count positively correlated with the percentage of LAA and negatively correlated with the diffusing capacity for carbon monoxide in the WT thin group. Lung specimen data showed an increased number of eosinophils in the peripheral lungs of COPD patients with LAA on chest CT scans compared to normal controls. CONCLUSIONS: Some COPD patients without concomitant asthma showed a phenotype of high blood eosinophils. Alveolar damage may be related to eosinophilic inflammation in patients with COPD without asthma and thickening of the central airway wall.

Molecular insights and the role of 18F-FDG-PET/CT in the diagnosis of spinal gliomas.

BACKGROUND: In recent years, molecular findings on spinal gliomas have become increasingly important. This study aimed to investigate the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the diagnosis of spinal glioma. METHODS: This study included patients diagnosed with spinal cord glioma who underwent 18F-FDG-PET examination at the Department of Neurosurgery, Nagoya University Hospital between January 2016 and November 2023. The gliomas were divided into two groups, high-grade and low-grade, based on pathological and molecular studies. The maximum standardized uptake values (SUVmax) of the tumors were quantified and subsequently represented using receiver operating characteristic (ROC) curves. RESULTS: Eighteen participants were included in this study. Of the participants, seven had high-grade glioma with an SUVmax of 6.76 ± 0.72, and eleven had low-grade glioma with an SUVmax of 4.02 ± 1.78, and a statistically significant difference between the two groups. The ROC curve delineated an SUVmax cutoff value of 5.650, with an area under the curve (AUC) of approximately 0.909. Based on the cutoff value, the results of the diagnostic performance rendered a sensitivity and negative predictive value of 1.0, whereas the specificity and positive predictive value were 0.909 and 0.875, respectively. CONCLUSIONS: The present study shows that 18F-FDG-PET exhibits a markedly sensitive and negative predictive value in the assessment of spinal gliomas. Additionally, these findings have potential implications for the qualitative assessment of spinal gliomas using 18F-FDG-PET/CT. This imaging modality may be useful for making timely treatment decisions in situations where a detailed diagnosis by molecular analysis is not possible.

Messenger RNA transcription levels of neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex components in the olfactory nerve system of the anadromous Pacific salmon, masu salmon Oncorhynchus masou.

Anadromous Pacific salmon (genus Oncorhynchus) are known for homing behavior to their natal rivers based on olfactory imprinted memories during seaward migration. The SNARE complex is a regulator of vesicle exocytosis from the presynaptic membrane. Our previous study suggested that its component genes (Snap25, Stx1, and Vamp2) are more highly expressed in the olfactory nervous system (ONS) during the migration stages associated with olfactory imprinting in the evolutionary species of Pacific salmon, such as chum (O. keta) and pink (O. gorbuscha) salmon. Masu salmon (O. masou) has a significantly different life history from these species, living longer in rivers and being a more primitive Pacific salmon species. In this study, the transcription of snare mRNAs in the ONS was analyzed using mainly male wild masu salmon. Five cDNAs encoding masu salmon SNAREs, which are well conserved among vertebrates, were isolated and sequenced. Each snare mRNA was highly expressed in age 1+ (yearling) parr prior to smoltification, particularly in the olfactory bulb. Their transcription status was significantly different from that of chum and pink salmon, which showed high expression in earlier under-yearling juveniles. The present results and our previous studies indicate that snare mRNAs are highly transcripted until the seaward migration, reflecting neural development and neuroplasticity of the ONS for olfactory imprinting.

Long-term Outcomes After Endoscopic Submucosal Dissection for Large Colorectal Epithelial Neoplasms: A Prospective, Multicenter, Cohort Trial From Japan.

BACKGROUND & AIMS: To determine the long-term outcomes after colorectal endoscopic submucosal dissection (ESD), we conducted a large, multicenter, prospective cohort trial with a 5-year observation period. METHODS: Between February 2013 and January 2015, we consecutively enrolled 1740 patients with 1814 colorectal epithelial neoplasms ≥20 mm who underwent ESD. Patients with noncurative resection (non-CR) lesions underwent additional radical surgery, as needed. After the initial treatment, intensive 5-year follow-up with planned multiple colonoscopies was conducted to identify metastatic and/or local recurrences. Primary outcomes were overall survival, disease-specific survival, and intestinal preservation rates. The rates of local recurrence and metachronous invasive cancer were evaluated as the secondary outcomes. RESULTS: The 5-year overall survival, disease-specific survival, and intestinal preservation rates were 93.6%, 99.6%, and 88.6%, respectively. Patients with CR lesions had no metastatic occurrence, and patients with non-CR lesions had 4 metastatic occurrences. Kaplan-Meier curves revealed that overall survival and disease-specific survival rates were significantly higher in patients with CR lesions than in those with non-CR lesions (P > .001 and P = .009, respectively). Local recurrence occurred in only 8 lesions (0.5%), which were successfully resected by subsequent endoscopic treatment. Multiple logistic regression analyses revealed that piecemeal resection (hazard ratio, 8.19; 95% CI, 1.47-45.7; P = .02) and margin-positive resection (hazard ratio, 8.06; 95% CI, 1.76-37.0; P = .007) were significant independent predictors of local recurrence after colorectal ESD. Fifteen metachronous invasive cancers (1.0%) were identified during surveillance colonoscopy, most of which required surgical resection. CONCLUSIONS: A favorable long-term prognosis indicates that ESD can be the standard treatment for large colorectal epithelial neoplasms. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000010136.

Oligonucleotide usage in coronavirus genomes mimics that in exon regions in host genomes.

BACKGROUND: Viruses use various host factors for their growth, and efficient growth requires efficient use of these factors. Our previous study revealed that the occurrence frequency of oligonucleotides in the influenza virus genome is distinctly different among derived hosts, and the frequency tends to adapt to the host cells in which they grow. We aimed to study the adaptation mechanisms of a zoonotic virus to host cells. METHODS: Herein, we compared the frequency of oligonucleotides in the genome of alpha- and betacoronavirus with those in the genomes of humans and bats, which are typical hosts of the viruses. RESULTS: By comparing the oligonucleotide frequency in coronaviruses and their host genomes, we found a statistically tested positive correlation between the frequency of coronaviruses and that of the exon regions of the host from which the virus is derived. To examine the characteristics of early-stage changes in the viral genome, which are assumed to accompany the host change from non-humans to humans, we compared the oligonucleotide frequency between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the beginning of the pandemic and the prevalent variants thereafter, and found changes towards the frequency of the host exon regions. CONCLUSIONS: In alpha- and betacoronaviruses, the genome oligonucleotide frequency is thought to change in response to the cellular environment in which the virus is replicating, and actually the frequency has approached the frequency in exon regions in the host.

Examination on Factors Affecting Symptom Change after Drug Withdrawal in Patients with Mild Erosive Gastroesophageal Reflux Disease Undergoing Symptom-Controlled Maintenance Therapy with Acid-Secretion Inhibition Drugs.

INTRODUCTION: In patients with gastroesophageal reflux disease (GERD) on maintenance therapy with acid-suppressive drugs, it is not clear what background factors allow patients to discontinue the drugs. The aims of this study were to examine the relationship of the changes in the frequency and severity of gastrointestinal symptoms after discontinuation of acid-secretion inhibitors for erosive GERD (eGERD) with possible patient background factors and to identify factors that influence these changes. METHODS: This is a multicenter, open-label, interventional, exploratory study. eGERD patients with mild mucosal injury whose symptoms were under control and who were on maintenance therapy with acid-suppressive drugs were withdrawn from the drug treatment for 4 weeks. We examined the relationship of patient backgrounds (sex, age, body mass index, alcohol consumption, smoking habits), esophageal hiatal hernia, Helicobacter pylori infection, pepsinogen I and II concentrations and I/II ratios, blood gastrin levels before and after drug discontinuation with total score change in Frequency Scale for the Symptoms of GERD (FSSG). RESULTS: Of the 92 patients whose symptoms could be assessed before and after drug withdrawal, 66 patients (71.7% of the total) had FSSG <8 and no symptom relapse after the withdrawal. Furthermore, patient background factors that may be related to symptom relapse/non-relapse were examined, but no related factors were detected. The maintenance medications before discontinuation in the above 92 patients were a proton pump inhibitor (PPI) and vonoprazan (VPZ, a potassium ion competitive acid blocker). Since PPI and VPZ were administered to about the same number of patients, though incidentally, we additionally examined the relationship between patient background factors and symptom relapse/non-relapse by treatment group. As a result, no relevant background factors were detected in both groups. Although there were no significant differences between the two groups, the severity and frequency of symptom recurrence in the VPZ group tended to be higher than in the PPI group. CONCLUSIONS: Consideration of background factors is unlikely to be required in the discontinuation of maintenance therapy for eGERD. There was no significant difference in the extent of disease or frequency of recurrence during the discontinuation period, regardless of whether the drug before discontinuation was a PPI or VPZ.

Clinical Guidelines for Diagnosis and Management of Peutz-Jeghers Syndrome in Children and Adults.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus, along with characteristic mucocutaneous pigmentation. It is caused by germline pathogenic variants of the STK11 gene, which exhibit an autosomal dominant mode of inheritance. Some patients with PJS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood and sometimes have serious complications that significantly reduce their quality of life. Hamartomatous polyps in the small bowel may cause bleeding, intestinal obstruction, and intussusception. Novel diagnostic and therapeutic endoscopic procedures such as small-bowel capsule endoscopy and balloon-assisted enteroscopy have been developed in recent years. SUMMARY: Under these circumstances, there is growing concern about the management of PJS in Japan, and there are no practice guidelines available. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labour and Welfare with specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of PJS together with four clinical questions and corresponding recommendations based on a careful review of the evidence and involved incorporating the concept of the Grading of Recommendations Assessment, Development and Evaluation system. KEY MESSAGES: Herein, we present the English version of the clinical practice guidelines of PJS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with PJS.

Association of changes in grip strength with second digit length adjusted for fourth digit length in young children.

OBJECTIVES: The factors involved in changes in grip strength (GS) during growth/development are not well known. Findings from cross-sectional studies have indicated that digit lengths are associated with physical fitness, including GS. This study aimed to investigate the association of changes in GS over 1 year and the second (2D) and fourth (4D) digit lengths in young children using the 4D as a covariate. METHODS: One hundred and three young children (54 boys and 49 girls) performed maximum voluntary GS and ultrasound-measured forearm muscle thickness measurements in the right hand. All participants completed the first measurement and underwent a second measurement 1 year after the first one. The 2D and 4D were taken on the palmar surface of the outstretched right hand at the second measurement. RESULTS: The 2D was inversely associated with the change in GS (B = -2.1, p = 0.023) adjusted for all covariates. Girls had numerically lower adjusted changes in grip strength, although this was not statistically significant [-0.61 (-1.2, 0.02) kg]. When sex was removed from the model, the 2D remained inversely associated with the change in GS (B = -2.39, p = 0.011). Finally, when only adjusting for the 4D, the 2D was inversely associated with the change in GS (B = -3.07, p = 0.004). CONCLUSION: This study documented the association between changes in GS over 1 year and digit lengths in young children. The difference in children's digit length needs to be recognized as a factor involved in weak GS in children.

Handgrip strength of young athletes differs based on the type of sport played and age.

OBJECTIVE: Handgrip strength may differ depending on the type of sport played during the developmental period. Youth sports in which athletes hold equipment in their hands may be the most effective for improving handgrip strength. This study aimed to examine the age at which differences in handgrip strength appear by comparing sports that involve gripping (kendo) with those that do not involve gripping (soccer) in young athletes. METHODS: Two hundred and twenty-two male athletes (115 kendo and 107 soccer) between 6 and 15 years old participated in this study. Handgrip strength was measured using a dynamometer, and the average value of both hands was used for analysis. Sports experience was determined when they started practicing each sport. Handgrip strength was compared between sports. Statistical moderation was used to determine if the relationship between sport and handgrip strength depended upon the age of the athlete. RESULTS: Kendo athletes had significantly higher handgrip strength than soccer athletes (4.77 kg [95% CI: 2.34, 7.19]) in the overall sample. We found that the relationship between sport and handgrip strength depended upon the age of the child (sport*age t = -3.6, p = .004). Using the Johnson-Neyman procedure, we found statistically significant differences between sports from 8.48 years and older. CONCLUSIONS: Our results suggest that the type of sport played, that is, whether or not an athlete plays with sports equipment in their hands, may influence the development of handgrip strength during the period of growth, and these sports may contribute to a higher level of handgrip strength in adulthood.

Athletes in sporting events with upper-body gripping movements have greater handgrip strength than those in sporting events that prioritize the lower body.

OBJECTIVE: Evidence suggests that acquiring a high level of handgrip strength early in life and maintaining that strength throughout life may be important for health. In addition, it is thought that sports activities performed during the developmental period are effective in improving handgrip strength, but it is unknown what types of sports are more effective. As a first step, we conducted a cross-sectional study to compare handgrip strength across different sports (upper-body gripping sports vs. lower body) in early adulthood. METHODS: We used the Juntendo Fitness Plus Study data from 1973 to 2018 and selected two types of sporting events with matching physiques (soccer, baseball, and kendo) but different degrees of gripping. Data on 7344 male first-year sports university students included 1127 soccer, 297 Kendo, and 698 baseball players. RESULTS: Those in the lower body-only (soccer) sports had -3.78 (95% CI: -4.27, -3.29) kg lower handgrip strength than those in the lower + upper (kendo and baseball). Comparing each individual sport found that each sport was different from each other with Kendo > Baseball > Soccer (between each sport, p < .001). In addition, the difference between sports has become greater across time. CONCLUSIONS: In early adulthood, handgrip strength is greatest in those participating in sports with upper-body movements compared to those participating in sports that mainly involved lower-body movements. The three sports we selected are natural activities that do not directly train handgrip strength. Therefore, sport may be one potential method to improve low handgrip strength in children/adolescents during the developmental period.

Sex segregation in strength sports: Do equal-sized muscles express the same levels of strength between sexes?

OBJECTIVES: Concerns have been raised against the current two-sex binary category in sports competitions. The thesis states that if males and females were separated based on muscle size, it would negate the strength advantage between the sexes. We tested the possible sex differences in various strength outcomes when pair-matched for muscle thickness. METHODS: A total of 16 different data sets (n = 963) were assessed to pair-match females with males who had a muscle thickness value within 2%. We further compared the competition performances of the smallest male weight class within the International Powerlifting Federation (IPF) to different weight classes in females. RESULTS: Overall, 76%-88% of the strength assessments were greater in males than females with pair-matched muscle thickness, regardless of contraction types (i.e., isotonic, isometric, isokinetic). Additionally, males in the lightest weight division in the IPF largely outperformed females in heavier weight divisions. CONCLUSIONS: Our results would suggest that segregation based on muscle mass or surrogates of muscle mass (e.g., lean body mass) might not be an appropriate classification to create fair competition within strength sports. This is not to refute the concept of the desegregation of the two-sex binary category but to present data that raises important concerns about the potential sex-based differences in strength performance.

Behavioral and brain- transcriptomic synchronization between the two opponents of a fighting pair of the fish Betta splendens.

Conspecific male animals fight for resources such as food and mating opportunities but typically stop fighting after assessing their relative fighting abilities to avoid serious injuries. Physiologically, how the fighting behavior is controlled remains unknown. Using the fighting fish Betta splendens, we studied behavioral and brain-transcriptomic changes during the fight between the two opponents. At the behavioral level, surface-breathing, and biting/striking occurred only during intervals between mouth-locking. Eventually, the behaviors of the two opponents became synchronized, with each pair showing a unique behavioral pattern. At the physiological level, we examined the expression patterns of 23,306 brain transcripts using RNA-sequencing data from brains of fighting pairs after a 20-min (D20) and a 60-min (D60) fight. The two opponents in each D60 fighting pair showed a strong gene expression correlation, whereas those in D20 fighting pairs showed a weak correlation. Moreover, each fighting pair in the D60 group showed pair-specific gene expression patterns in a grade of membership analysis (GoM) and were grouped as a pair in the heatmap clustering. The observed pair-specific individualization in brain-transcriptomic synchronization (PIBS) suggested that this synchronization provides a physiological basis for the behavioral synchronization. An analysis using the synchronized genes in fighting pairs of the D60 group found genes enriched for ion transport, synaptic function, and learning and memory. Brain-transcriptomic synchronization could be a general phenomenon and may provide a new cornerstone with which to investigate coordinating and sustaining social interactions between two interacting partners of vertebrates.

Comparative genomic analysis of the human genome and six bat genomes using unsupervised machine learning: Mb-level CpG and TFBS islands.

BACKGROUND: Emerging infectious disease-causing RNA viruses, such as the SARS-CoV-2 and Ebola viruses, are thought to rely on bats as natural reservoir hosts. Since these zoonotic viruses pose a great threat to humans, it is important to characterize the bat genome from multiple perspectives. Unsupervised machine learning methods for extracting novel information from big sequence data without prior knowledge or particular models are highly desirable for obtaining unexpected insights. We previously established a batch-learning self-organizing map (BLSOM) of the oligonucleotide composition that reveals novel genome characteristics from big sequence data. RESULTS: In this study, using the oligonucleotide BLSOM, we conducted a comparative genomic study of humans and six bat species. BLSOM is an explainable-type machine learning algorithm that reveals the diagnostic oligonucleotides contributing to sequence clustering (self-organization). When unsupervised machine learning reveals unexpected and/or characteristic features, these features can be studied in more detail via the much simpler and more direct standard distribution map method. Based on this combined strategy, we identified the Mb-level enrichment of CG dinucleotide (Mb-level CpG islands) around the termini of bat long-scaffold sequences. In addition, a class of CG-containing oligonucleotides were enriched in the centromeric and pericentromeric regions of human chromosomes. Oligonucleotides longer than tetranucleotides often represent binding motifs for a wide variety of proteins (e.g., transcription factor binding sequences (TFBSs)). By analyzing the penta- and hexanucleotide composition, we observed the evident enrichment of a wide range of hexanucleotide TFBSs in centromeric and pericentromeric heterochromatin regions on all human chromosomes. CONCLUSION: Function of transcription factors (TFs) beyond their known regulation of gene expression (e.g., TF-mediated looping interactions between two different genomic regions) has received wide attention. The Mb-level TFBS and CpG islands are thought to be involved in the large-scale nuclear organization, such as centromere and telomere clustering. TFBSs, which are enriched in centromeric and pericentromeric heterochromatin regions, are thought to play an important role in the formation of nuclear 3D structures. Our machine learning-based analysis will help us to understand the differential features of nuclear 3D structures in the human and bat genomes.

Unsupervised explainable AI for molecular evolutionary study of forty thousand SARS-CoV-2 genomes.

BACKGROUND: Unsupervised AI (artificial intelligence) can obtain novel knowledge from big data without particular models or prior knowledge and is highly desirable for unveiling hidden features in big data. SARS-CoV-2 poses a serious threat to public health and one important issue in characterizing this fast-evolving virus is to elucidate various aspects of their genome sequence changes. We previously established unsupervised AI, a BLSOM (batch-learning SOM), which can analyze five million genomic sequences simultaneously. The present study applied the BLSOM to the oligonucleotide compositions of forty thousand SARS-CoV-2 genomes. RESULTS: While only the oligonucleotide composition was given, the obtained clusters of genomes corresponded primarily to known main clades and internal divisions in the main clades. Since the BLSOM is explainable AI, it reveals which features of the oligonucleotide composition are responsible for clade clustering. Additionally, BLSOM also provided information concerning the special genomic region possibly undergoing RNA modifications. CONCLUSIONS: The BLSOM has powerful image display capabilities and enables efficient knowledge discovery about viral evolutionary processes, and it can complement phylogenetic methods based on sequence alignment.

Immune-related Liver Injury is a Poor Prognostic Factor in Patients with Nonsmall Cell Lung Cancer Treated with Immune Checkpoint Inhibitors.

It remains unclear whether severe liver immune-related adverse events (liver-irAEs) can affect the prognosis in nonsmall cell lung carcinoma (NSCLC) patients. Of the 365 NSCLC patients treated with immune checkpoint inhibitors (ICIs), 19 suffered from severe liver-irAEs (grade ≥3). The median time-to-onset of liver-irAEs was 53 days postinjection of the first ICI. The progression-free survival and overall survival of the liver-irAEs group (median 69 and 262 days, respectively) were significantly worse than the nonliver-irAEs group (128 and 722 days; P = 0.010 and P = 0.007; respectively). In conclusion, liver-irAEs were associated with poor prognosis in NSCLC patients.

Optimal surveillance interval after piecemeal endoscopic mucosal resection for large colorectal neoplasia: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Colorectal neoplastic lesions (≥ 20 mm) are commonly treated via piecemeal endoscopic mucosal resection (p-EMR) but have a high rate of local recurrence. We aimed to clarify the optimal surveillance interval after p-EMR for these neoplasias. METHODS: In this multicenter (15 participating institutions) prospective, randomized trial, 180 patients recruited over a 4-year period and were classified based on tumor location, tumor diameter, histological diagnosis, institution, and number of resected specimens. The patients underwent curative p-EMR followed by scheduled surveillance colonoscopy at 3, 6, 12, and 24 months after p-EMR (group A; n = 90) or at 6, 12, and 24 months after p-EMR (group B; n = 90). The primary endpoint was cumulative local recurrence at 6 months after p-EMR. Secondary endpoints included local recurrence and the cumulative surgical resection rate of recurrent tumors during the 24-month follow-up period. RESULTS: The median tumor diameter was 25 mm (IQR 20-30). Six months after p-EMR, 12 and 6 local recurrences were noted in groups A and B, which corresponded to 13 and 8 recurrences, respectively, during the 24-month surveillance period. The primary and secondary endpoints of recurrence were not significantly different between the groups on either intention-to-treat or per-protocol analysis; no surgery case was observed in group B when a strict surveillance protocol of 6-, 12-, and 24-month follow-up post-EMR was followed. CONCLUSIONS: For patients who underwent p-EMR for neoplastic lesions, additional postprocedural 3-month surveillance did not show superior results in detecting recurrence compared with a 6-month surveillance interval. CLINICAL TRIAL REGISTRATION: UMIN000015740.

A longitudinal study of handgrip strength asymmetry.

OBJECTIVE: The previous results from cross-sectional studies indicate that there could be alterations across time in handgrip strength (HGS) asymmetry. One way to investigate this is to test the same children multiple times. Therefore, we aimed to evaluate the laterality of HGS in healthy young children at two different time points separated by a year. METHODS: A total of 165 preschool children (79 males and 87 females) between the ages of 4.5 and 5.6 years participated and performed maximal voluntary HGS in both hands using a Smedley handgrip dynamometer. We ran a paired sample t-test on the difference scores (right - left vs. right - left) to determine if HGS (right vs. left) differed across time. RESULTS: The difference between hands (t = -4.804, p < .0001) did differ between time points. At the initial test, the mean value of the HGS in the right hand was approximately 15% higher than that of the left hand. This difference between hands was reduced following a year. The mean bias between tests (second test - initial test) and the 95% limits of agreement was -0.84 (-5.27, 3.58) kg. CONCLUSION: Contrary to our hypothesis, HGS asymmetry during the initial test (at age 5) was not observed in the second test completed a year later (at age 6). These results suggest that HGS asymmetry is uncertain in children between 5 and 6 years. In this short-term study, it was impossible to ascertain when HGS asymmetry first appeared. Longer term studies are required to better determine when these changes occur.