The role of pancreatoscopy in the diagnostic work-up of intraductal papillary mucinous neoplasms: a systematic review and meta-analysis.

BACKGROUND: Confirming the diagnosis, invasiveness, and disease extent of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas is challenging. The aim of this study was to summarize the literature on the efficacy and safety of peroral pancreatoscopy (POP) in the diagnosis of IPMN, including the impact of pre- and intraoperative POP on the management of IPMN. METHODS: The EMBASE, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar databases were systematically searched for articles. Eligible articles investigated cohorts of patients who underwent POP for (suspected) IPMN. RESULTS: 25 articles were identified and included in this review; with 22 of these reporting on the diagnostic yield of POP in IPMN and 11 reporting on the effect of pre- or intraoperative POP on clinical decision-making. Cannulation and observation rates, and overall diagnostic accuracy were high across all studies. Frequently reported visual characteristics of IPMN were intraductal fish-egg-like lesions, hypervascularity, and granular mucosa. Overall, the adverse event rate was 12 %, primarily consisting of post-endoscopic retrograde cholangiopancreatography pancreatitis, with a pooled rate of 10 %, mostly of mild severity. Regarding the impact of POP on clinical decision-making, POP findings altered the surgical approach in 13 %-62 % of patients. CONCLUSION: POP is technically successful in the vast majority of patients with (suspected) IPMN, has a consistently high diagnostic accuracy, but an adverse event rate of 12 %. Data on intraoperative pancreatoscopy are scarce, but small studies suggest its use can alter surgical management. Future studies are needed to better define the role of POP in the diagnostic work-up of IPMN.

Metabolomic profiling of Spathaspora passalidarum fermentations reveals mechanisms that overcome hemicellulose hydrolysate inhibitors.

Understanding the mechanisms involved in tolerance to inhibitors is the first step in developing robust yeasts for industrial second-generation ethanol (E2G) production. Here, we used ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) and MetaboAnalyst 4.0 for analysis of MS data to examine the changes in the metabolic profile of the yeast Spathaspora passalidarum during early fermentation of hemicellulosic hydrolysates containing high or low levels of inhibitors (referred to as control hydrolysate or CH and strategy hydrolysate or SH, respectively). During fermentation of SH, the maximum ethanol production was 16 g L-1 with a yield of 0.28 g g-1 and productivity of 0.22 g L-1 h-1, whereas maximum ethanol production in CH fermentation was 1.74 g L-1 with a yield of 0.11 g g-1 and productivity of 0.01 g L-1 h-1. The high level of inhibitors in CH induced complex physiological and biochemical responses related to stress tolerance in S. passalidarum. This yeast converted compounds with aldehyde groups (hydroxymethylfurfural, furfural, 4-hydroxybenzaldehyde, syringaldehyde, and vanillin) into less toxic compounds, and inhibitors were found to reduce cell viability and ethanol production. Intracellularly, high levels of inhibitors altered the energy homeostasis and redox balance, resulting in lower levels of ATP and NADPH, while that of glycolytic, pentose phosphate, and tricarboxylic acid (TCA) cycle pathways were the most affected, being the catabolism of glucogenic amino acids, the main cellular response to inhibitor-induced stress. This metabolomic investigation reveals interesting targets for metabolic engineering of ethanologenic yeast strains tolerant against multiple inhibitors for E2G production. KEY POINTS: • Inhibitors in the hydrolysates affected the yeast's redox balance and energy status. • Inhibitors altered the glycolytic, pentose phosphate, TCA cycle and amino acid pathways. • S. passalidarum converted aldehyde groups into less toxic compounds.

Diagnostic accuracy and interobserver agreement of digital single-operator cholangioscopy for indeterminate biliary strictures.

BACKGROUND AND AIMS: Digital single-operator cholangioscopy (d-SOC) with cholangioscopic biopsy sampling has shown promise in the evaluation of indeterminate biliary strictures. Some studies have suggested higher sensitivity for visual impression compared with biopsy sampling, although assessors were not blinded to previous investigations. We aimed to investigate the diagnostic accuracy and interobserver agreement (IOA) of d-SOC in the visual appraisal of biliary strictures when blinded to additional information. METHODS: A multicenter, international cohort study was performed. Cholangioscopic videos in patients with a known final diagnosis were systematically scored. Pseudonymized videos were reviewed by 19 experts in 2 steps: blinded for patient history and investigations and unblinded. RESULTS: Forty-four high-quality videos were reviewed of 19 benign and 25 malignant strictures. The sensitivity and specificity for the diagnosis of malignancy was 74.2% and 46.9% (blinded) and 72.7% and 62.5% (unblinded). Cholangioscopic certainty of a malignant diagnosis led to overdiagnosis (sensitivity, 90.6%; specificity, 33%), especially if no additional information was provided. The IOA for the presence of malignancy was fair for both assessments (Fleiss' κ = .245 [blinded] and κ = .321 [unblended]). For individual visual features, the IOA ranged from slight to moderate for both assessments (κ = .059-.400 vs κ = .031-.452). CONCLUSIONS: This study showed low sensitivity and specificity for blinded and unblinded d-SOC video appraisal of indeterminate biliary strictures, with considerable interobserver variation. Although reaching a consensus on the optical features of biliary strictures remains important, optimizing visually directed biopsy sampling may be the most important role of cholangioscopy in biliary stricture assessment.

Observation of Large Unidirectional Rashba Magnetoresistance in Ge(111).

Relating magnetotransport properties to specific spin textures at surfaces or interfaces is an intense field of research nowadays. Here, we investigate the variation of the electrical resistance of Ge(111) grown epitaxially on semi-insulating Si(111) under the application of an external magnetic field. We find a magnetoresistance term that is linear in current density j and magnetic field B, hence, odd in j and B, corresponding to a unidirectional magnetoresistance. At 15 K, for I=10 µA (or j=0.33 A m^{-1}) and B=1 T, it represents 0.5% of the zero field resistance, a much higher value compared to previous reports on unidirectional magnetoresistance (UMR). We ascribe the origin of this magnetoresistance to the interplay between the externally applied magnetic field and the pseudomagnetic field generated by the current applied in the spin-splitted subsurface states of Ge(111). This unidirectional magnetoresistance is independent of the current direction with respect to the Ge crystal axes. It progressively vanishes, either using a negative gate voltage due to carrier activation into the bulk (without spin-splitted bands), or by increasing the temperature due to the Rashba energy splitting of the subsurface states lower than ∼58k_{B}. We believe that UMR could be used as a powerful probe of the spin-orbit interaction in a wide range of materials.

Collaboration between a tertiary pain centre and community teams during the pandemic.

People with chronic pain faced potential treatment disruption during the COVID-19 pandemic in Singapore, as the focus of healthcare shifted. A model of rapid integration of a pain centre with community healthcare teams was implemented to care for vulnerable older patients with chronic pain and multiple comorbidities. Telemedicine and home visits by community nurses were used, with risk-mitigation measures, ensuring comprehensive assessment and treatment compliance. Medications from pain physicians were delivered at home through a hospital pharmacy. A secure national electronic health records system used by all teams ensured seamless access and documentation. Potential emergency department visits, admissions and delayed discharges were thus avoided. Integration of community teams with chronic pain management services can be recommended to ensure pandemic preparedness.

Efficacy and Safety of Digital Single-Operator Cholangioscopy for Difficult Biliary Stones.

BACKGROUND & AIMS: It is not clear whether digital single-operator cholangioscopy (D-SOC) with electrohydraulic and laser lithotripsy is effective in removal of difficult biliary stones. We investigated the safety and efficacy of D-SOC with electrohydraulic and laser lithotripsy in an international, multicenter study of patients with difficult biliary stones. METHODS: We performed a retrospective analysis of 407 patients (60.4% female; mean age, 64.2 years) who underwent D-SOC for difficult biliary stones at 22 tertiary centers in the United States, United Kingdom, or Korea from February 2015 through December 2016; 306 patients underwent electrohydraulic lithotripsy and 101 (24.8%) underwent laser lithotripsy. Univariate and multivariable analyses were performed to identify factors associated with technical failure and the need for more than 1 D-SOC electrohydraulic or laser lithotripsy session to clear the bile duct. RESULTS: The mean procedure time was longer in the electrohydraulic lithotripsy group (73.9 minutes) than in the laser lithotripsy group (49.9 minutes; P < .001). Ducts were completely cleared (technical success) in 97.3% of patients (96.7% of patients with electrohydraulic lithotripsy vs 99% patients with laser lithotripsy; P = .31). Ducts were cleared in a single session in 77.4% of patients (74.5% by electrohydraulic lithotripsy and 86.1% by laser lithotripsy; P = .20). Electrohydraulic or laser lithotripsy failed in 11 patients (2.7%); 8 patients were treated by surgery. Adverse events occurred in 3.7% patients and the stone was incompletely removed from 6.6% of patients. On multivariable analysis, difficult anatomy or cannulation (duodenal diverticula or altered anatomy) correlated with technical failure (odds ratio, 5.18; 95% confidence interval, 1.26-21.2; P = .02). Procedure time increased odds of more than 1 session of D-SOC electrohydraulic or laser lithotripsy (odds ratio, 1.02; 95% confidence interval, 1.01-1.03; P < .001). CONCLUSIONS: In a multicenter, international, retrospective analysis, we found D-SOC with electrohydraulic or laser lithotripsy to be effective and safe in more than 95% of patients with difficult biliary stones. Fewer than 5% of patients require additional treatment with surgery and/or extracorporeal shockwave lithotripsy to clear the duct.

Highly efficient and tunable spin-to-charge conversion through Rashba coupling at oxide interfaces.

The spin-orbit interaction couples the electrons' motion to their spin. As a result, a charge current running through a material with strong spin-orbit coupling generates a transverse spin current (spin Hall effect, SHE) and vice versa (inverse spin Hall effect, ISHE). The emergence of SHE and ISHE as charge-to-spin interconversion mechanisms offers a variety of novel spintronic functionalities and devices, some of which do not require any ferromagnetic material. However, the interconversion efficiency of SHE and ISHE (spin Hall angle) is a bulk property that rarely exceeds ten percent, and does not take advantage of interfacial and low-dimensional effects otherwise ubiquitous in spintronic hetero- and mesostructures. Here, we make use of an interface-driven spin-orbit coupling mechanism-the Rashba effect-in the oxide two-dimensional electron system (2DES) LaAlO3/SrTiO3 to achieve spin-to-charge conversion with unprecedented efficiency. Through spin pumping, we inject a spin current from a NiFe film into the oxide 2DES and detect the resulting charge current, which can be strongly modulated by a gate voltage. We discuss the amplitude of the effect and its gate dependence on the basis of the electronic structure of the 2DES and highlight the importance of a long scattering time to achieve efficient spin-to-charge interconversion.

Spin to Charge Conversion at Room Temperature by Spin Pumping into a New Type of Topological Insulator: α-Sn Films.

We present results on spin to charge current conversion in experiments of resonant spin pumping into the Dirac cone with helical spin polarization of the elemental topological insulator (TI) α-Sn. By angle-resolved photoelectron spectroscopy (ARPES), we first check that the Dirac cone (DC) at the α-Sn (0 0 1) surface subsists after covering Sn with Ag. Then we show that resonant spin pumping at room temperature from Fe through Ag into α-Sn layers induces a lateral charge current that can be ascribed to the inverse Edelstein effect by the DC states. Our observation of an inverse Edelstein effect length much longer than those generally found for Rashba interfaces demonstrates the potential of TIs for the conversion between spin and charge in spintronic devices. By comparing our results with data on the relaxation time of TI free surface states from time-resolved ARPES, we can anticipate the ultimate potential of the TI for spin to charge conversion and the conditions to reach it.

Type 1 autoimmune pancreatitis and IgG4-related sclerosing cholangitis is associated with extrapancreatic organ failure, malignancy, and mortality in a prospective UK cohort.

OBJECTIVES: Type I autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-related SC) are now recognized as components of a multisystem IgG4-related disease (IgG4-RD). We aimed to define the clinical course and long-term outcomes in patients with AIP/IgG4-SC recruited from two large UK tertiary referral centers. METHODS: Data were collected from 115 patients identified between 2004 and 2013, and all were followed up prospectively from diagnosis for a median of 33 months (range 1-107), and evaluated for response to therapy, the development of multiorgan involvement, and malignancy. Comparisons were made with national UK statistics. RESULTS: Although there was an initial response to steroids in 97%, relapse occurred in 50% of patients. IgG4-SC was an important predictor of relapse (P<0.01). Malignancy occurred in 11% shortly before or after the diagnosis of IgG4-RD, including three hepatopancreaticobiliary cancers. The risk of any cancer at diagnosis or during follow-up when compared with matched national statistics was increased (odds ratio=2.25, CI=1.12-3.94, P=0.02). Organ dysfunction occurred within the pancreas, liver, kidney, lung, and brain. Mortality occurred in 10% of patients during follow-up. The risk of death was increased compared with matched national statistics (odds ratio=2.07, CI=1.07-3.55, P=0.02). CONCLUSIONS: Our findings suggest that AIP and IgG4-SC are associated with significant morbidity and mortality owing to extrapancreatic organ failure and malignancy. Detailed clinical evaluation for evidence of organ dysfunction and associated malignancy is required both at first presentation and during long-term follow-up.

Spin pumping and inverse spin Hall effect in platinum: the essential role of spin-memory loss at metallic interfaces.

Through combined ferromagnetic resonance, spin pumping, and inverse spin Hall effect experiments in Co|Pt bilayers and Co|Cu|Pt trilayers, we demonstrate consistent values of ℓsfPt=3.4±0.4 nm and θSHEPt=0.056±0.010 for the respective spin diffusion length and spin Hall angle for Pt. Our data and model emphasize the partial depolarization of the spin current at each interface due to spin-memory loss. Our model reconciles the previously published spin Hall angle values and explains the different scaling lengths for the ferromagnetic damping and the spin Hall effect induced voltage.

Development of hemicellulolytic enzyme mixtures for plant biomass deconstruction on target biotechnological applications.

An essential step in the conversion of lignocellulosic biomass to ethanol and other biorefinery products is conversion of cell wall polysaccharides into fermentable sugars by enzymatic hydrolysis. The objective of the present study was to understand the mode of action of hemicellulolytic enzyme mixtures for pretreated sugarcane bagasse (PSB) deconstruction and wheat arabinoxylan (WA) hydrolysis on target biotechnological applications. In this study, five hemicellulolytic enzymes-two endo-1,4-xylanases (GH10 and GH11), two α-L-arabinofuranosidases (GH51 and GH54), and one ß-xylosidase (GH43)-were submitted to combinatorial assays using the experimental design strategy, in order to analyze synergistic and antagonistic effects of enzyme interactions on biomass degradation. The xylooligosaccharides (XOSs) released from hydrolysis were analyzed by capillary electrophoresis and quantified by high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD). Based on this analysis, it was possible to define which enzymatic combinations favor xylose (X1) or XOS production and thus enable the development of target biotechnological applications. Our results demonstrate that if the objective is X1 production from WA, the best enzymatic combination is GH11 + GH54 + GH43, and for xylobiose (X2) production from WA, it is best to combine GH11 + GH51. However, if the goal is to produce XOS, the five enzymes used in WA hydrolysis are important, but for PSB hydrolysis, only GH11 is sufficient. If the final objective is bioethanol production, GH11 is responsible for hydrolyzing 64.3 % of hemicellulose from PSB. This work provides a basis for further studies on enzymatic mechanisms for XOS production, and the development of more efficient and less expensive enzymatic mixtures, targeting commercially viable lignocellulosic ethanol production and other biorefinery products.

Spin-Momentum Locking and Ultrafast Spin-Charge Conversion in Ultrathin Epitaxial Bi1 - x Sbx Topological Insulator.

The helicity of three-dimensional (3D) topological insulator surface states has drawn significant attention in spintronics owing to spin-momentum locking where the carriers' spin is oriented perpendicular to their momentum. This property can provide an efficient method to convert charge currents into spin currents, and vice-versa, through the Rashba-Edelstein effect. However, experimental signatures of these surface states to the spin-charge conversion are extremely difficult to disentangle from bulk state contributions. Here, spin- and angle-resolved photo-emission spectroscopy, and time-resolved THz emission spectroscopy are combined to categorically demonstrate that spin-charge conversion arises mainly from the surface state in Bi1 - x Sbx ultrathin films, down to few nanometers where confinement effects emerge. This large conversion efficiency is correlated, typically at the level of the bulk spin Hall effect from heavy metals, to the complex Fermi surface obtained from theoretical calculations of the inverse Rashba-Edelstein response. Both surface state robustness and sizeable conversion efficiency in epitaxial Bi1 - x Sbx thin films bring new perspectives for ultra-low power magnetic random-access memories and broadband THz generation.

Impact of ERCP simulator training on early ERCP learning curves of novice trainees: a cohort study.

Background and study aim Simulator-based training has been extensively studied in training gastroduodenoscopy and colonoscopy and shown to significantly improve learning curves of novices. Data on simulator-based training in endoscopic retrograde cholangiopancreatography (ERCP) are scarce. We aimed to determine the impact of 2-day intensive hands-on simulator training on the course of the learning curve of novice trainees. Methods We conducted a prospective cohort study using a validated mechanical ERCP simulator (Boskoski-Costamagna ERCP Trainer). Six trainees were allocated to the simulation course program (SG). Each of these trainees were paired with an endoscopy trainee starting regular ERCP training at the same center who had no exposure to a simulation course program (control group; CG). The course included lectures, live ERCP demonstrations, and hands-on ERCP training to educate trainees in basic techniques related to cannulation, stent placement, stone extraction and stricture management. After the course, both the SG and CG started formal ERCP training in their respective centers. The Rotterdam Assessment Form for ERCP was used to register each performed ERCP. Simple moving average was applied to create learning curves based on successful common bile duct (CBD) cannulation. Outcomes were plotted against a historical cohort (HC). Results Thirteen trainees were included, six trainees in the SG and seven trainees in the CG, with a total of 717 ERCPs. Mean successful ERCP cannulation rate was higher for the simulator group at baseline compared to both CG and HC, 64% versus 43% and 42%, respectively. Differences became less explicit after 40 ERCPs, but persisted until a median of 75 ERCPs. Conclusions We demonstrate that 2-day hands-on simulator-based ERCP training course has a positive effect on the learning curves of ERCP trainees and should be considered an integral part of the training curricula for ERCP to develop skills prior to patient-based training.

Cholangiocarcinoma or IgG4-associated cholangitis: how feasible it is to avoid unnecessary surgical interventions?

OBJECTIVE: To evaluate the experience of a tertiary hepatopancreaticobiliary (HPB) center in the diagnostic approach and management of patients with suspicion of cholangiocarcinoma (CCa), focusing on excluding patients with IgG4-associated cholangitis (IAC) from unnecessary major surgical interventions. METHODS: Between January 2008 and September 2010, a total number of 152 patients with suspicion of CCa underwent evaluation through a HPB multidisciplinary team meeting. Patients without tissue diagnosis were managed surgically or medically on the basis of probable presence of IAC as underlying pathology. Serology, immunostaining, and imaging were reviewed and analyzed according to the HISORt (Histology, Imaging, Serology, Other organ involvement, Response to therapy) criteria for IAC. RESULTS: Tissue diagnosis during the diagnostic workup was achieved in 104 patients (68%), whereas the remaining 48 were classified as "highly suspicious for CCa" (n = 35) or as "probable IAC" (n = 13). Among 16 "highly suspicious for CCa" patients who underwent surgery, pathology revealed 2 patients harboring IAC (n = 1) and a benign chronic inflammatory biliary stricture (n = 1), respectively. Among the 13 patients with primarily medical management as "probable IAC," final diagnosis was CCa (n = 3) and IAC (n = 9), while 1 patient had no proven diagnosis. The accuracy of serum IgG4 for diagnosis of IAC reached 60%. Sensitivity and specificity of immunostaining for IAC in biopsy specimens were 56% and 89%, respectively. Imaging features suggesting IAC yielded sensitivity, specificity, and accuracy of 75%, 89%, and 83%, respectively. Initial imaging was revised at the referral institute in 75% of IAC patients (P = 0.009), while an isolated stricture (P = 0.038), a biliary mass (P = 0.006), and normal pancreas on computed tomography (P = 0.01) were statistically significant parameters for distinguishing between CCa and IAC. The mean time for establishing a diagnosis of IAC was 12.4 months (range: 2.5-32 months). CONCLUSIONS: Differential diagnosis between CCa and IAC mandates high index of suspicion and low threshold for referral in high volume institutes. The delayed establishment of diagnosis particularly for CCa needs to be balanced versus avoiding unnecessary surgery for IAC. Imaging features may be most helpful for optimal management.

Gate-controlled spin injection at LaAlO3/SrTiO3 interfaces.

We report results of electrical spin injection at the high-mobility quasi-two-dimensional electron system (2-DES) that forms at the LaAlO3/SrTiO3 interface. In a nonlocal, three-terminal measurement geometry, we analyze the voltage variation associated with the precession of the injected spin accumulation driven by perpendicular or transverse magnetic fields (Hanle and inverted Hanle effect). The influence of bias and back-gate voltages reveals that the spin accumulation signal is amplified by resonant tunneling through localized states in the LaAlO3 strongly coupled to the 2-DES by tunneling transfer.

Crossover from spin accumulation into interface states to spin injection in the germanium conduction band.

Electrical spin injection into semiconductors paves the way for exploring new phenomena in the area of spin physics and new generations of spintronic devices. However the exact role of interface states in the spin injection mechanism from a magnetic tunnel junction into a semiconductor is still under debate. In this Letter, we demonstrate a clear transition from spin accumulation into interface states to spin injection in the conduction band of n-Ge. We observe spin signal amplification at low temperature due to spin accumulation into interface states followed by a clear transition towards spin injection in the conduction band from 200 K up to room temperature. In this regime, the spin signal is reduced to a value compatible with the spin diffusion model. More interestingly, the observation in this regime of inverse spin Hall effect in germanium generated by spin pumping and the modulation of the spin signal by a gate voltage clearly demonstrate spin accumulation in the germanium conduction band.

A Systematic 10-Year Review of the Use of Arthroscopy in the Assessment and Treatment of Intercarpal Ligament Injuries Associated with Acute Distal Radius Fracture.

Background: To review the impact that arthroscopy has made on the assessment and treatment of intercarpal (scapholunate [SL] or lunotriquetral [LT]) ligament injuries associated with acute distal radius fractures (DRF). Methods: A systematic review of EMBASE, MEDLINE and COCHRANE databases for articles published between 2011 and 2021 was performed (PROSPERO ID: CRD42021273293) which included studies reported assessment and outcomes of intercarpal ligament injuries associated with acute DRF. Methodological quality was evaluated. The rate of concomitant injury detection, role of arthroscopy and different clinical outcome assessment measurements used were compared between studies. Results: A total of 20 articles were included with data from 1,346 patients (1,358 wrists). A total of 1,024 intra-articular fractures were included and 294 extra-articular fractures (40 not specified). There was a heterogeneous mix of studies; 10 comparative and 10 non-comparative. Some studies investigated initial assessment findings only, while others assessed radiological outcomes, functional outcomes or both domains over 0.3-99 months. The overall rate of SL ligament injury associated with DRF was 35.3%, while LT ligament injury overall was 18.2%. More frequent were concomitant triangular fibrocartilage complex (TFCC) injuries (44.8%), although this review did not aim to review these. The role of arthroscopy was reviewed, which included assistance in anatomic reduction of the articular surface and systematic inspection of the surrounding soft tissues. Included studies investigated either assessment or assessment and management of intercarpal ligament injury. Meaningful meta-analysis in this heterogeneous group of studies was not possible. Outcomes of comparative studies were described in detail. Conclusions: This review suggests that arthroscopy may have a role in improving reduction of intra-articular DRF and diagnosing and managing soft tissue injuries associated with such fractures. Randomised studies are needed to evaluate whether the detection of intercarpal ligament injury in acute distal radial fractures through arthroscopic assessment alters current management and improves clinical outcome. Level of Evidence: Level III (Therapeutic).

How lignin sticks to cellulose-insights from atomic force microscopy enhanced by machine-learning analysis and molecular dynamics simulations.

Elucidating cellulose-lignin interactions at the molecular and nanometric scales is an important research topic with impacts on several pathways of biomass valorization. Here, the interaction forces between a cellulosic substrate and lignin are investigated. Atomic force microscopy with lignin-coated tips is employed to probe the site-specific adhesion to a cellulose film in liquid water. Over seven thousand force-curves are analyzed by a machine-learning approach to cluster the experimental data into types of cellulose-tip interactions. The molecular mechanisms for distinct types of cellulose-lignin interactions are revealed by molecular dynamics simulations of lignin globules interacting with different cellulose Iß crystal facets. This unique combination of experimental force-curves, data-driven analysis, and molecular simulations opens a new approach of investigation and updates the understanding of cellulose-lignin interactions at the nanoscale.

Endoscopic retrograde cholangiography does not reliably distinguish IgG4-associated cholangitis from primary sclerosing cholangitis or cholangiocarcinoma.

BACKGROUND & AIMS: Distinction of immunoglobulin G4-associated cholangitis (IAC) from primary sclerosing cholangitis (PSC) or cholangiocarcinoma is challenging. We aimed to assess the performance characteristics of endoscopic retrograde cholangiography (ERC) for the diagnosis of IAC. METHODS: Seventeen physicians from centers in the United States, Japan, and the United Kingdom, unaware of clinical data, reviewed 40 preselected ERCs of patients with IAC (n = 20), PSC (n = 10), and cholangiocarcinoma (n = 10). The performance characteristics of ERC for IAC diagnosis as well as the κ statistic for intraobserver and interobserver agreement were calculated. RESULTS: The overall specificity, sensitivity, and interobserver agreement for the diagnosis of IAC were 88%, 45%, and 0.18, respectively. Reviewer origin, specialty, or years of experience had no statistically significant effect on reporting success. The overall intraobserver agreement was fair (0.74). The operating characteristics of different ERC features for the diagnosis of IAC were poor. CONCLUSIONS: Despite high specificity of ERC for diagnosing IAC, sensitivity is poor, suggesting that many patients with IAC may be misdiagnosed with PSC or cholangiocarcinoma. Additional diagnostic strategies are likely to be vital in distinguishing these diseases.