bluuebunny/crossref_metadata_2025 huggingface dataset:
Tranilast abrogates cisplatin‐induced testicular and epididymal injuries: An insight into its modulatory impact on apoptosis/proliferation
Authors: Makled Mirhan N. , Said Eman
Published: May 2021

Cisplatin is a chemotherapeutic agent whose therapeutic use is greatly limited by the associated organs' toxicity and particularly, testicular toxicity. Cisplatin‐induced testicular damage reported being mediated through mitochondria‐mediated apoptosis, inflammation, and oxidative stress. Evidence showed that tranilast (TRN) has the ability to restore the oxidative status and modulate TRAIL/caspase‐8 signaling. This led us to hypothesize that TRN could abrogate cisplatin‐induced testicular and epididymal injuries via inhibiting oxidative stress and modulating proliferation and TRAIL/caspase‐8/cJNK signaling. Cisplatin injection induced oligospermia and abnormalities in testicular and epididymal structure along with impaired oxidative status. TRN administration (100 or 300 mg/kg) for 7 days post‐cisplatin injection preserved spermatogenesis and restored testicular and epididymal architecture, but restoration was more so in TRN300 than TRN100. This was in line with the restoration of balanced oxidative status as indicated by the increased total antioxidant capacity, glutathione and superoxide dismutase activity, and the decreased malondialdehyde content in testes (p < 0.05 vs. cisplatin). TRN increased the cell proliferation revealed by the increased expression of proliferating cell nuclear antigen in a dose‐dependent manner (p < 0.05 vs. cisplatin) whereas only TRN300 decreased testicular cJNK, TRAIL, and caspase‐8 expression (p < 0.05 vs. cisplatin). Moreover, TRN dose‐dependently inhibited the pro‐inflammatory transcription factor NF‐kB and the cytokine TNF‐α expressions in testes. In conclusion, TRN300 was more effective than TRN100 in alleviating cisplatin‐induced testicular and epididymal injuries and in enhancing spermatogenesis. This curative effect of TRN might be mediated through its antioxidant and anti‐inflammatory impacts along with its modulatory impact on cJNK/TRAIL/caspase‐8 signaling favoring proliferation rather than apoptosis.
Universal p‐ary designs
Authors: Jolliffe Liam
Published: May 2021

We investigate ‐ary ‐designs which are simultaneously designs for all , which we call universal ‐ary designs. Null universal designs are well understood due to Gordon James via the representation theory of the symmetric group. We study non‐null designs and determine necessary and sufficient conditions on the coefficients for such a design to exist. This allows us to classify all universal designs, up to similarity.
Contours modeling of fascicular groups from micro‐computed tomography images of peripheral nerves
Authors: Zhong Yingchun , Qi Jian , Li Fang , Sun Siyu , Zhu Shuang , Wang Chao , Luo Peng
Published: May 2021

The objective is to explore the appropriate method to establish the mathematical model of fascicular groups' contours from micro‐CT images of peripheral nerves during the nonsplitting/merging phase. The original contours of fascicular groups from the micro‐CT image were described as the discrete pixel points. All discrete pixel points of shapes were extracted into a data set through image processing. The data set was modeled by Bezier, B‐spline method, respectively, in which each discrete point was used as a control point for modeling. In the Bezier method, the contour of a nerve bundle needs more than two different Bezier curves to model, making the junction points between two models discontinuous. The contour model described by B‐spline is very close to the original contour of nerve bundles when all discrete points are used as the control points. The models described by B‐spline have different terms and parameters, making it difficult to calculate in the following research. When the third‐order quasi‐uniform B‐spline method is employed, all nerve bundles models have the same number of terms. The modeling error of third‐order quasi‐uniform B‐spline is less than 3% when the Dice coefficient is more than 95%, and the appropriate number of sampling times is 21. The modeling accuracy is improved with increased sampling times when it is less than 21. However, the modeling accuracy remains stable while the number of sampling times is more than 21. The third‐order quasi‐uniform B‐spline is more efficient in modeling nerve bundles' contour, which is more accurate and straightforward.
Identification of microplastics using 4‐dimethylamino‐4′‐nitrostilbene solvatochromic fluorescence
Authors: Sancataldo Giuseppe , Ferrara Vittorio , Bonomo Francesco Paolo , Chillura Martino Delia Francesca , Licciardi Mariano , Pignataro Bruno Giuseppe , Vetri Valeria
Published: May 2021

In this work, we introduce the use of 4‐dimethylamino‐4′‐nitrostilbene (DANS) fluorescent dye for applications in the detection and analysis of microplastics, an impendent source of pollution made of synthetic organic polymers with a size varying from less than 5 mm to nanometer scale. The use of this dye revealed itself as a versatile, fast and sensitive tool for readily discriminate microplastics in water environment. The experimental evidences herein presented demonstrate that DANS efficiently absorbs into a variety of polymers constituting microplastics, and its solvatochromic properties lead to a positive shift of the fluorescence emission spectrum according to the polarity of the polymers. Therefore, under UV illumination, microplastics glow a specific emission spectrum from blue to red that allows for a straightforward polymer identification. In addition, we show that DANS staining gives access to different detection and analysis strategies based on fluorescence microscopy, from simple epifluorescence fragments visualization, to confocal microscopy and phasor approach for plastic components quantification.
A year away to 100th year of vitamin E synthesis
Authors: Kundu Subhradip , Sarkar Debayan
Published: May 2021

Vitamin E was discovered in the year 1922 as a dietary constituent by Herbert McLean Evans and Katharine J. Scott Bishop. Next year we will be celebrating 100th year anniversary of vitamin E discovery. This minireview highlights discoveries of eight naturally available forms (tocopherols and tocotrienols) of vitamin E and their most important synthetic attempts. This minireview is dedicated to the pioneers of vitamin E for serving a crucial biomolecule to the mankind.
Fully automated production of the fibroblast activation protein radiotracer [18F]FAPI‐74
Authors: Dahl Kenneth , Jussing Emma , Bylund Lovisa , Moein Mohammad Mahdi , Samén Erik , Tran Thuy
Published: May 2021

We report herein an efficient and fully automated protocol for the radiosynthesis of [18F]FAPI‐74, a new positron emission tomography (PET) radiopharmaceutical for in vivo detection of the fibroblast activation protein. [18F]FAPI‐74 was synthesized via a rapid [18F]aluminum fluoride coordination reaction, which was first developed on the flexible GE TRACERLab FX2N (FXN) platform and later translated to the cassette‐based module Trasis AllInOne (AIO). The results obtained with both modules were comparable in terms of yield and reproducibility. Automation of [18F]FAPI‐74 radiosynthesis on the FXN was carried out in 35 min with a radiochemical yield (RCY) of 18.5 ± 2.5% (n = 5, relative to starting [18F]fluoride). Method transfer to the AIO platform following minor optimizations allowed for the production of [18F]FAPI‐74 in an isolated RCY of 20 ± 2.5% [n = 3] with an overall synthesis time of 40 min. The radiochemical purity was greater than 95% for [18F]FAPI‐74, obtained from both modules. Overall, the protocol reliably provides a sterile and pyrogen‐free good manufacturing practice (GMP) compliant product of [18F]FAPI‐74 suitable for clinical PET imaging.
Echo Time‐Dependent Observed Lung T1 in Patients With Chronic Obstructive Pulmonary Disease in Correlation With Quantitative Imaging and Clinical Indices
Authors: Triphan Simon M. F. , Weinheimer Oliver , Gutberlet Marcel , Heußel Claus P. , Vogel‐Claussen Jens , Herth Felix , Vogelmeier Claus F. , Jörres Rudolf A. , Kauczor Hans‐Ulrich , Wielpütz Mark O. , Biederer Jürgen , Jobst Bertram J. ,   for the COSYCONET Study Group
Published: May 2021

Background

There is a clinical need for imaging‐derived biomarkers for the management of chronic obstructive pulmonary disease (COPD). Observed pulmonary T1 (T1(TE)) depends on the echo‐time (TE) and reflects regional pulmonary function.

Purpose

To investigate the potential diagnostic value of T1(TE) for the assessment of lung disease in COPD patients by determining correlations with clinical parameters and quantitative CT.

Study Type

Prospective non‐randomized diagnostic study.

Population

Thirty COPD patients (67.7 ± 6.6 years). Data from a previous study (15 healthy volunteers [26.2 ± 3.9 years) were used as reference.

Field Strength/Sequence

Study participants were examined at 1.5 T using dynamic contrast‐enhanced three‐dimensional gradient echo keyhole perfusion sequence and a multi‐echo inversion recovery two‐dimensional UTE (ultra‐short TE) sequence for T1(TE) mapping at TE1‐5 = 70 μsec, 500 μsec, 1200 μsec, 1650 μsec, and 2300 μsec.

Assessment

Perfusion images were scored by three radiologists. T1(TE) was automatically quantified. Computed tomography (CT) images were quantified in software (qCT). Clinical parameters including pulmonary function testing were also acquired.

Statistical Tests

Spearman rank correlation coefficients (ρ) were calculated between T1(TE) and perfusion scores, clinical parameters and qCT. A P‐value <0.05 was considered statistically significant.

Results

Median values were T1(TE1‐5) = 644 ± 78 msec, 835 ± 92 msec, 835 ± 87 msec, 831 ± 131 msec, 893 ± 220 msec, all significantly shorter than previously reported in healthy subjects. A significant increase of T1 was observed from TE1 to TE2, with no changes from TE2 to TE3 (P = 0.48), TE3 to TE4 (P = 0.94) or TE4 to TE5 (P = 0.02) which demonstrates an increase at shorter TEs than in healthy subjects. Moderate to strong Spearman's correlations between T1 and parameters including the predicted diffusing capacity for carbon monoxide (DLCO, ρ < 0.70), mean lung density (MLD, ρ < 0.72) and the perfusion score (ρ > −0.69) were found. Overall, correlations were strongest at TE2, weaker at TE1 and rarely significant at TE4‐TE5.

Data Conclusion

In COPD patients, the increase of T1(TE) with TE occurred at shorter TEs than previously found in healthy subjects. Together with the lack of correlation between T1 and clinical parameters of disease at longer TEs, this suggests that T1(TE) quantification in COPD patients requires shorter TEs. The TE‐dependence of correlations implies that T1(TE) mapping might be developed further to provide diagnostic information beyond T1 at a single TE.

Level of Evidence

2

Technical Efficacy

Stage 1
Long‐term stability of adjunctive use of enamel matrix protein derivative on porcine‐derived xenograft for the treatment of one‐wall intrabony defects: A 4‐year extended follow‐up of a randomized controlled trial
Authors: Lee Jae‐Hong , Jeong Seong‐Nyum
Published: May 2021

Background

The long‐term outcomes of demineralized porcine bone matrix (DPBM) in combination with enamel matrix protein derivative (EMD) for the treatment of one‐wall intrabony defects have not yet been evaluated. Therefore, this study aimed to assess the clinical, radiographic, and patient‐reported outcomes of regenerative therapy using DPBM with EMD (test group) in comparison with DPBM alone (control group) for the treatment of one‐wall intrabony defects in the molar regions.

Methods

Thirty‐four patients (control group, n = 18, and test group, n = 16) were available at the 4‐year follow‐up assessment. Clinical (probing pocket depth and clinical attachment level [CAL]), radiographic (defect depth and width), and patient‐reported (Oral Health Impact Profile [OHIP]‐14) parameters were evaluated at baseline, 2 years, and 4 years after regenerative treatment.

Results

Both treatment modalities, with and without adjunctive use of EMD, resulted in significant improvement of clinical (mean gain in CAL of 1.58 ± 1.34 mm), radiographic (mean defect width fill of 2.41 ± 0.90 mm), and oral health‐related quality of life outcomes at 2 years after regenerative treatment of one‐wall intrabony defects (P < 0.001), which has been sustained over a 4‐year follow‐up period. Particularly, OHIP‐14 scores revealed a statistically significant reduction in physical pain, psychological discomfort, and physical disability (P < 0.05).

Conclusions

The clinical, radiographic, and patient‐reported outcomes were significantly improved when DPBM was used in the regenerative treatment, but no additional benefits were observed with the adjunctive use of EMD.
Enhanced access to recommendations from the Cochrane Handbook for improving authors' judgments about risk of bias: A randomized controlled trial
Authors: Barcot Ognjen , Ivanda Matej , Buljan Ivan , Pieper Dawid , Puljak Livia
Published: May 2021

This randomized controlled trial (RCT) aimed to test the efficacy of enhanced access to Cochrane Handbook (Handbook) recommendations for judging the 2011 Cochrane risk of bias (RoB) domains for improving the adequacy of RoB judgments. Parallel‐group RCT with a 1:1 allocation ratio (N = 2271 per group) was conducted. Eligible participants were corresponding authors of all published Cochrane reviews and protocols. After allocation by a random number generator, participants received 20 scenarios for assessing RoB. The intervention group was shown tables from the Handbook with instructions for assessing 2011 RoB tool together with scenarios they were supposed to assess—enhanced access to the Handbook. The control group was shown only a general link to the Handbook. The primary outcome was the proportion of participants that made an adequate judgment of RoB scenarios for analyzed domains. There were 240 responses out of 2020 delivered e‐mail invitations in the intervention and 197/2254 in the control group. Only five participants from the intervention group judged RoB adequately in all the 20 scenarios and no one in the control group. The proportion of participants who adequately assessed all the scenarios within a domain was significantly higher in the intervention than in the control group. The frequency of adequate RoB judgments was 7.1% (95% CI: 5.0–9.3%, p < 0.001) higher in the intervention group (76.2%) than in the control group (69.0%). The enhanced access yields more adequate RoB assessments and could be incorporated in software supporting the RoB tool.
A prospective study of patient‐reported xerostomia‐related outcomes after parotidectomy
Authors: Brodie Kara D. , Zebolsky Aaron L. , Ochoa Edgar , Ha Patrick K. , Heaton Chase M. , El‐Sayed Ivan H. , Ryan William R.
Published: May 2021

Objective

There is a paucity of data on patient‐reported outcome measures regarding xerostomia after parotidectomy surgery. Although salivary flow rates after parotidectomy have been previously studied, they do not correlate with subjective xerostomia. This study was designed to evaluate if unilateral parotidectomy increases patient‐reported xerostomia.

Methods

A prospective cohort of patients undergoing unilateral partial, superficial, or total parotidectomy for benign or low‐grade malignant pathology without postoperative radiation at a tertiary care academic center was studied. We analyzed patient‐reported outcome measures of xerostomia using the Xerostomia Questionnaire (XQ) preoperatively and postoperatively. We compared pre‐ and postoperative cumulative and individual XQ scores using Wilcoxon signed‐rank tests. We stratified patients by the weight in grams (g) of the parotid tissue excised, pathology, smoking status, and xerostomia‐related medication use.

Results

Twenty‐two adults with benign or low grade malignant unilateral parotid tumors were included. Postoperative questionnaires were completed at a median of 10.2 months (interquartile range [IQR] 8.6‐11.9) after unilateral parotidectomy. Mean preoperative and postoperative cumulative XQ scores, on a 100‐point scale, with higher scores representing worse symptoms, were 10.33 (95% CI: 4.46‐16.20) and 10.54 (95% CI: 5.10‐15.98), respectively, with a mean change of +0.21 (p = 0.472). There were no statistically significant changes in individual XQ symptom scores. Neither type of parotidectomy, resection specimens weighing over 10 g, smoking habits, xerostomia‐related medication use, nor malignant pathology were associated with worse symptom scores.

Conclusion

Based on these data, unilateral parotidectomy does not appear to definitely, or at least consistently, increase xerostomia per patient reporting. More extensive parotid resections are not associated with worse symptom scores. These data can help guide preoperative counseling and postoperative expectations for parotidectomy.

Level of Evidence

2b.
Recombinant Bovine and Human Osteopontin Generated by Chlamydomonas reinhardtii Exhibit Bioactivities Similar to Bovine Milk Osteopontin When Assessed in Mouse Pups Fed Osteopontin‐Deficient Milk
Authors: Jiang Rulan , Tran Miller , Lönnerdal Bo
Published: May 2021

Scope

Osteopontin (OPN), a highly phosphorylated and glycosylated protein, is present in most body fluids, including milk. OPN appears at a high concentration in human milk (130–180 mg L−1), but not bovine milk (≈18 mg mL−1). It is previously shown that milk OPN is involved in various biological processes and therefore may be a valuable infant formula additive.

Methods and Results

In the present study, recombinant bovine OPN (rbOPN) and recombinant human OPN (rhOPN) are generated in a Chlamydomonas reinhardtii (C. reinhardtii) algal expression system. The rbOPN and rhOPN are phosphorylated but not glycosylated. To assess the bioactivities of rbOPN and rhOPN and compare their bioactivities to those of bovine milk OPN (bmOPN), wild‐type (WT) mouse pups nursed by OPN knock‐out (KO) dams are orally fed bmOPN, rbOPN, and rhOPN daily from postnatal days 1–21 (P1‐21). Effects of these OPNs on development of the brain, intestine, and immune function are evaluated. The results show that rbOPN and rhOPN exhibit effects similar to those of bmOPN as well as mouse milk OPN on stimulating proliferation of the small intestine, increasing brain myelination and cognitive development, and enhancing development of immune function.

Conclusion

rbOPN and rhOPN are likely to provide beneficial bioactivities when added to infant diets.
(Poly)phenol‐Rich Diets in the Management of Endothelial Dysfunction in Diabetes Mellitus: Biological Properties in Cultured Endothelial Cells
Authors: Rocha Sara , Oskolkova Olga , de Freitas Victor , Reis Ana
Published: May 2021

Processed and ready‐to‐eat foods become routinely consumed resulting in a sharp rise of sugar intake in people's daily diets. The inclusion of fresh fruits and vegetables rich in (poly)phenols has been encouraged by the World Health Organization (WHO) as part of the daily choices to ameliorate endothelial dysfunction and ease the socio‐economic burden of diabetes. Research in Food, Nutrition, and Cell Metabolism areas is revealing that the health benefits of (poly)phenol‐rich foods go beyond their antioxidant properties and are in fact key modulators of redox and glycaemia status, and inflammatory response contributing to improved endothelial function and vascular health in diabetes. Other beneficial aspects include appetite modulation, regulation of hydrolytic enzymes involved in sugar and lipid metabolism, and mediation of cell–cell aggregation events. This work overviews the current knowledge on the biological properties of ingested (poly)phenols in cultured endothelial cells with emphasis on the circulating (poly)phenols, providing support to (poly)phenol‐rich diets as alternatives to drug‐based therapies in the prevention, treatment, and management of diabetes. A critical evaluation on the caveats and challenges involve in current experimental cell‐based designs and approaches adopted is also discussed.
Electrical and thermal analysis of AlGaN/GaN HEMTs transferred onto diamond substrate through an aluminum nitride layer
Authors: Abou Daher Mahmoud , Lesecq Marie , Defrance Nicolas , Okada Etienne , Boudart Bertrand , Guhel Yannick , Tartarin Jean Guy , de Jaeger Jean Claude
Published: May 2021

In this paper, electrical and thermal analysis of short gate length AlGaN/GaN HEMTs (high electron mobility transistors) transferred onto diamond substrate through aluminum nitride (AlN) layer are provided. The specific transfer technology uses sputtered AlN as bonding layer. An improvement in maximum DC current density of 14% is observed after transfer on the diamond substrate, with attractive RF performances as well. Lag effects are evaluated thanks to pulsed measurement. Thermal analysis is also proposed to quantify the effects of bonding on self‐heating. Both electrical and thermal characterizations are used as markers to evaluate the impact of the transfer process on the developed HEMT.
Global and local brain connectivity changes associated with sudden unilateral sensorineural hearing loss
Authors: Minosse Silvia , Garaci Francesco , Martino Federica , Di Mauro Roberta , Melis Milena , Di Giuliano Francesca , Picchi Eliseo , Guerrisi Maria , Floris Roberto , Di Girolamo Stefano , Toschi Nicola
Published: May 2021

Recent studies suggest that even moderate sudden sensorineural hearing loss (SSNHL) causes reduction of gray matter volume in the primary auditory cortex, diminishing its ability to react to sound stimulation, as well as reorganization of functional brain networks. We employed resting‐state functional MRI (rs‐fMRI), in conjunction with graph‐theoretical analysis and a newly developed functional “disruption index,” to study whole‐brain as well as local functional changes in patients with unilateral SSNHL. We also assessed the potential of graph‐theoretical measures as biomarkers of disease, in terms of their relationship to clinically relevant audiological parameters. Eight patients with moderate or severe unilateral SSNHL and 15 healthy controls were included in this prospective pilot study. All patients underwent rs‐fMRI to study potential changes in brain connectivity. From rs‐fMRI data, global and local graph‐theoretical measures, disruption index, and audiological examinations were estimated. Mann‐Whitney U tests were used to study the differences between SSNHL patients and healthy controls. Associations between brain metrics and clinical variables were studied using multiple linear regressions, and the presence or absence of brain network hubs was assessed using Fisher's exact test. No statistically significant differences between SSNHL patients and healthy controls were found in global or local network measures. However, when analyzing brain networks through the disruption index, we found a brain‐wide functional network reorganization (p < 0.001 as compared with controls), whose extent was associated with clinical impairment (p < 0.05). We also observed several functional hubs in SSNHL patients that were not present in healthy controls and vice versa. Our results demonstrate a brain involvement in SSNHL patients, not detectable using conventional graph‐theoretical analysis, which may yield subtle disease clues and possibly aid in monitoring disease progression in clinical trials.
Economic Evaluations of Breast Cancer Care in Low- and Middle-Income Countries: A Scoping Review
Authors: Erfani Parsa , Bhangdia Kayleigh , Stauber Catherine , Mugunga Jean Claude , Pace Lydia E. , Fadelu Temidayo
Published: May 2021

Background

Understanding the cost of delivering breast cancer (BC) care in low- and middle-income countries (LMICs) is critical to guide effective care delivery strategies. This scoping review summarizes the scope of literature on the costs of BC care in LMICs and characterizes the methodological approaches of these economic evaluations.

Materials and Methods

A systematic literature search was performed in five databases and gray literature up to March 2020. Studies were screened to identify original articles that included a cost outcome for BC diagnosis or treatment in an LMIC. Two independent reviewers assessed articles for eligibility. Data related to study characteristics and methodology were extracted. Study quality was assessed using the Drummond et al. checklist.

Results

Ninety-one articles across 38 countries were included. The majority (73%) of studies were published between 2013 and 2020. Low-income countries (2%) and countries in Sub-Saharan Africa (9%) were grossly underrepresented. The majority of studies (60%) used a health care system perspective. Time horizon was not reported in 30 studies (33%). Of the 33 studies that estimated the cost of multiple steps in the BC care pathway, the majority (73%) were of high quality, but studies varied in their inclusion of nonmedical direct and indirect costs.

Conclusion

There has been substantial growth in the number of BC economic evaluations in LMICs in the past decade, but there remain limited data from low-income countries, especially those in Sub-Saharan Africa. BC economic evaluations should be prioritized in these countries. Use of existing frameworks for economic evaluations may help achieve comparable, transparent costing analyses.

Implications for Practice

There has been substantial growth in the number of breast cancer economic evaluations in low- and middle-income countries (LMICs) in the past decade, but there remain limited data from low-income countries. Breast cancer economic evaluations should be prioritized in low-income countries and in Sub-Saharan Africa. Researchers should strive to use and report a costing perspective and time horizon that captures all costs relevant to the study objective, including those such as direct nonmedical and indirect costs. Use of existing frameworks for economic evaluations in LMICs may help achieve comparable, transparent costing analyses in order to guide breast cancer control strategies.
Open government and the right to information: Implications for transparency and accountability in Asia
Authors: Zafarullah Habib , Siddiquee Noore Alam
Published: May 2021

Many countries in Asia have recently been following the global trend by introducing the right to information (RTI) law to build open and accountable government systems. This article compares the implementation of such law in four countries in the Asian region (India, Bangladesh, Indonesia and Thailand) to assess how they have produced outcomes supporting open government (OG) goals. Drawing on an extensive review of the conceptual literature, secondary sources and official publications, it shows that, notwithstanding many promising features, RTI laws have performed poorly within the overarching notion of OG. Implementation has suffered from numerous deficits and challenges implicating both the demand and supply‐side actors—those who seek information and those who are mandated to provide information under the law. Such challenges, together with an inherent flaw, deviation from rules, technical blunders and bureaucratic indifference and non‐compliance, have rendered the RTI law mostly ineffective. The paper highlights current deficits/snags and underscores the imperative of raising the awareness and capacity at both community and official levels and creating a culture where transparency and openness is valued over secrecy and confidentiality. This would require strong political commitment, selfless bureaucratic support and genuine citizen engagement.
Structural basis for the stereospecific inhibition of the dual proline/hydroxyproline catabolic enzyme ALDH4A1 by trans‐4‐hydroxy‐L‐proline
Authors: Bogner Alexandra N. , Stiers Kyle M. , McKay Cole M. , Becker Donald F. , Tanner John J.
Published: May 2021

Aldehyde dehydrogenase 4A1 (ALDH4A1) catalyzes the final steps of both proline and hydroxyproline catabolism. It is a dual substrate enzyme that catalyzes the NAD+‐dependent oxidations of L‐glutamate‐γ‐semialdehyde to L‐glutamate (proline metabolism), and 4‐hydroxy‐L‐glutamate‐γ‐semialdehyde to 4‐erythro‐hydroxy‐L‐glutamate (hydroxyproline metabolism). Here we investigated the inhibition of mouse ALDH4A1 by the six stereoisomers of proline and 4‐hydroxyproline using steady‐state kinetics and X‐ray crystallography. Trans‐4‐hydroxy‐L‐proline is the strongest of the inhibitors studied, characterized by a competitive inhibition constant of 0.7 mM, followed by L‐proline (1.9 mM). The other compounds are very weak inhibitors (approximately 10 mM or greater). Insight into the selectivity for L‐stereoisomers was obtained by solving crystal structures of ALDH4A1 complexed with trans‐4‐hydroxy‐L‐proline and trans‐4‐hydroxy‐D‐proline. The structures suggest that the 10‐fold greater preference for the L‐stereoisomer is due to a serine residue that hydrogen bonds to the amine group of trans‐4‐hydroxy‐L‐proline. In contrast, the amine group of the D‐stereoisomer lacks a direct interaction with the enzyme due to a different orientation of the pyrrolidine ring. These results suggest that hydroxyproline catabolism is subject to substrate inhibition by trans‐4‐hydroxy‐L‐proline, analogous to the known inhibition of proline catabolism by L‐proline. Also, drugs targeting the first enzyme of hydroxyproline catabolism, by elevating the level of trans‐4‐hydroxy‐L‐proline, may inadvertently impair proline catabolism by the inhibition of ALDH4A1.
Robotic surgery can be safely performed for patients and healthcare workers during COVID‐19 pandemic
Authors: Sparwasser Peter , Brandt Maximillian P. , Haack Maximillian , Dotzauer Robert , Boehm Katharina , Gheith Mohammed Kamal , Mager Rene , Jäger Wolfgang , Ziebart Alexander , Höfner Thomas , Tsaur Igor , Haferkamp Axel , Borgmann Hendrik
Published: May 2021

Objectives

To investigate the safety of robotic surgery during COVID‐19 pandemic concerning new‐acquired COVID‐19 infections for patients and healthcare workers.

Patients

We performed a retrospective single‐centre cohort study of patients undergoing robotic surgery in initial period of COVID‐19 pandemic. Patients and healthcare workers COVID‐19 infection status was assessed by structured telephone follow‐up and/or repeated nasopharyngeal swabs.

Results

After 61 robotic surgeries (93,5% cancer surgery), one patient (1.6%) had COVID‐19 infection. Sixty healthcare workers cumulatively exposed to 1187 h of robotic surgery had no infection. One patient with postoperative proof of SARS‐CoV‐2 had complete recovery. After this potentially contagious robotic surgery, eight healthcare workers had no COVID‐19 infection after follow‐up with each three nasopharyngeal swabs.

Conclusions

Early clinical experience of robotic surgery during COVID‐19 pandemic shows that robotic surgery can be safely performed for patients and healthcare workers. Despite our results we recommend elective surgery only for verified COVID‐19 negative patients.
The work of class: Cash transfers and community development in Tanzania
Authors: Green Maia
Published: May 2021

This article uses the concept of convenience as an analytical prompt to investigate how ideas about work organize a cash‐based social assistance program financed through foreign aid. Productive Social Safety Nets (PSSN) is a nationwide program providing small regular payments to very poor households in Tanzania. Cash transfers as components of social assistance not predicated on working confront assumptions many Tanzanians share about the importance of work as foundational to self‐reliance as the bedrock of personal and national development. The program uses existing architectures of community development to creatively combine Tanzanian values around poor people's responsibility for their own development with World Bank conceptualizations of social assistance as a productive investment. Ethnographic research at the interface between program implementors and beneficiaries provides insights into the attitudes many Tanzanians hold about development and their place in it and sheds light on the ambivalent feelings of insecure middle classes about changing forms of state‐managed social assistance. Implementation involves an intricate orchestration of prescriptive ideals about labor, entitlement, and value organized around labor‐intensive bureaucratic procedures, public works, and community sensitization sessions. Labor making and making visible different kinds of work characterize program implementation. Prevailing attitudes toward social assistance, and the class relations through which they are realized, are perpetuated through ostensibly novel programs.
Cleaning house before hosting new guests: A political path dependence model of political connection adaptation in the aftermath of anticorruption shocks
Authors: Jiang Han , Jia Nan , Bai Tao , Bruton Garry D.
Published: May 2021

Research Summary

We develop a political path dependence model that integrates the network embeddedness perspective and the literature on corporate political strategy to understand how firms adapt their political connections when anticorruption efforts lead to the turnover of government officials. We posit that although firms that have close associations with ousted corrupt officials can benefit from both removing existing political connections (“cleaning house”) and developing new connections with their successors (“hosting new guests”), political path dependence enables firms to do the former but constrains them from doing the latter. These effects are magnified when firms are highly dependent on the government, and when the ousted corrupt officials have great political power. Evidence from anticorruption campaigns in China between 2012 and 2018 lends support for our theoretical predictions.

Managerial Summary

It is common for firms to strive to stay connected with government officials. Of interest is, when political power shifts, can firms “update” their connections by severing ties with politicians who fall out of power and building new ones? Our political path dependent model demonstrates that it may not be a symmetric process. After the downfall and replacements of public officials due to corruption indictments, firms that are more closely associated with ousted, corrupt officials will indeed be more motivated and able to remove existing connections. However, the successors of ousted officials will more likely distance themselves from these firms, thereby undermining the firms' abilities to build new connections with them. Empirical evidence from anticorruption campaigns in China between 2012 and 2018 supports our predictions.
Metal–Organic Frameworks for Electrocatalysis: Beyond Their Derivatives
Authors: Yang Yongchao , Yang Yuwei , Liu Yangyang , Zhao Shenlong , Tang Zhiyong
Published: May 2021

Electrocatalysis is at the heart of many significant chemical transformation processes and advanced clean energy technologies. Traditional noble/transition metal oxides are widely used as electrocatalysts; however, they often suffer from intrinsic disadvantages, including low atom utilization, small surface area, and unfavorable tunability. Metal–organic frameworks (MOFs), as a new family of catalytic materials, are attracting extensive attention due to their unique physicochemical properties. The tremendous pristine MOF‐based materials are created using various synthetic approaches and further used for important energy conversions. Herein, a systematic overview on the unique merits and the state‐of‐the‐art design of MOF‐based electrocatalysts is offered. This review also presents recent advances in the development of various pristine MOFs and MOF‐based host–guest composite catalysts for electrocatalysis (i.e., oxygen reduction reaction, hydrogen oxidation reaction, hydrogen evolution reaction, oxygen evolution reaction, and CO2 reduction reaction) and discusses the future challenges and opportunities in this emerging field.
Rational Design of Superior Electrocatalysts for Water Oxidation: Crystalline or Amorphous Structure?
Authors: Guan Daqin , Zhou Wei , Shao Zongping
Published: May 2021

Crystalline, amorphous, and crystalline–amorphous materials have become three important electrode materials for the bottleneck oxygen‐evolving reaction (OER) in the promising hydrogen‐producing technology of water splitting. With the rapid development of in situ/ex situ characterizations, the understanding of active sites in electrocatalysts has been deepened via the structure–activity/stability relationships extracted from the observations on catalysts during/after the OER. Herein, the origins of changes in initial crystalline, amorphous, and crystalline–amorphous materials during/after the OER are systematically analyzed and the underlying variation effects on catalyst activity and stability are discussed based on recent representative studies, aiming at guiding OER catalyst design in the future.
Hierarchically Assembling CoFe Prussian Blue Analogue Nanocubes on CoP Nanosheets as Highly Efficient Electrocatalysts for Overall Water Splitting
Authors: Quan Li , Li Shuohan , Zhao Zhanpeng , Liu Jianqiao , Ran Yue , Cui Jiayi , Lin Wei , Yu Xuelian , Wang Lin , Zhang Yihe , Ye Jinhua
Published: May 2021

Efficient and durable electrocatalysts are highly desirable for overall water splitting. Herein, a facile strategy is demonstrated to rationally construct CoFe Prussian blue analogues (PBA)@CoP cube‐on‐sheet hierarchical structure by etching reaction with intermediated CoO to form PBA nanocubes. Benefitting from the heterostructured engineering, the as‐synthesized CoFe PBA@CoP presents remarkable electrocatalytic performance in 1.0 m KOH, only requiring overpotentials of 100 mV for hydrogen evolution reaction (HER) and 171 mV for oxygen evolution reaction (OER) to reach the 10 mA cm−2 current density with good stability. Extraordinarily enhanced electrocatalytic performance is ascribed to not only the rapid charge transfer of active species, but also the synergistic effect between each component to achieve tuned electronic structure and abundant electrocatalytic active sites. Especially, the assembled two‐electrode cell using CoFe PBA@CoP as both cathode and anode delivers the current densities of 10 mA cm−2 at a relatively low cell voltage of 1.542 V, outperforming most of low‐cost bifunctional electrocatalysts reported to date. The controllable and versatile strategy will open up an avenue to prepare hybrid films for advanced electrochemical energy storage and conversion.
Patterns of acute decompensation in hospitalized patients with cirrhosis and course of acute‐on‐chronic liver failure
Authors: Balcar Lorenz , Semmler Georg , Pomej Katharina , Simbrunner Benedikt , Bauer David , Hartl Lukas , Jachs Mathias , Paternostro Rafael , Bucsics Theresa , Pinter Matthias , Trauner Michael , Mandorfer Mattias , Reiberger Thomas , Scheiner Bernhard
Published: May 2021

Introduction

Recently, based on data from the PREDICT study, the European Foundation for the Study of Chronic Liver Failure (EF‐CLIF) consortium proposed pathophysiological/prognostic groups in hospitalized patients with cirrhosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre‐acute‐on‐chronic liver failure (pre‐ACLF), and ACLF. We evaluated the outcomes of these subgroups in a real‐life cohort of hospitalized patients with cirrhosis.

Methods

Patients with cirrhosis developing first AD between 09/2010 and 12/2017 at the Vienna General Hospital were evaluated for this retrospective analysis.

Results

Two hundred and ten patients with cirrhosis (aged 57.6 ± 11.8 years) including n = 45 (21.4%) SDC, n = 100 (47.6%) UDC, n = 28 (13.3%) pre‐ACLF, and n = 37 (17.6%) with ACLF were considered. The proposed AD subgroups discriminated between patients with favorable (1‐year mortality: SDC: 6.7% and UDC: 19.6%) and dismal prognosis (90‐day mortality: pre‐ACLF: 42.9%). Interestingly, systemic inflammation gradually increased (e.g., C‐reactive protein, SDC: 0.9 mg/dl, vs. UDC: 2.0 mg/dl vs. pre‐ACLF: 3.2 mg/dl, p < 0.001) while renal function was progressively deteriorating (creatinine levels, SDC: 0.8 mg/dl vs. UDC: 0.9 mg/dl vs. pre‐ACLF: 1.2 mg/dl, p < 0.001) across prognostic subgroups in patients with cirrhosis.

Discussion

The recently proposed pathophysiological/prognostic EF‐CLIF subgroups are also reproduceable in a real‐life cohort of cirrhotic patients. As ACLF is a common and important complication, patients at risk of pre‐ACLF at index AD should be evaluated and if disease proceeds, been treated early and aggressively to avoid excessive mortality.
Chiral massive news: null boundary symmetries in topologically massive gravity
Authors: Adami H. , Sheikh-Jabbari M.M. , Taghiloo V. , Yavartanoo H. , Zwikel C.
Published: May 2021

Abstract

We study surface charges on a generic null boundary in three dimensional topological massive gravity (TMG). We construct the solution phase space which involves four independent functions over the two dimensional null boundary. One of these functions corresponds to the massive chiral propagating graviton mode of TMG. The other three correspond to three surface charges of the theory, two of which can always be made integrable, while the last one can become integrable only in the absence of the chiral massive graviton flux through the null boundary. As the null boundary symmetry algebra we obtain Heisenberg ⊕ Virasoro algebra with a central charge proportional to the gravitational Chern-Simons term of TMG. We also discuss that the flux of the chiral massive gravitons appears as the (Bondi) news through the null surface.
5d and 4d SCFTs: canonical singularities, trinions and S-dualities
Authors: Closset Cyril , Giacomelli Simone , Schäfer-Nameki Sakura , Wang Yi-Nan
Published: May 2021

Abstract

Canonical threefold singularities in M-theory and Type IIB string theory give rise to superconformal field theories (SCFTs) in 5d and 4d, respectively. In this paper, we study canonical hypersurface singularities whose resolutions contain residual terminal singularities and/or 3-cycles. We focus on a certain class of ‘trinion’ singularities which exhibit these properties. In Type IIB, they give rise to 4d $$ \mathcal{N} $$
N
= 2 SCFTs that we call $$ {D}_p^b $$

D
p
b

(G)-trinions, which are marginal gaugings of three SCFTs with G flavor symmetry. In order to understand the 5d physics of these trinion singularities in M-theory, we reduce these 4d and 5d SCFTs to 3d $$ \mathcal{N} $$
N
= 4 theories, thus determining the electric and magnetic quivers (or, more generally, quiverines). In M-theory, residual terminal singularities give rise to free sectors of massless hypermultiplets, which often are discretely gauged. These free sectors appear as ‘ugly’ components of the magnetic quiver of the 5d SCFT. The 3-cycles in the crepant resolution also give rise to free hypermultiplets, but their physics is more subtle, and their presence renders the magnetic quiver ‘bad’. We propose a way to redeem the badness of these quivers using a class $$ \mathcal{S} $$
S
realization. We also discover new S-dualities between different $$ {D}_p^b $$

D
p
b

(G)-trinions. For instance, a certain E8 gauging of the E8 Minahan-Nemeschansky theory is S-dual to an E8-shaped Lagrangian quiver SCFT.
An experimental investigation on Inconel 718 interrupted cutting with ceramic solid end mills
Authors: Parenti Paolo , Puglielli Francesco , Goletti Massimo , Annoni Massimiliano , Monno Michele
Published: May 2021

Solid ceramic end mills for machining heat resistant super alloys (HRSA) have the potential to generate higher material removal rates, up to one order of magnitude, with respect to standard carbide tools. The machining operations in aerospace industry, where large removals are required to obtain tiny and slender parts like turbine blades, is a cost-intensive task that can benefit of the adoption of ceramic solid end mills. However, these tools show a quite limited tool life, especially when used with interrupted tool engagement strategies. Moreover, they might induce heat-related problems in the workpiece material surface integrity. This paper investigates the cutting and the tool wear during milling Inconel 718 with solid ø12 mm cutting end tool made by SiAlON. The wear mechanisms are studied together with their effects on process signals as cutting forces and power, measured via external and CNC integrated sensors. The carried experimental campaign allowed to find out that tool clogging and edge chipping were the primary cutting phenomena leading the tool wear. Cutting strategy (downmilling or upmilling) produced different results in terms of tool wear sensitivity and process outputs whereas upmilling configuration showed the best results in terms of cutting signals stability and surface integrity. At the same time, cutting speed was found to increase the cutting power more in upmilling than downmilling cutting. The analysis of the forces and power demonstrated that the typical tool wear mechanisms can be traced by signal monitoring due to their high impact on cutting processes. This fact shows the good potential of signal monitoring for a better tool life evaluation.
On the group of unit-valued polynomial functions
Authors: Al-Maktry Amr Ali
Published: May 2021

Let R be a finite commutative ring. The set $${{\mathcal{F}}}(R)$$

F
(
R
)

of polynomial functions on R is a finite commutative ring with pointwise operations. Its group of units $${{\mathcal{F}}}(R)^\times $$

F

(
R
)

×

is just the set of all unit-valued polynomial functions. We investigate polynomial permutations on $$R[x]/(x^2)=R[\alpha ]$$

R

[
x
]

/

(

x
2

)

=
R

[
α
]

, the ring of dual numbers over R, and show that the group $${\mathcal{P}}_{R}(R[\alpha ])$$

P
R

(
R

[
α
]

)

, consisting of those polynomial permutations of $$R[\alpha ]$$

R
[
α
]

represented by polynomials in R[x], is embedded in a semidirect product of $${{\mathcal{F}}}(R)^\times $$

F

(
R
)

×

by the group $${\mathcal{P}}(R)$$

P
(
R
)

of polynomial permutations on R. In particular, when $$R={\mathbb{F}}_q$$

R
=

F
q

, we prove that $${\mathcal{P}}_{{\mathbb{F}}_q}({\mathbb{F}}_q[\alpha ])\cong {\mathcal{P}}({\mathbb{F}}_q) \ltimes _\theta {{\mathcal{F}}}({\mathbb{F}}_q)^\times $$

P

F
q

(

F
q

[
α
]

)

≅
P

(

F
q

)

⋉
θ

F

(

F
q

)

×

. Furthermore, we count unit-valued polynomial functions on the ring of integers modulo $${p^n}$$

p
n

and obtain canonical representations for these functions.
Severe homocysteinemia in two givosiran-treated porphyria patients: is free heme deficiency the culprit?
Authors: Petrides Petro E. , Klein Michael , Schuhmann Elfriede , Torkler Heike , Molitor Brigitte , Loehr Christian , Obermeier Zahra , Beykirch Maria K.
Published: May 2021

Givosiran is a novel approach to treat patients with acute intermittent porphyrias (AIP) by silencing of ∂-ALA-synthase 1, the first enzyme of heme biosynthesis in the liver. We included two patients in the Envision study who responded clinically well to this treatment. However, in both patients, therapy had to be discontinued because of severe adverse effects: One patient (A) developed local injection reactions which continued to spread all over her body with increasing number of injections and eventually caused a severe systemic allergic reaction. Patient B was hospitalized because of a fulminant pancreatitis. Searching for possible causes, we also measured the patients plasma homocysteine (Hcy) levels in fluoride-containing collection tubes: by LC–MS/MS unexpectedly, plasma Hcy levels were 100 and 200 in patient A and between 100 and 400 μmol/l in patient B. Searching for germline mutations in 10 genes that are relevant for homocysteine metabolism only revealed hetero- and homozygous polymorphisms in the MTHFR gene. Alternatively, an acquired inhibition of cystathionine-beta-synthase which is important for homocysteine metabolism could explain the plasma homocysteine increase. This enzyme is heme-dependent: when we gave heme arginate to our patients, Hcy levels rapidly dropped. Hence, we conclude that inhibition of ∂-ALA-synthase 1 by givosiran causes a drop of free heme in the hepatocyte and therefore the excessive increase of plasma homocysteine. Hyperhomocysteinemia may contribute to the adverse effects seen in givosiran-treated patients which may be due to protein-N-homocysteinylation.