bluuebunny/crossref_metadata_2025 huggingface dataset:
Access to innovative therapies in pediatric oncology: Report of the nationwide experience in Canada
Authors: Judd Sandra , Revon‐Riviere Gabriel , Grover Stephanie A. , Deyell Rebecca J. , Vanan Magimairajan Issai , Lewis Victor A. , Pecheux Lucie , Zorzi Alexandra P. , Goudie Catherine , Santiago Raoul , Tran Thai Hoa , Abbott Lesleigh S. , Brossard Josee , Moorehead Paul , Alvi Saima , Portwine Carol , Denburg Avram , Whitlock James A. , Cohen‐Gogo Sarah , Morgenstern Daniel A.
Published: February 2024

Background

The need for new therapies to improve survival and outcomes in pediatric oncology along with the lack of approval and accessible clinical trials has led to “out‐of‐trial” use of innovative therapies. We conducted a retrospective analysis of requests for innovative anticancer therapy in Canadian pediatric oncology tertiary centers for patients less than 30 years old between 2013 and 2020.

Methods

Innovative therapies were defined as cancer‐directed drugs used (a) off‐label, (b) unlicensed drugs being used outside the context of a clinical trial, or (c) approved drugs with limited evidence in pediatrics. We excluded cytotoxic chemotherapy, cellular products, and cytokines.

Results

We retrieved data on 352 innovative therapy drug requests. Underlying diagnosis was primary CNS tumor 31%; extracranial solid tumor 37%, leukemia/lymphoma 22%, LCH 2%, and plexiform neurofibroma 6%. RAS/MAP kinase pathway inhibitors were the most frequently requested innovative therapies in 28% of all requests followed by multi‐targeted tyrosine kinase inhibitors (17%), inhibitors of the PIK3CA‐mTOR‐AKT pathway (8%), immune checkpoints inhibitors (8%), and antibody drug conjugates (8%). In 112 out of 352 requests, innovative therapies were used in combination with another anticancer agent. 48% of requests were motivated by the presence of an actionable molecular target. Compassionate access accounted for 52% of all requests while public insurance was used in 27%. Mechanisms of funding varied between provinces.

Conclusion

This real‐world data collection illustrates an increasing use of “out‐of‐trial” innovative therapies in pediatric oncology. This new field of practice warrants further studies to understand the impact on patient trajectory and equity in access to innovative therapies.
Prediction for oxaliplatin‐induced liver injury using patient‐derived liver organoids
Authors: Tatsumi Kumiko , Wada Hiroshi , Hasegawa Shinichiro , Asukai Kei , Nagata Shigenori , Ekawa Tomoya , Akazawa Takashi , Mizote Yu , Okumura Shintaro , Okamura Ryosuke , Ohue Masayuki , Obama Kazutaka , Tahara Hideaki
Published: February 2024

Background

Liver injury associated with oxaliplatin (L‐OHP)‐based chemotherapy can significantly impact the treatment outcomes of patients with colorectal cancer liver metastases, especially when combined with surgery. To date, no definitive biomarker that can predict the risk of liver injury has been identified. This study aimed to investigate whether organoids can be used as tools to predict the risk of liver injury.

Methods

We examined the relationship between the clinical signs of L‐OHP‐induced liver injury and the responses of patient‐derived liver organoids in vitro. Organoids were established from noncancerous liver tissues obtained from 10 patients who underwent L‐OHP‐based chemotherapy and hepatectomy for colorectal cancer.

Results

Organoids cultured in a galactose differentiation medium, which can activate the mitochondria of organoids, showed sensitivity to L‐OHP cytotoxicity, which was significantly related to clinical liver toxicity induced by L‐OHP treatment. Organoids from patients who presented with a high‐grade liver injury to the L‐OHP regimen showed an obvious increase in mitochondrial superoxide levels and a significant decrease in mitochondrial membrane potential with L‐OHP exposure. L‐OHP‐induced mitochondrial oxidative stress was not observed in the organoids from patients with low‐grade liver injury.

Conclusions

These results suggested that L‐OHP‐induced liver injury may be caused by mitochondrial oxidative damage. Furthermore, patient‐derived liver organoids may be used to assess susceptibility to L‐OHP‐induced liver injury in individual patients.
A case of indolent systemic mastocytosis responding to treatment with Avapritinib
Authors: Sun Terrence , Xavier Marin
Published: February 2024

Key Clinical Message

Low dose Avapritinib is a new medication that is a potential treatment option not just for advanced systemic mastocytosis, but also for the indolent form.
The use ofNibimaandImmunim, two Ghanaian herbal medicines in the management of mild COVID‐19: A case report
Authors: Boakye‐Yiadom Mavis , Yeboah Ronald , Offei‐Abrokwa David , Wilson Ekuwa Baisiwa , Darko Samuel Annang , Tamakloe Emmanuel
Published: February 2024

Key Clinical Message

NibimaandImmunimmanages mild COVID‐19 in 7 days.

Coronavirus Disease 2019 (COVID‐19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) can lead to severe complications and deaths. The search for phytotherapeutic agents to augment the fight against the current COVID‐19 pandemic is therefore of highest priority. A 52‐year‐old female with no history of chronic illness presented to our clinic facility with a 3 days loss of smell and headache which persisted after self‐medication. The patient tested positive for COVID‐19 in the SARS‐CoV‐2 Ag test as well as the Typhoid rapid antibody test. Routine laboratory tests were not remarkable. A 60 mL three times daily dose ofNibimaand 5 mL in 40 mL of warm water dose ofImmunimwere given to the patient for 7 days. Patient recovered sense of smell and regained appetite but cough although reduced persisted. She also tested negative for COVID‐19 after 7 days treatment. This case is the first documented case of COVID‐19 management with herbal medicines in Ghana. We strongly suggest a larger control trial on these products to ascertain these findings to repurpose them as viable treatments for COVID‐19.
The predictive value of laboratory parameters for no‐reflow phenomenon in patients with ST‐elevation myocardial infarction following primary percutaneous coronary intervention: A meta‐analysis
Authors: Wang LinLi , Huang ShuWei , Zhou Qiujun , Dou LiPing , Lin Dongming
Published: February 2024

To date, the predictive role of laboratory indicators for the phenomenon of no flow is unclear. Hence, our objective was to conduct a meta‐analysis to investigate the association between laboratory parameters and the risk of the no‐reflow phenomenon in patients with ST‐elevation myocardial infarction (STEMI) following primary percutaneous coronary intervention (PCI). This, in turn, aims to offer valuable insights for early clinical prediction of no‐reflow. We searched Pubmed, Embase, and Cochrane Library from the establishment of the database to October 2023. We included case‐control or cohort study that patients with STEMI following primary PCI. We excluded repeated publication, research without full text, incomplete information or inability to conduct data extraction and animal experiments, reviews, and systematic reviews. STATA 15.1 was used to analyze the data. The pooled results indicated that elevated white blood cell (WBC) count (odds ratio [OR] = 1.061, 95% confidence interval [CI]: 1.013–1.112), neutrophil count (OR = 1.324, 95% CI: 1.128–1.553), platelet (PLT) (OR = 1.002, 95% CI: 1.000–1.005), blood glucose (OR = 1.005, 95% CI: 1.002–1.009), creatinine (OR = 1.290, 95% CI: 1.070–1.555), total cholesterol (TC) (OR = 1.022, 95% CI: 1.012–1.032), d‐dimer (OR = 1.002, 95% CI: 1.001–1.004), and fibrinogen (OR = 1.010, 95% CI: 1.005–1.015) were significantly associated with increased risk of no‐reflow. However, elevated hemoglobin was significantly associated with decreased risk of no‐reflow. In conclusion, our comprehensive analysis highlights the predictive potential of various parameters in assessing the risk of no‐reflow among STEMI patients undergoing PCI. Specifically, WBC count, neutrophil count, PLT, blood glucose, hemoglobin, creatinine, TC, 
d‐dimer, and fibrinogen emerged as significant predictors. This refined risk prediction may guide clinical decision‐making, allowing for more targeted and effective preventive measures to mitigate the occurrence of no‐reflow in this patient population.
Sequences in the myosin A rod interact with UNC‐89/obscurin and the zinc‐finger protein UNC‐98 during thick filament assembly and M‐line formation in C. elegans striated muscle
Authors: Almuhanna Sarah A. , Oishi Humayra Z. , Lee Kar Men , Hoppe Pamela E.
Published: February 2024

The M‐line of striated muscle is a complex structure that anchors myosin‐containing thick filaments and also participates in signaling and proteostasis. While the physical associations among many M‐line components have been defined, the mechanism of thick filament attachment is not completely understood. In Caenorhabditis elegans, myosin A is essential for viability and forms the site of M‐line attachment at the center of the filament, whereas myosin B forms the filament arms. Using a mutant myosin A that forms ectopic filaments, we examined interactions between myosin A and M‐line proteins in intact muscle cells. Ectopic myosin A recruits the giant kinase UNC‐89/obscurin, a presumed scaffolding protein, in an interaction that requires the zinc‐finger protein UNC‐98, but not UNC‐82/NUAK, UNC‐97/PINCH, or UNC‐96. In myosin A mutants, UNC‐89/obscurin patterning is highly defective in embryos and adults. A chimeric myosin containing 169 residues of the myosin A C‐terminal rod, coincident with the UNC‐98/ZnF binding site, is sufficient for colocalization of UNC‐89/obscurin and UNC‐98/ZnF in M‐line structures whereas a myosin chimera lacking these residues colocalizes with UNC‐89/obscurin in M‐lines that lack UNC‐98. Thus, at least two myosin A rod regions contribute independently to M‐line organization. We hypothesize that these M‐line‐organizing functions correspond to the essential “filament initiation function” performed by this isoform.
Employment outcomes of adolescent and young adult cancer survivors and their partners: A Dutch population‐based study
Authors: Dankers Polle W. , Janssen Silvie H. M. , van Eenbergen Mies , Siflinger Bettina M. , van der Graaf Winette T. A. , Husson Olga
Published: February 2024

Background

The aim of this population‐based registry study was to examine the impact of cancer on employment outcomes in adolescent and young adult (AYA) survivors and their partners and associated sociodemographic and clinical characteristics.

Methods

A total of 2456 AYA cancer patients, diagnosed in 2013 and aged 18 through 39 years old, were selected from the Netherlands Cancer Registry and linked to employment data from Statistics Netherlands, from which 1252 partners of AYAs could be identified. For both patients and their partners, a control group with same age, migration background, and sex was selected. The impact (i.e., causal effect) was estimated by implementing a doubly robust difference‐in‐differences method, from 3 years before to 5 years after cancer diagnosis.

Results

Patients suffered a reduced employment probability (3.8 percentage points) and number of hours worked when employed (3.8%). This effect was larger for females, and individuals with a migration background, high tumor stage, or diagnosed with a central nervous system tumor/hematologic malignancy. In regard to employment, no significant effect could be found for the patients’ partners, although a 5.5 percentage‐point increase in employment probability was found in partners who were either unemployed or worked fewer than 400 hours.

Conclusions

A cancer diagnosis significantly affects employment outcomes of AYA patients with cancer. Patients at risk should have access to services such as job counseling to help them return into society in the best possible way. No objective impact on partners’ employment outcomes was found; however, subjective well‐being was not taken into account.

Plain Language Summary

This study estimated the causal effect of a cancer diagnosis on employment outcomes.

Adolescent and young adult cancer survivors face a reduction in both employment probability and the number of hours worked when employed.

Partners that were unemployed or worked the least number of hours a year before diagnosis had a 5.5 percentage‐point increased employment probability, but for other partners effects are small.
The 340B Program and oral specialty drugs for advanced prostate cancer
Authors: Faraj Kassem S. , Kaufman Samuel R. , Oerline Mary , Herrel Lindsey A. , Maganty Avinash , Caram Megan E. V. , Shahinian Vahakn B. , Hollenbeck Brent K.
Published: February 2024

Introduction

Expensive oral specialty drugs for advanced prostate cancer can be associated with treatment disparities. The 340B program allows hospitals to purchase medications at discounts, generating savings that can improve care of the socioeconomically disadvantaged. This study assessed the effect of hospital 340B participation on advanced prostate cancer.

Methods

The authors performed a retrospective cohort study of Medicare beneficiaries with advanced prostate cancer from 2012 to 2019. The primary outcome was use of an oral specialty drug. Secondary outcomes included monthly out‐of‐pocket costs and treatment adherence. We evaluated the effects of 1) hospital 340B participation, 2) a regional measure vulnerability, the social vulnerability index (SVI), and 3) the interaction between hospital 340B participation and SVI on outcomes.

Results

There were 2237 and 1100 men who received care at 340B and non‐340B hospitals. There was no difference in specialty drug use between 340B and non‐340B hospitals, whereas specialty drug use decreased with increased SVI (odds ratio, 0.95, p = .038). However, the interaction between hospital 340B participation and SVI on specialty drug use was not significant. Neither 340B participation, SVI, or their interaction were associated with out‐of‐pocket costs. Although hospital 340B participation and SVI were not associated with treatment adherence, their interaction was significant (p = .020). This demonstrated that 340B was associated with better adherence among socially vulnerable men.

Conclusions

The 340B program was not associated with specialty drug use in men with advanced prostate cancer. However, among those who were started on therapy, 340B was associated with increased treatment adherence in more socially vulnerable men.
Treatment and outcomes of clear cell sarcoma of the kidney: A report from the Children's Oncology Group studies AREN0321 and AREN03B2
Authors: Benedetti Daniel J. , Renfro Lindsay A. , Tfirn Ian , Daw Najat C. , Kalapurakal John A. , Ehrlich Peter F. , Khanna Geetika , Perlman Elizabeth , Warwick Anne , Gow Kenneth W. , Paulino Arnold C. , Seibel Nita L. , Grundy Paul , Fernandez Conrad V. , Geller James I. , Mullen Elizabeth A. , Dome Jeffrey S.
Published: February 2024

Background

On the fifth National Wilms Tumor Study, treatment for clear cell sarcoma of the kidney (CCSK) included combined vincristine, doxorubicin, cyclophosphamide, and etoposide (regimen I) plus radiation therapy (RT), yielding 5‐year event‐free survival (EFS) rates of 100%, 88%, 73%, and 29% for patients who had with stage I, II, III, and IV disease, respectively. In the Children’s Oncology Group study AREN0321 of risk‐adapted therapy, RT was omitted for stage I disease if lymph nodes were sampled, and carboplatin was added for stage IV disease (regimen UH‐1). Patients who had stage II/III disease received regimen I with RT.

Methods

Four‐year EFS was analyzed for patients enrolled on AREN0321 and on those enrolled on AREN03B2 who received AREN0321 stage‐appropriate chemotherapy.

Results

Eighty‐two patients with CCSK enrolled on AREN0321, 50 enrolled on AREN03B2 only. The 4‐year EFS rate was 82.7% (95% confidence interval [CI], 74.8%–91.4%) for AREN0321 and 89.6% (95% CI, 81.3%–98.7%) for AREN03B2 only (p = .28). When combining studies, the 4‐year EFS rates for patients who had stage I (n = 10), II (n = 47), III (n = 65), and IV (n = 10) disease were 90% (95% CI, 73.2%–100.0%), 93.4% (95% CI, 86.4%–100.0%), 82.8% (95% CI, 74.1%–92.6%), and 58.3% (95% CI, 34%–100.0%), respectively. There were no local recurrences among seven patients with stage I disease who were treated without RT. One stage I recurrence occurred in the brain, which was the most common site of relapse overall. Among patients with local stage III tumors, neither initial procedure type, margin status, nor lymph node involvement were prognostic.

Conclusions

Patients with stage I CCSK had excellent outcomes without local recurrences when treated without RT. Patients with stage IV disease appeared to benefit from a carboplatin‐containing regimen, although their outcomes remained unsatisfactory. Further research is needed to improve outcomes for patients with advanced‐stage disease (ClinicalTrials.gov identifiers NCT00335556 and NCT00898365).
The Hydrogen Evolution Activity of BaZrS3, BaTiS3, and BaVS3 Chalcogenide Perovskites
Authors: Humphrey Nicholas , Tsung Alicia , Singh Shantanu , Irshad Ahamed , Zhao Boyang , Narayan Sri , Ravichandran Jayakanth , Mallikarjun Sharada Shaama
Published: February 2024

Chalcogenide perovskites are a class of materials with electronic and optoelectronic properties desirable for solar cells, infrared optics, and computing. The oxide counterparts of these chalcogenides have been studied extensively for their electrocatalytic and photoelectrochemical properties. As chalcogenide perovskites are more covalent, conductive, and stable, we hypothesize that they are more viable as electrocatalysts than oxide perovskites. The goal of this synthetic, experimental, and computational study is to examine the hydrogen evolution reaction (HER) activity of three Barium‐based chalcogenides in perovskite and related structures: BaZrS3, BaTiS3, and BaVS3. Potential energy surfaces for hydrogen adsorption on surfaces of these materials are calculated using density functional theory and the computational hydrogen electrode model is used to contrast overpotentials with experiment. Although both experiments and computations agree that BaVS3 is the most active of the three materials, high overpotentials of these materials make them less viable than platinum for HER. Our work establishes a framework for future studies in the chemical and electrochemical properties of chalcogenide perovskites.
Artificial Antigen‐Presenting Cell Fabrication for Murine T Cell Expansion
Authors: Omotoso Mary O. , Lanis Mara R. , Schneck Jonathan P.
Published: February 2024

Antigen‐presenting cells (APCs), such as dendritic cells and macrophages, have a unique ability to survey the body and present information to T cells via peptide‐loaded major histocompatibility complexes (signal 1). This presentation, along with a co‐stimulatory signal (signal 2), leads to activation and subsequent expansion of T cells. This process can be harnessed and utilized for therapeutic applications, but the use of patient‐derived APCs can be complex and inefficient. Alternatively, artificial APCs (aAPCs) provide a simplified method to achieve T cell activation by presenting the two necessary stimulatory signals. This protocol describes the utilization of magnetic nanoparticles and stimulatory proteins to create aAPCs that can be employed for activating and expanding antigen‐specific T cells for both basic and translational immunology and immunotherapy studies. © 2024 Wiley Periodicals LLC.

Basic Protocol 1: Protein and particle modification for aAPC fabrication

Basic Protocol 2: aAPC validation by immunolabeling of conjugated protein

Support Protocol 1: Quantification of aAPC stock concentration

Basic Protocol 3: Determination of aAPC usage for murine CD8+ T cell activation

Support Protocol 2: Isolation of murine CD8+ T cells
Cold Sintering Enables the Reprocessing of LLZO‐Based Composites
Authors: Lan Yi‐Chen , Ghasemi Masoud , Hall Shelby L. , Fair Ryan A. , Maranas Christina , Shi Rui , Gomez Enrique D.
Published: February 2024

All‐solid‐state batteries have the potential for enhanced safety and capacity over conventional lithium ion batteries, and are anticipated to dominate the energy storage industry. As such, strategies to enable recycling of the individual components are crucial to minimize waste and prevent health and environmental harm. Here, we use cold sintering to reprocess solid‐state composite electrolytes, specifically Mg and Sr doped Li7La3Zr2O12 with polypropylene carbonate (PPC) and lithium perchlorate (LLZO−PPC−LiClO4). The low sintering temperature allows co‐sintering of ceramics, polymers and lithium salts, leading to re‐densification of the composite structures with reprocessing. Reprocessed LLZO−PPC−LiClO4 exhibits densified microstructures with ionic conductivities exceeding 10−4 S/cm at room temperature after 5 recycling cycles. All‐solid‐state lithium batteries fabricated with reprocessed electrolytes exhibit a high discharge capacity of 168 mA h g−1 at 0.1 C, and retention of performance at 0.2 C for over 100 cycles. Life cycle assessment (LCA) suggests that recycled electrolytes outperforms the pristine electrolyte process in all environmental impact categories, highlighting cold sintering as a promising technology for recycling electrolytes.
Translating the regulatory landscape of medical devices to create fit‐for‐purpose artificial intelligence (AI) cytometry solutions
Authors: Bogdanoski Goce , Lucas Fabienne , Kern Wolfgang , Czechowska Kamila
Published: February 2024

The implementation of medical software and artificial intelligence (AI) algorithms into routine clinical cytometry diagnostic practice requires a thorough understanding of regulatory requirements and challenges throughout the cytometry software product lifecycle. To provide cytometry software developers, computational scientists, researchers, industry professionals, and diagnostic physicians/pathologists with an introduction to European Union (EU) and United States (US) regulatory frameworks. Informed by community feedback and needs assessment established during two international cytometry workshops, this article provides an overview of regulatory landscapes as they pertain to the application of AI, AI‐enabled medical devices, and Software as a Medical Device in diagnostic flow cytometry. Evolving regulatory frameworks are discussed, and specific examples regarding cytometry instruments, analysis software and clinical flow cytometry in‐vitro diagnostic assays are provided. An important consideration for cytometry software development is the modular approach. As such, modules can be segregated and treated as independent components based on the medical purpose and risk and become subjected to a range of context‐dependent compliance and regulatory requirements throughout their life cycle. Knowledge of regulatory and compliance requirements enhances the communication and collaboration between developers, researchers, end‐users and regulators. This connection is essential to translate scientific innovation into diagnostic practice and to continue to shape the development and revision of new policies, standards, and approaches.
Metastatic upper tract urothelial carcinoma with nest‐like features presenting as malignant pleural effusion
Authors: Arienzo Francesca , Valenti Alessandra , Ricci Paolo , Ascoli Valeria
Published: February 2024

Metastatic urothelial carcinoma is a rare cause of pleural effusions. We report a case of urothelial carcinoma of the upper urinary tract in an oldest‐old male patient, a smoker, with situs inversus totalis, that presented uniquely with malignant pleural effusion at presentation without evidence of a primary tumor on imaging. Cytological smears of the massive left pleural effusion revealed epithelioid neoplastic cells arranged in short cords, small‐to‐large clusters, and raspberry‐like morules, mimicking mesothelioma; cell block preparations highlighted the presence of tubules and nest‐like structures. The tumor cells showed a high nuclear‐to‐cytoplasmic ratio, nuclear grooves, and mitotic figures. Cytomorphologic features coupled with the immunophenotype of neoplastic cells (p63, GATA3, and uroplakin II positive) allowed the diagnosis of metastatic urothelial carcinoma and a possible nested subtype. These findings were supported by a total body computed tomography (CT) showing no evidence of a mass in the bladder or elsewhere in the urinary tract but a concentric parietal thickening of the proximal left ureter, suggesting malignancy. To our knowledge, a malignant effusion as a primary manifestation of urothelial carcinoma with nest‐like features originating in the upper urinary tract has never been described previously. Our case focuses on the value of cell block in the working‐up of neoplastic effusions by revealing the architectural pattern of an uncommon malignancy and the correlation between cytopathology and imaging gross findings to reach an accurate diagnosis.
Network pharmacology analysis and experimental verification of the antitumor effect and molecular mechanism of isocryptomerin on HepG2 cells
Authors: Cao Jing‐Long , Li Shu‐Mei , Tang Yan‐Jun , Hou Wen‐Shuang , Wang An‐Qi , Li Tian‐Zhu , Jin Cheng‐Hao
Published: February 2024

Isocryptomerin (ISO) is a flavonoid isolated from the natural medicine Selaginellae Herba, which has various pharmacological activities. This study investigated the antitumor effect and underlying molecular mechanism of ISO on hepatocellular carcinoma (HCC) HepG2 cells. The cell viability assay revealed that ISO has a considerable killing effect on HCC cell lines. The apoptosis assay showed that ISO induced mitochondria‐dependent apoptosis through the Bad/cyto‐c/cleaved (cle)‐caspase‐3/cleaved (cle)‐PARP pathway. The network pharmacological analysis found 13 key target genes, and epidermal growth factor receptor (EGFR), AKT, mitogen‐activated protein kinase (MAPK), and reactive oxygen species (ROS) signaling pathways were strongly associated with ISO against HCC. Further verification of the results showed that ISO induced apoptosis by increasing p‐p38 and p‐JNK expression and decreasing p‐EGFR, p‐SRC, p‐ERK, and p‐STAT3 expression. Furthermore, ISO induced G0/G1 phase arrest by downregulating p‐AKT, Cyclin D, and CDK 4 expression and upregulating p21 and p27 expression in HepG2 cells. Moreover, ISO inhibited HepG2 cell migration by decreasing p‐GSK‐3β, β‐catenin, and N‐cadherin expression and increasing E‐cadherin expression. Additionally, ISO promoted ROS accumulation in HepG2 cells, and ISO‐induced apoptosis, arrest cell cycle, and inhibition of migration were reversed by an ROS scavenger, N‐acetyl‐
l‐cysteine. Overall, ISO induced cell apoptosis and cell cycle arrest and inhibited cell migration by ROS‐mediated EGFR, AKT, and MAPK signaling pathways in HepG2 cells.
Phenotypic plasticity in mass loss during chick rearing in the European starling (Sturnus vulgaris)
Authors: Hodinka Brett L. , Williams Tony D.
Published: February 2024

It has long been recognized that mass loss during breeding could be adaptive (e.g., by ameliorating the costs of increased parental activity). However, many studies still commonly interpret mass loss as evidence of “stress” or a cost of reproduction (i.e., a negative effect of high workload during chick provisioning). Despite several studies reporting evidence in support of both hypotheses, the ecological and/or life‐history contexts under which mass loss may be viewed as a “cost” or an adaptive strategy are still unclear. Here, we used a long‐term dataset from a breeding population of European starlings (Sturnus vulgaris) to investigate natural annual and individual variation in body mass and mass loss and to test whether mass loss during chick rearing represents a phenotypically plastic trait that varies predictably in relation to ecological context and individual quality. While there was significant annual variation in incubation mass, chick‐rearing mass, and mass change, there were no systematic relationships between mass loss and current breeding success or future fecundity and survival. In addition, we found no evidence of intra‐annual repeatability of mass loss between first and second broods ( = .00) but moderate interannual repeatability of mass loss (R = .61) during first broods, suggesting differences in mass loss under different selective pressures. However, we found no covariation between residual intra‐individual variation in mass loss for first broods and other reproductive or life‐history traits. We therefore found no support for the idea that mass loss reflects “reproductive stress” in our system: there were no negative relationships between mass loss and either current or future reproduction and survival (local return rate). Our results are consistent with mass loss being an individually plastic trait, with individuals using mass loss to “level the playing field” and individually optimize reproductive effort and fitness within their specific ecological context and relative to their individual quality for a given breeding attempt.
Microparticles from dental calculus disclose paleoenvironmental and palaeoecological records
Authors: D'Agostino Alessia , Di Marco Gabriele , Rolfo Mario Federico , Alessandri Luca , Marvelli Silvia , Braglia Roberto , Congestri Roberta , Berrilli Federica , Fuciarelli Maria Felicita , Ferracci Angelica , Canini Antonella , Gismondi Angelo
Published: February 2024

Plants have always represented a key element in landscape delineation. Indeed, plant diversity, whose distribution is influenced by geographic/climatic variability, has affected both environmental and human ecology. The present contribution represents a multi‐proxy study focused on the detection of starch, pollen and non‐pollen palynomorphs in ancient dental calculus collected from pre‐historical individuals buried at La Sassa and Pila archaeological sites (Central Italy). The collected record suggested the potential use of plant taxa by the people living in Central Italy during the Copper‐Middle Bronze Age and expanded the body of evidence reported by previous palynological and palaeoecological studies. The application of a microscopic approach provided information about domesticated crops and/or gathered wild plants and inferred considerations on ancient environments, water sources, and past health and diseases. Moreover, the research supplied data to define the natural resources (e.g., C4‐plant intake) and the social use of the space during that period. Another important aspect was the finding of plant clues referable to woody habitats, characterised by broad‐leaved deciduous taxa and generally indicative of a warm‐temperate climate and grassy vegetation. Other unusual records (e.g., diatoms, brachysclereids) participated in defining the prehistoric ecological framework. Thus, this work provides an overview on the potential of the human dental calculus analysis to delineate some features of the ancient plant ecology and biodiversity.
Subarachnoid haemorrhage‐induced reversible cardiac dysfunction: time course and potential mechanisms
Authors: Xiao Yichao , Lai Xin , Wang Zhuo , Wang Songyun , Wu Zhihong , Liu Qiming , Chen Mingxian , Zhou Shenghua
Published: February 2024

Aims

Cardiac dysfunction is commonly observed in patients with subarachnoid haemorrhage (SAH). However, the specific timeline of cardiac remodelling and the underlying mechanisms responsible for this effect following SAH remain unknown. This study aims to explore the impact of SAH on cardiac dysfunction and its potential mechanisms over time.

Methods and results

In Protocol 1, we investigated cardiac function and potential mechanisms in a Sprague‐Dawley rat model of SAH at six time points (baseline and Days 1, 3, 7, 14, and 28) while exploring the underlying mechanisms. Our assessments included the haemodynamic profile, echocardiography, and the concentrations of plasma biomarkers at various time points post‐SAH. We determined neuropeptide Y (NPY) 1–5 receptor protein expression levels through western blotting. In Protocol 2, we administered an NPY1 receptor antagonist to evaluate the effects of cardiac dysfunction induced by SAH on Day 3. In Protocol 1, SAH gradually provoked cardiac systolic dysfunction during the acute phase, reaching its peak on Day 3 without concurrent alterations in wall thickness. However, no significant changes were observed from Days 14 to 28 compared with Day 0. The changes in cardiac dysfunction were consistent with myocardial injury, inflammatory biomarkers, and NPY levels. SAH resulted in a heightened heart rate and systolic blood pressure, correlating with elevated epinephrine and norepinephrine levels. In Protocol 2, the administration of the NPY1 receptor antagonist effectively ameliorated cardiac dysfunction.

Conclusions

SAH induces transient cardiac dysfunction in the acute phase, and the underlying mechanisms for this response involve the NPY–NPY1 receptor pathway, otherwise known as catecholamines.
Is pain ever acceptable? A qualitative exploration concerning adult perceptions of chronic pain
Authors: Kahtan Hanaa , Jordan Abbie , Forget Patrice
Published: February 2024

Background

Although the challenges of living with chronic pain are widely documented within existing literature, to our knowledge, the acceptability of pain for people living with persistent pain, has not been fully explored. The current study aims to explore what ‘acceptable pain’ means to adults living with chronic non‐cancer pain (CPCP).

Methods

A total of 117 participants (aged 21 to 77 years) worldwide were recruited using opportunity sampling. Participants completed an online qualitative survey. Qualitative analysis of the data used inductive reflexive thematic analysis.

Results

Two themes were generated. The first theme—‘I grin and bear it’, described participants' desire and drive to push through their pain to live their daily lives to the best of their ability. Contrastingly, the second theme—‘Thriving versus surviving’, placed greater importance on leading meaningful and happy lives despite living with chronic pain. The acceptability of pain was found to be influenced by various factors including, but not limited to, pain severity, mental health, functionality, productivity and quality of life.

Conclusions

It can be difficult to identify when a clinically significant change in pain has occurred from numerical pain rating scales. We have identified two themes and a number of factors influencing the acceptability of pain. Understanding individuals' unique perceptions of what constitutes ‘acceptable pain’ is crucial for clinicians when assessing and managing chronic pain. Pain is a highly subjective experience, and what one person considers acceptable may differ significantly from another person's perspective. Recommendations to improve healthcare services for adults living with CNCP are proposed and directions for future research are explored.

Significance

Adults with CNCP have unique experiences of living with and managing their chronic pain. CNCP was found to affect biological, psychological, and social aspects of an individual's life. The acceptability of pain exists on a continuum where adjacent parts are not noticeably different from each other, but the extremes of the continuum appear very distinct. The acceptability of pain is determined by the different factors that influence an individuals' ability to function on a day‐to‐day basis as well as their quality of life. While acceptable pain and manageable pain represent distinct aspects of the pain experience, the relationship between them is complex and plays a crucial role in how individuals cope with and adapt to chronic pain.
Facile preparation of a conjugated polymer‐based biosensor for glucose monitoring
Authors: Bulut Umut , Cevher Şevki Can , Sayın Vuslat Öykü , Özbek Sevgi Sarıgül , Altın Nevra , Çırpan Ali , Söylemez Saniye
Published: February 2024

Diabetes is an important public health problem all over the world that affects the quality of life, and its late diagnosis leads to serious complications such as stroke, blindness, limb amputations, and kidney failure. Fabrication of economical and user‐friendly biosensor systems allows the rapid and early detection of prediabetes and type 2 diabetes. Accordingly, a novel, amino‐functionalized, conjugated, alternating polymer was synthesized, characterized, and coated on a glassy carbon electrode (GCE) to be used as an immobilization platform for the glucose oxidase (GOx) enzyme. The decline in oxygen level due to the enzymatic reaction at a potential of −0.7 V vs. silver/silver chloride (Ag/AgCl) is screened as a biosensor response. The proposed biosensor displayed high selectivity and specificity for glucose with a broad linear range, a low detection limit, good reproducibility and repeatability, and a long shelf life. Surface modifications were characterized using cyclic voltammetry (CV) and field emission scanning electron microscopy (FE‐SEM) techniques. The real‐life sample application of the constructed biosensor to determine the glucose amount was performed in human serum.
Efficiency Improvement of Lead‐Free La2NiMnO6‐Based Double Perovskite Solar Cells Using Numerical Simulation
Authors: Rehman Ubaid ur , Almufarij Rasmiah S. , Sahar Kashaf ul , Ashfaq Arslan , Saad H.‐E. M. Musa , Alsubhe Emaan , Albeydani Ohood , Alghamdi Shoug M. , Mahmood Khalid , Wang Chun‐Ming
Published: February 2024

In this work, the efficiency of lead‐free La2NiMnO6 (LNMO)‐based double perovskite solar cells is optimized using solar cell capacitance simulator (SCAPS‐1D). Herein, the device performance is boosted by using different combinations of electron‐transport layers, hole‐transport layers, absorber layer thickness, acceptor doping density, acceptor defect density, and bandgap tuning, and by modifying the electron affinity. To make the device more realistic, the performance of the proposed device is carefully modified in the presence of interface defect density ≈10−13 cm−3, series resistance ≈1 Ω cm2, and shunt resistance ≈6000 Ω cm2, respectively. From the findings, the optimized device exhibits a record open‐circuit voltage = 1.23 V, short‐circuit current density = 27.18 mA cm−2, fill factor = 87.14%, and power conversion efficiency = 29.20% for FTO/SnO2/LNMO/MoO3/Au configuration. Finally, the device performance is tested under different working temperatures, and 300 K is found as the best temperature for the device.
Nanoflowers of Ternary Cobalt–Copper–Manganese Oxide as an Efficient Electrocatalyst for Oxygen Evolution Reaction
Authors: Raghav Jyoti , Rosaiah P. , Al‐Asbahi Bandar Ali , Roy Soumyendu
Published: February 2024

Oxygen evolution reaction (OER) is an integral step in the water‐splitting process. Hence, to promote OER, efficient catalysts are required to lower the energy barriers at the electrode/electrolyte interface. Low‐cost and highly active catalysts are in great demand. Herein, a ternary metal oxide, CoCuMnOx, synthesized by a facile hydrothermal method is reported, which possesses excellent catalytic ability for OER in alkaline electrolytes. The nanoscale morphology of the catalyst with flower‐like nanostructures is instrumental in increasing the electrochemical surface area of the electrode. The presence of multivalent ions and the incorporation of copper greatly enhance the electrochemical properties of the catalysts. The catalysts typically demonstrate an overpotential value of 220 mV for achieving 10 mA cm−2 current density and a Tafel slope of 73 mV dec−1. The catalysts demonstrate good stability with minimal degradation in OER activity even after 20 h of chronopotentiometry test. For practical applications, this low‐cost material holds great potential.
From non‐doped to dopable: The impact of methoxy functionalization on doping and thermoelectric properties of conjugated polymers
Authors: Lee Hansol , Ayuningtias Landep , Kim Hoimin , Lee Jaehoon , Lee Jiyun , Kim Min‐Jae , Lee Dongki , Weon Byung Mook , Park Dong‐Am , Park Nam‐Gyu , Son Sung Yun , Kim Junki , Kim Yun‐Hi , Kang Boseok
Published: February 2024

The introduction of alkoxy side chains into the backbone of conjugated polymers is an effective way to change their properties. While the impact on the structure and optoelectronic properties of polymer thin films was well‐studied in organic solar cells and transistors, limited research has been conducted on their effects on doping and thermoelectric properties. In this study, the effects of methoxy functionalization of conjugated backbones on the doping and thermoelectric properties are investigated through a comparative study of diketopyrrolopyrrole‐based conjugated polymers with and without methoxy groups (P29DPP‐BTOM and P29DPP‐BT, respectively). Methoxy‐functionalization significantly enhances doping efficiency, converting undopable pairs to dopable ones. This dramatic change is attributed to the structural changes in the polymer film caused by the methoxy groups, which increases the lamellar spacing and facilitates the incorporation of dopants within the polymer crystals. Moreover, methoxy‐functionalization is advantageous in improving the Seebeck coefficient and power factor of the doped polymers, because it induces a bimodal orientational distribution in the polymer, which contributes to the increased splitting of Fermi and charge transport levels. This study demonstrates the impact of methoxy‐functionalization of a conjugated polymer on doping behavior and thermoelectric properties, providing a guideline for designing high‐performance conjugated polymers for thermoelectric applications.

image
Photocatalytic degradation of oxytetracycline using ZnO catalyst
Authors: Yildiz Sayiter , Canbaz Gamze Topal , Mihçiokur Hamdi
Published: February 2024

In the present study, the degradation of oxytetracycline (OTC) under ultraviolet (UV) light in the presence of ZnO catalyst was investigated, and optimum parameters for degradation efficiency were determined. Different pH values, ZnO dosages, reaction times, OTC concentrations, and UV lights were used in this study. The optimum conditions found were as follows: pH 4, ZnO 1 g L−1, reaction time 25 min, and OTC concentration 10 mg L−1. Degradation efficiency was 42.1%, 76%, 70.7%, and 61.7% for ZnO and photocatalytic (for UV‐A, UV‐B, and UV‐C) degradation at optimal conditions, respectively. The resulting products after the photocatalytic oxidation of OTC were determined in the study. To identify the toxicity of degradation products and OTC, the lowest LC 50 (50% lethal concentration) and EC 50 (50% effective concentration) values were found. The resulting ethanamine, 2‐(2,6‐dimethylphenoxy)‐N‐methyl‐ by‐products were observed to be more toxic than OTC. Furthermore, it was seen that isopropoxy carbamic acid, ethyl ester by‐products were formed, whose presence is environmentally risky for aquatic environments due to their low EC50 values.
Feasibility and utilization of a national virtual EEG course for Canadian residents and fellows
Authors: Shock Maria , Cerga Kristal , RamachandranNair Rajesh , Reid Aylin , Bui Esther , Kobayashi Eliane , Jones Kevin
Published: February 2024

Objective

Electroencephalography (EEG) is an essential tool for the diagnosis and management of epilepsy. There is a gap in EEG education for residents in Canadian neurology programs as EEG is only listed in the training requirements as a procedural skill. There is currently no standardized EEG curriculum among Canadian epilepsy fellowship programs.

Methods

We conducted two iterations of a structured virtual EEG course from June to October 2021, and from March to June 2022. Trainees were recruited via Canadian neurology residency and epilepsy fellowship programs and were required to join the Canadian League Against Epilepsy (CLAE) as junior members. We obtained trainee demographic information before and after each course as well as analytical data on the video recordings posted on the CLAE website.

Results

A total of 77 trainees registered for the two courses; majority of trainees were adult neurology residents (34%) and adult epilepsy fellows (32%). Prior theoretical EEG teaching was reported as limited by more than half (53%) of participants. The average number of unique viewers per recorded video in 2021 was 29.7 interquartile range (16–35.5), while in 2022, the average was 22.5, interquartile range (16–28). Post‐course questionnaire data revealed that 82% of participants strongly agreed that the course enhanced their knowledge. All participants were either likely (27%) or very likely (73%) to recommend the course to their peers.

Significance

National virtual EEG education is both feasible and accessible; therefore, this is a promising modality of teaching to meet the significant demand for high‐quality EEG education among neurology trainees.
Effect of turbine's torque and speed variation on hydraulic vibration analysis during transient processes
Authors: Shen Aili , Cui Weijie , Zhou Jianxu , Cai Fulin
Published: February 2024

With the rapid development of large‐capacity hydraulic turbines and pumped‐storage power stations, hydraulic vibration analysis attracts increasing attention nowadays. To explore the influence of torque and speed variation on hydraulic vibration characteristics during transient processes and ensure the stability of hydropower stations, an improved analytical formula of turbine impedance involving the torque and speed variation was then derived. The free vibration analysis and forced vibration analysis using the transfer matrix method and the hydraulic impedance method were carried out. According to the numerical simulations, the obtained attenuation factors show differences in magnitude which illustrates that the torque variation and speed variation in transients do affect the damping rate of the vibration. In addition, the results indicated the natural angular frequencies of hydropower system were mainly dependent on the length of water conveyance system and pipe characteristics. It can be inferred form vibration mode shapes that for some specific frequencies, the magnitude of oscillatory pressure head and flow rate along the downstream tail tunnel are influenced by the hydraulic turbine. The correlation between the turbine impedance and guide vane openings tells that the hydraulic impedance is getting smaller as the opening increases. What's more, the corresponding free vibration analysis shows that the absolute value of the damping rate is closely related to the value of the flow rate.
Long‐term effect of extreme temperature on cognitive function of middle‐aged and older adults in China
Authors: Ye Zirong , Li Xueru , Lang Haoxiang , Xin Jiawei , Xu Haibin , Fang Ya
Published: February 2024

Background

Several studies have explored the association between temperature and cognitive function. However, few studies have examined the effect of extreme temperature on cognitive function. In this study, we aimed to quantify the long‐term effect of extreme temperature (e.g., heat waves, cold spells, and hot night excess (HNE)) on cognitive performance in middle‐aged and older people in China.

Method

We investigated 7915 aged >45 years people from the China Health and Retirement Longitudinal Study (CHARLS), surveyed in 2011 and 2015. A structured questionnaire was utilized to assess cognitive function, including four dimensions: episodic memory, attention, orientation, and visuo‐construction. Hourly ambient temperature from the ERA5‐Land datasets were used to calculate variables indicating extreme temperature. We performed difference‐in‐difference (DID) models to assess the potential causal relationship between extreme temperature and cognitive function.

Results

Non‐linear analyses suggested that both sustained increases in temperature and excessive variability in temperature increased the risk of cognitive decline. Meanwhile, we observed the extra risk of global cognitive function decline was 2.3% (95% Confidence interval (95% CI): 0.2%, 4.4%) for heat waves (one unit increase) and 5.9% (95% CI: 0.6%, 11.6%) for HNE (one unit increase), while the association for cold spells was insignificant. Two cognitive dimensions, episodic memory and visuo‐construction, were sensitive to these two heat‐related factors.

Conclusion

Extreme temperature was inversely related to cognitive performance in middle‐aged and older adults, which was substantial for heat waves and HNE particularly. The effect size varied by cognitive dimensions.