bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronic properties of pentaorgano[60]fullerenes under an external electric field
Authors: Furutani Sho , Okada Susumu
Published: October 2016

The electronic properties of pentaorgano[60]fullerene under an external electric field were studied by combining the density functional theory with the effective screening medium method. Pentaorgano[60]fullerene possess a dipole moment because of their asymmetric molecular form owing to their five functionalized groups. When electrons and holes are injected into the molecule, the magnetic states of the molecule change from S = 1/2 to nonmagnetic and S = 1 triplet states for electron and hole doping, respectively. The asymmetric molecular shape causes the unusual distribution of the accumulated carriers depending on their mutual molecular arrangement in the electric field.
Prevalence and Characteristics of Physicians Engaged in Research in the US
Authors: Browne Alyssa
Published: September 2024

This cross-sectional study uses the Association of American Medical Colleges 2022 National Sample Survey of Physicians to offer a more complete understanding of the prevalence and characteristics of research-engaged physicians in the US.
Voice-Activated Cognitive Behavioral Therapy for Insomnia
Authors: Starling Claire M. , Greenberg Daniel , Lewin Daniel , Shaw Callen , Zhou Eric S. , Lieberman Daniel , Chou Jiling , Arem Hannah
Published: September 2024

Importance

Insomnia symptoms affect an estimated 30% to 50% of the 4 million US breast cancer survivors. Previous studies have shown the effectiveness of cognitive behavioral therapy for insomnia (CBT-I), but high insomnia prevalence suggests continued opportunities for delivery via new modalities.

Objective

To determine the efficacy of a CBT-I–informed, voice-activated, internet-delivered program for improving insomnia symptoms among breast cancer survivors.

Design, Setting, and Participants

In this randomized clinical trial, breast cancer survivors with insomnia (Insomnia Severity Index [ISI] score >7) were recruited from advocacy and survivorship groups and an oncology clinic. Eligible patients were females aged 18 years or older who had completed curative treatment more than 3 months before enrollment and had not undergone other behavioral sleep treatments in the prior year. Individuals were assessed for eligibility and randomized between March 2022 and October 2023, with data collection completed by December 2023.

Intervention

Participants were randomized 1:1 to a smart speaker with a voice-interactive CBT-I program or educational control for 6 weeks.

Main Outcomes and Measures

Linear mixed models and Cohen d estimates were used to evaluate the primary outcome of changes in ISI scores and secondary outcomes of sleep quality, wake after sleep onset, sleep onset latency, total sleep time, and sleep efficiency.

Results

Of 76 women enrolled (38 each in the intervention and control groups), 70 (92.1%) completed the study. Mean (SD) age was 61.2 (9.3) years; 49 (64.5%) were married or partnered, and participants were a mean (SD) of 9.6 (6.8) years from diagnosis. From baseline to follow-up, ISI scores changed by a mean (SD) of −8.4 (4.7) points in the intervention group compared with −2.6 (3.5) in the control group (P < .001) (Cohen d, 1.41; 95% CI, 0.87-1.94). Sleep diary data showed statistically significant improvements in the intervention group compared with the control group for sleep quality (0.56; 95% CI, 0.39-0.74), wake after sleep onset (9.54 minutes; 95% CI, 1.93-17.10 minutes), sleep onset latency (8.32 minutes; 95% CI, 1.91-14.70 minutes), and sleep efficiency (−0.04%; 95% CI, −0.07% to −0.01%) but not for total sleep time (0.01 hours; 95% CI, −0.27 to 0.29 hours).

Conclusions and Relevance

This randomized clinical trial of an in-home, voice-activated CBT-I program among breast cancer survivors found that the intervention improved insomnia symptoms. Future studies may explore how this program can be taken to scale and integrated into ambulatory care.

Trial Registration

ClinicalTrials.gov Identifier: NCT05233800
Survival Outcomes Among Patients With Hepatocellular Carcinoma in a Large Integrated US Health System
Authors: Yilma Mignote , Houhong Xu Richie , Saxena Varun , Muzzin Monica , Tucker Lue-Yen , Lee Jeffrey , Mehta Neil , Mukhtar Nizar
Published: September 2024

Importance

Hepatocellular carcinoma (HCC) is the leading oncologic cause of death among patients with cirrhosis, but large studies examining mortality trends are lacking.

Objective

To evaluate survival among patients with HCC in one of the largest integrated health care systems in the US.

Design, Setting, and Participants

This retrospective cohort study included 3441 adult patients who received a diagnosis of HCC between January 1, 2006, and December 31, 2019, with end of follow-up on December 31, 2020. The study period was further categorized as era 1, defined as 2006 to 2012, and era 2, defined as 2013 to 2019. Statistical analysis was conducted from January 2021 to June 2024.

Exposures

Patient demographic characteristics and disease factors.

Main Outcomes and Measures

All-cause and HCC-specific mortality were used as primary end points, and survival probabilities were estimated using the Kaplan-Meier method. Cox proportional hazards regression analyses were adjusted for age at diagnosis, sex, race and ethnicity, cause of disease, Barcelona Clinic Liver Cancer (BCLC) stage, alpha-fetoprotein level, and treatment type.

Results

Of 3441 patients with HCC, 2581 (75.0%) were men, and the median age was 65 years (IQR, 58-73 years). A total of 1195 patients (34.7%) received curative treatment, 1374 (39.9%) received noncurative treatment, and 872 (25.3%) received no treatment. During the study period, 2500 patients (72.7%) experienced all-cause mortality, and 1809 (52.6%) had HCC-specific mortality. In multivariable analysis, being 70 years of age or older (adjusted hazard ratio [AHR], 1.39; 95% CI, 1.22-1.59), male sex (AHR, 1.20; 95% CI, 1.07-1.35), BCLC stage C or D (AHR, 2.40; 95% CI, 2.15-2.67), increasing alpha-fetoprotein level (vs <20 ng/mL; 20-99 ng/mL: AHR, 1.20; 95% CI, 1.04-1.38; ≥1000 ng/mL: AHR, 2.84; 95% CI, 2.45-3.25), noncurative treatment (AHR, 2.51; 95% CI, 2.16-2.90), and no treatment (AHR, 3.15; 95% CI, 2.64-3.76) were associated with higher all-cause mortality, while Asian or Other Pacific Islander race and ethnicity (vs non-Hispanic White; AHR, 0.76; 95% CI, 0.65-0.88) was associated with lower all-cause mortality. Survival improved in diagnosis era 2 (2013-2019; n = 2007) compared with diagnosis era 1 (2006-2012; n = 1434).

Conclusions and Relevance

This large, racially and ethnically diverse cohort study of patients with HCC found improving survival over time, especially among individuals with early-stage HCC receiving potentially curative treatments. This study highlights the importance of surveillance for detection of HCC at early stages, particularly among groups at risk for poorer outcomes.
Hospital Readmissions Among Infants With Neonatal Opioid Withdrawal Syndrome
Authors: Gaither Julie R. , Drago Matthew J. , Grossman Matthew R. , Li Yi , Shabanova Veronika , Xu Xiao , Leventhal John M.
Published: September 2024

Importance

Although cases of neonatal opioid withdrawal syndrome (NOWS) increased 5-fold in recent years, no study has examined national hospital readmission rates for these infants.

Objective

To examine hospital readmissions for infants with and without NOWS.

Design, Setting, and Participants

This retrospective cohort study analyzed serial cross-sectional samples of US hospital discharge records from the Nationwide Readmissions Database for calendar years 2016 to 2020. Infants with NOWS were identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes. The data analysis was performed between January 5, 2023, and May 6, 2024.

Exposure

Neonatal opioid withdrawal syndrome.

Main Outcome and Measures

Survey-weighted logistic regression was used to examine 90-day all-cause and cause-specific hospital readmissions. Multivariable models adjusted for sex, low birth weight, gestational age, multiple gestation, type of insurance, and year of birth.

Results

Of the 13 855 246 newborns identified in this weighted analysis, 89 018 (0.6%) were diagnosed with NOWS, of whom 53.8% were male and 81.1% born full-term (>36 weeks gestation). The 90-day all-cause readmission rate was 4.2% for infants with NOWS compared with 3.0% for those without NOWS (P < .001). After risk adjustment, the odds of all-cause readmission were higher among infants with NOWS (adjusted odds ratio [AOR], 1.18; 95% CI, 1.08-1.29). Infants with NOWS had significantly higher odds of readmissions for seizures (AOR, 1.58; 95% CI, 1.01-2.46), failure to thrive (AOR, 1.99; 95% CI, 1.36-2.93), traumatic brain injury (AOR, 2.95; 95% CI, 1.76-4.93), and skull fractures (AOR 3.72; 95% CI, 2.33-5.93). Infants with NOWS had higher odds of receiving a diagnosis of confirmed maltreatment (AOR, 4.26; 95% CI, 2.19-8.27), including for neglect (AOR, 14.18; 95% CI, 5.55-36.22) and physical abuse (AOR, 2.42; 95% CI, 0.93-6.29); however, the latter finding was not statistically significant.

Conclusions and Relevance

In this nationally representative cohort study, infants with NOWS were at increased risk of readmission for any cause as well as for trauma and confirmed maltreatment. These findings may in part reflect the dual stressors that mothers with opioid use disorder face in caring for a newborn with NOWS in the context of a substance use disorder and underscore the need for family-based, in-home services that focus concurrently on substance use treatment and parenting support.
Association Between 25‐hydroxyvitamin D Levels and Adverse Pregnancy Outcomes in Systemic Lupus Erythematosus
Authors: Madanchi Nima , Fava Andrea , Goldman Daniel W. , Magder Laurence S. , Petri Michelle
Published: September 2024

Objective

We evaluated the association of 25‐hydroxyvitamin D (25(OH)D) levels with adverse pregnancy outcomes in systemic lupus erythematosus (SLE).

Methods

The Hopkins Lupus Cohort includes visits of pregnant patients, including assessment of 25(OH)D levels at each visit. We examined the relationship between 25(OH)D levels and adverse pregnancy outcomes (miscarriage, preterm delivery, and small for gestational age). We also used a time‐to‐event analysis to assess whether time‐varying of 25(OH)D levels were associated with time to miscarriage or preterm delivery.

Results

In subgroups of patients defined by the average of 25(OH)D levels, we observed significantly different risks of miscarriage (P = 0.0045), preterm delivery (P = 0.0007), and the composite measure of all three adverse pregnancy outcomes (P = 0.011). The highest risks were observed among those with the lowest or highest levels of vitamin D. Nine of 10 pregnant patients with low vitamin D levels during the second trimester resulted in having a premature delivery. The time‐to‐event model confirmed the same U‐shaped association after adjustment for SLE disease activity; however, the increased risk among those with highest levels of vitamin D was not statistically significant. Body mass index did not appear to be a confounding factor.

Conclusion

Our study is not able to prove causation, but the results strongly suggest an association of 25(OH)D at both lower and higher levels with adverse pregnancy outcomes. We recommend the monitoring of maternal serum 25(OH)D levels during SLE pregnancies, aiming for the ideal range of 40 to 59 ng/mL.
Bimetallic AgCo Nanoparticle Synthesis via Combinatorial Nanosecond Laser‐Induced Dewetting of Thin Films
Authors: Paduri Vikas Reddy , Harimkar Sandip , Sachan Ritesh
Published: September 2024

Herein, a combinatorial approach is developed to conduct high‐throughput studies on the nanosecond pulsed laser‐induced dewetting phenomenon of bilayer Ag–Co metallic thin films. Laser irradiation results in the spontaneous rupture of these films in nanosecond timescale, forming bimetallic nanoparticles (NPs) through intermediate stages of hole formation and bicontinuous nanostructures. This approach utilizes bilayer thin films with thickness gradients in both Ag and Co layers (referred to as bigradient samples) while maintaining a constant overall thickness. The laser irradiation on such bigradient bilayer films facilitates control on Ag and Co ratio in the thin films, thus enabling material libraries of Ag–Co NPs covering a large compositional variation. The evolution of NPs with a correlation between NP diameter and interparticle spacings is further studied. The study reveals monotonic increase in NP size and interparticle spacing in Co/Ag bilayer arrangement, while an increase and subsequent decrease in the NP size is observed at 50% Ag in Ag/Co bigradient films. A transition from intermediate stage hole formation to bicontinuous nanostructures with changing composition is also observed. These changes in intermediate stage morphologies and dewetting mechanism are attributed to variation of the free energy of the bilayer system dominated by intermolecular interaction forces.
A Rapid Thermal‐Radiation‐Assisted Sintering Strategy for Nd–Fe–B‐Type Magnets
Authors: Tomše Tomaž , Ivekovič Aljaž , Kocjan Andraž , Šturm Sašo , Žužek Kristina
Published: September 2024

The green transition has spiked demand for high‐performance sintered Nd–Fe–B permanent magnets, necessitating advanced powder consolidation technologies to enhance production efficiency. This study explores the rapid sintering methodology for an Nd–Fe–B powder using a radiation‐assisted sintering approach. The case study material is an industrially used powder, prepared through strip‐casting, hydrogen decrepitation, and jet milling, with a mean particle size of 5.5 μm. The powder is sintered to full density in a modified spark plasma sintering furnace, achieving pressureless conditions and eliminating electrical currents in the sample to preserve grain alignment and prevent decomposition of the hard‐magnetic phase. Fully dense samples are obtained with heating rates ranging from 10 to 200 °C min−1 and up to 5 min of dwell time at 1100 °C. Rapid heating results in grain size and microstructure comparable to conventionally sintered magnets prepared from the same powder, without compromising magnetic performance after postsinter annealing at 520 °C for 120 min. This sintering method contributes to a novel strategy for optimizing magnet production by utilizing efficient thermal‐radiation heat transfer. The combination of rapid heating and pressureless sintering drastically reduces heat‐up and dwell times, providing a fundamental advantage over slow conventional sintering.
Reprocessable and Mechanically Tailored Soft Architectures Through 3D Printing of Elastomeric Block Copolymers
Authors: Fergerson Alice S. , Gorse Benjamin H. , Maguire Shawn M. , Ostermann Emily C. , Davidson Emily C.
Published: September 2024

Thermoplastic elastomers (TPEs) are nanostructured, melt‐processable, elastomeric block copolymers. When TPEs that form cylindrical or lamellar nanostructures are macroscopically oriented, their material properties can exhibit several orders of magnitude of anisotropy. Here it is demonstrated that the flows applied during the 3D printing of a cylinder‐forming TPE enable hierarchical control over material nanostructure and function. It is demonstrated that 3D printing allows for control over the extent of nanostructural and mechanical anisotropy and that thermal annealing of 3D printed structures leads to highly anisotropic properties (up to 85 × anisotropic tensile modulus). This approach is leveraged to print functional soft 3D architectures with tunable local and macroscopic mechanical responses. Further, these printed TPEs intrinsically achieve melt‐reprocessability over multiple cycles, reprogrammability, and robust self‐healing via a brief period of thermal annealing, enabling facile fabrication of highly tunable, robust, and recyclable soft architectures.
A Novel Targeted Microtubules Transformable Nanopeptide System Yields Strong Anti‐Prostate Cancer Effects by Suppressing Nuclear Translocation of Androgen Receptors
Authors: Wang Lu , Kong Bin , Wang Jiaqi , Yang Guang , Wu Xiuhai , Zang Jiahui , Li Cong , Wang Xinyue , Si Minggui , Wang Zhijia , Liu Pan , Wang Yuting , Chen Huilin , Liu Feng , Yang Pei‐Pei , Wang Lei , Wang Hao , Xu Wanhai
Published: September 2024

The extended use of androgen deprivation therapy (ADT) may often lead to the progression from castration‐sensitive prostate cancer (CSPC) to castration‐resistant prostate cancer (CRPC) in prostate cancer. To address this, it is essential to inhibit the nuclear translocation of the androgen receptor (AR) as part of an effective disease‐modifying strategy. Microtubules play a central role in facilitating AR nuclear translocation, highlighting their importance as a therapeutic target. In this regard, a designated as the targeted microtubules transformable nanopeptide system (MTN) is developed. This system is designed to disrupt microtubule structure and function through dual‐targeting of prostate‐specific membrane antigen (PSMA) and β‐tubulin. Initially, MTN targets prostate cells via PSMA and then specifically binds to β‐tubulin within microtubules, leading to the formation of nanofibers. These nanofibers subsequently induce the polymerization of microtubules, thereby disrupting AR transport. Notably, MTN exhibits efficient and prolonged suppression of prostate cancer across the spectrum from CSPC to CRPC, with a highly favorable safety profile in normal cells. These findings highlight the potential of MTN as a novel and promising approach for comprehensive prostate cancer therapy throughout its entire progression.
Pressure‐Regulated Photovoltaic Response in Antimony Triiodide With Asymmetric Metal Contact
Authors: Xing Shengyang , Chen Shuxin , Fang Sixue , Tian Fuyu , Li Zonglun , Jin Xilian , Li Quanjun , Liu Bingbing
Published: September 2024

The effective modification of photovoltaic activities in photoelectric devices is significant for enhancing energy conversion efficiency. Here, the pressure‐tunable photovoltaic properties in the SbI3 device with Au/Pt asymmetric electrodes are demonstrated. At initial pressure, the SbI3 device exhibits an anticipated self‐driven photoresponse characteristic at zero external bias, and a significant enhancement in photocurrent response is observed with increasing bias to −0.2 V, nearly two orders of magnitude higher than the initial value. With increasing pressure, the SbI3 device exhibits tunable photocurrent response, reaching a maximum value at ≈1.2 GPa, while the photovoltage response decreases monotonously during compression, which is closely associated with the dynamic evolution of the work function and bandgap of SbI3 upon successive compression. These findings signify that SbI3 is a promising candidate for future photoelectric devices, which opens a new window of opportunity for further exploration, regulation, and understanding of high‐performance photovoltaic devices under extreme conditions.
Ultrahigh Thermal Rectification at Small Temperature Difference Achieved by Near‐Field Thermal Photon Manipulation
Authors: Deng Yan , Shi Kezhang , Bao Fanglin , Antezza Mauro , Evans Julian , He Sailing
Published: September 2024

Thermal diodes, which allow heat to flow in a preferential direction, are an essential component of thermal circuitry and will find applications in many fields ranging from thermal photon controls to quantum information. The quality of a thermal diode is defined by the thermal rectification ratio (TRR). Here, an ultrahigh TRR exceeding 105 at a small temperature difference (1–5 K) is presented based on near‐field thermal photon (NFTP) manipulation, by utilizing asymmetric gap‐variated dual terminals based on graphene/Si heterostructures and materials with contrasting thermal expansion coefficients. Analyses of the photon tunneling probability show that the colossal TRR comes from coupled and decoupled graphene surface plasmon polaritons under opposite temperature biases, remaining robust across a wide operating temperature range. Further enhancement can be achieved by tuning the Fermi level of graphene. This work demonstrates the significance of asymmetry in NFTP manipulation for thermal diode performance, achieving an ultrahigh TRR, which is at least three orders higher than the state‐of‐the‐art structures at the same small temperature difference (1–5 K), and is comparable to state‐of‐the‐art electronic diodes.
Thermally Triggered Interface for Simplified Organic Solar Cells
Authors: Kongsabay Suwapat , Roche Gilles Henri , Dautel Olivier , Promarak Vinich , Wantz Guillaume
Published: September 2024

Organic photovoltaic (OPV) cells are commonly produced by successive printing of four layers on top of a transparent conducting electrode, with the active layer sandwiched in between interlayers followed by the top electrode. Here, the simplification of OPV manufacturing without the need to coat a hole transport layer (HTL) in inverted OPV (n–i–p) is reported. To ensure the required hole selectivity, thermally trigged molecules are directly blended in the active layer during device casting. Following thermal annealing of the complete devices, organosulfur molecules self‐assembled to form a hole–transporting interface between the silver top electrode and the active layer, thereby enabling working devices. Device optimization is performed by varying the concentration of these molecules and the thermal annealing conditions. The performances of the simplified devices approach those of control devices with vacuum‐evaporated MoO3 HTLs. The solar cells exhibit very encouraging thermal and photostabilities. This work opens the route to high efficiency, simplified, and low‐cost organic solar cells.
Copper‐Catalyzed Tandem Cyclization of 2‐(Alkynylaryl)Acetonitriles and Amines: Access to 3‐Hydroxyisoindolinones
Authors: Li Jiatian , Pan Lin , Tan Xiangwen , Jiang Huanfeng , Wu Wanqing
Published: September 2024

Herein, we describe an approach to the synthesis of 3‐hydroxyisoindolinone derivatives via copper‐catalyzed tandem cyclization of 2‐(alkynylaryl)acetonitriles and amines. This reaction is compatible with 2‐(alkynylaryl)acetonitriles and primary alkyl amines containing various functional groups, providing the corresponding 3‐hydroxyindolinone derivatives with yields ranging from 44%–82%. Preliminary mechanistic studies suggest that the reaction involves oxidation of the benzylic carbon, amide formation, hydration of the alkyne and intramolecular cyclization to produce various 3‐hydroxyisoindolinones. The practicality of the strategy was further demonstrated by gram‐scale synthesis, late‐stage functionalizations, and the post modification of natural products.
Cell Type‐Specific Modulation of Acute Itch Processing in the Anterior Cingulate Cortex
Authors: Li Jiaqi , Bai Yang , Ge Junye , Zhang Yiwen , Zhao Qiuying , Li Dangchao , Guo Baolin , Gao Shasha , Zhu Yuanyuan , Cai Guohong , Wan Xiangdong , Huang Jing , Wu Shengxi
Published: September 2024

Despite remarkable progress in understanding the fundamental bases of itching, its cortical mechanisms remain poorly understood. Herein, the causal contributions of defined anterior cingulate cortex (ACC) neuronal populations to acute itch modulation in mice are established. Using cell type‐specific manipulations, the opposing functions of ACC glutamatergic and GABAergic neurons in regulating acute itching are demonstrated. Photometry studies indicated that ACC glutamatergic neurons are activated during scratching induced by both histamine and chloroquine, whereas the activation pattern of GABAergic neurons is complicated by GABAergic subpopulations and acute itch modalities. By combining cell type‐ and projection‐specific techniques, a thalamocortical circuit is further identified from the mediodorsal thalamus driving the itch‐scratching cycle related to histaminergic and non‐histaminergic itching, which is contingent on the activation of postsynaptic parvalbumin‐expressing neurons in the ACC. These findings reveal a cellular and circuit signature of ACC neurons orchestrating behavioral responses to itching and may provide insights into therapies for itch‐related diseases.
Bio‐Inspired Optoelectronic Neuromorphic Device Based on 2D vdW Ferroelectric Heterostructure for Nonlinearly Preprocessing Visual Information and Convolutional Operation
Authors: Guo Feng , Io Weng Fu , Dang Zhaoying , Zhao Yuqian , Pang Sin‐Yi , Zhao Yifei , Lao Xinyue , Hao Jianhua
Published: September 2024

The human visual system provides important inspiration for designing energy‐efficient and sophisticated artificial visual systems. However, integrating nonlinear preprocessing visual information and convolutional operations analogous to those of human in a single device is still in its infancy. In this work, a three‐terminal 2D ferroelectric heterostructure consisting of α‐In2Se3/WSe2 is proposed for designing optoelectronic neuromorphic device. In contrast to conventional ferroelectric materials, the narrow bandgap of the ferroelectric α‐In2Se3 enables the device to perceive visible light directly. Nonlinearly preprocessing is adopted by bipolar cells in the retina and computer algorithms. In the device, similar function is achieved by modulating the energy band based on ferroelectricity. The results demonstrate the ability of the device to suppress noise, and the image recognition accuracy is increased from 75% to 92%. Convolutional neural networks play an important role to extract and compress the image information for human to respond to external environment in real time. Based on the unique coupling of ferroelectricity in α‐In2Se3, the convolutional operation is imitated, thus allowing for reduction in image recognition time by 87%. The results provide a promising strategy to integrate diverse bio‐inspired neuromorphic behaviors in a single device for artificial intelligence to process high‐throughput visual information.
A framework for translating tauopathy therapeutics: Drug discovery to clinical trials
Authors: Feldman Howard H. , Cummings Jeffrey L. , Boxer Adam L. , Staffaroni Adam M. , Knopman David S. , Sukoff Rizzo Stacey J. , Territo Paul R. , Arnold Steven E. , Ballard Clive , Beher Dirk , Boeve Bradley F. , Dacks Penny A. , Diaz Kristophe , Ewen Colin , Fiske Brian , Gonzalez M. Isabel , Harris Glenn A. , Hoffman Beth J. , Martinez Terina N. , McDade Eric , Nisenbaum Laura K. , Palma Jose‐Alberto , Quintana Melanie , Rabinovici Gil D. , Rohrer Jonathan D. , Rosen Howard J. , Troyer Matthew D. , Kim Doo Yeon , Tanzi Rudolph E. , Zetterberg Henrik , Ziogas Nick K. , May Patrick C. , Rommel Amy
Published: September 2024

The tauopathies are defined by pathological tau protein aggregates within a spectrum of clinically heterogeneous neurodegenerative diseases. The primary tauopathies meet the definition of rare diseases in the United States. There is no approved treatment for primary tauopathies. In this context, designing the most efficient development programs to translate promising targets and treatments from preclinical studies to early‐phase clinical trials is vital. In September 2022, the Rainwater Charitable Foundation convened an international expert workshop focused on the translation of tauopathy therapeutics through early‐phase trials. Our report on the workshop recommends a framework for principled drug development and a companion lexicon to facilitate communication focusing on reproducibility and achieving common elements. Topics include the selection of targets, drugs, biomarkers, participants, and study designs. The maturation of pharmacodynamic biomarkers to demonstrate target engagement and surrogate disease biomarkers is a crucial unmet need.

Highlights

Experts provided a framework to translate therapeutics (discovery to clinical trials).

Experts focused on the “5 Rights” (target, drug, biomarker, participants, trial).

Current research on frontotemporal degeneration, progressive supranuclear palsy, and corticobasal syndrome therapeutics includes 32 trials (37% on biologics)

Tau therapeutics are being tested in Alzheimer's disease; primary tauopathies have a large unmet need.
Electronic Response and Charge Inversion at Polarized Gold Electrode
Authors: Andersson Linnéa , Sprik Michiel , Hutter Jürg , Zhang Chao
Published: September 2024

We have studied polarized Au(100) and Au(111) electrodes immersed in electrolyte solution by implementing finite‐field methods in density functional theory‐based molecular dynamics simulations. This allows us to directly compute the Helmholtz capacitance of electric double layer by including both electronic and ionic degrees of freedom, and the results turn out to be in excellent agreement with experiments. It is found that the electronic response of Au electrode makes a crucial contribution to the high Helmholtz capacitance and the instantaneous adsorption of Cl can lead to a charge inversion on the anodic polarized Au(100) surface. These findings point out ways to improve popular semi‐classical models for simulating electrified solid–liquid interfaces and to identify the nature of surface charges therein which are difficult to access in experiments.
Hollow Hydrogels for Excellent Aerial Water Collection and Autonomous Release
Authors: Liang Shumin , Al‐Handawi Marieh B. , Chen Tao , Naumov Panče , Zhang Lidong
Published: September 2024

Air moisture is a valuable and omnipresent resource of fresh water. However, traditional water collectors come with an enduring problem of the water‐release step, which requires special devices and additional energy to remove the water from the adsorbent, such as heat, sunlight, or both. Herein, we report the first composite conical hollow hydrogel architecture fabricated through a film‐to‐tube transforming protocol, designed to harvest water from aerial humidity. This hollow hydrogel device can rapidly collect water from humid air to a saturation point, whereupon it automatically and continually releases fresh water at room temperature. The entire water collection and release process does not require any external assistance. Therefore, this device is highly suitable for emergency water collection in arid areas. As an exemplary demonstration, positioning the hollow hydrogel device next to a plant turns into an individualized system for irrigation. Since the device is biodegradable, it eventually decomposes and becomes an organic fertilizer after the water supply is not required. For long‐term application, the water‐release process can be monitored in real time by an electronic device to indicate the amount of collected water. The hollow hydrogel combines the humidity‐adsorbing capacity with autonomous water release that carries the potential for harvesting water from humidity to address the shortage of fresh water, especially in arid locations where other sources of water are scarce or inaccessible.
Thermally‐Stable Single‐Site Pd on CeO2 Catalyst for Selective Amination of Phenols to Aromatic Amines without External Hydrogen
Authors: Wang Yaqin , Chen Bingfeng , Li Lina , Mei Xuelei , Gu Yucheng , Wu Haihong , He Mingyuan , Han Buxing
Published: September 2024

Developing a new route to produce aromatic amines as key chemicals from renewable phenols is a benign alternative to current fossil‐based routes like nitroaromatic hydrogenation, but is challenging because of the high dissociation energy of the Ar−OH bond and difficulty in controlling side reactions. Herein, an aerosolizing‐pyrolysis strategy was developed to prepare high‐density single‐site cationic Pd species immobilized on CeO2 (Pd1/CeO2) with excellent sintering resistance. The obtained Pd1/CeO2 catalysts achieved remarkable selectivity of important aromatic amines (yield up to 76.2 %) in the phenols amination with amines without external hydrogen sources, while Pd nano‐catalysts mainly afforded phenyl‐ring‐saturation products. The excellent catalytic properties of the Pd1/CeO2 are closely related to high‐loading Pd single‐site catalysts with abundant surface defect sites and suitable acid‐base properties. This report provides a sustainable route for producing aromatic amines from renewable feedstocks.
Achieving Controllable Thermochromic Fluorescence via Synergistic Intramolecular Charge Transfer and Molecular Packing
Authors: Feng Weixu , Lu Sumin , Wu Yanhui , Li Xiaotian , Han Dong , Zhao Yan , Tian Wei , Yan Hongxia
Published: September 2024

Thermochromic fluorescent materials (TFMs) have attracted significant attention due to their unique fluorescent colorimetric response to temperature. However, existing TFMs still suffer from weak stimulus responsiveness, broad temperature response ranges, uncontrollable emission color changes, and low quantum yields. In this study, we address these issues by designing and synthesizing three diketone‐boron complexes with distinct emission wavelengths (NWPU‐(2–4)). Utilizing a molecular engineering strategy to manipulate intramolecular charge transfer transitions and molecular packing modes, our synthesized complexes exhibit efficient fluorescence emission in both solution and solid states. Moreover, their emission wavelengths are highly sensitive to environmental polarity. By incorporating these compounds into thermosensitive matrices of long‐chain alkanes, we produced TFMs with varied fluorescence emission peak variation ranges. Notably, the TFM based on NWPU‐4, owing to its strong charge transfer transitions and dense J‐aggregate packing configuration, not only exhibits intense fluorescence emission spanning the deep red to near‐infrared spectrum but also displays a remarkable 90 nm broad range of thermochromic properties. Ultimately, it was successfully applied to programmable, thermally controlled, multi‐level information encryption.
Cross‐Coupling of Gaseous Alkanes with (Hetero)Aryl Bromides via Dual Nickel/Photoredox Catalysis
Authors: Nair Akshay M. , Martínez‐Balart Pol , Barbeira‐Arán Sergio , Fañanás‐Mastral Martín
Published: September 2024

Gaseous alkanes represent the most abundant carbon‐based chemical feedstocks in our planet. However, the intrinsic inertness of their C−H bonds has rendered the use of these alkanes very difficult for purposes beyond aerobic combustion and energy intensive processes. Thus, clean and energy‐efficient transformations for their use in synthetic organic chemistry are still rare. Here we report a catalytic methodology for the direct cross‐coupling of gaseous alkanes with (hetero)aryl bromides through the combination of metallaphotoredox‐mediated hydrogen atom transfer and nickel catalysis. This protocol provides an efficient platform for the addition of short alkyl groups into diverse (hetero) aromatic rings, providing a wide range of high‐value alkyl(hetero)arenes, and bypassing the longstanding need of using preactivated alkylating agents in C(sp2)‐C(sp3) cross‐couplings. The method features high chemoselectivity, regioselectivity and a remarkable functional group tolerance, operates under mild conditions, and exhibits operational simplicity
A Magnesium Organic Framework Fluorescent Sensor for Selective Detection of Nitrofuran Antibiotics and Inorganic Pollutants
Authors: Zhao Xiangyu , Yao Xiaoyan , Lv Xueyi , Zhang Xishuo , Sun Hanlei , Wang Hongzhi , Li Yuhan , Yao Shuo , Liu Licheng
Published: September 2024

A novel 3D magnesium‐based metal organic framework (Mg‐MOF) has been solvothermally synthesized using 5‐(pyridin‐4‐yl)isophthalic acid. The ligand has demonstrated to preserve two types of coordination modes depending on the connection mode of the pyridine group. The uncoordinated pyridine groups provide Lewis base sites (LBSs), whereas the coordinated ones promote to form a rarely reported eight‐connected tetranuclear Mg clusters. Benefiting from the multinuclearity with high number of connections, the framework keeps good performance of high thermal stability until 500°C. Furthermore, the framework exhibits potential open metal sites (OMSs) benefiting from the terminal coordinated water groups of the metal clusters. Owing to the abundant active sites, the Mg‐MOF exhibits good sensitivity to nitrofuran antibiotics and Cr2O72−, with high KSV (at 104 M−1 level) and low limit of detection (LOD) values (∼10−6 M). Density functional theory (DFT) investigation reveals that the interchange of the HOMO–LUMO energy levels of the framework and antibiotics is responsible for the sensing activity. In addition, the Mg‐MOF is greatly recyclable in five cycles while maintaining the structural rigidity and sensing activity, making it a promising luminescence probe material.
BAD2matrix: Phylogenomic matrix concatenation, indel coding, and more
Authors: Salinas Nelson R. , Eshel Gil , Coruzzi Gloria M. , DeSalle Rob , Tessler Michael , Little Damon P.
Published: September 2024

Premise

Common steps in phylogenomic matrix production include biological sequence concatenation, morphological data concatenation, insertion/deletion (indel) coding, gene content (presence/absence) coding, removing uninformative characters for parsimony analysis, recording with reduced amino acid alphabets, and occupancy filtering. Existing software does not accomplish these tasks on a phylogenomic scale using a single program.

Methods and Results

BAD2matrix is a Python script that performs the above‐mentioned steps in phylogenomic matrix construction for DNA or amino acid sequences as well as morphological data. The script works in UNIX‐like environments (e.g., LINUX, MacOS, Windows Subsystem for LINUX).

Conclusions

BAD2matrix helps simplify phylogenomic pipelines and can be downloaded from https://github.com/dpl10/BAD2matrix/tree/master under a GNU General Public License v2.
Customized Nano‐Confinement Effects of Metal‐Organic Frameworks for High‐Performance Lithium‐Sulfur Batteries
Authors: Weng Jingqia , Lu Haibin , Zeng Qinghan , Xiao Yingbo , Yang Junhua , Rong Jionghui , Zhang Qi , Huang Shaoming
Published: September 2024

Lithium‐sulfur batteries (LSBs) are considered one of the most promising next‐generation energy storage devices due to their significant theoretical energy density and high specific capacity of sulfur cathode. However, several critical challenges still must be addressed for practical application. The shuttle effect and sluggish redox kinetics severely impact their performance. Metal‐organic frameworks (MOFs) have garnered significant interest attributed to their high structural tunability. Their ability to nano‐confine lithium polysulfides (LiPSs) can be precisely controlled at the molecular level by regulating metal centers and organic ligands, thereby suppressing the shuttle effect and improving the electrochemical performance of LSBs. This review summarizes the nano‐confinement effects of MOFs in LSBs, and the discussion is divided into the selective confinement, repulsion, and nano‐confined adsorption by inert MOFs, as well as nano‐confined catalysis facilitated by catalytically active MOFs. Furthermore, the existing challenges and future prospects for application of MOFs in LSBs are proposed.
Pulsed electromagnetic fields attenuate human musculocutaneous nerve damage induced by biceps eccentric contractions
Authors: Kouzaki Karina , Nakazato Koichi
Published: September 2024

Pulsed electromagnetic field (PEMF) therapy, a noninvasive treatment, has shown promise in mitigating nerve damage. However, unaccustomed exercises, such as eccentric contractions (ECCs), can damage both muscle and nerve tissue. This study investigated whether magnetic stimulation (MS) with PEMF could aid in nerve recovery after ECCs in the elbow flexors. Twenty participants were randomly assigned to either a control (CNT) or an MS group. Following ECCs, we measured the latency of the M‐wave in the musculocutaneous nerve as an indicator of nerve function. Additionally, isometric torque, range of motion, and muscle pain were assessed for muscle function. Interestingly, only the CNT group exhibited a significant increase in latency on Day 2 (p < 0.05). The MS group, on the other hand, displayed an earlier recovery trend in isometric torque, range of motion, and muscle soreness. Notably, muscle soreness significantly decreased immediately after MS treatment compared to pretreatment levels. These findings suggest that MS treatment can effectively attenuate nerve damage induced by ECCs exercise.
Fließfertigung von variablen gekrümmten Modulen für dünnwandige Schalenkonstruktionen aus Beton
Authors: Ivaniuk Egor , Tošić Zlata , Lordick Daniel , Mechtcherine Viktor
Published: September 2024

Dünne Betonschalen ermöglichen eine erhebliche Materialeinsparung. Die herkömmlichen Herstellungsmethoden von Betonschalen, die auf der Betonage in einer Schalung basieren, sind jedoch aus heutiger Sicht unwirtschaftlich. Der modulare Ansatz kann den Schalenbau deutlich kosteneffizienter machen, insbesondere, wenn Module mit einem hohen Automatisierungsgrad gefertigt werden. Das laufende Projekt „Schalungsfreie Fließfertigung adaptiver Tragstrukturen aus variablen Rahmenelementen – ACDC and beyond“ zielt darauf ab, einen Ansatz für die vollautomatische Herstellung von Betonschalenmodulen mit variabler Geometrie zu entwickeln. Besonderes Augenmerk gilt dabei der Bewehrung der Module, die mittels automatisierter Verlegung von Carbongarnen erfolgt. Die Konturen der Module werden mit hochduktilem Beton (engl.: Strain‐Hardening Cementitious Composite, SHCC) 3D‐gedruckt. Dieser Aufsatz stellt die im Rahmen des Projekts erzielten Ergebnisse vor und gibt einen Überblick über die laufenden Arbeiten, zu denen die Herstellung nicht planarer Module, die Einführung von Nachbearbeitungstechniken und die Verbesserung der Nachhaltigkeit der Technologie gehören.
The efficacy of gemcitabine and docetaxel chemotherapy for the treatment of relapsed and refractory osteosarcoma: A systematic review and pre‐clinical study
Authors: Low Kaan , Foulkes Paola , Hills Frank , Roberts Helen C. , Stordal Britta
Published: September 2024

Introduction

Osteosarcoma is the most common primary malignancy of the bone. There is a lack of effective treatments for patients who experience relapsed osteosarcoma. One treatment for relapsed patients is gemcitabine and docetaxel combination chemotherapy (GEMDOX). This systematic review aimed to establish the efficacy of this chemotherapy regimen, as well as identify the common severe toxicities that are associated with it. Resistant osteosarcoma cell lines developed from MG‐63 and HOS‐143B were used to represent relapsed osteosarcoma patients in a pre‐clinical study.

Results

We identified 11 retrospective and Phase II studies that were suitable for inclusion in our review. 10.65% of patients had a response to gemcitabine and docetaxel combination therapy and the disease control rate was 35% (n = 197). 36%, 35.3% and 18.04% of patients experienced grade 3 or 4 neutropenia, thrombocytopenia and anaemia respectively (n = 133). Male patients (X2 = 9.14, p < 0.05) and those below the age of 18 (X 2 = 10.94, p < 0.05) responded better to GEMDOX treatment than females and patients older than 18 years. The resistant osteosarcoma cell lines remained sensitive to either single‐agent gemcitabine, docetaxel, and the combination of both. Cisplatin‐resistant models (MG‐63/CISR8 & HOS‐143B/CISR8) were the most responsive to GEMDOX treatment compared to doxorubicin, methotrexate, and triple‐combination resistant models.

Conclusion

GEMDOX treatment has potential efficacy in relapsed osteosarcoma patients especially those with cisplatin resistance. To directly compare the efficacy of GEMDOX therapy against other therapies randomised phase III clinical trials with adequate patient follow up must be performed to improve treatment options for osteosarcoma.
Phytochemical Investigation of an Ostrya carpinifolia L. Extract: An Effective Anti‐Pollution Cosmetic Active Ingredient.
Authors: Trinel Manon , Dubois Camille , Burger Pauline , Plainfossé Hortense , Azoulay Stéphane , Verger‐Dubois Gregory , Fernandez Xavier
Published: September 2024

Ostrya carpinifolia L., a member of the Betulaceae family, is a tree endemic to the Mediterranean basin that is well known for the hardness of its wood. In this study, we assess the anti‐pollution activities of a hydroalcoholic extract of O. carpinifolia twigs using several judiciously selected in vitro cosmetic bioassays. The extract's capacity to counteract excessive production of reactive oxygen species following a cutaneous exposure to atmospheric pollution was evaluated using a combination of several antioxidant assays: DPPH, FRAP and β‐carotene bleaching assays. These antioxidant assays were complemented by anti‐elastase, anti‐collagenase, anti‐hyaluronidase and anti‐lipoxygenase assays to evaluate the capacity of the extract to preserve the integrity of the skin. The hydroalcoholic extract of O. carpinifolia demonstrates intriguing biological antioxidant activities, with approximately 50 % inhibition observed in DPPH and β‐carotene assays. Furthermore, its anti‐lipoxygenase, anti‐hyaluronidase, and anti‐collagenase activities are noteworthy, exceeding 50 % inhibition. The two major compounds of O. carpinifolia ethanolic extract were isolated and identified as myricitrin (1) and quercitrin (2). Myricitrin and quercitrin exhibit antioxidant and anti‐hyaluronidase properties; we explored the correlation of these properties with the activity of the crude hydroalcoholic extract. Notably, these compounds have not been previously described in the Ostrya genus.
Procedural and clinical impact of intracoronary lithotripsy in heavily calcified aorto‐ostial coronary lesions
Authors: Oliveri Federico , Meijer Maura , Van Oort Martijn J. H. , Al Amri Ibtihal , Bingen Brian O. , Claessen Bimmer E. , Dimitriu‐Leen Aukelien C. , Kefer Joelle , Girgis Hany , Vossenberg Tessel , Van der Kley Frank , Jukema J. Wouter , Montero‐Cabezas Jose M.
Published: September 2024

Background

Percutaneous coronary intervention of calcified aorto‐ostial lesions (AOL) pose unique challenges due to anatomical propensity for recoil, leading to poorer outcomes compared to non‐AOL. Although intravascular lithotripsy (IVL) has shown excellent success and safety in heavily calcified plaques, evidence specific to AOL is limited. This study aims to evaluate the efficacy and safety of IVL in AOL versus non‐AOL.

Methods

Patients treated with IVL between 2019 and 2023 from an ongoing prospective multicenter registry were eligible for inclusion. Patients were therefore classified in AOL and non‐AOL groups, based on anatomical location. The primary technical endpoint was device success, defined as the ability to deliver the IVL catheter and pulses at the target lesion, without angiographic complications. Secondary technical endpoint encompassed procedural success <30%, consisting of device success with residual stenosis <30%, final thrombolysis in myocardial infarction grade 3 flow, and no in‐hospital major adverse cardiovascular events (MACE). The primary clinical endpoint was in‐hospital MACE, including cardiac death, nonfatal myocardial infarction, or target lesion revascularization.

Results

A total of 321 patients underwent IVL, including 48 with AOL. Device success showed no significant difference between AOL and non‐AOL groups (100% vs. 98.2%; p = 0.35). A nonsignificant trend toward worse procedural success with residual stenosis <30% was observed in the AOL arm (AOL 81.3% vs. non‐AOL 90.5%, p = 0.06). In‐hospital MACE was significantly higher in AOL (4.2% vs. 0.7%, p = 0.048), attributed entirely to cardiac deaths. At 6‐month follow‐up, the incidence of MACE (AOL 8.3% vs. non‐AOL 4.0%, p = 0.19), and cardiac deaths (AOL 4.2% vs non‐AOL1.1%, p = 0.11) were comparable between groups.

Conclusion

IVL treatment for heavily calcified AOL demonstrates comparable procedural and 6‐month clinical outcomes when compared to non‐AOL, despite a higher incidence of in‐hospital MACE.