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Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) allows spatial analysis of proteins, metabolites, or small molecules from tissue sections. Here, we present the simultaneous generation and analysis of MALDI-MSI, whole-exome sequencing (WES), and RNA-sequencing data from the same formalin-fixed paraffin-embedded (FFPE) tissue sections. Genomic DNA and total RNA were extracted from (i) untreated, (ii) hematoxylin-eosin (HE) stained, and (iii) MALDI-MSI-analyzed FFPE tissue sections from three head and neck squamous cell carcinomas. MALDI-MSI data were generated by a time-of-flight analyzer prior to preprocessing and visualization. WES data were generated using a low-input protocol followed by detection of single-nucleotide variants (SNVs), tumor mutational burden, and mutational signatures. The transcriptome was determined using 3'-RNA sequencing and was examined for similarities and differences between processing stages. All data met the commonly accepted quality criteria. Besides SNVs commonly identified between differently processed tissues, FFPE-typical artifactual variants were detected. Tumor mutational burden was in the same range for tissues from the same patient and mutational signatures were highly overlapping. Transcriptome profiles showed high levels of correlation. Our data demonstrate that simultaneous molecular profiling of MALDI-MSI-processed FFPE tissue sections at the transcriptome and exome levels is feasible and reliable. The authors present a workflow that allows the simultaneous measurement of the whole exome and the transcriptome by next-generation sequencing from formalin-fixed paraffin-embedded tissue sections that were analyzed by matrix-assisted laser desorption ionization mass spectrometry imaging. The data and analyses demonstrate the feasibility and reproducibility of this approach, which expands the possibilities of multi-omics integration in cancer research.

Many properties of real materials can be modeled using ab initio methods within a single-particle picture. However, for an accurate theoretical treatment of excited states, it is necessary to describe electron-electron correlations including interactions with bosons: phonons, plasmons, or magnons. In this work, by comparing spin- and momentum-resolved photoemission spectroscopy measurements to many-body calculations carried out with a newly developed first-principles method, we show that a kink in the electronic band dispersion of a ferromagnetic material can occur at much deeper binding energies than expected ( E b  = 1.5 eV). We demonstrate that the observed spectral signature reflects the formation of a many-body state that includes a photohole bound to a coherent superposition of renormalized spin-flip excitations. The existence of such a many-body state sheds new light on the physics of the electron-magnon interaction which is essential in fields such as spintronics and Fe-based superconductivity. The conduction electron and magnon interactions are essential for the understanding and development of spintronics and superconductivity. Here the authors show a deep binding energy kink in spin-resolved photoemission spectra which is understood as a signature the many-body spin flip excitation in Fe single crystal thin film.

Patients with moderately severe gallstone pancreatitis with substantial pancreatic and peripancreatic inflammation, but without organ failure, frequently have an open cholecystectomy to prevent recurrent pancreatitis. In these patients, prophylactic endoscopic retrograde cholangiography (ERC) with endoscopic sphincterotomy (ES) may prevent recurrent pancreatitis, permit laparoscopic cholecystectomy, and decrease risks. The medical records of all patients with pancreatitis undergoing cholecystectomy from 1999–2004 at the University of North Carolina Memorial Hospital were reviewed. Data regarding demographics, clinical course, etiology of pancreatitis, operative and endoscopic interventions, and outcome were extracted. Moderately severe gallstone-induced pancreatitis was defined as pancreatitis without organ failure but with extensive local inflammation. Thirty patients with moderately severe gallstone pancreatitis underwent ERC and ES and were discharged before cholecystectomy. Mean interval between ES and cholecystectomy was 102 ± 17 days. Cholecystectomy was performed laparoscopically in 27 (90%) patients, open in three (10%) patients, and converted to open in two (7%) patients, with a morbidity rate of 7% (two patients). No patient required drainage of a pseudocyst or developed recurrent pancreatitis. Interval complications resulted in hospital readmission in seven (23%) patients. In conclusion, recurrent biliary pancreatitis in patients with moderately severe gallstone pancreatitis is nil after ERC and ES. Hospital discharge of these patients permits interval laparoscopic cholecystectomy, but close follow-up is necessary in these potentially ill patients.

Patients with gastroesophageal reflux disease (GERD) and disordered esophageal motility are at risk for postoperative dysphagia, and are often treated with partial (270-degree) fundoplication as a strategy to minimize postoperative swallowing difficulties. Complete (360-degree) fundoplication, however, may provide more effective and durable reflux protection over time. Recently we reported that postfundoplication dysphagia is uncommon, regardless of preoperative manometric status and type of fundoplication. To determine whether esophageal function improves after fundoplication, we measured postoperative motility in patients in whom disordered esophageal motility had been documented before fundoplication. Forty-eight of 262 patients who underwent laparoscopic fundoplication between 1995 and 2000 satisfied preoperative manometric criteria for disordered esophageal motility (distal esophageal peristaltic amplitude ≤30 mm Hg and/or peristaltic frequency ≤80%). Of these, 19 had preoperative manometric assessment at our facility and consented to repeat study. Fifteen (79%) of these patients had a complete fundoplication and four (21%) had a partial fundoplication. Each patient underwent repeat four-channel esophageal manometry 29.5 ± 18.4 months (mean ± SD) after fundoplication. Distal esophageal peristaltic amplitude and peristaltic frequency were compared to preoperative data by paired t test. After fundoplication, mean peristaltic amplitude in the distal esophagus increased by 47% (56.8 ± 30.9 mm Hg to 83.5 ± 36.5 mm Hg; P < 0.001) and peristaltic frequency improved by 33% (66.4 ± 28.7% to 87.6 ± 16.3%; P < 0.01). Normal esophageal motor function was present in 14 patients (74%) after fundoplication, whereas in five patients the esophageal motor function remained abnormal (2 improved, 1 worsened, and 2 remained unchanged). Three patients with preoperative peristaltic frequencies of 0%, 10%, and 20% improved to 84%, 88%, and 50%, respectively, after fundoplication. In most GERD patients with esophageal dysmotility, fundoplication improves the amplitude and frequency of esophageal peristalsis, suggesting refluxate has an etiologic role in motor dysfunction. These data, along with prior data showing that postoperative dysphagia is not common, imply that surgeons should apply complete fundoplication liberally in patients with disordered preoperative esophageal motility. ( J Gastrointest Surg 2003;7:159–163.)

Abnormal esophageal motility is a relative contraindication to complete (360-degree) fundoplication because of a purported risk of postoperative dysphagia. Partial fundoplication, however, may be associated with increased postoperative esophageal acid exposure. Our aim was to determine if complete fundoplication is associated with increased postoperative dysphagia in patients with abnormal esophageal motor function. Medical records of 140 patients (79 females; mean age 48 ± 1.1 years) who underwent fundoplication for gastroesophageal reflux disease (GERD) were reviewed retrospectively to document demographic data, symptoms, and diagnostic test results. Of the 126 patients who underwent complete fundoplication, 25 met manometric criteria for abnormal esophageal motility (≤30 mm Hg mean distal esophageal body pressure or ≤80% peristalsis), 68 had normal esophageal function, and 33 had incomplete manometric data and were therefore excluded from analysis. Of the 11 patients who underwent partial fundoplication, eight met criteria for abnormal esophageal motility, two had normal esophageal function, and one had incomplete data and was therefore excluded. After a median follow-up of 2 years (range 0.5 to 5 years), patients were asked to report heartburn, difficulty swallowing, and overall satisfaction using a standardized scoring scale. Complete responses were obtained in 72%. Sixty-five patients who underwent complete fundoplication and had manometric data available responded (46 normal manometry; 19 abnormal manometry). Outcomes were compared using the Mann-Whitney U test. After complete fundoplication, similar postoperative heartburn, swallowing, and overall satisfaction were reported by patients with normal and abnormal esophageal motility. Likewise, similar outcomes were reported after partial fundoplication. This retrospective study found equally low dysphagia rates regardless of baseline esophageal motility; therefore a randomized trial comparing complete versus partial fundoplication in patients with abnormal esophageal motility is warranted.

Recent accumulating evidence suggests that the vagus nerve modulates the response to peripheral immunologic stimuli and that intact vagal mediation decreases the systemic inflammatory response. We hypothesized that patients who had vagotomy for complicated peptic ulcer disease would be at increased risk of an enhanced systemic inflammatory response compared to patients that did not have a vagotomy as part of their operative treatment. Ninety-six patients were identified from 1985 to 2000 and their medical records were reviewed. Patients were assigned to three groups based on the performance of a truncal vagotomy: truncal vagotomy (TV; N = 62 patients), nontruncal vagotomy (NTV; N = 34 patients), or a subgroup of the TV group, acute truncal vagotomy (ATV; N = 40 patients). Operative indications in the NTV and ATV groups were perforation (94% vs 47%) and bleeding (6% vs 53%). Systemic or organ-specific complications did not differ between groups (NTV vs ATV), and the sepsis (24% vs 23%) and mortality rates (29% vs 20%) were similar. The ICU and hospital length of stay did not differ substantially among the groups. This clinical study demonstrated that acute truncal vagotomy does not increase the risk of the systemic inflammatory response in surgical patients with complicated peptic ulcer disease.

Many properties of real materials can be modeled using ab initio methods within a single-particle picture. However, for an accurate theoretical treatment of excited states, it is necessary to describe electron-electron correlations including interactions with bosons: phonons, plasmons, or magnons. In this work, by comparing spin- and momentum-resolved photoemission spectroscopy measurements to many-body calculations carried out with a newly developed first-principles method, we show that a kink in the electronic band dispersion of a ferromagnetic material can occur at much deeper binding energies than expected (E_b=1.5 eV). We demonstrate that the observed spectral signature reflects the formation of a many-body state that includes a photohole bound to a coherent superposition of renormalized spin-flip excitations. The existence of such a many-body state sheds new light on the physics of the electron-magnon interaction which is essential in fields such as spintronics and Fe-based superconductivity.

Using angle-resolved photoelectron spectroscopy (ARPES), we investigate the surface electronic structure of the magnetic van der Waals compounds MnBi\\(_4\\)Te\\(_7\\) and MnBi\\(_6\\)Te\\(_{10}\\), the \\(n=\\)~1 and 2 members of a modular (Bi\\(_2\\)Te\\(_3\\))\\(_n\\)(MnBi\\(_2\\)Te\\(_4\\)) series, which have attracted recent interest as intrinsic magnetic topological insulators. Combining circular dichroic, spin-resolved and photon-energy-dependent ARPES measurements with calculations based on density functional theory, we unveil complex momentum-dependent orbital and spin textures in the surface electronic structure and disentangle topological from trivial surface bands. We find that the Dirac-cone dispersion of the topologial surface state is strongly perturbed by hybridization with valence-band states for Bi\\(_2\\)Te\\(_3\\)-terminated surfaces but remains preserved for MnBi\\(_2\\)Te\\(_4\\)-terminated surfaces. Our results firmly establish the topologically non-trivial nature of these magnetic van der Waals materials and indicate that the possibility of realizing a quantized anomalous Hall conductivity depends on surface termination.

Geometric perturbation theory is universal. A typical example is provided by the 3D wave equation, widely used in acoustics. We face vibrating eardrums as a binaural auditory input stemming from an external sound source. In the setup of internally coupled ears (ICE), which are present in more than half of the land-living vertebrates, the two tympana are coupled by an internal air-filled cavity, whose geometry determines the acoustic properties of the ICE system. The eardrums themselves are described by a 2-dimensional, damped, wave equation and are part of the spatial boundary conditions of the three-dimensional Laplacian belonging to the wave equation in the internal cavity that couples and internally drives the eardrums. In animals with ICE the resulting signal is the superposition of external sound arriving at both eardrums and the internal pressure coupling them. This is also the typical setup for geometric perturbation theory. In the context of ICE it boils down to acoustic boundary-condition dynamics (ABCD) for the coupled dynamical system of eardrums and internal cavity. In acoustics the deviations from equilibrium are extremely small (nm). Perturbation theory is therefore natural and shown to be appropriate. In doing so, we use a time-dependent perturbation theory à la Dirac in the context of Duhamel's principle. The relaxation dynamics of the tympanic-membrane system, which neuronal information processing stems from, is explicitly obtained in first order. Furthermore, both the initial and the quasi-stationary asymptotic state are derived and analyzed. Finally, we set the general stage for geometric perturbation theory where (d-1)-dimensional manifolds as subsets of the boundary of a d-dimensional domain are driven by their own dynamics with the domain pressure \\(p\\) and an external source term as input, at the same time constituting time-dependent boundary conditions for \\(p\\).

A systematic study of small, time-dependent, perturbations to geometric wave-equation domains is hardly existent. Acoustic enclosures are typical examples featuring locally reacting surfaces that respond to a pressure gradient or a pressure difference, alter the enclosure's volume and, hence, the boundary conditions, and do so locally through their vibrations. Accordingly, the Laplace-Beltrami operator in the acoustic wave equation lives in a temporally varying domain depending on the displacement of the locally reacting surface from equilibrium. The resulting partial differential equations feature nonlinearities and are coupled though the time-dependent boundary conditions. The solution to the afore-mentioned problem, as presented here, integrates techniques from differential geometry, functional analysis, and physics. The appropriate space is shown to be a (perturbation) fiber bundle. In the context of a systematic perturbation theory, the solution to the dynamical problem is obtained from a combination of semigroup techniques for operator evolution equations and metric perturbation theory as used in AdS/CFT. Duhamel's principle then yields a time-dependent perturbation theory, called geometric perturbation theory. It is analogous to, though different from, both Dirac's time-dependent perturbation theory and the Magnus expansion. Specifically, the formalism demonstrates that the stationary-domain approximation for vibrational acoustics only introduces a small error. Analytic simplifications methods are derived in the framework of the piston approximation. Globally reacting surfaces (so-called pistons) replace the formerly locally reacting surfaces and reduce the number of independent variables in the underlying partial differential equations. In this way, a straightforwardly applicable formalism is derived for scalar wave equations on time-varying domains.