A Novel Fluorescence-Based Leak Test Method for Rectal Anastomoses Using Aerosolized Indocyanine Green.

BACKGROUND: The intraoperative air leak test is commonly performed during rectal surgery to evaluate anastomotic integrity. However, its drawbacks include occasional difficulties in visualizing the exact point of the leak while maintaining the pelvis under saline, the need for repeat testing to identify the leak point, and a lack of continuous visualization of the leak point. OBJECTIVE: To evaluate the feasibility and clinical applicability of using aerosolized indocyanine green, a fluorescent tracer, for detecting rectal anastomotic leakage. DESIGN: Animal preclinical study. SETTING: Animal laboratory at Kagawa University. PATIENTS: Six healthy adult female beagles were included. INTERVENTIONS: An anastomotic leakage model with a single air leak point was created in each dog. Indocyanine green was aerosolized using a nebulizer kit with a stream of carbon dioxide flowing at 1.5 to 2.0 L/min. The aerosol was administered into the rectum transanally, and laparoscopic observations were performed. MAIN OUTCOME MEASURES: Air leak points were observed using a near-infrared fluorescence laparoscope, after which the presence of corresponding indocyanine green fluorescence was verified. RESULTS: Aerosolized indocyanine green was visualized laparoscopically at all anastomosis sites but not elsewhere. The median time from the administration of the aerosol to its visualization was 4.5 seconds. Pathological examinations were performed 4 weeks postsurgery in all dogs, and no histological abnormalities related to aerosolized indocyanine green administration were observed at the anastomosis sites. LIMITATIONS: The leak points were surgically created and did not occur naturally. CONCLUSIONS: Visualization of air leaks at the sites of rectal anastomosis was laparoscopically achievable by administering aerosolized indocyanine green transanally into the rectum in our canine model. This novel fluorescent leak test could be a valid alternative to established methods.

Hybrid Train-The-Trainer course for the Fundamental Use of Surgical Energy certificates improves self-confidence in knowledge of surgical energy and develops teaching skills: a feasibility study.

BACKGROUND: Several well-trained expert instructors who completed the "Train-The-Trainer (TTT)" course are required to disseminate the safe use of surgical energy devices, which can be learned through the Fundamental Use of Surgical Energy (FUSE) program. This study aimed to explore whether the hybrid FUSE TTT course is feasible and effective, which can improve teaching skills of surgical energy. METHODS: The hybrid TTT course, which was designed to train FUSE-certified personnel as instructors, comprised three virtual sessions spread over 5 h in total and a 1-day in-person training, followed by a 100-min FUSE electrosurgery hands-on workshop in practice as an instructor. The participants reported on self-confidence regarding knowledge of various energy devices or adverse events before, immediately after, and 6 months after the course. Participants and experienced FUSE instructors assessed the trainees' presentation skills at the beginning of the in-person training and after the hands-on workshop. The primary outcomes were the feasibility and completion rate of the entire course. RESULTS: Seventeen participants completed the entire couse; most (94%) were satisfied with the course. Self-confidence in knowledge about various contents improved significantly: the fundamentals of electrosurgery (post, p < 0.001; 6 months, p = 0.01), mechanism and prevention of adverse events (post, p = 0.001; 6 months, p = 0.04), monopolar instruments (post, p = 0.002; 6 months, p = 0.01), bipolar instruments (post, p = 0.01; 6 months, p = 0.06), and integration with other medical devices (post, p = 0.006; 6 months, p = 0.02). The presentation skill index scores of self- and peer assessments improved after the in-person training (self-assessment [pre 44 vs. post 56, p < 0.001], peer assessment [pre 39 vs. post 68, p < 0.001]). CONCLUSIONS: The hybrid TTT course can provide FUSE-certified personnel with an improved self-confidence concerning knowledge of surgical energy and improve their presentation skills with midterm retention. This can help build trainees' self-confidence as instructors.

Novel endoscopic duodenal observation protocol based on Seven Pictures Rule for detecting duodenal neoplasms during esophagogastroduodenoscopy: Prospective observational study.

OBJECTIVES: No protocol for esophagogastroduodenoscopic examination of the duodenum has been established. We examined the feasibility and ability to detect neoplasms of a novel duodenal examination protocol. METHODS: This was a two-facility, prospective, observational study. Our protocol, the Seven Pictures Rule (7PR), requires pictures of the following seven locations: anterior and posterior to the bulb, area of and contralateral to the superior duodenal angle, area of and contralateral to the ampulla, and the transverse duodenum. The primary outcome was rate of completion of 7PR. Secondary outcomes were overall rates of detecting neoplasms, rates of detecting neoplasms for each location, examination time, and completion rates for standard or ultrathin endoscopes. RESULTS: There were 1549 participants. The 7PR completion rate was 81.1% and the detection rates of overall neoplasms, adenomas, and carcinomas were 0.84%, 0.71%, and 0.06%, respectively. The area in which most neoplasms was detected was contralateral to the ampulla (69.2%), and the fewest the transverse duodenum (0%). Mean duration of duodenal examination was 53.1 s. Completion rates for standard vs. ultrathin were 84.4% (1077/1276) vs. 65.6% (179/273) (P < 0.01), respectively. CONCLUSIONS: Seven Pictures Rule is acceptable for duodenal examination and a potential quality indicator.

A quantum chemical study on the anti-SARS-CoV-2 activity of TMPRSS2 inhibitors.

Nafamostat and camostat are known to inhibit the spike protein-mediated fusion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by forming a covalent bond with the human transmembrane serine protease 2 (TMPRSS2) enzyme. Previous experiments revealed that the TMPRSS2 inhibitory activity of nafamostat surpasses that of camostat, despite their structural similarities; however, the molecular mechanism of TMPRSS2 inhibition remains elusive. Herein, we report the energy profiles of the acylation reactions of nafamostat, camostat, and a nafamostat derivative by quantum chemical calculations using a combined molecular cluster and polarizable continuum model (PCM) approach. We further discuss the physicochemical relevance of their inhibitory activity in terms of thermodynamics and kinetics. Our analysis attributes the strong inhibitory activity of nafamostat to the formation of a stable acyl intermediate and its low activation energy during acylation with TMPRSS2. The proposed approach is also promising for elucidating the molecular mechanisms of other covalent drugs.

Impact of the fundamental use of surgical energy certification on surgeons' behavior and awareness of safe use of energy devices: a cross-sectional survey research.

BACKGROUND: The Fundamental Use of Surgical Energy (FUSE) program was established to educate surgeons and trainees to promote awareness and behaviors for the safe use of surgical energy devices. Despite its implementation, the impact of FUSE certification on surgeons' behavior and safety awareness regarding practice of energy devices remains unclear. This study aimed to identify the perceived impact of FUSE certification on surgeons' behavior and awareness regarding the safe use of surgical energy devices. METHODS: We performed a descriptive cross-sectional survey study, using non probabilistic purposive sampling, and distributed 22-item web-based questionnaires among all 59 FUSE-certified surgeons in Japan, excluding operating room nurses and medical students. The questionnaire items covered demographics, surgical techniques using various energy devices, changes in behavior and safety awareness, communication with colleagues about surgical energy devices, and educational activities related to energy devices. RESULTS: Fifty-seven participants completed the questionnaire (response rate 96.6%). Most surgeons (91.3%) could apply material learned from the FUSE program in practice, especially material related to monopolar electrosurgery. Fifty-six surgeons (98.3%) reported increased awareness of surgical safety, and 35 (61.5%) reported increased communication with operating room personnel about the safe use of energy devices. Moreover, 56 participants (98.3%) indicated a need for systematic education in surgical energy, with participants recommending fellows (94.7% of participants specified that fellows should participate in further education), residents (75.4%), and attending surgeons (63.2%) as the target recipients of this training. Conclusions After FUSE certification, not only did surgeons' knowledge increase, but their energy-related surgical techniques in practice also improved. Furthermore, FUSE-certified surgeons felt that they were more aware of surgical-energy safety and were dedicated to its promotion.

Comparison of purse-string suture versus over-the-scope clip for gastric endoscopic full-thickness closure: traction and leak pressure testing in ex vivo porcine model.

BACKGROUND: The recently developed endoscopic full-thickness resection technique requires reliable closure. The main closure methods are the purse-string suture (PSS) technique and over-the-scope clip (OTSC) technique; however, basic data on the closure strength of each technique are lacking. This study was performed to compare the closure strengths of these two methods in an ex vivo porcine model. METHODS: In the traction test, a virtual 5-cm full-thickness closure line was closed by the following six methods three times each: conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture. The primary endpoint was the tension at the starting point of dehiscence, measured in Newtons (N) by an automatic traction machine. In the leak test, a 15-mm gastric full-thickness defect was closed by PSS or OTSC six times each, and the closed stomach was then pressurized in a water container. The primary endpoint was the leak pressure when air bubbles appeared. The secondary endpoints were the procedure time and presence of complete inverted closure. RESULTS: The mean tension was 2.16, 3.68, 5.15, 18.30, 19.30, and 62.40 N for conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture, respectively. Complete inverted closure was observed for seromuscular PSS, seromuscular OTSC, and surgical suture. The mean leak pressure was 13.7 and 24.8 mmHg in the PSS and OTSC group, respectively (P < 0.01). The mean procedure time was 541 and 169 s in the PSS and OTSC group, respectively (P < 0.01). Complete inverted closure was observed in OTSC alone. CONCLUSION: The OTSC, which allows complete inverted closure, showed greater closure strength than PSS. Considering the size limitation suitable for single OTSC, a therapeutic strategy for closing the larger size is further warranted.

Tumor metabolic alterations after neoadjuvant chemoradiotherapy predict postoperative recurrence in patients with pancreatic cancer.

OBJECTIVE: We investigated the metabolic changes in pancreatic ductal adenocarcinoma to identify the mechanisms of treatment response of neoadjuvant chemoradiation therapy. METHODS: Frozen tumor and non-neoplastic pancreas tissues were prospectively obtained from 88 patients with pancreatic ductal adenocarcinoma who underwent curative-intent surgery. Sixty-two patients received neoadjuvant chemoradiation therapy and 26 patients did not receive neoadjuvant therapy (control group). Comprehensive analysis of metabolites in tumor and non-neoplastic pancreatic tissue was performed by capillary electrophoresis-mass spectrometry. RESULTS: Capillary electrophoresis-mass spectrometry detected 90 metabolites for analysis among more than 500 ionic metabolites quantified. There were significant differences in 27 tumor metabolites between the neoadjuvant chemoradiation therapy and control groups. There were significant differences in eight metabolites [1-MethylnNicotinamide, Carnitine, Glucose, Glutathione (red), N-acetylglucosamine 6-phosphate, N-acetylglucosamine 1-phosphate, UMP, Phosphocholine] between good responder and poor responder for neoadjuvant chemoradiation therapy. Among these metabolites, phosphocholine, Carnitine and Glutathione were associated with recurrence-free survival only in the neoadjuvant chemoradiation therapy group. Microarray confirmed marked gene suppression of choline transporters [CTL1-4 (SLC44A1-44A4)] in pancreatic ductal adenocarcinoma tissue of neoadjuvant chemoradiation therapy group. CONCLUSION: The present study identifies several important metabolic consequences and potential neoadjuvant chemoradiation therapy targets in pancreatic ductal adenocarcinoma. Choline metabolism is one of the key pathways involved in recurrence of the patients with pancreatic ductal adenocarcinoma who received neoadjuvant chemoradiation therapy.

Outcomes of Patients with Left-Sided Obstructive Colorectal Cancer: Comparison between Self-Expandable Metallic Stent and Other Treatment Methods.

INTRODUCTION: This multi-institutional retrospective study aimed to evaluate the efficacy of preoperative self-expandable metallic stent (SEMS) placement for patients with left-sided obstructive colorectal cancer (OCRC). METHODS: Overall, 520 consecutive patients who received treatment for OCRC were enrolled. Of these, the data of 253 patients who underwent primary tumour resection for left-sided OCRC were reviewed. The short- and long-term outcomes were compared between the SEMS group and other three groups: transanal decompression tube (TaDT), decompressing stoma (DS), and emergency resection (ER). RESULTS: The SEMS group had a higher frequency of laparoscopic surgery (p < 0.001), lesser frequency of postoperative stoma (p < 0.001), and more dissected lymph nodes (p < 0.001) than the other groups. Moreover, the SEMS group had shorter postoperative hospital stays than the TaDT, DS, and ER groups (p = 0.005, p = 0.037, and p < 0.001, respectively). The Kaplan-Meier survival curves of recurrence-free survival and overall survival did not differ significantly between the SEMS group and the other three groups in patients with stage II and III diseases. DISCUSSION/CONCLUSION: Elective surgery after SEMS placement may improve short-term outcomes compared to other treatment strategies, with similar long-term outcomes.

Indocyanine green fluorescence imaging during laparoscopic rectal cancer surgery could reduce the incidence of anastomotic leakage: a single institutional retrospective cohort study.

BACKGROUND: There is insufficient evidence on whether indocyanine green (ICG) fluorescence angiography can reduce the incidence of anastomotic leakage (AL). This retrospective cohort study aimed to evaluate the effect of ICG fluorescence angiography on AL rates in laparoscopic rectal cancer surgery at a single institution. METHODS: Patients who underwent laparoscopic low anterior resection or intersphincteric resection with ICG fluorescence angiography (ICG group; n = 73) and patients who underwent a similar surgical procedure for rectal cancer without ICG fluorescence (non-ICG group; n = 114) were enrolled consecutively in this study. ICG fluorescence angiography was performed prior to transection of the proximal colon, and anastomosis was performed with sufficient perfusion using ICG fluorescence imaging. AL incidence was compared between both groups, and the risk factors for AL were analyzed. RESULTS: AL occurred in 3 (4.1%) and 14 (12.3%) patients in the ICG and non-ICG groups, respectively. In the ICG group, the median perfusion time from ICG injection was 34 s, and 5 patients (6.8%) required revision of the proximal transection line. None of the patients requiring revision of the proximal transection line developed AL. In univariate analysis, longer operating time (odds ratio: 2.758; 95% confidence interval: 1.023-7.624) and no implementation of ICG fluorescence angiography (odds ratio: 3.266; 95% confidence interval: 1.038-11.793) were significant factors associated with AL incidence, although the creation of a diverting stoma or insertion of a transanal tube was insignificant. CONCLUSION: ICG fluorescence angiography was associated with a significant reduction in AL during laparoscopic rectal cancer surgery. Changes in the surgical plan due to ICG fluorescence visibility may help improve the short-term outcomes of patients with rectal cancer.

Potential benefit of laparoscopic surgery for rectal cancer on postoperative male sexual function.

AIM: The aim of this retrospective study was to evaluate the incidence of male sexual dysfunction after mid to low rectal cancer surgery and to identify factors associated with postoperative erectile and ejaculatory dysfunction. METHODS: The subjects were 410 consecutive male patients who underwent surgery for mid to low rectal cancer from 2009 to 2015. Two questionnaires on sexual function were administered: the International Index of Erectile Function, and an original questionnaire on ejaculatory status. Erectile and ejaculatory dysfunction were examined before and 3, 6, 12 months after surgery. In patients without preoperative dysfunction, multivariate regression analyses were performed to identify factors associated with the incidence of erectile and ejaculatory dysfunction at 12 months after surgery. RESULTS: Of 410 patients, 234 (57%) gave complete responses to the questionnaires, of whom 108 (46%) and 155 (66%) had severe erectile dysfunction, while 115 (49%) and 168 (72%) had severe ejaculatory dysfunction before and 12 months after surgery, respectively. Of the patients who maintained sexual function preoperatively, the incidence of erectile and ejaculatory dysfunction at 12 months after surgery was 51% (64/126) and 49% (58/119), respectively. In multivariate analysis, age >60 years (P = 0.02), laparotomy (P = 0.002), and creation of a diverting ileostomy (P = 0.003) were independent factors associated with postoperative erectile dysfunction, while age >60 years (P = 0.005), laparotomy (P = 0.04), and lateral lymph node dissection (P = 0.001) were independent factors associated with postoperative ejaculatory dysfunction. CONCLUSION: Sexual dysfunction occurred in almost half of patients after rectal cancer surgery, and was independently associated with several factors, including laparotomy.

Early gastric cancer with an Adachi type VI (group 26) vascular anomaly diagnosed preoperatively and treated by laparoscopic surgery: a case report.

BACKGROUND: It is important to understand the branching pattern of the celiac artery for a safe surgery. Various branching anomalies of the celiac artery were classified by Adachi in 1928. In Adachi's classification, type VI (group 26) is a rare anatomical anomaly (0.4%) that requires care when carrying out a surgery in gastric cancer patients with this anomaly. Herein, we reported a case treated successfully with laparoscopic distal gastrectomy with D1+ lymph node dissection for early gastric cancer. CASE PRESENTATION: An 84-year-old female was referred to our division for an additional surgical treatment for early gastric cancer that was resected by endoscopic submucosal dissection. A three-dimensional computed tomography angiography revealed an angioplany of the common hepatic artery branching from the left gastric artery. According to Adachi's classification, the anomaly of this patient corresponded to type VI (group 26). Preoperative anatomical information of this rare anomaly helped us to safely perform a laparoscopic distal gastrectomy and lymph node dissection with common hepatic artery preservation. The patient had an uneventful postoperative course and was discharged on postoperative day 11. CONCLUSIONS: We consider that Group 26 anomalies require the most precise anatomical understanding among Adachi classification type VIs, since it affects hepatic blood flow and can cause serious complications. In this time, we reported a successful case to perform laparoscopic distal gastrectomy with safety and accuracy by preoperative understanding of the precise vascular anatomy.

Distribution of class IId bacteriocin-producing Virgibacillus salexigens in various environments.

We performed several experiments using three strains of Virgibacillus salexigens, namely, P2, NT N53, and C-20MoT (DSM 11483T), which were isolated from completely different sources, in relation to bacteriocin production ability. Results of whole-genome sequencing analysis revealed that all strains have very similar sequences encoding class IId bacteriocin. Although a partial amino acid sequence of the purified bacteriocin produced by strain P2 isolated from fermented food was previously reported, whole-genome sequencing and the N-terminal sequencing results in this study showed that its complete amino acid sequence consisted of 48 residues, which corresponded to that of the hypothetical bacteriocin encoded by the gene in Virgibacillus massiliensis strain Vm-5T (DSM 28587T) isolated from the human gut. From the results of 16S rRNA gene sequencing and whole-genome sequencing analyses, we taxonomically confirmed Vm-5T to be a strain of V. salexigens, and its broth culture showed antibacterial activity. Strain NT N53 isolated from the deep-sea floor produced two bacteriocins, namely, NTN-A and NTN-B. The results of N-terminal sequencing, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and whole-genome sequencing analyses showed that their amino acid sequences differed in only one residue, and NTN-A showed the same sequence as the bacteriocin produced by strain P2. Although strain C-20MoT isolated from a solar saltern had the coding sequence very similar to that of NTN-A, its broth culture showed no antibacterial activity. This finding suggests that class IId bacteriocin-producing or bacteriocin-gene-encoding V. salexigens strains are widely distributed in distinct environment sources with different geographical and material properties.

Diagnostic Value of Flow Cytometry Standardized Using the European LeukemiaNet for Myelodysplastic Syndrome.

BACKGROUND: Myelodysplastic syndromes (MDS) and idiopathic cytopenia of undetermined significance (ICUS) are heterogeneous hematological disorders characterized by hematopoietic dysplasia and/or chromosomal aberrancy. OBJECTIVES: This study aimed to evaluate the diagnostic value of flow cytometry standardized using the European LeukemiaNet (ELN) for MDS and ICUS by analyzing samples obtained from patients with cytopenia based on morphological examination, cytogenetic analysis, and flow cytometry. METHODS: We retrospectively analyzed bone marrow samples aspirated from 253 consecutive patients (median age: 66 years [range: 1-92]) to identify the cause of cytopenia. RESULTS: Sixty patients presented with MDS, and 16 with ICUS. MDS subtypes were distributed as follows: MDS with single-lineage dysplasia (n = 10); MDS with multi-lineage dysplasia (n = 10); MDS with ringed sideroblasts (n = 4); MDS with excess blasts-1 (n = 9); MDS with excess blasts-2 (n = 13), MDS unclassified (n = 5); 5q-syndrome (n = 6); and MDS/myeloproliferative neoplasms (n = 3). Four representative ELN indexes were used. Two or more ELN MDS indexes were in the abnormal range in 35 MDS cases (58.3%) and 4 ICUS cases (25.0%). CONCLUSIONS: Morphological examination remains the standard for MDS diagnosis. Considering the low incidence of genetically proven ICUS (20.2-27.5%), the low sensitivity of ELN MDS indexes for ICUS is considered a valuable alternative.

Association of IgG4-Related Arteritis With Recurrent Stroke.

Immunoglobulin G4-related disease (IgG4)-related disease is a newly recognized form of immune-mediated disease, which is characterized by IgG4+ lymphoplasmacytic infiltration and fibrosis in the systemic organs. Although aortitis/periaortitis is a phenotype of IgG4-related disease, the relationship between cerebrovascular disease and IgG4-related disease remains unclear. Herein, we report the case of a 49-year-old man with recurrent stroke induced by IgG4-related arteritis. Case reports or studies examining the association between IgG4-related arteritis and stroke are limited. Although a definitive link between IgG4-related arteritis and stroke has not been established, IgG4-related arteritis should be considered as an etiology in patients with recurrent idiopathic stroke.

A novel device designed to improve the operability of energy devices with foot pedals in endoscopic surgery: the Foot-Site Monitor.

PURPOSE: We developed the "Foot-Site Monitor" (FSM) to permit easy identification of multiple foot pedals of energy devices in endoscopic surgery. The purpose of this study was to evaluate the effectiveness of the use of the FSM. METHODS: Using a training box, 20 surgeons performed a task consisting of pressing foot pedals with and without the FSM. The time from showing a color on a PC monitor to pressing the foot pedal that corresponded to this color (defined as the completion time), and the distance of the movement of the tip of the surgeon's forceps from the beginning to the end of the task (defined as shaking of the forceps) were measured. RESULTS: The use of the FSM was associated with significantly reduced shaking of the forceps (1.95 vs. 2.47 mm; p = 0.014), and a tendency toward a shorter completion time (1.39 vs. 1.51 s; p = 0.053). CONCLUSIONS: The use of the FSM in endoscopic surgery contributes to reduced shaking of the forceps and may shorten the operative time.

Resection of the urinary bladder for locally advanced colorectal cancer: a retrospective comparison of partial versus total cystectomy.

BACKGROUND: The postoperative and survival outcomes of patients with primary advanced colorectal cancer who undergo partial versus total cystectomy have not been adequately compared, as studies of this topic are rare and comprise relatively small cohorts. This study aimed to investigate the short- and long-term outcomes of patients who underwent en bloc partial or total cystectomy for primary advanced colorectal cancer that was suspected of adhering to or invading the urinary bladder. METHODS: The study included 90 patients who underwent various degrees of cystectomy between 1993 and 2013 to treat locally advanced primary colorectal cancer that was suspected of involving the urinary bladder. Patients in whom total cystectomy was performed solely because of prostate-invading lower rectal cancer were excluded. Data on patient characteristics and their short- and long-term outcomes were collected retrospectively to evaluate differences between partial cystectomy (the P group; n = 72) and total cystectomy (the T group; n = 18). Postoperative and oncologic outcomes were also analyzed. RESULTS: The T group had significantly greater operating times than the P group (median, 572 vs. 346 min); blood loss volume was also greater in the T group (median, 3092 vs. 1112 mL). The postoperative overall complication rate was significantly greater in the T group than in the P group (94.4% vs. 51.4%). With a median follow-up duration of 62 months, local recurrences were observed in 22.2 and 6.9% of patients in the T and P groups, respectively. On multivariate Cox regression analyses using partial cystectomy as the reference, total cystectomy was independently associated with poorer local recurrence-free survival (hazard ratio [HR], 4.0 95% confidence interval [CI], 1.1-15.0), relapse-free survival (HR, 2.9; 95% CI, 1.2-6.9), and overall survival (HR, 2.1; 95% CI, 1.0-4.3). CONCLUSIONS: Patients who undergo en bloc total cystectomy for locally advanced colorectal cancers have worse postoperative and oncologic outcomes than those who undergo partial cystectomy.

A curvature-dependent membrane binding by tyrosine kinase Fer involves an intrinsically disordered region.

Tyrosine kinases are important enzymes that mediate signal transduction at the plasma membrane. While the significance of membrane localization of tyrosine kinases has been well evaluated, the role of membrane curvature in their regulation is unknown. Here, we demonstrate that an intrinsically disordered region in the tyrosine kinase Fer acts as a membrane curvature sensor that preferentially binds to highly curved membranes in vitro. This region forms an amphipathic α-helix upon interaction with curved membranes, aligning hydrophobic residues on one side of the helical structure. Further, the tyrosine kinase activity of Fer is significantly enhanced by the membrane in a manner dependent on curvature. We propose a model for the regulation of Fer based on an intramolecular interaction and the curvature-dependent membrane binding mediated by its intrinsically disordered region.

Magnetic-Field-Induced Kondo Metal Realized in YbB_{12}.

The specific heat of the Kondo insulator YbB_{12} has been measured up to 60 T. The Sommerfeld coefficient γ significantly increases at around 50 T, where the insulator metal transition occurs with a steep increase of the magnetization. γ reaches 67 mJ/(mol K^{2}) at high fields, which directly indicates that the quasiparticles gain a heavy thermodynamic effective mass and transform into a Kondo metal under magnetic fields. The field-induced Kondo metal has a rather high Kondo temperature around 200 K. The strong Kondo coupling proves that the energy gap collapse does not correspond to the breakdown of the Kondo bound state. The steep increase of the magnetization at the transition manifests the sharp density of states at the Fermi energy formed via the Kondo resonance.