Determinants of emissions pathways in the coupled climate-social system.

The ambition and effectiveness of climate policies will be essential in determining greenhouse gas emissions and, as a consequence, the scale of climate change impacts1,2. However, the socio-politico-technical processes that will determine climate policy and emissions trajectories are treated as exogenous in almost all climate change modelling3,4. Here we identify relevant feedback processes documented across a range of disciplines and connect them in a stylized model of the climate-social system. An analysis of model behaviour reveals the potential for nonlinearities and tipping points that are particularly associated with connections across the individual, community, national and global scales represented. These connections can be decisive for determining policy and emissions outcomes. After partly constraining the model parameter space using observations, we simulate 100,000 possible future policy and emissions trajectories. These fall into 5 clusters with warming in 2100 ranging between 1.8 °C and 3.6 °C above the 1880-1910 average. Public perceptions of climate change, the future cost and effectiveness of mitigation technologies, and the responsiveness of political institutions emerge as important in explaining variation in emissions pathways and therefore the constraints on warming over the twenty-first century.

Epigenetic repression of CHCHD2 enhances survival from single cell dissociation through attenuated Rho A kinase activity.

During in vitro culture, human pluripotent stem cells (hPSCs) often acquire survival advantages characterized by decreased susceptibility to mitochondrial cell death, known as "culture adaptation." This adaptation is associated with genetic and epigenetic abnormalities, including TP53 mutations, copy number variations, trisomy, and methylation changes. Understanding the molecular mechanisms underlying this acquired survival advantage is crucial for safe hPSC-based cell therapies. Through transcriptome and methylome analysis, we discovered that the epigenetic repression of CHCHD2, a mitochondrial protein, is a common occurrence during in vitro culture using enzymatic dissociation. We confirmed this finding through genetic perturbation and reconstitution experiments in normal human embryonic stem cells (hESCs). Loss of CHCHD2 expression conferred resistance to single cell dissociation-induced cell death, a common stress encountered during in vitro culture. Importantly, we found that the downregulation of CHCHD2 significantly attenuates the activity of Rho-associated protein kinase (ROCK), which is responsible for inducing single cell death in hESCs. This suggests that hESCs may survive routine enzyme-based cell dissociation by downregulating CHCHD2 and thereby attenuating ROCK activity. These findings provide insights into the mechanisms by which hPSCs acquire survival advantages and adapt to in vitro culture conditions.

The extracellular vesicle of depressive patient-derived Escherichia fergusonii induces vagus nerve-mediated neuroinflammation in mice.

BACKGROUND: Gut microbiota dysbiosis is closely associated with psychiatric disorders such as depression and anxiety (DA). In our preliminary study, fecal microbiota transplantation from volunteers with psychological stress and subclinical symptoms of depression (Vsd) induced DA-like behaviors in mice. Escherichia fergusonii (Esf) was found to be more abundant in the feces of Vsd compared to healthy volunteers. Therefore, we investigated the effect of Esf on DA-like behavior and neuroinflammation in mice with and without celiac vagotomy. METHODS AND RESULTS: Orally gavaged Esf increased DA-like behaviors, tumor necrosis factor (TNF)-α, and toll-like receptor-4 (TLR4) expression, and NF-κB+Iba1+ and lipopolysaccharide (LPS)+Iba1+ cell populations, while decreasing serotonin, 5-HT1A receptor, and brain-derived neurotrophic factor (BDNF) expression in the hippocampus and prefrontal cortex. However, celiac vagotomy attenuated Esf-induced DA-like behavior and neuroinflammation. Orally gavaged extracellular vesicle (EV) from Vsd feces (vfEV) or Esf culture (esEV) induced DA-like behavior and inflammation in hippocampus, prefrontal cortex and colon. However, celiac vagotomy attenuated vfEV- or esEV-induced DA-like behaviors and inflammation in the brain alone, while vfEV- or esEV-induced blood LPS and TNF-α levels, colonic TNF-α expression and NF-κB-positive cell number, and fecal LPS level were not. Although orally gavaged fluorescence isothiocyanate-labeled esEV was translocated into the blood and hippocampus, celiac vagotomy decreased its translocation into the hippocampus alone. CONCLUSIONS: esEVs may be translocated into the brain via the vagus nerve and bloodstream, subsequently inducing TNF-α expression and suppressing serotonin, its receptor, and BDNF expression through the activation of TLR4-mediated NF-κB signaling, thereby contributing to DA pathogenesis.

Lipopolysaccharide-producing Veillonella infantium and Escherichia fergusonii cause vagus nerve-mediated cognitive impairment in mice.

Gut microbiota communicates bidirectionally with the brain through the nervous, immune, and endocrine systems of the gut. In our preliminary study, the fecal microbiota of volunteers with mild cognitive impairment (Fmci) exhibited a higher abundance of Escherichia fergusonii (NK2001), Veillonella infantium (NK2002), and Enterococcus faecium (NK2003) populations compared with those of healthy volunteers. Therefore, we examined the effects of Fmci, NK2001 (gram-negative), NK2002 (gram-negative-like), and NK2003 (gram-positive) on cognitive impairment-like behavior, neuroinflammation, and colitis in mice with or without antibiotics. Fmci transplantation increased cognitive impairment-like behavior, hippocampal tumor necrosis factor (TNF)-α expression, and the size of toll-like receptor (TLR)4+Iba1+, TLR2+Iba1+, and NF-κB+Iba1+ cell populations independent of antibiotic treatment. Oral gavage of NK2001, NK2002, or NK2003, which induced TNF-α expression in Caco-2 cells, significantly increased cognitive impairment-like behavior and hippocampal TNF-α expression and Iba1-positive cell populations and decreased brain-derived neurotrophic factor (BDNF) expression in mice. Celiac vagotomy significantly decreased NK2001- or NK2002-induced cognitive impairment-like behavior and hippocampal Iba1+ cell population and TNF-α expression and increased NK2001- or NK2002-suppressed hippocampal BDNF expression. However, NK2003-induced cognitive impairment-like behavior and hippocampal Iba1+ cell population and TNF-α expression were partially, but not significantly, attenuated by celiac vagotomy. Furthermore, celiac vagotomy did not affect NK2001-, NK2002-, or NK2003-induced lipopolysaccharide (LPS) levels in the blood and feces and TNF-α expression and NF-κB-positive cell population in the colon. In conclusion, LPS-producing NK2001 and NK2002 and LPS-nonproducing NK2003 may induce NF-κB-mediated neuroinflammation through the translocation of byproducts such as LPS and peptidoglycan into the brain through gut-blood/vagus nerve-brain and gut-blood-brain pathways, respectively, resulting in cognitive impairment.

Adaptive autophagy reprogramming in Schwann cells during peripheral demyelination.

The myelin sheath is an essential structure for the rapid transmission of electrical impulses through axons, and peripheral myelination is a well-programmed postnatal process of Schwann cells (SCs), the myelin-forming peripheral glia. SCs transdifferentiate into demyelinating SCs (DSCs) to remove the myelin sheath during Wallerian degeneration after axonal injury and demyelinating neuropathies, and macrophages are responsible for the degradation of myelin under both conditions. In this study, the mechanism by which DSCs acquire the ability of myelin exocytosis was investigated. Using serial ultrastructural evaluation, we found that autophagy-related gene 7-dependent formation of a "secretory phagophore (SP)" and tubular phagophore was necessary for exocytosis of large myelin chambers by DSCs. DSCs seemed to utilize myelin membranes for SP formation and employed p62/sequestosome-1 (p62) as an autophagy receptor for myelin excretion. In addition, the acquisition of the myelin exocytosis ability of DSCs was associated with the decrease in canonical autolysosomal flux and was demonstrated by p62 secretion. Finally, this SC demyelination mechanism appeared to also function in inflammatory demyelinating neuropathies. Our findings show a novel autophagy-mediated myelin clearance mechanism by DSCs in response to nerve damage.

GPR55 Antagonist CID16020046 Attenuates Obesity-Induced Airway Inflammation by Suppressing Chronic Low-Grade Inflammation in the Lungs.

GPR55 is a receptor for lysophosphatidylinositols (LPIs) in digestive metabolites. Overnutrition leads to obesity, insulin resistance, and increased LPI levels in the plasma. The involvement of LPIs and GPR55 in adiposity, hepatic steatosis, and atherosclerosis has been previously elucidated. However, the therapeutic efficacy of GPR55 antagonists against obesity-induced airway inflammation has not been studied. The present study investigated whether CID16020046, a selective antagonist of GPR55, could modulate obesity-induced airway inflammation caused by a high-fat diet (HFD) in C57BL/6 mice. Administration of CID16020046 (1 mg/kg) inhibits HFD-induced adiposity and glucose intolerance. Analysis of immune cells in BALF showed that CID16020046 inhibited HFD-induced increase in immune cell infiltration. Histological analysis revealed the HFD induced hypersecretion of mucus and extensive fibrosis in the lungs. CID16020046 inhibited these HFD-induced pathological features. qRT-PCR revealed the HFD-induced increase in the expression of Ifn-γ, Tnf-α, Il-6, Il-13, Il-17A, Il-1ß, Nlrp3, and Mpo mRNAs in the lungs. CID16020046 inhibited the HFD-induced increases in these genes. The expression levels of adipokines were regulated by the HFD and CID16020046. AdipoQ in the lungs and gonadal white adipose tissue was decreased by the HFD and reversed by CID16020046. In contrast, Lep was increased by the HFD and suppressed by CID16020046. The findings suggest the potential application of the GPR55 antagonist CID16020046 in obesity-induced airway inflammation.

A Potential Pneumothorax Induced by Immune Checkpoint Inhibitors: A Case Report and Literature Review.

Background and Objectives: Immune checkpoint inhibitors (ICIs), which target immune checkpoints in cancer cells, are increasingly used as a mainstay in anticancer treatment. The combination of atezolizumab and bevacizumab is also a first-line treatment for hepatocellular carcinoma (HCC). However, ICIs can cause immune-related adverse events (IrAEs) which range from mild to severe, potentially leading to the need for discontinuing immunotherapy. We report a case of a pneumothorax, a rare side effect caused by IrAEs. Materials and Methods: This paper reports a case of a 78-year-old male HCC patient who developed a recurrent pneumothorax, suspected to be an adverse effect of ICIs. Results: The patient was a current smoker with a 30 pack-year smoking history. Prior to initiating ICIs, a chest CT scan showed mild emphysema and fibrosis attributable to smoking. Following ICI treatment, the patient developed a recurrent pneumothorax. Further tests revealed no underlying cause for the pneumothorax other than the ICIs and smoking, and there were no signs of intrapulmonary metastasis or pneumonitis. Conclusions: When a pneumothorax occurs in a patient undergoing immunotherapy, it is important to consider it as a potential adverse effect of the treatment. Special attention should be given to the possibility that immunotherapy may exacerbate underlying lung conditions. Patients should be advised on the importance of smoking cessation. As there are currently no guidelines for resuming immunotherapy after a pneumothorax, it is crucial to weigh the risks and benefits and consider dose reduction or discontinuation of the medication.

Atezolizumab-Induced Ulcerative Colitis in Patient with Hepatocellular Carcinoma: Case Report and Literature Review.

Background and Objectives: Immune check inhibitor (ICI) colitis is one of most common and adverse side effects of ICI. However, there was no case report of ulcerative colitis (UC)-mimicking colitis after atezolizumab use in hepatocellular carcinoma (HCC) to our knowledge. Materials and Methods: We would like to introduce the case of a patient with Stage IV HCC who complained of abdominal pain, diarrhea and rectal bleeding after two cycles of atezolizumab/bevacizumab chemotherapy and was then diagnosed with UC-mimicking colitis. Results: Endoscopy revealed typical findings of UC, suggesting diagnosis of UC-mimicking colitis. The patient was treated with systemic steroids and oral mesalamine, which significantly improved his symptoms, which were also supported by endoscopic findings. The patient resumed chemotherapy with atezolizumab and bevacizumab without any interruption to the chemotherapy schedule. Conclusions: Early endoscopic evaluation is pivotal to diagnosing UC-mimicking colitis. If diagnosed, UC-based treatments such as steroids and mesalamine should be strongly considered. Given previous reports of inflammatory bowel disease (IBD) flare-ups after immunotherapy, routine lower endoscopy, performed together with upper endoscopy before atezolizumab/bevacizumab therapy, is promising to patients.

COUP-TFII plays a role in cAMP-induced Schwann cell differentiation and in vitro myelination by up-regulating Krox20.

Schwann cells (SCs) are known to produce myelin for saltatory nerve conduction in the peripheral nervous system (PNS). Schwann cell differentiation and myelination processes are controlled by several transcription factors including Sox10, Oct6/Pou3f1, and Krox20/Egr2. Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII/NR2F2) is an orphan receptor that plays a role in the development and differentiation. However, the role of COUP-TFII in the transcriptional regulatory network of SC differentiation has not been fully identified yet. Thus, the objective of this study was to investigate the role and molecular hierarchy of COUP-TFII during cAMP-induced SC differentiation. Our results showed that dibutyryl-cAMP (db-cAMP) increased expression levels of COUP-TFII along with the expressions of Oct6, Krox20, and myelin-related genes known to be related to SC differentiation. Our mechanistic studies showed that COUP-TFII acted downstream of Hsp90/ErbB2/Gab1/ERK-AKT pathway during db-cAMP-induced SC differentiation. In addition, we found that COUP-TFII induced Krox20 expression by directly binding to Krox20-MSE8 as revealed by chromatin immunoprecipitation assay and promoter activity assay. In line with this, the expression of COUP-TFII was increased before up-regulation of Oct6, Krox20, and myelin-related genes in the sciatic nerves during early postnatal myelination period. Finally, COUP-TFII knockdown by COUP-TFII siRNA or via AAV-COUP-TFII shRNA in SCs inhibited db-cAMP-induced SC differentiation and in vitro myelination of sensory axons, respectively. Taken together, these findings indicate that COUP-TFII might be involved in postnatal myelination through induction of Krox20 in SCs. Our results present a new insight into the transcriptional regulatory mechanism in SC differentiation and myelination.

Regulation of the V-ATPase subunit ATP6V0D2 and its role in demyelination after peripheral nerve injury.

After peripheral nerve injury, demyelinating Schwann cells discharge myelin debris and macrophages execute myelin degradation, leading to demyelination of degenerating axons, which is essential for efficient nerve regeneration. In this study, we show that vacuolar-type proton ATPase subunit d2 (Atp6v0d2) is among the most highly upregulated genes in degenerating mouse sciatic nerves after nerve injury using microarray analysis. ATP6V0D2 is mostly expressed in macrophages of injured nerves. Atp6v0d2 knockout mice display delayed peripheral nerve demyelination and significantly attenuated myelin lipid digestion after nerve injury. However, macrophage recruitment and Schwann cell dedifferentiation are unaffected by loss of Atp6v0d2 expression. Taken together, these data demonstrate that ATP6V0D2 in macrophages is specifically required for demyelination during Wallerian degeneration.

Bifidobacterium bifidum and Lactobacillus paracasei alleviate sarcopenia and cognitive impairment in aged mice by regulating gut microbiota-mediated AKT, NF-κB, and FOXO3a signaling pathways.

Sarcopenia is closely associated with gut dysbiosis. Probiotics alleviate gut dysbiosis. Therefore, we selected probiotics Lactobacillus paracasei P62 (Lp) and Bifidobacterium bifidum P61 (Bb), which suppressed muscle RING-finger protein-1 (MuRF1) expression and NF-κB activation in C2C12 cells, and examined their effects on muscle mass loss and dysfunction in aged mice. Oral administration of Lp, Bb, or their mix (LB) increased grip strength and treadmill running distance and time. They significantly increased muscle weight in aged mice. They also increased AKT activation, PGC1α, SIRT1, and myosin heavy chain (MyHC) expression, MyHC-positive cell population, and cell size in the gastrocnemius (GA) muscle, while FOXO3a and NF-κB activation, MuRF1, muscle atrophy F-box, and p16 expression, and NF-κB+CD11c+ cell population decreased. Furthermore, they reduced cognitive impairment-like behavior, IL-6 expression, FOXO3a activation, and NF-κB-positive cell population in the hippocampus, GA, and colon, while hippocampal brain-derived neurotropic factor expression increased. They shifted gut microbiota composition in aged mice: they increased Akkermansiaceae and Bacteroidaceae populations, which were positively correlated with total muscle weight and MyHC expression, and decreased Odoribacteraceae and Deferribacteriaceae populations, which were positively correlated with MuRF1 and IL-6 expression. LB alleviated sarcopenia- and cognitive impairment-like symptoms more potently than Lp or Bb alone. Based on these findings, probiotics, particularly Lp, Bb, and LB, can alleviate aging-dependent sarcopenia and cognitive impairment by regulating gut microbiota-mediated AKT, NF-κB, and/or FOXO3a signaling pathways.

Association Between Oral Health and Airflow Limitation: Analysis Using a Nationwide Survey in Korea.

BACKGROUND: Although poor oral health is a common comorbidity in individuals with airflow limitation (AFL), few studies have comprehensively evaluated this association. Furthermore, the association between oral health and the severity of AFL has not been well elucidated. METHODS: Using a population-based nationwide survey, we classified individuals according to the presence or absence of AFL defined as pre-bronchodilator forced expiratory volume in 1 second/forced vital capacity < 0.7. Using multivariable logistic regression analyses, we evaluated the association between AFL severity and the number of remaining teeth; the presence of periodontitis; the Decayed, Missing, and Filled Teeth (DMFT) index; and denture wearing. RESULTS: Among the 31,839 participants, 14% had AFL. Compared with the control group, the AFL group had a higher proportion of periodontitis (88.8% vs. 79.4%), complete denture (6.2% vs. 1.6%), and high DMFT index (37.3% vs. 27.8%) (P < 0.001 for all). In multivariable analyses, denture status: removable partial denture (adjusted odds ratio [aOR], 1.12; 95% confidence interval [95% CI], 1.04-1.20) and complete denture (aOR, 1.52; 95% CI, 1.01-2.05), high DMFT index (aOR, 1.13; 95% CI, 1.02-1.24), and fewer permanent teeth (0-19; aOR, 1.32; 95% CI, 1.12-1.52) were significantly associated with AFL. Furthermore, those with severe to very severe AFL had a significantly higher proportion of complete denture (aOR, 2.41; 95% CI, 1.11-3.71) and fewer remaining teeth (0-19; aOR, 2.29; 95% CI, 1.57-3.01). CONCLUSION: Denture wearing, high DMFT index, and fewer permanent teeth are significantly associated with AFL. Furthermore, a reduced number of permanent teeth (0-19) was significantly related to the severity of AFL. Therefore, physicians should pay attention to oral health in managing patients with AFL, such as chronic obstructive pulmonary disease.

Sensor Data Reconstruction for Dynamic Responses of Structures Using External Feedback of Recurrent Neural Network.

An event of sensor faults in sensor networks deployed in structures might result in the degradation of the structural health monitoring system and lead to difficulties in structural condition assessment. Reconstruction techniques of the data for missing sensor channels were widely adopted to restore a dataset from all sensor channels. In this study, a recurrent neural network (RNN) model combined with external feedback is proposed to enhance the accuracy and effectiveness of sensor data reconstruction for measuring the dynamic responses of structures. The model utilizes spatial correlation rather than spatiotemporal correlation by explicitly feeding the previously reconstructed time series of defective sensor channels back to the input dataset. Because of the nature of spatial correlation, the proposed method generates robust and precise results regardless of the hyperparameters set in the RNN model. To verify the performance of the proposed method, simple RNN, long short-term memory, and gated recurrent unit models were trained using the acceleration datasets obtained from laboratory-scaled three- and six-story shear building frames.

Altered Lung Heat Shock Protein-70 Expression and Severity of Sepsis-Induced Acute Lung Injury in a Chronic Kidney Disease Rat Model.

Enhanced heat shock protein-70 (HSP-70) expression in the lungs is associated with attenuated acute lung injury (ALI) in a sepsis model. Chronic kidney disease (CKD) significantly contributes to the poor prognosis of patients with sepsis. This study examined the relationship between sepsis-induced ALI severity and altered lung HSP-70 expression in CKD. Experimental rats underwent a sham operation (control group) or 5/6 nephrectomy (CKD group). Sepsis was induced with cecal ligation and puncture (CLP). Laboratory tests and lung harvest were performed in the control group (without CLP and after 3, 12, 24, and 72 h of CLP) and in the CKD group (without CLP and after 72 h of CLP). ALI was the most severe after 12 h of sepsis. The mean lung injury score at 72 h after sepsis was significantly higher in the CKD group than in the control group (4.38 versus 3.30, p < 0.01). Nonetheless, enhanced lung HSP-70 expression was not observed in the CKD group. This study shows that altered lung HSP-70 expression is associated with the worsening of sepsis-induced ALI in patients with CKD. Enhancing lung HSP-70 is a novel treatment target for patients with CKD and sepsis-induced ALI.

ßPix Guanine Nucleotide Exchange Factor Regulates Regeneration of Injured Peripheral Axons.

Axon regeneration is essential for successful recovery after peripheral nerve injury. Although growth cone reformation and axonal extension are crucial steps in axonal regeneration, the regulatory mechanisms underlying these dynamic processes are poorly understood. Here, we identify ßPix (Arhgef7), the guanine nucleotide exchange factor for Rac1 GTPase, as a regulator of axonal regeneration. After sciatic nerve injury in mice, the expression levels of ßPix increase significantly in nerve segments containing regenerating axons. In regrowing axons, ßPix is localized in the peripheral domain of the growth cone. Using ßPix neuronal isoform knockout (NIKO) mice in which the neuronal isoforms of ßPix are specifically removed, we demonstrate that ßPix promotes neurite outgrowth in cultured dorsal root ganglion neurons and in vivo axon regeneration after sciatic nerve crush injury. Activation of cJun and STAT3 in the cell bodies is not affected in ßPix NIKO mice, supporting the local action of ßPix in regenerating axons. Finally, inhibiting Src, a kinase previously identified as an activator of the ßPix neuronal isoform, causes axon outgrowth defects in vitro, like those found in the ßPix NIKO neurons. Altogether, these data indicate that ßPix plays an important role in axonal regrowth during peripheral nerve regeneration.

Potential neuron-autonomous Purkinje cell degeneration by 2',3'-cyclic nucleotide 3'-phosphodiesterase promoter/Cre-mediated autophagy impairments.

Studies of neuroglial interaction largely depend on cell-specific gene knockout (KO) experiments using Cre recombinase. However, genes known as glial-specific genes have recently been reported to be expressed in neuroglial stem cells, leading to the possibility that a glia-specific Cre driver results in unwanted gene deletion in neurons, which may affect sound interpretation. 2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNP) is generally considered to be an oligodendrocyte (OL) marker. Accordingly, Cnp promoter-controlled Cre recombinase has been used to create OL-specific gene targeting mice. However, in this study, using Rosa26-tdTomato-reporter/Cnp-Cre mice, we found that many forebrain neurons and cerebellar Purkinje neurons belong to the lineages of Cnp-expressing neuroglial stem cells. To answer whether gene targeting by Cnp-Cre can induce neuron-autonomous defects, we conditionally deleted an essential autophagy gene, Atg7, in Cnp-Cre mice. The Cnp-Cre-mediated Atg7 KO mice showed extensive p62 inclusion in neurons, including cerebellar Purkinje neurons with extensive neurodegeneration. Furthermore, neuronal areas showing p62 inclusion in Cnp-Cre-mediated Atg7 KO mice overlapped with the neuronal lineage of Cnp-expressing neuroglial stem cells. Moreover, Cnp-Cre-mediated Atg7-KO mice did not develop critical defects in myelination. Our results demonstrate that a large population of central neurons are derived from Cnp-expressing neuroglial stem cells; thus, conditional gene targeting using the Cnp promoter, which is known to be OL-specific, can induce neuron-autonomous phenotypes.

Sex differences in body composition affect total airway resistance during puberty.

BACKGROUND: During puberty, changes in body composition due to sex hormones are associated with lung mechanics. However, little is known about the mediation effect of sex differences in body composition during puberty with total airway resistance. METHODS: We prospectively recruited 620 children (10-12 years old) from the general population and conducted a cross-sectional study. This study assessed pubertal status according to the five Tanner stages using a questionnaire, line drawings, and each subject's blood sex hormone profile. Both the impulse oscillation system for total lung mechanics and multifrequency bioelectrical impedance for body composition analyses were conducted. The effects of puberty on body composition and subsequent total lung resistance were evaluated using mediation analysis. RESULTS: Among the 503 children enrolled, there were 261 males (51.9%) and 242 females (48.1%). In males, higher testosterone levels corresponded with reduced total lung resistance (ß = -0.13, 95% CI = -0.21 to -0.05, p < 0.001), and the proportion of the mediating effect through the muscle-fat ratio was 19% (95% CI = 4 to 59, p = 0.02). In contrast, in females, pubertal status reduced total lung resistance (ß = -0.27, 95% CI = -0.58 to -0.05, p = 0.04), however, the proportion of the mediating effect through the body mass index was -51% (95% CI = -244 to -4%, p = 0.04). CONCLUSION: The muscle-fat ratio in adolescent males had a synergistic effect with testosterone on improving total airway resistance, whereas improvements in lung resistance by pubertal status were partially masked by body mass index in adolescent females. In conclusion, body composition changes during puberty between males and females have differing effects on total airway resistance.

The 2021 Association Research Circulation Osseous Classification for Early-Stage Osteonecrosis of the Femoral Head to Computed Tomography-Based Study.

BACKGROUND: The Association Research Circulation Osseous developed a novel classification for early-stage (precollapse) osteonecrosis of the femoral head (ONFH). We hypothesized that the novel classification is more reliable and valid when compared to previous 3 classifications: Steinberg, modified Kerboul, and Japanese Investigation Committee classifications. METHODS: In the novel classification, necrotic lesions were classified into 3 types: type 1 is a small lesion, where the lateral necrotic margin is medial to the femoral head apex; type 2 is a medium-sized lesion, with the lateral necrotic margin being between the femoral head apex and the lateral acetabular edge; and type 3 is a large lesion, which extends outside the lateral acetabular edge. In a derivation cohort of 40 early-stage osteonecrotic hips based on computed tomography imaging, reliabilities were evaluated using kappa coefficients, and validities to predict future femoral head collapse by chi-squared tests and receiver operating characteristic curve analyses. The predictability for future collapse was also evaluated in a validation cohort of 104 early-stage ONFH. RESULTS: In the derivation cohort, interobserver reliability (k = 0.545) and intraobserver agreement (63%-100%) of the novel method were higher than the other 3 classifications. The novel classification system was best able to predict future collapse (P < .05) and had the best discrimination between non-progressors and progressors in both the derivation cohort (area under the curve = 0.692 [0.522-0.863], P < .05) and the validation cohort (area under the curve = 0.742 [0.644-0.841], P = 2.46 × 10-5). CONCLUSION: This novel classification is a highly reliable and valid method of those examined. Association Research Circulation Osseous recommends using this method as a unified classification for early-stage ONFH. LEVEL OF EVIDENCE: Level III, diagnostic study.

Automated Dimension Estimation of Steel Pipes Stacked at Construction Sites Using Euclidean Distances Calculated by Overlapping Segmentation.

Pipes are construction materials for water and sewage, air conditioning, firefighting, and gas facilities at construction sites. The quantification and identification of pipes stacked at construction sites are indispensable and, thus, are directly related to efficient process management. In this study, an automated CNN-based technique for estimating the diameter and thickness of the pipe in an image is proposed. The proposed method infers the thickness of the pipe through the difference by segmentation, by overlapping the inside and outside circles for a single pipe. When multiple pipes are included in the image, the inside and outside circles for the identical pipe are matched through the spatial Euclidean distance. The CNN models are trained using pipe images of various sizes to segment the pipe circles. An error of less than 7.8% for the outer diameter and 15% for the thickness is verified through execution with a series of 50 testing pipe images.

Scaffolding protein Gab2 is involved in postnatal development and lipopolysaccharide-induced activation of microglia in the mouse brain.

Grb2-associated-binding protein-2 (Gab2) is a member of the Gab/DOS family and functions as an adapter protein downstream of several growth factor signaling pathways. Gab2 is considered an Alzheimer's disease susceptibility gene. However, the role of Gab2 in the brain is still largely unknown. Herein, we report that Gab2 is involved in the postnatal development of microglia in mice. The Gab2 expression in the brain was detected at postnatal day 1 (P1) and increased until P14 but decreased thereafter. The tyrosine phosphorylation of Gab2 (pGab2) was also detected at P1 and increased until P14. Next, we focused on microglial development in Gab2 knockout and heterozygous mice. Although differences were not detected in the cytoplasmic area of Iba1-labeled microglia between Gab2(±) and Gab2(-/-) mice, the analysis of CD68 and cathepsin D (indicators of microglial lysosomal activation) immunolabeling within Iba1+ cells revealed significant underdevelopment of microglial lysosomes in Gab2(-/-) mice at P60. In addition to the developmental abnormality of microglia in Gab2(-/-) mice, lipopolysaccharide-induced lysosomal activation was selectively suppressed in Gab2(-/-) mice compared to that in Gab2(±) mice. Our findings suggest that Gab2 is involved not only in postnatal development but also in lysosomal activation of microglia, therefore Gab2 dysfunction in microglia might potentially contribute to the development of neurodegenerative diseases.