bluuebunny/crossref_metadata_2025 huggingface dataset:
Gabapentin Treatment for Bipolar Disorders
Authors: Maidment Ian D
Published: June 2003

OBJECTIVE:

To review the effectiveness data on the use of gabapentin in bipolar disorders.

DATA SOURCES:

Clinical literature was accessed through MEDLINE (January 1985–November 2000). Key search terms included gabapentin, mood stabilizer, and bipolar disorder.

DATA SYNTHESIS:

Bipolar disorder is a complex condition that can be difficult to treat effectively. Mood stabilizers are increasingly being used to manage bipolar disorder. Studies that used gabapentin in bipolar disorders are evaluated.

CONCLUSIONS:

From the data presented, gabapentin cannot be recommended for treatment of bipolar disorder. Further studies are required to determine whether gabapentin has any role in the management of bipolar disorder.
Meta-Analysis of Proton Pump Inhibitors in Treatment of Bleeding Peptic Ulcers
Authors: Zed Peter J , Loewen Peter S , Slavik Richard S , Marra Carlo A
Published: June 2003

OBJECTIVE:

To evaluate the efficacy of proton pump inhibitors (PPIs) compared with placebo and histamine receptor antagonists (H2RAs) for reducing the incidence of rebleeding, surgery, and death in acute gastrointestinal bleeding (GIB) associated with peptic ulcer disease.

DATA SOURCES:

A systematic search of the English-language literature was performed using MEDLINE, EMBASE, and Pre-MEDLINE (from 1966 to September 2000) and a manual search of references.

STUDY SELECTION:

Randomized, controlled trials evaluating any PPI for acute GIB in adults with the end points of rebleeding, surgery or death.

DATA SYNTHESIS:

Nine trials (1829 pts.) were included. The relative odds of rebleeding indicated a 50% reduction in the PPI-treated group (OR 0.50, 95% CI 0.33 to 0.77; p = 0.002, NNTB 9; 95% CI NNTB 6 to 13). The relative odds of surgery indicated a 53% reduction in the PPI-treated group (OR 0.47, 95% CI 0.29 to 0.77; p = 0.003; NNTB 17, 95% CI 12 to 35). The relative odds for mortality indicated a nonsignificant 8% decrease in the odds of death in the PPI-treated group (OR 0.92, 95% CI 0.46 to 1.83, p = 0.81; NNTB 323, 95% CI NNTB 47 to ∞ to NNTH 33).

CONCLUSIONS:

PPIs are superior to H2RAs and placebo in preventing rebleeding and the need for surgery in patients with GIB, although they do not appear to reduce mortality.
Infrastructure of Pharmaceutical Research and Development in Japan
Authors: Ono Shunsuke , Kodama Yasuo , Nagao Taku
Published: June 2003

OBJECTIVE:

To examine the roles of different types of hospitals in implementation of multicenter Phase II/III trials in Japan, specifically focusing on two dichotomies: public versus private, and academic versus nonacademic. Possible explanation was sought as to why a hospital of one category was more likely to participate in specific types of trials in the Japanese medical environment.

METHODS:

A database containing attributes of published clinical trials (n = 217) was established from four journals featuring reports of clinical trial results. The preferences of public and academic hospitals for specific types of trials were estimated by applying a linear regression model. The trial compositions of these institutions were also estimated, taking the actual prevalence of trials in 1995 into consideration.

RESULTS:

Public sector hospitals, which were established for particular policy purposes in the national healthcare system, were more likely to accept trials in some fields (e.g., cardiovascular diseases, anesthesiology, antineoplastics, pediatrics) and of some kinds (e.g., Phase II rather than Phase III trials, trials supervised by the principal investigator in the public sector). Academic hospitals also showed preferences for some types of trials (e.g., cardiovascular diseases, dermatology; Phase II rather than Phase III trials). The analysis focusing on public hospitals suggested that policy purposes were achieved at least in some fields such as antineoplastics and anesthesiology.

CONCLUSIONS:

Japanese clinical trials were unevenly distributed between public and private sectors, and also between academic and nonacademic sectors. These data provide fundamental information about the clinical research environment for future pharmaceutical research and development strategies and policies.
Candida Lusitaniae Catheter-Related Sepsis
Authors: Pietrucha-Dilanchian Paula , Lewis Russell E , Ahmad Hussain , Lechin Alex E
Published: June 2003

OBJECTIVE:

To present a case describing Candida lusitaniae candidemia in an immunocompetent patient successfully treated with fluconazole antifungal therapy. Time—kill studies of the C. lusitaniae isolate using amphotericin B, and an extensive review of the literature are also presented.

CASE SUMMARY:

A 52-year-old immunocompetent Latin-American woman was admitted to the special care unit with severe sepsis. Her recent medical history included an exploratory laparotomy for gallstone pancreatitis, requiring cholecystectomy, segmental sigmoid colectomy, drainage of peritoneal abscesses, and a colostomy. In addition, the patient required a central venous catheter (CVC) placement for prolonged broad-spectrum antibiotic therapy and total parenteral nutrition therapy. Yeast was isolated from the abdominal abscess and blood cultures obtained on day 1, and from the catheter tip on day 5. The woman received initial empiric antifungal therapy with fluconazole, which was later changed to amphotericin B. After the yeast was identified as C. lusitaniae on day 8, this was changed to fluconazole for the duration of therapy. C. lusitaniae was not present in blood cultures taken two weeks after the CVC was removed, and the cultures remained negative thereafter. After a prolonged hospitalization, the patient was discharged home.

DISCUSSION:

Disseminated infections with C. lusitaniae usually occur in immunocompromised patients, although isolated reports of C. lusitaniae infections in immunocompetent patients have been described. Therapeutic challenges of C. lusitaniae treatment include its primary resistance to amphotericin B and species misidentification. Isolates recovered from our patient were submitted for fungus time—kill studies that suggested unique susceptibility patterns to amphotericin B, indicating a trend toward resistance.

CONCLUSIONS:

Based on variable susceptibility patterns of C. lusitaniae to amphotercin B and flucytosine, fluconazole is an appropriate choice as first-line therapy for C. lusitaniae candidemia.
Misoprostol in the Prevention of Postpartum Hemorrhage
Authors: Mategrano Vanessa A , Gabay Michael P
Published: June 2003

OBJECTIVE:

To evaluate the data regarding the use of misoprostol in the prevention of postpartum hemorrhage.

DATA SOURCES:

Pertinent literature was identified through a MEDLINE search (1966–January 2001) and through other secondary literature databases and/or bibliographies of pertinent articles.

DATA SYNTHESIS:

New strategies in the prevention of postpartum hemorrhage are being evaluated due to the obstacles surrounding conventional therapies. One therapeutic option is the use of misoprostol. This literature review evaluates the published clinical data involving misoprostol in the prevention of postpartum hemorrhage. Current data suggest that the use of misoprostol for the prevention of postpartum hemorrhage reduces mean estimated blood loss compared with placebo. However, no clinical trials have detected a statistically significant decrease in the incidence of postpartum hemorrhage in misoprostol-treated subjects. There is conflicting evidence regarding the efficacy of misoprostol compared with conventional uterotonics, such as oxytocin or Syntometrine.

CONCLUSIONS:

In situations where conventional oxytocics are not readily available, storage requirements for oxytocics cannot be met, or the equipment for parenteral administration is not obtainable, misoprostol may be an acceptable prophylactic option.
Intracerebral Hemorrhage following Possible Interaction between Celecoxib and Clopidogrel
Authors: Fisher Alex A , Le Couteur David G
Published: June 2003

OBJECTIVE:

To report a case of intracerebral hemorrhage following short-term, concomitant use of celecoxib and clopidogrel.

CASE SUMMARY:

An 86-year-old white woman with a medical history of paroxysmal atrial fibrillation, heart failure, osteoarthritis, peptic ulcer disease, chronic airway limitation, and surgery for carcinoma of the bowel and breast began clopidogrel therapy following a syncopal episode. She also began taking celecoxib for osteoarthritis at the same time. Three weeks later, she presented with headaches and left hemiparesis. Computed tomography scan revealed intracerebral hemorrhage that had not been previously detected. Celecoxib and clopidogrel were discontinued, and she recovered fully.

DISCUSSION:

This is the first case describing a possible interaction between celecoxib and clopidogrel. A pharmacokinetic interaction mediated by CYP2C9 is possible. However, the hemorrhage may have been secondary to the effects of either drug alone or concomitant disease.

CONCLUSIONS:

Celecoxib and clopidogrel have favorable risk profiles and, therefore, are prescribed widely among older people. However, clinicians should recognize that there may be an interaction between celecoxib and clopidogrel that increases the risk of hemorrhage in older people.
Cerivastatin and Gemfibrozil—Associated Rhabdomyolysis
Authors: Bruno-Joyce Jeanne , Dugas Jane M , MacCausland Owen E
Published: June 2003

OBJECTIVE:

To report a case of rhabdomyolysis resulting from concurrent use of cerivastatin and gemfibrozil.

CASE SUMMARY:

An 82-year-old white man presented to the emergency department with severe muscle weakness and inability to walk approximately one month after starting cerivastatin. He had been taking gemfibrozil for several years without any known adverse effects. Both medications were discontinued and the patient recovered. He was discharged with a diagnosis of rhabdomyolysis secondary to his medications.

DISCUSSION:

Four previous reports describing rhabdomyolysis in patients on concomitant cerivastatin and gemfibrozil have been cited. Although monotherapy with cerivastatin is well tolerated and has a low frequency of adverse events, the combination with nicotinic acid (i.e., niacin) or a fibric-acid derivative (i.e., gemfibrozil, fenofibrate) may result in severe skeletal muscle toxicity and rhabdomyolysis.

CONCLUSIONS:

According to the Naranjo scale, a probable relationship exists between the concomitant use of gemfibrozil and cerivastatin with the resulting development of rhabdomyolysis. Concurrent use of gemfibrozil and cerivastatin is therefore contraindicated.
Sedation Assessment in Critically Ill Adults
Authors: Devlin John W , Fraser Gilles L , Kanji Salmaan , Riker Richard R
Published: June 2003

OBJECTIVE:

To review methods for assessing sedation in critically ill adults, discuss their impact on patient outcomes, and provide recommendations for implementing these methods into clinical practice in the intensive care unit (ICU).

DATA SOURCES:

A computerized search of MEDLINE from 1980 through June 2000 and a manual search of abstracts presented at recent critical care meetings were performed.

STUDY SELECTION AND DATA EXTRACTION:

Sedation assessment tools that have been used to titrate therapy in adult, critically ill patients were identified. Special emphasis was placed on sedation assessment instruments that have been prospectively validated. Objective methods that have been used to assess sedation therapy were also identified.

DATA SYNTHESIS:

Twenty-three adult sedation assessment instruments were identified. Few scales have been prospectively evaluated for validity (n = 6) or reliability (n = 7). Other methods of sedation assessment were identified (e.g., bispectral index monitor); however, most of these methods have only been studied in small subsets of critically ill patients.

CONCLUSIONS:

Incorporation of sedation assessment into ICU clinical practice may improve patient care. These sedation assessment instruments must be further evaluated to determine their impact on quality of care and ICU length of stay.
Citalopram-Induced Bradycardia and Presyncope
Authors: Isbister Geoffrey K , Prior Felicity H , Foy Aidan
Published: June 2003

OBJECTIVE:

To report a case of symptomatic bradycardia and hypotension that resulted from the therapeutic use of citalopram and to review any previous reports in the literature, from the manufacturer, and the Australian Drug Reaction Advisory Committee (ADRAC).

CASE SUMMARY:

A 60-year-old white woman who had been taking citalopram 20 mg/d for two weeks presented to the hospital with a heart rate of 39 beats/min, mild hypotension (systolic BP 105 mm Hg), and a normal electrocardiogram (QTc <440 msec), following a presyncopal episode. The patient was admitted for cardiac monitoring, and citalopram was discontinued. The bradycardia and hypotension resolved in the 48-hour period following cessation of citalopram. No other medical or pharmacologic cause was found for the adverse drug reaction.

DISCUSSION:

Bradycardia has been reported rarely with citalopram in therapeutic doses, but this is the first detailed case with a dose of only 20 mg. The manufacturer reports bradycardia as an infrequent adverse effect (0.1–1%) of citalopram. There have been no reports to ADRAC or to the manufacturer in postmarketing surveillance. There is a case report of asymptomatic bradycardia in a patient whose dose was increased to 40 mg. In the case reported here, there was no QTc prolongation consistent with previous reports. The sinus bradycardia reported more often with therapeutic doses would appear to be distinct to QT abnormalities seen with citalopram overdose.

CONCLUSIONS:

Citalopram should be used with care in the elderly and in persons with a history of heart disease. Heart rate and blood pressure should be monitored in the first week of therapy and when doses are modified.
Burning Mouth Syndrome after Taking Clonazepam
Authors: Culhane Nicole S , Hodle Audrey D
Published: June 2003

OBJECTIVE:

To report the first published case of clonazepam-induced burning mouth syndrome (BMS).

CASE SUMMARY:

A 52-year-old white woman presented to the clinic with burning mouth symptoms. The patient was previously maintained on alprazolam therapy for anxiety, but was switched to clonazepam because of increased anxiety and panic. Clonazepam significantly relieved her symptoms, but after four weeks of therapy, she reported a constant, mild, oral burning sensation. An oral examination was negative for mucosal abnormalities, and laboratory tests were unremarkable. The clonazepam dose was reduced, and the symptoms decreased, but remained intolerable. Clonazepam was discontinued, and the burning mouth symptoms completely resolved. Since no other medications relieved the anxiety and panic symptoms, the patient requested clonazepam to be reinitiated, but she again developed intolerable burning mouth symptoms. As clonazepam was discontinued, the symptoms resolved.

DISCUSSION:

The clinical presentation of BMS includes burning and painful sensations of the mouth in the absence of mucosal abnormalities. Candidiasis, anemia, menopause, diabetes mellitus, medications, anxiety, and depression are some causes of this syndrome. Paradoxically, clonazepam has been studied for the treatment of BMS and has demonstrated mild to moderate improvement. In this patient, underlying causes of BMS were eliminated when possible. The association between clonazepam and BMS was highly probable according to the Naranjo probability scale.

CONCLUSIONS:

This is the first published report describing BMS with a benzodiazepine. Although uncommon, clinicians should be aware of this potential adverse effect due to the widespread use of benzodiazepines.
Health Insurance Coverage—Is Broader Always Better?
Authors: Hyman David A. , Letchuman Sunjay , Bai Ge
Published: January 2024

This Viewpoint discusses the traditional goals of health insurance and contrasts those with the current needs of insurance beneficiaries.
Concurrent Tissue and Circulating Tumor DNA Molecular Profiling to Detect Guideline-Based Targeted Mutations in a Multicancer Cohort
Authors: Iams Wade T. , Mackay Matthew , Ben-Shachar Rotem , Drews Joshua , Manghnani Kabir , Hockenberry Adam J. , Cristofanilli Massimo , Nimeiri Halla , Guinney Justin , Benson Al B.
Published: January 2024

Importance

Tissue-based next-generation sequencing (NGS) of solid tumors is the criterion standard for identifying somatic mutations that can be treated with National Comprehensive Cancer Network guideline–recommended targeted therapies. Sequencing of circulating tumor DNA (ctDNA) can also identify tumor-derived mutations, and there is increasing clinical evidence supporting ctDNA testing as a diagnostic tool. The clinical value of concurrent tissue and ctDNA profiling has not been formally assessed in a large, multicancer cohort from heterogeneous clinical settings.

Objective

To evaluate whether patients concurrently tested with both tissue and ctDNA NGS testing have a higher rate of detection of guideline-based targeted mutations compared with tissue testing alone.

Design, Setting, and Participants

This cohort study comprised 3209 patients who underwent sequencing between May 2020, and December 2022, within the deidentified, Tempus multimodal database, consisting of linked molecular and clinical data. Included patients had stage IV disease (non–small cell lung cancer, breast cancer, prostate cancer, or colorectal cancer) with sufficient tissue and blood sample quantities for analysis.

Exposures

Received results from tissue and plasma ctDNA genomic profiling, with biopsies and blood draws occurring within 30 days of one another.

Main Outcomes and Measures

Detection rates of guideline-based variants found uniquely by ctDNA and tissue profiling.

Results

The cohort of 3209 patients (median age at diagnosis of stage IV disease, 65.3 years [2.5%-97.5% range, 43.3-83.3 years]) who underwent concurrent tissue and ctDNA testing included 1693 women (52.8%). Overall, 1448 patients (45.1%) had a guideline-based variant detected. Of these patients, 9.3% (135 of 1448) had variants uniquely detected by ctDNA profiling, and 24.2% (351 of 1448) had variants uniquely detected by solid-tissue testing. Although largely concordant with one another, differences in the identification of actionable variants by either assay varied according to cancer type, gene, variant, and ctDNA burden. Of 352 patients with breast cancer, 20.2% (71 of 352) with actionable variants had unique findings in ctDNA profiling results. Most of these unique, actionable variants (55.0% [55 of 100]) were found in ESR1, resulting in a 24.7% increase (23 of 93) in the identification of patients harboring an ESR1 mutation relative to tissue testing alone.

Conclusions and Relevance

This study suggests that unique actionable biomarkers are detected by both concurrent tissue and ctDNA testing, with higher ctDNA identification among patients with breast cancer. Integration of concurrent NGS testing into the routine management of advanced solid cancers may expand the delivery of molecularly guided therapy and improve patient outcomes.
Outcomes in Mental Health Counseling From Conversational Content With Transformer-Based Machine Learning
Authors: Imel Zac E. , Tanana Michael J. , Soma Christina S. , Hull Thomas D. , Pace Brian T. , Stanco Sarah C. , Creed Torrey A. , Moyers Theresa B. , Atkins David C.
Published: January 2024

Importance

Use of asynchronous text-based counseling is rapidly growing as an easy-to-access approach to behavioral health care. Similar to in-person treatment, it is challenging to reliably assess as measures of process and content do not scale.

Objective

To use machine learning to evaluate clinical content and client-reported outcomes in a large sample of text-based counseling episodes of care.

Design, Setting, and Participants

In this quality improvement study, participants received text-based counseling between 2014 and 2019; data analysis was conducted from September 22, 2022, to November 28, 2023. The deidentified content of messages was retained as a part of ongoing quality assurance. Treatment was asynchronous text-based counseling via an online and mobile therapy app (Talkspace). Therapists were licensed to provide mental health treatment and were either independent contractors or employees of the product company. Participants were self-referred via online sign-up and received services via their insurance or self-pay and were assigned a diagnosis from their health care professional.

Exposure

All clients received counseling services from a licensed mental health clinician.

Main Outcomes and Measures

The primary outcomes were client engagement in counseling (number of weeks), treatment satisfaction, and changes in client symptoms, measured via the 8-item version of Patient Health Questionnaire (PHQ-8). A previously trained, transformer-based, deep learning model automatically categorized messages into types of therapist interventions and summaries of clinical content.

Results

The total sample included 166 644 clients treated by 4973 therapists (20 600 274 messages). Participating clients were predominantly female (75.23%), aged 26 to 35 years (55.4%), single (37.88%), earned a bachelor’s degree (59.13%), and were White (61.8%). There was substantial variability in intervention use and treatment content across therapists. A series of mixed-effects regressions indicated that collectively, interventions and clinical content were associated with key outcomes: engagement (multiple R = 0.43), satisfaction (multiple R = 0.46), and change in PHQ-8 score (multiple R = 0.13).

Conclusions and Relevance

This quality improvement study found associations between therapist interventions, clinical content, and client-reported outcomes. Consistent with traditional forms of counseling, higher amounts of supportive counseling were associated with improved outcomes. These findings suggest that machine learning–based evaluations of content may increase the scale and specificity of psychotherapy research.
Cardiovascular, Neurological, and Immunological Adverse Events and the 23-Valent Pneumococcal Polysaccharide Vaccine
Authors: Yoon Dongwon , Jeon Ha-Lim , Kim Ju Hwan , Lee Hyesung , Shin Ju-Young
Published: January 2024

Importance

Despite widespread immunization with the 23-valent pneumococcal polysaccharide vaccine (PPSV23), safety concerns remain owing to a lack of statistical power and largely outdated evidence.

Objective

To evaluate the association between cardiovascular, neurological, and immunological adverse events and PPSV23 vaccination in older adults.

Design, Setting, and Participants

This population-based cohort study using a self-controlled risk interval design used a large linked database created by linking the Korea Immunization Registry Information System and the National Health Information Database (2018 to 2021). Participants included patients aged 65 years or older with a history of PPSV23 vaccination and incident cardiovascular, neurological, or immunological events during the risk and control intervals. Data were analyzed from November 2022 to April 2023.

Exposure

23-valent pneumococcal polysaccharide vaccine.

Main Outcomes and Measures

The occurrence of 1 among 6 cardiovascular events (myocardial infarction, atrial fibrillation, cardiomyopathy, heart failure, hypotension, and myocarditis or pericarditis), 2 neurological events (Bell palsy and Guillain-Barré syndrome), and 3 immunological events (sepsis, thrombocytopenia, and anaphylaxis) during the risk and control periods. The risk and control intervals were defined as 1 to 28 and 57 to 112 days after PPSV23 vaccination, respectively. Conditional Poisson regression was used to estimate the incidence rate ratio (IRR) with a 95% CI.

Results

Altogether, 4355 of the 1 802 739 individuals who received PPSV23 vaccination and experienced at least 1 outcome event were included (mean [SD] age, 72.4 [8.2] years; 2272 male participants [52.1%]). For cardiovascular events, there were no significant associations for myocardial infarction (IRR, 0.96; 95% CI, 0.81-1.15), heart failure (IRR, 0.85; 95% CI, 0.70-1.04), and stroke (IRR, 0.92; 95% CI, 0.84-1.02). Similarly, no increased risks were observed for neurological and immunological outcomes: Bell palsy (IRR, 0.95; 95% CI, 0.72-1.26), Guillain-Barré syndrome (IRR, 0.27; 95% CI, 0.06-1.17), sepsis (IRR, 0.99; 95% CI, 0.74-1.32), and thrombocytopenia (IRR, 1.18; 95% CI, 0.60-2.35).

Conclusions and Relevance

In this self-controlled risk interval study, there was no appreciable increase in risk for most cardiovascular, neurological, or immunological adverse events following PPSV23. The updated safety profile of PPSV23 provides supportive evidence for the establishment of immunization strategies for older adults.
A virtual phantom for patient‐specific QA On A 1.5T MR‐linac
Authors: Ji Mingshuo , Li Zhenjiang , Tian Yuan , Zhang Ke , Li Minghui , Chen Yan
Published: January 2024

Create a virtual ArcCHECK‐MR phantom, customized for a 1.5T MR‐linac, with consideration of the different density regions within the quality assurance (QA) phantom, aiming to streamline the utilization of this specialized QA device. A virtual phantom was constructed in the treatment planning system (TPS) to replicate the ArcCHECK‐MR's composition, consisting of five distinct layers: “Outer” (representing the outer PMMA ring), “Complex” (simulating the printed circuit boards), “Detectors” (encompassing the detector area), “Inner” (signifying the inner PMMA ring) and “Insert” (representing the PMMA insert). These layers were defined based on geometric data and represented as contour points on a set of dummy CT images. Additionally, a setup platform was integrated as contoured structures. To determine the relative electron density (RED) values of the external and internal PMMA components, measurements were taken at 25 points in the insert using an ion chamber. A novel method for establishing the exit/entrance dose ratio (EEDR) for ArcCHECK‐MR was introduced. The RED of higher density region was derived by evaluating the local gamma index passing rate results with criteria of 2% dose difference and 2 mm distance‐to‐agreement. The performance of the virtual phantom was assessed for Unity 7 FFF beams with a 1.5T magnetic field. The radii of the five ring structures within the virtual phantom measured 133.0 mm, 110.0 mm, 103.4 mm, 100.0 mm, and 75.0 mm for the “Outer,” “Complex,” “Detectors,” “Inner” and “Insert” regions, respectively. The RED values were as follows: ArcCHECK‐MR PMMA had a RED of 1.130, “Detectors” were assumed to have a RED of 1.000, “Complex” had a RED of 1.200, and the setup QA phantom justified a RED of 1.350. Early validation results demonstrate that the 5‐layer virtual phantom, when compared to the commonly used bulk overridden phantom, offers improved capability in MR‐linac environments. This enhancement led to an increase in passing rates for the local gamma index by approximately 5 ∼ 6%, when applying the criteria of 2%, 2 mm. We have successfully generated a virtual representation of the distinct regions within the ArcCHECK‐MR using a TPS, addressing the challenges associated with its use in conjunction with a 1.5T MR‐linac. We consistently observed favorable local gamma index passing rates across two 1.5T MR‐linac and ArcCHECK‐MR unit combinations. This approach has the potential to minimize uncertainties in the creation of the QA phantom for ArcCHECK‐MR across various institutions.
Viscosity of Mono‐ and Polydisperse Mixtures of Photopolymer and Rigid Spheres for Manufacturing of Engineered Composite Materials Using Vat Photopolymerization
Authors: Reynolds John , Unterhalter John , Francoeur Mathieu , Bortner Michael , Raeymaekers Bart
Published: January 2024

Vat photopolymerization (VP) additive manufacturing involves selectively curing low‐viscosity photopolymers via exposure to ultraviolet light in a layer‐wise fashion. Dispersing filler materials in the photopolymer enables tailored end‐use properties, but also increases the viscosity and the timescale associated with interparticle network structural recovery postshear. These rheological properties influence self‐leveling and recoating of the liquid photopolymer mixture during VP. Herein, viscosity of photopolymer and rigid spherical glass microparticles (filler) is experimentally determined as a function of filler fraction, filler size distribution (mono‐ and polydisperse), shear rate, and temperature, which are important VP process parameters. Employing existing viscosity models for mono‐ and polydisperse polymer mixtures demonstrates that particle–particle interactions and the formation of nonspherical clusters of particles strongly affect the viscosity of both monodisperse and polydisperse mixtures with particle volume fractions > 0.05 due to agglomeration/deagglomeration of clusters at elevated shear rates. Consequently, unmodified viscosity models, which assume uniformly dispersed, rigid, spherical particles, are applicable only for mixtures with particle volume fractions < 0.05. It is shown that modifying model parameters such as the fluidity limit and intrinsic viscosity, which explicitly account for nonspherical clusters of particles, improves agreement between viscosity models and experiments, in particular when using a fractal approach.
Entropy Tuning Stabilizing P2‐Type Layered Cathodes for Sodium‐Ion Batteries
Authors: Liu Jie , Huang Weiyuan , Liu Renbin , Lang Jian , Li Yuhao , Liu Tongchao , Amine Khalil , Li Hongsen
Published: January 2024

The P2‐type layered transition metal oxide cathodes confront formidable challenges, including irreversible deleterious phase transitions, transition metals migration, and sluggish Na+ diffusion kinetics, which hamper their rapid commercial application in sodium ion batteries (SIB). In this work, an entropy tuning with dual‐site substitution strategy is proposed to address the aforementioned issues. In the tailored [Na0.67Zn0.05]Ni0.22Cu0.06Mn0.66Ti0.01O2 (NZNCMTO) cathodes, the strategic incorporation of Zn ions serves to occupy Na sites, intentionally disrupting the Na/vacancy ordering and establishing a reinforcing “pillar” effect within the layered framework. Furthermore, the substitution of Cu and Ti for Ni and Mn bolsters covalent bonding with the lattice oxygen, thereby impeding the migration of the transition metal ions and leading to a near‐zero strain structural evolution during charge and discharge process. Density functional theory calculations confirmed that entropy‐tuned NZNCMTO substantially lowered the migration energy barrier for Na+ ions diffusion and improved electronic conductivity. Consequently, the NZNCMTO cathode exhibits an impressive high practical capacity of 91.54 mAh g−1 at a high discharge rate of 10 C, along with outstanding cycling stability, maintaining near 100% capacity retention over 500 cycles at a current density of 10 C. This work presents an innovative blueprint for designing high‐performance sodium‐ion battery cathode materials.
The Promise and Potential of Brain Organoids
Authors: Smirnova Lena , Hartung Thomas
Published: January 2024

Brain organoids are 3D in vitro culture systems derived from human pluripotent stem cells that self‐organize to model features of the (developing) human brain. This review examines the techniques behind organoid generation, their current and potential applications, and future directions for the field. Brain organoids possess complex architecture containing various neural cell types, synapses, and myelination. They have been utilized for toxicology testing, disease modeling, infection studies, personalized medicine, and gene‐environment interaction studies. An emerging concept termed Organoid Intelligence (OI) combines organoids with artificial intelligence systems to generate learning and memory, with the goals of modeling cognition and enabling biological computing applications. Brain organoids allow neuroscience studies not previously achievable with traditional techniques, and have the potential to transform disease modeling, drug development, and the understanding of human brain development and disorders. The aspirational vision of OI parallels the origins of artificial intelligence, and efforts are underway to map a roadmap toward its realization. In summary, brain organoids constitute a disruptive technology that is rapidly advancing and gaining traction across multiple disciplines.
Printable Liquid Metal Foams That Grow When Watered
Authors: Krisnadi Febby , Kim Seoyeon , Im Sooik , Chacko Dennis , Vong Man Hou , Rykaczewski Konrad , Park Sungjune , Dickey Michael D.
Published: January 2024

Pastes and “foams” containing liquid metal (LM) as the continuous phase (liquid metal foams, LMFs) exhibit metallic properties while displaying paste or putty‐like rheological behavior. These properties enable LMFs to be patterned into soft and stretchable electrical and thermal conductors through processes conducted at room temperature, such as printing. The simplest LMFs, featured in this work, are made by stirring LM in air, thereby entraining oxide‐lined air “pockets” into the LM. Here, it is reported that mixing small amounts of water (as low as 1 wt%) into such LMFs gives rise to significant foaming by harnessing known reactions that evolve hydrogen and produce oxides. The resulting structures can be ≈4–5× their original volume and possess a fascinating combination of attributes: porosity, electrical conductivity, and responsiveness to environmental conditions. This expansion can be utilized for a type of 4D printing in which patterned conductors “grow,” fill cavities, and change shape and density with respect to time. Excessive exposure to water in the long term ultimately consumes the metal in the LMF. However, when exposure to water is controlled, the metallic properties of porous LMFs can be preserved.
Fluorine‐Free Lithium‐Ion Capacitor with Enhanced Sustainability and Safety Based on Bio‐Based ƴ‐Valerolactone and Lithium Bis(Oxalato)Borate Electrolyte
Authors: Teoh Khai Shin , Melchiorre Massimo , Darlami Magar Sandesh , Hermesdorf Marius , Leistenschneider Desirée , Oschatz Martin , Ruffo Francesco , Gómez Urbano Juan Luis , Balducci Andrea
Published: January 2024

In this work, the properties of a novel electrolyte based on the combination of bio‐based ƴ‐valerolactone (GVL) solvent with lithium bis(oxalato)borate (LiBOB) salt and its use for lithium‐ion capacitors (LICs) are presented. It is shown that the 1 m LiBOB in GVL electrolyte displays good transport properties, high thermal stability, and the ability to prevent anodic dissolution. Its impact on the performance of both battery‐type and capacitive‐type electrodes is evaluated. In this regard, special attention is paid to the filming properties associated with LiBOB and GVL decomposition at the electrode surfaces. To the best of the authors’ knowledge, the full‐cell devices assembled in this study are the first example of a fluorine‐free LIC. These devices exhibit a favorable energy‐to‐power ratio, delivering 80 Wh kg−1AM at 10 000 W kg−1AM along with excellent cycling stability, retaining 80% of the initial capacitance after 25 000 cycles. Furthermore, post‐mortem analysis of the LIC electrodes is conducted to gain deeper insights into the degradation mechanisms within the device.
Realization of Selector‐Memory Bi‐Functionality with Self‐Current Regulation Utilizing Poly‐Crystalline Based GST Electrolyte for Memristor Hardware Development
Authors: Hong Seokman , Park See‐On , Jeong Hakcheon , Park Taehoon , Cho YoonHo , Jang Tae‐Hwan , Sung Su‐Jin , Ahn Hyojung , Lee Jongwon , Choi Shinhyun
Published: January 2024

Conductive bridge random‐access memory (CBRAM) are two terminal devices that offer excellent switching performance. In addition, CBRAM shows various switching modes, including volatile threshold switching (TS) and nonvolatile threshold switching (N‐TS). These properties expand its applications to memory, selector, biological synapses, and neurons. However, due to the uncontrollable behavior of stochastic switching between TS and N‐TS in CBRAM devices, a novel approach is needed to improve the switching performance of CBRAM. Moreover, conventional devices that have different stacking between TS and N‐TS increase fabrication cost and worsen the device yield. Here, the selector‐memory bi‐functionality with self‐current regulation effect of Ag‐inserted Ge2Sb2Te5 (GST) thin films is demonstrated. Selector‐memory bi‐functionality, having TS behavior with an adjustable on/off current, with confined conductive filaments (CFs) improves the uniformity and reduces the fabrication cost by implementing TS/N‐TS in a single stack. From the material analysis, it becomes evident that confined Ag‐based CFs within GST films are key factors for realizing selector‐memory bi‐functionality. The selector‐memory bi‐functionality is achieved through the reaction of Ag metal cations with non‐bonded Te atoms in GST film depending on field polarity. These results suggest that the Ag‐inserted GST film contributes to the development of large‐scale nonvolatile memory and neuromorphic application.
Engineering of Diffuse Structural Colors
Authors: Billiet Yannis , Chevalier Victor , Kostcheev Sergei , Kadiri Hind , Blaize Sylvain , Rumyantseva Anna , Lérondel Gilles
Published: January 2024

Nowadays, structural colors successfully replace pigment‐based ones. Most of the newly proposed solutions rely on plasmonic systems, so speaking nanosized objects, exhibiting strongly size‐dependent optical properties. As a consequence, the fabrication requires high‐precision and time‐consuming technologies. A concept dealing with sub‐micronic surface features, easily reproducible on a large scale is proposed. The designed metasurface consists of randomly distributed holes serving both as cavity resonators and scatterers. The proposed solution grants an efficient control of the spatial distribution of diffuse light and offers a large palette of vibrant colors. The interferometric model and a two‐layer angular spectrum method provide a solid description of the physical origin of the phenomenon, with a high degree of agreement between simulations and experimental data.
Extremely Low Threshold Quasi‐CW Amplified Spontaneous Emission Achieving and Its Mechanism Study
Authors: Li Yuanzhao , Ying Shian , Xia Lifen , Zhang Xiaowei , Qiao Xianfeng , Yang Dezhi , Dai Yanfeng , Sun Qian , Peng Junbiao , Ma Dongge
Published: January 2024

The development of lasing materials with weak pile‐up effect from triplet excitons, low lasing threshold, and long operational lifetime is much significant for truly continuous wave operation and electrically pumping organic lasers. However, most of organic gain media has been verified to have extreme quenching effect from triplet excitons due to its wide‐band distribution of triplet absorption spectrum. Here, it is found that the phenanthroimidazole derivatives as gain media have congenital advantages on handling triplet's issues. A very low amplified spontaneous emission (ASE) threshold of 0.56 µJ cm−2 and a long operational lifetime of 5.77 × 105 pump pulses in air atmosphere are well obtained. When increasing the pump repetition frequency from 20 Hz to 20 kHz, the operational lifetimes of the thin films have small reduction. Under a high pump repetition frequency of 200 kHz, which is quasi‐continuous wave operational regime, the PI2PhDPO thin film exhibits very low ASE threshold of 0.78 µJ cm−2 due to the tiny overlap between triplet absorption and ASE spectra.
Achieving Multicolor Anti‐Counterfeiting via Simultaneous X‐Ray and UV/Blue Excitation in Ca2YMgScSi3O12: Mn2+
Authors: Wang Xinran , Dai Heng , Li Baozhu , Xu Xuhui , Zhang Jian , Liu Daiyuan , Liu Yichun , Liu Zhichao
Published: January 2024

Optical materials have attracted much attention in anti‐counterfeiting applications due to their visualization and multi‐emission modes. However, the unit occupancy predestines the material to only monochromatic emission, inhibiting the application of optical materials in advanced information encryption. Here, a green to yellow to deep‐red phosphor is reported in a Mn2+‐activated garnet compound Ca2YMgScSi3O12: Mn2+ (CYMSS: Mn2+), originating from the abundant lattice sites occupying within the crystal structure by Mn2+ ions. Three different photoluminescence (PL) emission bands peaked at 517, 576, and 720 nm from 4T1 (G) → 6A1 (S) are observed, which are attributed to the substitution of [Sc/MgO6] octahedron and [Ca/YO8] dodecahedron sites by Mn2+ ions, respectively. Hence, tunable emissions from green to deep‐red are realized in single Mn2+ doping by switching the excitation source of ultraviolet (UV)/blue and X‐ray, which can be further regulated by varying the Mn2+ concentration. Multi‐position occupying, color‐tunable light‐emitting materials offer the possibility of more advanced optical information encryption.
A Pro‐Regenerative Supramolecular Prodrug Protects Against and Repairs Colon Damage in Experimental Colitis
Authors: DeFrates Kelsey G. , Tong Elaine , Cheng Jing , Heber‐Katz Ellen , Messersmith Phillip B.
Published: January 2024

Structural repair of the intestinal epithelium is strongly correlated with disease remission in inflammatory bowel disease (IBD); however, ulcer healing is not addressed by existing therapies. To address this need, this study reports the use of a small molecule prolyl hydroxylase (PHD) inhibitor (DPCA) to upregulate hypoxia‐inducible factor one‐alpha (HIF‐1α) and induce mammalian regeneration. Sustained delivery of DPCA is achieved through subcutaneous injections of a supramolecular hydrogel, formed through the self‐assembly of PEG‐DPCA conjugates. Pre‐treatment of mice with PEG‐DPCA is shown to protect mice from epithelial erosion and symptoms of dextran sodium sulfate (DSS)‐induced colitis. Surprisingly, a single subcutaneous dose of PEG‐DPCA, administered after disease onset, leads to accelerated weight gain and complete restoration of healthy tissue architecture in colitic mice. Rapid DPCA‐induced restoration of the intestinal barrier is likely orchestrated by increased expression of HIF‐1α and associated targets leading to an epithelial‐to‐mesenchymal transition. Further investigation of DPCA as a potential adjunctive or stand‐alone restorative treatment to combat active IBD is warranted.
Ultrasound Activated Nanobowls with Deep Penetration for Enhancing Sonodynamic Therapy of Orthotopic Liver Cancer
Authors: Lin Xiahui , Chen Shan , Su Yina , Wu Ying , Huang Linjie , Ye Qin , Song Jibin
Published: January 2024

Owing to the high penetration ability and the safety of ultrasound (US) of sonodynamic therapy (SDT), it has gained significant attention in tumor treatment. However, its therapeutic efficiency depends on the performance of the sonosensitizers. The hypoxic microenvironment and abnormal stromal matrix restrict the full potential of sonosensitizers. In this study, a US‐activated bowl‐shaped nanobomb (APBN) is designed as a novel sonosensitizer to enhance the SDT effect through various means. This enhancement strategy combines three major characteristics: relieving tumor hypoxia, amplifying bubble cavitation damage, and US‐movement‐enhanced permeation. The unique bowl‐shaped structure of APBN provides more favorable attachment sites for the generated oxygen gas bubbles. Thus, when catalase‐like APBN catalyzes endogenous hydrogen peroxide to produce oxygen, bubbles accumulate at the groove, preventing the dissipation of oxygen and increasing the number of cavitation nuclei to improve the acoustic cavitation effect. This approach differs from traditional SDT strategies because it couples the sonodynamic effect with reactive oxygen species generation and bubble cavitation damage rather than a single action. Additionally, the asymmetric bowl‐shaped structure generates a driving force under the US field, improving the distribution of sonosensitizers in the tumors. Using US and photoacoustic imaging for dual localization, these sonosensitizers can improve the accuracy of orthotopic liver tumor treatment, which presents a promising avenue for the treatment of deep tumors.
Light‐Based 3D Multi‐Material Printing of Micro‐Structured Bio‐Shaped, Conducting and Dry Adhesive Electrodes for Bioelectronics
Authors: Dominguez‐Alfaro Antonio , Mitoudi‐Vagourdi Eleni , Dimov Ivan , Picchio Matias L. , Lopez‐Larrea Naroa , de Lacalle Jon Lopez , Tao Xudong , Serrano Ruben Ruiz‐Mateos , Gallastegui Antonela , Vassardanis Nikolaos , Mecerreyes David , Malliaras George G.
Published: January 2024

In this work, a new method of multi‐material printing in one‐go using a commercially available 3D printer is presented. The approach is simple and versatile, allowing the manufacturing of multi‐material layered or multi‐material printing in the same layer. To the best of the knowledge, it is the first time that 3D printed Poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) micro‐patterns combining different materials are reported, overcoming mechanical stability issues. Moreover, the conducting ink is engineered to obtain stable in‐time materials while retaining sub‐100 µm resolution. Micro‐structured bio‐shaped protuberances are designed and 3D printed as electrodes for electrophysiology. Moreover, these microstructures are combined with polymerizable deep eutectic solvents (polyDES) as functional additives, gaining adhesion and ionic conductivity. As a result of the novel electrodes, low skin impedance values showed suitable performance for electromyography recording on the forearm. Finally, this concluded that the use of polyDES conferred stability over time, allowing the usability of the electrode 90 days after fabrication without losing its performance. All in all, this demonstrated a very easy‐to‐make procedure that allows printing PEDOT:PSS on soft, hard, and/or flexible functional substrates, opening up a new paradigm in the manufacturing of conducting multi‐functional materials for the field of bioelectronics and wearables.
Protozoan‐Derived Cytokine‐Transgenic Macrophages Reverse Hepatic Fibrosis
Authors: Chen Ying , Wang Jie , Zhou Nan , Fang Qi , Cai Haijian , Du Zhuoran , An Ran , Liu Deng , Chen Xuepeng , Wang Xinxin , Li Fangmin , Yan Qi , Chen Lijian , Du Jian
Published: January 2024

Macrophage therapy for liver fibrosis is on the cusp of meaningful clinical utility. Due to the heterogeneities of macrophages, it is urgent to develop safer macrophages with a more stable and defined phenotype for the treatment of liver fibrosis. Herein, a new macrophage‐based immunotherapy using macrophages stably expressing a pivotal cytokine from Toxoplasma gondii, a parasite that infects ≈ 2 billion people is developed. It is found that Toxoplasma gondii macrophage migration inhibitory factor‐transgenic macrophage (Mφtgmif) shows stable fibrinolysis and strong chemotactic capacity. Mφtgmif effectively ameliorates liver fibrosis and deactivates aHSCs by recruiting Ly6Chi macrophages via paracrine CCL2 and polarizing them into the restorative Ly6Clo macrophage through the secretion of CX3CL1. Remarkably, Mφtgmif exhibits even higher chemotactic potential, lower grade of inflammation, and better therapeutic effects than LPS/IFN‐γ‐treated macrophages, making macrophage‐based immune therapy more efficient and safer. Mechanistically, TgMIF promotes CCL2 expression by activating the ERK/HMGB1/NF‐κB pathway, and this event is associated with recruiting endogenous macrophages into the fibrosis liver. The findings do not merely identify viable immunotherapy for liver fibrosis but also suggest a therapeutic strategy based on the evolutionarily designed immunomodulator to treat human diseases by modifying the immune microenvironment.