Orbital-resolved visualization of single-molecule photocurrent channels.

Given its central role in utilizing light energy, photoinduced electron transfer (PET) from an excited molecule has been widely studied1-6. However, even though microscopic photocurrent measurement methods7-11 have made it possible to correlate the efficiency of the process with local features, spatial resolution has been insufficient to resolve it at the molecular level. Recent work has, however, shown that single molecules can be efficiently excited and probed when combining a scanning tunnelling microscope (STM) with localized plasmon fields driven by a tunable laser12,13. Here we use that approach to directly visualize with atomic-scale resolution the photocurrent channels through the molecular orbitals of a single free-base phthalocyanine (FBPc) molecule, by detecting electrons from its first excited state tunnelling through the STM tip. We find that the direction and the spatial distribution of the photocurrent depend sensitively on the bias voltage, and detect counter-flowing photocurrent channels even at a voltage where the averaged photocurrent is near zero. Moreover, we see evidence of competition between PET and photoluminescence12, and find that we can control whether the excited molecule primarily relaxes through PET or photoluminescence by positioning the STM tip with three-dimensional, atomic precision. These observations suggest that specific photocurrent channels can be promoted or suppressed by tuning the coupling to excited-state molecular orbitals, and thus provide new perspectives for improving energy-conversion efficiencies by atomic-scale electronic and geometric engineering of molecular interfaces.

Nanocavity tuning and formation controlled by the phase change of sub-micron-square GST patterns on Si photonic crystals.

It has been well established that photonic crystal nanocavities with wavelength sized mode volume enable various integrable photonic devices with extremely small consumption energy and small footprint. In this study, we explore the possibility of non-volatile functionalities employing photonic crystal nanocavities and phase change material, Ge2Sb2Te5 (GST). Recently, non-volatile photonic devices based on GST have attracted significant interest and are expected to enable energy-efficient photonic processing, especially for optical computing. However, the device size and the area of GST in previous studies have been rather large. Here, we propose and fabricate Si photonic crystal nanocavities on which submicron-square GST patterns are selectively loaded. Because of the strong light confinement, extremely small area of GST is sufficient to manipulate the cavity mode. We have succeeded to fabricate 30-nm-thick and several-100nm-square GST blocks patterned at the center of photonic crystal cavity with a high alignment accuracy. We confirmed that the resonant wavelength and Q-factor of cavity modes are controlled by the phase change of GST. Moreover, cavity formation controlled by submicron-sized GST is also demonstrated by GST-loaded photonic-crystal line-defect waveguides. Our approach in which we place sub-micron-sized GST inside a photonic crystal nanocavity is promising for realizing extremely energy-efficient non-volatile integrable photonic devices, such as switches, modulators, memories, and reconfigurable novel devices.

In Vitro Digestion-In Situ Absorption Setup Employing a Physiologically Relevant Value of the Membrane Surface Area/Volume Ratio for Evaluating Performance of Lipid-Based Formulations: A Comparative Study with an In Vitro Digestion-Permeation Model.

The aim of this study is to establish and test an in vitro digestion-in situ absorption model that can mimic in vivo drug flux by employing a physiologically relevant value of the membrane surface area (S)/volume (V) ratio for accurate prediction of oral drug absorption from lipid-based formulations (LBFs). Three different types of LBFs (Type IIIA-MC, Type IIIA-LC, and Type IV) loaded with cinnarizine (CNZ), a lipophilic weak base with borderline permeability, and a control suspension were prepared. Subsequently, a simultaneous in vitro digestion-permeation experiment was conducted using a side-by-side diffusion cell with a dialysis membrane having a low S/V value. During digestion, CNZ partially precipitated for Type IV, while it remained solubilized in the aqueous phase for Type IIIA-MC and Type IIIA-LC in the donor compartment. However, in vitro drug fluxes for Type IIIA-MC and Type IIIA-LC were lower than those for Type IV due to the reduced free fraction of CNZ in the donor compartment. In pharmacokinetic studies, a similar improvement in in vivo oral exposure relative to suspension was observed, regardless of the LBFs used. Consequently, a poor correlation was found between in vitro permeation and areas under the plasma concentration-time curve (AUCoral) (R2 = 0.087). A luminal concentration measurement study revealed that this discrepancy was attributed to the extremely high absorption rate of CNZ in the gastrointestinal tract compared to that across a dialysis membrane evaluated by the in vitro digestion-permeation model, i.e., the absorption of CNZ in vivo was completed regardless of the extent of the free fraction, owing to the rapid removal of CNZ from the intestine. Subsequently, we aimed to predict the oral absorption of CNZ from the same formulations using a model that demonstrated high drug flux by employing the physiologically relevant S/V value and rat jejunum segment as an absorption sink (for replicating in vivo intestinal permeability). Predigested formulations were injected into the rat intestinal loop, and AUCloop values were calculated from the plasma concentration-time profiles. A better correlation was found between AUCloop and AUCoral (R2 = 0.72), although AUCloop underestimated AUCoral for Type IV due to the precipitation of CNZ during the predigestion process. However, this result indicated the importance of mimicking the in vivo drug absorption rate in the predictive model. The method presented herein is valuable for the development of LBFs.

Revealing Comprehensive Food Functionalities and Mechanisms of Action through Machine Learning.

Foods possess a range of unexplored functionalities; however, fully identifying these functions through empirical means presents significant challenges. In this study, we have proposed an in silico approach to comprehensively predict the functionalities of foods, encompassing even processed foods. This prediction is accomplished through the utilization of machine learning on biomedical big data. Our focus revolves around disease-related protein pathways, wherein we statistically evaluate how the constituent compounds collaboratively regulate these pathways. The proposed method has been employed across 876 foods and 83 diseases, leading to an extensive revelation of both food functionalities and their underlying operational mechanisms. Additionally, this approach identifies food combinations that potentially affect molecular pathways based on interrelationships between food functions within disease-related pathways. Our proposed method holds potential for advancing preventive healthcare.

TMEM2 suppresses TLR3-mediated IFN-ß/ISG56/CXCL10 expression in BEAS-2B bronchial epithelial cells.

BACKGROUND: Bronchial epithelial cells are at the front line of viral infections. Toll-like receptor 3 (TLR3) cascade causes the expression of interferon (IFN)-ß and IFN-stimulated genes (ISGs), which in turn induce an antiviral response. Members of the transmembrane protein (TMEM) family are expressed in various cell types. Although the prognostic value of TMEM2 in various cancers has been reported, its association with infectious diseases remains unknown. In this study, we investigated the effects of TMEM2 on antiviral immunity in BEAS-2B bronchial epithelial cells. METHODS AND RESULTS: TMEM2 protein was found in the cytoplasm of normal human bronchial epithelial cells and differed between organs using immunohistochemistry. Cultured BEAS-2B cells were transfected with TMEM2 siRNA, followed by administration of TLR3 ligand polyinosinic-polycytidylic acid (poly IC) or recombinant human (r(h)) IFN-ß. The expression of TMEM2, IFN-ß, ISG56, C-X-C motif chemokine ligand 10 (CXCL10) and hyaluronan were evaluated appropriately by western blotting, quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. TMEM2 expression was not altered by poly IC stimulation. Knockdown of TMEM2 increased poly IC-induced expression of IFN-ß, CXCL10, and ISG56, while IFN-ß-induced expression of ISG56 and CXCL10 were not changed by TMEM2 knockdown. The hyaluronan concentration in the medium was decreased by either TMEM2 knockdown or poly IC, but additive or synergistic effects were not observed. CONCLUSIONS: TMEM2 knockdown enhanced TLR3-mediated IFN-ß, CXCL10, and ISG56 expression in BEAS-2B cells. This implies that TMEM2 suppresses antiviral immune responses and prevents tissue injury in bronchial epithelial cells.

Risk factors for stoma prolapse after laparoscopic loop colostomy.

BACKGROUND: Stoma prolapse (SP) is a common stoma-related complication, particularly in loop colostomies. This study aimed to investigate potential risk factors for SP development after laparoscopic loop colostomy. METHODS: In total, data from 140 patients who underwent laparoscopic loop colostomy were analyzed between September 2016 and March 2022. Risk factors for SP were investigated retrospectively. RESULTS: The median follow-up duration after colostomy was 12.5 months, and SP occurred in 33 (23.6%) patients. Multivariate analysis showed that being overweight (body mass index ≥ 25; odds ratio [OR], 8.69; 95% confidential interval [CI], 1.61-46.72; p = 0.012) and having a thin rectus abdominis penetration of the stoma (< 8.9 mm; OR, 8.22; 95% CI, 2.50-27.05; p < 0.001) were independent risk factors for SP. Other patient characteristics and surgical factors associated with stoma construction were unrelated to SP development. CONCLUSIONS: Being overweight and the route penetrating the thinner rectus abdominis during stoma construction was associated with a significantly higher incidence of SP after laparoscopic loop colostomy. Selecting a construction site that penetrates the thicker rectus abdominis muscle may be crucial for preventing SP.

Left atrial volume index as a predictor for left atrial appendage thrombus in patients with non-valvular atrial fibrillation receiving appropriate oral anticoagulation therapy: A prospective multi-center study.

OBJECTIVES: We previously reported a higher left atrial volume index (LAVI) was independently associated with left atrial (LA) appendage (LAA) thrombus formation in 737 patients with non-valvular atrial fibrillation (NVAF) receiving appropriate oral anticoagulation therapy. Since our previous study was a retrospective single-center study, we designed and conducted a prospective multi-center study to verify our findings for LAVI as a predictor of LAA thrombus in patients with NVAF receiving appropriate oral anticoagulation therapy. METHODS: This prospective multi-center study comprised 746 consecutive patients with NVAF recruited between December 2021 and March 2023 from eight institutions in Japan, who were receiving appropriate oral anticoagulation therapy, had undergone transthoracic echocardiography and transesophageal echocardiography (TEE). RESULTS: LAA thrombi were observed in 21 patients (2.8%). The prevalence of LAA thrombus formation in patients with paroxysmal AF (PAF) was significantly lower than that in patients with non-PAF (0.7% vs. 4.1%, p = .006). LAA thrombus formation was detected in none (0/171) of the patients with normal size LA (LAVI ≤ 34 mL/m2 ). The prevalence of LAA thrombus formation in patients with mildly dilated LA (LAVI: 34-49.9 mL/m2 ) was 2.1% (6/283), but that in PAF patients was low at 1.0% (1/104). Furthermore, this prevalence in patients with severely dilated LA (LAVI ≥ 50 mL/m2 ) was high at 5.1% (15/292). CONCLUSIONS: The findings of this prospective multi-center study are consistent with those of our previous study. Thus, the need for TEE prior to catheter ablation or electrical cardioversion can be determined by the level of LAVI.

Total laparoscopic hysterectomy with posterior cul-de-sac obliteration: step-by-step procedures based on precise anatomical landmarks.

BACKGROUND: Dense adhesion due to severe endometriosis between the posterior cervical peritoneum and the anterior sigmoid or rectum obliterates the cul-de-sac and distorts normal anatomic landmarks. Surgery for endometriosis is associated with severe complications, including ureteral and rectal injuries, as well as voiding dysfunction. It is important to develop the retroperitoneal avascular space based on precise anatomical landmarks to minimize the risk of ureteral, rectal, and hypogastric nerve injuries. We herein report the anatomical highlights and standardized and reproducible surgical steps of total laparoscopic hysterectomy for posterior cul-de-sac obliteration. OPERATIVE TECHNIQUE: We approach the patient with posterior cul-de-sac obliteration using the following five steps. Step 1: Preparation (Mobilization of the sigmoid colon and bladder separation from the uterus). Step 2: Development of the lateral pararectal space and identification of the ureter. Step 3: Isolation of the ureter. Step 4: Development of the medial pararectal space and separation of the hypogastric nerve plane. Step 5: Reopening of the pouch of Douglas. CONCLUSION: Surgeons should recognize the importance of developing the retroperitoneal avascular space based on precise anatomical landmarks, and each surgical step must be reproducible.

Non-suppurative and necrotizing testicular arteritis in the male reproductive organs of a heavy draft horse.

Equine testicular arteritis commonly occurs as a consequence of the migration of nematode larvae or equine arteritis virus (EAV) infection. However, testicular arteritis without evidence of these infections has been reported, and the underlying pathogenesis remains unclear. We encountered testicular arteritis without evidence of nematode or EAV infection in a 3-year-old male heavy draft horse with scrotal enlargement. Grossly, the volume of the pampiniform plexus was markedly increased due to edema. Histologically, non-suppurative and necrotizing testicular arteritis, characterized by lymphocyte infiltration and fibrinoid necrosis of the arterial walls, was diffusely observed in the spermatic cord, pampiniform plexus (most severe), testis, and epididymis. We were unable to identify the cause of arteritis, such as a viral infection or autoimmune abnormality.

Novel Strategy for the Management of Cervical Multicystic Diseases.

PURPOSE: To investigate the clinical practices of diagnosing multicystic cervical lesions as a means to develop a more appropriate diagnostic algorithm for gastric-type adenocarcinoma (GAS) and its precursors. METHODS: Clinical information for 159 surgically treated patients for multicystic disease of the uterine cervix was collected from 15 hospitals. We performed a central review of the MRI and pathological findings. The MRI findings were categorized into four types including two newly proposed imaging features based on the morphology and distribution of cysts, and the diagnosis accuracy was assessed. Among the four MRI types, types 1 and 2 were categorized as benign lesions that included LEGH; type 3 were precancerous lesions (with an assumption of atypical LEGH); and type 4 were malignant lesions. RESULTS: The central pathological review identified 56 cases of LEGH, seven with GAS, four with another form of carcinoma, and 92 with benign disease. In clinical practice, over-diagnosis of malignancy (suspicion of MDA) occurred for 12/19 cases (63.2%) and under-diagnosis of malignancy occurred for 4/11 (36%). Among the 118 patients who had a preoperative MRI and underwent a hysterectomy, type 3 or 4 MRI findings in conjunction with abnormal cytology were positively indicative of premalignancy or malignancy, with a sensitivity and specificity of 61.1% and 96.7%, respectively. CONCLUSIONS: Although the correct preoperative diagnosis of cervical cancer with a multicystic lesion is challenging, the combination of cytology and MRI findings creates a more appropriate diagnostic algorithm that significantly improves the diagnostic accuracy for differentiating benign disease from premalignancy and malignancy.

Bisphosphonate FYB-931 Prevents High Phosphate-Induced Vascular Calcification in Rat Aortic Rings by Altering the Dynamics of the Transformation of Calciprotein Particles.

Patients with chronic kidney disease develop vascular calcification, owing to impaired calcium and phosphate metabolism. The prevention of vascular calcification is important to improve the prognosis of such patients. In this study, we investigated whether treatment with FYB-931, a novel bisphosphonate compound, prevents vascular calcification in rat aortic rings cultured in high-phosphate medium for 9 days, assessed by measurement of the calcium content and the degree of calcium deposition, visualized using von Kossa staining. The effect on the transformation of calciprotein particles (CPPs) from primary to secondary CPPs was assessed using a fluorescent probe-based flow cytometric assay. FYB-931 dose-dependently prevented high phosphate-induced aortic calcification, but failed to rapidly cause the regression of high phosphate-induced vascular calcification once it had developed. Furthermore, the treatment dose-dependently inhibited the high phosphate-induced transformation from primary to secondary CPPs. In addition, the treatment with FYB-931 prevented the transformation from primary to secondary CPPs in vitamin D3-treated rats as a model of ectopic calcification, consistent with the results from rat aortic rings. In conclusion, treatment with FYB-931 prevents high phosphate-induced rat aortic vascular calcification by altering the dynamics of CPP transformation. This finding suggests that inhibition of the transformation from primary to secondary CPPs is an important target for the prevention of vascular calcification in patients with chronic kidney disease.

Separate Evaluation of Fraction Absorbed and Intestinal Availability after Oral Administration of Drugs Based on the Measurement of Portal and Systemic Plasma Concentrations and Luminal Concentration.

There are several experimental methods to estimate the product of the fraction absorbed (Fa) and intestinal availability (Fg) in vivo after oral administration of drugs. Metabolic enzyme inhibitors are typically used to separate Fg from Fa·Fg. Since Fa·Fg can be regarded as Fa under metabolism-inhibited conditions, Fg can be isolated by dividing Fa·Fg by Fa. However, if the inhibition of intestinal metabolism is insufficient, Fa is overestimated, which results in an underestimation of Fg compared to the actual value. In this study, to avoid this problem, an experimental method for the separate estimation of Fa and Fg in rats without utilizing metabolic enzyme inhibitors was established. Buspirone, a CYP3A substrate, and ribavirin, a substrate of purine nucleoside phosphorylase and adenosine kinase, were selected as models. Following oral administration of the drugs with fluorescein isothiocyanate dextran 4000 (FD-4, an unabsorbable marker), Fa·Fg was pharmacokinetically calculated from portal and systemic plasma concentration-time profiles of model drugs and Fa was calculated from the difference in the ileal concentration profiles of the drugs and FD-4. Fg was evaluated by dividing Fa·Fg by Fa. Following oral administration, buspirone was not detected in any segment of the small intestine, indicating that the administered buspirone was completely absorbed. In addition, buspirone was extensively metabolized in enterocytes (Fg = 20.1). Ribavirin was primarily absorbed in the upper segment of the small intestine, and 64.4% of the ribavirin was absorbed before it reached the ileum. In addition, it was revealed that ribavirin was metabolized more extensively in the intestine than in the liver. Our method may be effective in quantitatively assessing Fa and Fg in vivo, which can help in the formulation design and prediction of drug-drug interactions.

Total laparoscopic hysterectomy when there is posterior cul-de-sac obliteration: a step-by-step nerve-sparing technique.

Dense adhesions because of severe endometriosis between the posterior cervical peritoneum and the anterior sigmoid or rectum obliterate the cul-de-sac and distort normal anatomic landmarks. Surgery for endometriosis is associated with severe complications, including ureteral and rectal injuries and voiding dysfunction. Surgeons should recognize the importance of not only avoiding ureteral and rectal injuries but also focusing on the preservation of the hypogastric nerves. Herein, we reported the anatomic highlights and surgical steps of laparoscopic hysterectomy for posterior cul-de-sac obliteration with the nerve-sparing technique.

Feasibility of two laparoscopic surgeries for colon cancer performed by the same surgeon on a single day.

BACKGROUND: Although the proportion of laparoscopic colectomies (LCs) for colon cancer is increasing, the feasibility of the same surgeon performing two LCs on a single day remains unknown. This study was conducted to clarify the feasibility of this practice by evaluating short-term and long-term outcomes. METHODS: This retrospective analysis enrolled patients with pathological stage I-III colon cancer who underwent LC at the Shizuoka Cancer Center between 2010 and 2020. Patients were divided into two groups based on the timing of the surgery for the surgeon. The first group (n = 1485) comprised patients who underwent LC as the first surgery of the day for the surgeon. The second group (n = 163) comprised patients who underwent LC as the second LC of the day for the surgeon. Propensity score matching was performed to balance the baseline characteristics of the first and second groups. The short-term and long-term outcomes of the two groups were compared. RESULTS: After propensity score matching, there were no significant differences in the incidence of postoperative complications of Clavien-Dindo classification grade II or higher between the first (10.4%, 17/163) and second groups (5.5%, 9/163). There were no significant differences in other perioperative outcomes, including operative time, intraoperative blood loss, and incidence of conversion to open surgery, between the two groups. Regarding long-term outcomes, there were no significant differences in overall survival or relapse-free survival between the two groups both in the full cohort and in the propensity score-matched cohort. In the propensity score-matched cohort, 5-year overall survival was 92.7% in the first group and 94.4% in the second group; 5-year relapse-free survival was 87.1% and 90.3%, respectively. CONCLUSION: Our results suggest that the same surgeon performing two LCs for colon cancer on a single day is feasible in terms of short-term and long-term outcomes.

Comparison of Berberine Bioavailability between Oral and Rectal Administrations in Rats.

The oral bioavailability of berberine is quite low due to extensive first-pass metabolism. To increase the bioavailability of berberine (BBR), the efficacy of rectal administration that can avoid intestinal and hepatic first-pass metabolism partly was evaluated using BBR sulfate in rats. BBR sulfate was administered intravenously (1 mg/kg as BBR), orally (10 mg/kg as BBR) and rectally (1, 3, or 10 mg/kg as BBR) using Witepsol® H15 suppository base to evaluate bioavailability in rats. Concentrations of BBR in plasma were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). When BBR sulfate was administered orally, the average oral bioavailability was 0.26%. When BBR sulfate was administered rectally, the average bioavailabilities were 17.0% at 1 mg/kg, 24.3% at 3 mg/kg, and 12.3% at 10 mg/kg as BBR, respectively. Thus, rectal administration of BBR sulfate greatly increased the bioavailability of BBR as compared with oral administration, which would also increase the pharmacological activities of BBR in vivo.

Efficacy of oral administration of ascofuranone with and without glycerol against Trypanosoma congolense.

In many developing countries, trypanosomosis in animals results in the reduction of livestock productivity. Since trypanosomosis is endemic to rural areas where medical and veterinary infrastructure is underdeveloped, development of affordable and easy-to-maintain drugs for treatment and prophylaxis against trypanosomosis is necessary. To this end, in this study, we evaluated the efficacy of oral administration of ascofuranone (AF), with and without glycerol (GOL), against trypanosomosis, using a mouse model. We used T. congolense IL3000, the most virulent animal-infecting trypanosome, and BALB/c mice in this study. Eight mice were assigned to either of Groups 1-7: non-infected, untreated, AF 10, 20, 30, 50, and 100 mg/kg with or without GOL, respectively. In the experiment with AF administered with GOL, survival rates were 0% in Group 2 (untreated) and Group 3 (AF 10 mg/kg), 37.5% in Group 4 (AF 20 mg/kg) and Group 5 (AF 30 mg/kg), 50% in Group 6 (AF 50 mg/kg), and 100% in Group 7 (AF 100 mg/kg). In groups in which AF was administered without GOL, survival rates were 0% in Group 2 (untreated), Group 3 (AF 10 mg/kg), Group 4 (AF 20 mg/kg), Group 5 (AF 30 mg/kg), and Group 6 (AF 50 mg/kg), and 12.5% in Group 7 (AF 100 mg/kg), with one mouse surviving till the end of the observation period. The results of the analysis showed that survival rates were significantly higher in all groups (Groups 3-7) than in the untreated group (Group 2) (p < 0.05). Furthermore, a comparison of groups with or without GOL at the same AF concentration revealed that the survival rate was significantly higher in the group treated with GOL. These results suggest that the treatment efficacy of AF against animal trypanosomosis caused by T. congolense is greater when co-administered with GOL, and that oral administration of AF could be a new therapeutic strategy for animal African trypanosomosis.

Partial Tracheal Defects Closure using Glutaraldehyde-Treated Autologous Pericardium.

BACKGROUND: The usefulness of autologous pericardium treated with glutaraldehyde (GA) for tracheal defect closure is unknown. This study preliminarily evaluated whether a GA-treated autologous pericardial graft can effectively close tracheal defects in a beagle model. METHODS: Defects of 10 mm × 10 mm were created on the trachea of 10 beagles and divided into a GA-treated group (n = 5), with tracheal reconstruction using GA-treated pericardium, and control group (n = 5), using fresh pericardium. Repair sites were evaluated through bronchoscopy and histology. Blood flows on graft were measured using laser Doppler technique on postoperative days (PODs) 0, 4, 7, 14, 28, and 56. Repair sites were histologically evaluated on POD 56. In addition, GA-treated pericardia of three other beagles were histologically evaluated 12 months postoperatively, for long-term follow-up. RESULTS: All animals survived; none developed anastomotic insufficiency. The mean suturing time and frequency of additional suture were significantly shorter and lower in the GA-treated group than in the control group (p = 0.002, 0.004). All animals in the control group exhibited graft contraction, whereas the GA-treated group healed with most graft residual and reepithelialization in the bronchoscopic and histological findings (p = 0.01, 0.004). Further, all long-term GA-treated pericardia of three beagles were confirmed as residual grafts with reepithelialization, without contraction, at 12 months postoperatively. Blood flows on graft using laser Doppler technique in the GA-treated group were detected at POD 14 or thereafter. CONCLUSION: GA-treated pericardium was easier to handle and provided favorable scaffolding, without graft contraction, compared with the nontreated pericardium at short- and long-term follow-up.

[A case of retrograde intussusception due to transverse colon cancer detected by abdominal ultrasonography].

A 78-year-old female patient presented to our hospital with abdominal pain and melena. Abdominal ultrasonography detected a multiple concentric ring sign and retrograde invagination mass near the hepatic flexure. Colonoscopy revealed a 40-mm diameter type 1 tumor in the transverse colon near the splenic flexure, and the biopsy specimen demonstrated a well-differentiated adenocarcinoma. Retrograde intussusception due to transverse colon cancer was diagnosed, and laparoscopic transverse colon resection with lymph node dissection was performed. The resected specimen revealed a 48×40mm diameter type 1 tumor in the transverse colon and was diagnosed as pT2N0M0 pStage I. Contrast-enhanced computed tomography was unavailable, but real-time assessment of the invaginated mass and bowel blood flow was possible by abdominal ultrasonography, which was useful in determining the diagnosis and treatment strategy.

A Switchable Near-Infrared-Absorbing Dye Based on Redox-Bistable Benzitetraazaporphyrin.

Activatable near-infrared (NIR) dyes responsive to external stimuli are used in medical and other applications. Here, we describe the design and synthesis of bench-stable 18π- and 20π-electron benzitetraazaporphyrins (BzTAPs) possessing redox-switchable NIR properties. X-Ray, NMR, and UV/Visible-NIR analyses revealed that 20π-electron BzTAP 1 exhibits NIR absorption and antiaromaticity with a paratropic ring-current, while 18π-electron BzTAP 2 shows weakly aromatic character with NIR inertness. Notably, the NIR-silent BzTAP 2 was readily converted to the NIR-active BzTAP 1 in the presence of mild reducing agents such as amine. The intense NIR absorption band of BzTAP 1 is in sharp contrast to the very weak absorption bands of previously reported antiaromatic porphyrinoids. Molecular orbital analysis revealed that symmetry-lowering perturbation of the 20π-electron porphyrinoid skeleton enables the HOMO-LUMO transition of 1 to be electric-dipole-allowed. BzTAPs are expected to be useful for constructing activatable NIR probes working in reductive environments.

Relation of overall tumor burden with severe immune-related adverse events in nivolumab plus ipilimumab treatment for lung cancer.

Compared to chemotherapy alone, monoclonal antibodies like ipilimumab and nivolumab, with or without chemotherapy, improve the prognosis of patients with non-small cell lung cancer (NSCLC), albeit with a higher incidence of immune-related adverse events (irAEs) than those with immune checkpoint inhibitor (ICI) monotherapy. Therefore, we aimed to investigate if baseline overall tumor burden was associated with the development of Grade ≥ 3 irAEs (severe irAEs) when treated with first-line ipilimumab plus nivolumab with or without chemotherapy.We retrospectively examined consecutive patients with advanced NSCLC who received nivolumab plus ipilimumab with or without chemotherapy at Hakodate Goryoukaku Hospital between December 2020 and December 2021. Baseline overall tumor burden was measured as the sum of unidimensional diameters of up to five target lesions according to the Response Evaluation Criteria in Solid Tumors, version 1.1. We defined irAEs as ICI therapy-related toxicities according to the Common Terminology Criteria for Adverse Events, version 5.0.A significant difference in tumor burden was observed between patients with and without severe irAEs (100 mm vs. 67.5 mm, p = 0.001). We evaluated various clinical parameters, including baseline overall tumor burden, before treatment initiation. Of the various parameters, only high tumor burden correlated with severe irAEs, independent of complementary chemotherapy. The multivariate odds ratio of severe irAEs and high tumor burden was 6.62.Conclusively, baseline overall tumor burden may be a risk factor for severe irAEs in patients treated with first-line combination ICI therapy. Therefore, patients with large tumor burden should be carefully monitored to prevent irAEs.