Prognostic impact of aberrant right hepatic artery involvement in patients with pancreatic cancer: A multicenter retrospective cohort study.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the prognostic value of aberrant right hepatic artery (A-RHA) involvement in patients with pancreatic cancer (PC). METHODS: This study enrolled 474 patients who underwent upfront pancreatectomy or neoadjuvant treatment for resectable (R) or borderline resectable (BR) PC from four institutions. The patients were divided into three groups: A-RHA involvement group (n = 12), patients who had sole A-RHA involvement without major arterial involvement; BR-A group (n = 104), patients who had major arterial involvement; R/BR-PV group (n = 358), others. RESULTS: All patients in the A-RHA involvement group underwent margin-negative resection. The median overall survival of the entire cohort in the A-RHA involvement, R/BR-PV, and BR-A groups was 41.2, 33.5, and 25.2 months, respectively. Although survival in the R/BR-PV group was significantly more favorable than that in the BR-A group (p = 0.0003), no significant difference was observed between the A-RHA involvement group and the R/BR-PV (p = 0.7332) and BR-A (p = 0.1485) groups. CONCLUSIONS: The prognosis of patients with PC and sole A-RHA involvement was comparable to that of patients with R/BR-PV.

What tool or method do you wish existed?

We asked researchers from a range of disciplines across biology, engineering, and medicine to describe a current technological need. The goal is to provide a sample of the various technological gaps that exist and inspire future research projects.

Magnetoelectric effect in multiferroic nickelate perovskite YNiO3.

The interaction of magnetic order and spontaneous polarization is a fundamental coupling with the prospect for the control of electronic properties and magnetism. The connection among magnetic order, charge localization and associated metal-insulator transition (MIT) are cornerstones for materials control. Materials that combine both effects are therefore of great interest for testing models that claim the occurrence of spontaneous polarization from magnetic and charge order. One class of materials proposed to combine these functionalities is the family of RNiO3 (R: Lanthanide or Yttrium), whose members show a clear MIT and an antiferromagnetic ground state and for which an electric polarization has been predicted. Here, using resonant magnetic x-ray scattering with circular polarization and an applied electric field we show that YNiO3 possess a magnetic structure containing domains of spin-rotations that are consistent with an electric polarization. We show a reversal of the magnetic structure with the applied electric field confirming that charge ordered RNiO3 are magnetoelectric type II multiferroics with a MIT.

Cortical parvalbumin neurons are responsible for homeostatic sleep rebound through CaMKII activation.

The homeostatic regulation of sleep is characterized by rebound sleep after prolonged wakefulness, but the molecular and cellular mechanisms underlying this regulation are still unknown. In this study, we show that Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent activity control of parvalbumin (PV)-expressing cortical neurons is involved in homeostatic regulation of sleep in male mice. Prolonged wakefulness enhances cortical PV-neuron activity. Chemogenetic suppression or activation of cortical PV neurons inhibits or induces rebound sleep, implying that rebound sleep is dependent on increased activity of cortical PV neurons. Furthermore, we discovered that CaMKII kinase activity boosts the activity of cortical PV neurons, and that kinase activity is important for homeostatic sleep rebound. Here, we propose that CaMKII-dependent PV-neuron activity represents negative feedback inhibition of cortical neural excitability, which serves as the distributive cortical circuits for sleep homeostatic regulation.

An automated sleep staging tool based on simple statistical features of mice electroencephalography (EEG) and electromyography (EMG) data.

Electroencephalogram (EEG) and electromyogram (EMG) are fundamental tools in sleep research. However, investigations into the statistical properties of rodent EEG/EMG signals in the sleep-wake cycle have been limited. The lack of standard criteria in defining sleep stages forces researchers to rely on human expertise to inspect EEG/EMG. The recent increasing demand for analysing large-scale and long-term data has been overwhelming the capabilities of human experts. In this study, we explored the statistical features of EEG signals in the sleep-wake cycle. We found that the normalized EEG power density profile changes its lower and higher frequency powers to a comparable degree in the opposite direction, pivoting around 20-30 Hz between the NREM sleep and the active brain state. We also found that REM sleep has a normalized EEG power density profile that overlaps with wakefulness and a characteristic reduction in the EMG signal. Based on these observations, we proposed three simple statistical features that could span a 3D space. Each sleep-wake stage formed a separate cluster close to a normal distribution in the 3D space. Notably, the suggested features are a natural extension of the conventional definition, making it useful for experts to intuitively interpret the EEG/EMG signal alterations caused by genetic mutations or experimental treatments. In addition, we developed an unsupervised automatic staging algorithm based on these features. The developed algorithm is a valuable tool for expediting the quantitative evaluation of EEG/EMG signals so that researchers can utilize the recent high-throughput genetic or pharmacological methods for sleep research.

Region-specific DNA hydroxymethylation along the malignant progression of IDH-mutant gliomas.

The majority of low-grade isocitrate dehydrogenase-mutant (IDHmt) gliomas undergo malignant progression (MP), but their underlying mechanism remains unclear. IDHmt gliomas exhibit global DNA methylation, and our previous report suggested that MP could be partly attributed to passive demethylation caused by accelerated cell cycles. However, during MP, there is also active demethylation mediated by ten-eleven translocation, such as DNA hydroxymethylation. Hydroxymethylation is reported to potentially contribute to gene expression regulation, but its role in MP remains under investigation. Therefore, we conducted a comprehensive analysis of hydroxymethylation during MP of IDHmt astrocytoma. Five primary/malignantly progressed IDHmt astrocytoma pairs were analyzed with oxidative bisulfite and the Infinium EPIC methylation array, detecting 5-hydroxymethyl cytosine at over 850,000 locations for region-specific hydroxymethylation assessment. Notably, we observed significant sharing of hydroxymethylated genomic regions during MP across the samples. Hydroxymethylated CpGs were enriched in open sea and intergenic regions (p < 0.001), and genes undergoing hydroxymethylation were significantly associated with cancer-related signaling pathways. RNA sequencing data integration identified 91 genes with significant positive/negative hydroxymethylation-expression correlations. Functional analysis suggested that positively correlated genes are involved in cell-cycle promotion, while negatively correlated ones are associated with antineoplastic functions. Analyses of The Cancer Genome Atlas clinical data on glioma were in line with these findings. Motif-enrichment analysis suggested the potential involvement of the transcription factor KLF4 in hydroxymethylation-based gene regulation. Our findings shed light on the significance of region-specific DNA hydroxymethylation in glioma MP and suggest its potential role in cancer-related gene expression and IDHmt glioma malignancy.

Enhancing Mass spectrometry-based tumor immunopeptide identification: machine learning filter leveraging HLA binding affinity, aliphatic index and retention time deviation.

Accurately identifying neoantigens is crucial for developing effective cancer vaccines and improving tumor immunotherapy. Mass spectrometry-based immunopeptidomics has emerged as a promising approach to identifying human leukocyte antigen (HLA) peptides presented on the surface of cancer cells, but false-positive identifications remain a significant challenge. In this study, liquid chromatography-tandem mass spectrometry-based proteomics and next-generation sequencing were utilized to identify HLA-presenting neoantigenic peptides resulting from non-synonymous single nucleotide variations in tumor tissues from 18 patients with renal cell carcinoma or pancreatic cancer. Machine learning was utilized to evaluate Mascot identifications through the prediction of MS/MS spectral consistency, and four descriptors for each candidate sequence: the max Mascot ion score, predicted HLA binding affinity, aliphatic index and retention time deviation, were selected as important features in filtering out identifications with inadequate fragmentation consistency. This suggests that incorporating rescoring filters based on peptide physicochemical characteristics could enhance the identification rate of MS-based immunopeptidomics compared to the traditional Mascot approach predominantly used for proteomics, indicating the potential for optimizing neoantigen identification pipelines as well as clinical applications.

Bioorthogonal chemical labeling of endogenous neurotransmitter receptors in living mouse brains.

Neurotransmitter receptors are essential components of synapses for communication between neurons in the brain. Because the spatiotemporal expression profiles and dynamics of neurotransmitter receptors involved in many functions are delicately governed in the brain, in vivo research tools with high spatiotemporal resolution for receptors in intact brains are highly desirable. Covalent labeling by chemical reaction (chemical labeling) of proteins without genetic manipulation is now a powerful method for analyzing receptors in vitro. However, selective target receptor labeling in the brain has not yet been achieved. This study shows that ligand-directed alkoxyacylimidazole (LDAI) chemistry can be used to selectively tether synthetic probes to target endogenous receptors in living mouse brains. The reactive LDAI reagents with negative charges were found to diffuse well over the whole brain and could selectively label target endogenous receptors, including AMPAR, NMDAR, mGlu1, and GABAAR. This simple and robust labeling protocol was then used for various applications: three-dimensional spatial mapping of endogenous receptors in the brains of healthy and disease-model mice; multi-color receptor imaging; and pulse-chase analysis of the receptor dynamics in postnatal mouse brains. Here, results demonstrated that bioorthogonal receptor modification in living animal brains may provide innovative molecular tools that contribute to the in-depth understanding of complicated brain functions.

Fulminant necrotizing fasciitis by Edwardsiella tarda in a patient with alcoholic liver cirrhosis: A case report.

We herein present a unique and extremely rare fulminant case of Edwardsiella tarda infection-related necrotizing fasciitis. The patient had alcoholic cirrhosis and preferred to consume raw fish. He experienced painful swelling of the right forearm one day after he got a minor injury when falling from the ladder, and visited our hospital. His accompanied symptoms were diarrhea and general fatigue. His consciousness got deteriorated after the admission. The lesion of the right forearm had spread and the color had deteriorated with epidermolysis in a few hours. Necrotizing soft-tissue infection was suspected, and emergency debridement of the swollen forearm was performed 4 hours after the admission. However, unfortunately, he died of sepsis approximately 5 hours later. Histological examination of the biopsy specimen revealed features consistent with those of necrotizing fasciitis. The bacterial cultures of blood and the wound identified E. tarda. Since this microorganism is usually isolated from aquatic environments and can cause intestinal infection, sometimes followed by bacteremia especially in immunocompromised hosts, two possible infection routes were suspected. One route was from the skin injury, leading to bacteremia. Another possible route was per oral: orally taken E. tarda invaded deeper tissues from the intestine and reach the bloodstream, leading to extraintestinal infections, although direct evidence remains elusive. Raw fish eaten 1 week prior is considered to be the most possible contaminated food. Overall mortality rate of E. tarda bacteremia is very high and the clinician should pay attention on characteristic clinical findings of E. tarda infection on cirrhotic patients.

Transient Non-Collinear Magnetic State for All-Optical Magnetization Switching.

Resonant absorption of a photon by bound electrons in a solid can promote an electron to another orbital state or transfer it to a neighboring atomic site. Such a transition in a magnetically ordered material could affect the magnetic order. While this process is an obvious road map for optical control of magnetization, experimental demonstration of such a process remains challenging. Exciting a significant fraction of magnetic ions requires a very intense incoming light beam, as orbital resonances are often weak compared to above-band-gap excitations. In the latter case, a sizeable reduction of the magnetization occurs as the absorbed energy increases the spin temperature, masking the non-thermal optical effects. Here, using ultrafast X-ray spectroscopy, this work is able to resolve changes in the magnetization state induced by resonant absorption of infrared photons in Co-doped yttrium iron garnet, with negligible thermal effects. This work finds that the optical excitation of the Co ions affects the two distinct magnetic Fe sublattices differently, resulting in a transient non-collinear magnetic state. The present results indicate that the all-optical magnetization switching (AOS) most likely occurs due to the creation of a transient, non-collinear magnetic state followed by coherent spin rotations of the Fe moments.

Non-equilibrium dynamics of spin-lattice coupling.

Quantifying the dynamics of normal modes and how they interact with other excitations is of central importance in condensed matter. Spin-lattice coupling is relevant to several sub-fields of condensed matter physics; examples include spintronics, high-Tc superconductivity, and topological materials. However, experimental approaches that can directly measure it are rare and incomplete. Here we use time-resolved X-ray diffraction to directly access the ultrafast motion of atoms and spins following the coherent excitation of an electromagnon in a multiferroic hexaferrite. One striking outcome is the different phase shifts relative to the driving field of the two different components. This phase shift provides insight into the excitation process of such a coupled mode. This direct observation of combined lattice and magnetization dynamics paves the way to access the mode-selective spin-lattice coupling strength, which remains a missing fundamental parameter for ultrafast control of magnetism and is relevant to a wide variety of materials.

Pancreatic cancer near the splenic hilum has a higher likelihood of splenic vessel invasion and unfavorable survival.

PURPOSE: This study aimed to investigate whether clinical outcomes varied based on the tumor location within the pancreatic body and tail in patients with pancreatic cancer (PC). METHODS: Ninety-five patients who had undergone a distal pancreatectomy for resectable (R) or borderline resectable (BR) PC within the pancreatic body or tail region were retrospectively investigated and divided into four groups (three subgroups of R-PC according to tumor location, and BR-PC): R-PC in the pancreatic body region (group A, n = 24), R-PC on the right side of the pancreatic tail region (group B, n = 17), R-PC on the left side of the pancreatic tail region (group C, n = 29), and BR-PC located in any region within the pancreatic body and tail (group BR, n = 25). RESULTS: Group C patients showed a higher incidence of pretreatment splenic artery and vein involvement than group A and B patients (splenic artery: 8.3/11.8/41.4%, p < 0.010; splenic vein: 25.0/23.5/79.3%, p < 0.010, in groups A/B/C, respectively). The overall survival of group C patients was significantly unfavorable compared to that of group A and B patients (median: 3.9/4.2/2.3 years in groups A/B/C, p = 0.029, respectively). Pretreatment clinical factors were comparable between group C and group BR. Median survival rates were comparable between group C and BR patients (2.3 and 2.0 years, respectively) (p = 0.93). CONCLUSIONS: Differences in anatomical location within the pancreatic body and tail characterize the unfavorable outcomes of PC near the splenic hilum.

Circadian ribosome profiling reveals a role for the Period2 upstream open reading frame in sleep.

Many mammalian proteins have circadian cycles of production and degradation, and many of these rhythms are altered posttranscriptionally. We used ribosome profiling to examine posttranscriptional control of circadian rhythms by quantifying RNA translation in the liver over a 24-h period from circadian-entrained mice transferred to constant darkness conditions and by comparing ribosome binding levels to protein levels for 16 circadian proteins. We observed large differences in ribosome binding levels compared to protein levels, and we observed delays between peak ribosome binding and peak protein abundance. We found extensive binding of ribosomes to upstream open reading frames (uORFs) in circadian mRNAs, including the core clock gene Period2 (Per2). An increase in the number of uORFs in the 5'UTR was associated with a decrease in ribosome binding in the main coding sequence and a reduction in expression of synthetic reporter constructs. Mutation of the Per2 uORF increased luciferase and fluorescence reporter expression in 3T3 cells and increased luciferase expression in PER2:LUC MEF cells. Mutation of the Per2 uORF in mice increased Per2 mRNA expression, enhanced ribosome binding on Per2, and reduced total sleep time compared to that in wild-type mice. These results suggest that uORFs affect mRNA posttranscriptionally, which can impact physiological rhythms and sleep.

Surgical anatomy of the dorsal pancreatic artery: Considering embryonic development.

OBJECTIVES: The dorsal pancreatic artery (DPA) is a pancreatic branch with various anatomical variations. Previous studies mostly focused on the origin of the DPA, and its pathways and branching patterns have rarely been examined. The purpose of this study was to investigate the branching patterns and pathways of the DPA. METHODS: This study included 110 patients who underwent computed tomography scans. We examined the pathways and branching patterns of the DPA. RESULTS: The DPA was identified in 101 patients (92%), and originated from the splenic artery in 30 patients (31%), the common hepatic artery in 17 patients (17%), the celiac trunk in 10 patients (10%), the superior mesenteric artery in 27 patients (27%), the replaced right hepatic artery in 7 patients (7%), the inferior pancreaticoduodenal artery in 5 patients (5%), and other arteries in 3 patients (3%). Four distinct types of branches were identified as follows: the superior branch (32%), the inferior branch (86%), the right branch (80%), and the accessory middle colic artery (12%). Additionally, the arcs of Buhler and Riolan were observed in two patients each and their anastomotic vessels followed almost the same pathway as the DPA. CONCLUSION: A number of variations of the DPA were observed with regard to its origin and branching pattern; however, the DPA and its branches always ran along the same pathway, as summarized in Fig. 4. The anatomical information gained from this study may contribute to performing safe pancreatic resections.

4D Visualization of a Nonthermal Coherent Magnon in a Laser Heated Lattice by an X-ray Free Electron Laser.

Ultrafast optical manipulation of magnetic phenomena is an exciting achievement of mankind, expanding one's horizon of knowledge toward the functional nonequilibrium states. The dynamics acting on an extremely short timescale push the detection limits that reveal fascinating light-matter interactions for nonthermal creation of effective magnetic fields. While some cases are benchmarked by emergent transient behaviors, otherwise identifying the nonthermal effects remains challenging. Here, a femtosecond time-resolved resonant magnetic X-ray diffraction experiment is introduced, which uses an X-ray free-electron laser (XFEL) to distinguish between the effective field and the photoinduced thermal effect. It is observed that a multiferroic Y-type hexaferrite exhibits magnetic Bragg peak intensity oscillations manifesting entangled antiferromagnetic (AFM) and ferromagnetic (FM) Fourier components of a coherent AFM magnon. The magnon trajectory constructed in 3D space and time domains is decisive to evince ultrafast field formation preceding the lattice thermalization. A remarkable impact of photoexcitation across the electronic bandgap is directly unraveled, amplifying the photomagnetic coupling that is one of the highest among AFM dielectrics. Leveraging the above-bandgap photoexcitation, this energy-efficient optical process further suggests a novel photomagnetic control of ferroelectricity in multiferroics.

Elucidation of the mechanism of amyloid A and transthyretin formation using mass spectrometry-based absolute quantification.

Amyloidosis is triggered by the truncation of amyloid precursor proteins, causing organ damages. While previous studies found the truncation of amyloid A (AA) and amyloid transthyretin (ATTR) occurs in C- and N-terminal, respectively, the detailed mechanism of the fibril formation remains unclear. Liquid chromatography mass spectrometry is usually applied for a qualitative purpose, and thus quantification of tryptic peptide residue is difficult. We therefore employed a mass spectrometry-based quantification by isotope-labeled cell-free (MS-QBIC) to analyze the truncation processes in amyloid fibrillogenesis of AA and ATTR using the formalin-fixed paraffin-embedded tissues of autopsy cases. In this study, the process of transthyretin from an 'early fibril state' consisting of full-length ATTR to a 'mature ATTR amyloid fibril' with a truncated low-amyloidogenic segment has been mathematically revealed. The amount of full-length ATTR was nine times higher than in mature fibers. Large cohort studies using MS-QBIC may shed light on the clinical significance of amyloid fibrils.

Chiral phonons in quartz probed by X-rays.

The concept of chirality is of great relevance in nature, from chiral molecules such as sugar to parity transformations in particle physics. In condensed matter physics, recent studies have demonstrated chiral fermions and their relevance in emergent phenomena closely related to topology1-3. The experimental verification of chiral phonons (bosons) remains challenging, however, despite their expected strong impact on fundamental physical properties4-6. Here we show experimental proof of chiral phonons using resonant inelastic X-ray scattering with circularly polarized X-rays. Using the prototypical chiral material quartz, we demonstrate that circularly polarized X-rays, which are intrinsically chiral, couple to chiral phonons at specific positions in reciprocal space, allowing us to determine the chiral dispersion of the lattice modes. Our experimental proof of chiral phonons demonstrates a new degree of freedom in condensed matter that is both of fundamental importance and opens the door to exploration of new emergent phenomena based on chiral bosons.