bluuebunny/crossref_metadata_2025 huggingface dataset:
Aster la vista: Unraveling the biochemical basis of carotenoid homeostasis in the human retina
Authors: Bandara Sepalika , von Lintig Johannes
Published: September 2022

Carotenoids play pivotal roles in vision as light filters and precursor of chromophore. Many vertebrates also display the colorful pigments as ornaments in bare skin parts and feathers. Proteins involved in the transport and metabolism of these lipids have been identified including class B scavenger receptors and carotenoid cleavage dioxygenases. Recent research implicates members of the Aster protein family, also known as GRAM domain‐containing (GRAMD), in carotenoid metabolism. These multi‐domain proteins facilitate the intracellular movement of carotenoids from their site of cellular uptake by scavenger receptors to the site of their metabolic processing by carotenoid cleavage dioxygenases. We provide a model how the coordinated interplay of these proteins and their differential expression establishes carotenoid distribution patterns and function in tissues, with particular emphasis on the human retina.
Generalized pairwise comparisons for censored data: An overview
Authors: Deltuvaite‐Thomas Vaiva , Verbeeck Johan , Burzykowski Tomasz , Buyse Marc , Tournigand Christophe , Molenberghs Geert , Thas Olivier
Published: September 2022

The method of generalized pairwise comparisons (GPC) is an extension of the well‐known nonparametric Wilcoxon–Mann–Whitney test for comparing two groups of observations. Multiple generalizations of Wilcoxon–Mann–Whitney test and other GPC methods have been proposed over the years to handle censored data. These methods apply different approaches to handling loss of information due to censoring: ignoring noninformative pairwise comparisons due to censoring (Gehan, Harrell, and Buyse); imputation using estimates of the survival distribution (Efron, Péron, and Latta); or inverse probability of censoring weighting (IPCW, Datta and Dong). Based on the GPC statistic, a measure of treatment effect, the “net benefit,” can be defined. It quantifies the difference between the probabilities that a randomly selected individual from one group is doing better than an individual from the other group. This paper aims at evaluating GPC methods for censored data, both in the context of hypothesis testing and estimation, and providing recommendations related to their choice in various situations. The methods that ignore uninformative pairs have comparable power to more complex and computationally demanding methods in situations of low censoring, and are slightly superior for high proportions (>40%) of censoring. If one is interested in estimation of the net benefit, Harrell's c index is an unbiased estimator if the proportional hazards assumption holds. Otherwise, the imputation (Efron or Peron) or IPCW (Datta, Dong) methods provide unbiased estimators in case of proportions of drop‐out censoring up to 60%.
The contribution of manufacturing companies to the achievement of sustainable development goals: An empirical analysis of the operationalization of sustainable business models
Authors: Bonfanti Angelo , Mion Giorgio , Brunetti Federico , Vargas‐Sánchez Alfonso
Published: September 2022

This study aims to identify the sustainable business practices operationalized in the sustainable business models of manufacturing companies and highlights these companies' contributions to achieving Sustainable Development Goals (SDGs). The results outline that a clear sustainable value proposition is operationalized through a large and various range of sustainable practices that, although some of them are legally promoted, are mostly voluntarily adopted. Unlike previous studies, this research shows a widespread commitment not only to the economic and environmental dimensions of sustainability but also to the social one, above all to promote workers' well‐being, improve the workplaces, and engage the employees. Furthermore, the study reveals an across‐the‐board dimension of sustainability operationalized by the adoption of local embeddedness strategies, networking development, and creation of a sustainable ecosystem and contributes to extending—and improving all dimensions of—the triple bottom line framework. Finally, the companies investigated contribute to the achievement of 11 of the 17 SDGs by highlighting dimensions in which companies already have a strong impact and those in which they could enhance their practice. Based on these results, this research advances theoretical knowledge and offers practical implications to improve sustainable business management further.
Boosting computer‐aided design pedagogy using interactive self‐assessmentgraphical tools
Authors: Pando Cerra Pablo , Fernández Álvarez Humberto , Busto Parra Bernardo , Castaño Busón Sofía
Published: September 2022

Computer‐aided design (CAD) tools are essential for any engineer and, thus, many researchers have focused on developing the most suitable method for acquiring CAD competences. In recent years, efforts have been devoted to designing new, innovative and helpful methodologies to improve the CAD pedagogy. The presented research aims at showing the advantages of integrating interactive self‐assessment tools into CAD learning methodologies, such as problem‐based learning (PBL). One hundred and ninety‐one first‐year Mechanical Engineering students participated in the research. They were evenly and randomly divided into two groups: a control group and an experimental group. Students belonging to the control group made use of PBL. The experimental group made use of PBL and a new interactive tool, called TrainCAD, that allows the self‐assessment of 2D‐CAD models designed in AutoCAD. The presented results show that experimental group students have considerably improved their academic performance and increased their motivation on the subject. Therefore, the combination of the two proposed approaches seems to be useful for helping students during the CAD learning process. On the other hand, gender was also a factor that has been analysed, to discern whether it influences the proposed academic learning process (based on the applied CAD pedagogy), concluding that there is no significant influence.
Construction of a cuproptosis‐related lncRNA signature for predicting prognosis and immune landscape in osteosarcoma patients
Authors: Ni Shumin , Hong Jinjiong , Li Weilong , Ye Meng , Li Jinyun
Published: September 2022

Background

Long noncoding RNAs (lncRNAs) influence the onset of osteosarcoma. Cuproptosis is a novel cell death mechanism. We attempted to identify a cuproptosis‐related lncRNA signature to predict the prognosis and immune landscape in osteosarcoma patients.

Methods

Transcriptional and clinical data of 85 osteosarcoma patients were derived from the TARGET database and randomly categorized into the training and validation cohorts. We implemented the univariate and multivariate Cox regression, along with LASSO regression analyses for developing a cuproptosis‐related lncRNA risk model. Kaplan–Meier curves, C‐index, ROC curves, univariate and multivariate Cox regression, and nomogram were used to assess the capacity of this risk model to predict the osteosarcoma prognosis. Gene ontology, KEGG, and Gene Set Enrichment (GSEA) analyses were conducted for determining the potential functional differences existing between the high‐risk and low‐risk patients. We further conducted the ESTIMATE, single‐smaple GSEA, and CIBERSORT analyses for identifying the different immune microenvironments and immune cells infiltrating both the risk groups.

Results

We screened out four cuproptosis‐related lncRNAs (AL033384.2, AL031775.1, AC110995.1, and LINC00565) to construct the risk model in the training cohort. This risk model displayed a good performance to predict the overall survival of osteosarcoma patients, which was confirmed by using the validation and the entire cohort. Further analyses showed that the low‐risk patients have more immune activation and immune cells infiltrating as well as a good response to immunotherapy.

Conclusions

We developed a novel cuproptosis‐related lncRNA signature with high reliability and accuracy for predicting outcome and immunotherapy response in osteosarcoma patients, which provides new insights into the personalized treatment of osteosarcoma.
Individualized number of induction chemotherapy cycles for locoregionally advanced nasopharyngeal carcinoma patients based on early tumor response
Authors: Jiang Yu‐Ting , Chen Kai‐Hua , Liang Zhong‐Guo , Yang Jie , Qu Song , Li Ling , Zhu Xiao‐Dong
Published: September 2022

Background

The optimal number of cycles of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) is unclear. We aimed to combine the tumor response during IC and tumor stage to individualize the number of IC cycles.

Methods

Totally, 498 LANPC patients who received IC plus CCRT between 2014 and 2018 were reviewed. Tumor response during IC was used to stratify patients with different risks. All patients were classified into those who received two cycles of IC and those who were treated with three cycles. Propensity score matching methods were performed to compare the treatment efficiency.

Results

After two cycles of IC, 340/498 (68.3%) cases showed complete tumor response (CR)/partial response (PR) and 158 (31.7%) achieved stable disease (SD)/disease progression (PD). Unfavorable responders (SD/PD) exhibited poor survival outcomes. The three‐cycle IC regimen was correlated with better OS and PFS than the two‐cycle regimen for N2‐3 patients in the CR/PR group. However, the use of different IC cycle strategies achieved similar survival outcomes for SD/PD or N0‐1 patients. The incidences of acute toxicities were higher in the IC = 3 group.

Conclusions

Tumor response during IC could be a powerful predictor of LANPC and could be used to guide the individualized number of IC cycles. A three‐cycle IC regimen seemed to be preferable for N2‐3 patients who received CR/PR during IC. However, an additional cycle of IC could not benefit N0‐1 or SD/PD patients, and the optimal treatment strategies for these patients require further consideration.
The need to tailor the omission of axillary lymph node dissection to patients with good prognosis and sentinel node micro‐metastases
Authors: Houvenaeghel Gilles , de Nonneville Alexandre , Chopin Nicolas , Classe Jean‐Marc , Mazouni Chafika , Chauvet Marie‐Pierre , Reyal Fabien , Tunon de Lara Christine , Jouve Eva , Rouzier Roman , Daraï Emile , Gimbergues Pierre , Coutant Charles , Azuar Anne Sophie , Villet Richard , Crochet Patrice , Rua Sandrine , Bannier Marie , Cohen Monique , Boher Jean‐Marie
Published: September 2022

Background

Results of IBCSG‐23‐01‐trial which included breast cancer patients with involved sentinel nodes (SN) by isolated‐tumor‐cells or micro‐metastases supported the non‐inferiority of completion axillary‐lymph‐node‐dissection (cALND) omission. However, current data are considered insufficient to avoid cALND for all patients with SN‐micro‐metastases.

Methods

To investigate the impact of cALND omission on disease‐free‐survival (DFS) and overall survival (OS), we analyzed a cohort of 1421 patients <75 years old with SN‐micro‐metastases who underwent breast conservative surgery (BCS). We used inverse probability of treatment weighting (IPTW) to obtain adjusted Kaplan–Meier estimators representing the experience in the analysis cohort, based on whether all or none had been subject to cALND omission.

Results

Weighted log‐rank tests comparing adjusted Kaplan–Meier survival curves showed significant differences in OS (p‐value = 0.002) and borderline significant differences in DFS (p‐value = 0.090) between cALND omission versus cALND. Cox's regression using stabilized IPTW evidenced an average increase in the risk of death associated with cALND omission (HR = 2.77, CI95% = 1.36–5.66). Subgroup analyses suggest that the rates of recurrence and death associated with cALND omission increase substantially after a large period of time in the half sample of women less likely to miss cALND.

Conclusions

Using IPTW to estimate the causal treatment effect of cALND in a large retrospective cohort, we concluded cALND omission is associated with an increased risk of recurrence and death in women of <75 years old treated by BCS in the absence of a large consensus in favor of omitting cALND. These results are particularly contributive for patients treated by BCS where cALND omission rates increase over time.
Impact of extracardiac vascular disease on outcomes of 1.4 million patients undergoing percutaneous coronary intervention
Authors: Bashar Hussein , Matetić Andrija , Curzen Nick , Mamas Mamas A.
Published: September 2022

Objectives

Extracardiac vascular disease (ECVD) is increasingly recognized as a cardiovascular risk factor, but its association with outcomes after percutaneous coronary intervention (PCI) has not been well characterized.

Methods

Using the National Inpatient Sample database, all patients undergoing PCI between October 2015 and December 2018 were stratified by the presence and organ‐specific extent of extracardiac vascular comorbidity (cerebrovascular disease (CeVD), renovascular, aortic and peripheral arterial disease (PAD)). Primary outcome was all‐cause mortality and secondary outcomes were (a) major adverse cardiovascular and cerebrovascular events (MACCE), (b) acute ischemic stroke and (c) major bleeding. Multivariable logistic regression was used to determine the adjusted odds ratios (aOR) and 95% confidence interval (95% CI).

Results

Of a total of 1,403,505 patients undergoing PCI during the study period, 199,470 (14.2%) had ECVD. Patients with ECVD were older (median of 72 years vs. 70 years, p < 0.001) and had higher comorbidity burden that their counterparts. All cause‐mortality was 22% higher in patients with any ECVD compared to those without ECVD. PAD patients had the highest odds of all‐cause mortality (aOR 1.48, 95% CI 1.40–1.56), followed by those with CeVD (aOR 1.15, 95% CI 1.10–1.19). Patients with extracardiac disease had increased odds of MACCE, ischemic stroke and bleeding, irrespective of the nature or extent (p < 0.05), compared to patients without ECVD.

Conclusion

ECVD is associated with worse outcomes in patients undergoing PCI including significantly higher rates of death and stroke. These data should inform our shared decision‐making process with our patients.
The Core/Shell Structure P Doped MoS2@Ni3S2Nanorods Array for High Current Density Hydrogen Evolution in Alkaline and Acidic Electrolyte
Authors: Gao Yong , Zhang Dani , Li Jingjing , Gong Hao , Jiang Cheng , Xue Hairong , Huang Xianli , Wang Tao , He Jianping
Published: September 2022

Electrocatalysis is the most promising strategy to generate clean energy H2, and the development of catalysts with excellent hydrogen evolution reaction (HER) performance at high current density that can resist strong alkaline and acidic electrolyte environment is of great significance for practical industrial application. Therefore, a P doped MoS2@Ni3S2nanorods array (named P‐NiMoS) was successfully synthesized through successive sulfuration and phosphorization. P‐NiMoS presents a core/shell structure with a heterojunction between MoS2(shell) and Ni3S2(core). Furthermore, the doping of P modulates the electronic structure of the P‐NiMoS; the electrons transfer from the t2gorbital of Ni element to the egempty orbital of Mo element through the Ni−S−Mo bond at the Ni3S2and MoS2heterojunction, facilitating the hydrogen evolution reaction. As a result, P‐NiMoS exhibits excellent HER activity; the overpotential is 290 mV at high current density of 250 mA cm−2in alkaline electrolyte, which is close to Pt/C (282 mV@250 mA cm−2), and P‐NiMoS can stably evolve hydrogen for 48 h.
Influence of Achiral Phosphine Ligands on a Synergistic Organo‐ and Palladium‐Catalyzed Asymmetric Allylic Alkylation
Authors: McLeod David , Inunnguaq Jessen Nicolaj , Nguyen Thanh V. Q. , Espe Marcus , Erickson Jeremy David , Anker Jørgensen Karl , Yang Limin , Houk K. N.
Published: September 2022

An unusual diastereodivergent stereoselective allylation reaction is presented. It consists of a palladium‐catalyzed allylation reaction of an organocatalytically generated amino isobenzofulvene, where the diastereoselectivity is controlled by the electronic properties of a monodentate, achiral ligand on palladium. One major diastereoisomer is formed using triarylphosphines substituted with neutral or electron‐donating substituents of the aryl group, while those with electron‐withdrawing substituents favor the other diastereoisomer. The diastereoselectivity correlates with the Taft inductive parameter of substituents on the triarylphosphine ligand on palladium. The synergistic reaction involves both a catalytic secondary amine catalyst for the indene‐aldehyde activation and the monodentate phosphine ligands on palladium, affording a highly enantioselective reaction with up to 98 % enantiomeric excess. Based on computational investigations, the role of the monodentate phosphine ligand on the diastereoselectivity is discussed.
Fault prediction of non‐linear multi‐mode industrial process based on MKPCA model
Authors: Ma Jie , Wang Xinyu , Lv Yongyan , Li Gang
Published: September 2022

The actual industrial process is regarded as a non‐linear multi‐mode process. If the system is described according to the model of the single‐mode or the linear multi‐mode, it will inevitably lead to a large number of false alarms or missed alarms. The fault detection, fault reconstruction, fault amplitude estimation, and prediction for non‐linear multi‐mode process based on the multi‐kernel principal component analysis (MKPCA) model are studied in this paper. First, the MKPCA model will be applied to fault detection in the steady‐state process of different modes, and a weighted algorithm will be adopted for fault detection in the transition process. Then, the fault degree will be described quantitatively, and the fault amplitude in the form of fault reconstruction will be solved by the optimization method, and the consistent estimation algorithm of fault amplitude under different modes will also be studied. Finally, the prediction model of support vector machine (SVM) prediction model will be applied to predict the development trend of the fault amplitude. Furthermore, the Tennessee Eastman (TE) process will be taken as an application object to verify the effectiveness and superiority of the method.
Phosphoregulation of the septin cytoskeleton in neuronal development and disease
Authors: Werner Bailey , Yadav Smita
Published: September 2022

Septins are highly conserved GTP‐binding proteins that oligomerize and form higher order structures. The septin cytoskeleton plays an important role in cellular organization, intracellular transport, and cytokinesis. Kinase‐mediated phosphorylation of septins regulates various aspects of their function, localization, and dynamics. Septins are enriched in the mammalian nervous system where they contribute to neurodevelopment and neuronal function. Emerging research has implicated aberrant changes in septin cytoskeleton in several human diseases. The mechanisms through which aberrant phosphorylation by kinases contributes to septin dysfunction in neurological disorders are poorly understood and represent an important question for future research with therapeutic implications. This review summarizes the current state of knowledge of the diversity of kinases that interact with and phosphorylate mammalian septins, delineates how phosphoregulation impacts septin dynamics, and describes how aberrant septin phosphorylation contributes to neurological disorders.
Reduced specificity and increased overgenerality of autobiographical memory persist as cognitive vulnerabilities in remitted major depression: A meta‐analysis
Authors: Hallford David John , Rusanov Danielle , Yeow Joseph J. E. , Barry Tom Joseph
Published: September 2022

Difficulty in accessing specific memories, referred to as reduced memory specificity or overgeneral memory (OGM), has been established as a marker of clinical depression. However, it is not clear if this deficit persists following the remission of depressive episodes. The current study involved a systematic review and meta‐analysis of empirical studies with the aim of establishing whether remitted depression was associated with retrieving fewer specific and more overgeneral autobiographical memories. Seventeen studies were identified as eligible. The results indicated that people with remitted depression recalled fewer specific memories (k = 15; g = −0.314, 95% CI [−0.543; −0.085], z = −2.69, p = .007) and more categoric memories (k = 9; g = 0.254, 95% CI [0.007; 0.501], z = 2.02, p = .043) compared to people who had never been depressed. Given these deficits have elsewhere been shown to be prognostic of future depressive symptoms, these findings suggest that reduced memory specificity/overgeneral memory persists following remission and may be a risk factor for future episodes of depression in those that are in remission. The findings are discussed in terms of how this knowledge might influence clinical understanding of relapse prevention and maintenance of remission in those with a history of depression.
Exploring Genes and Phenotypes Within Chromosomal Regions Using OMIM's GeneScout
Authors: Applegate Carolyn D. , Schiettecatte François , Hamosh Ada , Amberger Joanna S.
Published: September 2022

Structural variation in genomes, such as copy number variants (CNVs), is under scrutiny for its contribution to phenotypic expression and evolution. Regions of homozygosity (ROH) are ripe for phenotype‐gene discovery. Determining the genes and related phenotypes within genomic regions is key to studying potential functional and phenotypic consequences. Because individuals have multiple CNVs and ROHs in their genome, identifying genomic regions that are phenotypically significant is challenging. GeneScout is a web‐based tool that can be used to search genomic regions to display and filter the genes and their associated phenotypes within regions of interest. Phenotypes and their associated gene(s) can then be filtered to show only the genes with phenotypes that have a particular inheritance pattern and/or specific clinical feature(s). Phenotypes can then be selected to compare the clinical synopses side‐by‐side in Online Mendelian Inheritance in Man (OMIM®). Additionally, two coordinate sets can be compared to determine either the regions of overlap or the unique regions (subtraction). The resulting coordinate ranges are displayed on the results page, and the results table displays only the genes and phenotypes present within the coordinate ranges. The interactive table includes gene‐specific links to external resources such as ClinVar, ClinGen validity, ClinGen dosage, and gnomAD, and a diamond symbol next to the gene name indicates a gene that spans the start or end of a coordinate range. Searches and comparisons may be performed for coordinates in assemblies GRCh37 (hg19) and GRCh38 (hg38). The results page offers the option to liftover coordinates entered in GRCh37 to GRCh38 and updates the results table to display the gene content based on assembly GRCh38. The search coordinates and results table can be downloaded in a tab‐delimited or Excel file. © 2022 Wiley Periodicals LLC.

Basic Protocol: Searching GeneScout
Authenticity, student support grows enrollment
Authors: Hope Joan
Published: September 2022

When Steve Robinson became Senior Associate Vice President for Enrollment Management at the University of Utah two and a half years ago, what he learned about the institution during the job search process convinced him it was a sleeping giant.
Potential significance of uncovered self‐expandable metal stents for distal malignant biliary obstruction: A propensity score‐adjusted competing risk regression analysis
Authors: Torisu Yuichi , Chiba Masafumi , Kato Masayuki , Kinoshita Yuji , Akasu Takafumi , Kanai Tomoya , Tomita Yoichi , Shimamoto Nana , Abe Takahiro , Kanazawa Keisuke , Tsukinaga Shintaro , Nakano Masanori , Saeki Chisato , Sumiyama Kazuki , Saruta Masayuki
Published: September 2022

Objectives

Selection criteria for self‐expandable metal stents (SEMSs) with or without cover during palliative treatment of distal malignant biliary obstruction (DMBO) remain unclear. We evaluated factors associated with time to recurrent biliary obstruction (TRBO) in fully covered SEMSs (FCSEMSs) and uncovered SEMSs (UCSEMSs).

Methods

We retrospectively analyzed consecutive patients with DMBO who received a SEMS. TRBO was determined using the Kaplan–Meier analysis, and complications were compared between the FCSEMS and UCSEMS groups. After TRBO‐associated factors were extracted using multivariate competing‐risks regression (CRR), propensity score‐adjusted CRRs were performed to verify their robustness.

Results

There were 180 patients (66 FCSEMSs and 114 UCSEMSs) enrolled in this study. There was no significant difference between median TRBO in the FCSEMS and UCSEMS groups (275 vs. 255 days, p = 0.67). Complications were more frequent in the FCSEMS than UCSEMS group (21.2% vs. 8.8%; p = 0.023). Multivariate CRR for TRBO‐associated factors revealed that “pancreatic ductal carcinoma (PDAC) treated with UCSEMS” was the only independent predictor of TRBO (p = 0.03). Similarly, the propensity score‐adjusted CRRs showed no significant difference in TRBO in “FCSEMS” vs “UCSEMS” (p = 0.96); however, there was a significant difference in “PDAC using UCSEMS” vs “other” (p = 0.043). In the palliative care group including any DMBO without chemotherapy, the first quartile of the TRBO of UCSEMS was 100 days.

Conclusions

UCSEMSs are a possible option for both patients with DMBO arising from PDAC and for patients with any DMBO receiving palliative care who should avoid SEMS‐related complications.
Past climatic refugia and landscape resistance explain spatial genetic structure in Oriental beech in the South Caucasus
Authors: Sękiewicz Katarzyna , Danelia Irina , Farzaliyev Vahid , Gholizadeh Hamid , Iszkuło Grzegorz , Naqinezhad Alireza , Ramezani Elias , Thomas Peter A. , Tomaszewski Dominik , Walas Łukasz , Dering Monika
Published: September 2022

Predicting species‐level effects of climatic changes requires unraveling the factors affecting the spatial genetic composition. However, disentangling the relative contribution of historical and contemporary drivers is challenging. By applying landscape genetics and species distribution modeling, we investigated processes that shaped the neutral genetic structure of Oriental beech (Fagus orientalis), aiming to assess the potential risks involved due to possible future distribution changes in the species. Using nuclear microsatellites, we analyze 32 natural populations from the Georgia and Azerbaijan (South Caucasus). We found that the species colonization history is the most important driver of the genetic pattern. The detected west–east gradient of genetic differentiation corresponds strictly to the Colchis and Hyrcanian glacial refugia. A significant signal of associations to environmental variables suggests that the distinct genetic composition of the Azerbaijan and Hyrcanian stands might also be structured by the local climate. Oriental beech retains an overall high diversity; however, in the context of projected habitat loss, its genetic resources might be greatly impoverished. The most affected are the Azerbaijan and Hyrcanian populations, for which the detected genetic impoverishment may enhance their vulnerability to environmental change. Given the adaptive potential of range‐edge populations, the loss of these populations may ultimately affect the specie's adaptation, and thus the stability and resilience of forest ecosystems in the Caucasus ecoregion. Our study is the first approximation of the potential risks involved, inducing far‐reaching conclusions about the need of maintaining the genetic resources of Oriental beech for a species' capacity to cope with environmental change.
Double Prins Cyclisation Enabled Rapid Access to α,ω‐Hydroxytetrahydropyrans
Authors: Trevorrow Jonathan , O'Kearney‐McMullan Anne , Miller Potucka Lucie , Dobbs Adrian P.
Published: September 2022

The spiroketal moiety is an important substructure within many biological natural products. One method to access them is via the oxidative cyclisation of a pendant hydroxyl group on to a pre‐formed pyran. However access to such precursors has hitherto been challenging and requires multistep syntheses frequently with considerable protecting group manipulation. Herein we report a novel and high yielding method for the preparation of hydroxydi‐ and hydroxytetra‐hydropyrans, as spiroketal precursors, utilizing a novel double‐Prins cyclisation approach.
Solid‐State Direct Electrophilic Selenocyanation of (Hetero)Arenes using Mechanochemistry
Authors: Xiao Jun‐An , Liang Jin‐Shao , Zhang Huan , Meng Ru‐Fang , Su Wei , Lin Chenxiang , Cui Jian‐Guo , Huang Yan‐Min
Published: September 2022

A mechanochemical direct selenocyanation of arenes/heterocyclic arenes with electrophilic selenocyanating reagents to access (hetero)aryl selenocyanates has been developed. This protocol provided an efficient strategy to access various aromatic selenocyanates in yields up to 99 % under ball‐milling reaction conditions within 60 minutes. Gram‐scale reaction and further transformations of the product were conducted to demonstrate the synthetic utilities of this method.
Electrochemical Sensor for Selective Detection of Meldonium in Urine by Voltammetry
Authors: Mezentseva Olga L. , Slepchenko Galina B. , Dorozhko Elena V. , Moiseeva Eugenia S. , Kryukovskiy Vladimir P. , Zaycev Nikolay K.
Published: September 2022

A highly sensitive electrochemical sensor based on arenediazonium tosylates was designed to detect meldonium in urine. The effect of the concentration of ArN2+OTs− arenediazonium tosylate modifier and various substituents was studied. Basic operating parameters for voltammetric meldonium detection were established and the procedure for urine sample preparation was developed. The following values were obtained: limit of detection (LOD) 0.005 mg ⋅ L−1 (P=0.95) and limit of quantification (LOQ) 0.01 mg ⋅ L−1. The relationship between the analytical signal and meldonium concentration in the solution ranging from 0.01 to 400 mg ⋅ L−1 was described by a linear function. The meldonium concentration error did not exceed 18 %. The analysis time for a single urine sample was reduced to 15 minutes.
Studies of Phenol Electrooxidation Performed on Platinum Electrode in Dimethyl Sulphoxide Medium. Determination of Unreacted Phenol by the Effect of 4‐Vinylbenzenesulphonate on the Electrooxidation Process
Authors: Kiss László , Kunsági‐Máté Sándor , Szabó Péter
Published: September 2022

The electrooxidation of phenol was studied in the presence of sodium 4‐vinylbenzenesulfonate in various quantities. When the sulphonate was dissolved in equal or higher quantities than phenol the peak currents increased gradually and suppression of electropolymerization was observed. When the sulphonate quantity was smaller than that of phenol brown films fouled the electrode. The observed phenomenon was utilized in an analytical procedure namely determination of unreacted phenol in electrolysis solution with linear dynamic range between 0 and 50 mM and 2.96 mM detection limit. The shape of curve became saturated‐like above 50 mM.
Theoretical Modeling of Perovskite–Kesterite Tandem Solar Cells for Optimal Photovoltaic Performance
Authors: Jayan K. Deepthi
Published: September 2022

Herein, a solar cell device simulation study is performed using the solar cell capacitance simulator 1D tool to assess the performance parameters of a monolithic two‐terminal (2‐T) and a mechanically stacked four‐terminal (4‐T) tandem solar cell with a top perovskite subcell and a bottom subcell consisting of a perovskite material FA0.83Cs0.17PbI1.5Br1.5 and a kesterite photovoltaic material Cu2ZnSnSe4 as the light‐harvesting material, respectively. The 2‐T tandem device design furnishes a open‐circuit voltage, short‐circuit current density, fill factor, and power conversion efficiency (PCE) of 1.81 V, 18.18 mA cm−2, 66.18%, and 31.15%, respectively, while establishing the condition of matching the short‐circuit current density between the top perovskite and bottom kesterite cells. The 4‐T device furnishes a high PCE of 37.49% when the filtered spectrum is used for modeling the bottom subcell. Further, the optimization of the input parameters of the light active layers of the top and bottom cells leads to an increase in PCE of the 4‐T tandem device to 37.84%.
Metal‐organic framework derived porous structures towards lithium rechargeable batteries
Authors: Han Sang A , Qutaish Hamzeh , Lee Jong‐Won , Park Min‐Sik , Kim Jung Ho
Published: September 2022

Batteries are a promising technology in the field of electrical energy storage and have made tremendous strides in recent few decades. In particular, lithium‐ion batteries are leading the smart device era as an essential component of portable electronic devices. From the materials aspect, new and creative solutions are required to resolve the current technical issues on advanced lithium (Li) batteries and improve their safety. Metal‐organic frameworks (MOFs) are considered as tempting candidates to satisfy the requirements of advanced energy storage technologies. In this review, we discuss the characteristics of MOFs for application in different types of Li batteries. A review of these emerging studies in which MOFs have been applied in lithium storage devices can provide an informative blueprint for future MOF research on next‐generation advanced energy storage devices.

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Omnibus or Ominous immigration laws? Immigration policy and mental health of the Hispanic population
Authors: Luo Tianyuan , Kostandini Genti
Published: September 2022

This study examines the impact of Omnibus Immigration Laws on the mental health of the Hispanic populations in the U.S. We use a Difference‐in‐Differences framework and data from the Behavioral Risk Factor Surveillance System Survey of Centers for Disease Control and Prevention for the 2000–2016 period that contains information on more than 400 thousand Hispanics residing in the U.S. We find that the most stringent provision, namely, “show me your papers” laws, adversely affects the mental health of Hispanics and contributes to an increase of 12%–16% in the number of unhealthy mental days and an increase of 13%–18% in the probability of having frequent mental distress in the states with “show me your papers” laws. OIL provisions that enforced the use of E‐Verify or limited the use of public benefits to unauthorized immigrants did not have any effect on mental health. The study also examines (1) police stops, (2) physical health, insurance, and employment status, (3) co‐ethnic density, and (4) immigration enforcement awareness as potential mechanisms that could lead to a deterioration in the mental health of Hispanics. The evidence indicates their vulnerability to strict immigration enforcement. The social and public health cost should be carefully evaluated when formulating and implementing immigration policies.
Interleukin‐33 facilitates liver regeneration through serotonin‐involved gut‐liver axis
Authors: Wen Yankai , Emontzpohl Christoph , Xu Long , Atkins Constance L. , Jeong Jong‐Min , Yang Yang , Kim Kangho , Wu Chuan , Akira Shizuo , Ju Cynthia
Published: September 2022

Background and Aims:

Insufficient liver regeneration causes post‐hepatectomy liver failure and small‐for‐size syndrome. Identifying therapeutic targets to enhance hepatic regenerative capacity remains urgent. Recently, increased IL‐33 was observed in patients undergoing liver resection and in mice after partial hepatectomy (PHx). The present study aims to investigate the role of IL‐33 in liver regeneration after PHx and to elucidate its underlying mechanisms.

Approach and Results:

We performed PHx in IL‐33−/−, suppression of tumorigenicity 2 (ST2)−/−, and wild‐type control mice, and found deficiency of IL‐33 or its receptor ST2 delayed liver regeneration. The insufficient liver regeneration could be normalized in IL‐33−/− but not ST2−/− mice by recombinant murine IL‐33 administration. Furthermore, we observed an increased level of serotonin in portal blood from wild‐type mice, but not IL‐33−/− or ST2−/− mice, after PHx. ST2 deficiency specifically in enterochromaffin cells recapitulated the phenotype of delayed liver regeneration observed in ST2−/− mice. Moreover, the impeded liver regeneration in IL‐33−/− and ST2−/− mice was restored to normal levels by the treatment with (±)‐2,5‐dimethoxy‐4‐iodoamphetamine, which is an agonist of the 5‐hydroxytrytamine receptor (HTR)2A. Notably, in vitro experiments demonstrated that serotonin/HTR2A‐induced hepatocyte proliferation is dependent on p70S6K activation.

Conclusions:

Our study identified that IL‐33 is pro‐regenerative in a noninjurious model of liver resection. The underlying mechanism involved IL‐33/ST2‐induced increase of serotonin release from enterochromaffin cells to portal blood and subsequent HTR2A/p70S6K activation in hepatocytes by serotonin. The findings implicate the potential of targeting the IL‐33/ST2/serotonin pathway to reduce the risk of post‐hepatectomy liver failure and small‐for‐size syndrome.
A comprehensive overview of CRISPR/Cas 9 technology and application thereof in drug discovery
Authors: Khurana Amit , Sayed Nilofer , Singh Vishakha , Khurana Isha , Allawadhi Prince , Rawat Pushkar Singh , Navik Umashanker , Pasumarthi Sravan Kumar , Bharani Kala Kumar , Weiskirchen Ralf
Published: September 2022

Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)‐Cas technology possesses revolutionary potential to positively affect various domains of drug discovery. It has initiated a rise in the area of genetic engineering and its advantages range from classical science to translational medicine. These genome editing systems have given a new dimension to our capabilities to alter, detect and annotate specified gene sequences. Moreover, the ease, robustness and adaptability of the CRISPR/Cas9 technology have led to its extensive utilization in research areas in such a short period of time. The applications include the development of model cell lines, understanding disease mechanisms, discovering disease targets, developing transgenic animals and plants, and transcriptional modulation. Further, the technology is rapidly growing; hence, an overlook of progressive success is crucial. This review presents the current status of the CRISPR–Cas technology in a tailor‐made format from its discovery to several advancements for drug discovery alongwith future trends associated with possibilities and hurdles including ethical concerns.
Ginsenoside Rd ameliorates muscle wasting by suppressing the signal transducer and activator of transcription 3 pathway
Authors: Wijaya Yoseph Toni , Setiawan Tania , Sari Ita Novita , Park Keunwan , Lee Chan Hee , Cho Kae Won , Lee Yun Kyung , Lim Jae‐Young , Yoon Jeong Kyo , Lee Sae Hwan , Kwon Hyog Young
Published: September 2022

Background

The effects of some drugs, aging, cancers, and other diseases can cause muscle wasting. Currently, there are no effective drugs for treating muscle wasting. In this study, the effects of ginsenoside Rd (GRd) on muscle wasting were studied.

Methods

Tumour necrosis factor‐alpha (TNF‐α)/interferon‐gamma (IFN‐γ)‐induced myotube atrophy in mouse C2C12 and human skeletal myoblasts (HSkM) was evaluated based on cell thickness. Atrophy‐related signalling, reactive oxygen species (ROS) level, mitochondrial membrane potential, and mitochondrial number were assessed. GRd (10 mg/kg body weight) was orally administered to aged mice (23–24 months old) and tumour‐bearing (Lewis lung carcinoma [LLC1] or CT26) mice for 5 weeks and 16 days, respectively. Body weight, grip strength, inverted hanging time, and muscle weight were assessed. Histological analysis was also performed to assess the effects of GRd. The evolutionary chemical binding similarity (ECBS) approach, molecular docking, Biacore assay, and signal transducer and activator of transcription (STAT) 3 reporter assay were used to identify targets of GRd.

Results

GRd significantly induced hypertrophy in the C2C12 and HSkM myotubes (average diameter 50.8 ± 2.6% and 49.9% ± 3.7% higher at 100 nM, vs. control, P ≤ 0.001). GRd treatment ameliorated aging‐ and cancer‐induced (LLC1 or CT26) muscle atrophy in mice, which was evidenced by significant increases in grip strength, hanging time, muscle mass, and muscle tissue cross‐sectional area (1.3‐fold to 4.6‐fold, vs. vehicle, P ≤ 0.05; P ≤ 0.01; P ≤ 0.001). STAT3 was found to be a possible target of GRd by the ECBS approach and molecular docking assay. Validation of direct interaction between GRd and STAT3 was confirmed through Biacore analysis. GRd also inhibited STAT3 phosphorylation and STAT3 reporter activity, which led to the inhibition of STAT3 nuclear translocation and the suppression of downstream targets of STAT3, such as atrogin‐1, muscle‐specific RING finger protein (MuRF‐1), and myostatin (MSTN) (29.0 ± 11.2% to 84.3 ± 30.5%, vs. vehicle, P ≤ 0.05; P ≤ 0.01; P ≤ 0.001). Additionally, GRd scavenged ROS (91.7 ± 1.4% reduction at 1 nM, vs. vehicle, P ≤ 0.001), inhibited TNF‐α‐induced dysregulation of ROS level, and improved mitochondrial integrity (P ≤ 0.05; P ≤ 0.01; P ≤ 0.001).

Conclusions

GRd ameliorates aging‐ and cancer‐induced muscle wasting. Our findings suggest that GRd may be a novel therapeutic agent or adjuvant for reversing muscle wasting.
Clinical findings of patients with hyperammonemia affected by urea cycle disorders with hepatic encephalopathy
Authors: Lopes Franciele Fátima , Sitta Angela , de Moura Coelho Daniella , Ribas Graziela Schmitt , Faverzani Jéssica Lamberty , dos Reis Bianca Gomes , Wajner Moacir , Vargas Carmen Regla
Published: September 2022

Urea cycle disorders (UCD) are a group of genetic diseases caused by deficiencies in the enzymes and transporters involved in the urea cycle. The impairment of the cycle results in ammonia accumulation, leading to neurological dysfunctions and poor outcomes to affected patients. The aim of this study is to investigate and describe UCD patients' principal clinical and biochemical presentations to support professionals on urgent diagnosis and quick management, aiming better outcomes for patients. We explored medical records of 30 patients diagnosed in a referral center from Brazil to delineate UCD clinical and biochemical profile. Patients demonstrated a range of signs and symptoms, such as altered levels of consciousness, acute encephalopathy, seizures, progressive loss of appetite, vomiting, coma, and respiratory distress, in most cases combined with high levels of ammonia, which is an immediate biomarker, leading to a UCD suspicion. The most prevalent UCD detected were ornithine transcarbamylase deficiency, followed by citrullinemia type 1, hyperargininemia, carbamoyl phosphate synthase 1 deficiency, and argininosuccinic aciduria. Clinical symptoms were highly severe, being the majority developmental and neurological disabilities, with 20% of death rate. Laboratory analysis revealed high levels of ammonia (mean ± SD: 860 ± 470 μmol/L; reference value: ≤80 μmol/L), hypoglycemia, metabolic acidosis, and high excretion of orotic acid in the urine (except in carbamoyl phosphate synthetase 1 [CPS1] deficiency). We emphasize the need of urgent identification of UCD clinical and biochemical conditions, and immediate measurement of ammonia, to enable the correct diagnosis and increase the chances of patients' survival, minimizing neurological and psychomotor damage caused by hepatic encephalopathy.
Modulating disease phenotype in a songbird: A role for inflammation in disease tolerance?
Authors: Ruden Rachel M. , Adelman James S.
Published: September 2022

Individual animals vary greatly in their responses to infection, either killing off the invading pathogen (resistance) or minimizing the per‐pathogen costs of infection on host fitness (tolerance). Though we understand little about the physiological drivers of tolerance in wild animals, phenotypically, it manifests as milder clinical signs of disease. Here, we use a well‐described disease system, finch mycoplasmosis, to evaluate the role of inflammation in disease tolerance. House finches (Haemorhous mexicanus) infected with the bacterial pathogen Mycoplasma gallisepticum (MG) develop conjunctival pathology that satisfies the cardinal signs of inflammation. We report on a captive trial performed in 2016 and replicated in 2018 that tested whether chemotherapeutics, specifically nonsteroidal anti‐inflammatory drugs (NSAIDs), can reduce lesion severity, thus pushing individuals toward more tolerant phenotypes. Though birds treated with NSAIDs in the first trial developed milder pathology per unit pathogen load, we found no effect of treatment in the second trial, perhaps due to natural variation in baseline tolerance within the source population across years. Second‐trial control birds developed markedly milder pathology than first‐year controls, suggesting that the effect of trial swamped the effect of treatment in this study. Moving forward, using birds from a population in which the disease is absent or only recently emerged—and so tolerance has not yet been selected for—may better elucidate the role of pro‐inflammatory mediators in disease tolerance.
Genetic counselors' response types to prenatal patient deferring or attributing religious/spiritual statements: An exploratory study of US genetic counselors
Authors: Sitaula Alina , Veach Patricia McCarthy , MacFarlane Ian M. , Lee Whiwon , Redlinger‐Grosse Krista
Published: September 2022

Research shows religiosity and spirituality (R/S) influence genetic counseling patients' and families' risk perception, decision‐making, and coping. No published studies have examined how genetic counselors respond to patient‐initiated R/S statements. This exploratory study examined genetic counselors' response types and reasons for their responses to two prenatal patient's R/S statements. Genetic counselors (n = 225) recruited through a National Society of Genetic Counselors eblast completed a survey containing two hypothetical scenarios regarding a prenatal patient's receipt of a trisomy 18 diagnosis. Scenarios were identical except for the last patient statement: “God makes everything possible…we leave things in his hands” (a deferring statement) or “I feel like God is punishing me for something I did” (an attributing statement). Imagining they were the counselor, participants wrote a response to each scenario and provided reasons for their response. Responses were analyzed using the Helping Skills Verbal Response System. MANOVA and chi‐square tests, examining differences in response type based on patient statement (deferring or attributing), participant comfort with R/S, and years of experience, yielded a significant multivariate effect for scenario (p < 0.001). Responses to the deferring statement scenario contained a greater proportion of content statements (p < 0.001), closed questions (p < 0.001), and information‐giving (p < 0.001). Responses to the attributing statement scenario contained a greater proportion of open questions (p = 0.05), influencing statements (p < 0.001), and affective statements (p = 0.006). Neither comfort with R/S nor genetic counseling experience significantly affected response type. Thematic analysis of reasons for responses yielded nine themes. Most prevalent were exploration (of the patient's statement), validation, correction (of patient's beliefs), and reassurance. The findings reflect stylistic differences in how and why genetic counselors respond to patients.