bluuebunny/crossref_metadata_2025 huggingface dataset:
An experimental medicine study of the effects of simvastatin on emotional processing, reward learning, verbal memory, and inflammation in healthy volunteers
Authors: De Giorgi Riccardo , Quinton Alice M. G. , Waters Shona , Cowen Philip J. , Harmer Catherine J.
Published: May 2022

Rationale

Clinical studies suggest that the highly lipophilic, anti-inflammatory molecule, simvastatin, might be an ideal candidate for drug repurposing in the treatment of depression. The neuropsychological effects of simvastatin are not known, but their ascertainment would have significant translational value about simvastatin’s influence on mood and cognition.

Objectives

We aimed to investigate the effects of simvastatin on a battery of psychological tests and inflammatory markers in healthy volunteers.

Methods

Fifty-three healthy subjects were randomly assigned to 7 days of either simvastatin (N = 27) or sucrose-based placebo (N = 26) given in a double-blind fashion. Then, participants were administered questionnaires measuring subjective rates of mood and anxiety, and a battery of tasks assessing emotional processing, reward learning, and verbal memory. Blood samples for C-reactive protein were also collected.

Results

Compared to placebo, participants on simvastatin showed a higher number of positively valenced intrusions in the emotional recall task (F1,51 = 4.99, p = 0.03), but also an increase in anxiety scores (F1,51 = 5.37, p = 0.02). An exploratory analysis of the females’ subgroup (N = 27) showed lower number of misclassifications as sad facial expression in the simvastatin arm (F1,25 = 6.60, p = 0.02). No further statistically significant changes could be observed on any of the other outcomes measured.

Conclusions

We found limited evidence that 7-day simvastatin use in healthy volunteer induces a positive emotional bias while also being associated with an increase in anxiety, potentially reflecting the early effects of antidepressants in clinical practice. Such effect might be more evident in female subjects. Different drug dosages, treatment lengths, and sample selection need consideration in further experimental medicine and clinical studies.

Trial registration

Clinicaltrials.gov: NCT04652089.
Crossing and selection of Chlamydomonas reinhardtii strains for biotechnological glycolate production
Authors: Schad Antonia , Rössler Sonja , Nagel Raimund , Wagner Heiko , Wilhelm Christian
Published: May 2022

As an alternative to chemical building blocks derived from algal biomass, the excretion of glycolate has been proposed. This process has been observed in green algae such as Chlamydomonas reinhardtii as a product of the photorespiratory pathway. Photorespiration generally occurs at low CO2 and high O2 concentrations, through the key enzyme RubisCO initiating the pathway via oxygenation of 1.5-ribulose-bisphosphate. In wild-type strains, photorespiration is usually suppressed in favour of carboxylation due to the cellular carbon concentrating mechanisms (CCMs) controlling the internal CO2 concentration. Additionally, newly produced glycolate is directly metabolized in the C2 cycle. Therefore, both the CCMs and the C2 cycle are the key elements which limit the glycolate production in wild-type cells. Using conventional crossing techniques, we have developed Chlamydomonas reinhardtii double mutants deficient in these two key pathways to direct carbon flux to glycolate excretion. Under aeration with ambient air, the double mutant D6 showed a significant and stable glycolate production when compared to the non-producing wild type. Interestingly, this mutant can act as a carbon sink by fixing atmospheric CO2 into glycolate without requiring any additional CO2 supply. Thus, the double-mutant strain D6 can be used as a photocatalyst to produce chemical building blocks and as a future platform for algal-based biotechnology.

Key Points

• Chlamydomonas reinhardtii cia5 gyd double mutants were developed by sexual crossing

• The double mutation eliminates the need for an inhibitor in glycolate production

• The strain D6 produces significant amounts of glycolate with ambient air only
Os acromiale: prevalence and associated patient-related factors—a population-based study of three thousand and fifty participants
Authors: Fischer Cornelius Sebastian , Floß Matthias , Ittermann Till , Bülow Robin , Völzke Henry , Ahrend Marc-Daniel , Lange Jörn
Published: May 2022

Purpose

The presence of os acromiale is of clinical relevance before performing shoulder surgery but ethnic differences and little information regarding associated factors seem to be present. Population-based studies to clarify these topics are essential so the purpose of this study was to assess the prevalence, anatomy, and associations of os acromiale in a general adult population.

Methods

Both shoulders of 3050 participants from the population-based Study of Health in Pomerania (SHIP) were assessed on magnetic resonance imaging (MRI). Associations with the os acromiale were calculated for sex, age, body height, body weight, and heavy mechanical oscillations on the upper extremity.

Results

In total, 1.9% (58/3050) had an os acromiale, while 21 were unilateral left, 23 were unilateral right, and 14 were bilateral. Sixty-eight meso-acromions, three pre-acromions, and one meta-acromion were detected. Os acromiale were more frequent in men (right side: p = 0.037, left side: p = 0.005). Overall, no differences in sides (p = 0.808), to participants’ age (right: p = 0.993, left: p = 0.499), body height (right side: p = 0.241, left side: p = 0.154), and the exposure to heavy mechanical oscillations on the upper extremity (right: p = 0.054, left: p = 0.117) were detected.

Conclusion

Our results support the genetic theory for the aetiology of the os acromiale due to the lower prevalence of the os acromiale in north-eastern Germany compared to the worldwide prevalence (1.9 to 7%) and the lacking association to lifestyle, age, gender, or sides. Additionally, it is important to be aware of possible os acromiale before surgery.
A new algebraic approach to genome rearrangement models
Authors: Terauds Venta , Sumner Jeremy
Published: May 2022

We present a unified framework for modelling genomes and their rearrangements in a genome algebra, as elements that simultaneously incorporate all physical symmetries. Building on previous work utilising the group algebra of the symmetric group, we explicitly construct the genome algebra for the case of unsigned circular genomes with dihedral symmetry and show that the maximum likelihood estimate (MLE) of genome rearrangement distance can be validly and more efficiently performed in this setting. We then construct the genome algebra for a more general case, that is, for genomes that may be represented by elements of an arbitrary group and symmetry group, and show that the MLE computations can be performed entirely within this framework. There is no prescribed model in this framework; that is, it allows any choice of rearrangements that preserve the set of regions, along with arbitrary weights. Further, since the likelihood function is built from path probabilities—a generalisation of path counts—the framework may be utilised for any distance measure that is based on path probabilities.
Instantaneous flame front identification by Mie scattering vs. OH PLIF in low turbulence Bunsen flame
Authors: Zheng Yutao , Weller Lee , Hochgreb Simone
Published: May 2022

Simultaneous OH-PLIF and Mie scatter imaging were used to investigate turbulent premixed flame edge detection under a range of turbulence characteristics on a stabilised piloted Bunsen burner. A 527 nm wavelength laser beam is used to generate a Mie scattering sheet at 500 Hz, and a 283 nm wavelength laser sheet is created using 355 nm wavelength laser to pump an optical parametric oscillator to induce florescence from OH radicals at 5 Hz. A phase-locking technique is applied to synchronize and lock the two laser systems. The number density method has been used to detect flame edges in Mie scattering images, and three algorithms were applied to OH-PLIF images as a reference. A comparison of the methods and different parameter setting is made by using the metrics of location difference, flame surface density and curvature of flame edges. The processed data show that once a well-tuned window size is determined by applying the number density method, averaged spatial differences between Mie scattering images and OH-PLIF images are of the order of or smaller than the laminar flame thickness, demonstrating that under these conditions, high frequency Mie scatter measurements can be used as well as OH-PLIF images to define the flame edge at that spatial resolution. The positive result confirms that double-frame Mie scattering allows the measurement of high frequency conditional velocity distributions and flame properties simultaneously using solely Mie scattering, provided that the particle density is suitably designed to be around 16 px$$^2$$

2

per particle.

Graphic Abstract
Factors affecting mechanical complications of central venous access devices in children
Authors: Zhang Jessica J. , Nataraja Ramesh M. , Lynch Amiria , Barnes Richard , Ferguson Peter , Pacilli Maurizio
Published: May 2022

Purpose

Factors leading to mechanical complications following insertion of central venous access devices (CVADs) in children are poorly understood. We aimed to quantify the rates and elucidate the mechanisms of these complications.

Methods

Retrospective (2016–2021) review of children (< 18 years old) receiving a CVAD. Data, reported as number of cases (%) and median (IQR), were analysed by Fisher’s exact test, chi-squared test and logistic regression analysis.

Results

In total, 317 CVADs (245 children) were inserted. Median age was 5.0 (8.9) years, with 116 (47%) females. There were 226 (71%) implantable port devices and 91 (29%) Hickman lines. Overall, 54 (17%) lines had a mechanical complication after 0.4 (0.83) years from insertion: fracture 19 (6%), CVAD migration 14 (4.4%), occlusion 14 (4.4%), port displacement 6 (1.9%), and skin tethering to port device 1 (0.3%). Younger age and lower weight were associated with higher risk of complications (p < 0.0001). Hickman lines had a higher incidence of complications compared to implantable port devices [24/91 (26.3%) vs 30/226 (13.3%); p = 0.008].

Conclusion

Mechanical complications occur in 17% of CVADs at a median of < 6 months after insertion. Risk factors include younger age and lower weight. Implantable port devices have a lower complications rate.

Level of evidence

Level 4: case-series with no comparison group.
Surgical treatment of mechanical bowel obstruction: characteristics and outcomes of geriatric patients compared to a younger cohort
Authors: Paul Christian J. J. , Dohmen Jonas , van Beekum Cornelius J. , Willis Maria A. , Braun Lara , Kalff Jörg C. , Willms Arnulf G. , Vilz Tim O.
Published: May 2022

Purpose

Mechanical bowel obstruction (MBO) is one of the most common indications for emergency surgery. Recent research justifies the method of attempting 3–5 days of nonoperative treatment before surgery. However, little is known about specific characteristics of geriatric patients undergoing surgery compared to a younger cohort. We aimed to analyze patients with MBO that required surgery, depending on their age, to identify potential targets for use in the reduction in complications and mortality in the elderly.

Methods

Thirty-day and in-hospital mortality were determined as primary outcome. We retrospectively identified all patients who underwent surgery for MBO at the University Hospital of Bonn between 2009 and 2019 and divided them into non-geriatric (40–74 years, n = 224) and geriatric (≥ 75 years, n = 88) patients, using the chi-squared-test and Mann–Whitney U test for statistical analysis.

Results

We found that geriatric patients had higher 30-day and in-hospital mortality rates than non-geriatric patients. As secondary outcome, we found that they experienced a longer length of stay (LOS) and higher complication rates than non-geriatric patients. Geriatric patients who suffered from large bowel obstruction (LBO) had a higher rate of bowel resection, stoma creation, and a higher 30-day mortality rate. The time from admission to surgery was not shown to be crucial for the outcome of (geriatric) patients.

Conclusion

Geriatric patients suffering from mechanical bowel obstruction that had to undergo surgery had higher mortality and morbidity than non-geriatric patients. Especially in regard to geriatric patients, clinicians should treat patients in a risk-adapted rather than time-adapted manner, and conditions should be optimized before surgery.
Wertigkeit der CT und des transthorakalen Lungenultraschalls bei PatientInnen mit systemischer Sklerose
Authors: Grohs M. , Moazedi-Fuerst F. C. , Flick H. , Hackner K. , Haidmayer A. , Handzhiev S. , Kiener H. , Löffler-Ragg J. , Mathis G. , Mostbeck G. , Schindler O. , Widmann G. , Prosch H.
Published: May 2022

Die Lungenbeteiligung ist die häufigste Todesursache bei Patienten mit systemischer Sklerose (SSc). Da eine Lungenbeteiligung häufig asymptomatisch ist, wird derzeit empfohlen, bei allen Patienten mit einer neu diagnostizierten SSc eine Thorax-CT durchzuführen. Uneinigkeit herrscht derzeit darüber, wie SSc-Patienten, bei denen zum Diagnosezeitpunkt keine Lungenbeteiligung gefunden wurde, weiterverfolgt werden sollen. Basierend auf einem Konsensus österreichischer Rheumatologen, Pneumologen und Radiologen, wird empfohlen, bei asymptomatischen PatientInnen mit einer negativen CT zum Zeitpunkt der Erstdiagnose jährlich transthorakale Ultraschalluntersuchungen sowie Lungenfunktionsuntersuchungen alle 6 bis 12 Monate durchzuführen. Bei Vorliegen eines positiven Lungenultraschallbefundes wird eine ergänzende CT zur weiterführenden Abklärung empfohlen. Aufgrund der Datenlage werden bei PatientInnen mit einem höheren Risiko, definiert durch entsprechende Risikofaktoren, jährliche CT-Verlaufskontrollen empfohlen.
Dietary score associations with markers of chronic low-grade inflammation: a cross-sectional comparative analysis of a middle- to older-aged population
Authors: Millar Seán R. , Navarro Pilar , Harrington Janas M. , Shivappa Nitin , Hébert James R. , Perry Ivan J. , Phillips Catherine M.
Published: May 2022

Purpose

To assess relationships between the Dietary Approaches to Stop Hypertension (DASH), Mediterranean Diet (MD), Dietary Inflammatory Index (DII®) and Energy-adjusted DII (E-DII™) scores and pro-inflammatory cytokines, adipocytokines, acute-phase response proteins, coagulation factors and white blood cells.

Methods

This was a cross-sectional study of 1862 men and women aged 46–73 years, randomly selected from a large primary care centre in Ireland. DASH, MD, DII and E-DII scores were derived from validated food frequency questionnaires. Correlation and multivariate-adjusted linear regression analyses with correction for multiple testing were performed to examine dietary score relationships with biomarker concentrations.

Results

In fully adjusted models, higher diet quality or a less pro-inflammatory diet was associated with lower concentrations of c-reactive protein, neutrophils (all dietary scores), complement component 3 [C3], interleukin 6 [IL-6], tumour necrosis factor-alpha [TNF-α], white blood cell count [WBC], the neutrophil-to-lymphocyte ratio [NLR] (DASH, DII and E-DII), monocytes (DASH and DII) and resistin (DII and E-DII). After accounting for multiple testing, relationships with C3 (DASH: β = − 2.079, p = .011 and DII: β = 2.521, p = .036), IL-6 (DASH: β = − 0.063, p = .011), TNF-α (DASH: β = − 0.027, p = .034), WBC (DASH: β = − 0.028, p = .001 and DII: β = 0.029, p = .02), neutrophils (DASH: β = − 0.041, p = .001; DII: β = 0.043, p = .007; E-DII: β = 0.029, p = .009) and the NLR (DASH: β = − 0.035, p = .011) persisted.

Conclusions

Better diet quality, determined by the DASH score, may be more closely associated with inflammatory biomarkers related to health in middle- to older-aged adults than the MD, DII and E-DII scores.
Surgical management of tympanojugular paragangliomas using the flexible CO2 laser
Authors: Hackenberg Stephan , Meyer Till Jasper , Häfner Johannes , Scheich Matthias , Stöth Manuel , Al-Tinawi Fadi , Neun Tilmann , Mlynski Robert , Hagen Rudolf , Scherzad Agmal
Published: May 2022

Purpose

Surgery is a standard therapy for tympanojugular paragangliomas (TJP). Maintaining the quality of life (QoL) requires functional preservation. The flexible CO2 laser allows contact-free tumor removal. This retrospective study compares the postoperative functional outcomes of TJP surgery with and without the flexible CO2 laser.

Methods

Between 2005 and 2019, 51 patients with TJP were surgically treated at a tertiary hospital. Until 2012, 17 patients received conventional surgery. Thereafter, the flexible laser was used in 34 patients. Tumor extend, pre- and postoperative cranial nerve function, and complications were compared between the groups.

Results

The cohort consisted of 33 class A and B tumors and 18 class C and D tumors. Preoperative embolization was performed in 17 cases. Class C/D TJP were usually removed via an infratemporal fossa type A approach. Gross total tumor removal was achieved in 14/18 class C/D tumors. 3/51 patients suffered from long-term partial or complete facial palsy. No differences in post-therapeutic cranial nerve function or complications were noted between the conventional and laser group. One recurrence was observed after complete tumor resection.

Conclusion

The flexible CO2 laser was shown to be a safe and effective alternative to conventional bipolar cauterization, which is appreciated by the surgeon in these highly vascularized tumors. Both techniques allowed a high tumor control rate and good long-term results also from a functional point of view.
Prevalence and In-hospital outcomes of diabetes among acute ischemic stroke patients in china: results from the Chinese Stroke Center Alliance
Authors: Hu Guoliang , Gu Hongqiu , Jiang Yingyu , Yang Xin , Wang Chunjuan , Jiang Yong , Li Zixiao , Wang Yongjun , Wang Yilong
Published: May 2022

Background

Patients with ischemic stroke and diabetes are classified as extreme risk for secondary prevention, with much attention and specific management. However, the up-to-date information regarding the burden of diabetes in acute ischemic stroke (AIS) patients is lacking in China, and evidence for an association between diabetes and in-hospital outcomes after AIS remains controversial.

Methods

This quality improvement study was conducted at 1,476 participating hospitals in the Chinese Stroke Center Alliance between 2015 and 2019. Prevalence of diabetes was evaluated in the overall study population and different subgroups. The association between diabetes and in-hospital outcomes in AIS patients was analyzed by using multivariable logistic regression analysis and propensity score-matched analysis.

Results

Of 838,229 patients with AIS, 286,252 (34.2%) had diabetes/possible diabetes. The prevalence of diabetes/possible diabetes was higher in women than in men (37.6% versus 32.1%). Patients with diabetes/possible diabetes had higher rates of adverse in-hospital outcomes than those without. Multivariable analysis revealed a significant association between diabetes/possible diabetes and adverse in-hospital outcomes (all-cause mortality: odds ratio [OR], 1.30 [95% confidence interval [CI], 1.23–1.38]; major adverse cardiovascular events (MACEs): OR, 1.08 [95% CI, 1.06–1.10]) in AIS patients. The excess risk of in-hospital outcomes still remained in AIS patients with diabetes/possible diabetes after propensity score-matching analysis (all-cause mortality: OR, 1.26 [95% CI, 1.17–1.35]; MACEs: OR, 1.07 [95% CI, 1.05–1.10]).

Conclusion

Diabetes was highly prevalent among AIS patients in China and associated with worse in-hospital outcomes. Greater efforts to increase targeted approach to secondary prevention treatments of diabetes in AIS patients are warranted.
PERSEUS-IT 24-month analysis: a prospective observational study to assess the effectiveness of intravitreal aflibercept in routine clinical practice in Italy in patients with neovascular age-related macular degeneration
Authors: Nicolò Massimo , Ciucci Francesco , Nardi Marco , Parolini Barbara , Russo Andrea , Scupola Andrea , Torregrossa Salvatore , Vadalà Maria ,   on behalf of the PERSEUS-IT study investigators
Published: May 2022

Purpose

PERSEUS-IT (NCT02289924) was a prospective, observational, 2-year study evaluating the effectiveness and treatment patterns of intravitreal aflibercept (IVT-AFL) in patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice in Italy.

Methods

Treatment-naïve patients with nAMD receiving IVT-AFL per routine clinical practice were enrolled. The primary endpoint was mean change in visual acuity (VA; decimals) from baseline to month (M) 12 and M24. Outcomes were evaluated for the overall study population and independently for the 2 treatment cohorts: regular (3 initial monthly doses, ≥ 7 injections by M12, and ≥ 4 injections between M12 and M24) and irregular (any other pattern).

Results

Of 813 patients enrolled, 709 were included in the full analysis set (FAS); VA assessments were available for 342 patients at M12 (FAS1Y, 140 regular and 202 irregular) and 233 patients at M24 (FAS2Y, 37 regular and 196 irregular). In the overall FAS, the mean ± SD change in VA from baseline to M12 and M24 was + 0.09 ± 0.24 and + 0.02 ± 0.25 decimals, and there was a statistically significant difference between the regular and irregular cohorts in both FAS1Y (p = 0.0034) and FAS2Y (p = 0.0222). Ocular treatment-emergent adverse events were reported in 4.1% (n = 33/810 [safety set]) of patients.

Conclusion

In PERSEUS-IT, clinically relevant functional and anatomic improvements were observed within the first 12 months of IVT-AFL treatment in routine clinical practice in Italy in patients with treatment-naïve nAMD. These gains were generally maintained across the 2-year study. The safety profile of IVT-AFL was consistent with prior studies.

Trial registration number

ClinicalTrials.gov Identifier: NCT02289924.

Date of registration

November 13, 2014.
Endoplasmic reticulum stress and mitochondrial injury are critical molecular drivers of AlCl3-induced testicular and epididymal distortion and dysfunction: protective role of taurine
Authors: Khalaf Hanaa A. , Elsamanoudy Ayman Z. , Abo-Elkhair Salwa M. , Hassan Fatma E. , Mohie Passant M. , Ghoneim Fatma M.
Published: May 2022

Aluminum, the third most plentiful metal in the Earth’s crust, has potential for human exposure and harm. Oxidative stress plays an essential role in producing male infertility by inducing defects in sperm functions. We aimed to investigate the role of endoplasmic reticulum (ER) stress and mitochondrial injury in the pathogenesis of aluminum chloride (AlCl3)-induced testicular and epididymal damage at the histological, biochemical, and molecular levels, and to assess the potential protective role of taurine. Forty-eight adult male albino rats were separated into four groups (12 in each): negative control, positive control, AlCl3, and AlCl3 plus taurine groups. Testes and epididymis were dissected. Histological and immunohistochemical (Bax and vimentin) studies were carried out. Gene expression of vimentin, PCNA, CHOP, Bcl-2, Bax, and XBP1 were investigated via quantitative real-time polymerase chain reaction (qRT-PCR), besides estimation of malondialdehyde (MDA) and total antioxidant capacity (TAC). Light and electron microscopic examinations of the testes and epididymis revealed pathological changes emphasizing both mitochondrial injury and ER stress in the AlCl3 group. Taurine-treated rats showed a noticeable improvement in the testicular and epididymal ultrastructure. Moreover, they exhibited increased gene expression of vimentin, Bcl-2, and PNCA accompanied by decreased CHOP, Bax, and XBP1 gene expression. In conclusion, male reproductive impairment is a significant hazard associated with AlCl3 exposure. Both ER stress and mitochondrial impairment are critical mechanisms of the deterioration in the testes and epididymis induced by AlCl3, but taurine can amend this.
Phosphate intake, hyperphosphatemia, and kidney function
Authors: Rubio-Aliaga Isabel , Krapf Reto
Published: May 2022

Phosphate is essential in living organisms and its blood levels are regulated by a complex network involving the kidneys, intestine, parathyroid glands, and the skeleton. The crosstalk between these organs is executed primarily by three hormones, calcitriol, parathyroid hormone, and fibroblast growth factor 23. Largely due to a higher intake of ultraprocessed foods, dietary phosphate intake has increased in the last decades. The average intake is now about twice the recommended dietary allowance. Studies investigating the side effect of chronic high dietary phosphate intake suffer from incomplete dietary phosphate assessment and, therefore, often make data interpretation difficult. Renal excretion is quickly adapted to acute and chronic phosphate intake. However, at the high ends of dietary intake, renal adaptation, even in pre-existing normal kidney function, apparently is not perfect. Experimental intervention studies suggest that chronic excess of dietary phosphate can result in sustained higher blood phosphate leading to hyperphosphatemia. Evidence exists that the price of the homeostatic response (phosphaturia in response to phosphate loading/hyperphosphatemia) is an increased risk for declining kidney function, partly due by intraluminal/tubular calcium phosphate particles that provoke renal inflammation. High dietary phosphate intake and hyperphosphatemia are progression factors for declining kidney function and are associated with higher cardiovascular disease and mortality risk. This is best established for pre-existing chronic kidney disease, but epidemiological and experimental data strongly suggest that this holds true for subjects with normal renal function as well. Here, we review the latest advances in phosphate intake and kidney function decline.
Flexible and multifaceted: the plasticity of renin-expressing cells
Authors: Broeker Katharina A. E. , Schrankl Julia , Fuchs Michaela A. A. , Kurtz Armin
Published: May 2022

The protease renin, the key enzyme of the renin–angiotensin–aldosterone system, is mainly produced and secreted by juxtaglomerular cells in the kidney, which are located in the walls of the afferent arterioles at their entrance into the glomeruli. When the body’s demand for renin rises, the renin production capacity of the kidneys commonly increases by induction of renin expression in vascular smooth muscle cells and in extraglomerular mesangial cells. These cells undergo a reversible metaplastic cellular transformation in order to produce renin. Juxtaglomerular cells of the renin lineage have also been described to migrate into the glomerulus and differentiate into podocytes, epithelial cells or mesangial cells to restore damaged cells in states of glomerular disease. More recently, it could be shown that renin cells can also undergo an endocrine and metaplastic switch to erythropoietin-producing cells. This review aims to describe the high degree of plasticity of renin-producing cells of the kidneys and to analyze the underlying mechanisms.
Kidney metabolism and acid–base control: back to the basics
Authors: Imenez Silva Pedro Henrique , Mohebbi Nilufar
Published: May 2022

Kidneys are central in the regulation of multiple physiological functions, such as removal of metabolic wastes and toxins, maintenance of electrolyte and fluid balance, and control of pH homeostasis. In addition, kidneys participate in systemic gluconeogenesis and in the production or activation of hormones. Acid–base conditions influence all these functions concomitantly. Healthy kidneys properly coordinate a series of physiological responses in the face of acute and chronic acid–base disorders. However, injured kidneys have a reduced capacity to adapt to such challenges. Chronic kidney disease patients are an example of individuals typically exposed to chronic and progressive metabolic acidosis. Their organisms undergo a series of alterations that brake large detrimental changes in the homeostasis of several parameters, but these alterations may also operate as further drivers of kidney damage. Acid–base disorders lead not only to changes in mechanisms involved in acid–base balance maintenance, but they also affect multiple other mechanisms tightly wired to it. In this review article, we explore the basic renal activities involved in the maintenance of acid–base balance and show how they are interconnected to cell energy metabolism and other important intracellular activities. These intertwined relationships have been investigated for more than a century, but a modern conceptual organization of these events is lacking. We propose that pH homeostasis indissociably interacts with central pathways that drive progression of chronic kidney disease, such as inflammation and metabolism, independent of etiology.
A generalised path-following solver for robust analysis of material failure
Authors: Börjesson Elias , Remmers Joris J. C. , Fagerström Martin
Published: May 2022

When analysing complex structures with advanced damage or material models, it is important to use a robust solution method in order to trace the full equilibrium path. In light of this, we propose a new path-following solver based on the integral of the rate of dissipation in each material point, for solving problems exhibiting large energy dissipating mechanisms. The method is a generalisation and unification of previously proposed dissipation based path-following solvers, and makes it possible to describe a wider range of dissipation mechanisms, such as large strain plasticity. Furthermore, the proposed method makes it possible to, in a straightforward way, combine the effects from multiple dissipation mechanisms in a simulation. The capabilities of the solver are demonstrated on four numerical examples, from which it can be concluded that the proposed method is both versatile and robust, and can be used in different research domains within computational structural mechanics and material science.
Using ANN and OA techniques to determine the specific wear rate effectors of A356 Al-Si/Al2O3 MMC
Authors: Atta M. , Megahed M. , Saber D.
Published: May 2022

In the present work, it’s required to obtained the wear rate effectors’ values of A356 Al-Si/Al2O3 composite (Al2O3 wt%, applied load, hardness, and sliding distance) required to obtain a certain specific wear rate. So, the specific wear behavior of cast and heat-treated A356 Al-Si/Al2O3 metal matrix composites (MMC) were investigated as a function of its effectors. Five weight fractions of Al2O3 particles were used to produce specimens using stir casting. Two different hardness are obtained for each fraction (casted and heat-treated specimens). Sliding wear tests were done under three loads (20, 30, and 40 N), four sliding distances (310, 620, 930 and 1240 m) at constant speed (1 m/min). Experimental results indicated that the specific wear rate is generally reversed proportional to Al2O3 percentage. The impact of Al2O3 percentage was eliminated with the grown of applied load. Increasing the applied load decreases the specific wear rate, up to 20% Al2O3. However, at 25% Al2O3 the applied load increases the specific wear rate with a small graduation. Moreover, the heat treatment process improves the hardness and specific wear behavior of the casted MMC. Both Artificial neural network (ANN) and multiple regression techniques were used to predict the wear rate. The orthogonal array technique (OA) used in selecting the data set to train ANN and obtained a 2nd degree regression equation. ANN gives more realistic prediction then the regression equation. So, at the end, an algorithm is designed and tested to determine the weight fraction and other wear rate effectors for A356 Al-Si/Al2O3 MMC to obtain a certain wear rate, according to the uncertainty of the ANN. The used algorithm for obtaining the wear rate effectors provides a very good choices to produce a certain wear rate’s value, with error less than 1%.
Topology-based representative datasets to reduce neural network training resources
Authors: Gonzalez-Diaz Rocio , Gutiérrez-Naranjo Miguel A. , Paluzo-Hidalgo Eduardo
Published: May 2022

One of the main drawbacks of the practical use of neural networks is the long time required in the training process. Such a training process consists of an iterative change of parameters trying to minimize a loss function. These changes are driven by a dataset, which can be seen as a set of labeled points in an n-dimensional space. In this paper, we explore the concept of a representative dataset which is a dataset smaller than the original one, satisfying a nearness condition independent of isometric transformations. Representativeness is measured using persistence diagrams (a computational topology tool) due to its computational efficiency. We theoretically prove that the accuracy of a perceptron evaluated on the original dataset coincides with the accuracy of the neural network evaluated on the representative dataset when the neural network architecture is a perceptron, the loss function is the mean squared error, and certain conditions on the representativeness of the dataset are imposed. These theoretical results accompanied by experimentation open a door to reducing the size of the dataset to gain time in the training process of any neural network.
Hardy–Rellich and second order Poincaré identities on the hyperbolic space via Bessel pairs
Authors: Berchio Elvise , Ganguly Debdip , Roychowdhury Prasun
Published: May 2022

We prove a family of Hardy–Rellich and Poincaré identities and inequalities on the hyperbolic space having, as particular cases, improved Hardy-Rellich, Rellich and second order Poincaré inequalities. All remainder terms provided improve those already known in literature, and all identities hold with same constants for radial operators also. Furthermore, as applications of the main results, second order versions of the uncertainty principle on the hyperbolic space are derived.
An exterior overdetermined problem for Finsler N-Laplacian in convex cones
Authors: Ciraolo Giulio , Li Xiaoliang
Published: May 2022

We consider a partially overdetermined problem for anisotropic N-Laplace equations in a convex cone $$\Sigma $$
Σ
intersected with the exterior of a bounded domain $$\Omega $$
Ω
in $${\mathbb {R}}^N$$

R

N

, $$N\ge 2$$

N
≥
2

. Under a prescribed logarithmic condition at infinity, we prove a rigidity result by showing that the existence of a solution implies that $$\Sigma \cap \Omega $$

Σ
∩
Ω

must be the intersection of the Wulff shape and $$\Sigma $$
Σ
. Our approach is based on a Pohozaev-type identity and the characterization of minimizers of the anisotropic isoperimetric inequality inside convex cones.
Regularity of the free boundary for a parabolic cooperative system
Authors: Aleksanyan G. , Fotouhi M. , Shahgholian H. , Weiss G. S.
Published: May 2022

In this paper we study the following parabolic system $$\begin{aligned} \Delta \mathbf{u }-\partial _t \mathbf{u }=|\mathbf{u }|^{q-1}\mathbf{u }\,\chi _{\{ |\mathbf{u }|>0 \}}, \qquad \mathbf{u }= (u^1, \cdots , u^m) \ , \end{aligned}$$

Δ
u
-

∂
t

u
=

|
u
|

q
-
1

u

χ

{
|
u
|
>
0
}

,

u
=

(

u
1

,
⋯
,

u
m

)

,

with free boundary $$\partial \{|\mathbf{u }| >0\}$$

∂
{
|
u
|
>
0
}

. For $$0\le q<1$$

0
≤
q
<
1

, we prove optimal growth rate for solutions $$\mathbf{u }$$
u
to the above system near free boundary points, and show that in a uniform neighbourhood of any a priori well-behaved free boundary point the free boundary is $$C^{1, \alpha }$$

C

1
,
α

in space directions and half-Lipschitz in the time direction.
Rational inhibitor design for Pseudomonas aeruginosa salicylate adenylation enzyme PchD
Authors: Shelton Catherine L. , Meneely Kathleen M. , Ronnebaum Trey A. , Chilton Annemarie S. , Riley Andrew P. , Prisinzano Thomas E. , Lamb Audrey L.
Published: May 2022

Pseudomonas aeruginosa is an increasingly antibiotic-resistant pathogen that causes severe lung infections, burn wound infections, and diabetic foot infections. P. aeruginosa produces the siderophore pyochelin through the use of a non-ribosomal peptide synthetase (NRPS) biosynthetic pathway. Targeting members of siderophore NRPS proteins is one avenue currently under investigation for the development of new antibiotics against antibiotic-resistant organisms. Here, the crystal structure of the pyochelin adenylation domain PchD is reported. The structure was solved to 2.11 Å when co-crystallized with the adenylation inhibitor 5′-O-(N-salicylsulfamoyl)adenosine (salicyl-AMS) and to 1.69 Å with a modified version of salicyl-AMS designed to target an active site cysteine (4-cyano-salicyl-AMS). In the structures, PchD adopts the adenylation conformation, similar to that reported for AB3403 from Acinetobacter baumannii.

Graphical abstract
Effect of voxel size in cone-beam computed tomography on surface area measurements of dehiscences and fenestrations in the lower anterior buccal region
Authors: van Leeuwen B. J. , Dijkstra P. U. , Dieters J. A. , Verbeek H. P. J. , Kuijpers-Jagtman A. M. , Ren Y.
Published: May 2022

Objectives

This study aims to assess whether different voxel sizes in cone-beam computed tomography (CBCT) affected surface area measurements of dehiscences and fenestrations in the mandibular anterior buccal region.

Materials and methods

Nineteen dry human mandibles were scanned with a surface scanner (SS). Wax was attached to the mandibles as a soft tissue equivalent. Three-dimensional digital models were generated with a CBCT unit, with voxel sizes of 0.200 mm (VS200), 0.400 mm (VS400), and 0.600 mm (VS600). The buccal surface areas of the six anterior teeth were measured (in mm2) to evaluate areas of dehiscences and fenestrations. Differences between the CBCT and SS measurements were determined in a linear mixed model analysis.

Results

The mean surface area per tooth was 88.3 ± 24.0 mm2, with the SS, and 94.6 ± 26.5 (VS200), 95.1 ± 27.3 (VS400), and 96.0 ± 26.5 (VS600), with CBCT scans. Larger surface areas resulted in larger differences between CBCT and SS measurements (− 0.1 β, SE = 0.02,p < 0.001). Deviations from SS measurements were larger with VS600, compared to VS200 (1.3 β, SE = 0.05,P = 0.009). Fenestrations were undetectable with CBCT.

Conclusions

CBCT imaging magnified the surface area of dehiscences in the anterior buccal region of the mandible by 7 to 9%. The larger the voxel size, the larger the deviation from SS measurements. Fenestrations were not detectable with CBCT.

Clinical relevance

CBCT is an acceptable tool for measuring dehiscences but not fenestrations. However, CBCT overestimates the size of dehiscences, and the degree of overestimation depends on the actual dehiscence size and CBCT voxel size employed.
An L-shaped method with strengthened lift-and-project cuts
Authors: Glushko Pavlo , Fábián Csaba I. , Koberstein Achim
Published: May 2022

Lift-and-project (L &P) cuts are well-known general 0–1 programming cuts which are typically deployed in branch-and-cut methods to solve MILP problems. In this article, we discuss ways to use these cuts within the framework of Benders’ decomposition algorithms for solving two-stage mixed-binary stochastic problems with binary first-stage variables and continuous recourse. In particular, we show how L &P cuts derived for the master problem can be strengthened with the second-stage information. An adapted L-shaped algorithm and its computational efficiency analysis is presented. We show that the strengthened L &P cuts can significantly reduce the number of iterations and the solution time.
A random time-dependent noncooperative equilibrium problem
Authors: Barbagallo Annamaria , Guarino Lo Bianco Serena
Published: May 2022

The paper deals with the random time-dependent oligopolistic market equilibrium problem. For such a problem the firms’ point of view has been analyzed in Barbagallo and Guarino Lo Bianco (Optim. Lett. 14: 2479–2493, 2020) while here the policymaker’s point of view is studied. The random dynamic optimal control equilibrium conditions are expressed by means of an inverse stochastic time-dependent variational inequality which is proved to be equivalent to a stochastic time-dependent variational inequality. Some existence and well-posedness results for optimal regulatory taxes are obtained. Moreover a numerical scheme to compute the solution to the stochastic time-dependent variational inequality is presented. Finally an example is discussed.
Exploring cocatalyst type effect on the Ziegler–Natta catalyzed ethylene polymerizations: experimental and DFT studies
Authors: Masoori Maryam , Nekoomanesh Mehdi , Posada-Pérez Sergio , Rashedi Reza , Bahri-Laleh Naeimeh
Published: May 2022

Due to the important role of cocatalyst in the polymerization process employing industrially favored Ziegler–Natta catalysts, its effect on kinetic behavior, catalyst activity, and polymer properties is discussed. In this paper, triethyl aluminum (TEA) and triisobutyl aluminum (TIBA) have been used as the main cocatalyst ingredient with 10–20 mol percent of diethyl aluminum chloride (DEAC) and ethyl aluminum dichloride (EADC) cocatalysts, being neat TEA the cocatalysts with the highest activity. Moreover, TEA-DEAC and TEA-EADC cocatalysts revealed a built-up kinetic profile, while TIBA-DEAC and TIBA-EADC show a decay-type kinetic curve. According to melt flow index results, no considerable change in flowability was detected in the synthesized polyethylenes (PE). On the other hand, the ethylene insertion and chain termination mechanisms were investigated by means of density functional calculations using Ti active center located in (110) and (104) facets of the MgCl2 surface. To shed light on the bulkiness level of employed cocatalysts, buried volume (VBur) together with the two-dimensional map of cocatalyst systems were considered. Higher VBur of TIBA complex can explain its lower activity and decay type kinetic profile obtained by experimental studies.
Families of Legendrians and Lagrangians with unbounded spectral norm
Authors: Dimitroglou Rizell Georgios
Published: May 2022

Viterbo has conjectured that any Lagrangian in the unit co-disc bundle of a torus which is Hamiltonian isotopic to the zero-section satisfies a uniform bound on its spectral norm; a recent result by Shelukhin showed that this is indeed the case. The modest goal of our note is to explore two natural generalisations of this geometric setting in which the bound of the spectral norm fails: first, passing to Legendrian isotopies in the contactisation of the unit co-disc bundle (recall that any Hamiltonian isotopy can be lifted to a Legendrian isotopy) and, second, considering Hamiltonian isotopies but after modifying the co-disc bundle by attaching a critical Weinstein handle.
Exploring students’ mathematical discussions in a multi-level hybrid learning environment
Authors: Giberti Chiara , Arzarello Ferdinando , Bolondi Giorgio , Demo Heidrun
Published: May 2022

The research described in this paper focused on the issue of describing and understanding how mathematical discussion develops in a hybrid learning environment, and how students participate in it. The experimental plan involved several classes working in parallel, with pupils and teachers interacting both in their real classrooms and in a digital environment with other pupils and teachers. The research was based on a rich set of data collected from the M@t.abel 2020 project, which was developed in Italy during the Covid health crisis. Based on Complementary Accounts Methodology, the data analysis presented in this paper involved specialists from the fields of mathematics education and inclusive education. In the study we considered the complexity of learning and the different elements that have an impact on students’ activity and participation, when they are engaged in mathematical discussions within the multilevel-digital environment that emerged due to the pandemic. These parallel analyses showed that ‘mathematical discussion in the classroom’ is a complex (and sometimes chaotic) phenomenon wherein different factors interweave. A complementary approach assists in developing a global vision for this dynamic phenomenon and in highlighting local episodes that are crucial in this interplay of factors. It is precisely in these episodes that the role of the teacher is fundamental: these episodes appear as catalysts for the different variables, with the teacher acting as mediator.
Testing an Evaluation Tool to Facilitate Police Officers’ Peer Review of Child Interviews
Authors: Danby Meaghan C. , Sharman Stefanie J. , Guadagno Belinda
Published: May 2022

Providing child forensic interviewers with ongoing opportunities for feedback is critical to maintaining their interviewing skills. Given practical difficulties with engaging experts to provide this feedback (such as costs and workloads), the current paper explores whether a structured evaluation tool can assist police interviewers to accurately peer review interviews. A structured checklist of best practice skills was created, and participants in two studies used it to evaluate mock transcripts of child interviews that ranged in quality. Transcripts were manipulated to present the opening, transitional, and substantive interview phases as a strong, poor, or mixed performance of best practice skills. In Study 1, 57 police participants from one jurisdiction evaluated the opening and substantive phases of the transcript less accurately when the transcript contained a mixed performance of best practice and the transitional phase less accurately when it contained poor performance. In Study 2, a similar pattern of results was replicated with a sample of 37 police interviewers from a separate jurisdiction with shorter interview training. Results suggest that structured tools are helpful to inform peer review of child interviews, but tools that are too rigid might not be helpful when nuanced improvements are required.
On some non-linear systems of PDEs related to inverse problems in 3-d conductivity
Authors: Pedregal Pablo
Published: May 2022

We focus on certain non-linear, non-convex, non-coercive systems of PDEs in three dimensions that are directly motivated by inverse problems in conductivity for the three-dimensional case. It turns out that such systems are variational, as they formally are the Euler–Lagrange systems associated with an explicit first-order functional, and thus we exploit both its variational structure as well as its connection to inverse problems. In particular, boundary conditions play a central role.