bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical and experimental investigations of a microwave interferometer for the negative ion source SPIDER
Authors: Agnello R. , Cavazzana R. , Furno I. , Jacquier R. , Pasqualotto R. , Sartori E. , Serianni G.
Published: March 2023

The electron density close to the extraction grids and the co-extracted electrons represent a crucial issue when operating negative ion sources for fusion reactors. An excessive electron density in the plasma expansion region can indeed inhibit the negative ion production and introduce potentially harmful electrons in the accelerator. Among the set of plasma and beam diagnostics proposed for SPIDER upgrade, a heterodyne microwave (mw) interferometer at 100 GHz is currently being explored as a possibility to measure electron density in the plasma extraction region. The major issue in applying this technique in SPIDER is the poor accessibility of the probing microwave beam through the source metal walls and the long distance of 4 m at which mw modules should be located outside the vacuum vessel. Numerical investigations in a full-scale geometry showed that the power transmitted through the plasma source apertures was above the signal-to-noise ratio threshold for the microwave module sensitivity. An experimental proof-of-principle of the setup to assess the possibility of signal phase detection was then performed. The microwave system was tested on an experimental full-scale test-bench mimicking SPIDER viewports accessibility constraints, including the presence of a SPIDER-like plasma. The outcome of first tests revealed that, despite the geometrical constraints, in certain conditions, the phase detection, and, therefore, electron density measurements are possible. The main issue arises from decoupling the one-pass signal from spurious multipaths generated by mw beam reflections, requiring signal cross correlation analysis. These preliminary tests demonstrate that despite the 4 m distance between the mw modules and the presence of metal walls, plasma density measurement is possible when the 80 mm diameter ports are available. In this contribution, we discuss the numerical simulations, the preliminary experimental tests and suggest design upgrades of the interferometric setup to enhance signal transmission.
MUX64, an analogue 64-to-1 multiplexer ASIC for the ATLAS high granularity timing detector
Authors: Xu Z. , Zhang L. , Huang X. , Sha Q. , Ge Z. , Che Y. , Gong D. , Hou S. , Zhang J. , Liu T. , Liang Z. , Zhang L. , Ye J. , Qi M.
Published: March 2023

We present the design and the performance of MUX64, a 64-to-1 analogue multiplexer ASIC for the ATLAS High Granularity Timing Detector (HGTD). The MUX64 transmits one of its 64 inputs selected by six address lines for the voltages or temperatures being monitored to an lpGBT ADC channel. The prototype ASICs fabricated in TSMC 130 nm CMOS technology were prepared in wire-bonding and QFN88 packaging format. A total of 280 chips was examined for functionality and quality assurance. The accelerated aging test conducted at 85 °C shows negligible degradation over 16 days.
Low-rank approximations to accelerate hybrid functional enabled real-time time-dependent density functional theory within plane waves
Authors: Li Jielan , Wan Lingyun , Jiao Shizhe , Hu Wei , Yang Jinlong
Published: March 2023

Real-time time-dependent density functional theory (RT-TDDFT) is a powerful tool for predicting excited-state dynamics. Herein, we combine the adaptively compressed exchange (ACE) operator with interpolative separable density fitting (ISDF) algorithm to accelerate the hybrid functional calculations in RT-TDDFT (hybrid RT-TDDFT) dynamics simulations for molecular and periodic systems within plane waves. Under this low-rank representation, we demonstrate that the ACE-ISDF enabled hybrid RT-TDDFT can yield accurate excited-state dynamics, but much faster than conventional calculations. Furthermore, we describe a massively parallel implementation of ACE-ISDF enabled hybrid RT-TDDFT dynamics simulations containing thousands of atoms (1728 atoms), which can scale up to 3456 central processing unit cores on modern supercomputers.
The Ratios Conjecture and upper bounds for negative moments of 𝐿-functions over function fields
Authors: Bui Hung , Florea Alexandra , Keating Jonathan
Published: March 2023

We prove special cases of the Ratios Conjecture for the family of quadratic Dirichlet

L
L

-functions over function fields. More specifically, we study the average of

L
(
1

/

2
+
α
,

χ
D

)

/

L
(
1

/

2
+
β
,

χ
D

)

L(1/2+\alpha ,\chi _D)/L(1/2+\beta ,\chi _D)

, when

D
D

varies over monic, square-free polynomials of degree

2
g
+
1

2g+1

over

F

q

[
x
]

\mathbb {F}_q[x]

, as

g
→
∞

g \to \infty

, and we obtain an asymptotic formula when

ℜ
β
≫

g

−
1

/

2
+
ε

\Re \beta \gg g^{-1/2+\varepsilon }

. We also study averages of products of

2
2

over

2
2

and

3
3

over

3
3

L
L

-functions, and obtain asymptotic formulas when the shifts in the denominator have real part bigger than

g

−
1

/

4
+
ε

g^{-1/4+\varepsilon }

and

g

−
1

/

6
+
ε

g^{-1/6+\varepsilon }

respectively. The main ingredient in the proof is obtaining upper bounds for negative moments of

L
L

-functions. The upper bounds we obtain are expected to be almost sharp in the ranges described above.
Prophylactic onlay mesh placement techniques for optimal abdominal wall closure: randomized controlled trial in an ex vivo biomechanical model
Authors: Stephens Ian , Conroy Jack , Winter Des , Simms Ciaran , Bucholc Magda , Sugrue Michael
Published: March 2023

Background

Incisional hernias occur after up to 40 per cent of laparotomies. Recent RCTs have demonstrated the role of prophylactic mesh placement in reducing the risk of developing an incisional hernia. An onlay approach is relatively straightforward; however, a variety of techniques have been described for mesh fixation. The biomechanical properties have not been interrogated extensively to date.

Methods

This ex vivo randomized controlled trial using porcine abdominal wall investigated the biomechanical properties of three techniques for prophylactic onlay mesh placement at laparotomy closure. A classical onlay, anchoring onlay, and novel bifid onlay approach were compared with small-bite primary closure. A biomechanical abdominal wall model and ball burst test were used to assess transverse stretch, bursting force, and loading characteristics.

Results

Mesh placement took an additional 7–15 min compared with standard primary closure. All techniques performed similarly, with no clearly superior approach. The minimum burst force was 493 N, and the maximum 1053 N. The classical approach had the highest mean burst force (mean(s.d.) 853(152) N). Failure patterns fell into either suture-line or tissue failures. Classical and anchoring techniques provided a second line of defence in the event of primary suture failure, whereas the bifid method demonstrated a more compliant loading curve. All mesh approaches held up at extreme quasistatic loads.

Conclusion

Subtle differences in biomechanical properties highlight the strengths of each closure type and suggest possible uses. The failure mechanisms seen here support the known hypotheses for early fascial dehiscence. The influence of dynamic loading needs to be investigated further in future studies.
The occipital place area represents visual information about walking, not crawling
Authors: Jones Christopher M , Byland Joshua , Dilks Daniel D
Published: March 2023

Recent work has shown that the occipital place area (OPA)—a scene-selective region in adult humans—supports “visually guided navigation” (i.e. moving about the local visual environment and avoiding boundaries/obstacles). But what is the precise role of OPA in visually guided navigation? Considering humans move about their local environments beginning with crawling followed by walking, 1 possibility is that OPA is involved in both modes of locomotion. Another possibility is that OPA is specialized for walking only, since walking and crawling are different kinds of locomotion. To test these possibilities, we measured the responses in OPA to first-person perspective videos from both “walking” and “crawling” perspectives as well as for 2 conditions by which humans do not navigate (“flying” and “scrambled”). We found that OPA responded more to walking videos than to any of the others, including crawling, and did not respond more to crawling videos than to flying or scrambled ones. These results (i) reveal that OPA represents visual information only from a walking (not crawling) perspective, (ii) suggest crawling is processed by a different neural system, and (iii) raise questions for how OPA develops; namely, OPA may have never supported crawling, which is consistent with the hypothesis that OPA undergoes protracted development.
Junctional rhythm produces retrograde flow in the whole Fontan system: cardiac magnetic resonance–derived flow documentation—a case report
Authors: Ferrari Irene , Shehu Nerejda , Stern Heiko , Meierhofer Christian
Published: March 2023

Background

Arrhythmias after palliation of congenital malformations with functional monoventricle by different Fontan modifications are very common. Sinus node dysfunction and junctional rhythm are known to have a high prevalence and a detrimental impact on the optimal functioning of Fontan circulations. Maintaining sinus node function has high prognostic significance, and some cases have even been described where atrial pacing with restoring of atrioventricular synchrony was able to reverse protein-losing enteropathy with overt failure of the Fontan.

Case summary

A 12-year-old boy with a complex congenital malformation (double outlet right ventricle, transposition of the great arteries, pulmonary stenosis, and straddling atrioventricular valve) palliated through a modified Fontan (total cavopulmonary connection with a fenestrated extracardiac 18 mm Gore-Tex conduit) presented for cardiac magnetic resonance evaluation for mild asthenia and worsening of exercise tolerance. Flow profiles in all the regions of the Fontan (both caval veins and right and left pulmonary arteries) showed a small amount of retrograde flow; a four-chamber cine sequence clearly showed contraction of the atria against closed atrioventricular valve; this haemodynamic condition can be caused either by retro-conducted junctional rhythm (previously demonstrated in our patient) or by isorhythmic dissociation of sinus rhythm.

Discussion

Our finding directly demonstrates the profound impact of retro-conducted junctional rhythm on the haemodynamic of a Fontan circulation in which, with each cardiac beat, the pressure rise in the atria and pulmonary veins due to atrial contraction with closed atrioventricular valves is able to stop and invert the passive flow of the systemic venous return towards the lungs.
Safety and efficacy of surgical correction of anomalous aortic origin of coronary arteries: experiences from 2 tertiary cardiac centres
Authors: Pregaldini Fabio , Widenka Hannah , Barghout Mohamed , Gräni Christoph , Czerny Martin , Kari Fabian A , Chikvatia Salome , Kadner Alexander , Siepe Matthias
Published: March 2023

OBJECTIVES

This study aims to describe the outcomes of surgical correction for anomalous aortic origin of coronary artery (AAOCA) with regard to symptom relief.

METHODS

We performed a retrospective multicentre study including surgical patients who underwent correction for AAOCA between 2009 and 2022. Patients who underwent concomitant cardiac procedures were also included. However, to analyse symptom relief, we only assessed the subgroup of symptomatic patients who underwent isolated correction for AAOCA.

RESULTS

A total of 71 consecutive patients (median age 55, range 12–83) who underwent surgical correction for AAOCA were included in the study. Right-AAOCA was present in 56 patients (79%), left-AAOCA in 11 patients (15%) and single coronary ostium AAOCA in 4 patients (6%). Coronary unroofing was performed in 72% of the patients, coronary reimplantation in 28% and an additional neo-ostium patchplasty in 13% of the patients. In 39% of the patients, a concomitant cardiac procedure was performed. During follow-up, no cardiovascular-related death was observed. Three patients (4.2%) had a myocardial infarction and underwent postoperative coronary artery bypass grafting. Six patients (8.5%) needed postoperative temporary mechanical circulatory support. Among the 34 symptomatic patients who underwent isolated AAOCA correction, 70% were completely asymptomatic after surgery, 12% showed symptom improvement and no symptom improvement was observed in 18% of the patients (median follow-up 3.5 years, range 0.3–11.1).

CONCLUSIONS

Correction for AAOCA can be safely performed with or without concomitant cardiac procedures. Performing AAOCA correction leads to a significant improvement in symptoms for most patients.
The 26 November 2019 Durrës earthquake, Albania: coseismic displacements and occurrence of slow slip events in the year following the earthquake
Authors: Matraku Kristina , Jouanne François , Dushi Edmond , Koçi Rexhep , Kuka Neki , Grandin Raphael , Bascou Pascale
Published: March 2023

Outer Albanides experienced a seismic sequence starting on 21 September 2019, with an Mw 5.6 earthquake, considered a foreshock, and culminated with the main shock on 26 November 2019, followed by a paramount aftershock activity. We propose a model for the coseismic slip distribution using InSAR, permanent, and campaign GNSS measurements. We tested two hypotheses: an earthquake on a thrust plane with the direction N160° and along with a back thrust. By varying the depth and dip angle for the first hypothesis and only the dip angle for the second hypothesis, we concluded the optimal solution is a blind thrust at a 15-km depth dipping eastward 40°, a maximum slip of 1.4 m and an Mw 6.38. A GNSS time-series obtained after 2020 shows two slow slip events (SSEs): the first one is 200 d after the main shock up to 26 d, and the second one is 300 d after the main shock up to 28 d. We tested three hypotheses: SSE along the basement thrust where the main shock has been localized, SSE along the flat formed by the detachment layer of the cover, and SSE along these two faults. We concluded that SSE occurred along the detachment layer or along the two faults.
Examining the computation of the underlying components of DALYs
Authors: Verguet Stéphane , Chakrabarti Averi
Published: March 2023

Disability-adjusted life years (DALYs) capture the mortality and morbidity arising from a disease: they incorporate the years of life lost (YLLs) and the years of life lived with disability (YLD) due to a disease. The relative importance of YLLs and YLDs differs across diseases. The magnitudes of YLLs and YLDs depend on parameters such as the age of onset of disease, duration of disease, the case fatality ratio and disability weight. In this paper, we examine the mathematical computation of the DALY and its underlying components, YLDs and YLLs. We aim to demonstrate under which circumstances (e.g. sets of input parameters) disease-specific YLDs and YLLs become sizeable relative to one another using the parameters of a set of diseases in low-income country settings. Researchers could then focus on understanding the key inputs that drive the relative extents of YLDs and YLLs (e.g. determine whether a detailed estimation of disability weights is essential), while maintaining DALYs as their key outcome metric consistent with disease burden assessments.
Applications of a space-time FOSLS formulation for parabolic PDEs
Authors: Gantner Gregor , Stevenson Rob
Published: March 2023

In this work, we show that the space-time first-order system least-squares formulation (Führer, T. & Karkulik, M. (2021) Space–time least-squares finite elements for parabolic equations. Comput. Math. Appl.92, 27–36) for the heat equation and its recent generalization (Gantner, G. & Stevenson, R. (2021) Further results on a space-time FOSLS formulation of parabolic PDEs. ESAIM Math. Model. Numer. Anal.55, 283–299) to arbitrary second-order parabolic partial differential equations can be used to efficiently solve parameter-dependent problems, optimal control problems and problems on time-dependent spatial domains.
A systems approach evaluating the impact of SARS-CoV-2 variant of concern mutations on CD8+ T cell responses
Authors: Buckley Paul R , Lee Chloe H , Antanaviciute Agne , Simmons Alison , Koohy Hashem
Published: March 2023

T cell recognition of SARS-CoV-2 antigens after vaccination and/or natural infection has played a central role in resolving SARS-CoV-2 infections and generating adaptive immune memory. However, the clinical impact of SARS-CoV-2-specific T cell responses is variable and the mechanisms underlying T cell interaction with target antigens are not fully understood. This is especially true given the virus’ rapid evolution, which leads to new variants with immune escape capacity. In this study, we used the Omicron variant as a model organism and took a systems approach to evaluate the impact of mutations on CD8+ T cell immunogenicity. We computed an immunogenicity potential score for each SARS-CoV-2 peptide antigen from the ancestral strain and Omicron, capturing both antigen presentation and T cell recognition probabilities. By comparing ancestral vs. Omicron immunogenicity scores, we reveal a divergent and heterogeneous landscape of impact for CD8+ T cell recognition of mutated targets in Omicron variants. While T cell recognition of Omicron peptides is broadly preserved, we observed mutated peptides with deteriorated immunogenicity that may assist breakthrough infection in some individuals. We then combined our scoring scheme with an in silico mutagenesis, to characterise the position- and residue-specific theoretical mutational impact on immunogenicity. While we predict many escape trajectories from the theoretical landscape of substitutions, our study suggests that Omicron mutations in T cell epitopes did not develop under cell-mediated pressure. Our study provides a generalisable platform for fostering a deeper understanding of existing and novel variant impact on antigen-specific vaccine- and/or infection-induced T cell immunity.
Teicoplanin and vancomycin as treatment for glycopeptide-susceptible Enterococcus faecium bacteraemia: a propensity score-adjusted non-inferior comparative study
Authors: Yamaguchi Ryo , Yamamoto Takehito , Okamoto Koh , Harada Sohei , Echizenya Miho , Tsutsumi Takeya , Takada Tappei
Published: March 2023

Objectives

Limited evidence is available regarding alternative therapeutic agents to vancomycin in treating glycopeptide-susceptible Enterococcus faecium (GSEF) bacteraemia. This study assessed the effectiveness and safety of teicoplanin compared with vancomycin for treating GSEF bacteraemia.

Patients and methods

This was a retrospective, non-inferiority cohort study. Patients aged ≥18 years who developed GSEF bacteraemia and received either teicoplanin or vancomycin were included. The primary effectiveness outcome was the clinical success at the end of treatment, with a generalized linear model using the propensity score for selecting the agent as a covariate. We used an absolute difference of 20% in clinical success as the non-inferiority margin. Using multivariable logistic regression, the primary safety outcome was the incidence of acute kidney injury (AKI).

Results

In total, 164 patients (74 and 90 in the teicoplanin and vancomycin groups, respectively) were included. Overall, 64.9% (48/74) and 48.9% (44/90) of patients in the teicoplanin and vancomycin groups, respectively, achieved the primary effectiveness outcome. A generalized linear analysis showed an adjusted effectiveness difference of 9.9% (95% CI, −0.9% to 20.0%; P = 0.07), indicating non-inferiority of teicoplanin versus vancomycin. The incidence of AKI was 8.1% (6/74) and 24.4% (22/90) in the teicoplanin and vancomycin groups, respectively, with an adjusted OR of 0.242 (95% CI, 0.068 to 0.864; P = 0.029), indicating significantly lower AKI risk in the teicoplanin than in the vancomycin group.

Conclusions

Teicoplanin is a safe and useful alternative therapeutic agent for treating GSEF bacteraemia.
Validation of an administrative algorithm for transgender and gender diverse persons against self-report data in electronic health records
Authors: Streed Carl G , King Dana , Grasso Chris , Reisner Sari L , Mayer Kenneth H , Jasuja Guneet K , Poteat Tonia , Mukherjee Monica , Shapira-Daniels Ayelet , Cabral Howard , Tangpricha Vin , Paasche-Orlow Michael K , Benjamin Emelia J
Published: March 2023

Objective

To adapt and validate an algorithm to ascertain transgender and gender diverse (TGD) patients within electronic health record (EHR) data.

Methods

Using a previously unvalidated algorithm of identifying TGD persons within administrative claims data in a multistep, hierarchical process, we validated this algorithm in an EHR data set with self-reported gender identity.

Results

Within an EHR data set of 52 746 adults with self-reported gender identity (gold standard) a previously unvalidated algorithm to identify TGD persons via TGD-related diagnosis and procedure codes, and gender-affirming hormone therapy prescription data had a sensitivity of 87.3% (95% confidence interval [CI] 86.4–88.2), specificity of 98.7% (95% CI 98.6–98.8), positive predictive value (PPV) of 88.7% (95% CI 87.9–89.4), and negative predictive value (NPV) of 98.5% (95% CI 98.4–98.6). The area under the curve (AUC) was 0.930 (95% CI 0.925–0.935). Steps to further categorize patients as presumably TGD men versus women based on prescription data performed well: sensitivity of 97.6%, specificity of 92.7%, PPV of 93.2%, and NPV of 97.4%. The AUC was 0.95 (95% CI 0.94–0.96).

Conclusions

In the absence of self-reported gender identity data, an algorithm to identify TGD patients in administrative data using TGD-related diagnosis and procedure codes, and gender-affirming hormone prescriptions performs well.
Improved Stability-Indicating RP-UPLC Method for the Levamisole Hydrochloride Assay and Estimation of Its Related Compounds
Authors: Adhikari Sarju , Rustum Abu M
Published: March 2023

Background

Levamisole hydrochloride (LVM) is an anthelmintic drug substance with immunomodulatory and anticancer activities. LVM has also found usage as a cutting agent in street cocaine.

Objective

This study was aimed to develop and validate an alternative and improved stability-indicating reversed-phase ultraperformance liquid chromatography (RP-UPLC) method for the determination of LVM and the estimation of its related compounds.

Method

The UPLC method for the assay was optimized in terms of organic solvents consumed, pH, column temperature, and flow rate. Determination of LVM and its related compounds was performed using a gradient elution on a Waters ACQUITY UPLC® BEH C18 (50 mm × 2.1 mm i.d., 130 Å). The column temperature was maintained at 35°C. Mobile phase A was composed of aqueous 5 mM ammonium hydroxide, and mobile phase B was composed of acetonitrile. All the analytes were monitored by UV detection at 215 nm with a flow rate of 0.7 mL/min. The total runtime of the method with column equilibration is 4.0 min.

Results

The developed method met all the acceptance criteria of the current International Council for Harmonization [ICH Q2 (R1)] guidelines. The method was tested in terms of specificity, linearity (R2 > 0.999), limit of detection (LOD; 0.06 μg/mL), limit of quantitation (LOQ; 0.2 μg/mL), accuracy, precision, and robustness. With a short analysis time (<2.5 min) and reduced consumption of organic solvents, the proposed method is considered a greener alternative to conventional chromatographic methods.

Conclusions

An alternative and improved UPLC method was successfully developed and validated in accordance with the ICH guidelines for the determination of LVM and the estimation of its related compounds.

Highlights

Due to its high degree of selectivity, speed, and accuracy, the developed method can significantly benefit the end-users with laboratory efficiency and throughput during routine analysis of production batches and stability monitoring of LVM-related drug products.
A Novel, Sustainable, and Eco-Friendly Spectrophotometric and Chemometric Approach for Determination of Severely Overlapped Spectrum via Unified Regression Equation: Greenness and Whiteness Assessment
Authors: Magdy Ragaa , Fares Nermine V , Farouk Maha , Hemdan Ahmed
Published: March 2023

Background

Nebivolol and valsartan (VAL) in combination with each other successfully control blood pressure and improve hypertension patient outcomes.

Objective

To develop and validate innovative, simple, and sustainable spectrophotometric methods for the simultaneous analysis of nebivolol and valsartan.

Method

The new modified difference amplitude modulation (MD-AM) method uses only unified regression equation and does not require any resolution techniques. Other different approaches were also applied for the determination of the same mixture including univariate and multivariate spectrophotometric methods. The multivariate methods were PLS and PCR, whereas the univariate methods were derivative ratio (DD1), ratio difference (RD), constant center (CC), constant center spectrum subtraction (CC-SS), constant value coupled with amplitude difference (CV-AD), advanced concentration value (ACV), and amplitude difference (AD). The proposed methods use a green solvent; thus, the environmental impact of the presented procedures was evaluated qualitatively and quantitatively using six well-known evaluation tools.

Results

All methods were applied successfully for the analysis of the studied drugs in their bulk powder, pharmaceutical dosage form Byvalson®, and in vitro release at intestinal pH (7.4) using a USP dissolution tester. Results obtained were compared statistically with the reported method and with each other using a one-way ANOVA statistical test, and no significant differences were found.

Conclusions

All green and white analytical chemistry evaluation tools results confirm the safety, sustainability, and cost-effectiveness of the approaches, indicating that the methods are regarded green and sustainable. Results were agreeable, encouraging their applicability in quality control laboratories for dosage form and making these methods an eco-friendly substitute for the analysis of this combined dosage form and for evaluating the dissolution profile.

Highlights

For the first time, a severely overlapped spectrum was determined using a unified regression equation without the need of extended part or zero contribution regions by the novel method MD-AM. The proposed methods are the first study of in vitro dissolution profiling of nebivolol hydrochloride (NEB) and VAL and the first sustainable and green methods applied without compromising the analytical criteria.
Response to acute hyperglycemia and high fructose in cultured tenocytes
Authors: Kuan Rebecca , Nath Shilpa , Agrawal Devendra K , Thankam Finosh G
Published: March 2023

High monosaccharide levels are intimately associated with diabetes and impact tendon cells through inflammation and impairment in metabolic homeostasis. Experiments were designed to understand the responses elicited by cultured tenocytes under monosaccharide stress induced by hyperglycemia and hyperfructosemia. We simulated hyperglycemia and hyperfructosemia in vitro by treating tenocytes with media containing sublethal concentrations of glucose and fructose, respectively. Exposure of tenocytes to high glucose and high fructose altered the levels of IL-1β, IL-2, IL-6, IL10 and IL-17A. AMPK expression was increased in high-glucose and decreased in high-fructose groups. High fructose increased the level of IRS-1 compared with the control. Increased mitochondrial superoxide levels and compromised mitochondrial membrane integrity were exhibited by both the groups. The findings from the network analysis revealed many altered genes that are related to pathways for enzyme-linked receptor protein signaling, positive regulation of metabolic processes, transmembrane receptor tyrosine kinase pathway, insulin receptor signaling and regulation of cytokine production. Overall, the data suggest that the tenocytes under high monosaccharide levels exhibit survival responses by altering the expression status of cytokines and metabolic mediators that are involved in the underlying pathogenesis of tendinopathy.
iPS cell–derived model to study the interaction between tissue macrophage and HIV-1
Authors: Eltalkhawy Youssef M , Takahashi Naofumi , Ariumi Yasuo , Shimizu Jun , Miyazaki Kazuo , Senju Satoru , Suzu Shinya
Published: March 2023

Despite effective antiretroviral therapy, HIV-1 persists in cells, including macrophages, which is an obstacle to cure. However, the precise role of macrophages in HIV-1 infection remains unclear because they reside in tissues that are not easily accessible. Monocyte-derived macrophages are widely used as a model in which peripheral blood monocytes are cultured and differentiated into macrophages. However, another model is needed because recent studies revealed that most macrophages in adult tissues originate from the yolk sac and fetal liver precursors rather than monocytes, and the embryonic macrophages possess a self-renewal (proliferating) capacity that monocyte-derived macrophages lack. Here, we show that human induced pluripotent stem cell–derived immortalized macrophage-like cells are a useful self-renewing macrophage model. They proliferate in a cytokine-dependent manner, retain macrophage functions, support HIV-1 replication, and exhibit infected monocyte-derived macrophage–like phenotypes, such as enhanced tunneling nanotube formation and cell motility, as well as resistance to a viral cytopathic effect. However, several differences are also observed between monocyte-derived macrophages and induced pluripotent stem cell–derived immortalized macrophage-like cells, most of which can be explained by the proliferation of induced pluripotent stem cell–derived immortalized macrophage-like cells. For instance, proviruses with large internal deletions, which increased over time in individuals receiving antiretroviral therapy, are enriched more rapidly in induced pluripotent stem cell–derived immortalized macrophage-like cells. Interestingly, inhibition of viral transcription by HIV-1–suppressing agents is more obvious in induced pluripotent stem cell–derived immortalized macrophage-like cells. Collectively, our present study proposes that the model of induced pluripotent stem cell–derived immortalized macrophage-like cells is suitable for mimicking the interplay between HIV-1 and self-renewing tissue macrophages, the newly recognized major population in most tissues that cannot be fully modeled by monocyte-derived macrophages alone.
Reproduction drives changes in space use and habitat selection in a highly adaptable invasive mammal
Authors: Chinn Sarah M , Hepinstall-Cymerman Jeffrey , Beasley James C
Published: March 2023

For ungulates, it is not well understood how the interaction between habitat and reproduction affects movement behavior, space use, and habitat selection. We used known parturition (farrowing) data to validate First Passage Time (FPT) movement analysis to identify wild pig (Sus scrofa) parturition events from data collected with GPS collars. We examined home range and habitat selection during three physiologically distinct time periods in the reproductive cycle: late-gestation; farrowing; and neonate-care period. Sows exhibited a behavioral change 1-2 days prior to farrowing, suggesting FPT analysis can reliably identify parturition events for wide-ranging species that have a focused birthing area. Home range was smallest during the farrowing period, likely reflective of nest building, parturition, and protection of neonates. Home range size during the neonate-care period was intermediate between the late-gestation and farrowing periods, indicative of offspring care that may restrict maternal movement. Across all periods, sows avoided developed areas that have sparse canopy and ground cover and are associated with human activities. During late-gestation, sows avoided pine forests that have an open understory and less vegetative cover. During late-gestation and neonate-care, sows selected bottomland hardwood forests, habitat associated with ample food, cover, and water. During farrowing and neonate-care periods, sows selected upland hardwood forests, habitat with high quality food and cover for neonates. The physiological requirements of reproduction drive female habitat selection and spatial scale of movement patterns associated with parturition. Our study contributes to delineation of the appropriate scale at which to analyze movement data to provide insight about where individuals chose to place their home range, how much space to use, and how they use resources on the landscape to maximize reproductive success and fitness.
Dealing with Divergence: Intra-party Dynamics and Spoiler Management in Civil Wars
Authors: Nilsson Desirée , Kovacs Mimmi Söderberg
Published: March 2023

Civil war peace processes are frequently accompanied by spoiler behavior relating to intra-party divergence, such as leadership struggles or breakaway groups, which risk undermining the implementation of a peace accord. However, previous literature has not sufficiently explored how third-party actors can address spoiler behavior linked to such intra-party aspects. This study addresses this gap by providing an empirical analysis of a few illustrative cases of spoiler behavior by armed actors in two peace processes in West Africa—Sierra Leone after the 1999 Lomé peace accords and Liberia after the 2003 Accra peace agreement. We find that in contexts where there is a vertical divergence between the leader and the rest of the group, divisive strategies—aimed to divide and rule or marginalize—are effective. In contrast, in situations of horizontal divergence between different factions that are more equal in power, integrative strategies—aimed at unifying the ranks or reconciling a divided leadership—are more appropriate. This study enhances our understanding of how third-party strategies can be devised to manage intra-party divisions that otherwise may threaten a transition from war to peace.
Determining the accuracy of a medication history at the point of a Comprehensive Geriatric Assessments (CGA) within an inpatient setting on a Frailty Assessment Unit
Authors: Stratton Lucy , Thayer Nick , Channa Kiran
Published: March 2023

Objectives

This retrospective analysis aims to determine the accuracy of medication histories undertaken during a Comprehensive Geriatric Assessment (CGA) (at the point of admission) in an inpatient setting within an acute hospital. The CGA can be completed by a range of healthcare professionals, which will be directly compared. Medication reviews are an integral part of the CGA, therefore the accuracy of the history is integral to the review.

Methods

A retrospective analysis of patient electronic records between October 2018 and February 2020 was conducted. The accuracy of medication histories recorded as part of the CGA completed by Advanced Nurse Practitioners, Advanced Pharmacist Practitioners and Doctors was compared. This was done using electronic records, any discrepancies were captured. Descriptive statistics were applied.

Key findings

Across the 50 patients and 421 medicines identified, there were 59 discrepancies; 24 (48%) patients were noted with at least one discrepancy in their medication history. An omission of current medication was the most common error (49%), followed by incorrect dose (19%) and a record of a medication not taken pre-admission (15%). The total number of prescribed medications was found to positively correlate with the rate of error (Pearson’s correlation 0.455, P > 0.001). An independent t-test determined a significant difference between the rate of errors between pharmacists and nurses (t-test: −4.48, P < 0.001).

Conclusions

This study re-confirmed risks of medication errors when patients change care settings. This is more prevalent with higher numbers of medications, requiring greater care in instances of polypharmacy, particularly in frail patients. This can support risk stratification of patients. A difference in outcomes between pharmacists and nurses warrants further exploration to determine the reasons for this and structuring multi-disciplinary teams accordingly. Consideration to ensure that medication history taking is included as part of the Advanced Clinical Practitioner is important, particularly with the expansion of these roles in the UK.
Bayesian matrix completion for hypothesis testing
Authors: Jin Bora , Dunson David B , Rager Julia E , Reif David M , Engel Stephanie M , Herring Amy H
Published: March 2023

We aim to infer bioactivity of each chemical by assay endpoint combination, addressing sparsity of toxicology data. We propose a Bayesian hierarchical framework which borrows information across different chemicals and assay endpoints, facilitates out-of-sample prediction of activity for chemicals not yet assayed, quantifies uncertainty of predicted activity, and adjusts for multiplicity in hypothesis testing. Furthermore, this paper makes a novel attempt in toxicology to simultaneously model heteroscedastic errors and a nonparametric mean function, leading to a broader definition of activity whose need has been suggested by toxicologists. Real application identifies chemicals most likely active for neurodevelopmental disorders and obesity.
Single stage surgical management of a sigmoid gallstone ileus case
Authors: Tonog Paul , Clar Derek T , Ebalo Nicole , Appresai Ovie
Published: March 2023

Bowel obstruction/ileus is a relatively common occurrence in surgical practice with a predictable clinical presentation and management course. Rarely are these cases found consistent with gallstone etiology. Known as gallstone ileus (GI), this uncommon presentation is found primarily in elderly females (age > 65 years old) with multiple comorbid conditions; usually with coinciding presence of a cholecystoenteric fistula. Surgical management remains controversial due to the rarity of presentation and complexity of related pathological process. We present a case of a 69-year-old female who presented with typical signs/symptoms of bowel obstruction but found to have sigmoid GI on computed tomography imaging evaluation. A single stage exploratory laparotomy with simple enterolithotomy was performed with a positive outcome and uncomplicated postoperative recovery. The primary goal in reporting this case is to continue emphasizing the efficacy of a single stage simple enterolithotomy as the most ideal surgical management of this rare condition.
Displacement of maxillary third molar into the infratemporal fossa. A case report
Authors: Tilaveridis Ioannis , Karakostas Panagiotis , Tilaveridis Vasilios , Tilaveridis Stavros
Published: March 2023

Our study aims to present a new case of maxillary third molar dislodgement into the infratemporal fossa during the effort of extraction and the surgical approach performed to retrieve the tooth. Guidelines to prevent this complication are presented. We describe a new case of maxillary third molar displacement into the infratemporal fossa following an unsuccessful surgical procedure of tooth removal by a general dentist. The location of the displaced tooth was confirmed with computed tomography (CT) scanning with a 3D reconstruction. The tooth was removed under general anesthesia through an intraoral approach. It took less than 10 min for the whole procedure to be accomplished. CT examination is of paramount importance to precisely locate the dislodged tooth. Removal can be successfully accomplished via an intraoral approach with meticulous manipulations. An incision of adequate length and a long Langebeck retractor are valuable to ensure a wide surgical field.
Dynamic association of the plastid localized cysteine synthase complex is vital for efficient cysteine production, photosynthesis, and granal thylakoid formation in transgenic tobacco
Authors: Wirtz Markus , Leemhuis Wiebke , Hell Ruediger
Published: March 2023

Cysteine biosynthesis is essential for translation and represents the entry point of reduced sulfur into plant metabolism. The two consecutively acting enzymes serine acetyltransferase (SAT) and O-acetylserine-thiol-lyase catalyse cysteine production and form the cysteine synthase complex, in which SAT is activated. Here we show that tobacco (Nicotiana tabacum) expressing active SAT in plastids (referred to as PSA lines) shows substantial cysteine accumulation in plastids. Remarkably, enhanced cysteine production in plastids entirely abolished granal stack formation, impaired photosynthesis capacity, and decreased the number of chloroplasts in mesophyll cells of the PSA lines. A transgenic tobacco line expressing active SAT in the cytosol accumulated comparable amounts of thiols but displayed no phenotype. To dissect the consequences of cysteine synthase complex formation from enhanced SAT activity in tobacco plastids, we expressed an enzymatically inactive SAT that can still form the cysteine synthase complex in tobacco plastids (PSI lines). The PSI lines were indistinguishable from the PSA lines, although the PSI lines displayed no increase in plastid-localized SAT activity. Neither PSA lines nor PSI lines suffered from an oxidized redox environment in plastids that could have been causative for the disturbed photosynthesis. From these findings, we infer that the association of the plastid cysteine synthase complex itself triggers a signaling cascade controlling sulfur assimilation and photosynthetic capacity in leaves.
Large-Scale Atom Probe Tomography Data Mining: Methods and Application to Inform Hydrogen Behavior
Authors: Meier Martin S , Bagot Paul A J , Moody Michael P , Haley Daniel
Published: March 2023

A large number of atom probe tomography (APT) datasets from past experiments were collected into a database to conduct statistical analyses. An effective way of handling the data is shown, and a study on hydrogen is conducted to illustrate the usefulness of this approach. We propose to handle a large collection of APT spectra as a point cloud and use a city block distance–based metric to measure dissimilarity between spectra. This enables quick and automated searching for spectra by similarity. Since spectra from APT experiments on similar materials are similar, the point cloud of spectra contains clusters. Analysis of these clusters of spectra in this point cloud allows us to infer the sample materials. The behavior of contaminant hydrogen is analyzed and correlated with voltage, electric field, and sample base material. Across several materials, the H2+ /H+ ratio is found to decrease with increasing field, likely an indication of postionization of H2+ ions. The absolute amounts of H2+ and H+ are found to frequently increase throughout APT experiments.
Development ofLacuna pallidula(da Costa, 1778) from the White Sea (Caenogastropoda: Littorinimorpha) with emphasis on radula formation
Authors: Vortsepneva Elena , Herbert David G , Kantor Yuri
Published: March 2023

The gastropod radula is highly diverse in structure in comparison with that of other mollusсs. The main radular types in the different phylogenetic groups of gastropods differ not only in the general morphology and configuration of the teeth but also in the mode of tooth synthesis and the ultrastructure of the formation zone. Previously, the formation and anlage of the radula in the ontogeny of radulae of all major phylogenetic gastropods groups have been studied, with the exception of the taenioglossan radula of Caenogastropoda. The data obtained in this study on the radular anlage and synthesis in one littorinimorph species Lacuna pallidula supplement the existing knowledge of diversity in gastropod radula formation. The radula is initially formed at the stage of the post-torsion veliger, with five teeth in each transverse row, and acquires the adult morphology before hatching from the egg mass. The larval radula is synthesized by a few morphologically uniform cells in the radular sac. Synthesis of the adult radula also occurs at the blind end of the radular sac, where groups of numerous odontoblasts each form one tooth, and membranoblasts, located on the ventral side, form the membrane. Characteristic features of the adult radular sac are an additional supporting cartilage-like structure at the radula curve in the middle of the radular sac, a well-defined proliferation zone in the zone of radula formation and the presence of an additional extracellular matrix around the teeth in the maturation zone.
GCNA is a histone binding protein required for spermatogonial stem cell maintenance
Authors: Ribeiro Jonathan , Crossan Gerry P
Published: March 2023

Recycling and de-novo deposition of histones during DNA replication is a critical challenge faced by eukaryotic cells and is coordinated by histone chaperones. Spermatogenesis is highly regulated sophisticated process necessitating not only histone modification but loading of testis specific histone variants. Here, we show that Germ Cell Nuclear Acidic protein (GCNA), a germ cell specific protein in adult mice, can bind histones and purified GCNA exhibits histone chaperone activity. GCNA associates with the DNA replication machinery and supports progression through S-phase in murine undifferentiated spermatogonia (USGs). Whilst GCNA is dispensable for embryonic germ cell development, it is required for the maintenance of the USG pool and for long-term production of sperm. Our work describes the role of a germ cell specific histone chaperone in USGs maintenance in mice. These findings provide a mechanistic basis for the male infertility observed in patients carrying GCNA mutations.
Discovering cryptic splice mutations in cancers via a deep neural network framework
Authors: Teboul Raphaël , Grabias Michalina , Zucman-Rossi Jessica , Letouzé Eric
Published: March 2023

Somatic mutations can disrupt splicing regulatory elements and have dramatic effects on cancer genes, yet the functional consequences of mutations located in extended splice regions is difficult to predict. Here, we use a deep neural network (SpliceAI) to characterize the landscape of splice-altering mutations in cancer. In our in-house series of 401 liver cancers, SpliceAI uncovers 1244 cryptic splice mutations, located outside essential splice sites, that validate at a high rate (66%) in matched RNA-seq data. We then extend the analysis to a large pan-cancer cohort of 17 714 tumors, revealing >100 000 cryptic splice mutations. Taking into account these mutations increases the power of driver gene discovery, revealing 126 new candidate driver genes. It also reveals new driver mutations in known cancer genes, doubling the frequency of splice alterations in tumor suppressor genes. Mutational signature analysis suggests mutational processes that could give rise preferentially to splice mutations in each cancer type, with an enrichment of signatures related to clock-like processes and DNA repair deficiency. Altogether, this work sheds light on the causes and impact of cryptic splice mutations in cancer, and highlights the power of deep learning approaches to better annotate the functional consequences of mutations in oncology.