bluuebunny/crossref_metadata_2025 huggingface dataset:
Guselkumab, a Selective Interleukin‐23 p19 Subunit Inhibitor, Resolves Dactylitis in Patients With Active Psoriatic Arthritis: Pooled Results Through Week 52 From Two Phase 3 Studies
Authors: McGonagle Dennis , McInnes Iain B. , Deodhar Atul , Schett Georg , Shawi May , Chakravarty Soumya D. , Kollmeier Alexa P. , Xu Xie L. , Sheng Shihong , Xu Stephen , Ritchlin Christopher T. , Rahman Proton , Mease Phillip J.
Published: March 2023

Objective

Previous analyses of pooled DISCOVER‐1 and DISCOVER‐2 data through Week 24 showed significantly higher rates of dactylitis resolution in patients treated with guselkumab compared with placebo. Here, we investigate associations between dactylitis resolution and other outcomes through 1 year.

Methods

Patients were randomized 1:1:1 to receive subcutaneous injections of guselkumab 100 mg at Week 0, Week 4, and then every 4 or 8 weeks, or placebo with crossover to guselkumab at Week 24. Independent assessors determined dactylitis severity score (DSS; 0‐3/digit; total = 0‐60). Dactylitis resolution (DSS = 0) (prespecified) and at least 20%, at least 50%, and at least 70% DSS improvement from baseline (post hoc) were determined through Week 52 (nonresponder imputation for treatment failure through Week 24 and for missing data through Week 52). ACR50, tender/swollen joints, low disease activity (LDA) as assessed by composite indices, and radiographic progression (DISCOVER‐2 only) were assessed in patients with dactylitis versus without dactylitis resolution at Week 24 and Week 52.

Results

Patients with dactylitis at baseline (473 of 1118) had more severe joint and skin disease than those without dactylitis (645 of 1118). At Week 52, approximately 75% of guselkumab‐randomized patients with dactylitis at baseline had complete resolution; approximately 80% had at least 70% DSS improvement. Through Week 52, new‐onset dactylitis (DSS ≥1) was uncommon among patients with a DSS of 0 at baseline. Guselkumab‐randomized patients with dactylitis resolution were more likely to achieve ACR50, at least 50% reduction in tender and swollen joints, and LDA at Week 24 and Week 52 than those without resolution. At Week 52, patients with dactylitis resolution had numerically less radiographic progression from baseline (DISCOVER‐2).

Conclusion

Through 1 year, approximately 75% of guselkumab‐randomized patients had complete resolution of dactylitis; patients exhibiting resolution were more likely to achieve other important clinical outcomes. Given the high burden of dactylitis, resolution may be associated with better long‐term patient outcomes.
Self‐Healing Photochromic Elastomer Composites for Wearable UV‐Sensors
Authors: Yimyai Tiwa , Crespy Daniel , Pena‐Francesch Abdon
Published: March 2023

Photochromic materials have recently received strong interest for the development of wearable ultraviolet (UV) detection technologies because they do not require electronic components, resulting in systems and devices that change color upon irradiation. However, their implementation in wearable technology has lightweight, compliance, and durability (especially under mechanical stress) requirements that are limited by the materials’ properties. Here, a self‐healing photochromic elastomer composite (photoPUSH) consisting of phosphomolybdic acid (PMA) in a self‐healing polyurethane dynamic network with reversible disulfide bonds (PUSH) is presented. The unique properties of the dynamic polymer matrix enable multiple complementary functions in the UV‐sensing composite: i) photochromism via electron donor groups without requiring additional dopants, ii) stretchability and durability via elastomeric properties, iii) healing of extreme mechanical damage via dynamic bonds, and iv) multimaterial integration via adhesive properties. PhotoPUSH composites exhibit excellent durability, tunable sensing range, and no loss of performance under mechanical stress and severe damage, as well as in underwater environments (waterproof). Leveraging these properties, soft, portable, multimaterial photoPUSH‐based UV‐sensing devices are developed for applications in environmental monitoring, packaging, and healthcare wearable technology (including skin‐mounted, textile‐mounted, and wristband devices) in challenging environments and tunable to different skin types.
Photocrosslinkable, Injectable Locust Bean Gum Hydrogel Induces Chondrogenic Differentiation of Stem Cells for Cartilage Regeneration
Authors: Qu Yangyang , He Si , Luo Shixing , Zhao Jinmin , Liang Ruiming , Liao Chuanan , Zheng Li
Published: March 2023

Due to the limited therapeutic efficacy of current treatments, articular cartilage regeneration is still challenging work. Scaffold‐based tissue engineering provides a promising strategy for cartilage regeneration, but most scaffolds are limited by poor mechanical properties or unfavorable biocompatibility. Here, a novel photocrosslinkable, injectable locust bean gum (LBG)–methacrylate (MA) hydrogel is reported as a biomimetic extracellular matrix (ECM) for cartilage repair with minimal invasive operation. LBG‐MA hydrogels show controllable degradation rate and improve mechanical properties and excellent biocompatibility. More importantly, LBG‐MA hydrogel significantly induces bone mesenchymal stem cells to chondrogenic differentiation in vitro, as evidenced by high accumulation of cartilage‐specific ECM components glycosaminoglycan and upregulated expression of key chondrogenic genes (collagen type II, aggrecan, and sex determining region Y‐box9). Besides, the hydrogel is injectable, which can be in situ crosslinked via UV irradiation. Further, the photocrosslinkable hydrogels accelerate cartilage healing in vivo after 8 weeks of therapy. A strategy is provided here for photocrosslinkable, injectable, biodegradable scaffold fabrication based on native polysaccharide polymer for minimal invasive cartilage repair.
Functional traits and trait coordination change over the life of a leaf in a tropical fern species
Authors: Krieg Christopher P. , Seeger Kate , Campany Courtney , Watkins James E. , McClearn Deedra , McCulloh Katherine A. , Sessa Emily B.
Published: March 2023

Premise

Plant ecological strategies are often defined by the integration of underlying traits related to resource acquisition, allocation, and growth. Correlations between key traits across diverse plants suggest that variation in plant ecological strategies is largely driven by a fast–slow continuum of plant economics. However, trait correlations may not be constant through the life of a leaf, and it is still poorly understood how trait function varies over time in long‐lived leaves.

Methods

Here, we compared trait correlations related to resource acquisition and allocation across three different mature frond age cohorts in a tropical fern species, Saccoloma inaequale.

Results

Fronds exhibited high initial investments of nitrogen and carbon, but with declining return in photosynthetic capacity after the first year. In the youngest fronds, we found water‐use efficiency to be significantly lower than in the oldest mature fronds due to increased transpiration rates. Our data suggest that middle‐aged fronds are more efficient relative to younger, less water‐use efficient fronds and that older fronds exhibit greater nitrogen investments without higher photosynthetic return. In addition, several trait correlations expected under the leaf economics spectrum (LES) do not hold within this species, and some trait correlations only appear in fronds of a specific developmental age.

Conclusions

These findings contextualize the relationship between traits and leaf developmental age with those predicted to underlie plant ecological strategy and the LES and are among the first pieces of evidence for when relative physiological trait efficiency is maximized in a tropical fern species.
A case of severe paraquat poisoning treated by continuous hemodiafiltration without sequelae
Authors: Hisamura Masaki , Ogura Tomoyuki , Tokuda Mitsuhiro , Nakamura Motohiro , Kenichiro Sonoda , Ando Yoji , Nakata Kazuyuki , Taguchi Hirokazu
Published: March 2023

Background

In a suicide attempt, a 49‐year‐old male ingested pesticides. He arrived at the hospital restless and vomiting blue liquid.

Case Presentation

The patient was diagnosed with paraquat poisoning at a lethal dose and experienced renal dysfunction during treatment. He underwent continuous hemodiafiltration (CHDF). Hemodialysis was temporarily initiated and found to improve renal function. He was discharged on day 36 in good condition. He remains well with only mild renal impairment and no pulmonary fibrosis, 240 days after the incident. The fatality rate of paraquat poisoning is approximately 80%, regardless of the treatment. Early hemodialysis combined with CHDF within 4 h has been reported to be effective. In this case, CHDF was initiated approximately 3 h after paraquat administration and showed a successful outcome.

Conclusion

CHDF should be performed as soon as possible to treat paraquat poisoning.
Development of a Versatile Protein Labeling Tool for Live‐Cell Imaging Using Fluorescent β‐Lactamase Inhibitors
Authors: Minoshima Masafumi , Umeno Taro , Kadooka Kohei , Roux Margaux , Yamada Namiko , Kikuchi Kazuya
Published: March 2023

To understand the function of protein in live cells, real‐time monitoring of protein dynamics and sensing of their surrounding environment are important methods. Fluorescent labeling tools are thus needed that possess fast labeling kinetics, high efficiency, and long‐term stability. We developed a versatile chemical protein‐labeling tool based on fluorophore‐conjugated diazabicyclooctane β‐lactamase inhibitors (BLIs) and wild‐type TEM‐1 β‐lactamase protein tag. The fluorescent probes efficiently formed a stable carbamoylated complex with β‐lactamase, and the labeled proteins were visualized over a long period of time in live cells. Moreover, use of an α‐fluorinated carboxylate ester‐based BLI prodrug enabled the probe to permeate cell membranes and stably label intracellular proteins after unexpected spontaneous ester hydrolysis. Lastly, combining the labeling tool with a pH‐activatable fluorescent probe allowed visual monitoring of lysosomal protein translocation during autophagy.
Beladung von RNA mit Aminosäuren in einer putativen RNA‐Peptid‐Welt
Authors: Singer Johannes N. , Müller Felix M. , Węgrzyn Ewa , Hölzl Christina , Hurmiz Hans , Liu Chuyi , Escobar Luis , Carell Thomas
Published: March 2023

Die RNA ist ein Molekül, das sowohl genetische Informationen speichern als auch katalytische Reaktionen ausführen kann. Dieser beobachtete Dualismus rückt die RNA ins Rampenlicht der Konzepte über den Ursprung des Lebens. Die RNA‐Welt‐Hypothese geht davon aus, dass das Leben aus selbst replizierenden RNA‐Molekülen entstand, die sich zu immer komplexeren Strukturen entwickelten. Vor kurzem haben wir gezeigt, dass RNA mit Hilfe erhaltener nicht‐kanonischer Nukleoside, die potenzielle Relikte einer frühen RNA‐Welt sind, in der Lage ist, Peptide zu bilden, die kovalent an Nukleobasen der RNA gebunden sind, wodurch RNA‐Peptid‐Chimären entstehen. Es ist denkbar, dass solche Moleküle, welche die informationskodierenden Eigenschaften der RNA mit dem katalytischen Potenzial von Aminosäureseitenketten kombinieren können, einst die Strukturen waren, aus denen das Leben entstand. In diesem Artikel berichten wir über präbiotische Chemie, die es ermöglicht sowohl Nukleoside als auch RNA mit Aminosäuren zu beladen, was einen ersten Schritt zu einer RNA‐basierten Peptidsynthese in einer mutmaßlichen RNA‐Peptid‐Welt darstellt.
10–30‐day moist static energy evolutions related to the persistent heavy rainfall event in different stages of flood season over South China
Authors: Zheng Bin , Lin Ailan , Huang Yanyan
Published: March 2023

In this study, the flood season in South China (SC) was divided into three stages: two first rainy seasons (FRSs) around the South China Sea summer monsoon onset and one second rainy season when Typhoon prevails, denoted as FRS1, FRS2, and SRS, respectively, and then we diagnosed the moist static energy (MSE) budget associated with the 10–30‐day persistent heavy rainfall (PHR) over SC during these periods. The results indicate that there are great differences in the recharge of PHR‐related MSE in different stages of the flood season in SC: The FRS1 MSE associated with PHR moves southeastward from midlatitude; the large MSE is maintained in SC during the FRS2; during the SRS, the MSE perturbation propagates from the tropical western North Pacific to SC. From the perspective of the local MSE budget in SC, meridional and zonal advection play a key role in the maximum MSE change in the FRS1; the FRS2 and SRS MSE tendency is mainly determined by zonal advection and meridional advection, respectively. In contrast, the 10–30‐day propagating perturbation of MSE changes during both the FRS1 and FRS2 are mainly affected by the zonal advection, while the meridional circulation is dominant in the SRS. The cumulative contribution of external forcing (including radiation and surface heat fluxes) during the SRS to the propagation of PHR‐related MSE perturbation can reach more than 30%, and the closer to the land, the stronger the external forcing. During the FRS (including FRS1 and FRS2), however, the external forcing contributes little, even negatively.
Hidden population size estimation and diagnostics using two respondent‐driven samples with applications in Armenia
Authors: Kim Brian J. , Johnston Lisa G. , Grigoryan Trdat , Papoyan Arshak , Grigoryan Samvel , McLaughlin Katherine R.
Published: March 2023

Estimating the size of hidden populations is essential to understand the magnitude of social and healthcare needs, risk behaviors, and disease burden. However, due to the hidden nature of these populations, they are difficult to survey, and there are no gold standard size estimation methods. Many different methods and variations exist, and diagnostic tools are needed to help researchers assess method‐specific assumptions as well as compare between methods. Further, because many necessary mathematical assumptions are unrealistic for real survey implementation, assessment of how robust methods are to deviations from the stated assumptions is essential. We describe diagnostics and assess the performance of a new population size estimation method, capture–recapture with successive sampling population size estimation (CR‐SS‐PSE), which we apply to data from 3 years of studies from three cities and three hidden populations in Armenia. CR‐SS‐PSE relies on data from two sequential respondent‐driven sampling surveys and extends the successive sampling population size estimation (SS‐PSE) framework by using the number of individuals in the overlap between the two surveys and a model for the successive sampling process to estimate population size. We demonstrate that CR‐SS‐PSE is more robust to violations of successive sampling assumptions than SS‐PSE. Further, we compare the CR‐SS‐PSE estimates to population size estimations using other common methods, including unique object and service multipliers, wisdom of the crowd, and two‐source capture–recapture to illustrate volatility across estimation methods.
Synthesis and characterization of phenothiazine sensor for spectrophotometric and fluorescence detection of cyanide
Authors: Al‐Zahrani Fatimah A. M. , Al‐Ghamdi Huda A. , Abdel‐Lateef Mohamed A. , El‐Shishtawy Reda M.
Published: March 2023

A sensitive and selective phenothiazine‐based sensor (PTZ) has been successfully synthesized. The sensor PTZ displayed specific identification of CN− ‘turn‐off’ fluorescence responses with a quick reaction and strong reversibility in an acetonitrile:water (90:10, V/V) solution. The sensor PTZ for detecting CN− exhibits the marked advantages of quenching the fluorescence intensity, fast response time (60 s), and low value of the detection limit. The concentration that is authorized for drinking water by the WHO (1.9 μM) is far higher than the detection limit, which was found to be 9.11 × 10−9. The sensor displays distinct colorimetric and spectrofluorometric detection for CN− anion due to the addition of CN− anion to the electron‐deficient vinyl group of PTZ, which reduces intramolecular charge transfer efficiencies. The 1:2 binding mechanism of PTZ with CN− was validated by fluorescence titration, Job's plot, HRMS, 1H NMR, FTIR analysis, and density functional theory (DFT) investigations, among other methods. Additionally, the PTZ sensor was successfully used to precisely and accurately detect cyanide anions in actual water samples.
Socially responsible investments: A retrospective review and future research agenda
Authors: Beloskar Ved Dilip , Haldar Arunima , Rao S. V. D. Nageswara
Published: March 2023

Socially responsible investments (SRIs) have occupied the center stage of discussion in the finance and social discourses. This study aims to unravel the intellectual structure of the research on SRI. At present, SRI is undertheorized, and the extant literature is divided into multiple fragments. Existing review studies on SRI suffer from limitations related to definitions and methods. We organize the theoretical lines of extant research and tie them up with empirical studies in the field by using systematic literature review and bibliometric techniques on a corpus of as large as 976 research articles. Our study describes the current dynamics of the SRI field, clusters the fragments of research into meaningful themes, highlights the impediments to current research, and also proposes an agenda for future research. Although research on SRI occurs globally, the lack of academic collaboration among scholars and undertheorization are two major challenges of the field. Future research could examine ESG‐based asset pricing models, sustainable factor investing, and measures to tackle greenwashing.
Role of Sonazoid enhanced ultrasound assistant laparoscopic radiofrequency ablation in treating liver malignancy—A single‐center retrospective cohort study
Authors: Xu Jingyong , Liu Yuan , Wu Mingxiao , Song Jinghai , Li Chen
Published: March 2023

Aim

To evaluate the role of Sonazoid enhanced ultrasound assistant laparoscopic radiofrequency ablation in treating liver malignancy.

Methods

Consecutive patients are recruited. Rates of complication and postoperative length of stay are compared between the study and control groups. Progression‐free survival (PFS) of colorectal liver metastasis (CRLM) after ablation are compared. Complete ablation rates are compared and optimal tumor size is calculated by ROC curve analysis. Risk factors of incomplete ablation are determined by logistic regression analysis.

Results

Totally 73 patients with 153 lesions were included. No significant differences in the rate of complication were found between the study and control groups. PFS of CRLM in laparoscopic, intraoperative CEUS, and laparoscopic CEUS groups are all longer than their control groups. Complete ablation rates of laparoscopic, intraoperative CEUS, and laparoscopic CEUS groups are all higher than in their control groups with statistical significance. A tumor size of 2.15 cm is determined to be the optimal cut‐off with the area under the ROC curve of 0.854, 95% CI (0.764, 0.944), p = 0.001. In logistic regression analysis, tumor size [OR 20.425, 95% CI (3.136, 133.045), p = 0.002] and location of segments VII and VIII [OR 9.433, 95% CI (1.364, 65.223), p = 0.023] are calculated to be the risk factors of incomplete ablation, meanwhile, intraoperative CEUS shows to be a protective factor in univariate analysis [OR 0.110, 95% CI (0.013, 0.915), p = 0.041].

Conclusion

Sonazoid‐enhanced ultrasound assistant laparoscopic radiofrequency ablation is safe and effective to treat liver malignancy. We should pay attention to the ablation planning of larger tumors and tumors in special locations.
Advances in immune checkpoint inhibitors therapy for small cell lung cancer
Authors: Li Longhui , Liang Yangyueying , Yu Minghui , Zhao Lu , Mei Qingyun , Yu Yongchao , Wang Na , Zhang Dou , Wang Ziwei , Jia Yingjie , Kong Fanming
Published: March 2023

Background

As one of the most aggressive neuroendocrine tumors, small cell lung cancer (SCLC) has the most disappointing prognosis of all lung cancers. Although SCLC responds well to initial chemotherapy, the majority of patients experience disease recurrence within one year, and patient survival is poor. It is still necessary to explore the application of ICIs in SCLC since the beginning of the road to immunotherapy, which broke the 30‐year treatment deadlock of SCLC.

Methods

We searched PubMed, Web of Science, and Embase with search terms such as "SCLC", "ES‐SCLC", "ICIs", and "ICBs", and categorized and summarized the relevant literature obtained, and we compiled the latest progress about the application of ICIs in SCLC.

Results

We listed 14 clinical trials on ICIs, including 8 clinical trials on first‐line SCLC treatment, 2 clinical trials on second‐line SCLC treatment, 3 clinical trials on third‐line SCLC treatment, and 1 clinical trial on SCLC maintenance treatment.

Conclusion

ICIs in combination with chemotherapy can improve OS in SCLC patients, but the extent to which SCLC patients can benefit from ICIs is limited, and ICIs' combination treatment strategies still need to be continuously explored.
Evaluation of the efficacy of chemotherapy for tubular carcinoma of the breast: A Surveillance, Epidemiology, and End Results cohort study
Authors: Zhao Yuting , Chai Na , Li Shouyu , Yan Lutong , Zhou Can , He Jianjun , Zhang Huimin
Published: March 2023

Background

The use of systematic treatment for tubular carcinoma (TC) of the breast remained controversial. This study aimed to explore the efficacy of chemotherapy on TC to develop individualized treatment strategies.

Methods

Using the Surveillance, Epidemiology, and End Results (SEER) database, 6486 eligible cases with TC and 309,304 with invasive ductal carcinoma (IDC) were collected. Breast cancer‐specific survival (BCSS) was assessed through multivariable Cox analyses and Kaplan–Meier analyses. Differences between groups were balanced using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW).

Results

Compared with IDC patients, TC patients had a more favorable long‐term BCSS after PSM (hazard ratio = 0.62, p = 0.004) and IPTW (hazard ratio = 0.61, p < 0.001). Chemotherapy was an unfavorable predictor of BCSS for TC (hazard ratio = 3.20, p < 0.001). After stratifying by hormone receptor (HR) and lymph node (LN) status, chemotherapy was correlated with worse BCSS in the HR+/LN− subgroup (hazard ratio = 6.95, p = 0.001) but showed no impact on BCSS in the HR+/LN+ (hazard ratio = 0.75, p = 0.780) and HR−/LN− (hazard ratio = 7.87, p = 0.150) subgroups.

Conclusions

Tubular carcinoma is a low‐grade malignant tumor with favorable clinicopathological features and excellent long‐term survival. Adjuvant chemotherapy was not recommended for TC regardless of HR and LN status, while the therapy regimens should be carefully individualized.
How do counselling trainees describe group process and does this change over time?
Authors: Murphy Rick , Schofield Matt
Published: March 2023

Personal development groups or “group processes” are used in most counselling and psychotherapy trainings, but little is understood about how trainees change in their experience and descriptions of them over time. This study collected qualitative surveys (N = 70) from two groups of master's students (N = 35), at the mid‐ and end point of their first year of counselling training, to find out whether their descriptions of group process changed. We used content analysis to study the most common words and phrases used by trainee counsellors to describe group process and to monitor how positive, neutral and negative their descriptions were over time. We found a significant difference in the vocabulary and the ratio of positive to negative descriptions of group process at the midpoint of term, depending on the group the trainees were assigned to, with a levelling out of vocabulary words and positive and negative descriptions over time, converging towards a 70%–80% positive point at the end of term. Our results indicate that process groups need time to develop trainees above a positive threshold, by balancing group bonding against an ability to challenge and learn from difference, because individuals and groups start at different points in relation to their readiness and capacity for personal development. Further research should explore facilitation and trainee variables, as well as the impact of process groups on students' well‐being, because, while most of our students positively described the process, an important minority of students described negative experiences that were unresolved at the end of the study.
An Inclusive Review on the Assessment of Different Techniques for Natural Gas Liquid Recovery
Authors: Usman Muhammad , Pervaiz Erum
Published: March 2023

A comprehensive review is presented on the natural gas liquid (NGL) recovery process with emphasis on process description, energy requirements, NGL production, operating cost, and propane recovery. The industry standard single‐stage (ISS), recycle split vapor (RSV), cold residue reflux (CRR), and gas subcooled process (GSP) technologies focus on the improvement in the rectifying section of the demethanizer column, while the enhanced NGL recovery process (IPSI) focuses on the stripping section of the column. The fluor process consists of an absorber, a scrub column, and heavy hydrocarbon (HHC) separator, which form the integrated process of liquification and NGL separation. For rich feed, the economic performance, payback, and total annualized cost (TAC) of the IPSI process were lower than the other processes. For lean feed, the results of the scrub column scheme demonstrate the finest economic performance.
Capillary Pressure Determination Using Thermodynamic Desorption Isotherms and Porosity Measurements
Authors: Shigidi Ihab , Chemkhi Saber
Published: March 2023

Characterization of fluid flow in porous media depends on the capillary pressure. Experimental investigations on the capillary pressure are complicated and require advanced monitoring technologies. The objective of this study is to determine the capillary pressure by employing desorption isotherms measurements and using the Kelvin equation. The desorption isotherms curves were determined by the gravimetric method. The capillary pressure is presented as a function of the material's level of saturation, which is linked to the material moisture content and total porosity. Investigations were conducted over three types of clays to give classical behavior of their capillary pressure curves. The obtained results were compared with those of the literature concluding the reliability of the employed method to achieve good capillary pressure curve predictions.
Investigation of the Cold Flow Field in a Flow Reversal Reactor through Computational Fluid Dynamics Models
Authors: Liang Wenjun , Sun Yujie , Ju Haolin , Ren Sida , Li Xiang , Liu Jia
Published: March 2023

To optimize the flow field in a tubular reactor, new flow deflectors were added by using flow reversal technology. Two optimization structures, namely asterisk plate and composite plate, were designed. Numerical simulation was combined with physical experiments to verify the effectiveness of the flow field optimization. The results showed that the flow field uniformity of the reactor could be greatly improved by single plate and double plate. The uniformity index of the velocity in the axial section is greater than 0.95 within 15 cm, and the physical simulation results conform to the overall trend of the numerical simulation. However, the length of the optimized area of the single plate is about 5 cm shorter than that of the double plate, and it has better stability in the physical model.
Trapping of a Transient Base‐Stabilised Alumylene and Alumylene‐Type Reactivity of a Self‐Stabilising Dialumene towards Organic Azides
Authors: Dhara Debabrata , Jayaraman Arumugam , Härterich Marcel , Arrowsmith Merle , Jürgensen Malte , Michel Maximilian , Braunschweig Holger
Published: March 2023

The reduction of a carbene‐coordinated, sterically encumbered terphenyl‐substituted aluminium diiodide, (LRAlI2), yielded a “masked” dialumene (LRAl=AlRL), self‐stabilised through [2+2] cycloaddition with a peripheral aromatic group. During the course of the reaction, a carbene‐stabilised arylalumylene (LRAl:) was generated in situ, which was trapped using an alkyne, generating an aluminacyclopropene or a C−H activated product thereof, depending on the steric bulk of the alkyne. The masked dialumene also underwent intramolecular cycloreversion and dissociation into alumylene fragments, which reacted with various organic azides to yield monomeric or dimeric iminoalanes depending on the sterics of the azide substituent. The thermodynamics of monomeric and dimeric iminoalane formation were probed by theoretical calculations.
Exposure–response Modeling From the CLARITY Trial of Pimavanserin for Adjunctive Treatment of Major Depressive Disorder
Authors: Darwish Mona , Dirks Bryan , Passarell Julie , Jaworowicz David , Bihorel Sebastien , Howell Becky , Owen Joel , DeKarske Daryl , Stankovic Srdjan
Published: March 2023

In the 10‐week, phase 2 CLARITY study of patients with major depressive disorder, adjunctive therapy to antidepressants with pimavanserin 34 mg once daily statistically significantly improved the Hamilton Depression Rating Scale (HAMD‐17) total score (primary endpoint) and Sheehan Disability Scale (SDS) score (secondary endpoint) versus placebo. This analysis characterized the exposure–response (E–R) relationships of pimavanserin in this CLARITY patient population. Exposure measures were estimated for each patient based on population‐pharmacokinetic empirical Bayesian estimates. E–R models were developed to describe exposure–efficacy (HAMD‐17, SDS, and Clinical Global Impression‐Improvement [CGI‐I] scale) and exposure–safety relationships (Karolinska Sleepiness Scale [KSS], Massachusetts General Hospital Sexual Functioning Inventory [MGH‐SFI], and adverse events [AEs] of headache, sedation, and somnolence) relationships. For the primary efficacy endpoint (HAMD‐17 scores), a sigmoid maximum‐effect model described the time course of response, and a linear function of pimavanserin exposure was statistically significant. HAMD‐17 scores decreased steadily over time following placebo and pimavanserin treatment; separation from placebo increased as peak pimavanserin plasma concentration (Cmax) increased. At median pimavanserin Cmax (34‐mg dose), the reduction from baseline in HAMD‐17 scores was −11.1 and −13.5 at weeks 5 and 10, respectively. Relative to placebo, the model predicted comparable reductions in HAMD‐17 scores at weeks 5 and 10. Similar improvements in favor of pimavanserin were detected with SDS, CGI‐I, MGH‐SFI, and KSS scores. No E–R relationship was found for AEs. E–R modeling predicted a relationship between higher pimavanserin exposure and improvement in HAMD‐17 score and improvement across multiple secondary efficacy endpoints.
Teff: Food for the Future
Authors: Lamichhane Ritika , Walsh Olga S.
Published: March 2023

Teff (Eragrostis tef) is a native Ethiopian grain crop that is gaining popularity in the United States as a nutritious grain and a high quality forage crop. It is a reliable low‐risk crop that is relatively resistant to biotic and abiotic stresses and can be grown under moisture stress or waterlogged conditions. While it has a lot of potential, more research and education on teff is needed, particularly in the area of breeding and in the cropʼs nutrient and water requirements. Earn 0.5 CEUs in Crop Management by reading this article and taking the quiz at https://web.sciencesocieties.org/Learning‐Center/Courses.
Regenerative potential and limitations in a zebrafish model of hyperglycemia‐induced nerve degeneration
Authors: Sargent Sheridan , Brennan Anna , Clark Jessica Kennett
Published: March 2023

Background

Previous work from our lab has described a model of motor nerve degeneration in hyperglycemic zebrafish larvae which resembles mammalian models of diabetic peripheral neuropathy (DPN). Here, we optimized the hyperglycemic‐induction protocol, characterized deficits in nerve structure and behavioral function, and then examined the regenerative potential following recovery from the hyperglycemic state.

Results

In agreement with our previous work, hyperglycemia induced motor nerve degeneration and behavioral deficits. However, the optimized protocol initiated disruption of tight junctions within the blood‐nerve barrier, a phenotype apparent in mammalian models of DPN. Following a 10‐day recovery period, regeneration of motor nerve components was apparent, but behavioral deficits persisted. We next examined the effect of hyperglycemia on the musculoskeletal system and found subtle deficits in muscle that resolved following recovery, and robust deficits in the skeletal system which persisted following recovery.

Conclusion

Here we optimized our previous model of hyperglycemia‐induced motor nerve degeneration to more closely align with that observed in mammalian models and then characterized the regenerative potential following recovery from hyperglycemia. Notably, we observed striking impairments to skeletal development, which underscores the global impact hyperglycemia has across systems, and provides a framework for elucidating molecular mechanisms responsible for regenerative events moving forward.
Discordant growth of nasal cartilage and bone contributes to phenotypic variability of the skull in a mouse model
Authors: Book Shae A. , Moore Alyssa C. , Tourigny Madeline S. G. , Barr Kevin , Willmore Katherine E.
Published: March 2023

Background

We previously determined a nonlinear relationship between connexin 43 (Cx43) function and craniofacial phenotypic variation in the mutant mouse model G60S/+, and that this variation was driven by nasal bone deviation. While nonlinearities in the genotype‐phenotype map appear to be common, few studies have looked at the developmental processes that underlie this nonlinearity. Here, we investigated the potential tissue‐level developmental determinants of the variation in nasal bone phenotype in G60S/+ mice through postnatal development.

Results

The deviated nasal bone phenotype arises by postnatal day 21 and becomes more severe by 3 months in G60S/+ mice. Measures of nasal bone remodeling including the number of osteoclasts, mineralizing surface, mineral apposition rate, and bone formation rate are significantly greater in G60S/+ mice compared to wild‐type mice at 2 months, but these differences do not correspond with nasal bone deviation. The degree of nasal bone deviation does significantly and negatively correlate with the ratio between nasal bone and cartilaginous nasal septum length.

Conclusions

Our findings indicate that the mean phenotypic changes observed between G60S/+ and wild‐type mice are due to reduced bone growth, but the increased phenotypic variation found within mutant mice is due to discordant growth between nasal cartilage and bone.
Historically excluded groups in ecology are undervalued and poorly treated
Authors: Primack Richard B , Miller Tara K , Terry Carina , Marín‐Spiotta Erika , Templer Pamela H , Berhe Asmeret Asefaw , Diaz Vallejo Emily J , Hastings Meredith G , Magley Vicki J , Mattheis Allison , Schneider Blair B , Barnes Rebecca T
Published: March 2023

Hostile workplaces undermine efforts to make the ecological sciences more inclusive and welcoming. Survey responses by members of the Ecological Society of America (ESA) and subscribers to the ECOLOG‐L listserv provide a snapshot of a range of workplace experiences in ecology. The bottom line: identity matters. Although the majority of respondents reported positive workplace experiences (for instance, receiving mentorship), historically excluded groups – including scientists of color; women; lesbian, gay, bisexual, queer, pansexual, asexual, and other non‐heterosexual (LGBQPA+) individuals; and those who identify as disabled – on average were 1.5 times more likely to encounter negative workplace experiences (for instance, sexual harassment, interpersonal mistreatment, and insulting behaviors) as compared to their counterparts in the historical majority. Moreover, historically excluded groups were more likely to report opting out of professional opportunities, more likely to have considered leaving their institution, and twice as likely to consider a career change. We provide recommendations for professional associations, academic institutions, and other employers of ecologists to address interpersonal mistreatment through culture and policy changes.
Tensorial independent component analysis reveals social and reward networks associated with major depressive disorder
Authors: Dennison Jeff B. , Tepfer Lindsey J. , Smith David V.
Published: March 2023

Major depressive disorder (MDD) has been associated with changes in functional brain connectivity. Yet, typical analyses of functional connectivity, such as spatial independent components analysis (ICA) for resting‐state data, often ignore sources of between‐subject variability, which may be crucial for identifying functional connectivity patterns associated with MDD. Typically, methods like spatial ICA will identify a single component to represent a network like the default mode network (DMN), even if groups within the data show differential DMN coactivation. To address this gap, this project applies a tensorial extension of ICA (tensorial ICA)—which explicitly incorporates between‐subject variability—to identify functionally connected networks using functional MRI data from the Human Connectome Project (HCP). Data from the HCP included individuals with a diagnosis of MDD, a family history of MDD, and healthy controls performing a gambling and social cognition task. Based on evidence associating MDD with blunted neural activation to rewards and social stimuli, we predicted that tensorial ICA would identify networks associated with reduced spatiotemporal coherence and blunted social and reward‐based network activity in MDD. Across both tasks, tensorial ICA identified three networks showing decreased coherence in MDD. All three networks included ventromedial prefrontal cortex, striatum, and cerebellum and showed different activation across the conditions of their respective tasks. However, MDD was only associated with differences in task‐based activation in one network from the social task. Additionally, these results suggest that tensorial ICA could be a valuable tool for understanding clinical differences in relation to network activation and connectivity.
Comparison of a full and partial choice set design in a labeled discrete choice experiment
Authors: Thai Thao , Bliemer Michiel , Chen Gang , Spinks Jean , de New Sonja , Lancsar Emily
Published: March 2023

Labeled discrete choice experiments (DCEs) commonly present all alternatives using a full choice set design (FCSD), which could impose a high cognitive burden on respondents. In the setting of employment preferences, this study explored if a partial choice set design (PCSD) reduced cognitive burden whilst maintaining convergent validity compared with a FCSD. Respondents' preferences between the two designs were investigated. In the experimental design, labeled utility functions were rewritten into a single generic utility function using label dummy variables to generate an efficient PCSD with 3 alternatives shown in each choice task (out of 6). The DCE was embedded in a nationwide survey of 790 Australian pharmacy degree holders where respondents were presented with both a block of FCSD and PCSD tasks in random order. The PCSD's impact on error variances was investigated using a heteroscedastic conditional logit model. The convergent validity of PCSD was based on the equality of willingness‐to‐forgo‐expected‐salary estimates from Willingness‐to‐pay‐space mixed logit models. A nested logit model was used combined with respondents' qualitative responses to understand respondents' design preferences. We show a promising future use of PCSD by providing evidence that PCSD can reduce cognitive burden while satisfying convergent validity compared to FCSD.
Type H blood vessels in coupling angiogenesis‐osteogenesis and its application in bone tissue engineering
Authors: Xu Zhengyi , Kusumbe Anjali P. , Cai He , Wan Qianbing , Chen Junyu
Published: March 2023

One specific capillary subtype, termed type H vessel, has been found with unique functional characteristics in coupling angiogenesis with osteogenesis. Researchers have fabricated a variety of tissue engineering scaffolds to enhance bone healing and regeneration through the accumulation of type H vessels. However, only a limited number of reviews discussed the tissue engineering strategies for type H vessel regulation. The object of this review is to summary the current utilizes of bone tissue engineering to regulate type H vessels through various signal pathways including Notch, PDGF‐BB, Slit3, HIF‐1α, and VEGF signaling. Moreover, we give an insightful overview of recent research progress about the morphological, spatial and age‐dependent characteristics of type H blood vessels. Their unique role in tying angiogenesis and osteogenesis together via blood flow, cellular microenvironment, immune system and nervous system are also summarized. This review article would provide an insight into the combination of tissue engineering scaffolds with type H vessels and identify future perspectives for vasculized tissue engineering research.
Allantoin induces pruritus by activating MrgprD in chronic kidney disease
Authors: Yang Yan , Sun Yulin , Zhu Chan , Shen Xinyu , Sun Jianmei , Jing Tao , Jun Shi , Wang Changming , Yu Guang , Dong Xinzhong , Sheng Meixiao , Tang Zongxiang
Published: March 2023

Chronic kidney disease (CKD) is a disease with decreased, irreversible renal function. Pruritus is the most common skin symptom in patients with CKD, especially in end‐stage renal disease. The underlying molecular and neural mechanism of CKD‐associated pruritus (CKD‐aP) remains obscure. Our data show that the level of allantoin increases in the serum of CKD‐aP and CKD model mice. Allantoin could induce scratching behavior in mice and active DRG neurons. The calcium influx and action potential reduced significantly in DRG neurons of MrgprD KO or TRPV1 KO mice. U73122, an antagonist of phospholipase C, could also block calcium influx in DRG neurons induced by allantoin. Thus, our results concluded that allantoin plays an important role in CKD‐aP, mediated by MrgprD and TrpV1, in CKD patients.
Successful treatment of severe MSUD in Bckdhb−/− mice with neonatal AAV gene therapy
Authors: Pontoizeau Clément , Gaborit Clovis , Tual Nolan , Simon‐Sola Marcelo , Rotaru Irina , Benoist Marion , Colella Pasqualina , Lamazière Antonin , Brassier Anaïs , Arnoux Jean‐Baptiste , Rötig Agnès , Ottolenghi Chris , de Lonlay Pascale , Mingozzi Federico , Cavazzana Marina , Schiff Manuel
Published: March 2023

Maple syrup urine disease (MSUD) is rare autosomal recessive metabolic disorder caused by the dysfunction of the mitochondrial branched‐chain 2‐ketoacid dehydrogenase (BCKD) enzyme complex leading to massive accumulation of branched‐chain amino acids and 2‐keto acids. MSUD management, based on a life‐long strict protein restriction with nontoxic amino acids oral supplementation represents an unmet need as it is associated with a poor quality of life, and does not fully protect from acute life‐threatening decompensations or long‐term neuropsychiatric complications. Orthotopic liver transplantation is a beneficial therapeutic option, which shows that restoration of only a fraction of whole‐body BCKD enzyme activity is therapeutic. MSUD is thus an ideal target for gene therapy. We and others have tested AAV gene therapy in mice for two of the three genes involved in MSUD, BCKDHA and DBT. In this study, we developed a similar approach for the third MSUD gene, BCKDHB. We performed the first characterization of a Bckdhb−/− mouse model, which recapitulates the severe human phenotype of MSUD with early‐neonatal symptoms leading to death during the first week of life with massive accumulation of MSUD biomarkers. Based on our previous experience in Bckdha−/− mice, we designed a transgene carrying the human BCKDHB gene under the control of a ubiquitous EF1α promoter, encapsidated in an AAV8 capsid. Injection in neonatal Bckdhb−/− mice at 1014 vg/kg achieved long‐term rescue of the severe MSUD phenotype of Bckdhb−/− mice. These data further validate the efficacy of gene therapy for MSUD opening perspectives towards clinical translation.
The upsides and downsides of thought experiments in I‐O/OB
Authors: Latham Gary P.
Published: March 2023

Conducting thought experiments prior to conducting a pilot study followed by a field experiment or correlational study have proven invaluable to the author for selecting an issue worthy of study, generating testable hypotheses, ways of manipulating the independent variable, selecting/developing a reliable dependent variable, thinking through a doable procedure, and coming up with ways to persuade senior managers to approve the proposed studies/experiments. Nevertheless, arguments are presented as to why thought experiments are at best the beginning rather than the endpoint in the research process.
Ultrahighly Efficient Narrowband Red Luminescence of Uniquely Distorted Mn4+ Octahedron in the Feldspar‐Type LED Phosphor
Authors: Liu Yiyang , Zhang Rong , Yan Kaiyi , Sun Jian‐Feng
Published: March 2023

The mineral structure‐inspired discovery of red phosphors has become a research hotspot that can help compensate for the missing red components in cold white light‐emitting diodes (WLEDs). Herein, first the feldspar‐type structure is utilized to develop narrowband red‐emitting CaAl2Si2O8:Mn4+/Mn4+, Mg2+ phosphors. Rietveld refinement results confirm the Mn4+ occupation of the distorted [Ca1O6] octahedron, resulting in a strong nephelauxetic effect, and thus exhibits bright red luminescence with a narrow full width at half maximum (43 nm). Compared with CaAl2Si2O8:Mn4+, the fluorescence intensity of CaAl2Si2O8:Mn4+, Mg2+ is further enhanced by up to 210% owing to the decreasing nonradiative decay rate from 2Eg excited state, which weakens the concentration quenching effect resulting from energy migration along the adjacently aggregated Mn4+. CaAl2Si2O8:Mn4+, Mg2+ shows preferable thermal stability with an ultrahigh quantum efficiency (90.3%), surpassing other current Mn4+‐doped oxide phosphors and UCr4C4‐type nitride phosphors. A fabricated prototype WLED obtains ideal warm white light with a low correlated color temperature (3081 K) and a wide color gamut covering 112% of the National Television System Committee standard. Guided by natural mineral‐type structural prototypes, this study demonstrates the possibility of designing a uniquely distorted local structure to achieve a superior luminescence performance of Mn4+ for warm WLEDs.
Aggregate and disaggregate performance measurements: Inter‐temporally correlated performance measures with limited commitment
Authors: Yoo Junwook
Published: March 2023

This study employs the LEN model in analyzing aggregations and disaggregate use of inter‐temporally correlated performance measures in two‐period agencies with limited commitment. The optimal disaggregate use where an agent's incentive is on basic measures suffers information loss to depend on agency particulars. Induced action is restricted by the subsequent period action, and limited commitment leads to fostering late optimal effort inducement. Performance measure aggregation yields inaccurate inter‐temporal information relative to the disaggregate use and leads to raising early optimal effort inducement. Both the total informativeness and the difference in informativeness of performance measures fortify early optimal effort inducement.
Ground state solutions of a Klein–Gordon–Maxwell system for two scalar fields
Authors: Han Jongmin , Sohn Juhee
Published: March 2023

In this article, we consider a Klein–Gordon–Maxwell system for two scalar fields:

We show that there exists a ground state solution under the condition
and suitable constraints on
and
for
.