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Measuring mechanical forces of cell-cell interactions is important for studying morphogenesis in multicellular organisms. We previously reported an image-based statistical method for inferring effective mechanical potentials of pairwise cell-cell interactions by fitting cell tracking data with a theoretical model. However, whether this method is applicable to tissues with non-cellular components such as cavities remains elusive. Here we evaluated the applicability of the method to cavity-harboring tissues. Using synthetic data generated by simulations, we found that the effect of expanding cavities was added to the pregiven potentials used in the simulations, resulting in the inferred effective potentials having an additional repulsive component derived from the expanding cavities. Interestingly, simulations by using the effective potentials reproduced the cavity-harboring structures. Then, we applied our method to the mouse blastocysts, and found that the inferred effective potentials can reproduce the cavity-harboring structures. Pairwise potentials with additional repulsive components were also detected in two-dimensional cell sheets, by which curved sheets including tubes and cups were simulated. We conclude that our inference method is applicable to tissues harboring cavities and cell sheets, and the resultant effective potentials are useful to simulate the morphologies.
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Data-driven techniques could be used to enhance decision-making capacity of breeders and farmers. We used an RGB camera on an unmanned aerial vehicle (UAV) to collect time series data on sugar beet canopy coverage (CC) and canopy height (CH) from small-plot breeding fields including 20 genotypes per season over 3 seasons. Digital orthomosaic and digital surface models were created from each flight and were converted to individual plot-level data. Plot-level data including CC and CH were calculated on a per-plot basis. A multiple regression model was fitted, which predicts root weight (RW) (r = 0.89, 0.89, and 0.92 in the 3 seasons, respectively) and sugar content (SC) (r = 0.79, 0.83, and 0.77 in the 3 seasons, respectively) using individual time point CC and CH data. Individual CC and CH values in late June tended to be strong predictors of RW and SC, suggesting that early season growth is critical for obtaining high RW and SC. Coefficient of parentage was not a strong factor influencing SC. Integrals of CC and CH time series data were calculated for genetic analysis purposes since they are more stable over multiple growing seasons. Calculations of general combining ability and specific combining ability in F1 offspring demonstrate how growth curve quantification can be used in diallel cross analysis and yield prediction. Our simple yet robust solution demonstrates how state-of-the-art remote sensing tools and basic analysis methods can be applied to small-plot breeder fields for selection purpose.
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BACKGROUND: Inherited glycosylphosphatidylinositol (GPI) deficiency is an autosomal recessive disease and a set of syndromes caused by different genes involved in the biosynthesis of phosphatidylinositol characterized by severe cognitive disability, elevated serum alkaline phosphatase (ALP) levels, and distinct facial features. This report presents a patient with inherited GPI deficiency caused by a homozygous frameshift variant of PGAP3 due to uniparental isodisomy (UPiD) on chromosome 17. METHOD: Clinical characteristics of the patient were collected. Microarray analysis followed by adaptive sampling sequencing targeting chromosome 17 was used for the identification of variants. Sanger sequencing was used to confirm the variant in the target region. RESULTS: The patient was born at 38 weeks of gestation with a birthweight of 3893 g. He had a distinctive facial appearance with hypertelorism, wide nasal bridge, and cleft soft palate. Postnatal head magnetic resonance imaging revealed a Blake's pouch cyst. The serum ALP level was 940 IU/L at birth and increased to 1781 IU/L at 28 days of age. Microarray analysis revealed region of homozygosity in nearly the entire region of chromosome 17, leading to the diagnosis of UPiD. Adaptive sampling sequencing targeting chromosome 17 confirmed the homozygous variant NM_033419:c.778dupG (p.Val260Glyfs*14) in the PGAP3 gene, resulting in a diagnosis of inherited GPI deficiency. CONCLUSION: This is the first report of inherited GPI deficiency caused by UPiD. Inherited GPI deficiency must be considered in patients with unexplained hyperphosphatasemia.
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Glicosilfosfatidilinositoles , Disomía Uniparental , Humanos , Masculino , Hidrolasas de Éster Carboxílico , Mutación del Sistema de Lectura , Glicosilfosfatidilinositoles/deficiencia , Glicosilfosfatidilinositoles/genética , Homocigoto , Errores Innatos del Metabolismo/genética , Errores Innatos del Metabolismo/patología , Trastornos del Metabolismo del Fósforo/genética , Trastornos del Metabolismo del Fósforo/patología , Receptores de Superficie Celular , Convulsiones , Disomía Uniparental/genética , Disomía Uniparental/patología , Recién NacidoRESUMEN
Meconium, a non-invasive biomaterial reflecting prenatal substance accumulation, could provide valuable insights into neonatal health. However, the comprehensive protein profile of meconium across gestational ages remains unclear. Here, we conducted an extensive proteomic analysis of first meconium from 259 newborns across varied gestational ages to delineate protein composition and elucidate its relevance to neonatal diseases. The first meconium samples were collected, with the majority obtained before feeding, and the mean time for the first meconium passage from the anus was 11.9 ± 9.47 h. Our analysis revealed 5370 host-derived meconium proteins, which varied depending on sex and gestational age. Specifically, meconium from preterm infants exhibited elevated concentrations of proteins associated with the extracellular matrix. Additionally, the protein profiles of meconium also exhibited unique variations depending on both specific diseases, including gastrointestinal diseases, congenital heart diseases, and maternal conditions. Furthermore, we developed a machine learning model to predict gestational ages using meconium proteins. Our model suggests that newborns with gastrointestinal diseases and congenital heart diseases may have immature gastrointestinal systems. These findings highlight the intricate relationship between clinical parameters and meconium protein composition, offering potential for a novel approach to assess neonatal gastrointestinal health.
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Edad Gestacional , Aprendizaje Automático , Meconio , Proteómica , Humanos , Meconio/metabolismo , Recién Nacido , Femenino , Masculino , Proteómica/métodos , Recien Nacido Prematuro/metabolismo , Enfermedades Gastrointestinales/metabolismo , Cardiopatías Congénitas/metabolismo , Embarazo , Proteoma/metabolismoRESUMEN
BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is a syndrome characterized by a long-term muscle weakness often observed in sepsis-surviving patients during the chronic phase. Although ICU-AW is independently associated with increased mortality, effective therapies have yet to be established. Programmed death-1 (PD-1) inhibitors have attracted attention as potential treatments for reversing immune exhaustion in sepsis; however, its impact on ICU-AW remains to be elucidated. Here, we study how PD-1 deficiency affects sepsis-induced skeletal muscle dysfunction in a preclinical sepsis model. METHODS: Chronic sepsis model was developed by treating wild-type (WT) and PD-1 knockout (KO) mice with caecal slurry, followed by resuscitation with antibiotics and saline. Mice were euthanized on days 15-17. Body weights, muscle weights, and limb muscle strengths were measured. Interleukin 13 (IL-13) and PD-1 expressions were examined by flow cytometry. Messenger RNA (mRNA) expressions of slow-twitch muscles were measured by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). In an in vitro study, C2C12 myotubes were treated with lipopolysaccharide (LPS) and recombinant IL-13 followed by gene expression measurements. RESULTS: WT septic mice exhibited decreased muscle weight (quadriceps, P < 0.01; gastrocnemius, P < 0.05; and tibialis anterior, P < 0.01) and long-term muscle weakness (P < 0.0001), whereas PD-1 KO septic mice did not exhibit any reduction in muscle weights and strengths. Slow-twitch specific mRNAs, including myoglobin (Mb), troponin I type 1 (Tnni1), and myosin heavy chain 7 (Myh7) were decreased in WT skeletal muscle (Mb, P < 0.0001; Tnni1, P < 0.05; and Myh7, P < 0.05) after sepsis induction, but mRNA expressions of Tnni1 and Myh7 were increased in PD-1 KO septic mice (Mb, not significant; Tnni1, P < 0.0001; and Myh7, P < 0.05). Treatment of C2C12 myotube cells with LPS decreased the expression of slow-twitch mRNAs, which was restored by IL-13 (Mb, P < 0.0001; Tnni1, P < 0.001; and Myh7, P < 0.05). IL-13 production was significantly higher in ILC2s compared to T cells in skeletal muscle (P < 0.05). IL-13-producing ILC2s in skeletal muscle were examined and found to increase in PD-1 KO septic mice, compared with WT septic mice (P < 0.05). ILC2-derived IL-13 was increased by PD-1 KO septic mice and thought to protect the muscles from experimental ICU-AW. CONCLUSIONS: Long-term muscle weakness in experimental ICU-AW was ameliorated in PD-1 KO mice. ILC2-derived IL-13 production in skeletal muscles was increased in PD-1 KO mice, thereby suggesting that IL-13 alleviates muscle weakness during sepsis. This study demonstrates the effects of PD-1 blockade in preserving muscle strength during sepsis through an increase in ILC2-derived IL-13 and may be an attractive therapeutic target for sepsis-induced ICU-AW.
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The binding ratio of palmitic acid (PA) at the sn-2 position of triacylglycerols in infant formulas is lower than that in breast milk, resulting in higher levels of fecal PA. Even if the ratio is increased to 40-50%, fecal PA levels in formula-fed infants remain higher than those in breast-fed infants. In Japan, infant formulas with 50% or more of PA bound to sn-2 (high sn-2 PA milk) are commercially available; however, their effects on PA excretion have not been investigated. Therefore, this observational study aimed to preliminarily evaluate whether the feeding volume of high sn-2 PA milk is significantly associated with fecal total/soaped PA levels in newborns. Infant formulas were classified as high (≥50% of PA bound to sn-2) or low sn-2 (<50%) PA milk. Associations between feeding volume of high or low sn-2 PA milk and fecal PA levels were evaluated using multiple regression analysis models. The results showed that the feeding volume of low sn-2 PA milk was positively associated with fecal total/soaped PA levels, while there was no significant association between those of high sn-2 PA milk and fecal total/soaped PA levels. Our preliminary study suggests that high sn-2 PA milk may reduce increased fecal PA levels in formula-fed newborns.
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Heces , Fórmulas Infantiles , Ácido Palmítico , Triglicéridos , Humanos , Fórmulas Infantiles/química , Heces/química , Ácido Palmítico/análisis , Triglicéridos/análisis , Triglicéridos/química , Recién Nacido , Femenino , Masculino , Fenómenos Fisiológicos Nutricionales del Lactante , Leche Humana/química , JapónRESUMEN
BACKGROUND: Although patients with chronic pain show behavioral signs of impaired endogenous pain modulation, responsible cerebral networks have yet to be anatomically delineated. We used diffusion tensor imaging (DTI) to examine the white-matter alterations in patients with chronic pain compared with healthy subjects. We further measured thermal pain modulatory responses using the offset analgesia (OA) paradigm. We tested whether the white-matter indices be associated with psychophysical parameters reflecting morbidity and modulatory responses of pain in patients, and whether they could serve as diagnostic biomarkers of chronic pain. METHODS: Twenty-six patients with chronic pain and 18 age- and gender-matched healthy controls were enrolled. After completing psychophysical questionnaires, they underwent OA measurement and whole-brain DTI in a 3 Tesla magnetic resonance imaging scanner. Fractional anisotropy (FA) and radial diffusivity (RD) of the white-matter were computed and compared between the groups with tract-based spatial statistics using the FMRIB Software Library (FSL) software. Correlations were sought among white-matter indices, thermal pain responses, and psychophysical parameters. The white-matter indices and OA-related parameters were tested whether they distinguish patients from controls by receiver operating characteristic analysis. RESULTS: During OA, patients showed a shorter latency to the maximum (maximum visual analog scale [VAS] latency, 16.0 ± 3.7 vs 18.9 ± 3.1 second [mean ± standard deviation, SD]; P = .032) but a longer latency to the minimum pain (OA latency, 15.6 ± 3.5 vs 11.1 ± 4.2 seconds; P = .004) than controls. They showed a smaller mean FA (0.44 ± 0.12 vs 0.45 ± 0.11; P = .012) and a larger mean RD of the global white-matter (0.00057 ± 0.00002 vs 0.00056 ± 0.00002; P = .038) than controls, at specific areas including the corpus callosum, anterior thalamic radiation, and forceps major. FA of the splenium of the corpus callosum was associated with maximum VAS latency (r = 0.493) and OA latency (r = -0.552). The Pain Catastrophizing Scale scores showed strong negative correlations with FA across those specific areas (r = -0.405). Those latencies during OA and white-matter metrics distinguished patients from controls (P < .05). CONCLUSIONS: Patients with chronic pain showed dysfunction of the white matter concerned with interhemispheric communication of sensorimotor information as well as descending corticothalamic modulation of pain in association with affective morbidity and altered temporal dynamics of pain perception. We suggest that an impaired interhemispheric modulation of pain, through the corpus callosum, might be a novel cerebral mechanism in chronification of pain.
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BCL6-rearrangement (BCL6-R) is associated with a favorable prognosis of follicular lymphoma (FL), but the mechanism is unknown. We analyzed the clinicopathological, immune microenvironment (immune checkpoint, immuno-oncology markers), and mutational profiles of 10 BCL6-R-positive FL, and 19 BCL6-R-positive diffuse large B-cell lymphoma (DLBCL) cases (both BCL2-R and MYC-R negative). A custom-made panel included 168 genes related to aggressive B-cell lymphomas and FL. FL cases were nodal, histological grade 3A in 70%, low Ki67; and had a favorable overall and progression-free survival. DLBCL cases were extranodal in 60%, IPI high in 63%, non-GCB in 60%, EBER-negative; and had a progression-free survival comparable to that of DLBCL NOS. The microenvironment had variable infiltration of M2-like tumor-associated macrophages (TAMs) that were CD163, CSF1R, LAIR1, PD-L1, and CD85A (LILRB3) positive; but had low IL10 and PTX3 expression. In comparison to FL, DLBCL had higher TAMs, IL10, and PTX3 expression. Both lymphoma subtypes shared a common mutational profile with mutations in relevant pathogenic genes such as KMT2D, OSBPL10, CREBBP, and HLA-B (related to chromatin remodeling, metabolism, epigenetic modification, and antigen presentation). FL cases were characterized by a higher frequency of mutations of ARID1B, ATM, CD36, RHOA, PLOD2, and PRPRD (p < 0.05). DLBCL cases were characterized by mutations of BTG2, and PIM1; and mutations of HIST1H1E and MFHAS1 to disease progression (p < 0.05). Interestingly, mutations of genes usually associated with poor prognosis, such as NOTCH1/2 and CDKN2A, were infrequent in both lymphoma subtypes. Some high-confidence variant calls were likely oncogenic, loss-of-function. MYD88 L265P gain-of-function was found in 32% of DLBCL. In conclusion, both BCL6-R-positive FL and BCL6-R-positive DLBCL had a common mutational profile; but also, differences. DLBCL cases had a higher density of microenvironment markers.
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Biomarcadores de Tumor , Linfoma Folicular , Linfoma de Células B Grandes Difuso , Mutación , Proteínas Proto-Oncogénicas c-bcl-6 , Microambiente Tumoral , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/inmunología , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Linfoma Folicular/genética , Linfoma Folicular/patología , Linfoma Folicular/inmunología , Proteínas Proto-Oncogénicas c-bcl-6/genética , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Biomarcadores de Tumor/genética , Anciano de 80 o más Años , Reordenamiento Génico , Análisis Mutacional de ADN , Supervivencia sin ProgresiónRESUMEN
Ectopia cordis is a rare condition with expected low survival rate based on past studies. We encountered a case of a preterm and low birth weight infant with ectopia cordis. When the infant cried, the prolapse of the heart, liver, and intestinal tract worsened. A pressure-applying protector was used to protect the organs and reduce the prolapse. Upon application, the infant's tachypnea and desaturation worsened. Fluoroscopic examination suggested that the pressure from the prolapsed regions was impeding pulmonary expansion and negatively affecting circulation. It is essential to carefully design a protector that accommodates the infant's growth.
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BACKGROUND: Although neonatal disseminated intravascular coagulation (DIC) is associated with high mortality and severe complications, few studies have reported its clinical course. We aimed to describe the characteristics, treatments, and outcomes of neonatal DIC by using a national inpatient database. METHODS: Using the Japanese Diagnosis Procedure Combination database, we identified 5533 patients with neonatal DIC who were admitted to neonatal intensive care units between July 2010 and March 2020. We categorized the patients into those with asphyxia (n = 2911) and those without asphyxia (n = 2622). We investigated the patient characteristics, treatments, and outcomes. We further categorized neonates with asphyxia according to its severity. RESULTS: The gestational age of neonates with asphyxia was significantly lower than that of neonates without asphyxia (P < 0.001). Antithrombin was most commonly used for DIC (40%). Neonates with asphyxia were more likely to receive antithrombin (43% vs. 38%; P < 0.001), recombinant human soluble thrombomodulin (28% vs. 20%; P < 0.001), and fresh frozen plasma transfusion (68% vs. 51%; P < 0.001) than those without asphyxia. Neonates with asphyxia had higher in-hospital mortality (17% vs. 10%; P < 0.001), severe bleeding (11% vs. 6.8%; P < 0.001), and hospitalization costs than those without asphyxia. Additionally, neonates with severe asphyxia were more likely to receive several DIC therapies (such as recombinant human soluble thrombomodulin [30% vs. 24%]) and had higher in-hospital mortality (19% vs. 11%) and hospitalization costs than those with mild asphyxia. CONCLUSIONS: In this large retrospective study of neonatal DIC, patients with asphyxia received several treatments and demonstrated unfavorable outcomes when compared to those without asphyxia.
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Asfixia Neonatal , Coagulación Intravascular Diseminada , Enfermedades del Recién Nacido , Recién Nacido , Humanos , Trombomodulina/uso terapéutico , Japón , Estudios Retrospectivos , Asfixia/complicaciones , Asfixia/tratamiento farmacológico , Coagulación Intravascular Diseminada/etiología , Coagulación Intravascular Diseminada/terapia , Transfusión de Componentes Sanguíneos/efectos adversos , Plasma , Antitrombinas/uso terapéutico , Asfixia Neonatal/complicaciones , Asfixia Neonatal/terapiaRESUMEN
BACKGROUND/AIM: Lung adenocarcinoma and lung squamous cell carcinoma represent the most prevalent subtypes of non-small cell lung cancer eligible for surgery in the early stages. The emergence of immune checkpoint inhibitors as adjuvant therapy has shown promising potential in improving the postoperative prognosis of patients with lung cancer. Hence, a comprehensive understanding of the clinicopathological and molecular features of programmed cell death ligand-1 (PD-L1) expression in lung adenocarcinoma and squamous cell carcinoma is crucial. PATIENTS AND METHODS: In this retrospective study, we conducted a comparative analysis of clinicopathological features associated with the expression of PD-L1, stratifying patients who underwent surgical resection into two distinct groups: 289 patients with lung adenocarcinoma and 66 with lung squamous cell carcinoma. Furthermore, we investigated the associations between the expression of PD-L1 and genetic alterations in well-established oncogenic driver mutations. RESULTS: Among the cases, 52.9% exhibited negative PD-L1 expression, 32.9% had low PD-L1 expression, and 12.3% had high PD-L1 expression in adenocarcinoma, while the PD-L1 expression in squamous cell carcinoma showed a near-even distribution. Notably, male sex, smoking history, the presence of invasive pathological factors, and disease progression significantly influenced PD-L1 expression in adenocarcinoma, whereas none of these factors were associated with PD-L1 expression in squamous cell carcinoma. Additionally, the distribution of PD-L1 expression varied based on the type of specific driver gene mutation in adenocarcinoma. CONCLUSION: The present study revealed clinicopathological and molecular differences between lung adenocarcinoma and squamous cell carcinoma patients promoting the expression of PD-L1.
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Adenocarcinoma del Pulmón , Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Masculino , Adenocarcinoma , Adenocarcinoma del Pulmón/genética , Antígeno B7-H1/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Estudios RetrospectivosRESUMEN
INTRODUCTION: Milrinone is administered after patent ductus arteriosus (PDA) ligation to prevent and treat postoperative hemodynamic instability (i.e., postligation cardiac syndrome). We aimed to explore the effectiveness of milrinone on in-hospital outcomes in infants who underwent PDA ligation using a nationwide inpatient database in Japan. METHODS: Using the Japanese Diagnosis Procedure Combination database, we identified patients who received milrinone after PDA ligation (n = 428) in neonatal intensive care units between July 2010 and March 2021 and those who did not (n = 3,392). We conducted a 1:4 propensity score-matched analysis with adjustment for background characteristics (e.g., gestational age, birth weight, comorbidities, preoperative treatments, and hospital background) to compare morbidities (bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity), mortality, total hospitalization costs, and other outcomes. For sensitivity analysis, we performed an overlap propensity score-weighted analysis. RESULTS: In-hospital morbidity, bronchopulmonary dysplasia, intraventricular hemorrhage, and necrotizing enterocolitis occurred in 58%, 48%, 9.5%, and 7.1% of patients, respectively; the in-hospital mortality was 5.4%. After 1:4 propensity score matching, no significant difference was observed regarding mortality (7.1 vs. 5.7%), in-hospital morbidity (55 vs. 50%), bronchopulmonary dysplasia (44 vs. 41%), intraventricular hemorrhage (7.8 vs. 9.1%), necrotizing enterocolitis (8.5 vs. 8.9%), retinopathy of prematurity (21 vs. 22%), or total hospitalization costs (median: approximately 86,000 vs. 82,000 US dollars) between milrinone users (n = 425) and nonusers (n = 1,698). Sensitivity analyses yielded consistent results. CONCLUSIONS: Milrinone use after PDA ligation was not associated with improved in-hospital outcomes, such as mortality and morbidity.
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Displasia Broncopulmonar , Conducto Arterioso Permeable , Enterocolitis Necrotizante , Retinopatía de la Prematuridad , Lactante , Recién Nacido , Humanos , Conducto Arterioso Permeable/tratamiento farmacológico , Conducto Arterioso Permeable/cirugía , Conducto Arterioso Permeable/complicaciones , Milrinona/uso terapéutico , Estudios Retrospectivos , Enterocolitis Necrotizante/epidemiología , Displasia Broncopulmonar/epidemiología , Displasia Broncopulmonar/prevención & control , Displasia Broncopulmonar/complicaciones , Retinopatía de la Prematuridad/complicaciones , Recien Nacido Prematuro , Hemorragia Cerebral/complicaciones , Ligadura/efectos adversosRESUMEN
Bronchoscopy with radial-probe endobronchial ultrasound, a guide sheath, and electromagnetic navigation can improve the diagnostic yield of peripheral lung nodules. However, the suitability of specimens for genetic analysis remains unsatisfactory. We hypothesized that a transbronchial biopsy performed after closely approaching the bronchoscope tip to the lesion might provide more suitable specimens for genetic analysis. We enrolled 155 patients with peripheral pulmonary lesions who underwent bronchoscopy with a thin or ultrathin bronchoscope. Bronchoscopy was performed using virtual bronchoscopic navigation and radial-probe endobronchial ultrasound with a guide sheath. The bronchoscope tip was placed closer to the lesion during bronchoscopy to collect larger specimens with higher malignant cell content. The patients who underwent a close-to-lesion biopsy had higher rates of overall diagnostic yield, histopathological diagnostic yield, and specimen quality for genetic testing than those who did not. The significant determinants of the specimen's suitability were the close-to-lesion approach, within-the-lesion image, the use of standard 1.9-mm-forceps, and the number of cancer-cell-positive specimens. The significant predictors of the specimen's suitability for genetic analysis were close-to-lesion biopsy and the number of malignant cell-positive tissue samples. This study demonstrates that the close-to-lesion transbronchial biopsy significantly improves the suitability of bronchoscopic specimens for genetic analysis.
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Broncoscopía , Pruebas Genéticas , Humanos , Masculino , Biopsia , Endosonografía , PrepucioRESUMEN
Mechanical forces are critical for the emergence of diverse three-dimensional morphologies of multicellular systems. However, it remains unclear what kind of mechanical parameters at cellular level substantially contribute to tissue morphologies. This is largely due to technical limitations of live measurements of cellular forces. Here we developed a framework for inferring and modeling mechanical forces of cell-cell interactions. First, by analogy to coarse-grained models in molecular and colloidal sciences, we approximated cells as particles, where mean forces (i.e. effective forces) of pairwise cell-cell interactions are considered. Then, the forces were statistically inferred by fitting the mathematical model to cell tracking data. This method was validated by using synthetic cell tracking data resembling various in vivo situations. Application of our method to the cells in the early embryos of mice and the nematode Caenorhabditis elegans revealed that cell-cell interaction forces can be written as a pairwise potential energy in a manner dependent on cell-cell distances. Importantly, the profiles of the pairwise potentials were quantitatively different among species and embryonic stages, and the quantitative differences correctly described the differences of their morphological features such as spherical vs. distorted cell aggregates, and tightly vs. non-tightly assembled aggregates. We conclude that the effective pairwise potential of cell-cell interactions is a live measurable parameter whose quantitative differences can be a parameter describing three-dimensional tissue morphologies.
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Caenorhabditis elegans , Modelos Teóricos , Animales , Rastreo Celular , Desarrollo EmbrionarioRESUMEN
BACKGROUND: The soft X-ray projection microscope has been developed for high resolution imaging of hydrated bio-specimens. Image blurring due to X-ray diffraction can be corrected by an iteration procedure. The correction is not efficient enough for all images, especially for low contrast chromosome images. OBJECTIVE: The purpose of this study is to improve X-ray imaging techniques using a finer pinhole and reducing capture time, as well as to improve image correction methods. A method of specimen staining prior to the imaging was tested in order to capture images with high contrasts. The efficiency of the iteration procedure and its combined version with an image enhancement method was also assessed. METHODS: In image correction, we used the iteration procedure and its combined version with an image enhancement technique. To capture higher contrast images, we stained chromosome specimens with the Platinum blue (Pt-blue) prior to the imaging. RESULTS: The iteration procedure combined with image enhancement corrected the chromosome images with 329 or lower magnification effectively. Using the Pt-blue staining for the chromosome, images with high contrast have been captured and successfully corrected. CONCLUSIONS: The image enhancement technique combining contrast enhancement and noise removal together was effective to obtain higher contrast images. As a result, the chromosome images with 329 or lower times magnification were corrected effectively. With Pt-blue staining, chromosome images with contrasts of 2.5 times higher than unstained case could be captured and corrected by the iteration procedure.
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Algoritmos , Microscopía , Rayos X , Intensificación de Imagen Radiográfica/métodos , Tomografía Computarizada de Haz Cónico/métodos , Fantasmas de Imagen , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Radiation-induced bystander response (RIBR) is a response induced in non-irradiated cells that receive bystander signals from directly irradiated cells. X-ray microbeams are useful tools for elucidating the mechanisms underlying RIBR. However, previous X-ray microbeams used low-energy soft X-rays with higher biological effects, such as aluminum characteristic X-rays, and the difference from conventional X-rays and γ-rays has often been discussed. The microbeam X-ray cell irradiation system at the Central Research Institute of Electric Power Industry has been upgraded to generate higher energy titanium characteristic X-rays (TiK X-rays), which have a longer penetration distance sufficient to irradiate 3D cultured tissues. Using this system, we irradiated the nuclei of HeLa cells with high precision and found that the pan-nuclear induction of phosphorylated histone H2AX on serine 139 (γ-H2AX) in the non-irradiated cells increased 180 and 360 min after irradiation. We established a new method to quantitatively evaluate bystander cells, using the fluorescence intensity of γ-H2AX as an indicator. The percentage of bystander cells increased significantly to 23.2% ± 3.2% and 29.3% ± 3.5% at 180 and 360 min after irradiation, respectively. Our irradiation system and the obtained results may be useful for studies of cell competition as well as non-targeted effects.
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Diffuse large B-cell lymphoma with spindle cell morphology is a rare variant. We present the case of a 74-year-old male who initially presented with a right supraclavicular (lymph) node enlargement. Histological analysis showed a proliferation of spindle-shaped cells with narrow cytoplasms. An immunohistochemical panel was used to exclude other tumors, such as melanoma, carcinoma, and sarcoma. The lymphoma was characterized by a cell-of-origin subtype of germinal center B-cell-like (GCB) based on Hans' classifier (CD10-negative, BCL6-positive, and MUM1-negative); EBER negativity, and the absence of BCL2, BCL6, and MYC rearrangements. Mutational profiling using a custom panel of 168 genes associated with aggressive B-cell lymphomas confirmed mutations in ACTB, ARID1B, DUSP2, DTX1, HLA-B, PTEN, and TNFRSF14. Based on the LymphGen 1.0 classification tool, this case had an ST2 subtype prediction. The immune microenvironment was characterized by moderate infiltration of M2-like tumor-associated macrophages (TMAs) with positivity of CD163, CSF1R, CD85A (LILRB3), and PD-L1; moderate PD-1 positive T cells, and low FOXP3 regulatory T lymphocytes (Tregs). Immunohistochemical expression of PTX3 and TNFRSF14 was absent. Interestingly, the lymphoma cells were positive for HLA-DP-DR, IL-10, and RGS1, which are markers associated with poor prognosis in DLBCL. The patient was treated with R-CHOP therapy, and achieved a metabolically complete response.
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INTRODUCTION: Due to its many technical advantages, the scope of robot-assisted thoracic surgery (RATS) is expanding to include extended pulmonary resection. Among such procedures, right bilobectomy is one with a high risk of inducing development of a bronchial stump fistula. MATERIALS AND SURGICAL TECHNIQUE: The pericardial fat pad case involved a 71-year-old man with a 31-mm adenocarcinoma in the right lung that had progressed to the intermediate bronchus. During lower bilobectomy, to confirm the tumor margin, an L-shaped stapler was used with stapling only at the oral side, and the bronchus was cut using a scalpel blade grasped with robot forceps. After confirming a negative stump, the pericardial fat was collected at the pedicle and sewn onto the stump. The intercostal muscle (ICM) flap case involved a 61-year-old man with a 16-mm nodule shadow in the lower lobe of his lung and swollen #11i and 7 lymph nodes. Intraoperatively, the #7 lymph node was diagnosed as non-small-cell lung cancer by frozen sections, and lower bilobectomy was performed. The bronchus was divided using a stapler with a green cartridge, and the ICM flap was harvested by changing the direction of the camera to a look-up view and positioning the camera at the 5th intercostal site. His numeric rating score (NRS) at 30 and 90 days post-surgery was 2 and 0, respectively. DISCUSSION: Our RATS technique was useful for harvesting the ICM flap. More cases should be accumulated to extend the surgical indication for RATS.
Asunto(s)
Fístula Bronquial , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Neoplasias Pulmonares/cirugía , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Bronquios/cirugía , Fístula Bronquial/etiología , Fístula Bronquial/cirugía , Neumonectomía/métodosRESUMEN
Diffuse large B-cell lymphoma (DLBCL) with MYC alteration is classified as high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double/triple-hit lymphoma; DHL/THL), DLBCL with MYC rearrangement (single-hit lymphoma; SHL) and DLBCL with MYC-cluster amplification (MCAD). To elucidate the genetic features of DHL/THL, SHL, and MCAD, 23 lymphoma cases from Tokai University Hospital were analyzed. The series included 10 cases of DHL/THL, 10 cases of SHL and 3 cases of MCAD. The analysis used whole-genome copy number microarray analysis (OncoScan) and a custom-made next-generation sequencing (NGS) panel of 115 genes associated with aggressive B-cell lymphomas. The copy number alteration (CNA) profiles were similar between DHL/THL and SHL. MCAD had fewer CNAs than those of DHL/THL and SHL, except for +8q24. The NGS profile characterized DHL/THL with a higher "mutation burden" than SHL (17 vs. 10, p = 0.010), and the most relevant genes for DHL/THL were BCL2 and SOCS1, and for SHL was DTX1. MCAD was characterized by mutations of DDX3X, TCF3, HLA-A, and TP53, whereas MYC was unmutated. In conclusion, DHL/THL, SHL, and MCAD have different profiles.