bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel program for automatic calculation of EPG variables
Authors: Garzo Elisa , Álvarez Antonio Jesús , Moreno Aránzazu , Walker Gregory P , Tjallingii W Fred , Fereres Alberto
Published: June 2024

The electrical penetration graph (EPG) technique is the most powerful tool for studying the feeding behavior of pierce-sucking insects. However, calculating EPG variables is often very time-consuming, and consequently, several software programs have been developed for the automatic calculation of EPG variables. Here we present a new user-friendly Excel Workbook that uses a standardized list of EPG variables and follows expert guidelines for calculating them. The program developed in Visual Basic for Applications (VBA) is a step up from the existing software and allows easy data analysis and interpretation. It also includes a novel option for dealing with the common problem of “truncated”—waveforms artificially terminated by the end of recording. The only requirement to run the program is Microsoft Excel software running under a PC environment. The Workbook was validated by calculating variables from EPG recordings of aphids and psyllids and the results obtained were compared with those of existing software such as the Sarria Workbook. Our EPG Workbook provides researchers with a reliable and standardized tool for the automatic calculation of up to 127 EPG variables from phloem-sap-sucking insects.
Exploiting Intraday Decompositions in Realized Volatility Forecasting: A Forecast Reconciliation Approach
Authors: Caporin Massimiliano , Di Fonzo Tommaso , Girolimetto Daniele
Published: June 2024

We address the construction of Realized Variance (RV) forecasts by exploiting the hierarchical structure implicit in available decompositions of RV. We propose a post-forecasting approach that utilizes bottom-up and regression-based reconciliation methods. By using data referred to the Dow Jones Industrial Average Index and to its constituents we show that exploiting the informative content of hierarchies improves the forecast accuracy. Forecasting performance is evaluated out-of-sample based on the empirical MSE and QLIKE criteria as well as using the Model Confidence Set approach.
Using neurocognitive phenotypes to inform interventions for adult survivors of childhood cancer
Authors: Banerjee Pia , Phillips Nicholas S , Liu Wei , Ehrhardt Matthew J , Bhakta Nickhill , Brinkman Tara M , Williams Annalynn M , Yasui Yutaka , Khan Raja B , Srivastava Deokumar , Ness Kirsten K , Robison Leslie L , Hudson Melissa M , Krull Kevin R
Published: June 2024

Background

Neurocognitive impairments are sequelae of childhood cancer treatment, however little guidance is given to clinicians on common phenotypes of impairment or modifiable risk factors that could lead to personalized interventions in survivorship.

Methods

Standardized clinical testing of neurocognitive function was conducted in 2958 (74.1%) eligible survivors, who were at least 5 years postdiagnosis and aged older than 18 years, and 477 community controls. Impairment was examined across 20 measures, and phenotypes were determined by latent class analysis. Multinomial logistic regression was used to estimate risk for phenotype, predicted by cancer diagnosis and treatment exposures, chronic health conditions, and lifestyle, adjusted for sex and age. Associations between phenotypes and social attainment were examined.

Results

Five neurocognitive phenotypes were identified in survivors (global impairment 3.7%, impaired attention 5.0%, memory impairment 7.2%, processing speed and executive function impairment 9.3%, no impairment 74.8%). Risk of global impairment was associated with severe chronic health condition burden (odds ratio [OR] = 20.17, 95% confidence interval [CI] = 11.41 to 35.63) including cerebrovascular disease (OR = 14.5, 95% CI = 5.47 to 38.44) and cerebrovascular accident (OR = 14.7, 95% CI = 7.50 to 26.40). Modifiable risk factors, such as quitting smoking, reduced risk for global impairment (OR = 0.21, 95% CI = 0.06 to 0.66). Low physical activity increased risk for global impairment (OR = 4.54, 95% CI = 2.86 to 7.21), attention impairment (OR = 2.01, 95% CI = 1.41 to 2.87), processing speed and executive function impairment (OR = 1.90, 95% CI = 1.46 to 2.48), and memory impairment (OR = 2.09, 95% CI = 1.54 to 2.82).

Conclusions

Results support the clinical utility of neurocognitive phenotyping to develop risk profiles and personalized clinical interventions, such as preventing cerebrovascular disease in anthracycline-treated survivors by preventing hypercholesterolemia, smoking, and sedentary lifestyle, to reduce the risk for global impairment.
Chongqing Transit: Central European Jewish Refugees in China’s Wartime Capital and Interior*
Authors: Cheng Kimberly
Published: June 2024

While most central European Jewish refugees who transited through China during the Second World War lived in Shanghai, some found refuge in other Chinese cities. This article is a microhistory of two German-speaking refugee families, the Karfunkels and the Gottliebs, who spent the war in China’s interior—in the Nationalist wartime capital of Chongqing, amongst other locales. During the war, the relocation of the Nationalist seat of government to Chongqing and the arrival of Allied military missions in inner China led to great demographic upheaval in the city. On the margins of both foreign and Chinese society, the Karfunkels and the Gottliebs found themselves caught up in a significant population shift and a number of social changes. As Japan’s assault on China worsened, the families’ medical, mechanical, and technical expertise was increasingly in demand, elevating their position in Chongqing society. This article investigates the ways that the progression of the Second World War changed Jewish refugee individuals’ circumstances in China’s interior.
Antifungal efficacy of natural antiseptic products against Candida auris
Authors: Wu Wing-Gi , Luk Kristine Shik , Hung Mei-Fan , Tsang Wing-Yi , Lee Kin-Ping , Lam Bosco Hoi-Shiu , Cheng Ka-Lam , Cheung Wing-Sze , Tang Hau-Ling , To Wing-Kin
Published: June 2024

Candida auris is an emerging fungal pathogen responsible for healthcare-associated infections and outbreaks with high mortality around the world. It readily colonizes the skin, nares, respiratory and urinary tract of hospitalized patients, and such colonization may lead to invasive Candida infection in susceptible patients. However, there is no recommended decolonization protocol for C. auris by international health authorities. The aim of this study is to evaluate the susceptibility of C. auris to commonly used synthetic and natural antiseptic products using an in vitro, broth microdilution assay. Synthetic antiseptics including chlorhexidine, povidone-iodine, and nystatin were shown to be fungicidal against C. auris. Among the natural antiseptics tested, tea tree oil and manuka oil were both fungicidal against C. auris at concentrations less than or equal to 1.25% (v/v). Manuka honey inhibited C. auris at 25% (v/v) concentrations. Among the commercial products tested, manuka body wash and mouthwash were fungicidal against C. auris at concentrations less than or equal to 0.39% (w/v) and 6.25% (v/v) of products as supplied for use, respectively, while tea tree body wash and MedihoneyTM wound gel demonstrated fungistatic properties. In conclusion, this study demonstrated good in vitro antifungal efficacy of tea tree oil, manuka oil, manuka honey, and commercially available antiseptic products containing these active ingredients. Future studies are warranted to evaluate the effectiveness of these antiseptic products in clinical settings.
Unveiling lens light complexity with a novel multi-Gaussian expansion approach for strong gravitational lensing
Authors: He Qiuhan , Nightingale James W , Amvrosiadis Aris , Robertson Andrew , Cole Shaun , Frenk Carlos S , Massey Richard , Li Ran , Cao Xiaoyue , Lange Samuel C , França João Paulo C
Published: June 2024

In a strong gravitational lensing system, the distorted light from a source is analysed to infer the properties of the lens. However, light emitted by the lens itself can contaminate the image of the source, introducing systematic errors in the analysis. We present a simple and efficient lens light model based on the well-tested multi-Gaussian expansion (MGE) method for representing galaxy surface brightness profiles, which we combine with a semi-linear inversion scheme for pixelized source modelling. Testing it against realistic mock lensing images, we show that our scheme can fit the lensed images to the noise level, with relative differences between the true input and best-fitting lens light model remaining below 5 per cent. We apply the MGE lens light model to 38 lenses from the HST SLACS sample. We find that the new scheme provides a good fit for the majority of the sample with only 3 exceptions – these show clear asymmetric residuals in the lens light. We examine the radial dependence of the ellipticity and position angles and confirm that it is common for a typical lens galaxy to exhibit twisting non-elliptical isophotes and boxy / disky isophotes. Our MGE lens light model will be a valuable tool for understanding the hidden complexity of the lens mass distribution.
The nature of diffuse ionized gas in star-forming galaxies
Authors: McClymont William , Tacchella Sandro , Smith Aaron , Kannan Rahul , Maiolino Roberto , Belfiore Francesco , Hernquist Lars , Li Hui , Vogelsberger Mark
Published: June 2024

We present an analysis of the diffuse ionized gas (DIG) in a high-resolution simulation of an isolated Milky Way-like galaxy, incorporating on-the-fly radiative transfer and non-equilibrium thermochemistry. We utilize the Monte-Carlo radiative transfer code colt to self-consistently obtain ionization states and line emission in post-processing. We find a clear bimodal distribution in the electron densities of ionized gas ($n_{\rm e}$), allowing us to define a threshold of $n_{\rm e}=10\, \mathrm{cm}^{-3}$ to differentiate DIG from ${\rm H\, {\small II}}$ regions. The DIG is primarily ionized by stars aged 5 – 25 Myr, which become exposed directly to low-density gas after ${\rm H\, {\small II}}$ regions have been cleared. Leakage from recently formed stars ($\lt 5$ Myr) is only moderately important for DIG ionization. We forward model local observations and validate our simulated DIG against observed line ratios in [${\rm S\, {\small II}}$]/H$\alpha$, [${\rm N\, {\small II}}$]/H$\alpha$, [${\rm O\, {\small I}}$]/H$\alpha$, and [${\rm O\, {\small III}}$]/H$\beta$ against $\Sigma _{\rm H\alpha }$. The mock observations not only reproduce observed correlations, but also demonstrate that such trends are related to an increasing temperature and hardening ionizing radiation field with decreasing $n_{\rm e}$. The hardening of radiation within the DIG is caused by the gradual transition of the dominant ionizing source with decreasing $n_{\rm e}$ from 0 to 25 Myr stars, which have progressively harder intrinsic ionizing spectra primarily due to the extended Wolf–Rayet phase caused by binary interactions. Consequently, the DIG line ratio trends can be attributed to ongoing star formation, rather than secondary ionization sources, and therefore present a potent test for stellar feedback and stellar population models.
Disruption of bacterial biofilms by a green synthesized artemisinin nano-copper nanomaterial
Authors: Zhang Yan , Hua Xia , Han Xiaohu , Fang Xue , Li Peng , Zhai Jingbo , Xie Lin , Lv Yanming , Lai Yonghao , Meng Chengcheng , Zhang Yi , Liu Shiwei , Chen Zeliang
Published: June 2024

Bacterial biofilms are associated with antibiotic resistance and account for ∼80% of all bacterial infections. In this study, we explored novel nanomaterials for combating bacteria and their biofilms. Artemisinin nano-copper (ANC) was synthesized using a green synthesis strategy, and its shape, size, structure, elemental composition, chemical valence, zeta potential, and conductivity were characterized using transmission electron microscopy, X-ray diffractometer, X-ray photoelectron spectroscopy, zeta potential, and dynamic light scattering. The results showed that ANC was successfully synthesized utilizing a liquid phase chemical reduction method using chitosan as a modified protectant and l-ascorbic acid as a green reducing agent. The stability of ANC was evaluated using dynamic light scattering. The results showed that the particle size of ANC at different concentrations was comparable to that of the original solution after 7 days of storage, and there was no significant change in the polydispersity index (P > 0.05). The antibacterial effects of ANC on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were determined by disc diffusion and broth dilution methods. The results demonstrated that ANC inhibited and killed E. coli and S. aureus. The effect of ANC on bacterial biofilms was investigated using crystal violet staining, scanning electron microscopy, laser confocal microscopy, and quantitative polymerase chain reaction. The results showed that ANC treatment was able to destroy bacterial biofilms and downregulate biofilm- and virulence-related genes in E. coli (HlyA, gyrA, and F17) and S. aureus (cna, PVL, ClfA, and femB). Green-synthesized ANC possesses excellent antibiofilm properties and is expected to exhibit antibacterial and antibiofilm properties.
Integrating intersectionality into child health research: Key considerations
Authors: Salami Bukola , Bharwani Aleem , Johnson Nicole , Ladha Tehseen , Hart Michael , Dixit Jaya , Benseler Susanne
Published: June 2024

Child health inequities persist in Canada, particularly among sovereignty-deserving First Nations, Métis and Inuit groups and equity-deserving communities. We argue for a fundamental shift in research to remedy these inequities, via an intersectional lens that highlights how social identities and systems of power contribute to disparities. Specifically, we suggest (a) integrating intersectionality, from research conceptualization to results dissemination; (b) respectfully and reciprocally engaging with communities; (c) respectfully collecting and reporting data; (d) recognizing and explicating the diversity within social categories; (e) applying intersectional analytical approaches, and (f) using diverse, participatory and inclusive dissemination strategies. We further underscore the importance of researchers acknowledging their positionalities and their role in promoting reflexivity, as well as using equity, diversity and inclusion principles throughout the research process. We call for a collective commitment to adopt intersectional and EDI approaches in paediatric research, paving the way towards a more equitable health landscape for all children.
Can ultrasound-guided medial branch blocks be used to select patients for cervical facet joint radiofrequency neurotomy? A matched retrospective cohort validation study
Authors: Burnham Robert , Trow Rory , Trow James , Smith Ashley , Burnham Taylor
Published: June 2024

Background

Medial branch blocks are used to select patients for cervical facet joint radiofrequency neurotomy (CRFN). Blocks are typically performed under fluoroscopic guidance (ie, fluoroscopy-guided blocks [FLBs]). The validity of ultrasound-guided blocks (USBs) is not well established. No prior research has compared cervical USB validity and FLB validity with CRFN outcome used as the criterion standard.

Objective

To evaluate cervical USB versus FLB validity with CRFN outcome used as the criterion standard.

Methods

Demographic and outcome data were extracted from the electronic medical records of 2 affiliated musculoskeletal pain management clinics for all patients between 2015 and 2023 inclusive who had cervical USB leading to CRFN. CRFN outcomes of each USB patient were compared with those of a matched FLB patient from the radiofrequency neurotomy (RFN) outcome database of the same clinics. Matching variables included patient age, sex, pain duration, diagnostic/prognostic block paradigm, and CRFN number. Each patient completed a numeric rating scale (NRS) pain score and Pain Disability Quality-of-Life Questionnaire (PDQQ) just before and 3 months after CRFN. At repeat CRFN, patients provided a retrospective estimate of the duration and average magnitude (percentage) of relief after the CRFN.

Results

USB and FLB groups were comprised of 27 patients (58 RFNs) and 38 patients (58 RFNs), respectively. Post-RFN NRS pain severity and PDQQ-Spine scores demonstrated comparable (P > .05) absolute improvements, proportion of patients achieving ≥50% improvement, and attainment of the minimum clinically important difference. Retrospective estimates of pain relief magnitude and duration were also comparable.

Conclusions

This study finds cervical USB and FLB to be comparably valid as defined by their ability to predict CRFN outcome. Within the limitations of operator competence, USB can be used to select patients for CRFN.
Your Typical Criminal: Why White Americans Hate Voter Fraud
Authors: Udani Adriano , Manion Anita , Kimball David
Published: June 2024

Public concerns about voter fraud are widespread and are frequently cited to justify new voting restrictions and harsh punishment for violators. But to what extent do beliefs about a perpetrator’s identity shape public support for efforts to prevent and punish voter fraud? Antipathy toward racial and ethnic groups is a strong predictor of public beliefs about voter fraud. Yet, prior studies have only been able to approximate beliefs about deviant behavior, and not specifically casting an illegal ballot. Drawing from sociology and criminology, we use a “typification” strategy that more directly measures which people are perceived as typical perpetrators of casting illegal ballots. We utilize nationally representative surveys of US voters in the 2017–2020 modules of the Cooperative Election Study to apply and empirically test the typification theory. Among white respondents, we find that the typification of racially minoritized groups such as Blacks, Latinos, Arabs, and immigrants as illegal voters is widespread and is strongly associated with beliefs about voter fraud, support for restrictive election policies, and harsh punishment of illegal voting. The pictures of likely criminals that white voters carry in their heads shape their preferences for crime policies, and this extends to the domain of voter fraud.
The Role of Rivals in International Organizations: A Review Article
Authors: Carnegie Allison
Published: June 2024

This article reviews Discriminatory Clubs: The Geopolitics of International Organizations by Christina L. Davis. After highlighting the many contributions of this pathbreaking work to political science scholarship, it discusses one of the manuscript's core claims: that members of international organizations (IOs) use membership to favor their allies and exclude their rivals. Specifically, it examines a potential tension that leading states may face between keeping rivals out of these organizations for security reasons versus allowing them to join to constrain their behavior and socialize them into the IO's norms. It explores whether consideration of scope conditions, IO reforms, or international regime complexes can help explain IO behavior toward rivals. In doing so, the review suggests productive directions for future work and argues that Discriminatory Clubs will spark many exciting and fruitful research directions.
“They still phone even though they know I'm deaf”: exploring experiences of deaf people in health services in Wales, UK
Authors: Terry Julia , Meara Rhian , England Rachel
Published: June 2024

Background

Deaf and hard of hearing people persistently experience barriers accessing health services, largely due to ineffective communication systems, a lack of flexible booking arrangements, and a lack of Deaf awareness training for health professional staff.

Methods

Face to face focus groups were conducted with 66 Deaf and hard of hearing people in Deaf clubs across Wales, UK. Thematic analysis was undertaken.

Results

Responses identified from focus groups are reported as barriers faced using health services, improvements that would make a difference, impact of accessibility of health services, and a potential Sign language badge for healthcare staff.

Conclusions

Deaf people report that health professionals lack training on Deaf awareness and do not know how to communicate effectively with Deaf and hard of hearing people. Further research into Deaf awareness and training resources for health professionals are needed to establish what improves Deaf cultural competencies, and ultimately makes healthcare experiences more positive for people who are Deaf.
Genetic Structure of Ganoderma boninense Populations Associated with Oil Palm at Neighboring Fields with Different Planting Ages in Malaysia
Authors: Wong Wei-Chee , Goh You-Keng , Wong Choo-Kien , Goh Yit-Kheng , Marzuki Nurul Fadhilah , Choo Celine H. Y. , Tung Hun-Jiat
Published: June 2024

Ganoderma boninense is a basidiomycete pathogen of African oil palm (Elaeis guineensis) and the causal agent of basal stem rot (BSR) disease, which is the most destructive fungal disease of oil palm in Southeast Asia. The disease is fatal for infected palms and can result in 50 to 80% losses in oil yields because of a reduction in productive life span and a yield decline of infected oil palms. In this study, G. boninense isolates collected from different locations and planting blocks with different palm ages were molecularly characterized using microsatellite genotyping. Results showed high pathogen genetic diversity (He = 0.67 to 0.74) among planting blocks and between oil palm estates. Two nearby planting blocks with similar planting ages (i.e., 1999 and 2001) had a similar percentage of BSR incidence (>20%) but showed distinct Ganoderma genetic structure as detected using STRUCTURE. Similar results were obtained from another trial site where planting blocks differing in planting age but located only less than 1 km apart showed a diverse genetic background. The pathogen genetic admixture of the oldest planting (>30% BSR incidence) differed significantly from the younger planting (1.8 to 2.8% BSR incidence, breeding trial block), suggesting that the host–pathogen genotype interaction may impact the Ganoderma genetic variation over time. The genetic structure of G. boninense, as revealed in this study, implies positive selection resulting from the pathogen genetic variation, host–pathogen interaction, and possible introductions of novel genetic variants (through spores) from adjacent plantings. These findings offer new insights into the genetic changes of G. boninense over time. The information is essential to design disease management strategies and breeding for BSR resistance in oil palm.
Zearalenone modulates the function of goat endometrial cells via the mitochondrial quality control system
Authors: Zhang Guomin , Zeng Cheng , Sun Xuan , Zhang Qi , Wang Yifei , Xia Rongxin , Mai Qingyang , Xue Gang , Huang Han , Wang Feng
Published: June 2024

Zearalenone (ZEN) is a mycotoxin known for its estrogen‐like effects, which can disrupt the normal physiological function of endometrial cells and potentially lead to abortion in female animals. However, the precise mechanism by which ZEN regulates endometrial function remains unclear. In this study, we found that the binding receptor estrogen receptors for ZEN is extensively expressed across various segments of the uterus and within endometrial cells, and a certain concentration of ZEN treatment reduced the proliferation capacity of goat endometrial epithelial cells (EECs) and endometrial stromal cells (ESCs). Meanwhile, cell cycle analysis revealed that ZEN treatment leaded to cell cycle arrest in goat EECs and ESCs. To explore the underlying mechanism, we investigated the mitochondrial quality control systems and observed that ZEN triggered excessive mitochondrial fission and disturbed the balance of mitochondrial fusion‐fission dynamics, impaired mitochondrial biogenesis, increased mitochondrial unfolded protein response and mitophagy in goat EECs and ESCs. Additionally, ZEN treatment reduced the activities of mitochondrial respiratory chain complexes, heightened the production of hydrogen peroxide and reactive oxygen species, and caused cellular oxidative stress and mitochondrial dysfunction. These results suggest that ZEN has adverse effects on goat endometrium cells by disrupting the mitochondrial quality control system and affecting cell cycle and proliferation. Understanding the underlying molecular pathways involved in ZEN‐induced mitochondrial dysfunction and its consequences on cell function will provide critical insights into the reproductive toxicity of ZEN and contribute to safeguarding the health and wellbeing of animals and humans exposed to this mycotoxin.
How Many Imaging Studies Do Patients With Neuromuscular Early Onset Scoliosis (EOS) Receive?
Authors: Lin Adrian J. , Chen Vivian , Wong Cynthis , Tamrazi Benita , Skaggs David L. , Illingworth Kenneth D. , Heffernan Michael J. , Andras Lindsay M.
Published: June 2024

Background:

Children with neuromuscular early onset scoliosis (EOS) receive numerous radiographic studies both from orthopaedic and other specialties. Ionizing radiation doses delivered by computed tomography (CT) are reportedly 100 times higher than conventional radiography. The purpose of this study was to evaluate the number of radiographic studies ordered for neuromuscular EOS patients during their care.

Methods:

Retrospective review at a tertiary children’s hospital from January 2010 to June 2021 included all patients with neuromuscular EOS followed by an orthopaedic specialist for a minimum of 3 years. Patients were excluded if the majority of their nonorthopaedic care was provided by outside institutions.

Results:

Eighteen patients met inclusion criteria with mean follow up of 6.4±2.3 years. A total of 1312 plain radiographs and 35 CT scans were performed. Of the plain radiographs, 34.7% were ordered by orthopaedic providers and 65.3% (857/1312) were ordered by other providers. Of the CT scans, 4 were ordered by orthopaedic providers, while 88.5% (21/35) were ordered by other providers. An average of 74.7 (range: 29 to 124) radiographs and 1.9 (range: 0 to 9) CT scans ordered over the course of each patient’s treatment for an average of 13.0±6.0 radiographs and 0.3 CT scans per year.

Conclusions:

With an average of 75 radiographs and 1.9 CT scans performed per patient, consideration for steps to limit exposure to ionizing radiation should be made a particularly high priority in this unique subset of patients. This requires interdisciplinary coordination as 65% of the radiographs and over 80% of the CT scans were ordered by nonorthopaedic providers.

Level of Evidence:

Level III.
Donafenib inhibits PARP1 expression and induces DNA damage, in combination with PARP1 inhibitors promotes apoptosis in liver cancer cells
Authors: Jiang Jiuliang , Yang Pingping , Xu Xinyu , Yuan Huixiong , Zhu Haitao
Published: June 2024

Liver cancer is a prevalent malignant tumor globally. The newly approved first-line drug, donafenib, is a novel oral small molecule multi-tyrosine kinase inhibitor that has significant antitumor effects on liver cancer. This study aims to investigate the antitumor effects of donafenib on liver cancer and to explore its potential mechanisms. Donafenib significantly inhibited the viability of Huh-7 and HCCLM3 cells, inhibited malignant cell proliferation, and promoted cell apoptosis, as demonstrated by CCK-8, EdU, and Calcein/PI (propidium iodide) staining experiments. The results of DNA damage detection experiments and western blot analysis indicate that donafenib caused considerable DNA damage in liver cancer cells. The analysis of poly (ADP-ribose) polymerase 1 (PARP1) in liver cancer patients using online bioinformatics data websites such as TIMER2.0, GEPIA, UALCAN, cBioPortal, Kaplan–Meier Plotter, and HPA revealed a high expression of PARP1, which is associated with poor prognosis. Molecular docking and western blot analysis demonstrated that donafenib can directly target and downregulate the protein expression of PARP1, a DNA damage repair protein, thereby promoting DNA damage in liver cancer cells. Western blot and immunofluorescence detection showed that the group treated with donafenib combined with PARP1 inhibitor had significantly higher expression of γ-H2AX and 8-OHdG compared to the groups treated with donafenib or PARP1 inhibitors alone, the combined treatment suppresses the expression of the antiapoptotic protein Bcl2 and enhances the protein expression level of the proapoptotic protein Bcl-2-associated X protein (BAX). These data suggest that the combination of donafenib and a PARP1 inhibitor results in more significant DNA damage in cells and promotes cell apoptosis. Thus, the combination of donafenib and PARP1 inhibitors has the potential to be a treatment option for liver cancer.
Cutaneous “Microcystic” Microsecretory Adenocarcinoma With Marked Adnexal Hyperplasia: A Simulant of Microcystic Adnexal Carcinoma
Authors: Novice Taylor , Vellaichamy Gautham , McCalmont Timothy H. , Moesch John
Published: June 2024

Microsecretory adenocarcinoma (MSA) was first described in 2019 as a low-grade salivary gland neoplasm of intraoral origin with distinct histopathologic features and a characteristic MEF2C::SS18 fusion. Recently, skin was also identified as a primary site for MSA in a report by Bishop et al. Due to its rarity and resemblance to other adnexal tumors, MSA is a challenging diagnosis. Herein, we present a case of cutaneous MSA that was unique for the presence of a significant microcystic component and marked adnexal hyperplasia, which mimicked myxoid microcystic adnexal carcinoma (MAC). A 58-year-old presented with a 1 year history of an enlarging eyelid nodule. Histopathologic analysis revealed dermal tumor composed of small tubules containing inspissated bluish mucinous material. Accompanying marked adnexal hyperplasia and many microcysts were also present. Tumor cells expressed S100 protein, which is distinct from MAC, while p63 immunohistochemistry showed marked loss of myoepithelial labeling, as is common in primary adenocarcinomas. Next generation gene sequencing detected the characteristic MSA fusion protein MEF2c::SS18. We report a novel presentation of MSA that simulated MAC because of the presence of associated microcystic change. The presence of S100 immunopositivity and the identification of MEF2C::SS18 fusion confirmed the diagnosis of cutaneous MSA.
Impact of Illness Uncertainty on Health-Related Quality of Life in Patients With Unruptured Intracranial Aneurysms After Coil Embolization
Authors: Lee JiEun , Lee SukJeong
Published: June 2024

BACKGROUND: This study aimed to identify the impact of illness uncertainty on physical and mental health-related quality of life (HRQoL) in patients with unruptured intracranial aneurysms (UIAs) after coil embolization. METHODS: A cross-sectional study was conducted and HRQoL was evaluated using the Short Form-12 Health Survey Questionnaire, which assesses physical and mental HRQoL. RESULTS: The participants had a mean age of 56.4 years, and among them, 190 (71.2%) were women. Physical and mental HRQoL were negatively correlated with physical symptoms, anxiety, depression, and illness uncertainty. Mental HRQoL was positively correlated with social support. Physical HRQoL was significantly influenced by depression (β = −0.26, P = .004) and was not influenced by illness uncertainty (β = −0.10, P = .101). Mental HRQoL was significantly influenced by anxiety (β = −0.45, P < .001), depression (β = −0.19, P = .003), social support (β = 0.14, P = .004), and illness uncertainty (β = −0.14, P = .005). The finding that illness uncertainty influences HRQoL suggests a basis for interventions aimed at improving mental HRQoL by reducing illness uncertainty in patients with UIAs. CONCLUSION: The physical and mental HRQoL in patients with UIAs after coil embolization is negatively influenced by depression, whereas mental HRQoL is also affected by anxiety, illness uncertainty, and social support. These results may serve as reference data for the design and development of interventions to improve HRQoL in patients with UIAs after coil embolization.
Routine Versus Selective Distal Perfusion Catheter Use in Venoarterial Extracorporeal Membrane Oxygenation
Authors: Buda Kevin G. , Robinson Emilie C. , Titus Jessica , Eckman Peter M. , Chavez Ivan , Cravero Ellen , Stanberry Larissa , Hryniewicz Katarzyna
Published: June 2024

Although current studies support the use of prophylactic distal perfusion catheters (DPCs) to decrease limb ischemia in patients on venoarterial extracorporeal membrane oxygenation (VA ECMO), methods for monitoring limb ischemia differ between studies. We evaluated the safety of a selective rather than prophylactic DPC strategy at a single center with a well-established protocol for limb ischemia monitoring. Distal perfusion catheters were placed selectively if there was evidence of hypoperfusion at any point until decannulation. All patients were followed daily by vascular surgery with continuous regional saturation monitoring. Of 188 patients supported with VA ECMO, there were no significant differences in baseline characteristics between patients with upfront, delayed, and no DPC. Thirty day mortality was highest in patients with an upfront DPC (56% in the upfront DPC group, 19% in the delayed DPC group, and 22% in the no-DPC group, p < 0.001). The incidence of major bleeding, fasciotomy, and amputation in the entire cohort was 3.7%, 3.7%, and 0%, respectively. With strict adherence to a protocol for limb ischemia monitoring, a selective rather than prophylactic DPC strategy is safe and may obviate the risks of an additional arterial catheter.
Effects of Exercise on Balance in Cancer Survivors With Chemotherapy-Induced Peripheral Neuropathy
Authors: Khemthong Usa , Hawsawi Samah , Schneider Joanne Kraenzle
Published: June 2024

Background

Balance impairment in cancer survivors can be a consequence of chemotherapy-induced peripheral neuropathy (CIPN). Previous meta-analyses suggested that exercise significantly improved balance, but the results were only based on 3 and 4 primary studies.

Objectives

This meta-analysis examined the effects of exercise on balance in cancer survivors with CIPN and investigated the moderating effects of source, methods, interventions, and participant characteristics.

Methods

We searched 12 electronic databases and 5 websites without date restriction through December 18, 2023, for primary studies examining the effect of exercise to improve balance in cancer survivors with CIPN reported in English. We retrieved 12 studies that provided 14 comparisons (N = 576), coded them, assessed quality indicators, and evaluated effect sizes across studies.

Results

Using the random-effects model, the estimated summary effect (Hedges’ g) of exercise on balance was 0.68 (Knapp-Hartung adjusted 95% confidence interval, 0.41–0.94; P = .0001) compared with comparison groups. Subgroup analysis revealed that blinded data collectors, intervention fidelity examination, and difference in exercise protocol significantly influenced effect size. Meta-regression analysis showed that session minutes was associated with higher effect sizes.

Conclusion

Exercise with balance training significantly improved balance in cancer survivors. Balance training should be integrated into the current exercise guidelines for cancer survivors with CIPN.

Implications for Practice

Nurses should encourage cancer survivors to engage in exercise with balance training when undergoing chemotherapy. Physical function and barriers to exercise should be assessed before delivering exercise interventions. Exercises should be tailored according to individual performance.
Implementing a Frailty-Specific Postoperative Order Set to Improve Postoperative Outcomes in Frail Adults After Elective Thoracic Surgery
Authors: Allen Amani , Francisco Mary Ann , Jatis Jessica , Turner Yonous , Nordgren Rachel , Rubin Daniel , Huisingh-Scheetz Megan , Bryan Darren S. , Donington Jessica , Ferguson Mark K. , Gleason Lauren J. , Madariaga Maria Lucia
Published: June 2024

Background:

Frailty is independently associated with adverse patient outcomes after surgery. The current standards of postoperative care rarely consider frailty status.

Local Problem:

There was no standardized protocol to optimize specialized postoperative care for frail patients at an academic medical center.

Methods:

A quasi-experimental pre-/postimplementation study design, using the Reach, Effectiveness, Adoption, Implementation, Maintenance implementation framework, was utilized.

Interventions:

A frailty-specific postoperative order set (FPOS) was developed, including tailored nursing care, activity levels, and nutritional goals.

Results:

There were significant improvements in nurse’s self-reported familiarity with frailty (P = .003) and FPOS awareness (P < .001). The number of orders for delirium prevention, elimination, nutrition, sleep promotion, and sensory support increased (P < .001).

Conclusions:

Implementing an FPOS showed improvements in nurse frailty knowledge, awareness, and order set utilization.
Food and water uptake are regulated by distinct central amygdala circuits revealed using intersectional genetics
Authors: Fermani Federica , Chang Simon , Peters Christian , Gaitanos Louise , Morales Pilar L. Alcala , Ramakrishnan Charu , Deisseroth Karl , Klein Rüdiger
Published: June 2024

The central amygdala (CeA) plays a crucial role in defensive and appetitive behaviours. It contains genetically defined GABAergic neuron subpopulations distributed over three anatomical subregions, capsular (CeC), lateral (CeL), and medial (CeM). The roles that these molecularly- and anatomically-defined CeA neurons play in appetitive behavior remain unclear. Using intersectional genetics, we found that neurons driving food or water consumption are confined to the CeM. Separate CeM subpopulations exist for water only versus water or food consumption.In vivocalcium imaging revealed that CeMHtr2aneurons promoting feeding are responsive towards appetitive cues with little regard for their physical attributes. CeMSstneurons involved in drinking are sensitive to the physical properties of salient stimuli. Both CeM subtypes receive inhibitory input from CeL and send projections to the parabrachial nucleus to promote appetitive behavior. These results suggest that distinct CeM microcircuits evaluate liquid and solid appetitive stimuli to drive the appropriate behavioral responses.
A database of digital line drawings that depict expected and unexpected action-place relationships
Authors: Aydemir Sabiha Tezcan , Umul Seray Tezcan , Urgen Burcu A.
Published: June 2024

In the present study, we introduce an image database created with a simple digital line-drawing tool to represent the expected and unexpected action-place relationships. This database consists of 70 drawings. We validated the dataset with 207 participants. They evaluated the actions, places, and the probability of an action taking place in the respective location. The comprehensibility of each drawing was evaluated using three measures: H-statistics (entropy), which is a measure of the uncertainty of the definition; the definition similarity percentages which is a measure of the naming agreement that is consistent among participants; and the mean probability of the depicted action taking place in the depicted location. Each drawing includes different agents and environments, providing researchers with the opportunity to use this dataset in various fields of cognitive neuroscience, including visual recognition, memory, predictive coding, and novelty detection.
The iMab antibody selectively binds to intramolecular and intermolecular i-motif structures
Authors: Ruggiero Emanuela , Marusic Maja , Zanin Irene , Peña Martinez Cristian David , Plavec Janez , Christ Daniel , Richter Sara N.
Published: June 2024

i-Motifs are quadruplex nucleic acid conformations that form in cytosine-rich regions. Because of their acidic pH dependence, iMs were thought to form onlyin vitro. The recent development of an iM-selective antibody, iMab, has allowed iM detection in cells, which revealed their presence at gene promoters and their cell cycle dependence. However, recently evidence emerged which seemed to suggest that iMab recognizes C-rich sequences regardless of their iM conformation. To further investigate the selectivity of iMab, we examined the binding of iMab to C-rich sequences, using a combination of pull-down and Western blot assays. Here we observe that the composition of buffers used during binding and washing steps strongly influences the selectivity of antibody binding. In addition, we demonstrate by NMR that several of the previously reported C-rich sequences, which were not expected to form iMs, actually formintermoleculariMs which are selectively recognized by iMab. Our results highlight the specificity of the iMab antibody, emphasize the importance of optimizing DNA concentrations, blocking and washing conditions, and confirm iMab selectivity not only for intramolecular iMs, but also for intermolecular iMs.
Nanoparticles co-delivering siRNA and mRNA for simultaneous restoration and silencing of gene/protein expressionin vitroandin vivo
Authors: Manturthi Shireesha , El-Sahli Sara , Bo Yuxia , Durocher Emma , Kirkby Melanie , Popatia Alyanna , Mediratta Karan , Daniel Redaet , Lee Seung-Hwan , Iqbal Umar , Côté Marceline , Wang Lisheng , Gadde Suresh
Published: June 2024

RNA-based agents such as siRNA, miRNA, and mRNA can selectively manipulate gene expression/proteins and have the potential to revolutionize the current therapeutic strategies for various diseases, including cancer. To address the poor stability and inherent limitations of RNA agents, nanoparticle (NP) platforms have been developed to deliver functional mRNA or siRNA inside the cells. Recent studies have focused on either siRNA to knock down proteins causing drug resistance or mRNA technology to introduce tumor suppressors. However, complex diseases like cancer need multi-targeted approaches to selectively target multiple gene expressions/proteins. In this proof-of-concept study, we developed co-delivery nanoparticles containing Luc-mRNA and siRNA-GFP as model RNA agents ((M+S)-NPs) and assessed their effectsin vitroandin vivo. Our studies show that NPs can effectively deliver both functional mRNA and siRNA together, simultaneously impacting the expression of two genes/proteinsin vitro. Additionally, afterin vivoadministration, co-delivery NPs successfully knocked down GFP while introducing luciferase in a TNBC mouse model, indicating our NPs have the potential to develop RNA-based anticancer therapeutics. These studies pave the way to develop RNA-based, multitargeted, multi-delivery approaches for complex diseases like cancer.

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Restoring hippocampal glucose metabolism rescues cognition across Alzheimer’s disease pathologies
Authors: Minhas Paras S. , Jones Jeffrey R. , Latif-Hernandez Amira , Sugiura Yuki , Durairaj Aarooran S. , Uenaka Takeshi , Wang Qian , Mhatre Siddhita D. , Liu Ling , Conley Travis , Ennerfelt Hannah , Jung Yoo Jin , Prasad Praveena , Jenkins Brenita C. , Goodman Ryan , Newmeyer Traci , Heard Kelly , Kang Austin , Wilson Edward N. , Ullian Erik M. , Serrano Geidy E. , Beach Thomas G. , Rabinowitz Joshua D. , Wernig Marius , Suematsu Makoto , Longo Frank M. , McReynolds Melanie R. , Gage Fred H. , Andreasson Katrin I.
Published: June 2024

Impaired cerebral glucose metabolism is a pathologic feature of Alzheimer Disease (AD), and recent proteomic studies highlight a disruption of glial carbohydrate metabolism with disease progression. Here, we report that inhibition of indoleamine-2,3-dioxygenase 1 (IDO1), which metabolizes tryptophan to kynurenine (KYN) in the first step of the kynurenine pathway, rescues hippocampal memory function and plasticity in preclinical models of amyloid and tau pathology by restoring astrocytic metabolic support of neurons. Activation of IDO1 in astrocytes by amyloid-beta42and tau oligomers, two major pathological effectors in AD, increases KYN and suppresses glycolysis in an AhR-dependent manner. Conversely, pharmacological IDO1 inhibition restores glycolysis and lactate production. In amyloid-producingAPPSwe-PS1ΔE9and 5XFAD mice and in tau-producing P301S mice, IDO1 inhibition restores spatial memory and improves hippocampal glucose metabolism by metabolomic and MALDI-MS analyses. IDO1 blockade also rescues hippocampal long-term potentiation (LTP) in a monocarboxylate transporter (MCT)-dependent manner, suggesting that IDO1 activity disrupts astrocytic metabolic support of neurons. Indeed, in vitro mass-labeling of human astrocytes demonstrates that IDO1 regulates astrocyte generation of lactate that is then taken up by human neurons. In co-cultures of astrocytes and neurons derived from AD subjects, deficient astrocyte lactate transfer to neurons was corrected by IDO1 inhibition, resulting in improved neuronal glucose metabolism. Thus, IDO1 activity disrupts astrocytic metabolic support of neurons across both amyloid and tau pathologies and in a model of AD iPSC-derived neurons. These findings also suggest that IDO1 inhibitors developed for adjunctive therapy in cancer could be repurposed for treatment of amyloid- and tau-mediated neurodegenerative diseases.
ColocZStats: A Z-Stack Signal Colocalization Extension Tool for 3D Slicer
Authors: Chen Xiang , Thakur Teena , Jeyasekharan Anand D. , Benoukraf Touati , Meruvia-Pastor Oscar
Published: June 2024

Confocal microscopy has evolved as a widely adopted imaging technique in molecular biology and is frequently utilized to achieve accurate subcellular localization of proteins. Applying colocalization analysis on image z-stacks obtained from confocal fluorescence microscopes is a dependable method to reveal the association between different molecules. In addition, despite the established advantages and growing adoption of 3D visualization software in various microscopy research domains, there has been a scarcity of systems supporting colocalization analysis within a user-specified region of interest (ROI). In this context, several broadly employed biological image visualization platforms were meticulously explored in this study to comprehend the current landscape. It has been observed that while these applications can generate three-dimensional (3D) reconstructions for the z-stacks and in some cases transfer them into an immersive Virtual Reality (VR) scene, there is still a lack of support for performing quantitative colocalization analysis on such images based on a user-defined ROI and thresholding levels. To address these issues, an extension called ColocZStats has been developed for 3D Slicer, a widely used free and open-source software package for image analysis and scientific visualization. With a custom-designed user-friendly interface, ColocZStats allows investigators to conduct intensity thresholding and ROI selection on imported 3D image stacks. It can deliver several essential colocalization metrics for structures of interest and produce reports in the form of diagrams and spreadsheets.