bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Octagon at large M
Authors: Argurio Riccardo , Bertolini Matteo , Franco Sebastián , García-Valdecasas Eduardo , Meynet Shani , Pasternak Antoine , Tatitscheff Valdo 
Published: November 2022

Abstract
Recently, the first instance of a model of D-branes at Calabi-Yau singularities where supersymmetry is broken dynamically into stable vacua has been proposed. This construction was based on a system of N regular and M = 1 fractional branes placed at the tip of the so-called (orientifolded) Octagon singularity. In this paper we show that this model admits a large M generalization, having the same low energy effective dynamics. This opens up the possibility that the effect on geometry is smooth, and amenable to describing the gauge theory all along the RG flow, including the deep IR, in terms of a weakly coupled gravity dual background. The relevance of this result in the wider context of the string landscape and the Swampland program is also discussed.
Optimal Narain CFTs from codes
Authors: Angelinos Nikolaos , Chakraborty Debarghya , Dymarsky Anatoly 
Published: November 2022

Abstract
Recently established connection between additive codes and Narain CFTs provides a new tool to construct theories with special properties and solve modular bootstrap constraints by reducing them to algebraic identities. We generalize previous constructions to include many new theories, in particular we show that all known optimal Narain theories, i.e. those maximizing the value of spectral gap, can be constructed from codes. For asymptotically large central charge c we show there are code theories with the spectral gap growing linearly with c, with the coefficient saturating the conjectural upper bound. We therefore conjecture that optimal Narain theories for any value of c can be obtained from codes.
The role of tyrosine hydroxylase–dopamine pathway in Parkinson’s disease pathogenesis
Authors: Zhou Zhi Dong , Saw Wuan Ting , Ho Patrick Ghim Hoe , Zhang Zhi Wei , Zeng Li , Chang Ya Yin , Sun Alfred Xu Yang , Ma Dong Rui , Wang Hong Yan , Zhou Lei , Lim Kah Leong , Tan Eng-King 
Published: November 2022

Abstract
Background
Parkinson’s disease (PD) is characterized by selective and progressive dopamine (DA) neuron loss in the substantia nigra and other brain regions, with the presence of Lewy body formation. Most PD cases are sporadic, whereas monogenic forms of PD have been linked to multiple genes, including Leucine kinase repeat 2 (LRRK2) and PTEN-induced kinase 1 (PINK1), two protein kinase genes involved in multiple signaling pathways. There is increasing evidence to suggest that endogenous DA and DA-dependent neurodegeneration have a pathophysiologic role in sporadic and familial PD.

Methods
We generated patient-derived dopaminergic neurons and human midbrain-like organoids (hMLOs), transgenic (TG) mouse and Drosophila models, expressing both mutant and wild-type (WT) LRRK2 and PINK1. Using these models, we examined the effect of LRRK2 and PINK1 on tyrosine hydroxylase (TH)–DA pathway.

Results
We demonstrated that PD-linked LRRK2 mutations were able to modulate TH–DA pathway, resulting in up-regulation of DA early in the disease which subsequently led to neurodegeneration. The LRRK2-induced DA toxicity and degeneration were abrogated by wild-type (WT) PINK1 (but not PINK1 mutations), and early treatment with a clinical-grade drug, α-methyl-L-tyrosine (α-MT), a TH inhibitor, was able to reverse the pathologies in human neurons and TG Drosophila models. We also identified opposing effects between LRRK2 and PINK1 on TH expression, suggesting that functional balance between these two genes may regulate the TH–DA pathway.

Conclusions
Our findings highlight the vital role of the TH–DA pathway in PD pathogenesis. LRRK2 and PINK1 have opposing effects on the TH–DA pathway, and its balance affects DA neuron survival. LRRK2 or PINK1 mutations can disrupt this balance, promoting DA neuron demise. Our findings provide support for potential clinical trials using TH–DA pathway inhibitors in early or prodromic PD.
Correction to: Eigenvalue bifurcation in doubly nonlinear problems with an application to surface plasmon polaritons
Authors: Dohnal Tomáš , Romani Giulio 
Published: November 2022

AbstractThis erratum corrects some errors which appear in [Dohnal T., Romani G., Eigenvalue bifurcation in doubly nonlinear problems with an application to surface plasmon polaritons, Nonlinear Differ. Equ. Appl. 28, 9 (2021).]. In particular, it replaces the (unsuitable) definition of isolatedness of the linear eigenvalue, from which the bifurcation occurs.
Patients that maintain their pre-injury level of physical activity 3–5 years after ACL reconstruction are, 18 months after surgery, characterised by higher levels of readiness to return to sport
Authors: Beischer S. , Hamrin Senorski E. , Thomeé R. 
Published: November 2022

AbstractPurposeTo characterise patients who had returned to their pre-injury physical activity (PA) or higher at 18 months and maintained that level of PA 3–5 years after the primary ACL reconstruction and to describe the level, frequency, and type of PA participation during the first 5 years after ACL reconstruction MethodData, from follow-ups at 18 months and 3–5 years after an ACL reconstruction, were extracted from a rehabilitation-specific register. Patients, 15–65 years of age, were included. The data comprised patient-reported outcomes and the results from two questions with respect to the level, frequency, and type of PA. Comparisons were made between patients who had and had not maintained their pre-injury level of PA at the follow-up 3–5 years after an ACL reconstruction.ResultsA total of 272 patients met the inclusion criteria. The mean follow-up time was 3.8 years (min–max: 2.9–5.1) after the ACL reconstruction. Of patients who had returned to their pre-injury or a higher level of PA at the 18 month follow-up (n= 114), 68% (n= 78) maintained that level at the 3- to 5-year follow-up after ACL reconstruction. These patients reported a higher level of psychological readiness to return to sport (98 versus 79;p= 0.013). Moreover, these patients were 6.0 years older (p= 0.016) and were characterised by male sex (56% versus 44%;p= 0.028) and a lower level of pre-injury PA (p= 0.013). At the follow-up 3–5 years after the ACL reconstruction, more than 90% met the recommendations for PA. However, the prevalence of physical inactivity had increased and the involvement in organised PA had decreased compared with the 18-month follow-up.ConclusionsTwo out of three patients who have returned to their previous level of PA at 18 months can be expected to maintain that level, 3–5 years following ACL reconstruction. These patients were mainly characterised by a higher level of psychological readiness, especially in patients who participated in knee-strenuous sport and were younger than 20 years of age. The results of this study suggest that patients become more physically inactive over time, implicating the importance of clinicians helping patients find a suitable PA that may help patients maintain an active lifestyle.
Modeling a remanufacturing reverse logistics planning problem: some insights into disruptive technology adoption
Authors: Yu Hao 
Published: November 2022

AbstractRemanufacturing is the process to restore the functionality of high-value end-of-life (EOL) products, which is considered a substantial link in reverse logistics systems for value recovery. However, due to the uncertainty of the reverse material flow, the planning of a remanufacturing reverse logistics system is complex. Furthermore, the increasing adoption of disruptive technologies in Industry 4.0/5.0, e.g., the Internet of things (IoT), smart robots, cloud-based digital twins, and additive manufacturing, has shown great potential for a smart paradigm transition of remanufacturing reverse logistics operations. In this paper, a new mixed-integer program is modeled for supporting several tactical decisions in remanufacturing reverse logistics, i.e., remanufacturing setups, production planning and inventory levels, core acquisition and transportation, and remanufacturing line balancing and utilization. The model is further extended by incorporating utilization-dependent nonlinear idle time cost constraints and stochastic takt time to accommodate different real-world scenarios. Through a set of numerical experiments, the influences of different demand patterns and idle time constraints are revealed. The potential impacts of disruptive technology adoption in remanufacturing reverse logistics are also discussed from managerial perspectives, which may help remanufacturing companies with a smart and smooth transition in the Industry 4.0/5.0 era.
The effect of ketamine and D-cycloserine on the high frequency resting EEG spectrum in humans
Authors: Nottage J. F. , Gabay A. , De Meyer K. , Herrik K. F. , Bastlund J. F. , Christensen S. R. , Gijsen S. , Mehta M. A. 
Published: November 2022

Abstract
Rationale
Preclinical studies indicate that high-frequency oscillations, above 100 Hz (HFO:100–170 Hz), are a potential translatable biomarker for pharmacological studies, with the rapid acting antidepressant ketamine increasing both gamma (40–100 Hz) and HFO.

Objectives
To assess the effect of the uncompetitive NMDA antagonist ketamine, and of D-cycloserine (DCS), which acts at the glycine site on NMDA receptors on HFO in humans.

Methods
We carried out a partially double-blind, 4-way crossover study in 24 healthy male volunteers. Each participant received an oral tablet and an intravenous infusion on each of four study days. The oral treatment was either DCS (250 mg or 1000 mg) or placebo. The infusion contained 0.5 mg/kg ketamine or saline placebo. The four study conditions were therefore placebo-placebo, 250 mg DCS-placebo, 1000 mg DCS-placebo, or placebo-ketamine.

Results
Compared with placebo, frontal midline HFO magnitude was increased by ketamine (p = 0.00014) and 1000 mg DCS (p = 0.013). Frontal gamma magnitude was also increased by both these treatments. However, at a midline parietal location, only HFO were increased by DCS, and not gamma, whilst ketamine increased both gamma and HFO at this location. Ketamine induced psychomimetic effects, as measured by the PSI scale, whereas DCS did not increase the total PSI score. The perceptual distortion subscale scores correlated with the posterior low gamma to frontal high beta ratio.

Conclusions
Our results suggest that, at high doses, a partial NMDA agonist (DCS) has similar effects on fast neural oscillations as an NMDA antagonist (ketamine). As HFO were induced without psychomimetic effects, they may prove a useful drug development target.
Analysis of complex drugs by comprehensive two-dimensional gas chromatography and high-resolution mass spectrometry: detailed chemical description of the active pharmaceutical ingredient sodium bituminosulfonate and its process intermediates
Authors: Schwalb Lukas , Tiemann Ole , Käfer Uwe , Gröger Thomas , Rüger Christopher Paul , Gayko Guido , Zimmermann Ralf 
Published: November 2022

AbstractThe European pharmacopeia provides analytical methods for the chemical characterization of active pharmaceutical ingredients (APIs). However, the complexity of some APIs exceeds the limitations of the currently prevailing physicochemical methods. Sodium bituminosulfonate (SBS) is described by the collection of key parameters of generalizing criteria such as dry matter, sulfur and sodium content, and neutrality, but techniques to unravel the complexity on a molecular level are lacking. We present a study based on online derivatization with tetramethylammonium hydroxide in combination with comprehensive two-dimensional gas chromatography coupled to an electron ionization high-resolution time-of-flight mass spectrometer (GC × GC-HR-ToF–MS) for the chemical description of SBS as well as its process intermediates. The application of GC × GC allowed the comprehensive description of the chemical components in the API and the process intermediates for the first time. Furthermore, it was possible to classify peaks regarding their elemental and structural composition based on accurate mass information, elution behavior, and mass fragmentation pattern. This work demonstrates not only the general applicability, advantages but also limitations of GC × GC for the characterization of APIs for complex drugs.Graphical Abstract
A novel pentavalent vaccine candidate completely protects against Acinetobacter baumannii in a mouse model of peritonitis
Authors: Hagag Yomna A. , Said Heba Shehta , Kenawy Hany I. , Hassan Ramadan 
Published: November 2022

Abstract

Acinetobacter baumannii is considered as one of the most virulent and infectious organisms that have an increased ability to both evade host immune response and resist various classes of antibiotics, leading to life-threatening infections. Multiple virulence factors have been implicated in the high prevalence rate of A. baumannii in hospitalized and immunocompromised patients. Moreover, improper use of antibiotics has led to the emergence of extensive drug-resistant strains that urgently require alternative strategies to control this superbug. Unfortunately, the availability of a licensed vaccine against A. baumannii infections is still challenged by the vast diversity among A. baumannii strains. Here, we report the development of a novel pentavalent vaccine candidate composed of two recombinant proteins (Wza and YiaD) and a pool of capsular polysaccharides isolated from 3 clinical isolates. We tested this new vaccine in vivo in a mouse model of peritonitis against the standard strain ATCC 19606 in addition to 3 clinical isolates of A. baumannii. Immunization with this vaccine completely protected the challenged mice with 100% survival rate in the case of all the tested bacteria. Further clinical studies are urgently needed to evaluate the efficacy and safety of this proprietary vaccine to protect patients from A. baumannii lethal infections.

Key points
• Recombinant proteins pool (Wza and YiaD) immunization led to a synergistic immune response.
• Capsular polysaccharides pool induced up to 90% protection of tested clinical isolates.
• The pentavalent pool showed superiority with 100% survival of immunized mice.
Cephalosporins as key lead generation beta-lactam antibiotics
Authors: Lin Xuemei , Kück Ulrich 
Published: November 2022

Abstract
Antibiotics are antibacterial compounds that interfere with bacterial growth, without harming the infected eukaryotic host. Among the clinical agents, beta-lactams play a major role in treating infected humans and animals. However, the ever-increasing antibiotic resistance crisis is forcing the pharmaceutical industry to search for new antibacterial drugs to combat a range of current and potential multi-resistant bacterial pathogens. In this review, we provide an overview of the development, innovation, and current status of therapeutic applications for beta-lactams with a focus on semi-synthetic cephalosporins. Cephalosporin C (CPC), which is a natural secondary metabolite from the filamentous fungus Acremonium chrysogenum, plays a major and demanding role in both producing modern antibiotics and developing new ones. CPC serves as a core compound for producing semi-synthetic cephalosporins that can control infections with different resistance mechanisms. We therefore summarize our latest knowledge about the CPC biosynthetic pathway and its regulation in the fungal host. Finally, we describe how CPC serves as a key lead generation source for the in vitro and better, in vivo synthesis of 7-aminocephalosporanic acid (7-ACA), the major core compound for the pharmaceutical synthesis of current and future semi-synthetic cephalosporins.

Key points
•Latest literature on cephalosporin generations
•Biotechnical production of cephalosporins
•In vivo production of 7-ACA
The Impact of Depression in Patients Undergoing Emergency Abdominal Surgery: An Exploratory Study
Authors: Maroof Hanna , Van Chi Mai Dinh , El‐Kafsi Jihene , De'Ath Henry D. 
Published: November 2022

AbstractBackgroundDepression is associated with poorer outcomes in many disease states. However, its significance in abdominal surgery is unknown. This study investigated rates of depression in emergency abdominal surgery patients and its effects on outcomes.MethodsA retrospective cohort study was conducted across two UK sites and included all adult patients undergoing emergency abdominal surgery. Primary outcome was the complication rate in depressed patients, including the incidence of post‐operative delirium. Secondary outcomes included mortality, time to oral intake and analgesia.ResultsTwo hundred and ten patients were identified. The commonest indication for surgery was appendicitis (53.3%) followed by small bowel obstruction (9.5%). There was a 17% (n = 36) incidence of depression amongst patients, most of whom (n = 26, 72.2%) were taking antidepressants. Depression was associated with male sex (M:F 27:9 p = 0.003), higher median BMI (28 vs. 25 p = 0.013) and previous surgery (47.2% vs. 28.7% p = 0.032). Despite a higher incidence of post‐operative delirium, increased time to oral analgesia and greater 30‐day readmission rates in the depression cohort, multivariate analyses showed depression was not a significant independent predictor of these (OR 2.181, 95%CI 0.310–15.344; p = 0.433, OR 0.07, 95%CI 0.499–1.408; p = 0.348 and OR 1.367, 95%CI 0.102–18.34, respectively). Complication and mortality rates between depressed and non‐depressed individuals were similar.ConclusionSignificant numbers of patients undergoing emergency abdominal surgery have depression, but this did not adversely affect post‐operative outcomes. The study included relatively small numbers of participants undergoing procedures with straightforward recovery. Larger population studies are therefore required and should focus on investigating the association between major emergency surgeries with post‐operative delirium and uncontrolled pain.
Influence of the linewidth enhancement factor on the signal pattern of Fourier domain mode-locked lasers
Authors: Aşırım Özüm Emre , Huber Robert , Jirauschek Christian 
Published: November 2022

AbstractFourier domain mode-locked (FDML) lasers are frequency-swept lasers that operate in the near-infrared region and allow for the attainment of a large sweep-bandwidth, high sweep-rate, and a narrow instantaneous linewidth, all of which are usually quite desirable characteristics for a frequency-swept laser. They are used in various sensing and imaging applications but are most commonly noted for their practical use in optical coherence tomography (OCT). An FDML laser consists of three fundamental components, which are the semiconductor optical amplifier (SOA), optical fiber, and the wavelength-swept optical bandpass filter. Due to the complicated nonlinear dynamics of FDML lasers that stems from the coaction of these three components, often the output signal of an FDML laser is corrupted by frequent power-dips of varying depth and duration. The frequent recurrence of these dips in the FDML laser signal pattern lowers the quality of imaging and detection. This study examines the role of the linewidth enhancement factor (LWEF) of an SOA in reducing both the strength and the number of power-dips throughout the FDML laser operation. The results are obtained using numerical computations that are in agreement with experimental data. The study aims to show that using SOAs with low LWEFs, the number of power-dips can be reduced for a better detection and imaging quality.
Combined impact of ENSO and Antarctic Oscillation on austral spring precipitation in Southeastern South America (SESA)
Authors: Hu Xinjia , Eichner Jan , Gong Daoyi , Barreiro Marcelo , Kantz Holger 
Published: November 2022

AbstractSoutheastern South America (SESA)’s precipitation is thought to be influenced by both El Niño Southern Oscillation (ENSO) and Antarctic Oscillation (AAO), especially in austral spring. Previous studies conclude AAO can modulate ENSO’s impact on precipitation over the SESA region without differentiating between El Niño and La Niña events. In the present study, we use composite analysis to further explore the combined impact of AAO and ENSO on austral spring precipitation over Southeastern South America (SESA) to answer this question and explain the dynamic mechanisms. We found that different AAO phases can influence La Niña’s impact on SESA austral spring precipitation considerably, while this does not apply for El Niño events. From our analysis, we found that AAO exerts more impact on austral spring precipitation over SESA compared to ENSO during La Niña years by influencing northerly wind and southward water vapor flux, which contributes most of the moisture into the SESA region, due to the strengthening of South Atlantic subtropical anticyclone and stronger meridional gradient in low-level pressure. Besides, there is an upper-level trough (ridge) over subtropical South America indicating advection of cyclonic (anticyclonic) vorticity inducing anomalous increase (decrease) of precipitation over that region during La Niña/AAO− (La Niña/AAO+). We do not see this opposite difference within El Niño groups combined with different phases of AAO.
Save our surgeons (SOS) – an explorative comparison of surgeons’ muscular and cardiovascular demands, posture, perceived workload and discomfort during robotic vs. laparoscopic surgery
Authors: Krämer Bernhard , Neis Felix , Reisenauer Christl , Walter Christina , Brucker Sara , Wallwiener Diethelm , Seibt Robert , Gabriel Julia , Rieger Monika A. , Steinhilber Benjamin 
Published: November 2022

Abstract
Purpose
Conventional laparoscopic surgery (CLS) imposes an increased risk of work-related musculoskeletal disorders. Technical innovations, such as robotic-assisted laparoscopic surgery (RALS), may provide ergonomic benefits. We compare the surgeon`s work-related demands of CLS vs RALS for benign hysterectomies.

Methods
Five specialists (3 females, 2 males) each performed four RALS and four CLS as part of their daily clinical routine. During the surgical procedures, muscular demands were assessed by bipolar surface electromyograms of the descendent trapezius, extensor digitorum and flexor carpi radialis muscles as well as cardio-vascular demands by electrocardiography, and neck, arm and torso posture by gravimetrical position sensors. Additionally, the subjects rated their level of perceived workload (NASA TLX questionnaire with 6 dimension) and musculoskeletal discomfort (11-point Likert-scale, 0–10).

Results
Muscular demands of the trapezius and flexor carpi radialis muscles were lower with RALS but extensor digitorum demands increased. Cardiovascular demands were about 9 heart beats per minute (bpm) lower for RALS compared to CLS with a rather low median level for both surgical techniques (RALS = 84 bpm; CLS 90 bpm). The posture changed in RALS with an increase in neck and torso flexion, and a reduction in abduction and anteversion position of the right arm. The perceived workload was lower in the physical demands dimension but higher in the mental demands dimension during RALS. Subjective musculoskeletal discomfort was rare during both surgical techniques.

Conclusions
This explorative study identified several potential ergonomic benefits related to RALS which now can be verified by studies using hypothesis testing designs. However, potential effects on muscular demands in the lower arm extensor muscles also have to be addressed in such studies.