bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a 3D Printed Liquid-Core Hydrogel Platform for Real-Time Carbon Nanotube Sensors: A Breakthrough in Minimally Invasive Health Monitoring
Authors: Sadak Omer , Kuss Mitchell , Shi Wen , Duan Bin , Iverson Nicole M
Published: August 2024

The need for minimally invasive, real-time, and low-cost medical sensors holds great potential to revolutionize the healthcare industry. Single-walled carbon nanotube (SWNT)-based near-infrared (nIR) sensors are a relatively new field, able to provide high-quality spatial and temporal information regarding a wide range of cellular signaling molecules, including nitric oxide (NO), and hydrogen peroxide (H2O2). However, their use for in vitro and in vivo applications has been limited due to challenges related to their compatibility with packaging or immobilization techniques. Approaches like surface immobilization on solid substrates and dialysis bag confinement are costly, unstable, and unsuitable for use in settings with limited resources. SWNT sensors have recently been implanted into a large animal model as a proof-of-concept, but the challenge of retaining SWNT is currently restricting the advancement of hydrogel technology in wearable/implantable biosensors. We have developed and optimized a 3D printed liquid-core self-healing hydrogel platform that encapsulates the (AT)15 wrapped-SWNT, a NO sensor, and studied its mechanical and optical characterizations. Notably, after 90-days at 37 °C, the fluorescence intensity exhibited a negligible decrease. Statistical analysis indicates that the change in intensity from day 1 to day 90 was statistically insignificant, highlighting the sensor's robust and stable performance over the extended testing period. A linear calibration curve was obtained when the percent quenching was plotted against the logarithm of NO concentration. Furthermore, a polyvinyl alcohol (PVA) wrapped SWNT, a non-reactive sensor, was implanted into 3D printed liquid-core hydrogel platform and no quenching was observed when it was exposed to NO. Therefore, 3D printed liquid-core hydrogel platforms offer a solution for on-site detection of small-molecule analytes, overcoming a major challenge in real-time medical diagnostics and environmental monitoring.
(Invited) Quantitative in Vitro/In Vivo Fluorescence Bioimaging with Graphene Quantum Dots
Authors: Naumov Anton V.
Published: August 2024

Graphene Quantum Dots (GQDs) are novel carbon nanomaterials consisting of few layers of partially functionalized graphitic carbon. Their nanometer-scale size together with functional groups render GQDs more water soluble and biocompatible than many other nanocarbon constructs. Like many nanocarbons, GQDs possess structure-dependent optical properties, exhibiting confinement-defined fluorescence in the visible and defect-originated emission in the near-infrared (NIR). These properties give GQDs a certain advantage for applications in therapeutic tracking, imaging, analyte detection and targeted drug/gene delivery. In addition to tracing the location of therapeutic or analyte, GOD fluorescence allows for several modes of quantitative assessment within these applications. In vitro it is utilized to evaluate relative amounts of therapeutics or analytes present within the cells at a certain time period. In vivo NIR emission of the GQDs-based sensors implanted under the skin can help detect trace quantities of analyte in the body, while their NIR fluorescence in animal organs can quantify relative therapeutic uptake over time.

The present work introduces novel studies and analytical tools exploring and enhancing such imaging modalities. Although GQD in vitro fluorescence microscopy imaging is often used to quantitate their (and payload) uptake and excretion, this method suffers from multiple discrepancies including the analysis of dead cells, cellular debris and non-internalized nanomaterials, and can be also time and resource-consuming. Our work aiming to circumvent these issues utilizes Artificial Intelligence (AI) approach to provide more accurate quantification of the uptake/excretion of the GQDs and their payload. In this application the AI algorithms developed in house do not only optimize the imaging, but also provide automated image analysis streamlining the assessment of a variety of GQD biomedical applications including therapeutic delivery and targeting. In vivo quantitative animal imaging with several different types of GQDs, from pristine to doped with rare earth metals for NIR fluorescence enhancement, is performed to evaluate GQD organ accumulation over time. Defect or dopant-originated NIR GQD fluorescence in the range of 900 – 1060 nm due to its high penetration depth can be observed from the organs of sedated live mice and utilized for GQD uptake tracking. NIR imaging of the excised organs allows for quantitative biodistribution assessment with further microscopic confirmation of the GQD content in organ tissue slices. Quantitative optical imaging and analysis presented in this work for GQDs can aid the further advancement of these novel nanomaterials in therapeutic delivery and analyte detection applications in vitro and in vivo.
(Invited) Carbon Nanodots for Improved Plant Genetic Engineering
Authors: Galeana Jesus , Demirer Gozde S
Published: August 2024

Anthropogenic climate change has made the need for more nutritious and stress-tolerant plants indisputable for providing food security. Climate change has decreased the global agricultural productivity by 21% since 1961, and will continue to drop crop yields by 7.4% for every degree-Celsius increase in temperature. CRISPR genetic engineering can enable previously inaccessible crop tolerances to meet the demand for nutritionally-balanced and high-yielding crops. However, plant biomolecule delivery and transformation are two important bottlenecks that prevent plant genetic engineering from reaching its full potential.

Nanomaterials have already shown promise to deliver genetic cargoes into plant somatic cells for transient expression of proteins1. For most applications in agriculture, however, biomolecules need to be delivered to cells that can give rise to next generation of edited plants, such as germ or stem cells. These cell types are extremely challenging to penetrate and deliver cargoes using traditional approaches, hence forcing researchers to use undifferentiated tissues to transform and go through an arduous regeneration process in tissue culture. This time consuming, inefficient, and highly species dependent approach has been a critical obstacle in plant biology and bioengineering.

We have synthesized small (~3 nm) and positively charged (+35 mV) carbon nanodots (CNDs) from glycerol and polyethyleneimine (PEI) using the microwave method. These CNDs showed high entry efficiency into plant stem cells and ability to deliver DNA cargoes into a model plant Nicotiana benthamiana without affecting stem cell viability and differentiation capability. This is a first-time demonstration of nanoparticle uptake by plant stem cells and cargo expression in these cell types. Once we perform CRISPR gene editing in these stem cells, the edited germ cells and seeds will develop automatically from the stem cells, facilitating the creation of edited and improved new plant varieties.

References:

Demirer, Gozde S., et al. "High aspect ratio nanomaterials enable delivery of functional genetic material without DNA integration in mature plants." Nature nanotechnology 14.5 (2019): 456-464.
(Invited) Deep-Brain Imaging and Modulation with Carbon and Polymeric Nanomaterials
Authors: Hong Guosong
Published: August 2024

Optical approaches to image and modulate brain activity are limited in their penetration depth in live animals, owing to the strong scattering and absorption of photons in the visible spectrum. Carbon nanotubes and carbon-based polymers, in contrast, afford unique optical properties in the second near-infrared window (NIR-II window, 1000-1700 nm) with reduced scattering and absorption by the brain. In this talk, I will present my lab’s latest work on the imaging and modulation of brain activity with carbon nanotubes and carbon-based polymeric nanoparticles in the live mouse brain. Specifically, the NIR-II window enables through-scalp imaging of cerebrovasculature and modulation of deep-brain neural activity in freely behaving animals via a minimally invasive, implant-free, and tether-free optical interface. Our development of carbon- and polymer-based deep-brain imaging and neuromodulation has been published in Nature Photonics (2014), Nature Biomedical Engineering (2017), Nature Biomedical Engineering (2022), and ACS Nano (2023).
(Invited) Low-Frequency Noise in Flexible Carbon-Nanotube Analog Circuits
Authors: Ohno Yutaka
Published: August 2024

Since flexible devices can come into close contact with the human body, they are suitable for wearable sensor applications for long-term and non-invasive monitoring of biological and physiological signals in various fields such as medical/health care and sports, among others. In order to achieve a fully flexible sensor system, various electronic circuits need to be integrated on a flexible film, including the analog frontend (AFE) and radio-frequency (RF) frontend, as well as the sensors. Recently, we have demonstrated low-voltage CNT-based analog/digital mixed-signal circuits with excellent stability and robustness against variability, including the AFE. One remaining issue with CNT-based analog circuits is low-frequency noise, which directly impacts the sensitivity of the sensor system within the frequency range of physiological signals such as ECG and EEG.

Here, we study the low-frequency noise of flexible carbon nanotube thin-film transistors and their influence on analog circuits. The low-frequency noise exhibits a typical 1/f spectrum. Inserting an interface layer between the CNT channel layer and gate insulator layer reduces Hooge's parameter of the 1/f noise. The results indicate that maintaining distance from the channel to traps in the gate oxide is important for reducing low-frequency noise.
Single-Walled Carbon Nanotube Based Field-Effect Transistors Functionalized with Odorant Receptors for Biosensing Applications
Authors: Icin Izthak , Vainer Yuri , Avnon Asaf , Gal-Oz Reshef , Bohbot Jonathan , Eini Eran
Published: August 2024

Bioelectronic detection of volatile organic compounds (VOC) has been demonstrated in a wide range of applications, with early reports focusing on environmental exogenous VOCs due to their adverse effects on human health; bacterial VOC signatures used as disease biomarkers, etc. Carbon nanotube field-effect transistors (CNT-FETs) are considered promising devices for bioelectronic detection due to their sensitivity, robustness and compatibility with microelectronic fabrication technologies. However, implementation of CNT-FETs still faces many challenges. Current VOCs detection approaches rely on separation techniques coupled with mass spectrometry, necessitating expensive equipment, labor-intensive preparation steps and trained personnel, and are not suitable for field use. Overcoming the challenges in the development of bioelectronic CNT-FET sensors holds great promise for high-throughput screening of VOCs.

The natural insect odorant receptors (ORs) are highly attractive probes, potentially allowing ultrahigh specificity for VOC biosensing. Insect ORs exhibit remarkable sensitivities and the ability to selectively detect a vast number of VOCs. We have recently developed OR-functionalized carbon nanotube field-effect transistor (FET) devices. These FET devices comprise an isolated single-walled carbon nanotube (SWCNT), serving as the conducting channel material, functionalized with multiple insect ORs. These hybrid devices are capable of transducing ligand binding into an electronic current, without amplification. The insect OR-functionalized CNT FET were applied for the detection of several markers of environmental and clinical importance including Indole, Skatole, Octen-3-ol and Nonyl-aldehyde.

We have developed a bioelectronic assay platform that contains a chip with 61 ORs-functionalized CNT-FET devices. Our unique functionalization method is based on directing the attachment of a native ORs-containing nanovesicles (which we have exogenously expressed and functionally characterized) to a generated CNT-FET point defect. Target binding-induced ionic current and conformational changes of ORs affect an electric field that modulates the device conductance.
A Multiantenna Spectrum Sensing Method Based on HFDE‐CNN‐GRU under Non‐Gaussian Noise
Authors: Li Suoping , Han Yuzhou , Gaber Jaafar , Yang Qian
Published: August 2024

In many practical communication environments, traditional feature extraction methods in spectrum sensing fail to fully exploit the information of primary users. Additionally, conventional machine learning methods have weak learning capabilities, making it difficult to maintain efficient and stable spectrum sensing performance in complex noise environments. Furthermore, non‐Gaussian noise can significantly affect the detection performance of spectrum sensing. To address these issues, this paper first proposes a feature extraction method based on Hierarchical Fuzzy Dispersion Entropy (HFDE) to better extract high‐frequency and low‐frequency information from signal samples, providing more comprehensive features for subsequent models to optimize feature extraction effectiveness. Then, a parallel model combining Convolutional Neural Networks (CNN) with Gated Recurrent Units (GRU) is constructed to enhance learning ability. While CNN extracts local features, GRU processes temporal relationships, and the features output by both are concatenated to achieve effective feature learning and temporal modeling of primary user signal data represented by HFDE. Finally, using the feature vectors output by the CNN‐GRU model, detection statistics and detection thresholds for spectrum sensing are constructed for online detection. Simulation results validate the effectiveness and robustness of this method in spectrum sensing under non‐Gaussian noise. In the presence of significant non‐Gaussian noise intensity and a signal‐to‐noise ratio of −14 dB, the detection probability can reach 97.1%. Additionally, for the detection of unknown signals, the model can still maintain a detection probability of over 90%.
DNA Barcoding of Catfishes (Order: Siluriformes) with New Records of Two Species from Eastern Nepal
Authors: Limbu Jash Hang , Rajbanshi Dipak , Khanal Laxman , Hui Wang , Adhikari Ram Chandra , Thapa Sunita , Yang Jin Quan , Li Chenhong
Published: August 2024

The freshwater bodies of Nepal host a great deal of fish diversity; however, the molecular study of Nepalese fish is still in its early stages. Conservation management tactics require knowledge of the real species composition, often impeded by descriptions of intermittent species based on traditional taxonomy. Catfish, one of the most overfished taxa on the planet, are abundant and heavily exploited in the eastern region of Nepal. Hence, actual catfish diversity in this region needs to be examined using a combined morphological and molecular DNA barcoding approach. In this study, we sequenced the cytochrome oxidase subunit I (COI) gene in Nepalese fish species for the first time and used it for molecular identification. Altogether, 99 specimens representing 29 species belonging to 21 genera and 8 families were successfully barcoded. They were found to be 98.5–100% identical to the known sequences deposited in the GenBank and BOLD databases. Of these, two species, Amblyceps arunachalense and Erethistoides sicula, were recorded for the first time in Nepal. Out of 29 species, one species was found to be Endangered, one species under Vulnerable, two species under Near Threatened, one species under Data Deficient, and 24 species under Least Concern. The intraspecific genetic distances within species ranged from 0 to 5%. The highest intraspecific genetic distances (Kimura 2‐parameter) were found among the individuals of two species, namely, E. sicula (4%) and Glyptothorax telchitta (5%), indicating the presence of putative (sub)species. The interspecific genetic distances among the catfishes in eastern Nepal ranged between 8.47% (between Glyptothorax trilineatus and G. cavia) and 26.38% (between Amblyceps arunachalense and Chaca chaca). The GC content at the 1st, 2nd, and 3rd positions of the codons was found to be 42.4%, 49.3%, and 43.8%, respectively. These findings will support future initiatives for fish resource inventory, monitoring, and management. It is also an important input to the DNA barcode library of catfish in the eastern region of Nepal.
Factors Influencing Public Attitudes and Willingness to Utilize Telepharmacy Services in the UAE
Authors: Jarab Anan S. , Al-Qerem Walid , Mukattash Tareq , Al-Azayzih Ahmad , Kharaba Zelal , Heshmeh Shrouq Abu , Al-Momani Joud , Hamdan Rama , Al Hamarneh Yazid N. , Eberhardt Judith
Published: August 2024

Background: Telepharmacy, utilizing telecommunications to dispense pharmaceutical products and deliver patient care, offers numerous benefits for both the public and pharmacists. Previous research on exploring attitudes and willingness to use telepharmacy services has primarily focused on pharmacists rather than the general population.

Aim: This study is aimed at assessing the attitudes and willingness of the United Arab Emirates (UAE) population to utilize telepharmacy services and identifying the factors influencing their inclination to use these services.

Methods: In this cross‐sectional study, a survey was distributed using convenience and snowball sampling to individuals aged 18 or older across the UAE through various social media platforms, including Twitter, Facebook, and WhatsApp. The survey domains included sociodemographics, attitudes, and readiness to utilize a telepharmacy service. A binary logistic regression analysis was conducted to investigate the variables associated with participants’ willingness to utilize telepharmacy in the future.

Results: In total, 963 individuals participated in the study. Participants showed overall positive attitudes towards telepharmacy, with 70.9% believing that telepharmacy saved time and effort. While only 32% of the participants acknowledged that numerous telepharmacy services were available for use in the UAE, most were interested in using telepharmacy services in the future (79.2%). Participants who had higher attitude scores (AOR = 1.147, 95% confidence interval [CI]: 1.11–1.18) and those who had used these services previously (AOR = 3.270, 95% CI: 1.692–6.320) were more interested in using telepharmacy services in the future.

Conclusion: Forthcoming healthcare strategies should focus on expanding the availability of telepharmacy services throughout various regions of the country. This expansion will facilitate the broader utilization of these services and ultimately contribute to improved health outcomes.
The Effect of Preoperative Anxiety on Motor and Sensory Block Duration and Effectiveness in Spinal Anesthesia
Authors: Yılmaz Yadigar , Durmayuksel Esra , Erturk Tuna , Inal Ferda Yılmaz , Yamac Dilek Metin , Ersoy Aysin
Published: August 2024

Introduction. The aim was to evaluate the effect of preoperative anxiety on the sympathetic block that developed after spinal anesthesia and therefore the duration of motor and sensory blockade. Materials and Methods. After the approval of the ethics committee, 90 patients between the ages of 18 and 55 years who were to be operated under spinal anesthesia were included in the study. Preoperative anxiety of the patients was evaluated with the Spielberger trait and State Anxiety Scale and Visual Analog Scale (VAS). The Bromage scores of the patients were followed up intermittently. Onset time of sensory block, onset time of motor block, and motor block recovery time were recorded. Cases with bradycardia and hypotension were noted. Results. No statistically significant correlation was found between the duration of motor block onset (5.81 ± 4 min), the sensory block onset time (0.89 ± 0.4 min), and the motor block recovery time (92.06 ± 36.9 min) with other variables. VAS (5.81 ± 2.5), STAI‐1 (40.4 ± 9.8), and STAI‐2 (41.69 ± 8.2) values had a statistically significant effect on the occurrence of bradycardia (14.4%). The variables of VAS, STAI‐1, STAI‐2, sensory block onset, motor block onset, and motor block recovery time were statistically significantly higher in women (mean 5.24 ± 2.4, 38.97 ± 9.9, 41.43 ± 8.7, 0.89 ± 0.42, 5.64 ± 3.82, and 88.77 ± 38.74 in males and mean 7.15 ± 2.1, 43.74 ± 8.9, 42.30 ± 7.0, 0.88 ± 0.27, 6.20 ± 4.35, and 99.70 ± 31.70 in females, respectively). Conclusion. It was observed that preoperative anxiety had no effect on motor and sensory block onset and duration.
Hematologists/Physicians Need to Be Aware of Pseudohypercalcemia in Monoclonal Gammopathy: Lessons from a Case Report
Authors: Mennens Svenja F. B. J. , Van der Spek Ellen , Ruinemans-Koerts Janneke , Van Borren Marcel M. G. J.
Published: August 2024

We present a patient at risk of misdiagnosis with multiple myeloma due to pseudohypercalcemia. Examinations showed monoclonal protein, 50% monoclonal plasma cells in bone marrow, and hypercalcemia but no osteolytic bone lesions. Follow‐up tests revealed pseudohypercalcemia, with elevated total calcium, but normal ionized calcium: a discrepancy due to calcium binding to monoclonal paraprotein (confirmed by laboratory experiments). Accordingly, the patient was diagnosed with smouldering myeloma. After 900 days, the presence of bone lesions prompted the start of treatment for myeloma. Consequently, monoclonal paraprotein levels declined and pseudohypercalcemia dissolved. Hence, ionized calcium should be measured in monoclonal gammopathies to avoid misdiagnosis.
Long-Term Survival Outcomes and Risk Factors for Axillary and Locoregional Recurrence in Japanese Patients with Sentinel Node-Positive Breast Cancer Treated in Accordance with the ACOSOG Z0011 Strategy
Authors: Oyama Yuri , Kittaka Nobuyoshi , Higuchi Ayako , Togashi Yusa , Taniguchi Azusa , Seto Yukiko , Soma Ai , Park Sungae , Okuno Jun , Watanabe Noriyuki , Matsui Saki , Ishihara Mikiya , Nishio Minako , Honma Keiichiro , Nakayama Takahiro
Published: August 2024

Introduction: In 2018, we reported the results of a study to assess the feasibility of applying the ACOSOG Z0011 criteria to Japanese patients with early-stage breast cancer (median follow-up, 3 years). Their results over the longer term can now be presented. Risk factors for axillary and locoregional recurrence in Z0011-eligible patients are unknown. Methods: Long-term survival outcomes were investigated by analyzing data from patients enrolled in the feasibility study. Data from the feasibility study patients, and from patients eligible for the Z0011 strategy after its introduction into clinical practice, were subjected to multivariate logistic regression analysis to identify risk factors for axillary and locoregional recurrence. Results: Regarding long-term outcomes for the feasibility study patients (n = 189), distant disease-free survival rates at 5 and 7 years were 90.4 ± 2.1% and 85.9 ± 2.6%, respectively, and overall survival rates at 5 and 7 years were 97.3 ± 1.2% and 95.3 ± 1.7%, respectively. Analysis of data from these patients plus the 93 who received Z0011 in clinical practice (total, n = 282) identified the following independent risk factors for axillary recurrence: absence of high axillary tangential irradiation (OR, 5.87 [95% CI, 1.09–31.35], p = 0.04) and number of positive sentinel lymph nodes (OR, 4.65 [95% CI, 1.11–19.48], p = 0.04). Only high Ki67 labeling index (OR, 5.92 [95% CI, 1.31–26.70], p = 0.02) was identified as an independent risk factor for locoregional recurrence. Conclusion: Long-term survival outcome results of the feasibility study show that the Z0011 strategy can be used to treat Japanese patients with early-stage breast cancer. Our findings regarding risk factors suggest that high axillary tangent irradiation is necessary for the prevention of axillary recurrence and that irradiation, including of the regional lymph nodes, should be considered, especially in patients with high Ki67 index values.
Prevalence of RNF213 rs112735431 Genetic Polymorphism in Non-Cardioembolic Ischemic Cerebrovascular Disease: A Cross-Sectional Study in Thai Patients
Authors: Travanichakul Suporn , Chutinet Aurauma , Kijpaisalratana Naruchorn , Snabboon Thiti , Houngngam Natnicha , Suwanwela Nijasri C.
Published: August 2024

Introduction: Moyamoya disease (MMD) and non-MMD intracranial cerebral artery stenosis (ICAS) have been linked to the RNF213 rs112735431 gene in Korean and Japanese populations. This cross-sectional study investigates the prevalence of the RNF213 rs112735431 gene in non-cardioembolic ischemic stroke (NCIS) among Thai patients. Methods: A cross-sectional investigation was conducted on patients aged 18 years or older admitted to King Chulalongkorn Memorial Hospital between June 2015 and March 2016 with acute NCIS. ICAS and extracranial carotid artery stenosis (ECAS) were assessed through computer tomography angiography or magnetic resonance angiography. Blood samples were collected, and Sanger sequencing was performed. Results: Among 234 acute NCIS cases, 113 exhibited ICAS, 12 had ECAS, 20 had both, and 89 had neither. The RNF213 rs112735431 gene variant was detected in 2 patients, both heterozygous A/G. The frequency of the RNF213 rs112735431 variant was 0.9% (2/234; 95% CI: 0–2.1%) in acute NCIS patients and 1.8% (2/113; 95% CI: 0–4.2%) in ICAS. All individuals with the RNF213 variant were males with hypertension, diabetes mellitus, dyslipidemia, and ICAS, without a family history of ischemic stroke. Conclusion: This study reveals that the RNF213 rs112735431 gene variant is uncommon among Thai NCIS patients, suggesting a discrepancy in the prevalence of this genetic variation between Thai and other Eastern Asian populations.
Evaluation of Bioequivalence and Pharmacokinetic Profiles for Topical Desonide Cream Using Chinese Skins
Authors: Sun Yuanyuan , Yang Nan , Huang Jie , Yao An , Ye Ling , Yang Shuang , Xiao Min , Zhang Xuqing , Ding Jinsong , Kuang Yun , Zhou Yali , Yang Guoping
Published: August 2024

Introduction: Skin-blanching assay has been established as a surrogate method for assessing bioequivalence of topical corticosteroids. This study aimed to apply the skin-blanching assay to evaluate the bioequivalence of a test desonide cream (T) compared with the reference Desonide® (R) using Chinese skins. Additionally, the pharmacokinetics and safety profiles were also assessed. Methods: By detecting the degree of skin blanching under different dose durations in a pilot dose-duration-response study, the area under the observed effect-time curve (AUEC) and half of the maximum effect (ED50) was calculated. Based on this, the skin color of different time points after a dose duration of ED50, D1 (0.5 × ED50), and D2 (2 × ED50) were detected as a pharmacodynamic indicator to compare between test and reference creams. Single-center, single-dose, randomized, open-label, two-cycle crossover pharmacokinetic studies were designed to make sure the exposure of tested formulationswas not higher than that of the reference formulations. Subjects experiencing adverse events (AEs) were monitored and utilized for safety analysis. Results: These studies involved 12 subjects for the dose-duration-response study, 100 subjects for the bioequivalence study, and 12 subjects for the pharmacokinetic study. The results showed that the population ED50 was 0.88 ± 0.45 h; the mean ratio of area under effective curve from 0 to 24 h (AUEC0–24h) of test and reference preparations was 0.95, with a 90% confidence interval as 88.09–101.72%, indicating the bioequivalence of the test formulation and Desonide®. The maximum plasma concentration (Cmax) and area under the concentration time curve from time 0 to the last time point (AUC0–t) of T and R were 20.8 ± 11.5 pg/mL versus 19.7 ± 10.1 pg/mL, respectively, and 451.04 ± 363.65 pgh/mL versus 541.47 ± 581.41 pgh/mL, respectively. The systemic exposure of a single dose of the test cream was not higher than that of the reference preparation. All of the volunteers experienced grade 1 AEs, suggesting that single administration of the test desonide cream is well tolerated in the Chinese healthy population. Conclusions: This study demonstrated the applicability of skin-blanching assay in Chinese skins and established the bioequivalence of test and reference desonide creams.
Acute Kidney Disease in Oncology: A New Concept to Enhance the Understanding of the Impact of Kidney Injury in Patients with Cancer
Authors: Floris Matteo , Trevisani Francesco , Angioi Andrea , Lepori Nicola , Simeoni Mariadelina , Cabiddu Gianfranca , Pani Antonello , Rosner Mitchell Howard
Published: August 2024

Background: Cancer patients are prone to developing acute kidney disease (AKD), yet this phenomenon remains understudied compared to acute kidney injury (AKI). AKD, which often develops insidiously, can cause treatment interruptions, extended hospital stays, and increased mortality. Summary: This perspective article explores the intricate relationship between AKD and cancer, focusing on prevalence, risk factors, implications for anticancer therapy, and long-term outcomes, including chronic kidney disease progression. Key Messages: To emphasize the importance of early detection and intervention, this work advocates for increased research and awareness among clinicians to improve patient outcomes and manage healthcare burdens associated with AKD in cancer patients.
Association between Constipation and the Risk of Parkinson’s Disease among Participants in the UK Biobank
Authors: Zhang Jing , Shi Mengyao , Zhang Qilu , Chen Yi , Yin Xiangyan , Wang Xiaoxiao , Zhang Yonghong
Published: August 2024

Introduction: Constipation is common in patients with Parkinson’s disease (PD), but its impact on incident PD remains uncertain. We aimed to prospectively investigate constipation symptoms and the risk of PD. Methods: Participants without PD at baseline from the UK Biobank were included in the study. Information on the regular use of laxatives, bowel movement frequency, and the frequency of hard or lumpy stools was collected. Incident PD was defined by the ICD-10 code. Cox proportional hazards models were used to assess the association between constipation symptoms and incident PD. Results: In the analysis of regular laxative use and PD, 490,797 participants were included and 2,735 incident PD were detected. The multivariable adjusted HR of PD in participants who regularly used laxatives was 1.99 (95% confidence interval [CI], 1.70–2.33) compared with those who did not. In the analysis of bowel movement frequency and hard or lumpy stools and PD, 170,017 participants were included and 519 incident PD were detected. The multivariable adjusted HRs were 2.16 (95% CI, 1.74–2.68) and 2.57 (95% CI, 2.00–3.31) for participants with a bowel movement frequency of 3–6 times/week and <3 times/week, respectively, compared with those with a bowel movement frequency of ≥7 times/week; compared with participants who never had hard or lumpy stools, multivariable adjusted HRs were 1.31 (95% CI, 1.07–1.60), 2.32 (95% CI, 1.77–3.05), and 2.94 (95% CI, 2.14–4.05) for those who sometimes had hard or lumpy stools, often had hard or lumpy stools, and most of time/always had hard or lumpy stools, respectively. Conclusions: Constipation measured by the regular use of laxatives, bowel movement frequency, and the frequency of hard or lumpy stools was significantly associated with an increased risk of incident PD.
Academic Freedom & the Politics of the University
Authors: Scott Joan Wallach
Published: August 2024

In this essay, I explore the relationship between the politics of the production of knowledge and partisan attempts to interfere with it. I argue that, despite changing historical contexts, the line between this politics (understood as contests about meaning and power) and partisanship has never been secured. That is because there is a tension inherent in knowledge production that cannot be resolved by legislation, administrative fiat, or academic punditry. Academic freedom mediates the tension but does not resolve it because knowledge production is inherently critical of prevailing norms (whether in the sciences, social sciences, or humanities)-norms whose partisans seek to defend their integrity and their truth. The tension between politics and partisanship is the state (or the fate) of democratic higher education in America.
Mating with Multi-Armed Bandits: Reinforcement Learning Models of Human Mate Search
Authors: Conroy-Beam Daniel
Published: August 2024

Mate choice requires navigating an exploration-exploitation trade-off. Successful mate choice requires choosing partners who have preferred qualities; but time spent determining one partner’s qualities could have been spent exploring for potentially superior alternatives. Here I argue that this dilemma can be modeled in a reinforcement learning framework as a multi-armed bandit problem. Moreover, using agent-based models and a sample of k = 522 real-world romantic dyads, I show that a reciprocity-weighted Thompson sampling algorithm performs well both in guiding mate search in noisy search environments and in reproducing the mate choices of real-world participants. These results provide a formal model of the understudied psychology of human mate search. They additionally offer implications for our understanding of person perception and mate choice.
A new Anthurium (Araceae) species with silver leaves from Bahia Atlantic Forest, Brazil
Authors: NADRUZ COELHO MARCUS ALBERTO , MAGNO ALEXANDRE , VALADARES RODRIGO THEÓFILO
Published: August 2024

Anthurium argyrophyllum, a new species from the Atlantic Forest is described, illustrated and its morphological affinities with other species are discussed. This species is only known from cocoa agroforests in Southern Bahia State, Brazil.
Validating the names of three species of Passiflora from the northern portion of South America
Authors: KUETHE J.R. , BERNAL HERNAN DARIO , MOLINARI MIGUEL , VECCHIA MAURIZIO
Published: August 2024

Three species of Passiflora known primarily from cultivation under popular names are here validly described maintaining the names already given: Passiflora azulitensis (Bryonioides), a species brought into cultivation from Venezuela by Miguel Molinari in the early 2000s, P. cocuyensis from Colombia by Bleddyn Wynn-Jones in 2016, and P. rogitamensis, also Colombian, by Klaas Kingma and Rob McPhail in the mid-2010s. All three species were given “naked names” referring to their locations of origin, and this paper validates those names in accordance with the International Code of Nomenclature (ICN) criteria. In this manuscript, the species are here formally described and illustrated, with comments on their morphological relationships, environmental preferesnces and phenology. A geographic distribution map is provided, and a contemporary conservation status is assigned.
Myrcia cupreiflora (Myrtaceae), a new species from the Brazilian state of Rio de Janeiro
Authors: FERNANDES THIAGO , GAEM PAULO HENRIQUE , VASCONCELOS THAIS N.C. , BOVINI MASSIMO GIUSEPPE , BRAGA JOÃO MARCELO ALVARENGA
Published: August 2024

A new species of Myrcia (Myrtaceae) from the Brazilian Atlantic Forest in the state of Rio de Janeiro is described and illustrated. The species is recognizable by its strongly bullate leaf blades, long, axillary and terminal, coppery and strigose inflorescences and calyces completely fused in the flower buds, tearing deeply vertically into 4–5 homogeneous sepals at anthesis. We herein provide a morphological description of the new species along with taxonomic notes, preliminary conservation status, illustrations, and a map of occurrence records.
Eugenia rufula (Myrtaceae), a new species from São Paulo, Brazil
Authors: BÜNGER MARIANA DE OLIVEIRA , BARRETTO EDUARDO H.P. , SOBRAL MARCOS
Published: August 2024

N/A
A new genus of the tribe Blondeliini (Diptera: Tachinidae: Exoristinae) from the Oriental Region with morphological and molecular evidence
Authors: HUANG YU-ZEN , TACHI TAKUJI
Published: August 2024

In this study a new genus of the tribe Blondeliini, Shimamyia, is established. In this genus, Shimamyia exigua comb. nov., S. orientalis comb. nov., S. taiwanensis sp. nov., and S. vietnamensis sp. nov. are described and the key to species is provided. Shimamyia exigua and S. orientalis were initially identified as members of Medinodexia Townsend but were thought to belong to an undescribed genus based on external morphology and male and female postabdomens. The present study provides comprehensive descriptions of the four species. The phylogenetic tree reconstructed from 27 blondeliine species (including two from Shimamyia) and 6 outgroup using 16S, 28S, white, and CAD genes is also provided to discuss the placement of Shimamyia. Morphological and molecular evidence support the differentiation of Shimamyia from Medinodexia while confirming its inclusion in Blondeliini. Additionally, the modified female postabdomens of the new genus and other Blondeliini members are briefly discussed.
Artificial intelligence enabled interpretation of ECG images to predict hematopoietic cell transplantation toxicity
Authors: Shaffer Brian C. , Brown Samantha , Chinapen Stephanie , Mangold Kathryn E. , Lahoud Oscar , Lopez-Jimenez Francisco , Schaffer Wendy , Liu Jennifer , Giralt Sergio , Devlin Sean , Shah Gunjan , Scordo Michael , Papadopoulos Esperanza , Landau Heather , Usmani Saad , Perales Miguel-Angel , Friedman Paul A. , Gersh Bernard J. , Attia Itzhak Zachi , Noseworthy Peter A. , Kosmidou Ioanna
Published: August 2024

Artificial intelligence (AI)–enabled interpretation of electrocardiogram (ECG) images (AI-ECGs) can identify patterns predictive of future adverse cardiac events. We hypothesized that such an approach would provide prognostic information for the risk of cardiac complications and mortality in patients undergoing hematopoietic cell transplantation (HCT). We retrospectively subjected ECGs obtained before HCT to an externally trained, deep-learning model designed to predict the risk of atrial fibrillation (AF). Included were 1377 patients (849 autologous [auto] HCT and 528 allogeneic [allo] HCT recipients). The median follow-up was 2.9 years. The 3-year cumulative incidence of AF was 9% (95% confidence interval [CI], 7-12) in patients who underwent auto HCT and 13% (10%-16%) in patients who underwent allo HCT. In the entire cohort, pre-HCT AI-ECG estimate of AF risk correlated highly with the development of clinical AF (hazard ratio [HR], 7.37; 95% CI, 3.53-15.4; P < .001), inferior survival (HR, 2.4; 95% CI, 1.3-4.5; P = .004), and greater risk of nonrelapse mortality (NRM; HR, 95% CI, 3.36; 1.39-8.13; P = .007), without increased risk of relapse. Association with mortality was only noted in allo HCT recipients, where the risk of NRM was greater. The use of cyclophosphamide after transplantation resulted in greater 90-day incidence of AF (13% vs 5%; P = .01) compared to calcineurin inhibitor–based graft-versus-host disease prophylaxis, corresponding to temporal changes in AI-ECG AF prediction after HCT. In summary, AI-ECG can inform risk of posttransplant cardiac outcomes and survival in HCT patients and represents a novel strategy for personalized risk assessment.
Unmasking of molecular players: proteomic profiling of vitreous humor in pathologic myopia
Authors: Wen Yue , Ren Chi , Zhu Li , Huang Lvzhen , Qi Huijun , Yu Wenzhen , Wang Kai , Zhao Mingwei , Xu Qiong
Published: August 2024

Background

This study aimed to identify the differentially expressed proteins in the vitreous humor (VH) of eyes with and without pathologic myopia (PM), providing insights into the molecular pathogenesis.

Methods

A cross-sectional, observational study was conducted. VH samples were collected from patients undergoing vitrectomy for idiopathic epiretinal membrane (ERM), macular hole (MH), or myopic retinoschisis (MRS). Label-free quantitative proteomic analysis identified differential protein expression, with validation using ELISA.

Results

The proteomic profiling revealed significantly higher expressions of tubulin alpha 1a (TUBA1A) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) in PM groups (MH-PM, MRS-PM) compared to controls (MH, ERM). Conversely, xylosyltransferase 1 (XYLT1), versican core protein (VCAN), and testican-2 (SPOCK2) expressions were lower in PM. ELISA validation confirmed these findings.

Conclusions

Our study provides novel insights into the molecular mechanisms of PM. The differentially expressed proteins EEF1A1, TUBA1A, XYLT1, VCAN, and SPOCK2 may play crucial roles in chorioretinal cell apoptosis, scleral extracellular matrix (ECM) synthesis, and scleral remodeling in PM. These proteins represent potential new targets for therapeutic intervention in PM, highlighting the importance of further investigations to elucidate their functions and underlying mechanisms in disease pathogenesis.
Second-line pharmacotherapy intensification after metformin monotherapy in type 2 diabetes: a nationwide register study from Finland during 2011–2022
Authors: Rättö Hanna , Kurko Terhi , Pajunen Pia , Kastarinen Helena
Published: August 2024

Background

In this nationwide register study, we examined the initiation of a second-line antidiabetic medicine (ADM) among new patients receiving regular metformin monotherapy in Finland during 2011–2022. We also reflected the second-line treatment patterns on changes in the reimbursement policy, and the national type 2 diabetes (T2D) care guidelines.

Methods

Using register data on all reimbursed ADM purchases during 2010–2022, we defined nine annual cohorts of patients initiating regular metformin monotherapy during 2011–2019, each with a three-year follow-up. Descriptive methods were used to study the patterns of metformin monotherapy and second-line intensification over time. Proportional hazards models were used to analyse the take-up of the second-line ADM.

Results

The share of new patients initiating metformin use (11–13% of all metformin users) and regular metformin use (83–85% of all new metformin users) remained stable. In all cohorts, 16–19% of the patients took up a second-line ADM (median time to intensification 1.5 years). With the 2011 cohort as reference, the highest proportion of new regular metformin users taking up a second ADM (hazard ratio 1.12. 95% confidence interval 1.07 ; 1.16, P < .0001) was in the 2019 cohort. In the 2017 cohort, the proportion of patients initiating sodium-glucose cotransporter 2 inhibitors as second-line treatment surpassed those initiating dipeptidyl peptidase-4 inhibitors. The reimbursement policy restricted the use of GLP-1-analogues.

Conclusions

Second-line treatment intensification patterns over time paralleled the changes in the reimbursement system. Thus, our findings suggest that the reimbursement policy may influence the use of ADMs in Finland.
No evidence of Bartonella infections in host-seeking Ixodes scapularis and Ixodes pacificus ticks in the United States
Authors: Bai Ying , McClung Kristin L. , Osikowicz Lynn M. , Maes Sarah , Eisen Rebecca J.
Published: August 2024

Background

Bartonella spp. infect a variety of vertebrates throughout the world, with generally high prevalence. Several Bartonella spp. are known to cause diverse clinical manifestations in humans and have been recognized as emerging pathogens. These bacteria are mainly transmitted by blood-sucking arthropods, such as fleas and lice. The role of ticks in the transmission of Bartonella spp. is unclear.

Methods

A recently developed quadruplex polymerase chain reaction (PCR) amplicon next-generation sequencing approach that targets Bartonella-specific fragments on gltA, ssrA, rpoB, and groEL was applied to test host-seeking Ixodes scapularis ticks (n = 1641; consisting of 886 nymphs and 755 adults) collected in 23 states of the eastern half of the United States and Ixodes pacificus ticks (n = 966; all nymphs) collected in California in the western United States for the presence of Bartonella DNA. These species were selected because they are common human biters and serve as vectors of pathogens causing the greatest number of vector-borne diseases in the United States.

Results

No Bartonella DNA was detected in any of the ticks tested by any target.

Conclusions

Owing to the lack of Bartonella detection in a large number of host-seeking Ixodes spp. ticks tested across a broad geographical region, our results strongly suggest that I. scapularis and I. pacificus are unlikely to contribute more than minimally, if at all, to the transmission of Bartonella spp.

Graphical Abstract
Comparison of subjective cognitive decline and polygenic risk score in the prediction of all-cause dementia, Alzheimer’s disease and vascular dementia
Authors: Trares Kira , Stocker Hannah , Stevenson-Hoare Joshua , Perna Laura , Holleczek Bernd , Beyreuther Konrad , Schöttker Ben , Brenner Hermann
Published: August 2024

Background

Polygenic risk scores (PRS) and subjective cognitive decline (SCD) are associated with the risk of developing dementia. It remains to examine whether they can improve the established cardiovascular risk factors aging and dementia (CAIDE) model and how their predictive abilities compare.

Methods

The CAIDE model was applied to a sub-sample of a large, population-based cohort study (n = 5,360; aged 50–75) and evaluated for the outcomes of all-cause dementia, Alzheimer’s disease (AD) and vascular dementia (VD) by calculating Akaike’s information criterion (AIC) and the area under the curve (AUC). The improvement of the CAIDE model by PRS and SCD was further examined using the net reclassification improvement (NRI) method and integrated discrimination improvement (IDI).

Results

During 17 years of follow-up, 410 participants were diagnosed with dementia, including 139 AD and 152 VD diagnoses. Overall, the CAIDE model showed high discriminative ability for all outcomes, reaching AUCs of 0.785, 0.793, and 0.789 for all-cause dementia, AD, and VD, respectively. Adding information on SCD significantly increased NRI for all-cause dementia (4.4%, p = 0.04) and VD (7.7%, p = 0.01). In contrast, prediction models for AD further improved when PRS was added to the model (NRI, 8.4%, p = 0.03). When APOE ε4 carrier status was included (CAIDE Model 2), AUCs increased, but PRS and SCD did not further improve the prediction.

Conclusions

Unlike PRS, information on SCD can be assessed more efficiently, and thus, the model including SCD can be more easily transferred to the clinical setting. Nevertheless, the two variables seem negligible if APOE ε4 carrier status is available.