Visualizing electrostatic gating effects in two-dimensional heterostructures.

The ability to directly monitor the states of electrons in modern field-effect devices-for example, imaging local changes in the electrical potential, Fermi level and band structure as a gate voltage is applied-could transform our understanding of the physics and function of a device. Here we show that micrometre-scale, angle-resolved photoemission spectroscopy1-3 (microARPES) applied to two-dimensional van der Waals heterostructures4 affords this ability. In two-terminal graphene devices, we observe a shift of the Fermi level across the Dirac point, with no detectable change in the dispersion, as a gate voltage is applied. In two-dimensional semiconductor devices, we see the conduction-band edge appear as electrons accumulate, thereby firmly establishing the energy and momentum of the edge. In the case of monolayer tungsten diselenide, we observe that the bandgap is renormalized downwards by several hundreds of millielectronvolts-approaching the exciton energy-as the electrostatic doping increases. Both optical spectroscopy and microARPES can be carried out on a single device, allowing definitive studies of the relationship between gate-controlled electronic and optical properties. The technique provides a powerful way to study not only fundamental semiconductor physics, but also intriguing phenomena such as topological transitions5 and many-body spectral reconstructions under electrical control.

Quality of Life in Patients Undergoing Emergency Surgery for Complex Colorectal Cancer: Protocol and Piloting of the Surgical Utilization and Recovery Patterns for Advanced Stage Colorectal Cancer Study.

Introduction: Globally, cancer is the leading cause of mortality, with colorectal neoplasia ranking third in terms of incidence and mortality worldwide. Patients face disease- and treatment-specific impacts, which can significantly influence their quality of life (QoL). Aim: This study aimed to propose a protocol to measure in-hospital and long-term QoL in patients with complicated colorectal cancer (CRC). Material and Methods: multicenter prospective observational cohort study. Results: QoL is a multidimensional concept that includes criteria for physical, mental, emotional, and social functionality as perceived by the patient. Periodically evaluating QoL offers measurable and objective tools to intervene at the appropriate time to decrease the Years of Life Lost and Years Lived with Disabilities for CRC patients. However, a structured and functional system requires dedicated and common institutional effort. A pilot study using this protocol included 69 patients, 65.12+-10.92 years, M:F ratio = 56.5:43.5%. Surgical procedure was right hemicolectomy, left colectomy, transverse colectomy, sigmoidectomy, total colectomy, rectal resection, and colorectal resection with stoma (ileostomy or colostomy) in 21.7%, 11.6%, 2.9%, 11.6%, 1.4%, 23.2%, and 27.5% of the cases, respectively. The mean Global Health Status Score, Symptom Score, and Functional Score was 82.36+-18.60, 11.89+-10.27, and 86.27, 74.50-94.11, respectively. Conclusions: CRC diagnosis has major effects on patients physical and psychological status, and concentrated efforts should be made by the involved medical team and healthcare systems to improve QoL throughout the treatment pathway.

Surgery for Inflammatory Bowel Disease in the Era of Biologic Therapy: A Multicenter Experience from Romania.

Background and Objectives: Biologic therapy has fundamentally changed the opportunity of medical treatment to induce and maintain remission in inflammatory bowel disease (IBD). Nevertheless, the rate of surgery is still at a very high rate, profoundly affecting the quality of life. We aimed to analyze surgical cases at three major IBD units in order to identify the main risk factors and the impact of biologic therapy on pre- and postsurgical outcomes. Material and Methods: This was a multicenter retrospective cohort study that included 56 patients with IBD-related surgical interventions from 3 tertiary care hospitals in Bucharest, Romania. The study was conducted between January 2017 and June 2021. All data were retrospectively collected from the medical records of the patients and included the age at diagnosis, age at the time of surgery, IBD type and phenotype, biologic therapy before or/and after surgery, timing of biologic therapy initiation, extraintestinal manifestations, type of surgery (elective/emergency), early and long-term postoperative complications and a history of smoking. Results: A low rate of surgical interventions was noted in our cohort (10.3%), but half of these occurred in the first year after the IBD diagnosis. A total of 48% of the surgical interventions had been performed in an emergency setting, which seemed to be associated with a high rate of long-term postoperative complications. We found no statistically significant differences between IBD patients undergoing treatments with biologics before surgery and patients who did not receive biologics before the surgical intervention in terms of the IBD phenotype, type of surgery and postoperative complications. Conclusion: Our study showed that biologics initiated before the surgical intervention did not influence the postoperative complications. Moreover, we demonstrated that patients with Crohn's disease and no biologics were the most susceptible to having to undergo surgery. Conclusion: In conclusion, the management of patients with IBD requires a multidisciplinary approach that considers an unpredictable evolution.

Molecular profile of the NF-κB signalling pathway in human colorectal cancer.

The development and progression of colorectal cancer (CRC) have been associated with inflammation processes that involve the overactivation of the NF-κB signalling pathway. The characterization of the NF-κB expression profile in CRC is an important topic since the suppression of NF-κB represents a potential therapeutic approach. In this study, we assessed the expression levels of 84 NF-κB-related genes in paired tumoral (T) and peritumoral (PT) tissues from 18 CRC patients and 18 normal colonic mucosae, and the expression levels of three miRNAs targeting the most dysregulated genes revealed by the case-control analysis. Comparing the gene expression profile of T and controls, 60 genes were dysregulated. The comparison of T and PT revealed 17 dysregulated genes in the tumoral tissues, with IL1B, CXCL8, IL1A, and CSF2 being the most upregulated. Notably, through a bioinformatics analysis, the differential gene expression of 11 out of the 17 genes was validated on a larger cohort of 308 CRC patients compared with 41 controls. Moreover, a decrease in the levels of RELA, NOD1, CASP8, BCL2L1, ELK1, and IKBKB was identified in poorly differentiated tumours compared to moderately differentiated tumours. The analysis of the three miRNAs targeting IL1B, CXCL8, IL1A, and CSF2 showed that miR-182-5p was upregulated in T compared with PT, whereas miR-10b-5p was downregulated in T compared with PT and control tissues. Our results may contribute to the design of new experimental therapeutic strategies based on endogenous molecules, such as miRNAs, to target the genetic key players of the NF- κB pathway.

Impact of biliary stenting in endoscopic ultrasound-guided tissue acquisition among patients with pancreatic cancer.

INTRODUCTION: Pancreatic malignancies represent highly fatal diseases with poor prognosis and constantly increasing incidence despite modern diagnostic and therapeutic options. Both endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) are regarded as mainstays in pancreatic cancer management. The present study aims to evaluate whether accuracy EUS with fine-needle aspiration or biopsy (FNA or FNB) in pancreatic cancer diagnosis is influenced by prior biliary stenting or by technical or anatomical features (stent type, number of needle passes, common bile duct or Wirsung's diameter, topographical characteristics and diameter of the pancreatic tumor). MATERIALS AND METHODS: This retrospective study includes 243 patients with pancreatic cancer who underwent ERCP and EUS with fine-needle aspiration or biopsy (FNA or FNB). RESULTS AND DISCUSSION: Out of the total number of patients, 68 were stented prior to EUS. We found that the EUS-FNA diagnostic yield is not influenced either by the presence of biliary stent, nor by the type of stent (plastic or metallic). Moreover, the mean needle passes required were similar for both stented patients and not stented ones. CONCLUSIONS: Ultimately, given our results, we can state that EUS-FNA/FNB can be safely and accurately performed in the presence of biliary stents.

Endoscopic Retrograde Cholangiopancreatography in Acute Biliary Pancreatitis: Urgent vs. Delayed and the Outcome of Same-Admission Cholecystectomy.

Introduction: Acute pancreatitis (AP) represents a major burden for the medical system, associating important morbidity and mortality rates. This paper is focused on debatable aspects of the management of biliary AP, namely indications, timing and outcomes of endoscopic retrograde cholangiopancreatography (ERCP) on the hand and, on the other hand, same-admission cholecystectomy as a preventive measure for recurrent disease. Material and methods: This is a retrospective study including 108 patients with biliary AP in whom ERCP was performed, treated in the Clinical Emergency Hospital of Bucharest between 2016 and 2020. According to the urgency of the ERCP, we divided the patients into two groups: urgent versus delayed ERCP. Results: Urgent ERCP was performed in 52 patients, while delayed ERCP was performed in 56 patients; the hospital stay was higher in the urgent group than in the delayed group (10 days vs 8 days, p = 0.299) with no difference in morbidity rates. The mean time between ERCP and surgery was 5 days, without significant difference between the groups. The laparoscopic approach was the preferred method, with a conversion rate of 7%. Conclusion: ERCP with stone extraction followed by same-admission laparoscopic cholecystectomy is a safe therapeutic option, that prevents recurrent pancreatitis. The timing of the procedures remains debatable, further prospective studies being needed to achieve statistical significance.

The ONETEP linear-scaling density functional theory program.

We present an overview of the onetep program for linear-scaling density functional theory (DFT) calculations with large basis set (plane-wave) accuracy on parallel computers. The DFT energy is computed from the density matrix, which is constructed from spatially localized orbitals we call Non-orthogonal Generalized Wannier Functions (NGWFs), expressed in terms of periodic sinc (psinc) functions. During the calculation, both the density matrix and the NGWFs are optimized with localization constraints. By taking advantage of localization, onetep is able to perform calculations including thousands of atoms with computational effort, which scales linearly with the number or atoms. The code has a large and diverse range of capabilities, explored in this paper, including different boundary conditions, various exchange-correlation functionals (with and without exact exchange), finite electronic temperature methods for metallic systems, methods for strongly correlated systems, molecular dynamics, vibrational calculations, time-dependent DFT, electronic transport, core loss spectroscopy, implicit solvation, quantum mechanical (QM)/molecular mechanical and QM-in-QM embedding, density of states calculations, distributed multipole analysis, and methods for partitioning charges and interactions between fragments. Calculations with onetep provide unique insights into large and complex systems that require an accurate atomic-level description, ranging from biomolecular to chemical, to materials, and to physical problems, as we show with a small selection of illustrative examples. onetep has always aimed to be at the cutting edge of method and software developments, and it serves as a platform for developing new methods of electronic structure simulation. We therefore conclude by describing some of the challenges and directions for its future developments and applications.

Duodenoscope-Associated Infections beyond the Elevator Channel: Alternative Causes for Difficult Reprocessing.

OBJECTIVES: Duodenoscopes have been widely used for both diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) procedures, but recently, numerous outbreaks of multidrug-resistant organisms (MDRO) infections have been reported which has led to extensive research for their possible causes. Consequently, the aim of this study is to search for possible duodenoscope surface damages that could provide an alternative and plausible source of infections. MATERIALS AND METHODS: In order to assess both outer and inner surfaces, a duodenoscope was dismantled and samples were taken from the outer resin polymer and from the air/water, elevator, and working (biopsy) channels that were characterized by FTIR, DSC, TGA, AFM, SEM techniques and the antimicrobial activity were tested. RESULTS: Alterations were noticed on both the coating and working channel polymers, with external alterations increasing progressively from the proximal sample to the distal sample near the tip of the scope. However, the results showed that the coating surface was still efficient against bacterial adhesion. Changes in surface texture and also morphological changes were shown. CONCLUSIONS: The study describes the impact of routine procedural use and reprocessing cycles on the duodenoscope, showing that these may possibly make it susceptible to bacterial contamination and MDRO biofilm formation due to difficult reprocessing of the altered surfaces.

Geographic Distribution, Phenotype and Epidemiological Tendency in Inflammatory Bowel Disease Patients in Romania.

Background and objective: The incidence of inflammatory bowel disease (IBD) over the past years in Romania has been on the rise, but epidemiologic data are lacking. The aim of this study was to define the characteristics of IBD, the trends and phenotype among IBD patients in Romania. Material and methods: We conducted a prospective study over a period of 12 years, from 2006 to 2017. All patients diagnosed with IBD on clinical, radiological, endoscopic and histological features were included. We divided the country into eight regions: west (W), north-east (NE), north-west (NW), south-east (SE), south-west (SW), south (S), central (C) and Bucharest-Ilfov (B), and data were analyzed accordingly. Results: A total of 2724 patients were included in this database, but only 2248 were included in the final analysis, with all data available. Of the 2248 patients, 935 were Crohn's disease (CD), 1263 were ulcerative colitis (UC) and 50 were IBD-undetermined. In UC phenotypes we observed more frequent left-sided colitis (50.5%, p < 0.0001), and in CD phenotype we observed more frequent colonic and ileo-colonic localization (37.8% and 37.6%, p < 0.0001). The region with the most IBD cases was NE (25.1%) and with the least IBD cases was SW (4.9%). UC was found more frequently in NE (32%), while CD was found more frequently in Bucharest (28.6%). Conclusions: In Romania, ulcerative colitis is more frequent than CD. UC is predominant in the northern part of Romania, while CD has become predominant in the southern part of the country. IBD occurs more in the male population, and in urban and industrialized areas. There are differences between the regions in Romania regarding IBD phenotypes, gender distributions, age distribution, treatment, smoking status and complications.

EUS-Guided Transgastric Drainage of Intraabdominal Fluid Collections.

Intraabdominal fluid collections can be a significant cause of morbi-mortality among patients with acute pancreatitis and those who underwent surgery, especially oncological ones. Nowadays, the treatment tends to be minimally invasive, so that the patient's recovery would be shorter and the quality of life higher. EUS (endoscopic ultrasound) has emerged in the last decade to fulfill that demand, alongside percutaneous and surgical drainage in the management of perigastric collections. Objectives: The main objective of this paper is to evaluate the efficacy of EUS guided drainage in terms of techincal and clinical success. Secondary objectives refer to the assessment of complete resolution of intraabdominal collection, presence of infection after drainage, overall survival. Methods: We conducted a prospective study by enrolling 31 patients who were diagnosed using EUS with perigastric intraabdominal fluid collections, from an overall of 788 EUS performed over a period of 2 years. We analyzed their evolution during 6 months after treatment, by regular examinations (ultrasound/endoscopic/computed tomography). All of them were in-patients of Bucharest Clinical Emergency Hospital, either in Endoscopy or in Surgery Departments. Data collected was processed in IBM SPSS Statistics 20. Results: Overall mean age was 51 year and intraabdominal collections average was 109 mm (range 34 250 mm) and was correlated with the method of treatment (p 0.005). Patients underwent different methods for their intraabdominal collections: EUS drainage, CT (computed-tomography)- guided percutaneous drainage, surgical intervention, alone or combined when needed. Overall mortality was 9,3% and was mainly related to the severity of the case and sepsis. Conclusions: We conclude that endoscopic ultrasound can be the first choice for drainage of intraabdominal perigastric fluid collections because it is a safe and effective technique with 100 % technical success, and with over 80 % clinical success assures a better quality of life. For collections with a diameter larger than 127 mm, we can expect however the need of combined treatment, EUS and surgery.

Endoscopic Treatment of Benign Esophageal Fistulas Using Fully-covered Metallic Esophageal Stents.

Non-malignant esophageal fistulas have a wide spectrum of clinical and pathological features and it`s important to learn to detect and treat them, due to significant morbidity, mortality and costs. The need for minimally invasive, efficient and also quick procedures is imperative. Esophageal stenting using fully-covered expandable stents has become an increasingly preferred option and addresses to fistulas which arise from 2-3 cm beyond Killian's mouth and up to the gastroesophageal junction. The long-term purpose of the procedure is closure of the fistula and thus healing. A second goal would be avoiding the complications generated by long-term wearing of the stent, such as gastrointestinal perforation and stenosis. OBJECTIVES: This review focuses on the efficacy of fully-covered metallic stents in treating benign esophageal fistulas. To this effect, we performed a retrospective study on 21 patients admitted in our clinic between January 2014 and April 2017 for non-malignant esophageal fistulas. The selection criteria were the following: post-operative fistulas (gastric sleeve, fundoplication for transhiatal gastric hernia, even malignancies for which surgical tumor removal was performed), foreign body acquired fistulas, post-traumatic fistulas. Esophago-jejunal anastomotic fistulas were also included in the study (following complete gastrectomy). Results: The efficacy of esophageal stenting was proven in 76% of the cases, resulting in fistula closure. The rest of the patients either didn't achieve fistula closure or couldn't tolerate the stent, calling for early removal of the prosthesis. Reintervention procedures such as stent repositioning or stent replacement (with higher diameter) were carried out in 42% of the cases. A percentage of 19% of the patients who achieved fistula closure developed esophageal stricture on stent-induced ulcers and needed recalibration stenting or esophageal Savary dilation. 22% of the cases needed surgical drainage for infected collections developed simultaneously. We recorded 2 deaths, unrelated to the stenting procedure. Patients who didn't acquire fistula closure were referred to thoracic surgery in good physical condition. Conclusions: Fully-covered metallic esophageal stents can be successfully used to treat benign esophageal fistulas. Follow-up of the patient in order to see if stent repositioning or replacement is needed is crucial. Special design esophageal stents are highly recommended and must not lack. Close cooperation with thoracic surgery is indispensable.

Multipurpose Black-Phosphorus/hBN Heterostructures.

Black phosphorus (BP) has recently emerged as a promising semiconducting two-dimensional material. However, its viability is threatened by its instability in ambient conditions and by the significant decrease of its band gap in multilayers. We show that one could solve all the aforementioned problems by interfacing BP with hexagonal boron nitride (hBN). To this end, we simulate large, rotated hBN/BP interfaces using linear-scaling density functional theory. We predict that hBN-encapsulation preserves the main electronic properties of the BP monolayer, while hBN spacers can be used to counteract the band gap reduction in stacked BP. Finally, we propose a model for a tunneling field effect transistor (TFET) based on hBN-spaced BP bilayers. Such BP TFETs would sustain both low-power and fast-switching operations, including negative differential resistance behavior with peak-to-valley ratios of the same order of magnitude as those encountered in transition metal dichalcogenide TFETs.

Auspicious Management of a Acute Obstructive Left Colon Tumor in a 93-year-old Patient - Case Report and Literature Review.

We present the case of a 93-year-old patient with intestinal occlusion due to a descending colon tumor, with carcinomatous ascites and secondary liver and lung determinations. Considering the risks associated with a surgical act in such a patient and the impossibility of performing a curative intervention, a self-expanding metallic colonic stent was mounted. The post-intervention evolution was favorable, the patient being discharged 48 hours later. Left colon cancer is diagnosed in the occlusive phase in 8 to 26% of cases (1). It often requires an immediate surgical resolution due to the potential risk of death. Emergency surgery involves increased rates of morbidity and mortality (2). Thus, other ways of resolving these surgical emergencies have been developed. Colonic stents were first reported in the literature by Dohmoto (3). Initially, the use of stents was as the final method of palletising (4). Later, they were used as a bridge to minimally invasive programmed surgery (5).

Retained Common Bile Duct Lithiasis at a Pacient with Periampullary Duodenal Diverticulum.

Periampullary duodenal diverticula are associated with the presence of common bile duct stones, being encountered more frequently with the increase of age. We present the case of a 76 years old female patient, who underwents emergency surgery for a perforated lithiasic gangrenous acute cholecystitis and for whom we perform a cholecystectomy and an external biliary drainage using a transcystic tube. Both preoperative and postoperative imaging and endoscopic examinations certify the presence of a periampullary duodenal diverticulum. Postoperative cholangiography performed on the transcystic tube raises the suspicion of retained common bile duct lithiasis. An endoscopic retrograde cholangiopancreatography is performed, initially failing to cannulate the common bile duct. A precut sphincterotomy fistula technnique is performed, using as reference a guide inserted on the transcystic tube, with the extraction of biliay sludge from the common bile duct, and with subsequently favorable development. Association between common bile duct lithiasis and a periampullary duodenal diverticulum may represent a therapeutic challenge because of the increased risk of failure of the endoscopic treatment.

Updates in Diagnosis and Endoscopic Management of Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an adenocarcinoma originating from the epithelial cells of the bile ducts/hepatocytes or peribiliary glands. There are three types of cholangiocarcinoma: intrahepatic, perihilar and distal. CCA represents approximately 3% of the gastrointestinal malignancies. The incidence of CCA is higher in regions of the Eastern world compared to the Western countries. There are multiple risk factors associated with cholangiocarcinoma such as liver fluke, primary sclerosing cholangitis, chronic hepatitis B, liver cirrhosis and non-alcoholic fatty liver disease. Endoscopy plays an important role in the diagnosis and management of cholangiocarcinoma. The main endoscopic methods used for diagnosis, biliary drainage and delivering intrabiliary local therapies are endoscopic retrograde cholangiopancreatography and endoscopic ultrasound. The purpose of this review is to analyze the current data found in literature about cholangiocarcinoma, with a focus on the actual diagnostic tools and endoscopic management options.

Considering Histologic Remission in Ulcerative Colitis as a Long-Term Target.

Monitoring disease activity in inflammatory bowel disease (IBD) is challenging since clinical manifestations do not represent reliable surrogates for an accurate reflection of the inflammatory burden. Endoscopic remission had been the most significant endpoint target in the last years; nevertheless, a remarkable proportion of patients continue to relapse despite a normal-appearing mucosa, highlighting that endoscopy may underestimate the true extent of the disease. A subtle hint of the importance that histology plays in the long-term course of the disease has been endorsed by the STRIDE-II consensus, which recommends considering histologic healing for ulcerative colitis (UC), even though it is not stated to be a compulsory formal target. It is a continuum-changing paradigm, and it is almost a certainty that in the near future, histologic healing may become the new formal target for ulcerative colitis. It must be emphasized that there is great heterogeneity in defining histological remission, and the main criteria or cut-off values for inflammatory markers are still in an ill-defined area. The complexity of some histologic scores is a source of confusion among clinicians and pathologists, leading to low adherence in clinical practice when it comes to a homogenous histopathological report. Therefore, a standardized and more practical approach is urgently needed.

Composite MAX phase/MXene/Ni electrodes with a porous 3D structure for hydrogen evolution and energy storage application.

MXenes, a family of two-dimensional (2D) transition metal carbides, have been discovered as exciting candidates for various energy storage and conversion applications, including green hydrogen production by water splitting. Today, these materials mostly remain interesting objects for in-depth fundamental studies and scientific curiosity due to issues related to their preparation and environmental stability, limiting potential industrial applications. This work proposes a simple and inexpensive concept of composite electrodes composed of molybdenum- and titanium-containing MAX phases and MXene as functional materials. The concept is based on the modification of the initial MAX phase by the addition of metallic Ni, tuning Al- and carbon content and synthesis conditions, followed by fluoride-free etching under alkaline conditions. The proposed methodology allows producing a composite electrode with a well-developed 3D porous MAX phase-based structure acting as a support for electrocatalytic species, including MXene, and possessing good mechanical integrity. Electrochemical tests have shown a high electrochemical activity of such electrodes towards the hydrogen evolution reaction (HER), combined with a relatively high areal capacitance (up to 10 F cm-2).

Stacking in bulk and bilayer hexagonal boron nitride.

The stacking orders in layered hexagonal boron nitride bulk and bilayers are studied using high-level ab initio theory [local second-order Møller-Plesset perturbation theory (LMP2)]. Our results show that both electrostatic and London dispersion interactions are responsible for interlayer distance and stacking order, with AA' being the most stable one. The minimum energy sliding path includes only the AA' high-symmetry stacking, and the energy barrier is 3.4 meV per atom for the bilayer. State-of-the-art density functionals with and without London dispersion correction fail to correctly describe the interlayer energies with the exception of a Perdew-Burke-Ernzerhof functional intended for solid state and surface systems that agrees very well with our LMP2 results and experiment.

Recombinant Tissue Plasminogen Activator: The New Concept for Dissolving Septae in Loculated Peri-pancreatic Fluid Collection prior to Endoscopic Drainage. A Case Report.

Peri-pancreatic fluid collections are late complications of acute pancreatitis. Loculated peri-pancreatic fluid collections, even rare, remain the "black sheep" in terms of drainage, due to difficulty to puncture all compartments, thus prohibiting proper drainage of all compartments. Recombined tissue plasminogen activator (r-tPA) has been advocated as treatment of the loculated collections, due to its ability to dissolve the fibrinous strands and thus facilitate proper drainage. We report the case of a 58 years-old male presenting with a painful loculated peri-pancreatic fluid collection secondary to acute pancreatitis. We performed Alteplase injection, followed by successful endosonographic drainage with lumen apposing metal stent of the collection after 48 hours. Our observation suggests that r-tPA could be a new strategy for loculated collections management, ensuring better drainage and limiting the indication for surgical treatment.