bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytical validation of the 7-gene biosignature for prediction of recurrence risk and radiation therapy benefit for breast ductal carcinoma in situ
Authors: Dabbs David , Mittal Karuna , Heineman Scott , Whitworth Pat , Shah Chirag , Savala Jess , Shivers Steven C. , Bremer Troy
Published: May 2023

Purpose

Ductal carcinoma in situ (DCIS), is a noninvasive breast cancer, representing 20-25% of breast cancer diagnoses in the USA. Current treatment options for DCIS include mastectomy or breast-conserving surgery (BCS) with or without radiation therapy (RT), but optimal risk-adjusted treatment selection remains a challenge. Findings from past and recent clinical trials have failed to identify a ‘low risk’ group of patients who do not benefit significantly from RT after BCS. To address this unmet need, a DCIS biosignature, DCISionRT (PreludeDx, Laguna Hills, CA), was developed and validated in multiple cohorts. DCISionRT is a molecular assay with an algorithm reporting a recurrence risk score for patients diagnosed with DCIS intended to guide DCIS treatment. In this study, we present results from analytical validity, performance assessment, and clinical performance validation and clinical utility for the DCISionRT test comprised of multianalyte assays with algorithmic analysis.

Methods

The analytical validation of each molecular assay was performed based on the Clinical and Laboratory Standards Institute (CLSI) guidelines Quality Assurance for Design Control and Implementation of Immunohistochemistry Assays and the College of American Pathologists/American Society of Clinical Oncology (CAP/ASCO) recommendations for analytic validation of immunohistochemical assays.

Results

The analytic validation showed that the molecular assays that are part of DCISionRT test have high sensitivity, specificity, and accuracy/reproducibility (≥95%). The analytic precision of the molecular assays under controlled non-standard conditions had a total standard deviation of 6.6 (100-point scale), where the analytic variables (Lot, Machine, Run) each contributed <1% of the total variance. Additionally, the precision in the DCISionRT test result (DS) had a 95%CI ≤0.4 DS units under controlled non-standard conditions (Day, Lot, and Machine) for molecular assays over a wide range of clinicopathologic factor values. Clinical validation showed that the test identified 37% of patients in a low-risk group with a 10-year invasive IBR rate of ~3% and an absolute risk reduction (ARR) from RT of 1% (number needed to treat, NNT=100), while remaining patients with higher DS scores (elevated-risk) had an ARR for RT of 9% (NNT=11) and 96% clinical sensitivity for RT benefit.

Conclusion

The analytical performance of the PreludeDx DCISionRT molecular assays was high in representative formalin-fixed, paraffin-embedded breast tumor specimens. The DCISionRT test has been analytically validated and has been clinically validated in multiple peer-reviewed published studies.
Genetic alterations in LEP and ADIPOQ genes and risk for breast cancer: a meta-analysis
Authors: Peng Wei-zhao , Liu Xin , Li Chao-feng , Zhao Jin
Published: May 2023

Introduction

Breast cancer has a strong genetic predisposition, and its genetic architecture is not fully understood thus far. In this study, we aimed to perform a meta-analysis to evaluate the association of genetic alterations in LEP and ADIPOQ genes, as well as their receptor-encoded genes with risk for breast cancer.

Methods

Only published studies conducted in humans and written in English were identified by searching PubMed, SCOPUS, CINAHIL and Embase from their inception to October 2022. Eligibility assessment and data collection were completed independently by two researchers. Statistical analyses were done using the STATA software.

Results

After literature search, 33 publications were eligible for inclusion. Overall, LEP gene rs7799039-G allele (odds ratio [OR]: 0.78, 95% confidence interval [CI]: 0.62 to 0.98) and ADIPOQ gene rs1501299-T allele (OR: 1.41, 95% CI: 1.06 to 1.88) were associated with the significant risk of breast cancer. In subgroup analyses, differences in menopausal status, obesity, race, study design, diagnosis of breast cancer, genotyping method and sample size might account for the divergent observations of individual studies. Circulating leptin levels were comparable across genotypes of LEP gene rs7799039, as well as that of LEPR gene rs1137101 (P>0.05). Begg’s funnel plots seemed symmetrical, with the exception of LEPR gene rs1137100 and ADIPOQ gene rs1501299.

Discussion

Taken together, we found, in this meta-analysis, that LEP gene rs7799039 and ADIPOQ gene rs1501299 were two promising candidate loci in predisposition to breast cancer risk.
Little things with significant impact: miRNAs in hepatocellular carcinoma
Authors: Li Jiehan , Bao Haolin , Huang Ziyue , Liang Zixin , Wang Mei , Lin Ning , Ni Chunjie , Xu Yi
Published: May 2023

Hepatocellular carcinoma (HCC) has developed into one of the most lethal, aggressive, and malignant cancers worldwide. Although HCC treatment has improved in recent years, the incidence and lethality of HCC continue to increase yearly. Therefore, an in-depth study of the pathogenesis of HCC and the search for more reliable therapeutic targets are crucial to improving the survival quality of HCC patients. Currently, miRNAs have become one of the hotspots in life science research, which are widely present in living organisms and are non-coding RNAs involved in regulating gene expression. MiRNAs exert their biological roles by suppressing the expression of downstream genes and are engaged in various HCC-related processes, including proliferation, apoptosis, invasion, and metastasis. In addition, the expression status of miRNAs is related to the drug resistance mechanism of HCC, which has important implications for the systemic treatment of HCC. This paper reviews the regulatory role of miRNAs in the pathogenesis of HCC and the clinical applications of miRNAs in HCC in recent years.
Diminazen Aceturate Protects Pulmonary Ischemia-Reperfusion Injury via Inhibition of ADAM17-Mediated Angiotensin-Converting Enzyme 2 Shedding
Authors: Wang Li-Fang , Sun Yang-Yang , Pan Qian , Yin Yi-Qing , Tian Xiao-Ming , Liu Yue , Bu Tegeleqi , Zhang Qingy , Wang Yong-An , Zhao Jing , Luo Yuan
Published: May 2023

Lung ischemia-reperfusion (IR) injury is induced by pulmonary artery occlusion and reperfusion. Lung IR injury commonly happens after weaning from extracorporeal circulation, lung transplantation, and pulmonary thromboendarterectomy; it is a lethal perioperative complication. A definite therapeutic intervention remains to be determined. It is known that the enzyme activity of angiotensin-converting enzyme 2 (ACE2) is critical in maintaining pulmonary vascular tone and epithelial integrity. In a noxious environment to the lungs, inactivation of ACE2 is mainly due to a disintegrin and metalloprotease 17 (ADAM17) protein-mediated ACE2 shedding. Thus, we assumed that protection of local ACE2 in the lung against ADAM17-mediated shedding would be a therapeutic target for lung IR injury. In this study, we established both in vivo and in vitro models to demonstrate that the damage degree of lung IR injury depends on the loss of ACE2 and ACE2 enzyme dysfunction in lung tissue. Treatment with ACE2 protectant diminazen aceturate (DIZE) maintained higher ACE2 enzyme activity and reduced angiotensin II, angiotensin type 1 receptor, and ADAM17 levels in the lung tissue. Concurrently, DIZE-inhibited oxidative stress and nitrosative stress via p38MAPK and NF-κB pathways consequently reduced release of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. The underlying molecular mechanism of DIZE contributed to its protective effect against lung IR injury and resulted in the improvement of oxygenation index and ameliorating pulmonary pathological damage. We concluded that DIZE protects the lungs from IR injury via inhibition of ADAM17-mediated ACE2 shedding.
How do goats “read” 2D-images of familiar and unfamiliar conspecifics?
Authors: Langbein Jan , Moreno-Zambrano Mauricio , Siebert Katrin
Published: May 2023

To study individual recognition in animals, discrimination tasks are often conducted by presenting 2D images of real conspecifics. However, animals may discriminate the images merely as visual stimulus combinations without establishing referential relationships to the individuals depicted. In the current study, we investigated whether goats are able to discriminate photos of familiar and unfamiliar conspecifics, whether they not only process the photos as visual stimuli, but also understand them as virtual copies of real conspecifics and whether they grasp the concept of familiarity. Using a computer-controlled learning device, in three tests, goats of two experimental groups (A and B) had to discriminate portrait (Te1), profile (Te2) or headless body photos (Te3) of conspecifics. Tests were presented as 4-choice tasks, with one photo from Group A (rewarded) plus three photos from Group B (distractors). That is, the rewarded photo was familiar to Group A, but unfamiliar to Group B. Finally, in a reversal test (Te4) we reversed this principle. The goats learned the discriminations in Te1 to Te3 within two (Te1 and Te2) and three training days (Te3), respectively, and they needed between 91 [CL (66, 126)] and 174 [CL (126, 241)] trials to reach the learning criterion, with no statistically significant differences between the groups. In Te4, in contrast, the animals took 403 [Group A; CL (291, 557)] and 385 [Group B; CL (286, 519)] trials, respectively, to learn the task. The lack of spontaneous preferences for the photo of the familiar conspecific in the pretests of Te1 to Te3 in Group A, as well as the lack of differences in the number of trials to learn the discriminations between both groups, do not at first glance suggest that the goats established a correspondence between real conspecifics and their 2D representations. However, the higher number of trials in Te4 suggests that both groups formed the learning rule of choosing either the known (Group A) or the unknown goat (Group B) over the course of Te1 to Te3 and then failed after the rule was reversed, providing evidence that goats can associate 2D photos of conspecifics with real animals.
Racism and censorship in the editorial and peer review process
Authors: Strauss Dana , Gran-Ruaz Sophia , Osman Muna , Williams Monnica T. , Faber Sonya C.
Published: May 2023

Psychology aims to capture the diversity of our human experience, yet racial inequity ensures only specific experiences are studied, peer-reviewed, and eventually published. Despite recent publications on racial bias in research topics, study samples, academic teams, and publication trends, bias in the peer review process remains largely unexamined. Drawing on compelling case study examples from APA and other leading international journals, this article proposes key mechanisms underlying racial bias and censorship in the editorial and peer review process, including bias in reviewer selection, devaluing racialized expertise, censorship of critical perspectives, minimal consideration of harm to racialized people, and the publication of unscientific and racist studies. The field of psychology needs more diverse researchers, perspectives, and topics to reach its full potential and meet the mental health needs of communities of colour. Several recommendations are called for to ensure the APA can centre racial equity throughout the editorial and review process.
Empathic disequilibrium as a new framework for understanding individual differences in psychopathology
Authors: Shalev Ido , Eran Alal , Uzefovsky Florina
Published: May 2023

Introduction

Empathy is part of basic social cognition and is central to everyday interactions. Indeed, emotional and cognitive empathy deficits are related to various psychopathologies, yet the links reported have been inconsistent. Thus, the mechanism underlying these inconsistent links is poorly understood. At least a partial answer may lie in that the dependency between cognitive and emotional empathy has been overlooked. Here, we examined the (dis)equilibrium between emotional and cognitive empathy and how it relates to individual differences in clinical traits. We further examined a possible mediator of these links—emotional reactivity.

Methods

Participants (N = 425) from the general population reported on their empathy, emotional reactivity, autistic traits, psychopathic tendencies, and symptoms of depression and anxiety.

Results

Beyond empathy, both extremes of empathic disequilibrium were associated with various features of clinical conditions; Higher emotional relative to cognitive empathy was related to the social domain of autism and anxiety, while higher cognitive relative to emotional empathy was related to the non-social domain of autism, depression symptoms, and psychopathic tendencies. The associations with autistic traits, anxiety, and psychopathic tendencies were mediated by emotional reactivity.

Discussion

Our findings suggest a new framework for understanding how individual variability in empathy is expressed in various psychopathologies.
Varieties of suffering in the clinical setting: re-envisioning mental health beyond the medical model
Authors: Wong Paul T. P. , Laird Don
Published: May 2023

In this paper, we argue for the need to rethink mental health beyond the medical model because much of human suffering cannot be diagnosed by the DSM-5. During the pandemic and post-pandemic, people have learned to accept the fact that no one is immune from suffering. Given the universality and complexity of human suffering, it is natural for people to wrestle with existential questions such as “Why struggle when all life end in death?” and “How can one flourish when life is so hard?” Existential positive psychology (EPP or PP2.0) was developed to address these existential concerns. After explaining the inherent limitations of the medical model and the need for EPP as an alternative vision for mental health, we provide illustrative clinical cases to demonstrate the advantages of this broader existential framework for both case conceptualization and interventions. According to EPP, mental illness is reconceptualized as both deficiency in knowledge and skills in coping with the demands of life and deficiency in meeting the basic needs for livelihood and mental health, the Soul’s yearnings for faith, hope, and love. Finally, we introduce integrative meaning therapy as a therapeutic framework which can equip people with the needed skills to achieve healing, wholeness, and total wellbeing.
Problemas ligados ao álcool em centros de emergência (PLACE)—People experiencing homelessness with alcohol-related problems in Lisbon's emergency shelters during the COVID-19 pandemic: a description and analysis of a harm reduction intervention
Authors: Azevedo Filipe Oliveira , Neto Ana , Gama Ana , Subtil Ana , Fuertes Ricardo , Pereira Claúdia , Tavares Joana , Medinas Raquel Luis , Silva Ana V. , Dias Sónia
Published: May 2023

Introduction

Alcohol-related problems disproportionally affect people experiencing homelessness. As the first wave of the COVID-2019 pandemic spread in 2020, a number of emergency shelters were opened in Lisbon. Increased difficulties in obtaining alcohol could have led to an increased incidence of alcohol withdrawal. Therefore, a low-threshold harm reduction intervention was introduced to these emergency shelters. This consisted of a fixed medication treatment, made available immediately for those with specific conditions, without the need for a medical evaluation or abstinence from alcohol, together with an offer of subsequent access to specialized addiction centers. The Problemas Ligados ao Álcool em Centros de Emergência (PLACE) study (alcohol-related problems in emergency shelters) is a retrospective mixed-methods observational study. It describes the demographic, health, and social characteristics of shelter users participating in the program and aims to evaluate the intervention as well as the experience of the patients, professionals, and decision-makers involved.

Results

A total of 69 people using shelters self-reported alcohol-related problems. Among them, 36.2% of the people accepted a pharmacological intervention, and 23.2% selected an addiction appointment. The take-up of the intervention was associated with better housing outcomes. A description of an individual's trajectory after leaving the shelter is provided.

Discussion

This study suggests that non-abstinence-focused interventions can be useful and well-tolerated in treating addiction in this population.
Effects of varenicline on the serum levels of olanzapine in male patients with Schizophrenia: a randomized controlled trial
Authors: Deng Mengling , Yang Zhi , Ni Yanfei , Zhu Lingli , Xu Jiating , Zheng Lifeng , Zhou Bo
Published: May 2023

Background

Smoking in patients with Schizophrenia is more common than in the general population. Varenicline, a partial agonist at α4β2 nicotinic acetylcholine receptors, is an effective smoking cessation pharmacotherapy in patients with Schizophrenia. However, its effects on the serum levels of antipsychotics in Schizophrenia are understudied. This study investigated the impact of smoking cessation with varenicline on the serum concentration of olanzapine in patients with Schizophrenia.

Methods

Adult smokers with Schizophrenia were enrolled in a 12-week course of varenicline and placebo for smoking cessation. The serum concentration of olanzapine was measured at baseline and weeks 1, 2, 4, 8, and 12. Data were analyzed with the generalized additive mixed model.

Results

During the 12-week study, the results indicated that olanzapine concentrations increased nonlinearly in the varenicline and placebo groups. Threshold effect analysis suggested that the olanzapine concentrations increased over time until the turning point (week 4). However, there was no significant difference between the two treatment groups.

Conclusion

Varenicline showed safety and efficacy in smoking cessation in people with Schizophrenia.
Urban and individual correlates of subjective well-being in China: An application of gradient boosting decision trees
Authors: Huang Xiaoyan , Kang Chenchen , Yin Chun , Li Yu
Published: May 2023

Introduction

Subjective well-being (SWB) is attributable to both individual and environmental attributes. However, extant studies have paid little attention to the contribution of environmental attributes at the urban level to SWB or their nonlinear associations with SWB.

Methods

This study applies a machine learning approach called gradient boosting decision trees (GBDTs) to the 2013 China Household Income Survey data to investigate the relative importance of urban and individual attributes to and their nonlinear associations with SWB.

Results

The urban and individual attributes make similar relative contributions to SWB. Income and age are the most important predictors. Urban facilities make a larger contribution than urban development factors. Moreover, urban attributes exert nonlinear and threshold effects on SWB. Cultural facilities and green space have inverted U-shaped correlations with SWB. Educational facilities, medical facilities, and population size are monotonically associated with SWB and have specific thresholds.

Discussion

Improving urban attributes is important to enhancing residents’ SWB.
Social capital and loneliness among older adults in community dwellings and nursing homes in Zhejiang Province of China
Authors: Chen Yan , Zhou Yuchen , Li Min , Hong Yanyan , Chen Hongkun , Zhu Shanshan , Zhou Yiying , Yang Shuangyu , Wu Xianlan , Wang Dahui
Published: May 2023

Background

Loneliness is an important problem afflicting the health of older adults, and has been proven to be associated with social capital. Previous research in China rarely investigated the differences of social capital and loneliness between older adults living in community dwellings and nursing homes. This study aims to examine the status of social capital and loneliness among older adults living in community dwellings and nursing homes, and analyze the relationship between them.

Methods

A total of 1,278 older adults were recruited for the study from the cities of Hangzhou, Huzhou, and Lishui in Zhejiang Province of China from July to October 2021 by using multi-stage stratified random sampling. Questionnaires were used to collect data on the participants’ sociodemographic characteristics, social capital, and loneliness. Hierarchical multiple regression was used to examine the relationship between social capital and loneliness. The interaction of social capital and institutionalization on loneliness was also explored.

Results

Compared with community-dwelling older adults, institutionalized older adults had higher levels of loneliness and lower degrees of social support, social connection, trust, cohesion, and reciprocity. A further analysis of the social capital showed that low levels of social support, trust, and cohesion were related to high levels of loneliness among adults in both community dwellings and nursing homes. Social connection was negatively correlated with loneliness among older adults living in community dwellings. Institutionalization itself demonstrated a strong effect on loneliness.

Conclusion

Health-related policies should help older adults gain more social support, trust and cohesion to alleviate their loneliness. This is particularly crucial for older adults living in nursing homes, as they have higher levels of loneliness and lower levels of social capital than noninstitutionalized older adults.
Access to anticancer medicines in public hospitals of Northwestern China
Authors: Ma Yue , Peng Jin , Yao Xuelin , Feng Liuxin , Shi Xinke , Jiang Minghuan
Published: May 2023

Objective

We aimed to evaluate the accessibility of anticancer medicines in public hospitals of Shaanxi, a representative province of Northwestern China.

Methods

Thirty-one anticancer medicines were investigated in 146 designated public hospitals in 10 cities of Shaanxi Province. We used medicine procurement data from the Shaanxi Drug Centralized Purchasing Platform during 2019–2021. Primary outcomes included the availability, drug utilization, and affordability of anticancer medicines.

Results

The mean availability of 31 anticancer medicines increased significantly from 5.45% in 2019 to 14.72% in 2021. The mean availability of nationally negotiated medicines was significantly lower than that of Class B medicines (8.72% vs. 12.85%, p = 0.048), whilst the availability of injectable medicines was significantly greater than that of oral medicines (13.66% vs. 8.77%, p = 0.007). In 2019–2021, the annual mean amount purchased increased significantly from CNY 6.51 million to CNY 18.56 million (p = 0.007). The mean defined daily doses of 31 medicines significantly rose from 225.50 to 1019.50 (p = 0.008) whereas their defined daily drug cost significantly decreased from CNY 551.15 to CNY 404.50 (p < 0.001). The percentage of catastrophic health expenditure decreased from 71.0 to 51.65% and from 90.30 to 80.60% for urban and rural residents, respectively. The affordability of nationally negotiated medicines was significantly lower than that of Class B medicines (p = 0.032), and the affordability of injectable medicines had no significant difference compared to that of oral medicines (p = 0.124) for both urban and rural residents.

Conclusion

The accessibility of anticancer medicines improved dramatically in public hospitals of Northwestern China during the period 2019–2021.
Development of the self-regulation assessment and content validation using cognitive interviews in a multicultural post-rehabilitation population
Authors: Mol Tanja , Scholten Eline , van Bennekom Coen , Post Marcel
Published: May 2023

Aim

Self-regulation is one of the main goals of medical rehabilitation. Four themes of self-regulation were identified by former patients and rehabilitation physicians in a previous study. Based on these themes, a measure for self-regulation, the self-regulation assessment (SeRA), was developed. This study aimed to establish the content validity of the SeRA in a multicultural and multi-diagnostic post-rehabilitation population.

Methods

The Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology was applied. First, cognitive interviews were held with eight former rehabilitation patients. Feedback was obtained on relevance, comprehensibility, and comprehensiveness of the items. Items with problems were revised. Then, a second series of cognitive interviews was held with 16 former rehabilitation patients with non-Western migration backgrounds. Again, feedback was obtained on relevance, comprehensibility, and comprehensiveness of the items.

Results

The first series of cognitive interviews revealed good comprehensiveness, and also comprehensibility or relevance problems with 12 of the 25 items. These items were revised or deleted. Two missing concepts were identified and these were added. There was no need to revise the items based on the results of the second series of cognitive interviews.

Conclusion

The final version of the SeRA demonstrated content validity for the studied population. The measure is ready for psychometric analyses in subsequent validation studies.
Experiences of newly qualified dentists in delivering oral health advice to parents/caregivers of young children—challenges and solutions
Authors: Rutter Lucy , Duara Raginie , Vinall-Collier Karen A. , Owen Jenny , Haley Isabelle , Gray-Burrows Kara A. , Hearnshaw Simon , Marshman Zoe , Day Peter F.
Published: May 2023

Introduction

A key skill for dental professionals to master is their ability to have effective preventive oral health conversations. On qualifying, UK dentists undertake a one-year foundation training programme in general practice. This study explored with Foundation Dentists, the barriers and facilitators to undertaking oral health conversations with parents/caregivers and their children, aged 0–11 years old.

Materials and methods

Approximately 100 Foundation Dentists from the Yorkshire and Humber region attended a series of focus groups. They discussed how they and their wider dental team undertake oral health conversations with parents/caregivers of young children, aged 0–11 years old. The data was analysed using thematic analysis.

Results

Five themes were identified as barriers and facilitators to providing oral health advice: (1) Lack of knowledge around parenting skills and child development; (2) Parental receptivity; (3) Motivation for changing behaviours; (4) Information content and inconsistency; and (5) Current National Health Service (NHS) structures of general dental practice.

Discussion

A multi-faceted approach is needed to develop the training of Foundation Dentists to undertake preventive oral health conversations with parents/caregivers and children. Such an approach has the potential to improve the patient-practitioner relationship and increase effective behaviour change conversations taking place in general dental care, thus improving children's oral health.
Recipient TIM4 signaling regulates ischemia reperfusion-induced ER stress and metabolic responses in liver transplantation: from mouse-to-human
Authors: Hirao Hirofumi , Kageyama Shoichi , Nakamura Kojiro , Kadono Kentaro , Kojima Hidenobu , Siyuan Yao , Farmer Douglas G. , Kaldas Fady M. , Dery Kenneth J. , Kupiec-Weglinski Jerzy W.
Published: May 2023

T-cell immunoglobulin and mucin (Tim)4 is expressed on APCs, including macrophages, as one of the main amplifiers in the mechanism of liver ischemia-reperfusion injury (IRI) following orthotopic liver transplantation (OLT). Though donor Tim4 selectively expressed on Kupffer cells serves as a checkpoint regulator of innate immune-driven IRI cascades, its role on cells outside the OLT remains unclear. To dissect the role of donor vs. recipient-specific Tim4 signaling in IR-induced stress and hepatocellular function, we employed a murine OLT model utilizing Tim4-knockout (KO) mice as either donor or recipient (WT → WT, WT → Tim4-KO, Tim4-KO → WT). In the experimental arm, disruption of donor Tim4 attenuated IRI-OLT damage, while recipient Tim4-null mutation aggravated hepatic IRI concomitant with disturbed lipid metabolism, enhanced endoplasmic reticulum stress, and activated pro-apoptotic signaling in the grafts. In the in vitro study, murine hepatocytes co-cultured with Tim4-null adipose tissue showed enhanced C/EBP homologous protein (CHOP) expression pattern and susceptibility to hepatocellular death accompanied by activated caspase cascade in response to TNF-α stimulation. In the clinical arm, liver grafts from forty-one transplant patients with enhanced TIM4 expression showed higher body mass index, augmented hepatic endoplasmic reticulum stress, enhanced pro-apoptotic markers, upregulated innate/adaptive immune responses, exacerbated hepatocellular damage, and inferior graft survival. In conclusion, although TIM4 is considered a principal villain in peri-transplant early tissue injury, recipient TIM4 signaling may serve as a savior of IR-triggered metabolic stress in mouse and human OLT recipients.
Paving a pathway for large-scale utilization of genomics in precision medicine and population health
Authors: Walton Nephi A. , Christensen G. Bryce
Published: May 2023

Having worked with two large population sequencing initiatives, the separation between the potential for genomics in precision medicine and the current reality have become clear. To realize this potential requires workflows, policies, and technical architectures that are foreign to most healthcare systems. Many historical processes and regulatory barriers currently impede our progress. The future of precision medicine includes genomic data being widely available at the point of care with systems in place to manage its efficient utilization. To achieve such vision requires substantial changes in billing, reimbursement, and reporting as well as the development of new systemic and technical architectures within the healthcare system. Clinical geneticist roles will evolve into managing precision health frameworks and genetic counselors will serve crucial roles in both leading and supporting precision medicine through the implementation and maintenance of precision medicine architectures. Our current path has many obstacles that hold us back, leaving preventable deaths in the wake. Reengineering our healthcare systems to support genomics can have a major impact on patient outcomes and allow us to realize the long-sought promises of precision medicine.
Characterization of canine adipose- and endometrium-derived Mesenchymal Stem/Stromal Cells and response to lipopolysaccharide
Authors: Phyo Hlaing , Aburza Amira , Mellanby Katie , Esteves Cristina L.
Published: May 2023

Mesenchymal stem/stromal cells (MSCs) are used for regenerative therapy in companion animals. Their potential was initially attributed to multipotency, but subsequent studies in rodents, humans and veterinary species evidenced that MSCs produce factors that are key mediators of immune, anti-infective and angiogenic responses, which are essential in tissue repair. MSCs preparations have been classically obtained from bone marrow and adipose tissue (AT) in live animals, what requires the use of surgical procedures. In contrast, the uterus, which is naturally exposed to external insult and infection, can be accessed nonsurgically to obtain samples, or tissues can be taken after neutering. In this study, we explored the endometrium (EM) as an alternative source of MSCs, which we compared with AT obtained from canine paired samples. Canine AT- and EM-MSCs, formed CFUs when seeded at low density, underwent tri-lineage differentiation into adipocytes, osteocytes and chondrocytes, and expressed the CD markers CD73, CD90 and CD105, at equivalent levels. The immune genes IL8, CCL2 and CCL5 were equally expressed at basal levels by both cell types. However, in the presence of the inflammatory stimulus lipopolysaccharide (LPS), expression of IL8 was higher in EM- than in AT-MSCs (p < 0.04) while the other genes were equally elevated in both cell types (p < 0.03). This contrasted with the results for CD markers, where the expression was unaltered by exposing the MSCs to LPS. Overall, the results indicate that canine EM-MSCs could serve as an alternative cell source to AT-MSCs in therapeutic applications.
Aeroelastic Stability of an Aerial Refueling Hose–Drogue System with Aerodynamic Grid Fins
Authors: Salehi Paniagua Keyvan , García-Fogeda Pablo , Arévalo Félix
Published: May 2023

In this work, the aeroelastic stability of an aerial refueling system is investigated. The system is formed by a classical hose and drogue, and the novelty of our work is the inclusion of a grid fin configuration to improve its stability. The unsteady aerodynamic forces on the grid fins are determined using the concept of a unit grid fin (UGF). For each UGF, the unsteady aerodynamic forces are computed using the Doublet-Lattice Method, and the forces on the complete grid fins are calculated using interfering factors obtained from wind tunnel measurements for the steady case. The static equilibrium position of the system influences the linearized perturbed unsteady motion of the ensemble. This effect, together with the phase lag angle introduced to account for the unsteady aerodynamic forces in the hose, makes the flutter computation of the complete system a non-typical one. The results show that, by adding the grid fins, the stability of the refueling system is improved, delaying or annulling flutter occurrence.
“Golden” Tomato Consumption Ameliorates Metabolic Syndrome: A Focus on the Redox Balance in the High-Fat-Diet-Fed Rat
Authors: Gambino Giuditta , Giglia Giuseppe , Allegra Mario , Di Liberto Valentina , Zummo Francesco Paolo , Rappa Francesca , Restivo Ignazio , Vetrano Filippo , Saiano Filippo , Palazzolo Eristanna , Avellone Giuseppe , Ferraro Giuseppe , Sardo Pierangelo , Di Majo Danila
Published: May 2023

Tomato fruits defined as “golden” refer to a food product harvested at an incomplete ripening stage with respect to red tomatoes at full maturation. The aim of this study is to explore the putative influence of “golden tomato” (GT) on Metabolic Syndrome (MetS), especially focusing on the effects on redox homeostasis. Firstly, the differential chemical properties of the GT food matrix were characterized in terms of phytonutrient composition and antioxidant capacities with respect to red tomato (RT). Later, we assessed the biochemical, nutraceutical and eventually disease-modifying potential of GT in vivo in the high-fat-diet rat model of MetS. Our data revealed that GT oral supplementation is able to counterbalance MetS-induced biometric and metabolic modifications. Noteworthy is that this nutritional supplementation proved to reduce plasma oxidant status and improve the endogenous antioxidant barriers, assessed by strong systemic biomarkers. Furthermore, consistently with the reduction of hepatic reactive oxygen and nitrogen species (RONS) levels, treatment with GT markedly reduced the HFD-induced increase in hepatic lipid peroxidation and hepatic steatosis. This research elucidates the importance of food supplementation with GT in the prevention and management of MetS.
Oxidative Stress, Reductive Stress and Antioxidants in Vascular Pathogenesis and Aging
Authors: Mladenov Mitko , Lubomirov Lubomir , Grisk Olaf , Avtanski Dimiter , Mitrokhin Vadim , Sazdova Iliyana , Keremidarska-Markova Milena , Danailova Yana , Nikolaev Georgi , Konakchieva Rossitza , Gagov Hristo
Published: May 2023

This review is focused on the mechanisms that regulate health, disease and aging redox status, the signal pathways that counteract oxidative and reductive stress, the role of food components and additives with antioxidant properties (curcumin, polyphenols, vitamins, carotenoids, flavonoids, etc.), and the role of the hormones irisin and melatonin in the redox homeostasis of animal and human cells. The correlations between the deviation from optimal redox conditions and inflammation, allergic, aging and autoimmune responses are discussed. Special attention is given to the vascular system, kidney, liver and brain oxidative stress processes. The role of hydrogen peroxide as an intracellular and paracrine signal molecule is also reviewed. The cyanotoxins β-N-methylamino-l-alanine (BMAA), cylindrospermopsin, microcystins and nodularins are introduced as potentially dangerous food and environment pro-oxidants.
Model-Based Analysis and Optimization of Acidic Tin–Iron Flow Batteries
Authors: Chen Fuyu , Wang Ying , Shi Ying , Chen Hui , Ma Xinzhi , Zhang Qinfang
Published: May 2023

Acidic tin–iron flow batteries (TIFBs) employing Sn/Sn2+ and Fe2+/Fe3+ as active materials are regarded as promising energy storage devices due to their superior low capital cost, long lifecycle, and high system reliability. In this paper, the performance of TIFBs is thoroughly investigated via a proposed dynamic model. Moreover, their design and operational parameters are comprehensively analyzed. The simulation results show that (i) a flow factor of two is favorable for practical TIFBs; (ii) about 20% of the system’s efficiency is decreased as the current density increases from 40 mA cm−2 to 200 mA cm−2; (iii) the optimal electrode thickness and electrode aspect ratio are 6 mm and 1:1, respectively; and (iv) reducing the compression ratio and increasing porosity are effective ways of lowering pump loss. Such in-depth analysis can not only provide a cost-effective method for optimizing and predicting the behaviors and performance of TIFBs but can also be of great benefit to the design, management, and manufacture of tin–iron flow batteries.
Mediating Lithium Plating/Stripping by Constructing 3D Au@Cu Pentagonal Pyramid Array
Authors: Liang Yaohua , Ding Wei , Yao Bin , Zheng Fan , Smirnova Alevtina , Gu Zhengrong
Published: May 2023

Lithium (Li) metal is perceived as the “holy grail” of anodes for secondary batteries due to its innate merits. Regrettably, the commercial application of Li metal anodes (LMAs) has been hampered by problems derived from the uncontrollable growth of Li dendrites, which could result in formation of short-circuits, thereby leading to fatal safety accidents. Here, a three-dimensional lithiophilic gold (Au)-coated copper (Cu) pentagonal pyramid array (Au@CuPPA) is constructed on planar Cu foil via electrodeposition followed by a chemical reduction method. Owing to the features of the lithiophilic layer and 3D porous structure, the proposed Au@CuPPA can not only facilitate Li-ion migration and charge transfer, but also effectively diminish the nucleation overpotential. Consequently, an even and steady Li plating/stripping process for up to 460 h and with a charge capacity of 3 mAh cm−2 is accomplished by using the Au@CuPPA current collector. The Li@Au@CuPPA|LiFePO4 full cell achieves a high Coulombic efficiency (CE) of 99.4% for 150 cycles at 0.5 C with a capacity retention of 92.4%.
The COVID-19 Pandemic: How Technology Is Reshaping Public Health and Medicine
Authors: Coelho Luís , Glotsos Dimitrios , Reis Sara
Published: May 2023

The outbreak of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been a watershed moment in human history, causing a profound shift in the global landscape that has affected every aspect of our lives [...]
TRPM4 Blocking Antibody Protects Cerebral Vasculature in Delayed Stroke Reperfusion
Authors: Chen Bo , Wei Shunhui , Low See Wee , Poore Charlene Priscilla , Lee Andy Thiam-Huat , Nilius Bernd , Liao Ping
Published: May 2023

Reperfusion therapy for acute ischemic stroke aims to restore the blood flow of occluded blood vessels. However, successful recanalization is often associated with disruption of the blood-brain barrier, leading to reperfusion injury. Delayed recanalization increases the risk of severe reperfusion injury, including severe cerebral edema and hemorrhagic transformation. The TRPM4-blocking antibody M4P has been shown to alleviate reperfusion injury and improve functional outcomes in animal models of early stroke reperfusion. In this study, we examined the role of M4P in a clinically relevant rat model of delayed stroke reperfusion in which the left middle cerebral artery was occluded for 7 h. To mimic the clinical scenario, M4P or control IgG was administered 1 h before recanalization. Immunostaining showed that M4P treatment improved vascular morphology after stroke. Evans blue extravasation demonstrated attenuated vascular leakage following M4P treatment. With better vascular integrity, cerebral perfusion was improved, leading to a reduction of infarct volume and animal mortality rate. Functional outcome was evaluated by the Rotarod test. As more animals with severe injuries died during the test in the control IgG group, we observed no difference in functional outcomes in the surviving animals. In conclusion, we identified the potential of TRPM4 blocking antibody M4P to ameliorate vascular injury during delayed stroke reperfusion. If combined with reperfusion therapy, M4P has the potential to improve current stroke management.
Research on One-to-Two Internal Resonance of Sling and Beam of Suspension Sling–Beam System
Authors: Gu Lixiong , Dong Chunguang , Zhang Yi , Zhen Xiaoxia , Liu Guiyuan , Ji Jianyi
Published: May 2023

An approach is presented to investigate the 1:2 internal resonance of the sling and beam of a suspension sling–beam system. The beam was taken as the geometrically linear Euler beam, and the sling was considered to be geometrically nonlinear. The dynamic equilibrium equation of the structures was derived using the modal superposition method, the D’Alembert principle and the Hamilton principle. The nonlinear dynamic equilibrium equations of free vibration and forced oscillation were solved by the multiple-scales method. We derived the first approximation solutions for the single-modal motion of the system. Numerical examples are provided to verify the correctness of formula derivation and obtain the amplitude–time response of free vibration, the primary resonance response, the amplitude–frequency response, and the amplitude–force response of forced oscillation. According to the analysis, it is evident that the combination system exhibits robust nonlinear coupling properties due to the presence of internal resonance, which are useful for engineering design.
Can Public Spaces Alleviate Poverty-Related Feelings? Content Analysis of Vision 2030 and Egyptian Residents’ Storytelling
Authors: Abusaada Hisham , Elshater Abeer
Published: May 2023

This study argues that Vision 2030 and social housing should consider the elements of the sociocultural dimension of urban design (SDUD) to alleviate urban poverty-induced feelings. By examining public spaces in the context of Vision 2030 and the implementation of social housing projects, this study aims to provide a theoretical framework that may assist city policymakers in rethinking the role of public spaces in alleviating poverty-related feelings. A review of the relevant literature explores the SDUD elements and builds an index to measure poverty through bibliometric and content analysis. This index was used to analyze the gaps in Vision 2030 in South Africa, Kenya, and Egypt, which we randomly chose. It focused on SDUD elements, social housing, and public spaces. We empirically examined the role of public spaces in alleviating poverty-related feelings using the SDUD index. We applied episodic narrative and interview-based storytelling techniques to a limited group of poor residents in the Al Asmarat Housing Project in Mokattam, Cairo, Egypt. This interview discusses the role of public spaces in reducing poverty-related feelings. The results focus on exploring the four SDUD elements of poverty and examining how public spaces alleviate poverty-induced feelings. Vision 2030 revolves around SDUD elements, social housing, and public spaces. Urban design policies can alleviate poverty in development projects for the poor. Integrating urban design policies into Vision 2030 makes city dwellers in developing countries feel less inferior.
Comparison between Nasopharyngeal and Saliva Samples for the Detection of Respiratory Viruses in Children with Acute Lower Respiratory Tract Infections: A Pilot Study
Authors: Buonsenso Danilo , Valentini Piero , Mariani Francesco , Di Noi Silvia , Mazza Sofia , Palucci Ivana , Sanguinetti Maurizio , Sali Michela
Published: May 2023

Purpose: During the COVID-19 pandemic, the use of salivary swabs (SS) to detect the SARS-CoV-2 virus has been implemented and widely studied in adults and children. However, the role of SS in detecting other common respiratory viruses in children is poorly investigated. Methods: Children younger than 18 years of age admitted with respiratory signs and symptoms underwent both nasopharyngeal and SS procedures. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of SS were calculated, considering the nasopharyngeal swab result as the gold standard. Results: A total of 83 patients (44 females, 53%) underwent both nasopharyngeal and SS procedures. Overall, the sensitivity of SS was 49.4%. Sensitivity according to different respiratory viruses ranged from 0% to 71.43%, while the specificity ranged from 96% to 100%. Negative predictive value ranged from 68.06% to 98.8%, while positive predictive value ranged from 0 to 100%. SS sensitivity in patients younger than 12 months of age was 39.47%, while in patients older than or equal to 12 months of age it was 57.78%. Patients with negative SS had a significantly lower median age (8.5 months (15.25) vs. 23 months (34), p = 0.001) and a significantly lower quantity of median saliva collected for salivary analysis (0 μL (213) vs. 300 μL (100), p < 0.001). Conclusions: SS has a relatively low sensitivity in detecting common respiratory viruses in children with LRTI, with a lower probability in younger children (and in particular those younger than 6 months of age) or those from whom we have collected lesser amounts of saliva. New strategies to improve saliva collection are needed for testing on a larger study population.
Whole Exome-Trio Analysis Reveals Rare Variants Associated with Congenital Pouch Colon
Authors: Gupta Sonal , Mathur Praveen , Mishra Ashwani Kumar , Medicherla Krishna Mohan , Bandapalli Obul Reddy , Suravajhala Prashanth
Published: May 2023

Anorectal malformations (ARM) are individually common, but Congenital Pouch Colon (CPC) is a rare anorectal anomaly that causes a dilated pouch and communication with the genitourinary tract. In this work, we attempted to identify de novo heterozygous missense variants, and further discovered variants of unknown significance (VUS) which could provide insights into CPC manifestation. From whole exome sequencing (WES) performed earlier, the trio exomes were analyzed from those who were admitted to J.K. Lon Hospital, SMS Medical College, Jaipur, India, between 2011 and 2017. The proband exomes were compared with the unaffected sibling/family members, and we sought to ask whether any variants of significant interest were associated with the CPC manifestation. The WES data from a total of 64 samples including 16 affected neonates (11 male and 5 female) with their parents and unaffected siblings were used for the study. We examined the role of rare allelic variation associated with CPC in a 16 proband/parent trio family, comparing the mutations to those of their unaffected parents/siblings. We also performed RNA-Seq as a pilot to find whether or not the genes harboring these mutations were differentially expressed. Our study revealed extremely rare variants, viz., TAF1B, MUC5B and FRG1, which were further validated for disease-causing mutations associated with CPC, further closing the gaps of surgery by bringing intervention in therapies.