bluuebunny/crossref_metadata_2025 huggingface dataset:
Organic Anion Transporter Gene Variants Associated With Plasma Exposure and Long‐Term Response to Atrasentan in Patients With Diabetic Kidney Disease
Authors: Smeijer J. David , Koomen Jeroen V. , Kohan Donald E. , McMurray John J. V. , Bakris George L. , Correa‐Rotter Ricardo , Hou Fan‐Fan , Kitzman Dalane W. , Makino Hirofumi , Mayer Gert , Nowicki Michal , Perkovic Vlado , Rossing Peter , Tobe Sheldon , Parving Hans‐Henrik , de Zeeuw Dick , Heerspink Hiddo J. L.
Published: July 2022

Plasma exposure of the endothelin receptor antagonist atrasentan varies between individuals and is associated with nephroprotective effects and the risk of heart failure. We examined the influence of genetic polymorphisms on atrasentan plasma exposure and pharmacodynamic effects. We performed a substudy of the Study of Diabetic Nephropathy With Atrasentan (SONAR) trial which enrolled adults with type 2 diabetes and chronic kidney disease (estimated glomerular filtration rate: 25–75 mL/min/1.73 m2, and a urine albumin‐to‐creatinine ratio of 300–5,000 mg/g). Single nucleotide polymorphisms (SNPs) were determined for prespecified membrane transporters, metabolizing enzymes, and the endothelin‐1 peptide. The associations among genotype, atrasentan plasma exposure, and the effect of atrasentan on the prespecified kidney and heart failure hospitalization (HHF) outcomes was assessed with Cox proportional hazards regression models. Of 3,668 patients randomized, 2,329 (63.5%) consented to genotype analysis. Two SNPs in the SLCO1B1 gene (rs4149056 and rs2306283), encoding the hepatic organic anion transporter 1B1 (OATP1B1), showed the strongest association with atrasentan plasma exposure. Based on their SLCO1B1 genotype, patients were classified into normal (atrasentan area under the plasma‐concentration time curve from zero to infinity (AUC0−inf) 41.3 ng·h/mL) or slow (atrasentan AUC0−inf 49.7 ng·h/mL, P < 0.001) OATP1B1 transporter phenotypes. Among patients with a normal OATP1B1 phenotype, the hazard ratio (HR) with atrasentan for the primary kidney and HHF outcomes were 0.61 (95% confidence interval (CI): 0.45–0.81) and 1.35 (95% CI: 0.84–2.13), respectively. In the slow transporter phenotype, HRs for kidney and HHF outcomes were 1.95 (95% CI: 0.95–4.03, P‐interaction normal phenotype = 0.004), and 4.18 (95% CI: 1.37–12.7, P‐interaction normal phenotype = 0.060), respectively. OATP1B1 gene polymorphisms are associated with significant between‐patient variability in atrasentan plasma exposure and long‐term efficacy and safety.
SP3‐FAIMS‐Enabled High‐Throughput Quantitative Profiling of the Cysteinome
Authors: Desai Heta S. , Yan Tianyang , Backus Keriann M.
Published: July 2022

Cysteine‐directed chemoproteomic profiling methods yield high‐throughput inventories of redox‐sensitive and ligandable cysteine residues and therefore are enabling techniques for functional biology and drug discovery. However, the cumbersome nature of many sample preparation workflows, the requirements for large amounts of input material, and the modest yields of labeled peptides are limitations that hinder most chemoproteomics studies. Here, we report an optimized chemoproteomic sample‐preparation workflow that combines enhanced peptide labeling with single‐pot, solid‐phase‐enhanced sample preparation (SP3) to improve the recovery of biotinylated peptides, even from small samples. We further tailor our SP3 method to specifically probe the redox proteome, which showcases the utility of the SP3 platform in multistep sample‐preparation workflows. By implementing a customized workflow in the FragPipe computational pipeline, we achieve accurate MS1‐based quantification, including for peptides containing multiple cysteine residues. Collectively these innovations enable enhanced high‐throughput quantitative analysis of the cysteinome. This article includes detailed protocols for cysteine labeling with isotopically labeled iodoacetamide alkyne probes, biotinylation with CuAAC, sample cleanup with SP3, enrichment of cysteines with NeutrAvidin agarose beads, LC‐FAIMS‐MS/MS analysis, and FragPipe‐IonQuant analysis. © 2022 Wiley Periodicals LLC.

Basic Protocol 1: Labeling of cysteines in human proteome and SP3‐based sample cleanup

Alternate Protocol 1: Labeling of cysteines in human proteome, SP3‐based sample cleanup, and enrichment of cysteines for isoTOP‐ABPP analysis

Alternate Protocol 2: Labeling of cysteines in human proteome and SP3‐based sample cleanup for redox proteome analysis

Basic Protocol 2: Peptide‐level cysteine enrichment

Basic Protocol 3: LC‐FAIMS‐MS/MS analysis

Basic Protocol 4: FragPipe data analysis
Suzuki‐Miyaura Coupling, Heck Alkenylation, and Amidation of DMTr‐Protected 5‐Iodo‐2′‐Deoxyuridine via Palladium‐catalyzed Reactions
Authors: Kori Santosh , Khandagale Deepali , Sanghvi Yogesh S. , Serrano Jose L. , Lozano Pedro , Kapdi Anant R.
Published: July 2022

Modification of nucleosides via cross‐coupling processes has been carried out extensively on unprotected halonucleosides to produce functionalized nucleosides that are often developed for incorporation into oligonucleotides or used as fluorescent probes. This approach requires protection of the 5′‐OH with the 4,4′‐dimethoxytrityl (DMTr) group, which is complicated and a common cause of reaction failure. Here we report a method for direct functionalization of 5′‐O‐DMTr‐5‐iodo‐2′‐deoxyuridine via Suzuki‐Miyaura cross‐coupling, Heck alkenylation, and carboamidation. This approach facilitates rapid synthesis of a variety of C5‐substituted 5′‐O‐DMTr‐2′‐deoxyuridine derivatives. © 2022 Wiley Periodicals LLC.

Basic Protocol 1: Synthesis of the SerrKap palladacycle complex

Basic Protocol 2: Suzuki‐Miyaura coupling of 5′‐O‐DMTr‐5‐iodo‐2′‐deoxyuridine using SerrKap palladacycle

Basic Protocol 3: Heck coupling of 5′‐O‐DMTr‐5‐iodo‐2′‐deoxyuridine using SerrKap palladacycle

Basic Protocol 4: Heck coupling of 5′‐O‐DMTr‐5‐iodo‐2′‐deoxyuridine with Ruth linker using Pd(OAc)2/PTABS

Basic Protocol 5: Carbonylative amidation of 5′‐O‐DMTr‐5‐iodo‐2′‐deoxyuridine using Pd(OAc)2/PTABS
Reconfigurable circular patch MIMO antenna for 5G (sub‐6 GHz) and WLAN applications
Authors: Singh Ajit Kumar , Mahto Santosh Kumar , Kumar Praveen , Mistri Raj Kumar , Sinha Rashmi
Published: July 2022

In this article, a circular patch microstrip feed line monopole radiator with a dimension of 15 × 20 × 1.6 mm3 is proposed. An inverted L‐shaped stub is employed in the partial ground plane to achieve optimum bandwidth, radiation pattern and radiation efficiency. To further cover the sub‐6 GHz spectrum (3.4–3.8 GHz) for future 5G communications, a two‐element MIMO antenna configuration is designed by utilising the single element antenna. The edge‐to‐edge distance between the two elements is 0.15λ0 (15 mm). The propose antenna achieved dual‐operating bands of 3.35–4.60 and 4.93–5.19 GHz in the diode (D) = ON state. The minimum isolation between 3.35–3.94 and 4.99–5.16 GHz frequency range is −14.5 and −12.5 dB, respectively, by incorporating a rectangular stub between two inverted L‐shaped stubs. The MIMO antenna has a peak gain of 2.68 dBi at 5.1 GHz frequency. The average total efficiency at port‐1 between 3.35–3.94 and 4.93–5.19 GHz frequency range is 65%, whereas at port‐2 is 75%. In terms of the envelop correlation coefficient (ECC), mean effective gain (MEG) and total active reflection coefficient (TARC), the proposed antenna's diversity performance characteristics are investigated and the obtained values are 0.09, ±3 and −3 dB, respectively. The suggested MIMO antenna is designed on a FR4 substrate with a dielectric constant of 4.4 and an electrical dimension of 0.34λ0 × 0.20λ0 × 0.015λ0 mm3 (where λ0 represents the free space wavelength at lower cut‐off frequency [2.95 GHz]). Therefore, the proposed antenna can find applications for rain or fog as well as for identification and tracking (weather radar) on S‐band at 3 GHz frequency, 5G (sub‐6 GHz) and WLAN applications.
Advances in periodontal stem cells and the regulating niche: From in vitro to in vivo
Authors: Yi Yating , Liu Yinghong , Men Yi , Wang Jun , Zhao Hu
Published: July 2022

Periodontium possesses stem cell populations for its self‐maintenance and regeneration, and has been proved to be an optimal stem cell source for tissue engineering. In vitro studies have shown that stem cells can be isolated from periodontal ligament, alveolar bone marrow and gingiva. In recent years, more studies have focused on identification of periodontal stem cells in vivo. Multiple genetic markers, including Gli1, Prx1, Axin2, αSMA, and LepR, were identified with the lineage tracing approaches. Characteristics, functions, and regulatory mechanisms of specific populations expressing one of these markers have been investigated. In vivo studies also revealed that periodontal stem cells can be regulafrted by different niche and mechanisms including intercellular interactions, ECM and multiple secreted factors. In this review, we summarized the current knowledge of in vitro characteristics and in vivo markers of periodontal stem cells, and discussed the specific regulating niche.
Evaluation of tick control tube month of placement and modifications to increase visitation by small mammals
Authors: Green Kylie D. , Tiffin Hannah S. , Brown Jessica E. , Burgess Edwin R. , Machtinger Erika T.
Published: July 2022

Tick control tubes are a host‐targeted tick control method targeting immature Ixodes scapularis ticks attached to mice or found within mouse burrows and nests. Tick control tubes contain permethrin‐treated cotton inside cardboard tubes that mice use as nesting material. Ticks attached to mice or present in their burrows are exposed to the treated cotton. However, there have been variable results using these tubes for tick control. Rodent visitation and use of these tubes may influence their effectiveness. The aim of this study was to evaluate small mammal use of tick control tube cotton and to evaluate whether cotton size or odor attractants changed small mammal tube visitations and cotton removal. For the cotton size experiment, three different cotton sizes were used. In the odor attractant experiment, three different odor attractants were used (peanut butter, safflower oil, and vanillin) along with a commercially available tube as a control. A negative control group that had no cotton present in the tube was used for both experiments. Cotton loss was determined by weighing cotton in deployed tubes weekly, and mouse and nontarget species interactions were evaluated using camera‐trap data collected at each site. While the tested cotton sizes and odor attractants did not affect cotton use, mice did increasingly use cotton during cooler fall months, with the highest use of cotton in October and least use in July. These results suggest that mouse use of cotton was not related to cotton size or odor attractants but was dependent on season. This warrants future research on temporal small mammal use of tick control tubes to determine optimal deployment times for tick control.
Quantifying the resilience of coldwater lake habitat to climate and land use change to prioritize watershed conservation
Authors: Hansen Gretchen J. A. , Wehrly Kevin E. , Vitense Kelsey , Walsh Jake R. , Jacobson Peter C.
Published: July 2022

Managing ecological systems for resilience can increase their capacity to maintain key functions even under global change. Oxygenated coldwater (oxythermal) habitat in lakes is an important ecological resource that is threatened by both climate change and eutrophication. Here, we quantify the resilience of oxythermal habitat in over 10,000 glacial lakes in the upper Midwestern United States to climate change and watershed disturbance and classify lakes for conservation prioritization based on their current conditions and resilience. Oxythermal habitat was predicted by lake morphometry, July air temperatures, and watershed land use. Temperatures are projected to increase by mid‐century, and the magnitude of warming, its effect on oxythermal habitat, and the uncertainty surrounding that effect varied among lakes. Under mid‐century climate conditions, the number of lakes containing suitable coldwater habitat was predicted to decline by 67%, while the number of lakes with unsuitable habitat was predicted to increase by over 200%. Lakes varied in the amount of temperature increase that they could sustain without a resultant change in habitat tier (i.e., their climate resilience). Median climate resilience was 4.3°C, with some lakes capable of remaining in their habitat tier even with temperature increases up to 14°C. Changing watershed land use was predicted to influence oxythermal habitat in 24% of lakes (n = 2391). We used the magnitude of increase in watershed development that a lake could sustain while remaining in its current habitat class as a measure of its resilience to watershed disturbance. Conversely, decreased watershed development may improve oxythermal habitat conditions and push a lake into an improved condition, and this value represented a lake's restoration potential. We classified lakes into seven management classes based on their current oxythermal habitat conditions and the resilience of oxythermal habitat to climate and watershed disturbance. To facilitate management on individual lakes, we also assessed the vulnerability and resilience of individual lakes and the uncertainty surrounding these estimates. By quantifying the resilience of lakes and how it is influenced by local action across a multistate region, we can prioritize conservation action across multiple scales to maintain the critical habitat and ecosystem function of glacial lakes.
Early snowmelt by an extreme warming event affects understory more than overstory trees in Japanese temperate forests
Authors: Makoto Kobayashi , Templer Pamela H. , Katayama Ayumi , Seki Osamu , Takagi Kentaro
Published: July 2022

The occurrence of extreme warm events and early snowmelt is predicted to increase in high‐latitude ecosystems, even during periods of time when there is no coincident reduction in total precipitation. However, because extreme events like these occur unpredictably, little is known about how advancing snowmelt by a single extreme warm event, without a reduction in precipitation amount, influences overstory trees and understory vegetation simultaneously in an ecosystem. We conducted a warming experiment (four 20 × 20 m plots) in temperate forests of Japan to determine the effects of earlier snowmelt on both understory dwarf bamboo plants and overstory birch trees. Our experimental treatment advanced snowmelt by about 10 days and increased soil temperatures that were associated with increased rates of soil nitrogen (N) mineralization and nitrification. Furthermore, these changes led to lower C:N ratios of leaves together with the greater growth of understory bamboo vegetation, with no changes in leaf C:N or growth rates of overstory birch trees. Together, our results demonstrate that advancing snowmelt by an extreme warm event in temperate forests is likely to affect N cycling and will benefit understory vegetation without a commensurate change in overstory vegetation, likely due to the increase in available soil N. These results also demonstrate that with the projected increase in the frequency of extreme warm events and advanced snowmelt, understory vegetation is likely to benefit more than overstory trees in Japanese temperate forests with heavy snow.
Systematic review of efficacy of direct oral anticoagulants and vitamin K antagonists in left ventricular thrombus
Authors: Huang Lei , Tan Yuan , Pan Yilong
Published: July 2022

Aims

Left ventricular thrombus (LVT) increases the risk of thrombotic events and mortality. Vitamin K antagonists (VKAs) used to treat LVT have several known risks, as a result of which direct oral anticoagulant (DOAC) use has recently increased. We aimed to evaluate the safety and efficacy of DOACs and VKAs in treating LVT.

Methods and results

We searched PubMed, Embase, Cochrane Library trials, and Web of Science databases for studies published before 19 April 2022, involving DOAC versus VKA treatment for patients with LVT. This meta‐analysis comprised 21 studies (total patients, n = 3172; DOAC group, n = 888; VKA group, n = 2284). A statistically significant reduction in bleeding events was observed in patients on DOACs vs. those on VKAs (risk ratio (RR) = 0.73, P = 0.004). Patients on DOACs residing in North American and European regions and those with ischaemic heart disease (IHD) had a significantly lower risk of bleeding events than patients residing in other regions or those with a different LVT aetiology, respectively (RR = 0.78, P = 0.04; RR = 0.38, P = 0.02; and RR = 0.63, P = 0.009). A statistically significant reduction in stroke in patients on DOACs versus VKAs (RR = 0.72, P = 0.03) was observed, and patients on DOACs residing in North America and those with IHD had a significantly lower risk of stroke (RR = 0.73, P = 0.04, and RR = 0.61, P = 0.03, respectively). Compared with VKAs, DOACs are statistically associated with an increase in LVT resolution at 1 month (RR = 1.96, P = 0.008). No statistical between‐group difference in all‐cause mortality (RR = 0.72, P = 0.05), systemic embolism (RR = 0.87, P = 0.74), stroke or systemic embolism (RR = 0.90, P = 0.50), and LVT resolution at the end of follow‐up (RR = 1.06, P = 0.13) was observed.

Conclusions

Compared with VKAs, DOACs significantly reduce the risk of bleeding events and stroke in LVT patients, but mortality was similar in both groups. The advantages are apparent not only in patients belonging to the predominantly white residential areas such as North American and European regions but also in patients with LVT due to IHD. DOACs show promising effects in treating LVT compared with VKAs.
Prognostic value of various markers in recovery from peripartum cardiomyopathy: a systematic review and meta‐analysis
Authors: Hosseinpour Alireza , Hosseinpour Hamidreza , Kheshti Fatemeh , Abdollahifard Saeed , Attar Armin
Published: July 2022

Aims

The aetiology of peripartum cardiomyopathy (PPCM) is still not clear, and it is unknown who would recover from PPCM. In this meta‐analysis, for the first time, we aimed to explore the prognostic value of potential baseline factors that may help predict recovery in patients with PPCM.

Methods

A systematic approach following the Meta‐analysis of Observational Studies in Epidemiology guideline was taken by using appropriate keywords in PubMed, Scopus, and Embase databases. Studies that had compared different clinical and paraclinical markers at the time of diagnosis related to cardiovascular function between recovered and non‐recovered patients with PPCM were included. To find potential predictors of recovery, the odds ratio (OR) was calculated for different parameters using the random‐effects model.

Results

Eighteen cohort studies including 1047 patients with PPCM were enrolled. Six markers out of the 11 potentially eligible markers were associated with PPCM recovery. Baseline echocardiographic parameters [left ventricular ejection fraction (LVEF) (OR = 4.84 [2.53; 9.26]), left ventricular end‐diastolic diameter (OR = 3.67 [2.58; 5.23]), left ventricular end‐systolic diameter (OR = 3.99 [2.27; 7.02]), and fractional shortening (OR = 6.14 [1.81; 20.85])] were strong predictors of PPCM recovery. Systolic blood pressure (OR = 2.16 [1.38; 3.38]) and diastolic blood pressure (OR = 2.06 [1.07; 3.96]) at diagnosis were also associated with recovery.

Conclusions

Patients with PPCM who have a higher baseline LVEF, lower left ventricular diameters, and higher blood pressure levels have a greater chance to recover from PPCM.
Right ventricular and atrial strain in patients with advanced melanoma undergoing immune checkpoint inhibitor therapy
Authors: Pohl Julia , Totzeck Matthias , Mincu Raluca‐I. , Margraf Simone M. , Scheipers Lena , Michel Lars , Mahabadi Amir A. , Zimmer Lisa , Rassaf Tienush , Hendgen‐Cotta Ulrike B.
Published: July 2022

Aims

While immune checkpoint inhibitor (ICI) therapy significantly improves survival rates in advanced melanoma, ICI can evoke severe immune‐related cardiovascular adverse events. Right ventricular (RV) dysfunction negatively impacts the outcomes in cardiovascular diseases and may be an early sign for overall cardiotoxicity. We aimed to assess RV function in melanoma patients undergoing ICI therapy using conventional echocardiographic and strain imaging techniques.

Methods and results

We retrospectively examined 30 patients (40% women, age 59 ± 13 years) with advanced melanoma (stage III/IV) before and 4 weeks after the start of ICI therapy (follow‐up at 39 ± 15 days); n = 15 of the patients received nivolumab, and n = 15 received the combination therapy nivolumab/ipilimumab. Two‐dimensional echocardiography with assessment of RV longitudinal strain of the free wall (RV‐LSFW) and assessment of right atrial (RA) strain from speckle tracking was performed at baseline and after the start of ICI therapy. Short‐term ICI therapy caused a reduction of RV‐LSFW (−25.5 ± 6.4% vs. −22.4 ± 4.3%, P = 0.002) and of RA strain during contraction phase (−10.6 ± 3.5% vs. −7.7 ± 3.1%, P = 0.001). Conventional parameters including tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and pulmonary artery systolic pressure were not different between the two time points (TAPSE 26 ± 5 vs. 25 ± 5 mm, P = 0.125; FAC 38 ± 13% vs. 38 ± 14%, P = 0.750; and pulmonary artery systolic pressure 27 ± 10 vs. 25 ± 8 mmHg, P = 0.268).

Conclusions

Analysis of RV and RA strain shows alterations even in a short‐term follow‐up, while changes in RV function are not visible by conventional RV parameters. Alterations in RV and RA strain could be early signs of cardiotoxicity and therefore should be assessed in patients undergoing ICI therapy.
Hypotension on cardiopulmonary stress test predicts 90 day mortality after LVAD implantation in INTERMACS 3–6 patients
Authors: Maharaj Valmiki , Agdamag Arianne C. , Duval Sue , Edmiston Jonathan , Charpentier Victoria , Fraser Meg , Hall Alexandra , Schultz Jessica , John Ranjit , Shaffer Andrew , Martin Cindy M. , Thenappan Thenappan , Francis Gary S. , Cogswell Rebecca , Alexy Tamas
Published: July 2022

Aims

Cardiopulmonary stress test (CPX) is routinely performed when evaluating patient candidacy for left ventricular assist device (LVAD) implantation. The predictive value of hypotensive systolic blood pressure (SBP) response during CPX on clinical outcomes is unknown. This study aims to determine the effect of hypotensive SBP response during to clinical outcomes among patients who underwent LVAD implantation.

Methods and results

This was a retrospective single center study enrolling consecutive patients implanted with a continuous flow LVAD between 2011 and 2022. Hypotensive SBP response was defined as peak exercise SBP below the resting value. Multivariable Cox‐regression analysis was performed to evaluate the relationship between hypotensive SBP response and all‐cause mortality within 30 and 90 days of LVAD implantation. A subgroup analysis was performed for patients implanted with a HeartMate III (HM III) device. Four hundred thirty‐two patients underwent LVAD implantation during the pre‐defined period and 156 with INTERMACS profiles 3–6 met our inclusion criteria. The median age was 63 years (IQR 54–69), and 52% had ischaemic cardiomyopathy. Hypotensive SBP response was present in 35% of patients and was associated with increased 90 day all‐cause mortality (unadjusted HR 9.16, 95% CI 1.98–42; P = 0.0046). Hazard ratio remained significant after adjusting for age, INTERMACS profile, serum creatinine, and total bilirubin. Findings were similar in the HM III subgroup.

Conclusions

Hypotensive SBP response on pre‐LVAD CPX is associated with increased perioperative and 90 day mortality after LVAD implantation. Additional studies are needed to determine the mechanism of increased mortality observed.
Secondary rituximab‐associated versus primary immunodeficiencies: The enigmatic border
Authors: Ottaviano Giorgio , Sgrulletti Mayla , Moschese Viviana
Published: July 2022

Rituximab (RTX), a chimeric monoclonal antibody targeting CD20‐positive cells, is a valuable treatment option for malignant and benign immune‐related disorders. The rationale of targeting the CD20 antigen relies on depletion of both healthy and autoreactive/malignant CD20‐espressing cells, but normal B‐cell reconstitution is expected within months after treatment. Nevertheless, a number of recent studies have documented prolonged B‐cell deficiency associated with new‐onset hypogammaglobulinemia in patients receiving RTX. Awareness of post‐RTX hypogammaglobulinemia has become wider among clinicians, with a growing number of reports about the increased incidence, especially in children. Although these patients were previously regarded as affected by secondary/iatrogenic immunodeficiency, atypical clinical and immunological manifestations (e.g., severe or opportunistic infections; prolonged B‐cell aplasia) raise concerns of delayed manifestations of genetic immunological disorders that have been unveiled by B‐cell perturbation. As more patients with undiagnosed primary immune deficiency receiving RTX have been identified, it remains the challenge in discerning those that might display a higher risk of persistent RTX‐associated hypogammaglobulinemia and need a tailored immunology follow‐up. In this review, we summarize the principal evidence regarding post‐RTX hypogammaglobulinemia and provide a guideline for identifying patients at higher risk of RTX‐associated hypogammaglobulinemia that could harbor an inborn error of immunity.
N‐Heterocyclic Carbene and Cyclic (Alkyl)(amino)carbene Adducts of Germanium(IV) and Tin(IV) Chlorides and Organyl Chlorides
Authors: Philipp Michael S. M. , Bertermann Rüdiger , Radius Udo
Published: July 2022

A study on the reactivity of N‐heterocyclic carbenes (NHCs) and the cyclic (alkyl)(amino)carbene cAACMe with selected germanium(IV) and tin(IV) chlorides and organyl chlorides is presented. The reactions of the NHCs Me2ImMe, iPr2ImMe and Dipp2Im with the methyl chlorides ECl2Me2 afforded the adducts NHC ⋅ ECl2Me2 (E=Ge (1), Sn (2)), NHC=Me2ImMe (a), iPr2ImMe (b), Dipp2Im (c)). The reaction of Me2ImMe with GeCl4 led to isolation of Me2ImMe ⋅ GeCl4 (3), the reaction of iPr2ImMe with SnCl4 in THF afforded the THF adduct iPr2ImMe ⋅ SnCl4 ⋅ THF (4). Dipp2Im ⋅ GeCl2Me2 (1 c) isomerized into the backbone coordinated imidazolium salt [aDipp2Im ⋅ GeClMe2][Cl] (5) upon thermal treatment. The reactions of cAACMe with (i) ECl2R2 (E=Ge, Sn) gave the adducts cAACMe ⋅ ECl2R2 (R=Me: E=Ge (6); Sn (7); Ph: E=Ge (8)), with (ii) GeClMe3 and GeCl4 the salts [cAACMe ⋅ GeMe3][Cl] (9) and [cAACMeCl][GeCl3] (10), and (iii) with SnCl4 the salt [cAACMeCl][SnCl3] (11) and the adduct cAACMe ⋅ SnCl4 (12). Reduction of 2 a with KC8 afforded the NHC‐stabilized stannylene Me2ImMe ⋅ SnMe2 13, reduction of 7 with either KC8 or 1,4‐bis‐(trimethylsilyl)‐1,4‐dihydropyrazin in the presence of SnCl2Me2 yielded cAACMe ⋅ SnMe2 ⋅ SnMe2Cl2 (14).
Organocatalytic Synthesis and Anti‐Trypanosomal Activity Evaluation of L‐Pentofuranose‐Mimetic Iminosugars
Authors: Mesa Juan M. , Comini Marcelo A. , Dibello Estefanía , Gamenara Daniela
Published: July 2022

A series of L‐lyxo and L‐xylo‐ pentofuranose‐mimetic iminosugars and derivatives were efficiently synthesized in a stereoselective manner, through a concise strategy which involves an organocatalyzed Mannich reaction of an imine and a protected dioxanone as key step, using D‐proline as catalyst. A preliminary evaluation of their activity as potential anti‐trypanosomal agents was studied. One of the synthesized compounds showed an interesting activity against bloodstream Trypanosoma brucei brucei (EC50=3.8±1.0 μM).
Trifluoromethylated Indolopyranones through Regioselective Annulation of Indole Carboxylic Acids with Unsymmetric Internal Trifluoromethylated Alkynes
Authors: Zhang Xingxing , Liu Guangyuan , Peng Yiyuan , Li Hua , Zhou Yirong
Published: July 2022

A rhodium‐catalyzed oxidative cross coupling/annulation of indole carboxylic acids with unsymmetric internal trifluoromethylated alkynes was accomplished, which enabled direct access to diverse trifluoromethylated indolopyranones, by combining indole, pyranone and trifluoromethyl, three valid pharmacophores, into one molecule. Diverse indole‐3‐carboxylic acids and indole‐2‐carboxylic acids were proved to be suitable reaction partners. Excellent regioselectivity was dominated by electron difference of unsymmetric alkynes. Moderate to good yields, high efficiency and atom economy were achieved for a broad substrate scope with high functional group tolerance.
Stereospecific Access to α‐ and β‐N‐Glycosylamine Derivatives by a Metal Free O‐to‐N [3,3]‐Sigmatropic Rearrangement
Authors: Pratesi Debora , Mirabella Stefania , Petrucci Giulia , Matassini Camilla , Faggi Cristina , Cardona Francesca , Goti Andrea
Published: July 2022

Glycosylamine derivatives are biologically relevant compounds widespread in Nature, but the synthesis of this motif has been little addressed and its access with control of configuration at the anomeric carbon is challenging. Glycals substituted at C‐3 with a carbamate group undergo, upon dehydration, a prompt allyl cyanate to isocyanate rearrangement to the isomeric N‐glycosyl isocyanates, which can be conveniently trapped by one‐pot nucleophilic addition with alcohols or amines to afford N‐glycosyl carbamates and ureas, respectively. The rearrangement follows a [3,3]‐sigmatropic pericyclic mechanism as illustrated by the stereospecificity of the reaction, with nitrogen being delivered at the anomeric position to the same face from which the oxygen at C‐3 has departed. Thus, glucal and galactal give β‐N‐glycosides exclusively while allal furnishes α‐N‐glycosides. cis‐Dihydroxylation of the synthesized unsaturated N‐glycosides afford different 1‐aminosugars with good selectivity.
Copper‐Catalyzed Asymmetric Allylic Alkylation of Racemic Cyclic Allyl Bromides with Organolithium Compounds
Authors: Li Jun , Song Xiao , Wu Fusong , You Hengzhi , Chen Fen‐Er
Published: July 2022

Organolithium reagents are one of the most widely used reagents in chemical synthesis. Herein, we reported the first study of organolithium reagents used in asymmetric allylic alkylation (AAA) reactions with racemic cyclic substrates. A simple and efficient Cu‐catalyzed synthesis of enantiomerically enriched cycloalkene derivatives from various racemic cyclic allylic bromides was developed. The standard method employed 5 % CuBr⋅SMe2 in combination with phosphoramidite ligand L2 in DCM. Meanwhile, transfer of the reactions into flow condition for more convenient application was also studied. This new Cu‐catalyzed protocol was speculated to undergo an enantioconvergent transformation mechanism here.
An experimental study on synthesis of ternary biodiesel through potassium hydroxide catalyst transesterification
Authors: Murugesan Elango , Kannan G. Radhakrishnan
Published: July 2022

The novelty of this study is synthesis fuel of biodiesel from the Brassica napus seed oil (BN‐B), Linum usitatissimum seed oil (LU‐B) and diesel to improve the performance of SCDE and minimize the CO2 emissions. BN‐B and LU‐B were produced using a 0.1 N potassium hydroxide catalyst and methanol to synthesis biodiesel from B. napus and L. usitatissimum seed oil. The glycerine and biodiesel are separated using the transesterification filtration process. The research was carried out without any modifications with the objective of analyzing performance and emissions in a SCDE at variable load and constant speed. SCDE investigates the impact of five different triple combinations of BN‐B and LU‐B blended with diesel. The experiments yielded the following results, B1‐B and B2‐B have calorific values of 42.2 and 41.6 MJ/kg, respectively. The fuel consumption of the triple blend combination was lower than that of the diesel at full load and constant speed. The triple blend combination emits less nitrogen dioxide (NO2) and carbon monoxide (CO) than diesel, according to the results of the emission tests.
Genotype–environment interaction of crocin in Gardenia jasminoides by AMMI and GGE biplot analysis
Authors: Liu Qian , Huang Lili , Fu Chao , Zhang Ting , Ding Wei , Yang Chunxia
Published: July 2022

To investigate the effect of genotype–environment interaction (GEI) on Gardenia jasminoides crocin contents, this study combined the additive main effects and multiplicative interactions (AMMI) model and genotype × environment interaction (GGE) biplot method to investigate the adaptation and stability of 11 Gardenia jasminoides genotypes at three experimental sites in Jiangxi Province with replications. The AMMI analysis showed that genotype, environment, and the GEI had extremely significant effects on Gardenia jasminoides crocin contents (p < .001). The GEI was the main factor causing the content variation, followed by genotype. The AMMI model and biplot analysis showed that the HC20 genotype had high and stable crocin contents. The GGE biplot analysis showed that Fengcheng and Gongqingcheng were optimal test sites for the selection of Gardenia jasminoides genotypes based on their crocin contents; additionally, the HC20 genotype was a suitable dominant genotype to promote cultivation in the test areas, and the GY8 genotype could be widely planted in the Gongqingcheng area. Therefore, the AMMI and GGE biplot genotype evaluation results were basically consistent. Comprehensive and effective evaluation of genotype and regional test sites can provide a theoretical basis for the breeding and development of Gardenia jasminoides clones with high and stable crocin contents and the selection of test sites.
Knowledge, attitudes, and practices on food safety and hygiene of wet and dry fish handlers in Cox's Bazar, Bangladesh
Authors: Sobuj Mohammad Khairul Alam , Rabby Ahmad Fazley , Rahman Shafiqur , Hasan Shanur Jahedul , Bhowmik Shuva , Islam Md. Ariful , Islam Md. Mohidul , Mostofa Md. Golam , Mamun Abdullah‐Al
Published: July 2022

This study aimed to provide the very first description of the current scenario of knowledge, attitudes, and practices (KAP) concerning the food safety and hygiene subjects among wet fish handlers (WFHs) and dry fish handlers (DFHs) in Cox's Bazar, Bangladesh. Data collection was performed through the application of face‐to‐face interviews with 234 WFHs and 258 DFHs. The overall score of the correct answer assessed components was 55.95% and 57.05% in WFHs and DFHs, respectively. Among the different knowledge categories, both the respondents showed the highest positive response in the time, temperature, and quality control category and the lowest positive responses noted in the foodborne disease occurrence category. For attitudes, obtained results showed positive attitude with a mean score of 37.82 ± 4.28 and 35.58 ± 5.48 for WFHs and DFHs, respectively. The WFHs gained a mean score of 23.08 ± 4.24 for practices, and the score was 22.78 ± 4.47 in the case of DFHs. A positively significant correlation coefficient (rs) was observed among fish handlers' KAP of 0.326–0.584. Although the association between the three levels was acceptable, several food safety principles and hygiene practices remained unsatisfactory. These findings highlighted the need for rapid action to enhance food safety and hygiene KAP through an intensive training program to assure the production of safe fisheries products for human consumption.
Enzymatic Laser‐Induced Graphene Biosensor for Electrochemical Sensing of the Herbicide Glyphosate
Authors: Johnson Zachary T. , Jared Nathan , Peterson John K. , Li Jingzhe , Smith Emily A. , Walper Scott A. , Hooe Shelby L. , Breger Joyce C. , Medintz Igor L. , Gomes Carmen , Claussen Jonathan C.
Published: July 2022

Glyphosate is a globally applied herbicide yet it has been relatively undetectable in‐field samples outside of gold‐standard techniques. Its presumed nontoxicity toward humans has been contested by the International Agency for Research on Cancer, while it has been detected in farmers’ urine, surface waters and crop residues. Rapid, on‐site detection of glyphosate is hindered by lack of field‐deployable and easy‐to‐use sensors that circumvent sample transportation to limited laboratories that possess the equipment needed for detection. Herein, the flavoenzyme, glycine oxidase, immobilized on platinum‐decorated laser‐induced graphene (LIG) is used for selective detection of glyphosate as it is a substrate for GlyOx. The LIG platform provides a scaffold for enzyme attachment while maintaining the electronic and surface properties of graphene. The sensor exhibits a linear range of 10–260 µm, detection limit of 3.03 µm, and sensitivity of 0.991 nA µm−1. The sensor shows minimal interference from the commonly used herbicides and insecticides: atrazine, 2,4‐dichlorophenoxyacetic acid, dicamba, parathion‐methyl, paraoxon‐methyl, malathion, chlorpyrifos, thiamethoxam, clothianidin, and imidacloprid. Sensor function is further tested in complex river water and crop residue fluids, which validate this platform as a scalable, direct‐write, and selective method of glyphosate detection for herbicide mapping and food analysis.
A comment on overlooked storm sensitivity of the carbonate factory recorded in the Mississippian Mobarak Formation (Alborz Mountains, Iran)
Authors: Sardar Abadi Mehrdad , Voeten Dennis F. A. E. , Kulagina Elena I. , Boulvain Frédéric , Da Silva Anne‐Christine
Published: July 2022

New interpretations of depositional palaeoenvironments in the Mississippian (Lower Carboniferous) Mobarak Formation (Alborz Mountains, Iran) suggest a significant and persistent influence of storms. This deviates from previous conclusions that these deposits recorded mounds, patch reefs, and extensive lagoons deposited under stagnant environmental conditions. We here clarify and discuss the origin and nature of this misconception by explaining “unexpected” observations that are informed by outdated interpretations of the depositional environment of the Mobarak Formation. This evaluation offers the context required for appropriately interpreting and correlating Mississippian depositional records across the Alborz Basin.
Spatiotemporal variation and sustainability of NDVI in the Yellow River basin
Authors: Dai Qin , Cui Chen‐feng , Wang Shuo
Published: July 2022

Accurately determining vegetation coverage and its changes is very important to detect the effectiveness of the Grain for Green Project (GGP) in vegetation construction in the Yellow River basin. Moreover, an understanding of the impact of human activities and the future trends of vegetation cover allows for more effective maintenance of the achievements of ecological construction. Based on the normalized difference vegetation index (NDVI) of SPOT/VEGETATION satellite remote sensing data from 2000 to 2017, the spatiotemporal patterns of the vegetative cover in the Yellow River basin in the last 18 years were studied using linear regression, residual analysis, and the Hurst index. The vegetation coverage of the Yellow River basin was higher in the southeast and lower in the northwest, with a relatively slow growth trend. The whole basin NDVI was relatively stable, and only approximately one‐fifth of the region had a large fluctuation, mainly distributed in Ningxia and northern Shaanxi. The residual trend of the NDVI was positive in 87% of the areas in the basin, and the overall impact of human activities on the increase in NDVI was mainly promoted. The characteristics of vegetation change in the future with the same directionality were stronger than the reverse characteristics, but the area showing continuous degradation in the future still accounted for 7%, mainly distributed in Xining City, Lanzhou City, Ningxia Plain, Hetao Plain, etc., which needs further strengthening of ecological construction and protection. This study is helpful for predicting and evaluating the vegetation dynamics of the Yellow River basin under the background of GGP implementation and provides a theoretical basis for regional environmental protection and the future adjustment of GGP work.
The challenges of cloud adoption among South African small to medium enterprises: A thematic analysis
Authors: Mudzamba Ronald , van der Schyff Karl , Renaud Karen
Published: July 2022

The successful use of Information and Communication Technologies (ICTs) by Small to Medium Enterprises (SMEs) remains a persistent problem within developing economies where they face several technical and skills‐related challenges. Although cloud services can mitigate some of these challenges, many SMEs fail to adopt cloud services. Therefore, the main objective of this paper was to develop key recommendations (based on a high‐level cloud services adoption framework) which South African SMEs could use to guide them in their adoption of cloud services. To develop our recommendations, we conducted 13 semi‐structured interviews with nine South African SMEs within the Eastern Cape province. These were thematically analyzed and the findings used to create a high‐level cloud services adoption framework. Our findings indicate that technical expertise (i.e., knowledge) amongst SMEs plays a vital role in the cloud adoption process. Those SMEs who do realize the importance of such technical expertise often use intermediaries to achieve successful adoption of cloud services. We also found evidence to suggest that SMEs generally do not carry out comprehensive cloud adoption preparatory activities, consequently failing in their adoption of cloud services.
Visible red light does not induce DNA damage in human dermal fibroblasts
Authors: Wang Jennifer Y. , Austin Evan , Jagdeo Jared
Published: July 2022

Visible red light (RL) therapy is a rapidly expanding treatment option for dermatological conditions, including acne, psoriasis and chronic wounds. It is currently unknown if high fluences of RL induce DNA damage via reactive oxygen species (ROS) stress or other pathways. Our lab previously demonstrated that RL generates ROS in human dermal fibroblasts (HDFs). Other studies show that UV and blue light generate ROS and DNA damage in fibroblasts. This study aims to determine if RL induces DNA damage in HDFs. We found that 320 J/cm2, 640 J/cm2 and 1280 J/cm2 RL (633 ± 6 nm) did not measurably increase DNA damage in the form of cyclobutane pyrimidine dimers (CPD) or 6‐4 photoproducts (6‐4PP) immediately, 3 hours and 24 hours following irradiation. Our study further supports that RL therapy is safe in human skin fibroblasts.
The proteomic and particle composition of human platelet lysate for cell therapy products
Authors: Rodrigues Raul M. , Valim Vanessa de Souza , Berger Markus , da Silva Annelise P. M. , Fachel Flávia N. S. , Wilke Ianaê I. , da Silva Walter O. B. , Santi Lucélia , da Silva Maria A. L. , Amorin Bruna , Sehn Filipe , Yates John R. , Guimarães Jorge A. , Silla Lucia
Published: July 2022

Following health agencies warning, the use of animal origin supplements should be avoided in biological products proposed as therapy in humans. Platelet lysate and several other growth factors sources are alternatives to replace fetal calf serum, the current gold standard in clinical‐grade cell culture. However, the platelet supplement's content lacks data due to different production methods. The principle behind these products relays on the lysis of platelets that release several proteins, some of which are contained in heterogeneous granules and coordinate biological functions. This study aims to analyze the composition and reproducibility of a platelet lysate produced with a standardized method, by describing several batches' protein and particle content using proteomics and dynamic light scattering. Proteomics data revealed a diversified protein content, with some related to essential cellular processes such as proliferation, morphogenesis, differentiation, biosynthesis, adhesion, and metabolism. It also detected proteins responsible for activation and binding of transforming growth factor beta, hepatocyte growth factor, and insulin‐like growth factor. Total protein, biochemical, and growth factors quantitative data showed consistent and reproducible values across batches. Novel data on two major particle populations is presented, with high dispersion level at 231 ± 96 d.nm and at 30 ± 8 d.nm, possibly being an important way of protein trafficking through the cellular microenvironment. This experimental and descriptive analysis aims to support the content definition and quality criteria of a cell supplement for clinical applications.
Vasorin plays a critical role in vascular smooth muscle cells and arterial functions
Authors: Louvet Loïc , Lenglet Gaëlle , Krautzberger A. Michaela , Mentaverri Romuald , Hague Frédéric , Kowalewski Clara , Mahtal Nassim , Lesieur Julie , Bonnet Anne‐Laure , Andrique Caroline , Gaucher Céline , Gomila Cathy , Schrewe Heinrich , Tharaux Pierre‐Louis , Kamel Said , Chaussain Catherine , Six Isabelle
Published: July 2022

Within the cardiovascular system, the protein vasorin (Vasn) is predominantly expressed by vascular smooth muscle cells (VSMCs) in the coronary arteries and the aorta. Vasn knockout (Vasn−/−) mice die within 3 weeks of birth. In the present study, we investigated the role of vascular Vasn expression on vascular function. We used inducible Vasn knockout mice (VasnCRE‐ERT KO and VasnSMMHC‐CRE‐ERT2 KO, in which respectively all cells or SMCs only are targeted) to analyze the consequences of total or selective Vasn loss on vascular function. Furthermore, in vivo effects were investigated in vitro using human VSMCs. The death of VasnCRE‐ERT KO mice 21 days after tamoxifen injection was concomitant with decreases in blood pressure, angiotensin II levels, and vessel contractibility to phenylephrine. The VasnSMMHC‐CRE‐ERT2 KO mice displayed concomitant changes in vessel contractibility in response to phenylephrine and angiotensin II levels. In vitro, VASN deficiency was associated with a shift toward the SMC contractile phenotype, an increase in basal intracellular Ca2+ levels, and a decrease in the SMCs' ability to generate a calcium signal in response to carbachol or phenylephrine. Additionally, impaired endothelium‐dependent relaxation (due to changes in nitric oxide signaling) was observed in all Vasn knockout mice models. Our present findings highlight the role played by Vasn SMC expression in the maintenance of vascular functions. The mechanistic experiments suggested that these effects are mediated by SMC phenotype switching and changes in intracellular calcium homeostasis, angiotensin II levels, and NO signaling.
A critical role of AMP‐activated protein kinase in regulating intestinal nutrient absorption, barrier function, and intestinal diseases
Authors: Wu Zhihui , Xu Chengfei , Zheng Tenghui , Li Qihui , Yang Siwang , Shao Jiayuan , Guan Wutai , Zhang Shihai
Published: July 2022

As one of the most important organs in animals, the intestine is responsible for nutrient absorption and acts as a barrier between the body and the environment. Intestinal physiology and function require the participation of energy. 5′‐adenosine monophosphate‐activated protein kinase (AMPK), a classical and highly expressed energy regulator in intestinal cells, regulates the process of nutrient absorption and barrier function and is also involved in the therapy of intestinal diseases. Studies have yielded findings that AMPK regulates the absorption of glucose, amino acids, and fatty acids in the intestine primarily by regulating transportation systems, as we detailed here. Moreover, AMPK is involved in the regulation of the intestinal mechanical barrier and immune barrier through manipulating the expression of tight junctions, antimicrobial peptides, and secretory immunoglobulins. In addition, AMPK also participates in the regulation of intestinal diseases, which indicates that AMPK is a promising therapeutic target for intestinal diseases and cancer. In this review, we summarized the current understanding regarding how AMPK regulates intestinal nutrient absorption, barrier function, and intestinal diseases.