bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety, Pharmacokinetics, and Efficacy of AMG 706, an Oral Multikinase Inhibitor, in Patients With Advanced Solid Tumors
Authors: Rosen Lee S. , Kurzrock Razelle , Mulay Marilyn , Van Vugt Andy , Purdom Michelle , Ng Chaan , Silverman Jeffrey , Koutsoukos Antonis , Sun Yu-Nien , Bass Michael B. , Xu Ren Y. , Polverino Anthony , Wiezorek Jeffrey S. , Chang David D. , Benjamin Robert , Herbst Roy S.
Published: June 2007

Purpose

AMG 706 is an investigational, orally bioavailable inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptor, and stem-cell factor receptor. This phase I, dose-finding study evaluated the safety, pharmacokinetics, and pharmacodynamics of AMG 706 in patients with refractory advanced solid tumors.

Patients and Methods

AMG 706 was administered at escalating doses of 50 to 175 mg once daily or 25 mg bid for the first 21 days of a 28-day cycle. The 125-mg once-daily dose was also administered continuously. The maximum-tolerated dose (MTD), safety, pharmacokinetics, tumor response, and serum levels of proangiogenic markers were determined.

Results

Seventy-one patients received AMG 706. The MTD was 125 mg once daily administered continuously. The most frequent adverse events were fatigue (55%), diarrhea (51%), nausea (44%), and hypertension (42%). Plasma AMG 706 concentrations increased in a dose-proportional manner with no accumulation after multiple doses. Five patients (7%) had a partial response, 35 patients (49%) had stable disease (at least through day 50), and 31 patients (44%) had progressive disease. Changes in tumor size correlated significantly with an increase in placental growth factor (P = .003) and a decrease in soluble kinase domain receptor (P = .001).

Conclusion

In this study of patients with advanced refractory solid tumors, AMG 706 was well tolerated and displayed favorable pharmacokinetics and evidence of antitumor activity. Additional studies of AMG 706 as monotherapy and in combination with various agents are ongoing.
Randomized Controlled Trial of the Effects of Print Materials and Step Pedometers on Physical Activity and Quality of Life in Breast Cancer Survivors
Authors: Vallance Jeffrey K.H. , Courneya Kerry S. , Plotnikoff Ronald C. , Yasui Yutaka , Mackey John R.
Published: June 2007

Purpose

To determine the effects of breast cancer–specific print materials and step pedometers on physical activity (PA) and quality of life (QoL) in breast cancer survivors.

Patients and Methods

Breast cancer survivors (N = 377) were randomly assigned to receive one of the following: a standard public health recommendation for PA, previously developed breast cancer–specific PA print materials, a step pedometer, or a combination of breast cancer–specific print materials and step pedometers. The primary outcome was self-reported moderate/vigorous PA minutes per week. Secondary outcomes were QoL (Functional Assessment of Cancer Therapy–Breast), fatigue, self-reported brisk walking, and objective step counts. Assessments were conducted at baseline and postintervention (12 weeks).

Results

Attrition was 10.3% (39 of 377). On the basis of linear mixed-model analyses, PA increased by 30 minutes/week in the standard recommendation group compared with 70 minutes/week in the print material group (mean difference, 39 minutes/week; 95% CI = −10 to 89; d = 0.25; P = .117), 89 minutes/week in the pedometer group (mean difference, 59 minutes/week; 95% CI, 11 to 108; d = 0.38; P = .017), and 87 minutes/week in the combined group (mean difference, 57 minutes/week; 95% CI, 8 to 106; d = 0.37; P = .022). For brisk walking minutes/week, all three intervention groups reported significantly greater increases than the standard recommendation group. The combined group also reported significantly improved QoL (mean difference, 5.8; 95% CI, 2.0 to 9.6; d = 0.33; P = .003) and reduced fatigue (mean difference, 2.3; 95% CI, 0.0 to 4.7; d = 0.25; P = .052) compared with the standard recommendation group.

Conclusion

Breast cancer–specific PA print materials and pedometers may be effective strategies for increasing PA and QoL in breast cancer survivors. A combined approach appears to be optimal.

Clinical Trial Registration

ClinicalTrials.gov Identifier NCT00221221
Understanding Parents’ Approaches to Care and Treatment of Children With Cancer When Standard Therapy Has Failed
Authors: Bluebond-Langner Myra , Belasco Jean Bello , Goldman Ann , Belasco Carmen
Published: June 2007

Purpose

To examine US and United Kingdom (UK) parents’ approaches to care and treatment when standard therapy has failed and consider implications for clinical practice.

Methods

We conducted a prospective, ethnographic study of parents, patients, and staff, including participant-observation; open-ended, semistructured interviews; and review of medical records at a US and UK pediatric oncology center. Thirty-four children (n = 17 US, 17 UK), whose disease had recurred with less than 30% chance of cure, were enrolled between March 2001 and June 2002 and followed until death (n = 11 US, 14 UK) or close of study in December 2005 (n = 6 US, 3 UK).

Results

There were no major differences between parents’ approaches in the US and UK despite differences in health care systems, institutions, and parents’ religion or ethnicity. All parents continued to have or request meetings with the oncologist and investigative procedures. No parent initiated discontinuation of cancer- or symptom-directed interventions. In 28 of 34 cases (13 US, 15 UK), parents continued to pursue cancer-directed therapies; in 16 of 28 cases (seven US, nine UK), parents initiated inquires beyond what was offered.

Conclusion

Understanding parents’ behavior requires attention to the reason and emotion they bring to decision making and their children's care, their unique responsibilities as parents, and what they learn throughout the illness. Parents do not see cancer-directed therapy and symptom-directed care as mutually exclusive, alternative approaches. Parents will not be constrained by what the oncologist offers. Physicians and parents discuss and negotiate care and treatment throughout the illness. Our findings suggest developing integrative care models incorporating cancer-directed, symptom-directed, and supportive care throughout the illness; they are most consistent with parents’ approaches and advances in pediatric oncology.
Referral Patterns, Treatment Choices, and Outcomes in Locoregional Esophageal Cancer: A Population-Based Analysis of Elderly Patients
Authors: Steyerberg Ewout W. , Neville Bridget , Weeks Jane C. , Earle Craig C.
Published: June 2007

Purpose

To determine the impact of demographics and comorbidity on access to specialists' services, treatment, and outcome for patients with locoregional esophageal cancer.

Patients and Methods

We performed a retrospective cohort study of 3,538 patients older than age 65 years who were diagnosed with locoregional esophageal cancer between 1991 and 1999 in one of 11 regions monitored by the Surveillance, Epidemiology, and End Results tumor program. We examined linked Medicare claims for assessment by a surgeon, radiation oncologist, or medical oncologist and subsequent treatment with surgery, radiation, or chemotherapy. Logistic regression analyses were performed for seeing a specialist and for undergoing treatment according to age, sex, race, socioeconomic status, geographic region, and presence of comorbidities. Cox proportional hazards analyses were performed to estimate hazard ratios (HRs) for survival with and without adjustment for treatment received.

Results

Seeing a cancer specialist depended especially on age and region of diagnosis. These same factors were also related to subsequent treatment decisions, but associations were reversed in some regions, such that treatment depended less on region. Older patients had poorer survival (HR = 2.0 for 85+ v 65 to 69 years), which was partly explained by treatment received (HR decreased to 1.5 when adjusted for treatment).

Conclusion

Older patients have less intensive treatment of esophageal cancer, which is explained by both a lower rate of seeing a cancer specialist and by less intensive treatment once seen. Referring physicians and treating specialists must ensure that elderly patients are not deprived of the opportunity to consider all of their treatment options.
Cost Effectiveness of Adjuvant Interferon in Node-Positive Melanoma
Authors: Cormier Janice N. , Xing Yan , Ding Meichun , Cantor Scott B. , Salter Kristi J. , Lee Jeffrey E. , Mansfield Paul F. , Gershenwald Jeffrey E. , Ross Merrick I.
Published: June 2007

Purpose

To assess the benefits of adjuvant high-dose interferon alfa (HDI) treatment for patients with high-risk melanoma.

Methods

We designed a decision-analytic probabilistic Markov model to simulate the natural history of patients with stage IIIA, IIIB, and IIIC melanoma and evaluate the outcomes with and without HDI treatment. Outcomes were in quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). Probability estimates and costs were derived from primary patient level data, while the efficacy of HDI and associated utilities were determined from published reports. The base-case analysis was a cohort of 50-year-old patients.

Results

HDI increased the median life expectancy in patients with stage III melanoma from 3.75 years in the observation cohort to 4.42 years in the HDI cohort. The difference in QALYs ranged from 0.31 years for stage IIIA patients to 0.60 years for stage IIIC patients treated with HDI. HDI was cost effective in patients with stage IIIB and IIIC melanoma, with ICERs of $95,304 and $76,068 per QALY gained, respectively. Using a threshold of $100,000 per QALY gained, HDI was cost effective for all stage III patients younger than 52 years. HDI was not cost effective for patients with stage IIIA disease and for subsets of patients older than 63 years with stage IIIB disease.

Conclusion

Our model demonstrates that the probability of HDI being cost effective varies substantially by melanoma substage. HDI showed the greatest benefit in terms of QALYs and was most cost effective in patients younger than 60 years with stage IIIC disease.
American imperialism?
Authors: Reyna Steve
Published: June 2007

This essay is concerned with where the current of global political and economic events runs. It addresses this concern by erecting an argument in three stages. First, a string being theory (SBT) is outlined. Second, this theory is used to formulate an SBT approach to imperialism, one that might be imagined as Lenin by alternative (theoretical) means, emphasizing the role of violent force. The 'seven deadly sirens'—generalizations that predict the exercise of violent force under different conditions in imperial systems—are introduced. Third, certain post-1945 US government uses of violence are analyzed in terms of their fit with the seven sirens' predictions. Oil depletion is considered as contributing to systemic crisis in capital accumulation, and its role in Gulf War II is explored. It is concluded that US government violence is consistent with the sirens' predictions. The essay terminates with speculation about where the current runs.
Quality at some point became quantity
Authors: Rew Alan , Rew Martin
Published: June 2007

The 'qualitative' pole of (Q-squared) combined methods has been defined in mainly residual ways as 'non-numerical' or 'noneconomics'. There is need, instead, for a critical social theorization of qualitative methods. Evidence from a development program for chronically poor, tribal, northern Orissa is used to examine the communicative action of 'participatory assessment' (PA). PA assumes that 'group' and 'visual' synergies can challenge the power relations that restrict communication and poor people's emancipation. The authors' ethnographies show that participants sequestered information from PA village seminars. Although well trained, the PA organizers increasingly ignored cultural context and substituted universalized techniques that produced only quantities of noncontextualized attitudes. The core PA routines therefore gave misleading results; they mistakenly replaced substantive accounts of communication in relation to lifeworlds with abstract seminar techniques. To obtain more reliable results, methods of 'embedded' economic anthropology were used instead to assess poverty.
Critiquing governmentality
Authors: de Vries Pieter
Published: June 2007

This article sets out to test the Foucauldian concept of governmentality as it has been applied by social theorists working on the topic of neoliberal managerialism. It starts with a critical discussion of the 'good governance' agenda as developed by the World Bank. The question that the article poses is whether such technologies of governance are as successful in shaping new fields of intervention as assumed in the (managerial) governmentality literature. This question is answered negatively by way of a case study of an extensionist, working in an integrated rural development project in the Atlantic zone of Costa Rica, who developed his own 'participatory extension style of operation' for dealing with farmer beneficiaries. At a more theoretical level, the article takes issue with current notions regarding the malleability of the Self and the 'social'. The article concludes that the governmentality approach has perverse consequences for the anthropological project as it leads to an impoverished kind of ethnography.
Die eidgenössische Waldgesetzgebung aus der Sicht der Vollzugsbehörde des Bundes | The Swiss forest legislation from the viewpoint of the federal authority responsible for its implementation
Authors: Schärer Werner
Published: June 2007

The paper takes stock of the key provisions of the forest legislation. It does not examine individual articles from the legislation in detail. Instead, it explores the legislative provisions from the controversial perspectives of «centralism versus federalism» and «general rule versus detailed regulation». The question of the extent to which the forest legislation represents a visionary step forward or a mere continuation of the old forest police legislation is also raised. By and large, some ten years after its coming into force, the enactment of the forest legislation can be seen as a positive development. From the viewpoint of the implementing authority, a series of circulars and various other supports have facilitated its implementation. They have also helped in the identification of new and innovative solutions, and improved and intensified cooperation between the state and the cantons, the administration,research and practice. However, this does not free us from the obligation to strive for further improvements in the coming years; adaptation to the increasing pace of socio-political development is unavoidable.
Trends in Sexual Harassment Prevalence and Recognition During Intern Year
Authors: Frank Elena , Zhao Zhuo , Fang Yu , Cleary Jennifer L. , Viglianti Elizabeth M. , Sen Srijan , Guille Constance
Published: March 2024

This cohort study uses Internal Health Study and Sexual Experiences Questionnaire data to assess changes in sexual harassment prevalence and recognition among training physicians.
Enrollment in High-Deductible Health Plans and Incident Diabetes Complications
Authors: McCoy Rozalina G. , Swarna Kavya S. , Jiang David H. , Van Houten Holly K. , Chen Jie , Davis Esa M. , Herrin Jeph
Published: March 2024

Importance

Preventing diabetes complications requires monitoring and control of hyperglycemia and cardiovascular risk factors. Switching to high-deductible health plans (HDHPs) has been shown to hinder aspects of diabetes care; however, the association of HDHP enrollment with microvascular and macrovascular diabetes complications is unknown.

Objective

To examine the association between an employer-required switch to an HDHP and incident complications of diabetes.

Design, Setting, and Participants

This retrospective cohort study used deidentified administrative claims data for US adults with diabetes enrolled in employer-sponsored health plans between January 1, 2010, and December 31, 2019. Data analysis was performed from May 26, 2022, to January 2, 2024.

Exposures

Adults with a baseline year of non-HDHP enrollment who had to switch to an HDHP because their employer offered no non-HDHP alternative in that year were compared with adults who were continuously enrolled in a non-HDHP.

Main Outcomes and Measures

Mixed-effects logistic regression models examined the association between switching to an HDHP and, individually, the odds of myocardial infarction, stroke, hospitalization for heart failure, lower-extremity complication, end-stage kidney disease, proliferative retinopathy, treatment for retinopathy, and blindness. Models were adjusted for demographics, comorbidities, and medications, with inverse propensity score weighting used to account for potential selection bias.

Results

The study included 42 326 adults who switched to an HDHP (mean [SD] age, 52 [10] years; 19 752 [46.7%] female) and 202 729 adults who did not switch (mean [SD] age, 53 [10] years; 89 828 [44.3%] female). Those who switched to an HDHP had greater odds of experiencing all diabetes complications (odds ratio [OR], 1.11; 95% CI, 1.06-1.16 for myocardial infarction; OR, 1.15; 95% CI, 1.09-1.21 for stroke; OR, 1.35; 95% CI, 1.30-1.41 for hospitalization for heart failure; OR, 2.53; 95% CI, 2.38-2.70 for end-stage kidney disease; OR, 2.23; 95% CI, 2.17-2.29 for lower-extremity complication; OR, 1.17; 95% CI, 1.13-1.21 for proliferative retinopathy; OR, 2.35; 95% CI, 2.18-2.54 for blindness; and OR, 2.28; 95% CI, 2.15-2.41 for retinopathy treatment).

Conclusions and Relevance

This study found that an employer-driven switch to an HDHP was associated with increased odds of experiencing all diabetes complications. These findings reinforce the potential harm associated with HDHPs for people with diabetes and the importance of affordable and accessible chronic disease management, which is hindered by high out-of-pocket costs incurred by HDHPs.
The Cloke–Wilson Rearrangement
Authors: Reyes Efraím , Prieto Liher , Manzano Rubén , Carrillo Luisa , Uria Uxue , Vicario Jose L.
Published: March 2024

The Cloke–Wilson rearrangement is a reaction that converts cyclopropanes bearing a carbonyl, thiocarbonyl, or imino group into dihydrofurans, dihydrothiophenes, or dihydropyrroles, respectively, in a transformation that is generally driven by the release of ring strain leading to the formation of significantly less‐strained five‐membered heterocyclic compounds. Although the Cloke–Wilson rearrangement has typically been carried out through thermal activation of the substrate (and very often requires harsh reaction conditions), more recent research has shown that this reaction can also be carried out using Brønsted acids, Lewis acids, Lewis bases, or organometallic complexes as catalysts or promoters. These advances have contributed to broadening the functional‐group tolerance of this transformation, and have allowed the Cloke–Wilson rearrangement to be used in the synthesis of densely functionalized heterocyclic scaffolds.

This chapter covers all the examples reported in the literature in which a Cloke–Wilson rearrangement has been observed, including the standard reaction that involves formyl‐ or acyl‐substituted cyclopropanes that lead to dihydrofurans, and the heteroatom variants such as the aza‐ and sulfa‐Cloke–Wilson rearrangements. In addition, a detailed mechanistic explanation of the different general modes of substrate activation operating with each type of catalyst/promoter has also been included, together with representative examples of practical experimental protocols and some reports in which this reaction has been applied to total synthesis.
The Kinugasa Reaction
Authors: Chmielewski Marek , Kutaszewicz Rafał , Ulikowski Artur , Michalak Michał , Wołosewicz Karol , Stecko Sebastian , Furman Bartłomiej
Published: March 2024

Among the methods of synthesizing the β‐lactam ring, the copper(I)‐mediated reaction between a nitrone and a terminal alkyne in the presence of an organic base is a remarkably simple and direct strategy. This transformation, known as the Kinugasa reaction, is a cascade process that involves a 1,3‐dipolar cycloaddition of a copper acetylide onto the nitrone, followed by a rearrangement step. Initially reported in 1972, this reaction stereoselectively allows access to
cis
‐substituted β‐lactam products. Achiral, diastereoselective, and catalytic enantioselective versions of the Kinugasa reaction have been described, both in inter‐ and intramolecular contexts. To date, only aldimine‐derived nitrones have been demonstrated in the reaction.

This chapter presents a comprehensive overview of the Kinugasa reaction. Mechanistic proposals and the factors involved in the stereochemistry of the reaction are followed by a discussion of the scope of the reaction and its limitations. Specifically, the combinations of aldonitrones and terminal alkynes that can be used in the achiral and diastereoselective Kinugasa reaction are presented. Enantioselective and intramolecular variants of the reaction are discussed in detail, as are successful synthetic applications, with an emphasis on the preparation of β‐lactam antibiotics. The Kinugasa reaction is compared with more classical and well‐established methods of β‐lactam synthesis, and finally, typical experimental conditions and examples of procedures for selected variants of the Kinugasa reaction are provided. The Tabular Survey covers Kinugasa reactions performed through the end of 2021.
A Bodipy‐Based Aggregation‐Induced Emission Nanoagent for Sonodynamic Antibacterial Studies
Authors: Xu Yan , Tang Dongsheng , Li Leijiao , Li Xuan , Chang Qi , Xiao Haihua , Li Wenliang
Published: March 2024

Sonodynamic therapy (SDT) has demonstrated significant potential in addressing multidrug‐resistant bacterial infections due to its noninvasive nature and independence from antibiotics and light sources. However, the majority of current sonosensitizers exhibit aggregation‐caused quenching (ACQ), leading to low reactive oxygen species (ROS) generation efficiency. Herein, a novel nonplanar structured sonodynamic (4,4‐difluoro‐4‐boron‐3a,4‐diaza‐indandiene) BODIPY derivative, BODN, with aggregation‐induced emission (AIE) properties, and rapid generation of substantial ROS by ultrasound is introduced. The BODN is co‐assembled with the commercial amphiphilic polymer, mDSPE‐PEG2000, forming BODN nanoparticles (BODN‐NP). Under ultrasound conditions, BODN‐NP demonstrates potent antimicrobial activity and improves the inflammatory response to promote healing wounds infected by both Staphylococcus aureus and methicillin‐resistant Staphylococcus aureus. This work expands the use of AIE sonodynamic materials in antimicrobial therapy and provides new perspectives for innovative solutions against multidrug‐resistant bacterial infections.
Synergistic Inter‐ and Intramolecular Aggregation of Dimeric Cyanine Dyes Affords Highly Efficient In Vivo Self‐Delivery and Photothermal Therapy
Authors: Hou Yanxian , Li Jianwei , Jiang Guanyu , Xia Tianping , Li Zipeng , Gu Hua , Liu Xiaogang , Yao Qichao , Zhang Changyu , Liu Wenkai , Du Jianjun , Sun Wen , Fan Jiangli , Peng Xiaojun
Published: March 2024

Advancing photothermal therapy hinges on developing PTAs with robust in vivo delivery and therapeutic efficacy. However, effective molecular design approaches for high‐performance PTAs remain lacking. Herein a strategic design of dimeric heptamethine cyanine (Cy7) molecules is presented, covalently linked via ortho/meta/para‐phenyldithiol. These designs facilitate spontaneous nanoparticle assembly in water, attributed to efficient intermolecular aggregation, enhancing in vivo delivery. Additionally, aggregation between intramolecular Cy7 units promotes superior photothermal conversion efficiency (PCE) up to 74.1% for meta‐dimer. Remarkably, the para‐dimer variant not only achieves a high PCE of 61.1% but also exhibits the most effective pharmacokinetic profile, leading to unparalleled anticancer efficacy in vivo. This dual aggregation strategy, leveraging both inter‐ and intramolecular dynamics, equips dimeric Cy7 with superior self‐delivery and photothermal efficacy, offering a promising approach for the next generation of photothermal therapeutics.
Functional Liquid Metal Polymeric Composites: Fundamentals and Applications in Soft Wearable Electronics
Authors: Liang Fang‐Cheng , Tee Benjamin C. K.
Published: March 2024

Wearable and self‐healing soft electronics have led to a significant emphasis on their potential in creating versatile, conformable, and sustainable electronic modules. Among conductive additives, Liquid metals (LMs), combining both solid and liquid characteristics, have gained widespread attention due to their versatile physical, chemical, and electrical properties as well as self‐healing capability, biocompatibility, and recyclability. The fluidity of LMs facilitates adaptability to various experimental conditions and components for specific applications. Moreover, the oxide shell on LMs exhibits strong compatibility with surface functionalization and polymerization processes, enhancing the development of reliable composite materials. Herein, an in‐depth analysis of the fundamental properties and characteristics of LMs while addressing their current drawbacks, such as unpredictable reactivity and poor surface stability, is presented. To harness the advantages of LMs, their integration is extensively discussed with polymeric materials through various grafting strategies, leading to the development of macromolecular composites with exceptional softness, solubility, surface functionalization, and versatility. Furthermore, the applications of LMs within LM‐elastomer composites, particularly focusing on their relevance in specific fields such as flexible electronics, are investigated. Finally, LMs' future prospects are emphasized by highlighting their compatibility with self‐healing polymers, thereby providing pathways for major breakthroughs of LMs based devices.
Epitaxially Stacked 12‐Layer Perovskite Oxide Heterostructure as a Double‐Level Double‐Gate Field‐Effect Transistor
Authors: Kim Juhan , Seo Jihoon , Lee Hahoon , Chang Celesta S. , Char Kookrin
Published: March 2024

Perovskite oxide semiconductor is unique for its capability to form epitaxial heterostructures with both dielectric and metallic perovskite oxides. The study underscores the potential of perovskite oxides for multi‐layer stacking, a key aspect in advancing semiconductor technology as silicon‐based devices evolve toward 3D stacked structures. Fabrication of the first double‐level double‐gate field‐effect transistors (DL DG‐FETs) is demonstrated, where each layer is epitaxially grown using all‐perovskite oxides. This resulted in improvements in subthreshold swing, current drivability, and field effect mobility. This innovation not only highlights the distinctive potential of perovskite oxides but also provides new avenues for integration with other perovskite oxides on Si for more advanced electronic functions.
Fine‐Tuning the Optoelectronic and Redox Properties of an Electropolymerized Thiophene Derivative for Highly Selective OECT‐Based Zinc Detection
Authors: Nicolini Tommaso , Shinde Shekhar , El‐Attar Reem , Salinas Gerardo , Thuau Damien , Abbas Mamatimin , Raoux Matthieu , Lang Jochen , Cloutet Eric , Kuhn Alexander
Published: March 2024

Organic mixed ionic‐electronic conductors (OMIEC) have emerged as pivotal materials in organic bioelectronics, particularly when integrated into organic electrochemical transistors (OECTs). Conducting polymer‐based devices have indeed demonstrated their capability to transduce biological signals into amplified output signals, harnessing the high transconductance of OECTs. The OECT operating principle and sensing capability strongly depend on ion‐conjugated backbone coupling: the dual nature of OMIECs, i.e. ion‐conductor and electron/hole‐conductor, presents an intrinsic interface in the bulk of the thin film across which transduction of ionic signals into electronic signals and vice versa occurs. Recent works have shown how selective sodium and potassium detection can be achieved by direct chemical modification of the polymer. Such modifications introduce ligands with affinity for the cations of interest as substituents on the polymer chain. The present work explores the integration of specifically modified conducting polymers into OECT channels, offering selectivity for zinc cations. Zinc fluxes are crucial in various biological processes, and their reliable detection, especially at low concentrations, is an important challenge. By electropolymerizing a thiophene‐based trimer, modified with a dipicolylamine (DPA) substituent, a conducting polymer‐based OECT is obtained that can selectively detect Zn2+ in the 10−6 to 10−3 mol L−1 concentration range in physiological buffers.
Bioprinting Soft 3D Models of Hematopoiesis using Natural Silk Fibroin‐Based Bioink Efficiently Supports Platelet Differentiation
Authors: Di Buduo Christian Andrea , Lunghi Marco , Kuzmenko Volodymyr , Laurent Pierre‐Alexandre , Della Rosa Giulia , Del Fante Claudia , Dalle Nogare Damian Edward , Jug Florian , Perotti Cesare , Eto Koji , Pecci Alessandro , Redwan Itedale Namro , Balduini Alessandra
Published: March 2024

Hematopoietic stem and progenitor cells (HSPCs) continuously generate platelets throughout one's life. Inherited Platelet Disorders affect ≈ 3 million individuals worldwide and are characterized by defects in platelet formation or function. A critical challenge in the identification of these diseases lies in the absence of models that facilitate the study of hematopoiesis ex vivo. Here, a silk fibroin‐based bioink is developed and designed for 3D bioprinting. This bioink replicates a soft and biomimetic environment, enabling the controlled differentiation of HSPCs into platelets. The formulation consisting of silk fibroin, gelatin, and alginate is fine‐tuned to obtain a viscoelastic, shear‐thinning, thixotropic bioink with the remarkable ability to rapidly recover after bioprinting and provide structural integrity and mechanical stability over long‐term culture. Optical transparency allowed for high‐resolution imaging of platelet generation, while the incorporation of enzymatic sensors allowed quantitative analysis of glycolytic metabolism during differentiation that is represented through measurable color changes. Bioprinting patient samples revealed a decrease in metabolic activity and platelet production in Inherited Platelet Disorders. These discoveries are instrumental in establishing reference ranges for classification and automating the assessment of treatment responses. This model has far‐reaching implications for application in the research of blood‐related diseases, prioritizing drug development strategies, and tailoring personalized therapies.
Magnetic Nanoparticles and Methylprednisolone Based Physico‐Chemical Bifunctional Neural Stem Cells Delivery System for Spinal Cord Injury Repair
Authors: Zhang Wencan , Liu Mingshan , Ren Jie , Han Shuwei , Zhou Xiaolong , Zhang Dapeng , Guo Xianzheng , Feng Haiwen , Ye Lei , Feng Shiqing , Song Xizi , Jin Lin , Wei Zhijian
Published: March 2024

Neural stem cells (NSCs) transplantation is an attractive and promising treatment strategy for spinal cord injury (SCI). Various pathological processes including the severe inflammatory cascade and difficulty in stable proliferation and differentiation of NSCs limit its application and translation. Here, a novel physico‐chemical bifunctional neural stem cells delivery system containing magnetic nanoparticles (MNPs and methylprednisolone (MP) is designed to repair SCI, the former regulates NSCs differentiation through magnetic mechanical stimulation in the chronic phase, while the latter alleviates inflammatory response in the acute phase. The delivery system releases MP to promote microglial M2 polarization, inhibit M1 polarization, and reduce neuronal apoptosis. Meanwhile, NSCs tend to differentiate into functional neurons with magnetic mechanical stimulation generated by MNPs in the static magnetic field, which is related to the activation of the PI3K/AKT/mTOR pathway. SCI mice achieve better functional recovery after receiving NSCs transplantation via physico‐chemical bifunctional delivery system, which has milder inflammation, higher number of M2 microglia, more functional neurons, and axonal regeneration. Together, this bifunctional NSCs delivery system combined physical mechanical stimulation and chemical drug therapy is demonstrated to be effective, which provides new treatment insights into clinical transformation of SCI repair.
Alternative Splicing Underpins the ALMT9 Transporter Function for Vacuolar Malic Acid Accumulation in Apple
Authors: Li Chunlong , Krishnan Srinivasan , Zhang Mengxia , Hu Dagang , Meng Dong , Riedelsberger Janin , Dougherty Laura , Xu Kenong , Piñeros Miguel A. , Cheng Lailiang
Published: March 2024

Vacuolar malic acid accumulation largely determines fruit acidity, a key trait for the taste and flavor of apple and other fleshy fruits. Aluminum‐activated malate transporter 9 (ALMT9/Ma1) underlies a major genetic locus, Ma, for fruit acidity in apple, but how the protein transports malate across the tonoplast is unclear. Here, it is shown that overexpression of the coding sequence of Ma1 (Ma1α) drastically decreases fruit acidity in “Royal Gala” apple, leading to uncovering alternative splicing underpins Ma1's function. Alternative splicing generates two isoforms: Ma1β is 68 amino acids shorter with much lower expression than the full‐length protein Ma1α. Ma1β does not transport malate itself but interacts with the functional Ma1α to form heterodimers, creating synergy with Ma1α for malate transport in a threshold manner (When Ma1β/Ma1α ≥ 1/8). Overexpression of Ma1α triggers feedback inhibition on the native Ma1 expression via transcription factor MYB73, decreasing the Ma1β level well below the threshold that leads to significant reductions in Ma1 function and malic acid accumulation in fruit. Overexpression of Ma1α and Ma1β or genomic Ma1 increases both isoforms proportionally and enhances fruit malic acid accumulation. These findings reveal an essential role of alternative splicing in ALMT9‐mediated malate transport underlying apple fruit acidity.
Pyridine N‐Modulated Adsorption Equilibrium of Highly Dispersed Atomic W‐P Clusters toward Advanced Potassium‐Ion Hybrid Capacitors
Authors: Hu Shuxiao , Chu Shile , Zeng Fanyan , Pan Yang , Liu Baoquan , He Wenxiu , Ma Dui , Xie Meilan , Luo Shenglian
Published: March 2024

Improving the atomic utilization of storage sites and developing isotropic transport characteristics become crucial to enhance the performance of potassium‐ion hybrid capacitors (PIHCs), and the disordered strategy and coordination modulation of the electrodes can satisfy the above structure‐activity requirements. Herein, the highly dispersed atomic W‐P clusters are chosen as a platform for the electronic restructuring. Studies and calculations indicate that replacing O in W‐O2/P2 with pyridine N can modulate the electron distribution and electronegativity, and enrich the edge‐dangling bonds of the amorphous clusters (W‐N2/P2), resulting in proper adsorption equilibrium and high affinity for K+ storage. In addition, the clusters have isotropic and bulk‐phase‐indifferent fast ion storage, and in situ protection of carbon nanosheets can provide stable support for ion storage and electron transfer in the clusters. As an anode, the composite (W‐N/P@C) exhibits superior storage properties of K+ (reversible capacity of 181.6 mAh g−1 after 3000 cycles at 5.0 A g−1), with high energy density (163.7 Wh Kg−1) at the high‐power output (3500 W Kg−1) in PIHCs. This work systematically delineates the effects of disordered design and pyridine N‐coordination on energy storage, and provides new research ideas for studying high‐performance PIHCs.
Historic corn yield, production, and economic value trends in Kansas
Authors: Holman Johnathan D. , Obour Augustine K. , O'Brien Daniel , Prasad P. V. V. , Assefa Yared
Published: March 2024

World corn (Zea mays L.) production has tripled since the 1960s. However, without new breakthrough innovations the trend is expected to plateau or decrease in the future. The objective of this study was to quantify Kansas corn production, economic value, productivity, annual production variation, yield gap trends, and in due course, identify future areas for research. Corn variety performance tests and United States Department of Agriculture (USDA) data were used for this study. Results showed that the area planted to corn in Kansas increased from 0.5 million in 1880s to over 2 million ha by 2022, with an increase of 0.05 million ha year−1 between 1984 and 2022. The value of corn produced in Kansas also increased significantly from below $1 billion annually prior to 1990s to the current value of approximately $3–$4 billion. The average corn yield gain from 1972 to 2000 was 132 kg ha−1 year−1, which declined to 12 kg ha−1 year−1 during 2000 to the early 2020s. Also, a relatively high yield variability occurred from 1970 to the early 2020s compared with earlier years (1866–1970), and a 42%–68% gap between the potential and actual corn yields was identified. We concluded that there is a decrease in the rate of corn yield increase and developing farmer awareness and their adoption of new corn production technology, increasing longevity of the Ogallala Aquifer, and integrated research should be priorities to avert the decreasing trend of corn productivity and further increase corn economic value.
High‐Performance Ammonia Electrosynthesis from Nitrate in a NaOH−KOH−H2O Ternary Electrolyte
Authors: Shahid Usman Bin , Kwon Yongjun , Yuan Yuan , Gu Shuang , Shao Minhua
Published: March 2024

A glut of dinitrogen‐derived ammonia (NH3) over the past century has resulted in a heavily imbalanced nitrogen cycle and consequently, the large‐scale accumulation of reactive nitrogen such as nitrates in our ecosystems has led to detrimental environmental issues. Electrocatalytic upcycling of waste nitrogen back into NH3 holds promise in mitigating these environmental impacts and reducing reliance on the energy‐intensive Haber–Bosch process. Herein, we report a high‐performance electrolyzer using an ultrahigh alkalinity electrolyte, NaOH−KOH−H2O, for low‐cost NH3 electrosynthesis. At 3,000 mA/cm2, the device with a Fe−Cu−Ni ternary catalyst achieves an unprecedented faradaic efficiency (FE) of 92.5±1.5 % under a low cell voltage of 3.83 V; whereas at 1,000 mA/cm2, an FE of 96.5±4.8 % under a cell voltage of only 2.40 V was achieved. Techno‐economic analysis revealed that our device cuts the levelized cost of ammonia electrosynthesis by ~40 % ($30.68 for Fe−Cu−Ni vs. $48.53 for Ni foam per kmol‐NH3). The NaOH−KOH−H2O electrolyte together with the Fe−Cu−Ni ternary catalyst can enable the high‐throughput nitrate‐to‐ammonia applications for affordable and scalable real‐world wastewater treatments.
Rhodium‐Catalyzed Enantio‐ and Regioselective Allylation of Indoles with gem‐Difluorinated Cyclopropanes
Authors: Yang Hui , Zeng Yaxin , Song Xiangyu , Che Lin , Jiang Zhong‐Tao , Lu Gang , Xia Ying
Published: March 2024

The use of gem‐difluorinated cyclopropanes (gem‐DFCPs) as fluoroallyl surrogates under transition‐metal catalysis has drawn considerable attention recently but such reactions are restricted to producing achiral or racemic mono‐fluoroalkenes. Herein, we report the first enantioselective allylation of indoles under rhodium catalysis with gem‐DFCPs. This reaction shows exceptional branched regioselectivity towards rhodium catalysis with gem‐DFCPs, which provides an efficient route to enantioenriched fluoroallylated indoles with wide substrate scope and good functional group tolerance.
Understanding Defects in Amorphous Silicon with Million‐Atom Simulations and Machine Learning
Authors: Morrow Joe D. , Ugwumadu Chinonso , Drabold David A. , Elliott Stephen R. , Goodwin Andrew L. , Deringer Volker L.
Published: March 2024

The structure of amorphous silicon (a‐Si) is widely thought of as a fourfold‐connected random network, and yet it is defective atoms, with fewer or more than four bonds, that make it particularly interesting. Despite many attempts to explain such “dangling‐bond” and “floating‐bond” defects, respectively, a unified understanding is still missing. Here, we use advanced computational chemistry methods to reveal the complex structural and energetic landscape of defects in a‐Si. We study an ultra‐large‐scale, quantum‐accurate structural model containing a million atoms, and thousands of individual defects, allowing reliable defect‐related statistics to be obtained. We combine structural descriptors and machine‐learned atomic energies to develop a classification of the different types of defects in a‐Si. The results suggest a revision of the established floating‐bond model by showing that fivefold‐bonded atoms in a‐Si exhibit a wide range of local environments–analogous to fivefold centers in coordination chemistry. Furthermore, it is shown that fivefold (but not threefold) coordination defects tend to cluster together. Our study provides new insights into one of the most widely studied amorphous solids, and has general implications for understanding defects in disordered materials beyond silicon alone.
Temperature dependence of polymer melt viscosity obtained based on DSC data and the consistency between thermodynamic and kinetic fragility
Authors: Fang Chenghui , Chen Huanhuan , Zhou Juan , Chen Liping , Guo Zichao , Chen Wanghua
Published: March 2024

The viscosity of the polymer melt has an impact on both the processing and properties of the product. However, conventional viscosity measurement methods have limitations such as strict testing conditions, large sample sizes, and long response times. This paper proposes a simplified method that utilizes differential scanning calorimetry to determine the viscosity–temperature relationship of the polymer melt. The research subjects consist of four noncrystalline polymers and five crystalline polymers. A new thermodynamic fragility formula of crystalline polymer is obtained. Additionally, high‐temperature limiting viscosity shows a good linear relationship with fragility. Compared with the traditional viscosity measurement, this method is a simpler and more effective way to model the viscosity of polymer melt and has broad prospects in application.
Urethral meatus edema with peno‐scrotal edema in a patient with transfusion‐dependent beta‐thalassemia major
Authors: Nasrallah Oussama G. , Mahdi Jana H. , Bachir Bassel G.
Published: March 2024

Key Clinical Message

Urethral meatus edema is a rare finding and may infer a more severe form of volume overload. Management of patients with thalassemia vary in terms of the severity of the kidney injury due to transfusion, chronicity, and severity of volume overload.
Adipocyte enhancer binding protein 1 knockdown alleviates osteoarthritis through inhibiting NF‐κB signaling pathway‐mediated inflammation and extracellular matrix degradation
Authors: Cao Le , Gao Weilu , Yang Haitao , Zeng Ran , Yin Zongsheng
Published: March 2024

Inflammation promotes the degradation of the extracellular matrix, which contributes to the development of osteoarthritis (OA). Adipocyte enhancer binding protein 1 (AEBP1) participates in multiple pathological processes related to inflammatory diseases. However, the role of AEBP1 in OA development is unknown. We found a higher AEBP1 expression in articular cartilage of OA patients (n = 20) compared to their normal controls (n = 10). Thus, we inferred that AEBP1 might affect OA progression. Then mice with destabilization of the medial meniscus (DMM) surgery and chondrocytes with IL‐1β treatment (10 ng/mL) were used to mimic OA. The increased AEBP1 expression was observed in models of OA. AEBP1 knockdown in chondrocytes reversed IL‐1β‐induced inflammation and extracellular matrix degradation, which was mediated by the inactivation of NF‐κB signaling pathway and the increased IκBα activity. Co‐immunoprecipitation assay indicated the interaction between AEBP1 and IκBα. Importantly, IκBα knockdown depleted the protective role of AEBP1 knockdown in OA. Moreover, AEBP1 knockdown in mice with OA showed similar results to those in chondrocytes. Collectively, our findings suggest that AEBP1 knockdown alleviates the development of OA, providing a novel strategy for OA treatment.
Monitoring Ethanol Fermentation in Real Time by a Robust State Observer for Uncertainties
Authors: Aguilar‐López Ricardo , Alvarado‐Santos Eduardo , Thalasso Frederic , López‐Pérez Pablo A.
Published: March 2024

In this article, the problem of real‐time estimation of the fermentative ethanol process is tackled. The considered observer is a model‐based technique that is robust regarding the model parameter uncertainties and inline noisy measurements. An unstructured kinetic model was used to describe the production of ethanol in a batch bioreactor for Saccharomyces cerevisiae. The biomass concentration was selected as the measured bioreactor´s output via an inline device, where the estimate variables were the substrate and ethanol concentrations. An experimental prototype was constructed to demonstrate the observer's real‐time performance. The experimental results show that the robust, smooth sliding mode observer performs better than the standard proportional sliding mode observer.
Designing Powerful Biindole‐Based Inherently Chiral Selectors: Enhancing Enantiodiscrimination by Core Functionalization with Additional Coordination Elements
Authors: Grecchi Sara , Bonetti Giorgia , Emanuele Elisa , Ludvík Jiří , Koláčná Lucie , Liška Alan , Hromadová Magdaléna , Arnaboldi Serena , Cirilli Roberto , Mussini Patrizia R. , Benincori Tiziana
Published: March 2024

Among inherently chiral selectors of axial stereogenicity, usually resulting in very good enantiodiscrimination performances, the biindole‐based family has the additional advantage of very easy functionalization of the two nitrogen atoms with a variety of substituents with desirable properties. Aiming to evaluate the possibility of exploiting such feature to enhance the enantiodiscrimination ability of the archetype structure, a series of three inherently chiral monomers were designed and synthesized, characterised by a 2,2’‐biindole atropisomeric core conjugated to bithiophene wings enabling fast and regular electrooligomerization, and functionalised at the nitrogen atoms with an ethyl, a methoxyethyl, or a hydroxyethyl substituent. Nitrogen alkylation was also exploited to obtain for the first time the chemical resolution of the biindole selectors without employing chiral HPLC. The enantiodiscrimination ability of the selector series was comparatively evaluated in proof‐of‐concept chiral voltammetry experiments with a “benchmark” chiral ferrocenyl probe as well as with chiral non‐steroidal anti‐inflammatory drugs naproxen and ketoprofen. The large enantiomer potential differences for all probes increased in the ethyl < methoxyethyl ≪ hydroxyethyl sequence of selector substituents, supporting our assumption on the beneficial role of an additional coordination element. The powerful hydroxyethyl selector was also applied to ketoprofen in a commercial drug matrix.