Renal Failure Without Hemodialysis Is a Risk Factor for Postoperative Complications in Colorectal Cancer Surgery.

Background/Aim: Surgical outcomes of colorectal cancer (CRC) in patients with renal failure (RF) remain to be clarified. The objective of this research was to investigate how RF impacts the surgical outcomes in patients with CRC. Patients and Methods: A retrospective analysis was performed on clinical data from 633 patients who underwent colorectal resection for CRC between January 2017 and December 2021. Outcomes of the patients with and without RF were compared. RF was defined as estimated Glomerular Filtration Rate less than 30. Results: Forty-five (7%) patients with RF were identified. RF was a significant risk factor for postoperative complications after colorectal cancer surgery (odds ratio=2.19, 95% confidence interval=1.08-4.42, p=0.0284). The patients with RF had significantly more comorbidity (p=0.016), and higher American Society of Anesthesiologists physical status (p<0.01). Hemoglobin level (p<0.01) and PNI (p<0.01) were significantly lower in those with RF. Postoperative complications were significantly higher (p=0.016), and the postoperative hospital stay was significantly longer (p<0.01) among patients with RF compared to those without RF. Patients with RF, excluding those undergoing hemodialysis, had significantly more complications compared to those without RF (p=0.004). Conclusion: Careful attention should be paid to perioperative management in RF colorectal cancer patients.

YJMob100K: City-scale and longitudinal dataset of anonymized human mobility trajectories.

Modeling and predicting human mobility trajectories in urban areas is an essential task for various applications including transportation modeling, disaster management, and urban planning. The recent availability of large-scale human movement data collected from mobile devices has enabled the development of complex human mobility prediction models. However, human mobility prediction methods are often trained and tested on different datasets, due to the lack of open-source large-scale human mobility datasets amid privacy concerns, posing a challenge towards conducting transparent performance comparisons between methods. To this end, we created an open-source, anonymized, metropolitan scale, and longitudinal (75 days) dataset of 100,000 individuals' human mobility trajectories, using mobile phone location data provided by Yahoo Japan Corporation (currently renamed to LY Corporation), named YJMob100K. The location pings are spatially and temporally discretized, and the metropolitan area is undisclosed to protect users' privacy. The 90-day period is composed of 75 days of business-as-usual and 15 days during an emergency, to test human mobility predictability during both normal and anomalous situations.

Risk factors and clinical significance of subcutaneous emphysema after robot-assisted laparoscopic rectal surgery: a single-center experience.

Subcutaneous emphysema (SE) is a complication of laparoscopic surgery, potentially resulting in severe respiratory failure. No reports to date have focused on SE during robot-assisted (RA) rectal surgery. We aimed to reveal the risk factors and clinical significance of SE after RA/laparoscopic rectal surgery. We retrospectively reviewed 221 consecutive patients who underwent RA/laparoscopic rectal surgery. The occurrence of SE was evaluated on postoperative radiographs. Laparoscopic surgery was performed in 120 patients and RA in 101. SE developed in 55 (24.9%) patients. Logistic regression analysis identified RA surgery (odds ratio [OR]: 4.89, 95% confidence interval [CI] 2.13-11.22, p < 0.001), higher age (OR: 1.06, 95% CI 1.03-1.11, p < 0.001), lower body mass index (BMI) (OR: 0.79, 95% CI 0.67-0.93, p = 0.004), thinner subcutaneous layer (OR: 0.88, 95% CI 0.79-0.98, p = 0.02), and lateral lymph node dissection (OR: 9.43, 95% CI 2.44-36.42, p < 0.001) as risk factors for SE. Maximum end-tidal CO2 was significantly higher in the SE than the non-SE cohort (p < 0.001). There was no difference in postoperative complication rate or length of hospital stay. Lower BMI (OR: 0.79, 95% CI 0.62-0.97, p = 0.02) and thinner subcutaneous layer (OR: 0.84, 95% CI 0.71-0.97, p = 0.01) were predictive factors in the RA cohort. SE occurs more frequently in RA compared with laparoscopic surgery. SE has a modest impact on short-term outcomes, but may occasionally cause severe problems. The indication of RA surgery should be considered carefully in high-risk elderly patients.

Changes in Urinary Uric Acid Concentration after Dotinurad Administration to Patients with Hyperuricemia: A Post Hoc Analysis of Two Clinical Trials in Japan.

Dotinurad has been approved in Japan as a selective urate reabsorption inhibitor for the treatment of gout and hyperuricemia. The relationship between uric acid crystallization and the use of uricosuric drugs is widely acknowledged; however, the relationship between changes in urinary uric acid concentration and urine pH or volume has not been sufficiently analyzed. Therefore, we investigated the changes in urinary uric acid concentration following dotinurad administration as well as the relationship between urine pH or volume and urinary uric acid concentration. This post hoc analysis used data from 2 clinical trials that included 12 and 26 patients with hyperuricemia who received dotinurad treatment (for 7 days on an inpatient basis and 14 weeks on an outpatient basis, respectively). The urinary uric acid concentration transiently increased in the early stages of dotinurad use and when its dose was increased, but decreased over time. No uric acid concentrations exceeded the soluble limit at any urine pH. An inverse correlation was observed between urine volume and urinary uric acid concentration. This study highlights the significance of adequately managing urinary uric acid concentrations by increasing urine volume and alkalinizing urine to prevent uric acid crystallization during dotinurad administration.

Optimal Surgical Method and Timing for Low-birth-weight Esophageal Atresia Babies: Multi-institutional Observational Study.

AIM OF THE STUDY: Previous research has shown that low birth weight is one of the risk factors for esophageal atresia. However, there remains a paucity of evidence on the timing and the treatment method. METHOD: Data were collected using a multi-institutional observational study in 11 hospitals that performed surgeries on esophageal atresia babies whose birth weights were ≤1500 g from 2001 to 2020. RESULTS: Of the 46 patients analyzed, median birth weight was 1233 (IQR 1042-1412) g. Within 46 cases, 19 (41%) underwent definitive esophageal anastomosis at the median of age in 8 (IQR 2-101) days. Thirteen out of 19 experienced either closure of tracheoesophageal fistula, gastrostomy, or esophageal banding at the first operation, followed by esophageal anastomosis. Seven infants, including four cases of <1000 g, underwent anastomosis after one month of age to wait for weight gain (variously 2-3000 g). Twenty-one out of 27 infants (78%) who did not receive anastomosis died within one year of age, including 21 (78 %) with major cardiac anomalies and 24 (89%) with severe chromosomal anomalies (trisomy 18). Six survivors in this group, all with trisomy 18, lived with palliative surgical treatments. CONCLUSION: In our study, the definitive esophageal anastomosis was effective either at the first operation or as a later treatment after gaining weight. Although having severe anomalies, some infants receive palliative surgical treatments, and the next surgery was considered depending on their condition. EVIDENCE LEVEL: II.

American crows that excel at tool use activate neural circuits distinct from less talented individuals.

Tools enable animals to exploit and command new resources. However, the neural circuits underpinning tool use and how neural activity varies with an animal's tool proficiency, are only known for humans and some other primates. We use 18F-fluorodeoxyglucose positron emission tomography to image the brain activity of naïve vs trained American crows (Corvus brachyrhynchos) when presented with a task requiring the use of stone tools. As in humans, talent affects the neural circuits activated by crows as they prepare to execute the task. Naïve and less proficient crows use neural circuits associated with sensory- and higher-order processing centers (the mesopallium and nidopallium), while highly proficient individuals increase activity in circuits associated with motor learning and tactile control (hippocampus, tegmentum, nucleus basorostralis, and cerebellum). Greater proficiency is found primarily in adult female crows and may reflect their need to use more cognitively complex strategies, like tool use, to obtain food.

Monitoring the Kinase Activity of Heme-Based Oxygen Sensors and Its Dependence on O2 and Other Ligands Using Phos-Tag Electrophoresis.

The nonradioactive method, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) in the presence of Phos-tag (Phos-tag electrophoresis), is used to evaluate a kinase autophosphorylation and/or phosphotransfer reaction from a kinase/ATP to its protein substrate. This method outperforms radioisotope methods using [32P]ATP for detecting trace amounts of phosphorylated protein in fresh protein preparations. Phos-tag electrophoresis has been used to perform detailed analyses of the kinase activity of a heme-based oxygen sensor-specifically, a globin-coupled histidine kinase from the soil bacterium Anaeromyxobacter sp. Fw109-5 (AfGcHK).

Hydrogen/Deuterium Exchange Mass Spectrometry of Heme-Based Oxygen Sensor Proteins.

Hydrogen/deuterium exchange (HDX) is a well-established analytical technique that enables monitoring of protein dynamics and interactions by probing the isotope exchange of backbone amides. It has virtually no limitations in terms of protein size, flexibility, or reaction conditions and can thus be performed in solution at different pH values and temperatures under controlled redox conditions. Thanks to its coupling with mass spectrometry (MS), it is also straightforward to perform and has relatively high throughput, making it an excellent complement to the high-resolution methods of structural biology. Given the recent expansion of artificial intelligence-aided protein structure modeling, there is considerable demand for techniques allowing fast and unambiguous validation of in silico predictions; HDX-MS is well-placed to meet this demand. Here we present a protocol for HDX-MS and illustrate its use in characterizing the dynamics and structural changes of a dimeric heme-containing oxygen sensor protein as it responds to changes in its coordination and redox state. This allowed us to propose a mechanism by which the signal (oxygen binding to the heme iron in the sensing domain) is transduced to the protein's functional domain.

Characterization of the interaction between the tumour suppressor p53 and heme and its role in the protein conformational dynamics studied by various spectroscopic techniques and hydrogen/deuterium exchange coupled with mass spectrometry.

The tumour suppressor p53 regulates the expression of a myriad of proteins that are important for numerous cellular processes, including apoptosis, cell cycle arrest, DNA repair, metabolism, and even autophagy and ferroptosis. Aside from DNA, p53 can interact with many types of partners including proteins and small organic molecules. The ability of p53 to interact with heme has been reported so far. In this study, we used various spectroscopic studies to conduct a thorough biophysical characterization of the interaction between p53 and heme concerning the oxidation, spin, coordination, and ligand state of heme iron. We found that the p53 oligomeric state and zinc biding ability are preserved upon the interaction with heme. Moreover, we described the effect of heme binding on the conformational dynamics of p53 by hydrogen/deuterium exchange coupled with mass spectrometry. Specifically, the conformational flexibility of p53 is significantly increased upon interaction with heme, while its affinity to a specific DNA sequence is reduced by heme. The inhibitory effect of DNA binding by heme is partially reversible. We discuss the potential heme binding sites in p53 with respect to the observed conformational dynamics changes and perturbed DNA-binding ability of p53 upon interaction with heme.

Signal transduction mechanisms in heme-based globin-coupled oxygen sensors with a focus on a histidine kinase (AfGcHK) and a diguanylate cyclase (YddV or EcDosC).

Heme is a vital cofactor of proteins with roles in oxygen transport (e.g. hemoglobin), storage (e.g. myoglobin), and activation (e.g. P450) as well as electron transfer (e.g. cytochromes) and many other functions. However, its structural and functional role in oxygen sensing proteins differs markedly from that in most other enzymes, where it serves as a catalytic or functional center. This minireview discusses the mechanism of signal transduction in two heme-based oxygen sensors: the histidine kinase AfGcHK and the diguanylate cyclase YddV (EcDosC), both of which feature a heme-binding domain containing a globin fold resembling that of hemoglobin and myoglobin.

Genome-wide meta-analysis between renal overload type and renal underexcretion type of clinically defined gout in Japanese populations.

Despite progress in understanding of the genetic basis of gout, the precise factors affecting differences in gout susceptibility among different gout subtypes remain unclear. Using clinically diagnosed gout patients, we conducted a genome-wide meta-analysis of two distinct gout subtypes: the renal overload type and the renal underexcretion type. We provide genetic evidence at a genome-wide level of significance that supports a positive association between ABCG2 dysfunction and acquisition of the renal overload type.

A strategy to prevent tracheo-innominate artery fistula in the course of laryngotracheal separation: 9-year experience in a children's hospital.

AIM OF THE STUDY: Laryngotracheal separation (LTS) is known to be the definitive solution for intractable aspiration pneumonia in neurologically impaired children. Postoperatively, a tracheostomy cannula is usually required. However, there are fatal cannula related complications such as a tracheo-innominate artery fistula (TIAF). We present our methods of preventing TIAF. METHODS: A retrospective review in a single center from 2011 to 2019 identified 57 cases treated with LTS. We divided them into three groups: no pre-existing tracheostomy (n = 26), pre-existing tracheostomy with preservation of the pre-existing fistula (n = 20), and pre-existing tracheostomy without preservation of the pre-existing fistula (n = 11). The first group underwent traditional modified Lindeman's procedure. The second received transection of the trachea above the tracheostomy site, while the third had transection of the trachea at the tracheostomy site and creation of a distal end tracheostomy. Proper length and the angle of the cannula were selected to prevent damaging the innominate artery by the tip of the cannula. If the innominate artery compressed the trachea anteriorly, prophylactic arterial transection was considered. RESULTS: Three patients (5.3%) died from causes unrelated to the surgical treatment. Only one patient had a postoperative TIAF followed by LTS (1.8%). Other postoperative complications were: wound infection (8.8%), intratracheal granuloma (12.3%), intratracheal minor bleeding (10.5%), wound granuloma (43.9%), leakage (1.8%). No one required revision of LTS. CONCLUSION: Success rates of LTS were high without major complications in all three groups and implies a safe operation and a definitive solution to intractable aspiration.

American Crow Brain Activity in Response to Conspecific Vocalizations Changes When Food Is Present.

Social interaction among animals can occur under many contexts, such as during foraging. Our knowledge of the regions within an avian brain associated with social interaction is limited to the regions activated by a single context or sensory modality. We used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to examine American crow (Corvus brachyrhynchos) brain activity in response to conditions associated with communal feeding. Using a paired approach, we exposed crows to either a visual stimulus (the sight of food), an audio stimulus (the sound of conspecifics vocalizing while foraging) or both audio/visual stimuli presented simultaneously and compared to their brain activity in response to a control stimulus (an empty stage). We found two regions, the nucleus taenia of the amygdala (TnA) and a medial portion of the caudal nidopallium, that showed increased activity in response to the multimodal combination of stimuli but not in response to either stimulus when presented unimodally. We also found significantly increased activity in the lateral septum and medially within the nidopallium in response to both the audio-only and the combined audio/visual stimuli. We did not find any differences in activation in response to the visual stimulus by itself. We discuss how these regions may be involved in the processing of multimodal stimuli in the context of social interaction.

Portosystemic shunt for portal hypertension after Kasai operation in patients with biliary atresia.

PURPOSE: Many biliary atresia (BA) patients will eventually develop liver failure even after a successful Kasai portoenterostomy. A common complication of long-term BA survivors with their native liver is problematic portal hypertension. The aim of this study was to defend the view that portosystemic shunts can delay or negate the need for transplantation in these children. METHODS: A retrospective single center review of the efficacy of portosystemic shunts in BA patients after a successful Kasai portoenterostomy was conducted. RESULTS: From 1991 to 2017, 11 patients received portosystemic shunts. Median age of Kasai operation was 48 (36-61) days. Shunts were performed at the median age of 6.2 (4.1-6.8) years. Three of these eleven patients required subsequent liver transplantation. OS at 5 and 10 years were 90.9% and 81.8%, respectively. TFS at 5 and 10 years were 90.9% and 72.7%, respectively. Long-term complications included mild encephalopathy in 2 patients, hypersplenism in 3, and cholestasis in 1. CONCLUSION: Portosystemic shunt for the treatment of portal hypertension in carefully selected BA patients is an effective option in delaying or negating the need for liver transplantation.

Identification of the Novel Variants in Patients With Chronic Thromboembolic Pulmonary Hypertension.

Background Although chronic thromboembolic pulmonary hypertension (CTEPH) and acute pulmonary embolism (APE) share some clinical manifestations, a limited proportion of patients with CTEPH have a history of APE. Moreover, in histopathologic studies, it has been revealed that pulmonary vasculature lesions similar to pulmonary arterial hypertension existed in patients with CTEPH. Thus, it remains unknown whether these 3 disorders also share genetic backgrounds. Methods and Results Whole exome screening was performed with DNA isolated from 51 unrelated patients with CTEPH of Japanese ancestry. The frequency of genetic variants associated with pulmonary arterial hypertension or APE in patients with CTEPH was compared with those in the integrative Japanese Genome Variation Database 3.5KJPN. Whole exome screening analysis showed 17 049 nonsynonymous variants in patients with CTEPH. Although we found 6 nonsynonymous variants that are associated with APE in patients with CTEPH, there was no nonsynonymous variant associated with pulmonary arterial hypertension. Patients with CTEPH with a history of APE had nonsynonymous variants of F5, which encodes factor V. In contrast, patients with CTEPH without a history of APE had a nonsynonymous variant of THBD, which encodes thrombomodulin. Moreover, thrombin-activatable fibrinolysis inhibitor, which is one of the pathogenic proteins in CTEPH, was significantly more activated in those who had the variants of THBD compared with those without it. Conclusions These results provide the first evidence that patients with CTEPH have some variants associated with APE, regardless of the presence or absence of a history of APE. Furthermore, the variants might be different between patients with CTEPH with and without a history of APE.

Subtype-specific gout susceptibility loci and enrichment of selection pressure on ABCG2 and ALDH2 identified by subtype genome-wide meta-analyses of clinically defined gout patients.

OBJECTIVES: Genome-wide meta-analyses of clinically defined gout were performed to identify subtype-specific susceptibility loci. Evaluation using selection pressure analysis with these loci was also conducted to investigate genetic risks characteristic of the Japanese population over the last 2000-3000 years. METHODS: Two genome-wide association studies (GWASs) of 3053 clinically defined gout cases and 4554 controls from Japanese males were performed using the Japonica Array and Illumina Array platforms. About 7.2 million single-nucleotide polymorphisms were meta-analysed after imputation. Patients were then divided into four clinical subtypes (the renal underexcretion type, renal overload type, combined type and normal type), and meta-analyses were conducted in the same manner. Selection pressure analyses using singleton density score were also performed on each subtype. RESULTS: In addition to the eight loci we reported previously, two novel loci, PIBF1 and ACSM2B, were identified at a genome-wide significance level (p<5.0×10-8) from a GWAS meta-analysis of all gout patients, and other two novel intergenic loci, CD2-PTGFRN and SLC28A3-NTRK2, from normal type gout patients. Subtype-dependent patterns of Manhattan plots were observed with subtype GWASs of gout patients, indicating that these subtype-specific loci suggest differences in pathophysiology along patients' gout subtypes. Selection pressure analysis revealed significant enrichment of selection pressure on ABCG2 in addition to ALDH2 loci for all subtypes except for normal type gout. CONCLUSIONS: Our findings on subtype GWAS meta-analyses and selection pressure analysis of gout will assist elucidation of the subtype-dependent molecular targets and evolutionary involvement among genotype, phenotype and subtype-specific tailor-made medicine/prevention of gout and hyperuricaemia.

Brain activity underlying American crow processing of encounters with dead conspecifics.

Animals utilize a variety of auditory and visual cues to navigate the landscape of fear. For some species, including corvids, dead conspecifics appear to act as one such visual cue of danger, and prompt alarm calling by attending conspecifics. Which brain regions mediate responses to dead conspecifics, and how this compares to other threats, has so far only been speculative. Using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) we contrast the metabolic response to visual and auditory cues associated with a dead conspecific among five a priori selected regions in the American crow (Corvus brachyrhynchos) brain: the hippocampus, nidopallium caudolaterale, striatum, amygdala, and the septum. Using a repeated-measures, fully balanced approach, we exposed crows to four stimuli: a dead conspecific, a dead song sparrow (Melospiza melodia), conspecific alarm calls given in response to a dead crow, and conspecific food begging calls. We find that in response to observations of a dead crow, crows show significant activity in areas associated with higher-order decision-making (NCL), but not in areas associated with social behaviors or fear learning. We do not find strong differences in activation between hearing alarm calls and food begging calls; both activate the NCL. Lastly, repeated exposures to negative stimuli had a marginal effect on later increasing the subjects' brain activity in response to control stimuli, suggesting that crows might quickly learn from negative experiences.

Disruption of the dimerization interface of the sensing domain in the dimeric heme-based oxygen sensor AfGcHK abolishes bacterial signal transduction.

The heme-based oxygen sensor protein AfGcHK is a globin-coupled histidine kinase in the soil bacterium Anaeromyxobacter sp. Fw109-5. Its C-terminal functional domain exhibits autophosphorylation activity induced by oxygen binding to the heme-Fe(II) complex located in the oxygen-sensing N-terminal globin domain. A detailed understanding of the signal transduction mechanisms in heme-containing sensor proteins remains elusive. Here, we investigated the role of the globin domain's dimerization interface in signal transduction in AfGcHK. We present a crystal structure of a monomeric imidazole-bound AfGcHK globin domain at 1.8 Å resolution, revealing that the helices of the WT globin dimer are under tension and suggesting that Tyr-15 plays a role in both this tension and the globin domain's dimerization. Biophysical experiments revealed that whereas the isolated WT globin domain is dimeric in solution, the Y15A and Y15G variants in which Tyr-15 is replaced with Ala or Gly, respectively, are monomeric. Additionally, we found that although the dimerization of the full-length protein is preserved via the kinase domain dimerization interface in all variants, full-length AfGcHK variants bearing the Y15A or Y15G substitutions lack enzymatic activity. The combined structural and biophysical results presented here indicate that Tyr-15 plays a key role in the dimerization of the globin domain of AfGcHK and that globin domain dimerization is essential for internal signal transduction and autophosphorylation in this protein. These findings provide critical insights into the signal transduction mechanism of the histidine kinase AfGcHK from Anaeromyxobacter.

Cyclophilin A as a biomarker for the therapeutic effect of balloon angioplasty in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Although cardiac troponin and natriuretic peptide have been shown to decrease after balloon pulmonary angioplasty (BPA) with improved right ventricular afterload in chronic thromboembolic pulmonary hypertension (CTEPH), biomarkers to evaluate the effects of BPA independently of heart failure status remain to be developed. METHODS: In 39 consecutive CTEPH patients including 31 who underwent BPA, we measured plasma levels of cyclophilin A (CyPA), which we demonstrated is secreted from pulmonary vascular smooth muscle cells in response to mechanical stretch and hypoxia. RESULTS: CyPA levels were elevated in CTEPH patients (12.7, IQR: 7.6-16.0) compared with 8 thromboembolic controls with a history of venous thromboembolism (4.9, IQR: 2.4-11.2) or 18 healthy controls (4.1, IQR: 2.4-6.8) (both p< 0.05) and were linearly correlated with mean pulmonary arterial pressure (r=0.50, p = 0.0003) and pulmonary vascular resistance (r=0.32, p= 0.026). BPA reduced CyPA levels and tended to lower brain-type natriuretic peptide (BNP) levels (p< 0.01 and p = 0.07). When comparing the changes in CyPA before and after BPA in the two subgroups with higher (≥35pg/mL) and normal (<35pg/mL) BNP at baseline, CyPA decreased both in patients with higher BNP and those with normal BNP (both p< 0.05). In contrast, BNP decreased only in patients with higher BNP (p< 0.05). Also, CyPA decreased both in patients with lower (<25 kg/m2) and higher (≥25kg/m2) body mass index (BMI) at baseline (both p<0.05), whereas BPA tended to reduce BNP in patients with lower BMI (p = 0.12) but not in those with higher BMI (p = 0.55). CONCLUSIONS: CyPA could be a useful biomarker to evaluate the effects of BPA even in patients with normal BNP or high BMI.