bluuebunny/crossref_metadata_2025 huggingface dataset:
Graft‐versus‐leukaemia immunity is retained following treatment with post‐transplant cyclophosphamide alone or combined with tocilizumab in humanised mice
Authors: Sligar Chloe , Reilly Ellie , Cuthbertson Peter , Vine Kara L , Bird Katrina M , Elhage Amal , Alexander Stephen I , Sluyter Ronald , Watson Debbie
Published: March 2024

Objectives

Donor haematopoietic stem cell transplantation treats leukaemia by inducing graft‐versus‐leukaemia (GVL) immunity. However, this benefit is often mitigated by graft‐versus‐host disease (GVHD), which is reduced by post‐transplant cyclophosphamide (PTCy) alone or combined with tocilizumab (TOC) in humanised mice. This study established a preclinical humanised mouse model of GVL and investigated whether PTCy alone or combined with TOC impacts GVL immunity.

Methods

NOD‐scid‐IL2Rγnull mice were injected with 2 × 107 human peripheral blood mononuclear cells (hPBMCs) on day 0 and with 1 × 106 THP‐1 acute myeloid leukaemia cells on day 14. In subsequent experiments, mice were also injected with PTCy (33 mg kg−1) or Dulbecco's phosphate buffered saline (PBS) on days 3 and 4, alone or combined with TOC or control antibody (25 mg kg−1) twice weekly for 28 days. Clinical signs of disease were monitored until day 42.

Results

Mice with hPBMCs from three different donors and THP‐1 cells showed similar survival, clinical score and weight loss. hCD33+ leukaemia cells were minimal in mice reconstituted with hPBMCs from two donors but present in mice with hPBMCs from a third donor, suggesting donor‐specific GVL responses. hPBMC‐injected mice treated with PTCy alone or combined with TOC (PTCy + TOC) demonstrated prolonged survival compared to control mice. PTCy alone and PTCy + TOC‐treated mice with hPBMCs showed minimal hepatic hCD33+ leukaemia cells, indicating sustained GVL immunity. Further, the combination of PTCy + TOC reduced histological damage in the lung and liver.

Conclusion

Collectively, this research demonstrates that PTCy alone or combined with TOC impairs GVHD without compromising GVL immunity.
Optimization strategies and advances in the research and development of AAV‐based gene therapy to deliver large transgenes
Authors: Kolesnik Valeria V. , Nurtdinov Ruslan F. , Oloruntimehin Ezekiel Sola , Karabelsky Alexander V. , Malogolovkin Alexander S.
Published: March 2024

Adeno‐associated virus (AAV)‐based therapies are recognized as one of the most potent next‐generation treatments for inherited and genetic diseases. However, several biological and technological aspects of AAV vectors remain a critical issue for their widespread clinical application. Among them, the limited capacity of the AAV genome significantly hinders the development of AAV‐based gene therapy. In this context, genetically modified transgenes compatible with AAV are opening up new opportunities for unlimited gene therapies for many genetic disorders. Recent advances in de novo protein design and remodelling are paving the way for new, more efficient and targeted gene therapeutics. Using computational and genetic tools, AAV expression cassette and transgenic DNA can be split, miniaturized, shuffled or created from scratch to mediate efficient gene transfer into targeted cells. In this review, we highlight recent advances in AAV‐based gene therapy with a focus on its use in translational research. We summarize recent research and development in gene therapy, with an emphasis on large transgenes (>4.8 kb) and optimizing strategies applied by biomedical companies in the research pipeline. We critically discuss the prospects for AAV‐based treatment and some emerging challenges. We anticipate that the continued development of novel computational tools will lead to rapid advances in basic gene therapy research and translational studies.
Relay node selection scheme and deep sleep period for power management in energy‐harvesting wireless sensor networks
Authors: Bengheni Abdelmalek
Published: March 2024

This paper presents Relay node selection scheme and Deep sleep period for power management in Energy Harvesting Wireless Sensor Networks (RD‐EHWSN), a new energy‐saving scheme founded on asynchronous duty cycling. RD‐EHWSN reduces sensor node energy consumption and guarantees equilibrium energy use between sensor nodes in WSN with the energy harvesting capacity by adjusting these sensor nodes duty cycles more drastically and deeply by according to the estimated value of its residual energy on the basis of future‐presented harvested energy, and this is done through the use of a new proposed energy threshold policy. RD‐EHWSN also grips the benefit of transmitter initiated using the low power listening (LPL) technique with short preamble messages and uses a new relay node selection procedure to achieve the load balancing in WSN. We implemented RD‐EHWSN by using OMNeT++/MiXiM. For evaluation, we compared it with PS‐EHWSN, under multiple concurrent multihop traffic flows scenarios and scenarios in which nodes can harvest different energy harvesting rate. In all experiments, RD‐EHWSN significantly outperformed the PS‐EHWSN scheme; the results of simulation demonstrate that our scheme enhances the general yielding of WSN thru lessening the energy consumption and the mean latency, as well as raising the packet delivery ratio and the throughput. Moreover, RD‐EHWSN improves the WSN lifetime and ensures it operates in good condition in the case where the energy harvesting rate is lower by comparing it with the PS‐EHWSN scheme.
Analytical investigation of CdSe/CdS/ZnSe‐based single‐core double‐shell nanotextured vertical nanopillar array antenna for broadband photodetection applications
Authors: Baruah Smriti , Borah Janmoni , Maity Santanu , Rajasekaran Subramaniam
Published: March 2024

The photon‐trapping nanostructures greatly contributes in minimizing the light reflectance losses occurring due to air–semiconductor refractive mismatch in photodetector devices. Here we have proposed a vertically oriented CdSe/CdS/ZnSe tri material‐based multiple core–shell nanopillar array structure to act as a light‐trapping efficient antenna for broadband photodetection applications. The nanopillar structure consist of diamond shaped nanotexturization over its three layer pillar interfaces. The proposed nanotexturization over the triple‐layered nanopillar structure would feature multiple scattering mechanisms for the trapped photons enhancing their optical path length along with the defect‐free confinement of the exciton pairs. The lattice compatibility of the CdS and ZnS shell layers forms a bridge between the lattice‐mismatched CdSe core and ZnSe shell leading towards the attainment of a reduced strain as well as high photochemical stability and photo quantum efficiency. As compared to the single‐layered CdSe/ZnSe nanotextured core–shell nanopillar structure the double‐layered nanotextured CdSe/CdS/ZnSe exhibits a high photoresponsivity of 0.425 A/W and external quantum efficiency of 0.98 is attained. The obtained results exhibit that the double‐shell layered‐based nanotextured nanopillar array structure would be a well‐competent alternative as compared to the planar counterpart for next‐generation photodetector applications.
Commentary: Can an effective end‐of‐life intervention for advanced dementia be viewed as moral?
Authors: Scheeres‐Feitsma Trijntje M. , Schaafsma Petruschka , van der Steen Jenny T. , van Delden Johannes J. M.
Published: March 2024

We comment on Dr. Terman's considerations on the moral justification of ceasing assisted feeding and hydration for people with advanced dementia. The core idea of his paper is that an advance directive can solve future dilemmas regarding assisted feeding. We submit that this static instrument is unfit for the complex and dynamic nature of assessing how to deal with refusals to eat, in particular for people with dementia. It overvalues the past in relation to the present situation and leaves no room for the possibility of changing wishes. Moreover, the perspectives of professional caregivers and families are not addressed because the focus is entirely on individual autonomy in early dementia. Multiple perspectives should be considered in interpreting directives and the actual situation in light of the patient's view of life in order to realistically account for what is morally justifiable in care in advanced dementia.
Fasting to stop suffering in advanced dementia
Authors: Allen William Lawrence
Published: March 2024

Many healthcare providers think withholding food and fluids from advance dementia patients, even if those patients requested that when competent, is immoral. This means such patients suffer unnecessarily long. Patients have the ethical right when capacitated to specify that they want assistance with food and drink stopped when they have advanced dementia. Physicians should implement these patient choices when advance dementia patients can no longer feed themselves. In some states there may be legal barriers to this practice.

The perpetual placement of food and drink within reach of patients who are unable to feed themselves is futile, so there is no need for it. The best way for persons concerned about suffering in advanced dementia is to add a supplement to one's advance directive specifying under what circumstances one wants food and fluids assistance stopped.
Solitary fibrous tumor of deep parotid gland preoperatively classified as salivary gland neoplasm of uncertain malignant potential by the Milan system for reporting salivary gland cytopathology: A common diagnosis for a rare entity
Authors: Gokozan Hamza Numan , Scognamiglio Theresa
Published: March 2024

Solitary fibrous tumor (SFT) is a rare fibroblastic tumor with spindle cell morphology, which is characterized by a prominent branching vasculature and a NAB2‐STAT6 gene rearrangement. SFT may occur in any anatomical site and may involve salivary glands, including the parotid gland. We present a young female with a primary parotid SFT diagnosed as “neoplasm—Salivary gland neoplasm of uncertain malignant potential (SUMP)” per the Milan system for reporting salivary gland cytopathology by fine‐needle aspiration (FNA) with surgical pathology follow‐up. Cytomorphology of SFT is diverse and overlaps with more common entities causing a diagnostic challenge. Non‐diagnostic FNA results are not uncommon. Thankfully, the majority of SFTs involving the salivary gland can be identified as “neoplasm” on FNA. The Neoplasm‐SUMP subcategory is considered for the majority of cases, which would warrant a diagnostic excision with clear surgical margins, which is also curative in most cases. The Neoplasm‐SUMP also perfectly encompasses the neoplastic behavior of SFT, which runs on a scale from indolent to malignant.
Improving therapeutic potential in breast cancer via histone deacetylase inhibitor loaded nanofibrils
Authors: Senthilkumar Praveetha , Gogoi Bhaskar , Dhan Swati Smita , Subramani Ramesh , Pushparaj Charumathi , Mahesh Ayyavu
Published: March 2024

Epigenetic modifications play a significant role in cancer progression, making them potential targets for therapy. Histone deacetylase inhibitors have shown promise in inhibiting cancer cell growth, including in breast cancer (BC). In this research, we examined the potential of using suberoyl anilide hydroxamic acid (SAHA)‐loaded β‐lg nanofibrils as a drug delivery system for triple‐negative BC cell lines. We assessed their impact on cell cycle progression, apoptosis, levels of reactive oxygen species, and mitochondrial membrane potential in cancer cells. The combination of SAHA and β‐lg nanofibrils demonstrated enhanced efficacy in inhibiting cell growth, inducing cell cycle arrest, and promoting apoptosis (43.78%) compared to SAHA alone (40.09%). Moreover, it effectively targeted cancer cells without promoting drug resistance while using a low concentration of the nanofibrils. These findings underscore the promising potential of nanofibril‐based drug delivery systems for BC treatment.
A rare case of resection of a mucinous cystic neoplasm originating from the extrahepatic bile duct with cholangioscopic imaging
Authors: Masaki Yoshiharu , Kawakami Yujiro , Ishigami Keisuke , Murota Ayako , Shitani Masahiro , Kukita Kazuharu , Kimura Yasutoshi , Segawa Keiko , Hasegawa Tadashi , Nakase Hiroshi
Published: March 2024

A 29‐year‐old woman was admitted to our hospital for examination of obstructive jaundice and an extrahepatic bile duct lesion. Contrast‐enhanced computed tomography revealed a 20 mm cystic lesion with a thin external capsule in the common hepatic duct. Cholangioscopy revealed translucent oval masses with capillary vessels attached to the bile duct walls. The surface was mostly smooth yet partially irregular with redness, suggesting that the masses were epithelial neoplasms. Histological findings of cholangioscopy‐guided targeted biopsies of the mass showed subepithelial spindle cell proliferation with no atypical epithelium. The patient underwent an extrahepatic bile duct resection to confirm the pathological diagnosis. Immunohistochemistry of surgical specimens revealed that the spindle cells were positive for estrogen and progesterone receptors. Finally, the cystic lesion with ovarian‐like stroma was diagnosed as a mucinous cystic neoplasm with low‐grade intraepithelial neoplasia. This is the first report of cholangioscopic imaging of a biliary mucinous cyctic neoplasm. Cholangioscopic imaging can be helpful in the differential diagnosis of biliary neoplasms and in the determination of treatment strategies.
Advances and efficacy in specimen handling for endoscopic ultrasound‐guided fine needle aspiration and biopsy: A comprehensive review
Authors: Iwashita Takuji , Uemura Shinya , Ryuichi Tezuka , Senju Akihiko , Iwata Shota , Ohashi Yosuke , Shimizu Masahito
Published: March 2024

Endoscopic ultrasound‐guided fine needle aspiration and biopsy have significantly evolved since they offer a minimally invasive approach for obtaining pathological specimens from lesions adjacent to or within the intestine. This paper reviews advancements in endoscopic ultrasound‐guided fine needle aspiration and biopsy techniques and devices, emphasizing the importance of handling specimens for diagnostic accuracy. Innovations of fine needle biopsy needles with features like side holes and Franseen shapes have enhanced histological sampling capabilities. Techniques for specimen handling, including rapid on‐site evaluation and macroscopic on‐site evaluation, play pivotal roles in assessing sample adequacy, thereby influencing diagnostic outcomes. The utility of artificial intelligence in augmenting rapid on‐site evaluation and macroscopic on‐site evaluation, although still in experimental stages, presents a promising avenue for improving procedural efficiency and diagnostic precision. The choice of specimen handling technique is dependent on various factors including endoscopist preference, procedure objectives, and available resources, underscoring the need for a comprehensive understanding of each method's characteristics to optimize diagnostic efficacy and procedural safety.
Performance‐enhancing substances in sport: A scientometric review of 75 years of research
Authors: Carollo Alessandro , Corazza Ornella , Mantovani Maria , Silvestrini Nicolò , Rabin Olivier , Esposito Gianluca
Published: March 2024

The use of performance‐enhancing substances not only undermines the core values of sports but also poses significant health risks to athletes. In a fast‐evolving doping environment, where sport professionals are constantly seeking novel and illegal means to bypass doping tests, and new substances are regularly detected on the drug market, it is crucial to inform authorities with updated evidence emerging from scientific research. The current study aims to (i) outline the structure of knowledge in the literature on performance enhancers in sports (i.e., most active countries, main sources, most productive authors, and most frequently used keywords); (ii) identify the most impactful documents in the field; and (iii) uncover the main domains of research in the literature. To do so, we conducted a comprehensive scientometric analysis of the literature on doping, sourcing our data from Scopus. Our research involved a document co‐citation analysis of 193,076 references, leading to the identification of the 51 most influential documents and seven key thematic areas within the doping literature. Our results indicate that the scientific community has extensively studied the most prevalent doping classes, such as anabolic agents and peptide hormones, and little is still known about the use of contaminated supplements or other types of enhancers identified as emergent trends. Concurrently, technological advancements contributed to the development of more sophisticated doping detection techniques, using blood or urine samples. More recently, the focus has shifted towards the athlete biological passport, with research efforts aimed at identifying biomarkers indicative of doping. The dynamic nature of doping methods underlines the necessity for more robust educational campaigns, aiming at raising awareness among sports professionals and their entourage about the dangers of doping and the intricacies of its control mechanisms.
Deficits in olfactory system neurogenesis in neurodevelopmental disorders
Authors: Sweat Sean C. , Cheetham Claire E. J.
Published: March 2024

The role of neurogenesis in neurodevelopmental disorders (NDDs) merits much attention. The complex process by which stem cells produce daughter cells that in turn differentiate into neurons, migrate various distances, and form synaptic connections that are then refined by neuronal activity or experience is integral to the development of the nervous system. Given the continued postnatal neurogenesis that occurs in the mammalian olfactory system, it provides an ideal model for understanding how disruptions in distinct stages of neurogenesis contribute to the pathophysiology of various NDDs. This review summarizes and discusses what is currently known about the disruption of neurogenesis within the olfactory system as it pertains to attention‐deficit/hyperactivity disorder, autism spectrum disorder, Down syndrome, Fragile X syndrome, and Rett syndrome. Studies included in this review used either human subjects, mouse models, or Drosophila models, and lay a compelling foundation for continued investigation of NDDs by utilizing the olfactory system.
Examining co‐occurring social anxiety in cognitive behavioral therapy for eating disorders: Does it change and does it moderate eating disorder outcomes?
Authors: Ho Pheobe L. , Erceg‐Hurn David M. , McEvoy Peter M. , Campbell Bruce N. C. , Mathersul Danielle C. , Correia Helen M. , Raykos Bronwyn C.
Published: March 2024

Objective

Eating disorders (EDs) often co‐occur with social anxiety disorder (SAD). However, little research has examined the influence of SAD symptoms on ED treatment outcomes in the context of individual outpatient cognitive‐behavior therapy for eating disorders (CBT‐ED). It is plausible that SAD symptom severity could improve as a result of ED treatment, given the high overlap between EDs and SAD. We sought to test whether baseline SAD symptoms moderate early response to CBT‐ED or post‐treatment outcomes in CBT‐ED, and the degree to which SAD symptoms improve during therapy despite SAD not being an explicit treatment target.

Method

ED clients (N = 226) aged ≥16 years were treated with CBT‐ED. Outcomes were ED symptoms, clinical impairment, and SAD symptoms measured at baseline, session 5 and post‐treatment.

Results

Baseline SAD was a weak moderator of early and post‐treatment ED symptoms and impairment. SAD symptoms improved moderately over treatment among clients who started with elevated levels of SAD symptomology.

Discussion

Clients with EDs can experience good therapeutic outcomes regardless of their social anxiety severity at pre‐treatment. SAD symptoms reduced over CBT‐ED, but protocol enhancements such as exposure‐based strategies that directly target co‐occurring social‐evaluative concerns may help achieve larger reductions in SAD symptoms.

Public significance

Eating disorders often co‐occur with anxiety disorders such as social anxiety. We found people who had both social anxiety and an eating disorder benefited as much from eating disorder treatment as people who did not have social anxiety. People who were socially anxious became less anxious as a by‐product of receiving eating disorder treatment. It may be possible to reduce social anxiety further by enhancing eating disorder treatment protocols.
First documented movement of a humpback whale between the Cape Verde Islands and West Greenland
Authors: Chosson Valerie , Wyss Virginie , Jann Beatrice , Wenzel Frederick W. , Sigurðsson Guðjón Már , Simon Malene , Hansen Rikke Guldborg , Jones Lindsey S.
Published: March 2024

The endangered population of humpback whales (Megaptera novaeangliae) breeding and calving off the Cape Verde Islands (CVI) are known to migrate to feeding areas located along the eastern margin of the North Atlantic Ocean (Iceland, and Norway). Here, we report for the first time a confirmed migration of an individual humpback whale from CVI breeding ground to a western North Atlantic feeding ground of West Greenland. This individual humpback, which was photographed and identified off the coast of West Greenland in 2021, was previously documented in CVI 22 years before (1999). An annual subsistence hunt for humpbacks occurs in West Greenland and the resighting at this location with a humpback whale from CVI has strong implications for the conservation efforts of the small CVI population.
δ2H isotopic offsets in xylem water measurements under cryogenic vacuum distillation: Quantifying and correcting wood‐water hydrogen exchange influences
Authors: Younger Seth E. , Blake John , Jackson C. Rhett , Aubrey Doug P.
Published: March 2024

Stable isotopes δ18O and δ2H are used to infer vegetation water sources. In some studies, significant xylem water δ2H offsets from potential source waters have been observed. The offsets appear to be more prevalent with cryogenic vacuum distillation (CVD) of plant water. Hypothesized mechanisms for these offsets include changes during plant water uptake and transport, and methodological problems. We propose that a large portion of the offsets are due to hydrogen isotope exchange between xylem water and non‐crystalline hydroxyl groups of wood cellulose and hemicellulose during CVD. We present a method for estimating the hypothesized isotopic exchange between wood tissues and water, which is the result of Rayleigh and equilibrium fractionation. To estimate the exchange, we use published wood properties for North American tree species and isotope chemical relationships as a function of moisture content, CVD temperature and water extraction efficiency. A simple model of exchange between xylem water and hydroxyl groups captures the range of observations in studies in which CVD and non‐CVD methods were compared. To evaluate the model, we compared observed δ2H offsets (sw‐excess) values from two field datasets (90°C, n = 364, and 170°C, n = 43) to δ2H offsets estimated with our chemical model. We found good agreement between observed and estimated δ2H offsets for samples extracted at 90°C (r2 = 0.69) but not for samples extracted at 170°C (r2 = 0.20). The offset may be eliminated by increasing the extraction temperature to 229°C or by adding a standard sufficient to raise the moisture content to >150%. A correction can also be approximated by applying a theoretical calculation based on the extraction temperature, moisture content and water extraction efficiency.
Akebia fruit: A review on its extraction, phytochemicals, bioactivities and applications
Authors: Li Yanhui , Yang Zongqi , Jin Chengyong , Liu Ye , Zhang Yu , Ma Xin , Song Wei , Cai Rui , Feng Kewei , Zhao Wanni , Yuan Yahong , Yue Tianli , Sheng Qinglin
Published: March 2024

Akebia fruit is a plant used for both medicinal and edible purposes. In recent years, due to the rich phytochemical composition with bioactive effects, Akebia fruit has attracted increasing attention on its composition analysis, active ingredients identification, and product applications. For example, the protein, sugar, amino acids, and vitamin C content of the pulp is higher than that of ordinary fruit. The seeds are not only processed into edible oil, it is also rich in protein and have the potential to be developed into a new resource with beneficial effects on human health. However, the research on the understanding of Akebia as a plant fruit is relatively lacking. In this review, an overview of Akebia fruit from food perspectives, including extraction methods and phytochemicals, bioactive functions, and various applications, were summarized. Finally, based on the current status and existing challenges, the prospect and future development direction of Akebia fruit were discussed.
Obesity: the perfect storm for heart failure
Authors: Lembo Maria , Strisciuglio Teresa , Fonderico Celeste , Mancusi Costantino , Izzo Raffaele , Trimarco Valentina , Bellis Alessandro , Barbato Emanuele , Esposito Giovanni , Morisco Carmine , Rubattu Speranza
Published: March 2024

Obesity condition causes morphological and functional alterations involving the cardiovascular system. These can represent the substrates for different cardiovascular diseases, such as atrial fibrillation, coronary artery disease, sudden cardiac death, and heart failure (HF) with both preserved ejection fraction (EF) and reduced EF. Different pathogenetic mechanisms may help to explain the association between obesity and HF including left ventricular remodelling and epicardial fat accumulation, endothelial dysfunction, and coronary microvascular dysfunction. Multi‐imaging modalities are required for appropriate recognition of subclinical systolic dysfunction typically associated with obesity, with echocardiography being the most cost‐effective technique. Therapeutic approach in patients with obesity and HF is challenging, particularly regarding patients with preserved EF in which few strategies with high level of evidence are available. Weight loss is of extreme importance in patients with obesity and HF, being a primary therapeutic intervention. Sodium–glucose co‐transporter‐2 inhibitors have been recently introduced as a novel tool in the management of HF patients. The present review aims at analysing the most recent studies supporting pathogenesis, diagnosis, and management in patients with obesity and HF.
Optimal combination of right ventricular functional parameters using echocardiography in pulmonary arterial hypertension
Authors: Li Qimou , Zhang Yu , Cui Xiaopei , Lu Weida , Ji Qiushang , Zhang Mei
Published: March 2024

Aims

Novel echocardiographic parameters of right ventricular (RV) function, including speckle‐tracking‐derived, three‐dimensional, and RV–pulmonary artery coupling parameters, have emerged for the evaluation of pulmonary arterial hypertension (PAH). The relative role of these parameters in the risk stratification of PAH patients is unclear. We compared the performance of multiple RV parameters and sought to establish an optimal model for identifying the risk profile of patients with PAH.

Methods and results

Comprehensive risk assessments were performed for 70 patients with PAH. The risk profile of every patient was determined based on the guideline recommendations. Conventional parameters, including fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE), novel speckle‐tracking‐derived RV longitudinal strain (RVLS), and three‐dimensional RV ejection fraction (3D‐RVEF), were used to evaluate RV function. Pressure–strain loops were measured for the assessment of RV myocardial work, including RV global wasted work (RVGWW). RV–pulmonary artery coupling was assessed by indexing RV parameters to the estimated pulmonary artery systolic pressure (PASP). The median age was 34 (30–43) years, and 62 (88.6%) patients were female. Forty‐five patients were classified into the low‐risk group, while 25 patients were classified into the intermediate–high‐risk group. Most RV parameters could be used to determine the risk profile and exhibited significantly improved diagnostic performance after indexing to PASP (including FAC/PASP, TAPSE/PASP, and 3D‐RVEF/PASP). RVLS/PASP showed the best performance, with an area under the curve of 0.895. In multivariate analysis (Model 1), only RVGWW (>90.5 mmHg%), RVLS (> −16.7%), and TAPSE (<17.5 mm) remained significant (all P < 0.05). Model 1 outperformed every single RV parameter, with a significantly larger area under the curve (all P < 0.05). With PASP indexing in Model 2, RVLS/PASP > −0.275 [odds ratio (OR) 20.63, 95% confidence interval (CI) 4.62–92.11, P < 0.001] and RVGWW > 90.5 mmHg% (OR 6.17, 95% CI 1.37–27.76, P = 0.018) independently identified a higher risk profile. The addition of RVGWW to two models determined incremental value in identification (continuous net reclassification improvement 1.058, 95% CI 0.639–1.477, P < 0.001).

Conclusions

The combination models for RV function outperformed any single parameter in identifying the risk profile of patients with PAH. Comprehensive assessment of RV–pulmonary artery coupling using multiparametric methods is clinically meaningful in patients with PAH.
Synthesis of β‐Aryl‐α,β‐Dehydroaminophosphonates by Pd‐Catalyzed Fujiwara–Moritani C−C Coupling
Authors: Sáez Javier , Dalmau David , Sayago Francisco J. , Urriolabeitia Esteban P.
Published: March 2024

The treatment of diethyl α,β‐dehydroaminophosphonate 1 with various arenes (ArH=toluene 2 a, benzene 2 b, anisole 2 c, bromobenzene 2 d, chlorobenzene 2 e, benzyl alcohol 2 f, p‐xylene 2 g) in acetic acid (AcOH) at 120 °C for 8 h in the presence of Pd(OAc)2 (10 % mol, OAc=acetate) and AgOAc (3.4 equivalents) results in the formation of the corresponding β‐aryl derivatives E‐Ar(H)C=C(NHAc)P(O)(OEt)2 3 a–3 g. The reaction proceeds through double C−H activation (arene and alkene) and subsequent C−C oxidative coupling (Fujiwara–Moritani reaction), processes catalyzed by Pd and assisted by Ag. The obtained products 3 a–3 g are isosteric analogs of phenylalanine and are obtained with high selectivity. Thus, geometrical E‐isomers have been obtained in all studied cases, however mixtures of ortho‐/meta‐/para‐isomers are observed when the activated position in the starting arene 2 is considered.
Thermal Performance Factor of Impinging Jet‐Angled Corrugated Solar Air Heaters
Authors: Raheem Aneeq , Siddique Waseem , Waheed Khalid , Aziz Imran , Javed Irfan , Qureshi Kamran , Zaki Muhammad , Raheem Muhammad Tabish , Yaseen Muhammad Muneeb
Published: March 2024

Solar energy is a clean and sustainable source of power generation. There are various industrial and domestic applications of Solar Air Heaters (SAHs), but their low thermal efficiency poses a challenge. To improve thermal efficiency, a novel‐angled corrugated jet‐impinging channel has been proposed for the absorbing plate of SAHs. A numerical study has been performed for four different arrangements of jets, i.e., single circular, single square, 2 × 2 square, and 3 × 3 square jet array with four channels, i.e., 30°, 45°, 60°, and 90° corrugated over the Reynolds number range of 1600–2700 for the jet to target plate range of 4.9–15. It is observed that multiple jets impinging increases the heat transfer significantly. The optimization has been performed by instigating the parametric study. Flow and thermal profiles are studied. The 45° corrugated target plate with 3 × 3 multiple jet impingement, 4.9 jet‐to‐target plate distance, and 2700 Reynolds number is chosen to have the best thermal efficiency. A Thermal Performance Factor of around 8 was achieved as compared to the base case.
Evaluation of Chronic Effects of Potassium Chloride and Nickel on Survival, Growth, and Reproduction of a Unionid Mussel (Lampsilis siliquoidea)
Authors: Wang Ning , Kunz James L. , Cleveland Danielle , Dorman Rebecca A. , Steevens Jeffery A. , Raimondo Sandy , Augspurger Tom , Chris Barnhart M.
Published: March 2024

The ASTM International standard test method for freshwater mussels (E2455‐13) recommends 4‐week toxicity testing with juveniles to evaluate chronic effects on survival and growth. However, concerns remain that the method may not adequately address the sensitivity of mussels to longer term exposures (>4 weeks), particularly in relation to potential reproductive impairments. No standard method directly evaluates toxicant effects on mussel reproduction. The objectives of the present study were to (1) evaluate toxicity endpoints related to reproduction in fatmucket (Lampsilis siliquoidea) using two common reference toxicants, potassium chloride (KCl) and nickel (Ni); (2) evaluate the survival and growth of juvenile fatmucket in standard 4‐week and longer term (12‐week) KCl and Ni tests following a method refined from the standard method; and (3) compare the sensitivity of the reproductive endpoints with the endpoints obtained from the juvenile mussel tests. Reproductive toxicity tests were conducted by first exposing female fatmucket brooding mature larvae (glochidia) to five test concentrations of KCl and Ni for 6 weeks. Subsamples of the glochidia were then removed from the adults to determine three reproductive endpoints: (1) the viability of brooded glochidia; (2) the viability of free glochidia in a 24‐h exposure to the same toxicant concentrations as their mother; and (3) the success of glochidia parasitism on host fish. Mean viability of brooded glochidia was significantly reduced in the high KCl concentration (26 mg K/L) relative to the control, with a 20% effect concentration (EC20) of 14 mg K/L, but there were no significant differences between the control and any Ni treatment (EC20 > 95 µg Ni/L). The EC20s for viability of free glochidia after the additional 24‐h exposure and parasitism success were similar to the EC20s of brooded glochidia. The EC20s based on the most sensitive biomass endpoint in the 4‐week juvenile tests were 15 mg K/L and 91 µg Ni/L, similar to or greater than the EC20s from the reproductive KCl and Ni tests, respectively. When exposure duration in the juvenile tests was extended from 4 to 12 weeks, the EC20s decreased by more than 50% in the KCl test but by only 8% in the Ni test. Overall, these results indicate that a standard 4‐week test with juvenile mussels can prove effective for estimating effects in chronic exposures with different life stages although a longer term 12‐week exposure with juvenile mussels may reveal higher sensitivity of mussels to some toxicants, such as KCl. Environ Toxicol Chem 2024;43:1097–1111. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Assessment of Mitochondrial Function in the AmE-711 Honey Bee Cell Line: Boscalid and Pyraclostrobin Effects
Authors: Martinović-Weigelt Dalma , Dang Minh-Anh , Mord Alex , Goblirsch Michael J.
Published: March 2024

There is a growing concern that chronic exposure to fungicides contributes to negative effects on honey bee development, life span, and behavior. Field and caged-bee studies have helped to characterize the adverse outcomes (AOs) of environmentally relevant exposures, but linking AOs to molecular/cellular mechanisms of toxicity would benefit from the use of readily controllable, simplified host platforms like cell lines. Our objective was to develop and optimize an in vitro-based mitochondrial toxicity assay suite using the honey bee as a model pollinator, and the electron transport chain (ETC) modulators boscalid and pyraclostrobin as model fungicides. We measured the effects of short (~30 min) and extended exposures (16–24 h) to boscalid and pyraclostrobin on AmE-711 honey bee cell viability and mitochondrial function. Short exposure to pyraclostrobin did not affect cell viability, but extended exposure reduced viability in a concentration-dependent manner (median lethal concentration = 4175 µg/L; ppb). Mitochondrial membrane potential (MMP) was affected by pyraclostrobin in both short (median effect concentration [EC50] = 515 µg/L) and extended exposure (EC50 = 982 µg/L) scenarios. Short exposure to 10 and 1000 µg/L pyraclostrobin resulted in a rapid decrease in the oxygen consumption rate (OCR), approximately 24% reduction by 10 µg/L relative to the baseline OCR, and 64% by 1000 µg/L. Extended exposure to 1000 µg/L pyraclostrobin reduced all respiratory parameters (e.g., spare capacity, coupling efficiency), whereas 1- and 10-µg/L treatments had no significant effects. The viability of AmE-711 cells, as well as the MMP and cellular respiration were unaffected by short and extended exposures to boscalid. The present study demonstrates that the AmE-711-based assessment of viability, MMP, and ETC functionality can provide a time- and cost-effective platform for mitochondrial toxicity screening relevant to bees. Environ Toxicol Chem 2024;43:976–987. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Local discontinuous Galerkin method coupled with the implicit‐explicit Runge–Kutta method for the time‐dependent micropolar fluid equations
Authors: Li Mengqi , Liu Demin
Published: March 2024

In this article, the spatial local discontinuous Galerkin (LDG) approximation coupled with the temporal implicit‐explicit Runge–Kutta (RK) evolution for the micropolar fluid equations are adopted to construct the discretization method. To avoid the incompressibility constraint, the artificial compressibility strategy method is used to convert the micropolar fluid equations into the Cauchy–Kovalevskaja type equations. Then the LDG method based on the modal expansion and the implicit‐explicit RK method are properly combined to construct the expected third‐order method. Theoretically, the unconditionally stable of the fully discrete method are derived in multidimensions for triangular meshs. And the numerical experiments are given to verify the theoretical and effectiveness of the presented methods.
The effects of governance quality on renewable and nonrenewable energy consumption: An explainable decision frame
Authors: Weng Futian , Cheng Dongsheng , Zhuang Muni , Lu Xin , Yang Cai
Published: March 2024

This study analyzes the effect of governance quality (six aspects: government effectiveness; control of corruption; voice and accountability; regulatory quality; political stability and absence of violence; and rule of law) on the renewable and nonrenewable energy consumption prediction based on the SHapely Additive exPlanations method for model analysis and interpretability. The empirical findings indicate that the time‐varying contributions of six aspects of governance quality on nonrenewable (renewable) energy consumption predicting vary greatly in E‐7 and G‐7 countries. The time‐varying contribution of governance quality within countries is heterogeneous and asymmetrical, especially India (Germany) in E‐7 countries (G‐7 countries). The prediction contribution distribution of governance quality between countries is more discrete in G‐7 countries than E‐7 countries. Our results are of great importance to policymakers and investors for enhancing the renewable energy consumption level in overcoming environmental challenges based on the country itself through governance quality.
Experiments meet simulations: Understanding skeletal muscle mechanics to address clinical problems
Authors: Ateş Filiz , Röhrle Oliver
Published: March 2024

This article aims to present some novel experimental approaches and computational methods providing detailed insights into the mechanical behavior of skeletal muscles relevant to clinical problems associated with managing and treating musculoskeletal diseases. The mechanical characterization of skeletal muscles in vivo is crucial for better understanding of, prevention of, or intervention in movement alterations due to exercise, aging, or pathologies related to neuromuscular diseases. To achieve this, we suggest an intraoperative experimental method including direct measurements of human muscle forces supported by computational methodologies. A set of intraoperative experiments indicated the major role of extracellular matrix (ECM) in spastic cerebral palsy. The force data linked to joint function are invaluable and irreplaceable for evaluating individual muscles however, they are not feasible in many situations. Three‐dimensional, continuum‐mechanical models provide a way to predict the exerted muscle forces. To obtain, however, realistic predictions, it is important to investigate the muscle not by itself, but embedded within the respective musculoskeletal system, for example, a 6‐muscle upper arm model, and the ability to obtain non‐invasively, or at least, minimally invasively material parameters for continuum‐mechanical skeletal muscle models, for example, by presently proposed homogenization methodologies. Botulinum toxin administration as a treatment option for spasticity is exemplified by combining experiments with modeling to find out the mechanical outcomes of altered ECM and the controversial effects of the toxin. The potentials and limitations of both experimental and modeling approaches and how they need each other are discussed.
Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment, cerebrovascular disease and Parkinson disease: A cross sectional and longitudinal study
Authors: Rashidi‐Ranjbar Neda , Churchill Nathan W. , Black Sandra E. , Kumar Sanjeev , Tartaglia Maria C. , Freedman Morris , Lang Anthony , Steeves Thomas D. L. , Swartz Richard H. , Saposnik Gustavo , Sahlas Dametrios , McLaughlin Paula , Symons Sean , Strother Stephen , Pollock Bruce G. , Rajji Tarek K. , Ozzoude Miracle , Tan Brian , Arnott Stephen R. , Bartha Robert , Borrie Michael , Masellis Mario , Pasternak Stephen H. , Frank Andrew , Seitz Dallas , Ismail Zahinoor , Tang‐Wai David F. , Casaubon Leanne K. , Mandzia Jennifer , Jog Mandar , Scott Christopher J. M. , Dowlatshahi Dar , Hassan Ayman , Grimes David , Marras Connie , Zamyadi Mojdeh , Munoz David G. , Ramirez Joel , Berezuk Courtney , Holmes Melissa , Fischer Corinne E. , Schweizer Tom A.
Published: March 2024

Objectives

Neuropsychiatric symptoms (NPS) increase risk of developing dementia and are linked to various neurodegenerative conditions, including mild cognitive impairment (MCI due to Alzheimer's disease [AD]), cerebrovascular disease (CVD), and Parkinson's disease (PD). We explored the structural neural correlates of NPS cross‐sectionally and longitudinally across various neurodegenerative diagnoses.

Methods

The study included individuals with MCI due to AD, (n = 74), CVD (n = 143), and PD (n = 137) at baseline, and at 2‐years follow‐up (MCI due to AD, n = 37, CVD n = 103, and PD n = 84). We assessed the severity of NPS using the Neuropsychiatric Inventory Questionnaire. For brain structure we included cortical thickness and subcortical volume of predefined regions of interest associated with corticolimbic and frontal‐executive circuits.

Results

Cross‐sectional analysis revealed significant negative correlations between appetite with both circuits in the MCI and CVD groups, while apathy was associated with these circuits in both the MCI and PD groups. Longitudinally, changes in apathy scores in the MCI group were negatively linked to the changes of the frontal‐executive circuit. In the CVD group, changes in agitation and nighttime behavior were negatively associated with the corticolimbic and frontal‐executive circuits, respectively. In the PD group, changes in disinhibition and apathy were positively associated with the corticolimbic and frontal‐executive circuits, respectively.

Conclusions

The observed correlations suggest that underlying pathological changes in the brain may contribute to alterations in neural activity associated with MBI. Notably, the difference between cross‐sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences.
The Tao Hong Si Wu Decoction ameliorates diabetes‐associated cognitive dysfunction by inhibiting the formation of amyloid plaques
Authors: Cai Ming , Chen Zhen , Zhang Mengling , Xia Wenwen , Dai Wentao , Zhao Mengdie , Xie Ruonan , Ji Zhaojie , Han Lan , Peng Daiyin
Published: March 2024

Objectives

The herbs in Tao Hong Si Wu Decoction (THSWD) are beneficial in the treatment of cognitive impairment. However, the underlying mechanisms of THSWD in treating diabetes‐associated cognitive dysfunction (DACD) are not entirely explored. This study is aimed to investigate the therapeutic effects of THSWD in DACD model rats and the underlying mechanism.

Methods

Ultra‐high‐phase liquid chromatography was employed to identify the main compounds contained in the THSWD extract. DACD rat model was induced by feeding with a high‐sugar and high‐fat diet and injecting streptozotocin (35 mg/kg). DACD rats were gavaged with THSWD for 1 week. The learning and memory abilities of the rats were measured by using the Morris water maze. Western blotting was used to detect the changes in DACD rat targets. Statistical methods were used to evaluate the correlation between proteins.

Results

The results show that THSWD effectively reduced the escape latency, hippocampal neuron damage, glycosylated hemoglobin, type A1C, and blood lipid levels in DACD rats. Furthermore, DACD rats showed significantly increased amyloid precursor protein, β‐secretase, Aβ1−40, Aβ1−42, Tau phosphorylation, and advanced glycation end products (AGEs) expression. However, THSWD treatment can reverse this phenomenon.

Conclusions

THSWD can improve the learning and memory abilities of DACD rats by inhibiting the expression of AEGs‐AGE receptors pathway, which provides an experimental basis for the clinical application of THSWD. In addition, the experiment combines pharmacological and statistical methods, which offers a new perspective for the study of Chinese herbal medicine.
Functional and structural gradients reveal atypical hierarchical organization of Parkinson's disease
Authors: Wu Jinglong , Ma Lihua , Luo Di , Jin Zhaohui , Wang Li , Wang Luyao , Li Ting , Zhang Jian , Liu Tiantian , Lv Diyang , Yan Tianyi , Fang Boyan
Published: March 2024

Parkinson's disease (PD) patients exhibit deficits in primary sensorimotor and higher‐order executive functions. The gradient reflects the functional spectrum in sensorimotor‐associated areas of the brain. We aimed to determine whether the gradient is disrupted in PD patients and how this disruption is associated with treatment outcome. Seventy‐six patients (mean age, 59.2 ± 12.4 years [standard deviation], 44 women) and 34 controls participants (mean age, 58.1 ± 10.0 years [standard deviation], 19 women) were evaluated. We explored functional and structural gradients in PD patients and control participants. Patients were followed during 2 weeks of multidisciplinary intensive rehabilitation therapy (MIRT). The Unified Parkinson's Disease Rating Scale Part III (UPDRS‐III) was administered to patients before and after treatment. We investigated PD‐related alterations in the principal functional and structural gradients. We further used a support vector machine (SVM) and correlation analysis to assess the classification ability and treatment outcomes related to PD gradient alterations, respectively. The gradients showed significant differences between patients and control participants, mainly in somatosensory and visual networks involved in primary function, and higher‐level association networks (dorsal attentional network (DAN) and default mode network (DMN)) related to motor control and execution. On the basis of the combined functional and structural gradient features of these networks, the SVM achieved an accuracy of 91.2% in discriminating patients from control participants. Treatment reduced the gradient difference. The altered gradient exhibited a significant correlation with motor improvement and was mainly distributed across the visual network, DAN and DMN. This study revealed damage to gradients in the brain characterized by sensorimotor and executive control deficits in PD patients. The application of gradient features to neurological disorders could lead to the development of potential diagnostic and treatment markers for PD.