Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus.

Eukaryotic genomes are packaged into a 3-dimensional structure in the nucleus. Current methods for studying genome-wide structure are based on proximity ligation. However, this approach can fail to detect known structures, such as interactions with nuclear bodies, because these DNA regions can be too far apart to directly ligate. Accordingly, our overall understanding of genome organization remains incomplete. Here, we develop split-pool recognition of interactions by tag extension (SPRITE), a method that enables genome-wide detection of higher-order interactions within the nucleus. Using SPRITE, we recapitulate known structures identified by proximity ligation and identify additional interactions occurring across larger distances, including two hubs of inter-chromosomal interactions that are arranged around the nucleolus and nuclear speckles. We show that a substantial fraction of the genome exhibits preferential organization relative to these nuclear bodies. Our results generate a global model whereby nuclear bodies act as inter-chromosomal hubs that shape the overall packaging of DNA in the nucleus.

The low-energy Goldstone mode in a trapped dipolar supersolid.

A supersolid is a counter-intuitive state of matter that combines the frictionless flow of a superfluid with the crystal-like periodic density modulation of a solid1,2. Since the first prediction3 in the 1950s, experimental efforts to realize this state have focused mainly on helium, in which supersolidity remains unobserved4. Recently, supersolidity has also been studied in ultracold quantum gases, and some of its defining properties have been induced in spin-orbit-coupled Bose-Einstein condensates (BECs)5,6 and BECs coupled to two crossed optical cavities7,8. However, no propagating phonon modes have been observed in either system. Recently, two of the three hallmark properties of a supersolid-periodic density modulation and simultaneous global phase coherence-have been observed in arrays of dipolar quantum droplets9-11, where the crystallization happens in a self-organized manner owing to intrinsic interactions. Here we directly observe the low-energy Goldstone mode, revealing the phase rigidity of the system and thus proving that these droplet arrays are truly supersolid. The dynamics of this mode is reminiscent of the effect of second sound in other superfluid systems12,13 and features an out-of-phase oscillation of the crystal array and the superfluid density. This mode exists only as a result of the phase rigidity of the experimentally realized state, and therefore confirms the superfluidity of the supersolid.

Endoscopic vacuum therapy (eVAC) combined with continuous perianastomotic irrigation for prevention of anastomotic leak after surgical ampullectomy.

PURPOSE: Transduodenal surgical ampullectomy (tAMP) with papillary reimplantation is a valid alternative to pancreaticoduodenectomy for lesions of the periampullary region not amenable to endoscopic resection. As tAMP is burdened by high rates of biliopancreatic-enteric anastomotic leak, we tested preventive endoluminal vacuum therapy (eVAC) combined with post-operative continuous perianastomotic irrigation (CPI) to reduce such anastomotic leak. METHODS: Between 10/2013 and 09/2023, 37 patients undergoing laparotomic tAMP (with or without jejunal transposition) and papillary reimplantation at Hirslanden Klinik Zurich were retrospectively analysed; of these, 16 received prophylactic eVAC combined with CPI, while the remaining represented the historical cohort. RESULTS: The eVAC-CPI-group and the historical-cohort were homogeneous in demographic characteristics. Surgery in the prophylactic eVAC-CPI-group lasted about 30 min longer due to eVAC application (p = 0.008). The biliopancreatico-enteric anastomotic leak rates were 6.2% in the eVAC-CIP-group vs. 19.0% in the historical-cohort (p = 0.266). Along, a strong trend of less severe post-operative complications in general (p = 0.073), and borderline-significantly less cases of acute pancreatitis (p = 0.057) and tAMP-related re-operations or re-interventions (p = 0.057) in particular, were observed in the eVAC-CPI-group. The only anastomotic leak in the eVAC-CPI-group was successfully managed through repeated cycles of eVAC. The device was well tolerated by all patients; no vacuum/irrigation-related complications or malfunctioning occurred. CONCLUSION: Our study is the first to provide some technical insights demonstrating the safety and feasibility of a prophylactic approach with eVAC and perianastomotic irrigation to reduce anastomotic leak after tAMP. Increasing the number of subjects will confirm the benefit of our promising results.

Classical Drift in the Arnold Web Induces Quantum Delocalization Transition.

We demonstrate that quantum dynamical localization in the Arnold web of higher-dimensional Hamiltonian systems is destroyed by an intrinsic classical drift. Thus quantum wave packets and eigenstates may explore more of the intricate Arnold web than previously expected. Such a drift typically occurs, as resonance channels widen toward a large chaotic region or toward a junction with other resonance channels. If this drift is strong enough, we find that dynamical localization is destroyed. We establish that this drift-induced delocalization transition is universal and is described by a single transition parameter. Numerical verification is given using a time-periodically kicked Hamiltonian with a four-dimensional phase space.

Case report: "A healthy woman with exertional dyspnea: Indication of a pacemaker or not?"

The selection of patients with chronotropic incompetence (CI) for cardiac pacing therapy remains challenging. Here, we present a case of a 40-year-old woman with severe exertional dyspnea. The exercise test revealed a blunted increase in the heart rate (HR) (maximum of 110 bpm). Her exercise capacity significantly improved under atrial stimulation at 170 bpm using a temporary pacing lead. Therefore, we implanted a rate-adaptive dual-chamber pacemaker with a blended sensor. During follow-up exercise capacity normalized, and she had no residual exertional dyspnea at 6 months. This case highlights the potential value for individual assessments of CI to identify clear indications for pacemaker implantation.

Correlated fluorescence blinking in two-dimensional semiconductor heterostructures.

'Blinking', or 'fluorescence intermittency', refers to a random switching between 'ON' (bright) and 'OFF' (dark) states of an emitter; it has been studied widely in zero-dimensional quantum dots and molecules, and scarcely in one-dimensional systems. A generally accepted mechanism for blinking in quantum dots involves random switching between neutral and charged states (or is accompanied by fluctuations in charge-carrier traps), which substantially alters the dynamics of radiative and non-radiative decay. Here, we uncover a new type of blinking effect in vertically stacked, two-dimensional semiconductor heterostructures, which consist of two distinct monolayers of transition metal dichalcogenides (TMDs) that are weakly coupled by van der Waals forces. Unlike zero-dimensional or one-dimensional systems, two-dimensional TMD heterostructures show a correlated blinking effect, comprising randomly switching bright, neutral and dark states. Fluorescence cross-correlation spectroscopy analyses show that a bright state occurring in one monolayer will simultaneously lead to a dark state in the other monolayer, owing to an intermittent interlayer carrier-transfer process. Our findings suggest that bilayer van der Waals heterostructures provide unique platforms for the study of charge-transfer dynamics and non-equilibrium-state physics, and could see application as correlated light emitters in quantum technology.

Wake-Up Receiver for Underwater Acoustic Communication Using in Shallow Water.

A data frame transmitted over the underwater acoustic channel usually begins with a preamble. Therefore, underwater communication systems have a dedicated receiver that constantly listens to the preamble signals. A receiver that is to work effectively in shallow waters must have solutions that effectively reduce the impact of the permanently occurring multipath propagation. The article presents a solution based on complementary broadband signals. Initial tests were carried out using the Watermark simulator to determine its reliability in such a difficult propagation environment. The results of experimental tests carried out in a model pool are also included. Details of the implementation of the wake-up receiver are presented.

The RIG-I-like receptor LGP2 inhibits Dicer-dependent processing of long double-stranded RNA and blocks RNA interference in mammalian cells.

In vertebrates, the presence of viral RNA in the cytosol is sensed by members of the RIG-I-like receptor (RLR) family, which signal to induce production of type I interferons (IFN). These key antiviral cytokines act in a paracrine and autocrine manner to induce hundreds of interferon-stimulated genes (ISGs), whose protein products restrict viral entry, replication and budding. ISGs include the RLRs themselves: RIG-I, MDA5 and, the least-studied family member, LGP2. In contrast, the IFN system is absent in plants and invertebrates, which defend themselves from viral intruders using RNA interference (RNAi). In RNAi, the endoribonuclease Dicer cleaves virus-derived double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) that target complementary viral RNA for cleavage. Interestingly, the RNAi machinery is conserved in mammals, and we have recently demonstrated that it is able to participate in mammalian antiviral defence in conditions in which the IFN system is suppressed. In contrast, when the IFN system is active, one or more ISGs act to mask or suppress antiviral RNAi. Here, we demonstrate that LGP2 constitutes one of the ISGs that can inhibit antiviral RNAi in mammals. We show that LGP2 associates with Dicer and inhibits cleavage of dsRNA into siRNAs both in vitro and in cells. Further, we show that in differentiated cells lacking components of the IFN response, ectopic expression of LGP2 interferes with RNAi-dependent suppression of gene expression. Conversely, genetic loss of LGP2 uncovers dsRNA-mediated RNAi albeit less strongly than complete loss of the IFN system. Thus, the inefficiency of RNAi as a mechanism of antiviral defence in mammalian somatic cells can be in part attributed to Dicer inhibition by LGP2 induced by type I IFNs. LGP2-mediated antagonism of dsRNA-mediated RNAi may help ensure that viral dsRNA substrates are preserved in order to serve as targets of antiviral ISG proteins.

The meV XUV-RIXS facility at UE112-PGM1 of BESSY II.

Resonant inelastic X-ray scattering in the XUV-regime has been implemented at BESSY II, pushing for a few-meV bandwidth in inelastic X-ray scattering at transition metal M-edges, rare earth N-edges and the K-edges of light elements up to carbon with full polarization control. The new dedicated low-energy beamline UE112-PGM1 has been designed to provide 1 µm vertical and 20 µm horizontal beam dimensions that serve together with sub-micrometre solid-state sample positioning as the source point for a high-resolution plane grating spectrometer and a high-transmission Rowland spectrometer for rapid overview spectra. The design and commissioning results of the beamline and high-resolution spectrometer are presented. Helium autoionization spectra demonstrate a resolving power of the beamline better than 10 000 at 64 eV with a 300 lines mm-1 grating while the measured resolving power of the spectrometer in the relevant energy range is 3000 to 6000.

New states of matter with fine-tuned interactions: quantum droplets and dipolar supersolids.

Quantum fluctuations can stabilize Bose-Einstein condensates (BEC) against the mean-field collapse. Stabilization of the condensate has been observed in quantum degenerate Bose-Bose mixtures and dipolar BECs. The fine-tuning of the interatomic interactions can lead to the emergence of two new states of matter: liquid-like self-bound quantum droplets and supersolid crystals formed from these droplets. We review the properties of these exotic states of matter and summarize the experimental progress made using dipolar quantum gases and Bose-Bose mixtures. We conclude with an outline of important open questions that could be addressed in the future.

Does interprofessional team-training affect nurses' and physicians' perceptions of safety culture and communication practices? Results of a pre-post survey study.

BACKGROUND: Many hospitals seek to increase patient safety through interprofessional team-trainings. Accordingly, these trainings aim to strengthen important key aspects such as safety culture and communication. This study was designed to investigate if an interprofessional team-training, administered to a relatively small group of nurses and physicians would promote a change in healthcare professionals' perceptions on safety culture and communication practices throughout the hospital. We further sought to understand which safety culture aspects foster the transfer of trained communication practices into clinical practice. METHODS: We conducted a pre-post survey study using six scales to measure participants' perceptions of safety culture and communication practices. Mean values were compared according to profession and participation in training. Using multiple regression models, the relationship between safety culture and communication practices was determined. RESULTS: Before and after the training, we found high mean values for all scales. A significant, positive effect was found for the communication practices of the physicians. Participation in the training sessions played a variably relevant role in the communication practices. In addition, the multiple regression analyses showed that specific safety culture aspects have a cross-professional influence on communication practices in the hospital. CONCLUSIONS: This study suggest that interprofessional team-trainings of a small group of professionals can successfully be transferred into clinical practice and indicates the importance of safety culture aspects for such transfer processes. Thus, we recommend the consideration of safety culture aspects before starting a training intervention.

Anteversion Angle Measurement in Suspected Torsional Malalignment of the Femur in 3-Dimensional EOS vs Computed Tomography-A Validation Study.

BACKGROUND: Computed tomography (CT) scan is the standard for assessment of femoral torsion. This observational study was conducted to evaluate the comparability of the EOS radiation dose scanning system (EOS imaging, Paris, France) and the CT scan in patients with suspected torsional malalignment of the femur. METHODS: Patients with suspected torsional malalignment of the femur were included in a study for surgical planning. The primary endpoint was to compare the 3-dimensional radiological (EOS) imaging system with the CT scan to determine femoral anteversion (AV) angle. Three independent raters performed measurements. Comparability of CT scan and EOS values was assessed by Pearson correlation, t test, interobserver reliability, and intraobserver reliability (Cronbach alpha). RESULTS: About 34 femora were examined. Interobserver reliability/intraobserver reliability was 0.911 of 0.955 for EOS and 0.934 of 0.934 for CT scan. EOS system revealed an AV angle of 12.2° ± 10.0° (-15.0° to 32.0°). CT examinations showed an AV angle of 12.6° ± 9.2° (-3.2° to 35.6°). About 11 hips featured physiological AV, 14 hips showed decreased AV (<10°) or retroversion (<0°), and 9 hips showed increased AV (>20°). Overall, a strong Pearson correlation of τ = 0.855 and a highly significant correlation in the t test for both methods was seen. In patients with decreased AV, retroversion, or increased AV, Pearson correlation only resulted in a moderate/low correlation of τ = 0.495 and τ = 0.292. The t test showed no significant correlation at malrotation. CONCLUSION: In torsional malalignment, EOS does not have correlation with CT measurements. In contrast to CT scan, EOS allows femoral torsion measurement independent of legs' positioning.

Study of the Performance of DSSS UAC System Depending on the System Bandwidth and the Spreading Sequence.

A signal transmitted in an Underwater Acoustic Communication (UAC) system operating in a shallow-water channel suffers from strong time dispersion due to multipath propagation. This causes the Inter-Symbol Interference (ISI) observed in the received signal, which significantly limits the communication system's reliability and transmission rate. In such propagation conditions, the Direct-Sequence Spread Spectrum (DSSS) method is one of the solutions that make reliable data transmission possible. In systems with one-to-one communication, it ensures communication with a satisfactory Bit Error Rate (BER). Additionally, it makes it possible to implement the Code-Division Multiple Access (CDMA) protocol in underwater acoustic networks. This paper presents the results of simulation and experimental communication tests on a DSSS-based UAC system using three types of spreading sequence, namely m-sequences, Kasami codes and Gold codes, and occupying different bandwidths from 1 kHz to 8 kHz around a carrier frequency equal to 30 kHz. The UAC channel was simulated by impulse responses calculated by the virtual sources method and the UAC chanel models available in the Watermark simulator. The experimental tests were conducted in a model pool. Based on the obtained results, a transmission rate was estimated, which is possible to achieve in strong multipath propagation conditions, assuming reliability expressed as BER less than 0.001.

Intra-Individual Variability of Human Dental Pulp Stem Cell Features Isolated from the Same Donor.

It is primarily important to define the standard features and factors that affect dental pulp stem cells (DPSCs) for their broader use in tissue engineering. This study aimed to verify whether DPSCs isolated from various teeth extracted from the same donor exhibit intra-individual variability and what the consequences are for their differentiation potential. The heterogeneity determination was based on studying the proliferative capacity, viability, expression of phenotypic markers, and relative length of telomere chromosomes. The study included 14 teeth (6 molars and 8 premolars) from six different individuals ages 12 to 16. We did not observe any significant intra-individual variability in DPSC size, proliferation rate, viability, or relative telomere length change within lineages isolated from different teeth but the same donor. The minor non-significant variances in phenotype were probably mainly because DPSC cell lines comprised heterogeneous groups of undifferentiated cells independent of the donor. The other variances were seen in DPSC lineages isolated from the same donor, but the teeth were in different stages of root development. We also did not observe any changes in the ability of cells to differentiate into mature cell lines-chondrocytes, osteocytes, and adipocytes. This study is the first to analyze the heterogeneity of DPSC dependent on a donor.

The Effects of Cryogenic Storage on Human Dental Pulp Stem Cells.

Dental pulp stem cells (DPSCs) are a type of easily accessible adult mesenchymal stem cell. Due to their ease of access, DPSCs show great promise in regenerative medicine. However, the tooth extractions from which DPSCs can be obtained are usually performed at a period of life when donors would have no therapeutic need of them. For this reason, it is imperative that successful stem cell storage techniques are employed so that these cells remain viable for future use. Any such techniques must result in high post-thaw stem cell recovery without compromising stemness, proliferation, or multipotency. Uncontrolled-rate freezing is not a technically or financially demanding technique compared to expensive and laborious controlled-rate freezing techniques. This study was aimed at observing the effect of uncontrolled-rate freezing on DPSCs stored for 6 and 12 months. Dimethyl sulfoxide at a concentration of 10% was used as a cryoprotective agent. Various features such as shape, proliferation capacity, phenotype, and multipotency were studied after DPSC thawing. The DPSCs did not compromise their stemness, viability, proliferation, or differentiating capabilities, even after one year of cryopreservation at -80 °C. After thawing, they retained their stemness markers and low-level expression of hematopoietic markers. We observed a size reduction in recovery DPSCs after one year of storage. This observation indicates that DPSCs can be successfully used in potential clinical applications, even after a year of uncontrolled cryopreservation.

Irrigation and passive drainage of pancreatic stump after distal pancreatectomy in high-risk patients: an innovative approach to reduce pancreatic fistula.

INTRODUCTION: Postoperative pancreatic fistula (POPF) represents the most common form of morbidity after distal pancreatectomy (DP). The aim of this study was to illustrate an innovative technique of irrigation and passive drainage to reduce clinically relevant POPF (CR-POPF) incidence in high-risk patients undergoing DP. MATERIAL AND METHODS: Twelve consecutive high-risk patients received irrigation and passive drainage of the pancreatic stump with a Salem sump drainage after DP. The Salem sump was irrigated with 100 ml/h of Ringer solution for 2 postoperative days (POD). In the case of low-drain amylase and lipase levels on POD 3, the irrigation was reduced to 50 ml/h. Persistence of low-drain pancreatic enzymes on POD 4 allowed for interruption of irrigation and subsequent removal of drainage from POD 7 onward in the absence of evidence of any pancreatic fistula. RESULTS: Overall, 16.6% of the patients experienced a grade 3 or higher surgical complication. We experienced only one case of POPF: the fistula was classified as grade B and it was managed with radiologic drainage of the fluid collection. We did not experience any case of re-operation nor in-hospital mortality. CONCLUSIONS: Irrigation with passive drainage of the pancreatic stump after DP is an interesting approach for CR-POPF prevention in high-risk patients.

Clinical safety of the ProMRI implantable cardioverter-defibrillator systems during head and lower lumbar magnetic resonance imaging at 3 T: results of the ProMRI 3T ENHANCED Master study.

AIMS: There have been no published studies on the safety of magnetic resonance imaging (MRI) at 3 Tesla (3 T) in patients with MRI-conditional implantable cardioverter-defibrillators (ICDs). The aim of this study was to assess clinical safety of the Biotronik ProMRI ICD system during non-diagnostic head and lower lumbar scans under 3 T MRI conditions. METHODS AND RESULTS: The study enrolled 129 patients at 12 sites in Australia, Singapore, and Europe. Predefined head and lower lumbar MR scans (total duration ≈30 min) were performed in 112 patients. Three primary endpoints were evaluated from the pre-MRI to the 1-month post-MRI visit: (i) freedom from serious adverse device effects (SADEs) related to MRI (hypothesized to be >90%); (ii) pacing threshold invariance for all leads (geometric mean of the patient-wise ratios for 1 month vs. pre-MRI was hypothesized to be <1.07); and (iii) sensing amplitude invariance (geometric mean of the ratios was hypothesized to be >0.993). No MRI-related SADE occurred (SADE-free rate 100%, 95% confidence interval 95.98-100%). Pacing threshold and sensing amplitudes fulfilled the invariance hypotheses with high statistical significance (P < 0.0013). No threshold increase >0.5 V or sensing amplitude decrease by >50% was observed (secondary endpoints). Lead impedances, battery capacity, and detection and treatment of arrhythmias by ICDs were not affected by MRI scans. CONCLUSION: The head and lower lumbar scans under specific 3 T MRI conditions were safe in the investigated MR-conditional ICD systems. There was no evidence of harm to the patients or any negative influence of the MRI scan on the implanted systems.

Avoiding inappropriate therapy of single-lead implantable cardioverter-defibrillator by using atrial-sensing electrodes.

INTRODUCTION: The single-chamber implantable cardioverter-defibrillator (ICD) can be associated with more frequent inappropriate therapies compared with dual-chamber ICDs, when they are accompanied by a simpler implantation procedure. The aim of this study was to investigate whether the use of a single-lead ICD system with atrial-sensing electrodes results in a reduction of inappropriate ICD therapy. METHODS AND RESULTS: The study population consisted of 212 consecutive patients, who underwent primary prophylactic single-lead ICD implantation at our institute. A ventricular lead with atrial-sensing electrodes was implanted in 77 patients (36%; Group-VDD) and a ventricular lead without atrial-sensing electrodes was implanted in 135 patients (64%; Group-VVI). Procedural and follow-up data were collected in a prospective registry. A higher prevalence of atrial fibrillation was present in Group-VDD. There were no other significant differences in patient baseline characteristics (age, sex, and other comorbidities) or follow-up period between the two groups. The operative parameters including fluoroscopic burden showed no significant differences between Group-VDD and Group-VVI. During a mean follow-up period of 697 ± 392 days, 26 patients (12%) experienced appropriate ICD therapies and 13 patients (6%) suffered inappropriate ICD therapies. The incidence of inappropriate ICD therapies in Group-VDD was significantly lower as compared to that of Group-VVI (1/77 [1%] vs 12/135 [9%]; log-rank, P = 0.028). The incidence of appropriate ICD therapies and the occurrence of device-related complications showed no significant difference between the two groups. CONCLUSION: Single-lead ICD with atrial-sensing electrodes shows a lower incidence of inappropriate ICD therapy compared with the absence of atrial-sensing electrodes, without additional operative burden or increased complications.

Anisotropic Superfluid Behavior of a Dipolar Bose-Einstein Condensate.

We present transport measurements on a dipolar superfluid using a Bose-Einstein condensate of ^{162}Dy with strong magnetic dipole-dipole interactions. By moving an attractive laser beam through the condensate we observe an anisotropy in superfluid flow. This observation is compatible with an anisotropic critical velocity for the breakdown of dissipationless flow, which, in the spirit of the Landau criterion, can directly be connected to the anisotropy of the underlying dipolar excitation spectrum. In addition, the heating rate above this critical velocity reflects the same anisotropy. Our observations are in excellent agreement with simulations based on the Gross-Pitaevskii equation and highlight the effect of dipolar interactions on macroscopic transport properties, rendering dissipation anisotropic.

Human heterologous liver cells transiently improve hyperammonemia and ureagenesis in individuals with severe urea cycle disorders.

BACKGROUND: Urea cycle disorders (UCDs) still have a poor prognosis despite several therapeutic advancements. As liver transplantation can provide a cure, liver cell therapy (LCT) might be a new therapeutic option in these patients. METHODS: Twelve patients with severe UCDs were included in this prospective clinical trial. Patients received up to six infusions of cryopreserved human heterologous liver cells via a surgically placed catheter in the portal vein. Portal vein pressure, portal vein flow, and vital signs were monitored continuously. Calcineurin inhibitors and steroids were used for immunosuppression. In four patients, ureagenesis was determined with stable isotopes. Number and severity of hyperammonemic events and side effects of immunosuppression were analyzed during an observation period of up to 2 years. RESULTS: No study-related mortality was observed. The application catheter dislocated in two children. No significant side effects of catheter application or cell infusion were noted in the other ten patients. The overall incidence of infections did not differ significantly from a historical control group, and no specific side effects of immunosuppression were found. Seven patients were treated per protocol and could be analyzed for efficacy. Severe metabolic crises could be prevented in all of these patients, moderate crises in four of seven. Ureagenesis increased after cell infusion in all patients investigated. CONCLUSIONS: We found a favorable safety profile with respect to catheter placement, intraportal liver cell infusion, and immunosuppression. More than half of the children treated per protocol experienced metabolic stabilization and could be safely bridged to liver transplantation.