bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of beta-casein gene polymorphism in dairy cattle populations of Ukraine
Authors: Ladyka Volodymyr , Skliarenko Yuriy , Pavlenko Yuliia , Malikova Alona
Published: November 2023

Using real-time polymerase chain reaction methods, we have researched the CSN2 polymorphism gene in 2 populations of cows in the North-East of Ukraine. The observed distributions of genotype frequencies А1А1, А1А2, А2А2 and A1 or A2 alleles varies considerably in different cattle populations of cows: population of brown cattle – 1.7%, 38.5, 59.8% (0.209 and 0.791); black and spotted population – 18.3%, 44.7%, 37.0% (0.406 and 0.594). The ratio of genotypes were found significant differences when comparing genotypes A1A1 (p<0.001) and A2A2 (p<0.001). The results of DNA testing of the beta-casein locus for A1 and A2-allelic variants in stud bulls of the studied populations have shown that the highest frequency of the A2A2 desired homozygous genotype is characteristic of the breeders of brown cattle (46%). The obtained results indicate the prospects of breeding work to create herds with genotype A2A2 animals - specifically with the brown cattle.
Cardio-respiratory endurance of individuals with different blood pressure levels
Authors: Vadzyuk Stepan , Tabas Petro
Published: November 2023

Evaluation of cardio-respiratory endurance in individuals with different levels of blood pressure is one of the key factors in preventing the development of diseases of the cardiovascular system. The purpose of the study was to conduct a comparative assessment of cardio-respiratory endurance, the level of maximum oxygen consumption, and the results of the Ruffier test in individuals with different blood pressure levels. 320 people were examined, of which 4 groups were formed according to the initial level of blood pressure. After measuring baseline blood pressure and heart rate, all subjects underwent a Ruffier test (30 sit-ups for 45 seconds), followed by repeated heart rate measurements at 15 seconds, 1 minute, and blood pressure measurements at 3 minutes. Determination of the level of maximum oxygen consumption was performed according to the formula. Representatives of the group with normal-low and normal blood pressure have a significantly higher level of maximum oxygen consumption. Individuals with normal-high blood pressure and first-degree hypertension had higher levels of systolic and diastolic blood pressure during daily blood pressure monitoring, both during the day and at night, compared to individuals with normal and normal-low blood pressure. It was established that people with normal-low blood pressure have a higher cardio-respiratory endurance than people with normal-high blood pressure and first-degree hypertension. The findings of the study can be used by cardiologists and general practitioners for early detection and prevention of diseases of the cardiovascular system, and physiologists in further investigation of the features of the functioning of the cardiovascular system
Lower bounds on expressions dependent on functions φ(n), ψ(n) and σ(n)
Authors:   Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Dimitrov Stoyan
Published: November 2023

The inequalities \varphi^2(n)+\psi^2(n)+\sigma^2(n) \geq 3n^2+2n+3 , \varphi(n)\psi(n)+\varphi(n)\sigma(n)+\sigma(n)\psi(n) \geq 3n^2+2n-1 connecting \varphi(n), \psi(n) and \sigma(n)-functions are formulated and proved.
Indole produced during dysbiosis mediates host–microorganism chemical communication
Authors: Yang Rui-Qiu , Chen Yong-Hong , Wu Qin-yi , Tang Jie , Niu Shan-Zhuang , Zhao Qiu , Ma Yi-Cheng , Zou Cheng-Gang
Published: November 2023

An imbalance of the gut microbiota, termed dysbiosis, has a substantial impact on host physiology. However, the mechanism by which host deals with gut dysbiosis to maintain fitness remains largely unknown. In Caenorhabditis elegans, Escherichia coli, which is its bacterial diet, proliferates in its intestinal lumen during aging. Here, we demonstrate that progressive intestinal proliferation of E. coli activates the transcription factor DAF-16, which is required for maintenance of longevity and organismal fitness in worms with age. DAF-16 up-regulates two lysozymes lys-7 and lys-8, thus limiting the bacterial accumulation in the gut of worms during aging. During dysbiosis, the levels of indole produced by E. coli are increased in worms. Indole is involved in the activation of DAF-16 by TRPA-1 in neurons of worms. Our finding demonstrates that indole functions as a microbial signal of gut dysbiosis to promote fitness of the host.
Single-cell RNA sequencing unravels the transcriptional network underlying zebrafish retina regeneration
Authors: Celotto Laura , Rost Fabian , Machate Anja , Bläsche Juliane , Dahl Andreas , Weber Anke , Hans Stefan , Brand Michael
Published: November 2023

In the lesioned zebrafish retina, Müller glia produce multipotent retinal progenitors that generate all retinal neurons, replacing lost cell types. To study the molecular mechanisms linking Müller glia reactivity to progenitor production and neuronal differentiation, we used single-cell RNA sequencing of Müller glia, progenitors and regenerated progeny from uninjured and light-lesioned retinae. We discover an injury-induced Müller glia differentiation trajectory that leads into a cell population with a hybrid identity expressing marker genes of Müller glia and progenitors. A glial self-renewal and a neurogenic trajectory depart from the hybrid cell population. We further observe that neurogenic progenitors progressively differentiate to generate retinal ganglion cells first and bipolar cells last, similar to the events observed during retinal development. Our work provides a comprehensive description of Müller glia and progenitor transcriptional changes and fate decisions in the regenerating retina, which are key to tailor cell differentiation and replacement therapies for retinal dystrophies in humans.
Condensin positioning at telomeres by shelterin proteins drives sister-telomere disjunction in anaphase
Authors: Colin Léonard , Reyes Celine , Berthezene Julien , Maestroni Laetitia , Modolo Laurent , Toselli Esther , Chanard Nicolas , Schaak Stephane , Cuvier Olivier , Gachet Yannick , Coulon Stephane , Bernard Pascal , Tournier Sylvie
Published: November 2023

The localization of condensin along chromosomes is crucial for their accurate segregation in anaphase. Condensin is enriched at telomeres but how and for what purpose had remained elusive. Here, we show that fission yeast condensin accumulates at telomere repeats through the balancing acts of Taz1, a core component of the shelterin complex that ensures telomeric functions, and Mit1, a nucleosome remodeler associated with shelterin. We further show that condensin takes part in sister-telomere separation in anaphase, and that this event can be uncoupled from the prior separation of chromosome arms, implying a telomere-specific separation mechanism. Consistent with a cis-acting process, increasing or decreasing condensin occupancy specifically at telomeres modifies accordingly the efficiency of their separation in anaphase. Genetic evidence suggests that condensin promotes sister-telomere separation by counteracting cohesin. Thus, our results reveal a shelterin-based mechanism that enriches condensin at telomeres to drive in cis their separation during mitosis.
Frustrated Microphase Separation Produces Interfacial Environment within Biological Condensates
Authors: Latham Andrew P. , Zhu Longchen , Sharon Dina A. , Ye Songtao , Willard Adam P. , Zhang Xin , Zhang Bin
Published: November 2023

The phase separation of intrinsically disordered proteins is emerging as an important mechanism for cellular organization. However, efforts to connect protein sequences to the physical properties of condensates, i.e., the molecular grammar, are hampered by a lack of effective approaches for probing high-resolution structural details. Using a combination of multiscale simulations and fluorescence lifetime imaging microscopy experiments, we systematically explored a series of systems consisting of diblock elastin-like polypeptides (ELP). The simulations succeeded in reproducing the variation of condensate stability upon amino acid substitution and revealed different microenvi-ronments within a single condensate, which we verified with environmentally sensitive fluorophores. The interspersion of hydrophilic and hydrophobic residues and a lack of secondary structure formation result in a frustrated microphase separation, which explains both the strong correlation between ELP condensate stability and interfacial hydrophobicity scales, as well as the prevalence of protein-water hydrogen bonds. Our study uncovers new mechanisms for condensate stability and organization that may be broadly applicable.
Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation
Authors: Schmassmann Philip , Roux Julien , Dettling Steffen , Hogan Sabrina , Shekarian Tala , Martins Tomás A. , Ritz Marie-Françoise , Herter Sylvia , Bacac Marina , Hutter Gregor
Published: November 2023

Glioblastoma (GBM) harbors a highly immunosuppressive tumor microenvironment (TME) which influences glioma growth. Major efforts have been undertaken to describe the TME on a single-cell level. However, human data on regional differences within the TME remain scarce. Here, we performed high-depth single-cell RNA sequencing (scRNAseq) on paired biopsies from the tumor center, peripheral infiltration zone and blood of five primary GBM patients. Through analysis of > 45’000 cells, we revealed a regionally distinct transcription profile of microglia (MG) and monocyte-derived macrophages (MdMs) and an impaired activation signature in the tumor-peripheral cytotoxic-cell compartment. Comparing tumor-infiltrating CD8
+
T cells with circulating cells identified CX3CR1
high
and CX3CR1
int
CD8
+
T cells with effector and memory phenotype, respectively, enriched in blood but absent in the TME. Tumor CD8
+
T cells displayed a tissue-resident memory phenotype with dysfunctional features. Our analysis provides a regionally resolved mapping of transcriptional states in GBM-associated leukocytes, serving as an additional asset in the effort towards novel therapeutic strategies to combat this fatal disease.
Anti-Arthritis, Antioxidant and Anti - Inflammatory Potential of Ethanolic Extract of Guava Leaves on Rats Exposed to High Fat Diet and Freud Adjuvant
Authors: Chinatu Nwosu Patience , Elekima Ibioku , Adeline Ben-Chioma , Holy Brown
Published: November 2023

Guava leaves (Psidium guajava) have been used traditionally for years to treat common ailments such as Diabetes, diarrhoea, and hypertension. This study was designed to determine the anti-arthritic, anti-inflammatory, and antioxidant effect of the ethanolic extract of guava leaf (Psidium guajava) on rats fed with a high-fat diet and induced arthritis using complete Freud Adjuvant. Seventy-two male and female albino rats were used in this study, the rats were grouped into 12 with 6 rats in each group, rats were fed a high-fat diet to cause hyperlipidaemia and induced rheumatoid arthritis by injecting 0.1ml of Complete Freund’s Adjuvant into their right hind paw. Group 1 was fed with normal feed and water, group 2 was made of healthy rats, fed with normal feed, water, and guava leaf extract, group 3 was fed with a high-fat diet and induced arthritis with complete Freund’s Adjuvant (CFA) and water, group 4 received dexamethasone (6.75 mg.kg-1 orally), and groups 5 to 12 received the extract at oral doses of 250 and 750 mg/kg, respectively for a period of 28days. ELISA technique was used to analyse the inflammatory markers, antioxidants; SOD, and MDA, while the lipid profile was on a spectrophotometer. The inflammatory markers TNF-α, IL-6, and C-reactive protein were significantly reduced in test subjects at p<0.05, HDL and SOD had no statically significant difference, while MDA was markedly reduced at p<0.05. This study demonstrates that Psidium guajava extract has significant anti-arthritic and lipid-lowering effects. Psidium guajava leaves can be developed into an alternative anti-arthritis and lipid-lowering treatment.
The Project of Conceptual Framework for Financial Accounting: A Literature Review
Authors: Anssari Majid Ahmed AL
Published: November 2023

This study was conducted in light of numerous effects on the growth of the modern accounting thinking model, which started as an accounting theory at the beginning of the past century, notably in the 1920s and 1930s. The research begins with the early theorists' attempts to find theoretical rules or foundations that lead to accounting applications and works to confront and solve their increasing problems from that period until recently. The main concern is the enhancement of financial accounting criteria, instead of the development of accounting theory. The current study aims to trace the course of the conceptual framework project to evaluate its experience and role in the standards project. The research also tries to give answers about the effectiveness of the conceptual framework presently and in the future directions of the joint framework project.
State Reporting Requirements for Involuntary Holds, Court-Ordered Guardianship, and the US National Firearm Background Check System
Authors: Betz Marian E. , Bowen Deirdre M. , Rowhani-Rahbar Ali , McCourt Alexander D. , Rivara Frederick P.
Published: November 2023

Importance

Firearm violence is a leading cause of death in the US. There is broad public agreement that individuals at high risk of perpetrating violence should not be allowed to purchase or possess firearms. The National Instant Criminal Background Check System (NICS) is a national system intended to stop firearm purchases or possession by prohibited persons, but there is heterogeneity in how states interact with and report data to NICS.

Objective

To examine variability in state requirements for NICS reporting for mental health prohibitions.

Design and Setting

This cross-sectional study in the US reviewed current statutes for all 50 states and the District of Columbia (enacted through the 2021 legislative session) regarding reporting mental health prohibitions to NICS or state systems. Data were analyzed from October 2022 to April 2023.

Main Outcomes and Measures

For each state, the following were recorded: reliance on Federal Bureau of Investigation vs state point of contact for NICS checks; regulation requiring or allowing reporting to NICS for 3 hypothetical cases; and details on reporting responsibility and time frame. The number of NICS listings for adjudicated mental health reasons was obtained, and state rates per 1000 population were calculated. To compare states, we developed 3 hypothetical cases of individuals with risk of firearm violence, whether possibly temporary (involuntary commitment for decompensated psychosis, or involuntary short-term psychiatric hold for suicidal ideation) or chronic and progressive (court-appointed guardianship for dementia).

Results

A total of 40 states required and 5 allowed reporting to NICS for court-ordered, involuntary psychiatric hospitalization. Thirteen states required and 5 allowed reporting to NICS when a court determines an individual is mentally incompetent to manage their affairs (with or without guardianship). One state required NICS reporting for short-term emergency psychiatric holds. Five states and the District of Columbia had no legislation explicitly requiring or allowing NICS reporting in the 3 scenarios.

Conclusions and Relevance

In this cross-sectional study of state laws, there was substantial heterogeneity in NICS reporting requirements and lack of clarity around processes. This raises questions about the ability of NICS to be used to block firearm purchases or possession by individuals with court-identified high risk of perpetrating violence toward themselves or others.
Statin Use, Cholesterol Level, and Mortality Among Females With Breast Cancer
Authors: Murto Mika O. , Simolin Niklas , Arponen Otso , Siltari Aino , Artama Miia , Visvanathan Kala , Jukkola Arja , Murtola Teemu J.
Published: November 2023

Importance

Several studies have reported an association between the use of statins and breast cancer (BC) mortality. However, most of these studies did not take into account the underlying cholesterol level.

Objective

To investigate the association between serum cholesterol, statin use, and BC mortality.

Design, Setting, and Participants

This cohort study included females with invasive BC that was newly diagnosed between January 1, 1995, and December 31, 2013, in Finland. The cohort had available hormone receptor data and at least 1 cholesterol measurement. All data were obtained from Finnish national registries. Statistical analyses were performed from January to May 2022.

Exposure

Use of statins; statin dose; and serum cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels measured separately before and after BC diagnosis.

Main Outcomes and Measures

Breast cancer mortality and overall mortality between date of BC diagnosis and December 31, 2015.

Results

A total of 13 378 female patients with BC (median [IQR] age, 62 [54-69] years) participated in the study. The median (IQR) follow-up was 4.5 (2.4-9.8) years after BC diagnosis, during which 16.4% of patients died and 7.0% died of BC. Prediagnostic statin use was a risk factor for BC death even after adjustment for total cholesterol level (hazard ratio [HR], 1.22; 95% CI, 1.02-1.46; P = .03). Reduced risk for BC death was seen for postdiagnostic statin use (HR, 0.85; 95% CI, 0.73-1.00; P = .05). The risk reduction was robust in participants whose cholesterol level decreased after starting statins (HR, 0.49; 95% CI, 0.32-0.75; P = .001) but was nonsignificant if cholesterol level did not subsequently decrease (HR, 0.69; 95% CI, 0.34-1.40; P = .30). Reduced BC mortality among statin users was also observed in females with estrogen receptor–positive tumors (HR, 0.82; 95% CI, 0.68-0.99; P = .03). Overall mortality was lower among statin users vs nonusers when adjusted for serum cholesterol level (HR, 0.80; 95% CI, 0.72-0.88; P < .001).

Conclusions and Relevance

Results of this cohort study showed that postdiagnostic use of statins was associated with reduced BC mortality compared with nonuse, and the risk was associated with subsequent change in serum cholesterol level. This finding suggests that cholesterol-lowering interventions with statins may be beneficial for patients with BC.
Food Insecurity, Memory, and Dementia Among US Adults Aged 50 Years and Older
Authors: Qian Haobing , Khadka Aayush , Martinez Suzanna M. , Singh Sonali , Brenowitz Willa D. , Zeki Al Hazzouri Adina , Hill-Jarrett Tanisha G. , Glymour M. Maria , Vable Anusha M.
Published: November 2023

Importance

Despite existing federal programs to increase access to food, food insecurity is common among US older adults. Food insecurity may affect Alzheimer disease and Alzheimer disease–related dementias via multiple mechanisms, yet there is almost no quantitative research evaluating this association.

Objective

To examine whether food insecurity in older adults is associated with later-life cognitive outcomes.

Design, Setting, and Participants

This cohort study of US residents aged 50 years and older from the US Health and Retirement Study was restricted to respondents with food insecurity data in 2013 and cognitive outcome data between calendar years 2014 and 2018. Analyses were conducted from June 1 to September 22, 2023.

Exposure

Food insecurity status in 2013 was assessed using the validated US Department of Agriculture 6-item Household Food Security Module. Respondents were classified as being food secure, low food secure, and very low food secure.

Main Outcomes and Measures

Outcomes were dementia probability and memory score (standardized to 1998 units), estimated biennially between 2014 and 2018 using a previously validated algorithm. Generalized estimation equations were fit for dementia risk and linear mixed-effects models for memory score, taking selective attrition into account through inverse probability of censoring weights.

Results

The sample consisted of 7012 participants (18 356 person-waves); mean (SD) age was 67.7 (10.0) years, 4131 (58.9%) were women, 1136 (16.2%) were non-Hispanic Black, 4849 (69.2%) were non-Hispanic White, and mean (SD) duration of schooling was 13.0 (3.0) years. Compared with food-secure older adults, experiencing low food security was associated with higher odds of dementia (odds ratio, 1.38; 95% CI, 1.15-1.67) as was experiencing very low food security (odds ratio, 1.37; 95% CI, 1.11-1.59). Low and very low food security was also associated with lower memory levels and faster age-related memory decline.

Conclusions and Relevance

In this cohort study of older US residents, food insecurity was associated with increased dementia risk, poorer memory function, and faster memory decline. Future studies are needed to examine whether addressing food insecurity may benefit brain health.
Economic Evaluation of Blood Pressure Monitoring Techniques in Patients With Hypertension
Authors: Hayek Michelle A. , Giannouchos Theodoros , Lawley Mark , Kum Hye-Chung
Published: November 2023

Importance

Blood pressure monitoring is critical to the timely diagnosis and treatment of hypertension. At-home self-monitoring techniques are highly effective in managing high blood pressure; however, evidence regarding the cost-effectiveness of at-home self-monitoring compared with traditional monitoring in clinical settings remains unclear.

Objective

To identify and synthesize published research examining the cost-effectiveness of at-home blood pressure self-monitoring relative to monitoring in a clinical setting among patients with hypertension.

Evidence Review

A systematic literature search of 5 databases (PubMed, MEDLINE, Embase, EconLit, and CINAHL) followed by a backward citation search was conducted in September 2022. Full-text, peer-reviewed articles in English including patients with high blood pressure (systolic blood pressure ≥130 mm Hg and diastolic blood pressure ≥80 mm Hg) at baseline were included. Data from studies comparing at-home self-monitoring with clinical-setting monitoring alternatives were extracted, and the outcomes of interest included incremental cost-effectiveness and cost-utility ratios. Non–peer-reviewed studies or studies with pregnant women and children were excluded. To ensure accuracy and reliability, 2 authors independently evaluated all articles for eligibility and extracted relevant data from the selected articles.

Findings

Of 1607 articles identified from 5 databases, 16 studies met the inclusion criteria. Most studies were conducted in the US (6 [40%]) and in the UK (6 [40%]), and almost all studies (14 [90%]) used a health care insurance system perspective to determine costs. Nearly half the studies used quality-adjusted life-years gained and cost per 1–mm Hg reduction in blood pressure as outcomes. Overall, at-home blood pressure monitoring (HBPM) was found to be more cost-effective than monitoring in a clinical setting, particularly over a minimum 10-year time horizon. Among studies comparing HBPM alone vs 24-hour ambulatory blood pressure monitoring (ABPM) or HBPM combined with additional support or team-based care, the latter were found to be more cost-effective.

Conclusions and Relevance

In this systematic review, at-home blood pressure self-monitoring, particularly using automatic 24-hour continuous blood pressure measurements or combined with additional support or team-based care, demonstrated the potential to be cost-effective long-term compared with care in the physical clinical setting and could thus be prioritized for patients with hypertension from a cost-effectiveness standpoint.
Physicians’ Perceptions of Clinical Decision Support to Treat Patients With Heart Failure in the ED
Authors: Casey Scott D. , Reed Mary E. , LeMaster Chris , Mark Dustin G. , Gaskin Jesse , Norris Robert P. , Sax Dana R.
Published: November 2023

Importance

Clinical decision support (CDS) could help emergency department (ED) physicians treat patients with heart failure (HF) by estimating risk, collating relevant history, and assisting with medication prescribing if physicians’ perspectives inform its design and implementation.

Objective

To evaluate CDS usability and workflow integration in the hands of ED physician end users who use it in clinical practice.

Design, Setting, and Participants

This mixed-methods qualitative study administered semistructured interviews to ED physicians from 2 community EDs of Kaiser Permanente Northern California in 2023. The interview guide, based on the Usability Heuristics for User Interface Design and the Sociotechnical Environment models, yielded themes used to construct an electronic survey instrument sent to all ED physicians.

Main Outcomes and Measures

Main outcomes were physicians’ perceptions of using CDS to complement clinical decision-making, usability, and integration into ED clinical workflow.

Results

Seven key informant physicians (5 [71.4%] female, median [IQR] 15.0 [9.5-15.0] years in practice) were interviewed and survey responses from 51 physicians (23 [45.1%] female, median [IQR] 14.0 [9.5-17.0] years in practice) were received from EDs piloting the CDS intervention. Response rate was 67.1% (51 of 76). Physicians suggested changes to CDS accessibility, functionality, and workflow integration. Most agreed that CDS would improve patient care and fewer than half of physicians expressed hesitation about their capacity to consistently comply with its recommendations, citing workload concerns. Physicians preferred a passive prompt that encouraged, but did not mandate, interaction with the CDS.

Conclusions and Relevance

In this qualitative study of physicians who were using a novel CDS intervention to assist with ED management of patients with acute HF, several opportunities were identified to improve usability as well as several key barriers and facilitators to CDS implementation.
Restoring eastern hellbender (Cryptobranchus a. alleganiensis) populations through translocation of headstarted individuals
Authors: Kaunert Matthew D. , Brown Ryan K. , Spear Stephen , Johantgen Peter B. , Popescu Viorel D.
Published: November 2023

Freshwater biodiversity is declining at a fast pace despite significant efforts directed toward the management and conservation of aquatic systems. Eastern hellbenders are one of North America's most iconic stream amphibian species, a sentinel of stream health, and are experiencing rapid population declines throughout most of their range. Common conservation strategies include headstarting; however, the success of this strategy for rebuilding hellbender populations and the most optimal release scenarios have largely been unassessed. We use a cohort of 205 animals released in several Ohio watersheds to evaluate the success of headstarting and reintroduction efforts over 3 years. Using PIT‐tag surveys over 25 occasions between July 2018 and November 2021 and capture–recapture models, we found that 3‐year apparent survival post‐release was 0.162 ± 0.061, with lower survival in year 1 (0.383 ± 0.058) and greater in years 2 (0.696 ± 0.086) and 3 (0.609 ± 0.154). Using demographic simulations, we found that releasing cohorts of N = 100 individuals at fewer suitable sites several times (e.g., 3 releases, 2 or 3 years apart) would be a better strategy compared to single release events across multiple sites. Additional simulations showed that eastern hellbender headstarting programs using wild eggs can be highly beneficial in producing more animals reaching adulthood (up to 7 times, if survival in captivity is assumed to be 100%) compared to development in the wild. This study emphasizes the need to monitor the success of reintroduction programs and provides evidence that headstarting can be a viable strategy for rebuilding eastern hellbender populations.
Incorporating variable RBE in IMPT optimization for ependymoma
Authors: Goudarzi Hadis Moazami , Lim Gino , Grosshans David , Mohan Radhe , Cao Wenhua
Published: November 2023

Purpose

To study the dosimetric impact of incorporating variable relative biological effectiveness (RBE) of protons in optimizing intensity‐modulated proton therapy (IMPT) treatment plans and to compare it with conventional constant RBE optimization and linear energy transfer (LET)‐based optimization.

Methods

This study included 10 pediatric ependymoma patients with challenging anatomical features for treatment planning. Four plans were generated for each patient according to different optimization strategies: (1) constant RBE optimization (ConstRBEopt) considering standard‐of‐care dose requirements; (2) LET optimization (LETopt) using a composite cost function simultaneously optimizing dose‐averaged LET (LETd) and dose; (3) variable RBE optimization (VarRBEopt) using a recent phenomenological RBE model developed by McNamara et al.; and (4) hybrid RBE optimization (hRBEopt) assuming constant RBE for the target and variable RBE for organs at risk. By normalizing each plan to obtain the same target coverage in either constant or variable RBE, we compared dose, LETd, LET‐weighted dose, and equivalent uniform dose between the different optimization approaches.

Results

We found that the LETopt plans consistently achieved increased LET in tumor targets and similar or decreased LET in critical organs compared to other plans. On average, the VarRBEopt plans achieved lower mean and maximum doses with both constant and variable RBE in the brainstem and spinal cord for all 10 patients. To compensate for the underdosing of targets with 1.1 RBE for the VarRBEopt plans, the hRBEopt plans achieved higher physical dose in targets and reduced mean and especially maximum variable RBE doses compared to the ConstRBEopt and LETopt plans.

Conclusion

We demonstrated the feasibility of directly incorporating variable RBE models in IMPT optimization. A hybrid RBE optimization strategy showed potential for clinical implementation by maintaining all current dose limits and reducing the incidence of high RBE in critical normal tissues in ependymoma patients.
Cardiovascular Risk Factors and the Risk of Discontinuation of Advanced Therapies Due to Treatment Failure in Rheumatoid Arthritis: Results From the Ontario Best Practices Research Initiative
Authors: Aboulenain Samar , Li Xiuying , Movahedi Mohammad , Bombardier Claire , Kuriya Bindee
Published: November 2023

Objectives

Our goal was to investigate whether cardiovascular disease (CVD) risk factors are associated with the retention of biologic disease‐modifying antirheumatic drugs (bDMARDs) or targeted‐synthetic DMARDs (tsDMARDs) in patients with rheumatoid arthritis (RA).

Methods

We included participants in the Ontario Best Practices Initiative RA registry who initiated their first bDMARD or tsDMARD. Participants were grouped by the number of baseline CVD risk factors (0, 1, or ≥2). The primary outcome was time‐to‐discontinuation of therapy for any reason. Secondary outcomes included discontinuation for primary failure, secondary failure, or due to adverse events. Competing risks hazards model, adjusted for clinically important confounders, estimated the association between CVD risk factors and treatment retention.

Results

The sample included 872 patients, of which 58% (n = 508) discontinued their b/tsDMARD after a median of 13 months from the time of initiation. The most common causes for treatment discontinuation were primary failure (n = 72), secondary failure (n = 126), or adverse events (n = 133). Patients with no CVD risk factors experienced significantly longer treatment survival compared to patients with 1 or ≥2 CVD risk factors. In multivariable‐adjusted analysis, there was no association between all‐cause discontinuation and CVD risk factors. However, there was a significant association between the presence of >1 CVD risk factor and treatment discontinuation, notably due to secondary treatment failure, but not due to adverse events.

Conclusion

Multiple CVD risk factors increase the risk of treatment failure in RA, particularly for secondary treatment failure. To improve patient outcomes, future research should focus on developing strategies to identify early treatment nonresponse and investigate the potential modifiability of this association.
Graphene‐Based Silicon Photonic Devices for Optical Interconnects
Authors: Wang Zheng , Cai Yan , Jiang Haitao , Tian Ziao , Di Zengfeng
Published: November 2023

The exponential growth of global data traffic is driven by the unprecedented digitalization of the world. To meet the demands of next‐generation high‐capacity data communication systems, innovative solutions are required. Silicon photonics has gained significant attention due to its ability to integrate multiple core functions of optical interconnects into small‐scale chips, offering cost‐effective and scalable manufacturing capabilities. By leveraging silicon photonics, it becomes possible to address the challenge of scaling system complexity while reducing size, cost, and energy consumption. Despite its advantages, silicon has inherent limitations that restrict its application range, such as the weak plasma dispersion effect and relatively large bandgap. Recently, graphene has emerged as a promising solution for traditional silicon photonics because of its exceptional electrical and optical properties. For instance, graphene on a silicon chip enables nearly pure phase modulation and ultrafast photodetection beyond 500 GHz. Moreover, the demonstrated compatibility of graphene with wafer‐level integration paves the way for mass production of graphene‐based silicon photonic devices, offering improved yield, scalability, and cost‐effectiveness. In this work, a comprehensive review is provided, focusing on graphene‐based silicon photonic devices and their applications in optical interconnects, aiming to explore the potential of graphene in advancing silicon photonic technology.
Vacuum Processed Metal Halide Perovskite Light‐Emitting Diodes
Authors: Zhou Chun , Meng Wenyuan , Kong Lingmei , Zhang Chengxi , Zhang Jianhua , Liu Fangze , Li Hongbo , Jia Guohua , Yang Xuyong
Published: November 2023

Metal halide perovskite light‐emitting diodes (PeLEDs) are expected to be the next‐generation display technology due to their unique optoelectronic properties. Currently, the external quantum efficiencies of PeLEDs based on solution‐processed fabrication methods already exceed 20%. However, there are still many challenges existing in solution‐based PeLEDs that inhibit their commercialization. Recently, vacuum deposition techniques of perovskites have drawn much attention because of the ability to grow dense and uniform large‐area perovskite films with precisely controlled thickness, which is compatible with state‐of‐the‐art organic LED manufacturing processes. Despite the promising prospects of vacuum‐based PeLEDs, some challenges remain to be addressed to achieve PeLEDs with both high efficiency and high stability that are required for practical applications such as active‐matrix displays. This requires precise control of the film morphology, composition, and interface during the deposition process through fine‐tuning of the substrate temperature, deposition rate, vacuum level, precursor formulation, and post‐treatment conditions. In this review, it focuses on the key requirements for vacuum‐processed PeLEDs, highlights the recent advances in materials and devices of PeLEDs, and emphasize vacuum evaporation methods as well as the corresponding device performance. Possible approaches to improve the efficiency and the long‐term operational stability of vacuum‐processed PeLEDs are discussed.
Highly Conductive n‐Type Polymer Fibers from the Wet‐Spinning of n‐Doped PBDF and Their Application in Thermoelectric Textiles
Authors: Sarabia‐Riquelme Ruben , Noble Leah E. , Alarcon Espejo Paula , Ke Zhifan , Graham Kenneth R. , Mei Jianguo , Paterson Alexandra F. , Weisenberger Matthew C.
Published: November 2023

The field of electronic textiles currently lacks n‐type polymer fibers that can complement the more established p‐type polymer fibers. Here, a highly conductive n‐type polymer fiber is obtained via wet‐spinning of n‐doped poly(3,7‐dihydrobenzo[1,2‐b:4,5‐b’]difuran‐2,6‐dione) (n‐PBDF). The electrical conductivity of the fibers increases from 1000 to 1600 S cm−1 with increased draw during processing and correlates well with Young's modulus. Wide‐angle X‐ray scattering reveals the existence of a bimodal orientation of the polymer chains, favoring parallel alignment to the fiber axis with increased draw. After 14 d in 80% humid air, fiber conductivity stabilizes maintaining 81% of the initial conductivity. Although the electrical conductivity drops slightly over time, the Seebeck coefficient increases, resulting in the highest thermoelectric power factor being measured at 91 µW m−1 K−2 for the most drawn fiber 14 d after its fabrication. A proof‐of‐concept two‐couple thermoelectric textile is crafted by embroidering bundles of n‐type PBDF fibers and p‐type PEDOT:PSS fibers. The device generates 2.40 nW at a 22 °C temperature gradient. This work represents the initial steps and a crucial advancement toward fabricating high‐performance n‐type polymer fibers that can complement their p‐type counterparts to close the existing performance gap.
Biomimetic Conductive Hydrogel Scaffolds with Anisotropy and Electrical Stimulation for In Vivo Skeletal Muscle Reconstruction
Authors: Xue Yan , Li Jieling , Jiang Tianhe , Han Qingquan , Jing Yafeng , Bai Shuo , Yan Xuehai
Published: November 2023

The nature of the hydrogel scaffold mimicking extracellular matrix plays a crucial role in tissue engineering like skeletal muscle repair. Herein, an anisotropic and conductive hydrogel scaffold is fabricated using gelatin methacryloyl (GelMA) as the matrix hydrogel and silver nanowire (AgNW) as the conductive dopant, through a directional freezing technique for muscle defect repair. The scaffold has an anisotropic structure composed of a directional longitudinal section and a honeycomb cross‐section, with high mechanical strength of 10.5 kPa and excellent conductivity of 0.26 S m−1. These properties are similar to native muscle extracellular matrix (ECM) and allow for cell orientation under the guidance of contact cues and electrical stimulation synergistically. In vitro experiments show that the scaffold's oriented structure combined with electrical stimulation results in enhanced myotube formation, with a length of up to 863 µm and an orientation rate of 81%. Furthermore, the electrically stimulated scaffold displays a promoted muscle reconstruction ability when transplanted into rats with muscle defects, achieving a muscle mass and strength restoration ratio of 95% and 99%, respectively, compared to normal levels. These findings suggest that the scaffold has great potential in muscle repair applications.
Materials and Device Designs for Wireless Monitoring of Temperature and Thermal Transport Properties of Wound Beds during Healing
Authors: Ryu Hanjun , Song Joseph W. , Luan Haiwen , Sim Youngmin , Kwak Sung Soo , Jang Hokyung , Jo Young Jin , Yoon Hong‐Joon , Jeong Hyoyoung , Shin Jaeho , Park Do Yun , Kwon Kyeongha , Ameer Guillermo Antonio , Rogers John A.
Published: November 2023

Chronic wounds represent a major health risk for diabetic patients. Regeneration of such wounds requires regular medical treatments over periods that can extend for several months or more. Schemes for monitoring the healing process can provide important feedback to the patient and caregiver. Although qualitative indicators such as malodor or fever can provide some indirect information, quantitative measurements of the wound bed have the potential to yield important insights. The work presented here introduces materials and engineering designs for a wireless system that captures spatio‐temporal temperature and thermal transport information across the wound continuously throughout the healing process. Systematic experimental and computational studies establish the materials aspects and basic capabilities of this technology. In vivo studies reveal that both the temperature and the changes in this quantity offer information on wound status, with indications of initial exothermic reactions and mechanisms of scar tissue formation. Bioresorbable materials serve as the foundations for versions of this device that create possibilities for monitoring on and within the wound site, in a way that bypasses the risks of physical removal.
Microenvironment‐Driven Fenton Nanoreactor Enabled by Metal‐Phenolic Encapsulation of Calcium Peroxide for Effective Control of Dental Caries
Authors: Yang Xiaoru , Shao Jinlong , Zhang Yandi , Wang Ting , Ge Shaohua , Li Jianhua
Published: November 2023

Caries are one of the most common oral diseases caused by pathogenic bacterial infections, which are widespread and persistently harmful to human health. Using nanoparticles to invade biofilms and produce reactive oxygen species (ROS) in situ is a promising strategy for killing bacteria and disrupting the structure of biofilms. In this work, a biofilm‐targeting Fenton nanoreactor is reported that can generate ROS responsive to the cariogenic microenvironment. The nanoreactor is constructed by metal‐phenolic encapsulation of calcium peroxide (CaO2) followed by modification with a biofilm targeting ligand dextran. Within the cariogenic biofilm, the Fenton nanoreactor is activated by an acidic microenvironment to be decomposed into H2O2 and iron ions, triggering a Fenton‐like reaction to generate ROS that can eliminate the biofilm by breaking down extracellular polymeric substances (EPS) and killing cariogenic bacteria. Meanwhile, the depletion of excess protons in biofilm leads to a reversal of the cariogenic microenvironment. The Fenton nanoreactor can effectively inhibit the biofilm formation of Streptococcus mutans on ex vivo human teeth and is effective in preventing caries meanwhile maintaining the oral microbial diversity in rat caries infection model. This work provides a novel and efficient modality for acid microenvironment‐driven ROS therapy.
Intracellular Nitroreductase‐Triggered “On” and “Enhanced” Photoacoustic Signals for Sensitive Imaging of Tumor Hypoxia
Authors: Sun Xianbao , Xu Lingling , Xu Hai‐Dong , Xie Limin , Wang Rui , Yang Zhimou , Zhan Wenjun , Shen Shurong , Liang Gaolin
Published: November 2023

Current molecular photoacoustic (PA) probes are designed with either stimulus‐turned “on” or assembly‐enhanced signals to trace biological analytes/events. PA probes based on the nature‐derived click reaction between 2‐cyano‐6‐aminobenzothiazole (CBT) and cysteine (Cys) (i.e., CBT‐Cys click reaction) possess both “turn‐on” and “enhanced” PA signals; and thus, should have higher sensitivity. Nevertheless, such PA probes, particularly those for sensitive imaging of tumor hypoxia, remain scarce. Herein, a PA probe NI‐Cys(StBu)‐Dap(IR780)‐CBT (NI‐C‐CBT) is rationally designed, which after being internalized by hypoxic tumor cells, is cleaved by nitroreductase under the reduction condition to yield cyclic dimer C‐CBT‐Dimer to turn the PA signal “ON” and subsequently assembled into nanoparticles C‐CBT‐NPs with additionally enhanced PA signal (“Enhanced”). NI‐C‐CBT exhibits 1.7‐fold “ON” and 3.2‐fold overall “Enhanced” PA signals in vitro. Moreover, it provides 1.9‐fold and 2.8‐fold overall enhanced PA signals for tumor hypoxia imaging in HeLa cells and HeLa tumor‐bearing mice, respectively. This strategy is expected to be widely applied to design more “smart” PA probes for sensitive imaging of important biological events in vivo in near future.
Attenuating Epithelial‐to‐Mesenchymal Transition in Cancer through Angiopoietin‐Like 4 Inhibition in a 3D Tumor Microenvironment Model
Authors: Liao Zehuan , Lim Joseph Jing Heng , Lee Jeannie Xue Ting , Chua Damien , Vos Marcus Ivan Gerard , Yip Yun Sheng , Too Choon Boon , Cao Huan , Wang Jun Kit , Shou Yufeng , Tay Andy , Lehti Kaisa , Cheng Hong Sheng , Tay Chor Yong , Tan Nguan Soon
Published: November 2023

Epithelial‐to‐mesenchymal transition (EMT) plays a crucial role in metastatic cancer progression, and current research, which relies heavily on 2D monolayer cultures, falls short in recapitulating the complexity of a 3D tumor microenvironment. To address this limitation, a transcriptomic meta‐analysis is conducted on diverse cancer types undergoing EMT in 2D and 3D cultures. It is found that mechanotransduction is elevated in 3D cultures and is further intensified during EMT, but not during 2D EMT. This analysis reveals a distinct 3D EMT gene signature, characterized by extracellular matrix remodeling coordinated by angiopoietin‐like 4 (Angptl4) along with other canonical EMT regulators. Utilizing hydrogel‐based 3D matrices with adjustable mechanical forces, 3D cancer cultures are established at varying physiological stiffness levels. A YAP:EGR‐1 mediated up‐regulation of Angptl4 expression is observed, accompanied by an upregulation of mesenchymal markers, at higher stiffness during cancer EMT. Suppression of Angptl4 using antisense oligonucleotides or anti‐cAngptl4 antibodies leads to a dose‐dependent abolishment of EMT‐mediated chemoresistance and tumor self‐organization in 3D, ultimately resulting in diminished metastatic potential and stunted growth of tumor xenografts. This unique programmable 3D cancer cultures simulate stiffness levels in the tumor microenvironment and unveil Angptl4 as a promising therapeutic target to inhibit EMT and impede cancer progression.
Heterogenized Molecular Electrocatalyst Based on a Hydroxo‐Bridged Binuclear Copper(II) Phenanthroline Compound for Selective Reduction of CO2 to Ethylene
Authors: Liu Na , Bartling Stephan , Springer Armin , Kubis Christoph , Bokareva Olga S. , Salaya Evaristo , Sun Jiameng , Zhang Zhonghua , Wohlrab Sebastian , Abdel‐Mageed Ali M. , Liang Hong‐Qing , Francke Robert
Published: November 2023

Molecular copper catalysts have emerged as promising candidates for the electrochemical reduction of CO2. Notable features of such systems include the ability of Cu to generate C2+ products and the well‐defined active sites that allow for targeted structural tuning. However, the frequently observed in situ formation of Cu nanoclusters has undermined the advantages of the molecular frameworks. It is therefore desirable to develop Cu‐based catalysts that retain their molecular structures during electrolysis. In this context, a heterogenized binuclear hydroxo‐bridged phenanthroline Cu(II) compound with a short Cu···Cu distance is reported as a simple yet efficient catalyst for electrogeneration of ethylene and other C2 products. In an aqueous electrolyte, the catalyst demonstrates remarkable performance, with excellent Faradaic efficiency for C2 products (62%) and minimal H2 evolution (8%). Furthermore, it exhibits high stability, manifested by no observable degradation during 15 h of continuous electrolysis. The preservation of the atomic distribution of the active sites throughout electrolysis is substantiated through comprehensive characterizations, including X‐ray photoelectron and absorption spectroscopy, scanning and transmission electron microscopy, UV–vis spectroscopy, as well as control experiments. These findings establish a solid foundation for further investigations into targeted structural tuning, opening new avenues for enhancing the catalytic performance of Cu‐based molecular electrocatalysts.