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The effect of lifelong dynamics on host longevity of the gut microbiome is largely unknown. Herein, we analyzed the longitudinal fecal samples of seven sibling mice across their lifespan from birth to natural death, spanning over 1,000 days of age, and maintained them under controlled environmental and dietary conditions. Our 16S-rRNA sequencing analysis revealed 38 common “life-core” bacterial species/OTUs (operational taxonomic units) detected in ≥80% of all samples collected across the lifespan of individual mice. Despite the shared genetic background and dietary habits, the gut microbiome structure significantly diversified with age and among individuals. We found a strong positive correlation between longevity and the alpha diversity in middle age (500-700 days) and negative correlation in old age (>800 days). Furthermore, host longevity was significantly associated with the abundance of 17 bacterial species/OTUs, most of which were “life-core” species. Our data suggest that temporal dynamics of the gut microbiome are strongly linked to host longevity.

The gastrointestinal tract is constitutively exposed to proteases including trypsin, a serine protease originating from the pancreas1. Elevated trypsin levels in the large intestine have been implicated in pathological conditions including infectious and inflammatory bowel disease2-4. Here we show that trypsin is regulated via degradation by members of the gut microbiota. After passing through the small intestine, trypsin activity is markedly reduced in the caecum of specific pathogen-free (SPF) mice, whereas germ-free (GF) mice have high luminal trypsin levels. We have successfully identified and isolated Paraprevotella strains from the faecal microbiome of healthy human donors as potent trypsin-degrading commensals. Mechanistically, Paraprevotella recruit trypsin to the bacterial surface through type IX secretion system-dependent polysaccharide-anchoring proteins and promote trypsin autolysis. Paraprevotella colonization protects IgA from trypsin degradation and enhances the effectiveness of oral vaccines against Citrobacter rodentium. Moreover, Paraprevotella colonization inhibits lethal infection with murine hepatitis virus, a mouse coronavirus dependent on trypsin and trypsin-like proteases for entry into host cells5,6. Congruently, carriage of putative genes involved in trypsin degradation in the gut microbiome was associated with reduced diarrhoea severity in patients with SARS-CoV2 infection. Therefore, trypsin-degrading commensal colonization may contribute to the maintenance of intestinal homeostasis and protection from pathogen infection.

OBJECTIVE The aim of the study was to investigate the effect of abdominal drainage at appendectomy for complicated appendicitis in children. SUMMARY OF BACKGROUND DATA Although an abdominal drain placement at appendectomy is an option for reducing or preventing postoperative infectious complication, there is controversy regarding its effect for complicated appendicitis. METHOD The study used the data on appendectomies for complicated appendicitis in children (≤15 years old) that were operated in 2015 and registered in the National Clinical Database, a nationwide surgical database in Japan. One-to-two propensity score matching was performed to compare postoperative outcomes between patients with and without drainage at appendectomy. RESULT The study included 1762 pediatric appendectomies for complicated appendicitis, 458 of which underwent abdominal drainage at appendectomy. In the propensity-matched analysis, the drainage group showed a significant increase in wound dehiscence [drain (-) vs drain (+); 0.3% vs 2.4%, P = 0.001], and postoperative hospital stay (median: 7 days vs 9 days, P < 0.001). There were no significant differences in the incidence of any complications, organ space surgical site infection, re-admission, and reoperation.Subgroup analyses in perforated appendicitis and perforated appendicitis with abscess, and open and laparoscopic appendectomy all demonstrated that drain placement was not associated with a reduction in any complication or organ space surgical site infection. However, it was significantly associated with longer hospital stays. CONCLUSION This study suggested that an abdominal drain placement at appendectomy for complicated appendicitis among children has no advantage and can be harmful for preventing postoperative complications.

Increased levels of proteases, such as trypsin, in the distal intestine have been implicated in intestinal pathological conditions1–3. However, the players and mechanisms that underlie protease regulation in the intestinal lumen have remained unclear. Here we show that Paraprevotella strains isolated from the faecal microbiome of healthy human donors are potent trypsin-degrading commensals. Mechanistically, Paraprevotella recruit trypsin to the bacterial surface through type IX secretion system-dependent polysaccharide-anchoring proteins to promote trypsin autolysis. Paraprevotella colonization protects IgA from trypsin degradation and enhances the effectiveness of oral vaccines against Citrobacter rodentium. Moreover, Paraprevotella colonization inhibits lethal infection with murine hepatitis virus-2, a mouse coronavirus that is dependent on trypsin and trypsin-like proteases for entry into host cells4,5. Consistently, carriage of putative genes involved in trypsin degradation in the gut microbiome was associated with reduced severity of diarrhoea in patients with SARS-CoV-2 infection. Thus, trypsin-degrading commensal colonization may contribute to the maintenance of intestinal homeostasis and protection from pathogen infection.

Congenital H-type fistula is a rare congenital rectourogenital anomaly and is less common in males than in females. A one-year-and-eight-month-old boy with an ectopic perineal fistula was incidentally diagnosed with H-type fistula when he underwent voiding cystourethrography for vesicoureteral reflux. Further examination revealed that the H-type fistula was an ano-bulbar urethral fistula. At two years of age, the patient underwent fistulectomy and also anterior sagittal anorectoplasty for the ectopic perineal fistula during the same surgery.

In this study, an optical gain chip using emission-wavelength-controlled self-assembled InAs quantum dots (QDs) was developed for swept-source optical coherence tomography (SS-OCT) applications. The optical characterizations indicated that the QDs emission wavelength and optical gain spectra were controlled in the 1.1μm waveband by optimizing the QDs growth conditions. This waveband is useful for obtaining a large imaging depth of OCT because of an optimal balance between absorption and scattering in biological samples. In addition, continuous tunable lasing in the waveband was achieved by introducing the QD-based gain chip into a grating-coupled external cavity. This tunable laser was introduced into an SS-OCT setup, and the point spread function (PSF) was evaluated. The PSF position was observed to vary according to the optical path length differences. These results demonstrate the feasibility of the application of emission-wavelength-controlled QDs for SS-OCT.

Purpose Pneumothorax often develops in patients with Marfan syndrome (MFS). Here, we examined the effects of conservative and surgical pneumothorax treatments in children with MFS. Methods In this study, 23 patients, less than 20 years old, diagnosed with both MFS and pneumothorax between 1999 and 2019 were included. All data were collected retrospectively from patients’ medical records. Results In total, 18 of 23 patients (78%) had relapsed pneumothorax either on the ipsilateral or contralateral side. Among these 18 patients, 6 (26%) patients had multiple relapses. Conservative and surgical treatments of pneumothorax were attempted in 33 and 29 lungs, respectively. The conservative treatment was attempted as a definitive therapy in 21 lungs. Twelve conservative treatments (57%) failed, which required surgical intervention. In 9 lungs (43%) with successful conservative treatment, 6 (67%) had ipsilateral relapses. In contrast to the above findings, only 4 (13%) ipsilateral relapses were observed in 29 surgical treatments. Conclusions Our study revealed a low response and high relapse rate when MFS adolescents who diagnosed pneumothorax were subjected to the conservative treatment modality. Thus, we recommend surgical intervention as the first line of therapy to treat pneumothorax in adolescents diagnosed with MFS. Level of Evidence Ⅲ (Treatment Study)

IntroductionGiven an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methodsWe registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.ResultsOf the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.ConclusionsAlogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting.

Summary Host-microbe interactions orchestrate skin homeostasis, the dysregulation of which has been implicated in chronic inflammatory conditions such as atopic dermatitis and psoriasis. Here, we show that Staphylococcus cohnii is a skin commensal capable of beneficially inhibiting skin inflammation. We find that Tmem79−/− mice spontaneously develop interleukin-17 (IL-17)-producing T-cell-driven skin inflammation. Comparative skin microbiome analysis reveals that the disease activity index is negatively associated with S. cohnii. Inoculation with S. cohnii strains isolated from either mouse or human skin microbiota significantly prevents and ameliorates dermatitis in Tmem79−/− mice without affecting pathobiont burden. S. cohnii colonization is accompanied by activation of host glucocorticoid-related pathways and induction of anti-inflammatory genes in the skin and is therefore effective at suppressing inflammation in diverse pathobiont-independent dermatitis models, including chemically induced, type 17, and type 2 immune-driven models. As such, S. cohnii strains have great potential as effective live biotherapeutics for skin inflammation.

Background. Sagittal spino-pelvic malalignment in patients with chronic low back pain (CLBP) have been reported in the past, which may also affect cervical spine lesions. The purpose of this study is to investigate the cervical alignment in patients with CLBP.Method. Of the patients who visited an orthopedic specialist due to low back pain lasting more than three months, 121 cases (average 71.5 years old, 46 male and 75 female) with whole standing spinal screening radiographs were reviewed (CLBP group). Cervical parameters included cervical lordosis (CL), C2-C7 sagittal vertical axis (C2-7 SVA), and the T1 slope minus CL (T1S-CL). Cervical spine deformity was defined as C2-7 SVA>4cm, CL

Bubbles at the interface of two-dimensional layered materials in van der Waals heterostructures cause deterioration in the quality of materials, thereby limiting the size and design of devices. In this paper, we report a simple all-dry transfer technique, with which the bubble formation can be avoided. As a key factor in the technique, a contact angle between a picked-up flake on a viscoelastic polymer stamp and another flake on a substrate was introduced by protrusion at the stamp surface. Using this technique, we demonstrated the fabrication of high-quality devices on the basis of graphene/hexagonal boron nitride heterostructures with a large bubble-free region. Additionally, the technique can be used to remove unnecessary flakes on a substrate under an optical microscopic scale. Most importantly, it improves the yield and throughput for the fabrication process of high-quality van der Waals heterostructure-based devices.

We developed a compact dual-wavelength surface-emitting light source using InAs quantum dots (QDs) embedded in a vertical cavity (VC). The VC was designed to possess two optical cavity modes that resonate with the discrete emission lines of the QDs. The fabricated light source exhibited significant enhancements in the vertical light emission corresponding to the VC modes. In addition, the light source demonstrated selectivity to the enhanced emission wavelengths with changes in temperature. Compared to conventional dual-wavelength vertical external cavity surface-emitting lasers, these QD-based dual-wavelength emission devices allow for the realization of simple structures because the InAs QDs act as dual-light-emitting materials. These results can be applied to simple dual-wavelength surface-emitting light sources.

Goreisan, a traditional Japanese medicine, has previously been used for hydrostatic modulation. This retrospective study investigated the efficacy of goreisan for spermatic cord hydrocele resolution in children. Seventy-two boys treated for spermatic cord hydrocele between 2012 and 2015 were included; Goreisan was administered to 16 [group G, median age 3 (1–8) years], and 56 were followed without medication [group C, median age 1 (0–8) years]. An age-matched comparison was conducted between 14/16 group G patients (group g) and 14/56 group C patients (group c). Incidences of resolution were higher in groups G and g than in groups C and c, respectively, both during the study period and within the first 6-month observation period; groups G and g also had a significantly lower incidence of surgery for hydrocele than in groups C and c, respectively. The interval from the commencement of observation until hydrocele resolution was significantly shorter in group G than in group C, but not in group g than in group c. Goreisan can effectively promote the resolution of spermatic cord hydrocele in children and may be a valid treatment choice for this condition.

As a first step to develop a diamond integrated circuit, hydrogenated diamond not and nor logic circuits composed of depletion-mode (D-mode) and enhancement-mode (E-mode) metal–oxide–semiconductor field-effect transistors (MOSFETs) are fabricated. The D- and E-modes MOSFETs act as load and driver devices for the logic circuits, respectively, which provides complementary transistor actions. The extrinsic transconductance maxima for both the MOSFETs are almost the same value of 17 mS mm $^{-1}$ and insensitive to device processing. With supply voltage changing from −5 to −25 V, gain maximum for not logic circuit increases from 1.2 to 26.1. The nor logic circuit shows clear nor gate characteristics.

Logarithmical increase of the longitudinal resistivity ( ρ x x ) between 10 K and 80 K and its saturation at low temperature were observed in the graphene synthesized by the chemical vapor deposition (CVD) with various applied gate voltage. In the two-dimensional system, it is considerably difficult to identify the origin of the logarithmic temperature (Log-T) increase of the resistivity, because there are three corrections to exhibit the Log-T behavior: the weak localization, the electron-electron interaction (EEI) in the disordered system and the Kondo effect. In order to distinguish the origin of the Log-T behavior, we contrived a new method utilizing the magnetotransport property in tilted magnetic fields. As a result, we have assigned the Log-T behavior in the CVD graphene to the correction of the EEI.

Purpose To establish and validate risk models of mortality and morbidity associated with 12 major pediatric surgical procedures using the National Clinical Database-Pediatric (NCD-P) data. Methods We used the NCD-P data for the development and validation datasets. By using multivariate logistic regression to analyze the development dataset, we created a prediction model for 30-day mortality and morbidity in 12 major pediatric surgical procedures, including tracheoplasty, pneumonectomy, fundoplication, total/subtotal excision of malignant tumor, and surgeries for Hirschsprung disease, anorectal malformation, biliary atresia, choledocal cyst, midgut volvulus, funnel chest, gastrointestinal perforation, and intestinal obstruction. We selected variables that were almost identical to those used in the American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-P). The primary outcomes were 30-day mortality and composite morbidity. We assessed the obtained models using the C-indices of the development and validation datasets. Results Overall, 10 and 20 variables were identified for mortality and morbidity, respectively. C-indices of mortality were 0.940 and 0.924 in the development and validation datasets, respectively. C-indices of morbidity were 0.832 and 0.830 in the development and validation datasets, respectively. Conclusions Based on the NCD-P data, we developed satisfactory risk models for mortality and morbidity prediction in major pediatric surgeries. Level of evidence. LEVEL I (Prognosis Study).

We developed a near-infrared (NIR) superluminescent diode (SLD) based on self-assembled InAs quantum dots (QDs) and demonstrated high-axial-resolution optical coherence tomography (OCT) imaging using this QD-based SLD (QD-SLD). The QD-SLD utilized InAs QDs with controlled emission wavelengths as a NIR broadband light emitter, and a tilted waveguide with segmented electrodes was prepared for edge-emitting broadband electroluminescence (EL) spanning approximately 1–1.3 μm. The bandwidth of the EL spectrum was increased up to 144 nm at a temperature of 25 °C controlled using a thermoelectric cooler. The inverse Fourier transform of the EL spectrum predicted a minimum resolution of 3.6 μm in air. The QD-SLD was subsequently introduced into a spectral-domain (SD)-OCT setup, and SD-OCT imaging was performed for industrial and biological test samples. The OCT images obtained using the QD-SLD showed an axial resolution of ~4 μm, which was almost the same as that predicted from the spectrum. This axial resolution is less than the typical size of a single biological cell (~5 μm), and the practical demonstration of high-axial-resolution OCT imaging shows the application of QD-SLDs as a compact OCT light source, which enables the development of a portable OCT system.

Graphene superlattices have recently been attracting growing interest as an emergent class of quantum metamaterials. In this paper, we report the observation of nonlocal transport in bilayer graphene (BLG) superlattices encapsulated between two hexagonal boron nitride (hBN) layers, which formed hBN/BLG/hBN moir\'e superlattices. We then employed these superlattices to detect a long-range charge-neutral valley current using an all-electrical method. The moir\'e superlattice with broken inversion symmetry leads to a hot spot with Berry curvature accumulating at the charge neutral point (CNP), and it harbors satellites of the CNP. We observed nonlocal resistance on the order of 1 $\text{k}\Omega$, which obeys a scaling relation. This nonlocal resistance evolves from the quantum Hall effect but without magnetic field/time-reversal symmetry breaking, which is associated with a hot-spot-induced topological valley current. This study should pave the way to developing a Berry-phase-sensitive probe to detect hot spots in gapped Dirac materials with inversion-symmetry breaking., Comment: 9 pages, 3 figures

Ankle sprains are the most common lower extremity injuries associated with sports activity. Although ligament repair techniques are popular, reconstruction methods using free tendons are considered when the ligament remnant is insufficiently strong, when high-demand athletes sustain repeat ankle sprains, or in revision cases after repair. Recently, some arthroscopic reconstruction techniques have been reported. The distal fibular end is thin; therefore, surgeons must be careful while drilling the fibular tunnel. This report indicates the safe creation method of an anatomical fibular tunnel during anatomical arthroscopic reconstruction of the anterior talofibular ligament and calcaneofibular ligament. This also provides a stronger reconstruction using a 2-strand tendon graft for the anterior talofibular ligament substitute, which is thought to have less risk for postoperative graft failure.

We fabricated and characterized a grating-coupled external cavity laser with gain chips including self-assembled InAs quantum dots (QDs) for swept-source optical coherence tomography applications. By controlling the emission wavelength of the self-assembled InAs QDs, tunable lasing at a wavelength band of 1–1.1 μm was obtained, which represents an optimal balance between absorption and scattering in biological tissues. Straight and J-shaped edgeemitting ridge waveguides (RWGs) were fabricated on a GaAs-based waveguide layer containing four InAs QDs layers. A diffraction grating with the quasi-Littrow configuration was employed as an external cavity for the fiber-coupled diodes. Electroluminescence spectra from the QD-based diodes revealed that broadband amplified spontaneous emissions appeared in a J-shaped RWG, whereas Fabry–Perot lasing occurred in the straight RWG. The external cavity was then introduced for the diode with a J-shaped RWG, and a tuning range of 65 nm centered at approximately 1100 nm was obtained from the QD gain chip with the J-shaped RWG.

Herein, we report an emission wavelength control technique for self-assembled InAs quantum dots (QDs) grown via molecular beam epitaxy using an As2 source (As2-QDs). The As2-QDs exhibited photoluminescence with a shorter center wavelength and larger bandwidth than those of the QDs grown using an As4 source. In addition, the emission center wavelength could be controlled by adjusting the time between the growth and capping of the As2-QDs. We utilized the multilayer stack of emission-wavelength-controlled As2-QDs to fabricate an electrically-driven light source and demonstrated its broadband (approximately 130 nm) emission in the 1–1.3 μm wavelength range.

Effective mobility in top-gated MoS 2 metal-oxide-semiconductor field-effect transistors (MOSFETs) with HfO 2 /TaN gates was investigated. We propose a model for effective mobility in MoS 2 MOSFETs and discuss its usefulness. Parameter fitting of the proposed effective mobility model makes possible a discussion of how the scattering mechanism limits the effective mobility. Charged impurities, phonons, and surface roughness were presumed to be possible causes of scattering, and the effect of contact resistance was also taken into account. In the device exhibiting the better mobility of 17.4 cm 2 /Vs, phonon-assisted hopping carrier transport probably limited the mobility. In contrast, in the device exhibiting the worse mobility of 2.8 cm 2 /Vs, scattering caused by charged impurities dominated the transport characteristics. The proposed model facilitates device-to-device comparisons of carrier transport characteristics of MoS 2 transistors at room temperature and accelerates their further development.

Biliary atresia (BA) is a destructive inflammatory obliterative cholangiopathy of the neonate that affects various parts of the bile duct. If early diagnosis followed by Kasai portoenterostomy is not performed, progressive liver cirrhosis frequently leads to liver transplantation in the early stage of life. Therefore, prompt diagnosis is necessary for the rescue of BA patients. However, the prompt diagnosis of BA remains challenging because specific and reliable biomarkers for BA are currently unavailable. In this study, we discovered potential biomarkers for BA using deep proteome analysis by data-independent acquisition mass spectrometry (DIA–MS). Four patients with BA and three patients with neonatal cholestasis of other etiologies (non-BA) were recruited for stool proteome analysis. Among the 2110 host-derived proteins detected in their stools, 49 proteins were significantly higher in patients with BA and 54 proteins were significantly lower. These varying stool protein levels in infants with BA can provide potential biomarkers for BA. As demonstrated in this study, the deep proteome analysis of stools has great potential not only in detecting new stool biomarkers for BA but also in elucidating the pathophysiology of BA and other pediatric diseases, especially in the field of pediatric gastroenterology.

Carbon-based superlattices represent a novel class of quantum metamaterials having promising prospects. Here, we show the first fabrication of folded bilayer-bilayer graphene (fBBLG)/hexagonal boron nitride (hBN) superlattices. In the transport properties at low temperatures, satellite peaks are observed due to the crystallographic angle alignment of fBBLG and hBN. The peculiar resistance peaks appear away from the charge neutrality point and the hBN-induced satellites, which may be signatures of possible competing orders. Our results suggest the emergence of a unique electronic band-structure in the fBBLG, providing a way for investigating the correlated electron phenomena by performing energy-band engineering with superlattice structures.

Colorectal cancer is a rare disease in children. It is often diagnosed at an advanced stage, meaning that these patients often require a multidisciplinary treatment approach. This is a case report of advanced cecal cancer in a teenager who was treated with cytoreductive surgery and long-term chemotherapy with molecular targeted agents.A previously healthy 15-year-old boy was referred to our hospital with a two-month history of abdominal pain and diarrhea. On physical examination, his abdomen was distended and a tender mass was palpable in the right lower quadrant. Laboratory data revealed severe anemia and elevated tumor markers. Computed tomography showed thickening of the cecal wall and multiple peritoneal nodules. He was diagnosed with advanced cecal cancer with peritoneal metastasis, and underwent right colectomy, followed by 5-fluorouracil-based chemotherapy with molecular targeted agents. However, his disease continued to progress, and the patient died 17 months after his initial diagnosis.The rarity of this disease means diagnosis is difficult and that there is little evidence on best treatment; therefore, more research is needed in these areas. Keywords: Colorectal cancer, Peritoneal carcinomatosis, Pediatrics

Our aim was to compare postoperative outcomes of laparoscopic and open appendectomies for acute appendicitis in children under the circumstance of widespread use of laparoscopic surgery. This study included data on laparoscopic and open appendectomies in children with acute appendicitis from the National Clinical Database, which is a Japanese nationwide surgical database, in 2015. The occurrence rates of complications within 30 days after the surgery and postoperative hospital stay were compared by univariate and multivariate analyses. p