bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic stress targets mitochondrial respiratory efficiency in the skeletal muscle of C57BL/6 mice
Authors: Nikolic Aleksandra , Fahlbusch Pia , Wahlers Natalie , Riffelmann Nele-Kathrien , Jacob Sylvia , Hartwig Sonja , Kettel Ulrike , Dille Matthias , Al-Hasani Hadi , Kotzka Jörg , Knebel Birgit
Published: March 2023

Episodes of chronic stress can result in psychic disorders like post-traumatic stress disorder, but also promote the development of metabolic syndrome and type 2 diabetes. We hypothesize that muscle, as main regulator of whole-body energy expenditure, is a central target of acute and adaptive molecular effects of stress in this context. Here, we investigate the immediate effect of a stress period on energy metabolism in Musculus gastrocnemius in our established C57BL/6 chronic variable stress (Cvs) mouse model. Cvs decreased lean body mass despite increased energy intake, reduced circadian energy expenditure (EE), and substrate utilization. Cvs altered the proteome of metabolic components but not of the oxidative phosphorylation system (OXPHOS), or other mitochondrial structural components. Functionally, Cvs impaired the electron transport chain (ETC) capacity of complex I and complex II, and reduces respiratory capacity of the ETC from complex I to ATP synthase. Complex I-OXPHOS correlated to diurnal EE and complex II-maximal uncoupled respiration correlated to diurnal and reduced nocturnal EE. Bioenergetics assessment revealed higher optimal thermodynamic efficiencies (ƞ-opt) of mitochondria via complex II after Cvs. Interestingly, transcriptome and methylome were unaffected by Cvs, thus excluding major contributions to supposed metabolic adaptation processes. In summary, the preclinical Cvs model shows that metabolic pressure by Cvs is initially compensated by adaptation of mitochondria function associated with high thermodynamic efficiency and decreased EE to manage the energy balance. This counter-regulation of mitochondrial complex II may be the driving force to longitudinal metabolic changes of muscle physiological adaptation as the basis of stress memory.
Finiteness properties of automorphism spaces of manifolds with finite fundamental group
Authors: Bustamante Mauricio , Krannich Manuel , Kupers Alexander
Published: March 2023

Given a closed smooth manifold M of even dimension $$2n\ge 6$$

2
n
≥
6

with finite fundamental group, we show that the classifying space $$B\textrm{Diff}(M)$$

B
Diff
(
M
)

of the diffeomorphism group of M is of finite type and has finitely generated homotopy groups in every degree. We also prove a variant of this result for manifolds with boundary and deduce that the space of smooth embeddings of a compact submanifold $$N\subset M$$

N
⊂
M

of arbitrary codimension into M has finitely generated higher homotopy groups based at the inclusion, provided the fundamental group of the complement is finite. As an intermediate result, we show that the group of homotopy classes of simple homotopy self-equivalences of a finite CW complex with finite fundamental group is up to finite kernel commensurable to an arithmetic group.
Unauthorized change of immunosuppressants by patients with rheumatic diseases in the COVID-19 pandemic: a cross-sectional analysis of a patient survey
Authors: Dahm Simon , Henes Joerg C. , Saur Sebastian J.
Published: March 2023

This study provides insight in behavior and perspective of rheumatic patients during the first COVID-19 wave. Especially, we analyzed the patients’ fear of COVID-19 and unauthorized change of immunosuppressive medication in consequence of their fear. We hereby provide data from 877 patients with valuable insights into the patients’ point of view. We retrospectively interviewed patients of our rheumatic university outpatient clinic. This way, we collected information about the patients’ personal point of view. Data like the rheumatic diagnosis and immunosuppressive medication was extracted from the health records. Statistical analysis was conducted using IBM® SPSS® Statistics (version 26). A total of 877 patients were included into our study. We could show that fear of COVID-19 was clearly present in rheumatic patients. Higher fear levels seem to be associated with comorbidity burden. Unauthorized change of immunosuppressive medication was rare in our study (5%). In our study we provide novel insight into patients’ point of view and behavior of rheumatic patients. Unauthorized change of immunosuppressive medication was rare (5%) as seen in other studies. The low rate of unauthorized change and high rate of compliance is reassuring since good disease control appears to be prognostically important in the progression of COVID-19 disease. Therefore, as the pandemic continues, treatment decisions should be made in close consultation between patient and practitioner to improve adherence and reduce morbidity and mortality.
Topographic patterns of retinal lesions in multiple evanescent white dot syndrome
Authors: Ong Ariel Yuhan , Birtel Johannes , Agorogiannis Eleftherios , Sharma Srilakshmi M. , Charbel Issa Peter
Published: March 2023

Purpose

To demonstrate different topographic distributions of multiple-evanescent white dot syndrome (MEWDS) and secondary MEWDS disease and to describe possible associations.

Methods

Clinical evaluation and multimodal retinal imaging in 27 subjects with MEWDS (29 discrete episodes of MEWDS). Ophthalmic assessment included best-corrected visual acuity testing and multimodal retinal imaging with OCT, blue-light autofluorescence, fluorescein and indocyanine green angiography, fundus photography, and widefield pseudocolor and autofluorescence fundus imaging.

Results

The topographic distribution of MEWDS lesions was centered on or around the optic disc (n = 17, 59%), centered on the macula (n = 7, 24%), sectoral (n = 2, 7%), or was indeterminate (n = 3, 10%). The MEWDS episodes either occurred in the absence (‘primary MEWDS’; n = 14, 48%) or presence of concurrent chorioretinal pathology (‘secondary MEWDS’; n = 15, 52%). In patients with the latter, MEWDS lesions were often centered around a coexisting chorioretinal lesion. The majority of patients in both groups experienced resolution of their symptoms and retinal changes on multimodal imaging by 3 months.

Conclusions

Distinct distributions of MEWDS lesions were identified. MEWDS may occur in tandem with other chorioretinal pathology, which may impact the topography of MEWDS lesions.
Value of palliative surgery in perihilar cholangiocarcinoma
Authors: Dondorf Felix , Rohland Oliver , Deeb Aladdin Ali , Ardelt Michael , Settmacher Utz , Rauchfuss Falk
Published: March 2023

Purpose

The survival rate of patients
with irresectable perihilar cholangiocarcinoma is remarkably poor. An essential part of palliation is treatment of obstructive cholestasis caused by the tumor. Currently, this is mainly performed endoscopically by stent or via PTBD, requiring frequent changes of the stents and limiting health-related quality of life due to the multiple hospital stays needed. The aim of this study was to evaluate surgical palliation via extrahepatic bile duct resection as an option for palliative treatment.

Methods

Between 2005 and 2016, we treated 120 pCCC patients with primary palliative care. Three treatment strategies were retrospectively considered: extrahepatic bile duct resection (EBR), exploratory laparotomy (EL), and primary palliative (PP) therapy.

Results

The EBR group required significantly less stenting postoperatively, and the overall morbidity was 29.4% (EBR). After the surgical procedure, fewer subsequent endoscopic treatments for stenting or PTBD were necessary in the EBR group over time. The 30-day mortality was 5.9% (EBR) and 3.4% (EL). The median overall survival averaged 570 (EBR), 392 (EL), and 247 (PP) days.

Conclusions

In selected pCCC patients, palliative extrahepatic bile duct resection is a feasible option for treatment of obstructive cholestasis and should be reconsidered as a therapy option for these patients even in a palliative setting.
Pendrin abundance, subcellular distribution, and function are unaffected by either αENaC gene ablation or by increasing ENaC channel activity
Authors: Loffing Johannes , Pech Vladimir , Loffing-Cueni Dominique , Abood Delaney C. , Kim Young Hee , Chen Chao , Pham Truyen D. , Verlander Jill W. , Wall Susan M.
Published: March 2023

The intercalated cell Cl−/HCO3− exchanger, pendrin, modulates ENaC subunit abundance and function. Whether ENaC modulates pendrin abundance and function is however unknown. Because αENaC mRNA has been detected in pendrin-positive intercalated cells, we hypothesized that ENaC, or more specifically the αENaC subunit, modulates intercalated cell function. The purpose of this study was therefore to determine if αENaC is expressed at the protein level in pendrin-positive intercalated cells and to determine if αENaC gene ablation or constitutively upregulating ENaC activity changes pendrin abundance, subcellular distribution, and/or function. We observed diffuse, cytoplasmic αENaC label in pendrin-positive intercalated cells from both mice and rats, with much lower label intensity in pendrin-negative, type A intercalated cells. However, while αENaC gene ablation within principal and intercalated cells of the CCD reduced Cl− absorption, it did not change pendrin abundance or subcellular distribution in aldosterone-treated mice. Further experiments used a mouse model of Liddle’s syndrome to explore the effect of increasing ENaC channel activity on pendrin abundance and function. The Liddle’s variant did not increase either total or apical plasma membrane pendrin abundance in aldosterone-treated or in NaCl-restricted mice. Similarly, while the Liddle’s mutation increased total Cl− absorption in CCDs from aldosterone-treated mice, it did not significantly affect the change in Cl− absorption seen with pendrin gene ablation. We conclude that in rats and mice, αENaC localizes to pendrin-positive ICs where its physiological role remains to be determined. While pendrin modulates ENaC abundance, subcellular distribution, and function, ENaC does not have a similar effect on pendrin.
Perturbed eigenvalues of polyharmonic operators in domains with small holes
Authors: Felli Veronica , Romani Giulio
Published: March 2023

We study singular perturbations of eigenvalues of the polyharmonic operator on bounded domains under removal of small interior compact sets. We consider both homogeneous Dirichlet and Navier conditions on the external boundary, while we impose homogeneous Dirichlet conditions on the boundary of the removed set. To this aim, we develop a notion of capacity which is suitable for our higher-order context, and which permits to obtain a description of the asymptotic behaviour of perturbed simple eigenvalues in terms of a capacity of the removed set, in dependence of the respective normalized eigenfunction. Then, in the particular case of a subset which is scaling to a point, we apply a blow-up analysis to detect the precise convergence rate, which turns out to depend on the order of vanishing of the eigenfunction. In this respect, an important role is played by Hardy–Rellich inequalities in order to identify the appropriate functional space containing the limiting profile. Remarkably, for the biharmonic operator this turns out to be the same, regardless of the boundary conditions prescribed on the exterior boundary.
DEM study of an “avatar” railway ballast with real particle shape, fabric and contact mechanics
Authors: Tolomeo Mathias , McDowell Glenn R.
Published: March 2023

In this paper we show DEM simulations of static and cyclic large triaxial tests on a sample of railway ballast. The sample is reconstructed from X-Ray tomography images of an untested laboratory sample, recovered by impregnation with an epoxy resin. Measurements of both shape and fabric are carried out; the sample shows a high anisotropy of particle orientations due to the preparation procedure and a high shape heterogeneity. A DEM model is then generated using clumps to model single particles, preserving the shape of each particle and the fabric of the sample. Results of static and cyclic simulations are shown and compared with previous simulations on numerically generated samples, showing the importance of an accurate representation of the whole range of particle shapes, as well as confirming the effect of particle anisotropy on the mechanical response.

Graphical Abstract
Robust estimation of fixed effect parameters and variances of linear mixed models: the minimum density power divergence approach
Authors: Saraceno Giovanni , Ghosh Abhik , Basu Ayanendranath , Agostinelli Claudio
Published: March 2023

Many real-life data sets can be analyzed using linear mixed models (LMMs). Since these are ordinarily based on normality assumptions, under small deviations from the model the inference can be highly unstable when the associated parameters are estimated by classical methods. On the other hand, the density power divergence (DPD) family, which measures the discrepancy between two probability density functions, has been successfully used to build robust estimators with high stability associated with minimal loss in efficiency. Here, we develop the minimum DPD estimator (MDPDE) for independent but non-identically distributed observations for LMMs according to the variance components model. We prove that the theoretical properties hold, including consistency and asymptotic normality of the estimators. The influence function and sensitivity measures are computed to explore the robustness properties. As a data-based choice of the MDPDE tuning parameter $$\alpha$$
α
is very important, we propose two candidates as “optimal” choices, where optimality is in the sense of choosing the strongest downweighting that is necessary for the particular data set. We conduct a simulation study comparing the proposed MDPDE, for different values of $$\alpha$$
α
, with S-estimators, M-estimators and the classical maximum likelihood estimator, considering different levels of contamination. Finally, we illustrate the performance of our proposal on a real-data example.
The architecture of procurement in sustainable and zero-emission neighborhood projects—strategic challenges and new realities
Authors: Hamdan Hasan A. M. , de Boer Luitzen , Andersen Poul Houman
Published: March 2023

As an intermediate layer located between buildings and cities, neighborhoods are considered critical with regard to the transition to low-carbon cities and zero-emission societies. Sustainable and zero-emission neighborhood (ZEN) projects can be characterized as both complex and multi-organizational. However, there is currently only limited research available concerning collaboration among organizations in relation to ZEN projects. In particular, there is a lack of evidence as to how lead organizations arrange procurement for ZEN projects. Using a case study approach, this paper explores the potential of procurement to serve as a system integrator in ZEN projects. Our findings indicate that system integration by means of procurement in ZEN projects is difficult due to several challenges. Among the identified challenges, the most important are the complex ownership structure, the lack of supporting regulations, and the unclear mandate of the procurement department. In light of these findings, we propose a conceptual model that lead organizations could apply to support the realization of ZEN projects.
Markers of arterial stiffness and urinary metabolomics in young adults with early cardiovascular risk: the African-PREDICT study
Authors: du Toit Wessel L. , Kruger Ruan , Gafane-Matemane Lebo F. , Schutte Aletta E. , Louw Roan , Mels Catharina M. C.
Published: March 2023

Introduction

Increased exposure to risk factors in the young and healthy contributes to arterial changes, which may be accompanied by an altered metabolism.

Objectives

To increase our understanding of early metabolic alterations and how they associate with markers of arterial stiffness, we profiled urinary metabolites in young adults with cardiovascular disease (CVD) risk factor(s) and in a control group without CVD risk factors.

Methods

We included healthy black and white women and men (N = 1202), aged 20–30 years with a detailed CVD risk factor profile, reflecting obesity, physical inactivity, smoking, excessive alcohol intake, masked hypertension, hyperglycemia, dyslipidemia and low socio-economic status, forming the CVD risk group (N = 1036) and the control group (N = 166). Markers of arterial stiffness, central systolic blood pressure (BP) and pulse wave velocity were measured. A targeted metabolomics approach was followed by measuring amino acids and acylcarnitines using a liquid chromatography-tandem mass spectrometry method.

Results

In the CVD risk group, central systolic BP (adjusted for age, sex, ethnicity) was negatively associated with histidine, arginine, asparagine, serine, glutamine, dimethylglycine, threonine, GABA, proline, methionine, pyroglutamic acid, aspartic acid, glutamic acid, branched chain amino acids (BCAAs) and butyrylcarnitine (all P ≤ 0.048). In the same group, pulse wave velocity (adjusted for age, sex, ethnicity, mean arterial pressure) was negatively associated with histidine, lysine, threonine, 2-aminoadipic acid, BCAAs and aromatic amino acids (AAAs) (all P ≤ 0.044). In the control group, central systolic BP was negatively associated with pyroglutamic acid, glutamic acid and dodecanoylcarnitine (all P ≤ 0.033).

Conclusion

In a group with increased CVD risk, markers of arterial stiffness were negatively associated with metabolites related to AAA and BCAA as well as energy metabolism and oxidative stress. Our findings may suggest that metabolic adaptations may be at play in response to increased CVD risk to maintain cardiovascular integrity.
Measurement Invariance of the Meaning in Life Questionnaire Across 17 Countries
Authors: Schutte Lusilda , Brdar Ingrid , Wissing Marié P. , Tončić Marko , Araujo Ulisses , Carlquist Erik , Castro Solano Alejandro , Freire Teresa , Hernández-Pozo María del Rocío , Jose Paul E. , Martos Tamás , Nakamura Jeanne , Nuñez del Prado Chaves Pamela , Russo-Netzer Pninit , Singh Kamlesh , Slezackova Alena , Soosai-Nathan Lawrence , Unanue Wenceslao , Vella-Brodrick Dianne A. , Delle Fave Antonella
Published: March 2023

The Meaning in Life Questionnaire assesses presence of and search for meaning in life. Although the questionnaire has shown promising psychometric properties in samples from different countries, the scale’s measurement invariance across a large number of nations has yet to be assessed. This study is aimed at addressing this gap, providing insight into how meaning in life is constructed and experienced across countries and into the extent to which cross-country comparisons can be made. A total of 3867 adult participants from 17 countries, aged 30–60, balanced by gender, and with at least secondary education, completed the questionnaire as part of the Eudaimonic and Hedonic Happiness Investigation. Single sample confirmatory factor analysis, multigroup confirmatory factor analysis, and alignment optimization were applied to investigate the scale’s performance across the samples. Good psychometric properties and high levels of approximate measurement invariance emerged for the Presence subscale after removal of item 9, the only reverse-phrased item. Performance of the Search subscale varied more across samples, suggesting caution in interpreting related results supporting approximate measurement invariance. The conceptualization of presence of meaning operationalized in the corresponding subscale (without item 9) appears consistent across countries, whereas search for meaning seems to be less universally homogenous and requires further exploration. Moreover, the Meaning in Life Questionnaire does not reflect the conceptual distinction between “purpose” and “meaning” currently acknowledged by researchers. This issue should be further explored in studies addressing the scale’s performance across cultures.
Spinal pseudoarthrosis following osteoporotic vertebral fracture: prevalence, risk factors, and influence on patients’ activities of daily living 1 year after injury
Authors: Wakao Norimitsu , Sakai Yoshihito , Watanabe Tsuyoshi , Osada Naoaki , Sugiura Takaya , Iida Hiroki , Ozawa Yuto , Murotani Kenta
Published: March 2023

Purpose

To investigate the prevalence and risk factors and influence of pseudoarthrosis on activities of daily living (ADL) of patients with osteoporotic vertebral fracture (OVF).

Methods

Spinal pseudoarthrosis is defined as the presence of a cleft in the vertebral body on a lateral X-ray image in the sitting position at 1 year after admission. Of the total 684 patients treated for OVF between January 2012 and February 2019 at our institution, 551 patients (mean age, 81.9 years; a male-to-female ratio, 152:399) who could be followed up to 1 year were included in this study. Prevalence, risk factors, and influence of pseudoarthrosis on the ADL of patients as well as fracture type and location were investigated. Pseudoarthrosis was set as the objective variable. Total bone mineral density, skeletal muscle mass index, sex, age, history of osteoporosis treatment, presence of dementia, vertebral kyphosis angle, fracture type (presence of posterior wall injury), degree of independence before admission, history of steroid use, albumin level, renal function, presence of diabetes, and diffuse idiopathic skeletal hyperostosis were set as explanatory variables for multivariate analysis of the influence of pseudoarthrosis on the walking ability and ADL independence before and 1 year after OVF.

Results

In total, 54 (9.8%) patients were diagnosed with pseudarthrosis 1 year after injury (mean age, 81.3 ± 6.5 years; male-to-female ratio, 18:36). BKP was performed in nine patients who did not develop pseudoarthrosis after 1 year. In the multivariate analysis, only the presence of posterior wall injury was significantly correlated with the presence of pseudoarthrosis (OR = 2.059, p = 0.039). No significant difference was found between the pseudarthrosis group and the non-pseudarthrosis group in terms of walking ability and ADL independence at 1 year.

Conclusions

The prevalence of pseudoarthrosis following OVF was 9.8%, and its risk factor was posterior wall injury. The BKP group was not included in the pseudoarthrosis group, which may have led to an underestimation of the prevalence of pseudoarthrosis.

The prevalence, risk factors, and influence of spinal pseudoarthrosis on patients’ ADL following osteoporotic vertebral fracture (OVF) were investigated. Pseudoarthrosis occurs in 9.8% 1 year after the injury in patients with OVF. Posterior wall injury was the risk factor of pseudoarthrosis.
A pair of gametologous genes provides further insights into avian comparative cytogenomics
Authors: Sazanov Alexei A. , Sazanova Anna L. , Nefedov Mikhail D. , Griffin Darren K. , Romanov Michael N.
Published: March 2023

Exploration of avian gametologous genes, i.e., homologous genes located on both the Z and W chromosomes, provides a crucial information about the underlying mechanism pertaining to the evolution of these chromosomes. The domestic chicken (Gallus gallus (Linnaeus 1758); GGA) traditionally serves as the primary reference subject of these comparative cytogenomic studies. Using bioinformatic, molecular (overgo BAC library scanning), and cytogenetic (BAC-based FISH) techniques, we have investigated in detail a pair of UBE2R2/UBE2R2L gametologs. By screening a gridded genomic jungle fowl BAC library, CHORI-261, with a short labeled UBE2R2L gene fragment called overgo probe, we detected seven specific clones. For three of them, CH261-019I23, CH261-105E16, and CH261-114G22, we identified their precise cytogenetic location on the Gallus gallus W chromosome (GGAW). They also co-localized with the UBAP2L2 gene on the, as was shown previously, along with the CH261-053P09 BAC clone also containing the GGAW-specific UBE2R2L DNA sequence. The fine mapping of the UBE2R2/UBE2R2L homologs in the chicken genome also shed the light on comparative cytogenetic aspects in birds. Our findings provided further evidence that bird genomes moderately changed only during evolution and are suitable for successful use of interspecies hybridization using both overgo-based BAC library screen and BAC-based FISH.
Sexual and reproductive complications and concerns of survivors of childhood, adolescent and adult cancer
Authors: Gerstl Brigitte , Signorelli Christina , Wakefield Claire E. , Deans Rebecca , Vaishnav Tejnei , Johnston Karen , Neville Kristen , Cohn Richard J. , Anazodo Antoinette
Published: March 2023

Purpose

Cancer survivors may experience infertility and sexual dysfunction following cancer treatment. Survivors report significant gaps in oncofertility care and consider these issues important, yet they are rarely discussed. The aims of this study were to evaluate survivors’ sexual and reproductive complications across age groups and to identify specific groups of survivors at risk for sexual and reproductive complications.

Method

We report data collected from survivors of cancers diagnosed in childhood, adolescence and adulthood following the development and piloting of a reproductive survivorship patient reported outcome measure (RS-PROM).

Results

One hundred and fifty survivors participated in the study (mean age at cancer diagnosis was 23.2 years [SD, 10.3 years]). About 68% of participants expressed concerns about their sexual health and function. Survivors (50%) expressed at least one body image concern, with the female gender the most common risk factor for all subgroups. A total of 36% of participants reported at least one concern regarding their fertility, with more male than female survivors reporting fertility preservation prior to treatment. Females compared with male participants were more likely to feel less physically attractive after treatment (OR = 3.83, 95% CI = 1.84–7.95, p < 0.001). More females than males were also more likely to feel dissatisfied with the appearance of a scar(s) after treatment (OR = 2.36, 95% CI = 1.13–4.91, p = 0.02).

Conclusion

The RS-PROM identified multiple reproductive complications and concerns for cancer survivors in the survivorship period.

Implications for Cancer Survivors

Utilising the RS-PROM in conjunction with a clinic appointment could help identify and address cancer patients’ concerns and symptoms.
Sustaining HIV Research in Resource-Limited Settings Using PLAN (People, Learning, Adapting, Nurturing): Evidence from the 4 Youth by Youth Project in Nigeria
Authors: Iwelunmor Juliet , Tucker Joseph D. , Ezechi Oliver , Nwaozuru Ucheoma , Obiezu-Umeh Chisom , Gbaja-Biamila Titilola , Oladele David , Musa Adesola Z. , Airhihenbuwa Collins O.
Published: March 2023

Purpose of Review

Sustaining evidence-based interventions in resource-limited settings is a perennial challenge. Despite growing research on the significance of sustainability, few frameworks describe why and how to plan for sustainability in settings limited with resources. Drawing on a synthesis of the literature on sustainability, including the Dynamic Sustainability Framework, we review lessons learned from research to date, to point out a path forward for sustaining evidence-based interventions in resource-limited settings.

Recent Findings

We describe PLAN or why people learning, adapting, and nurturing the core values of an intervention can enhance its sustainability over time. PLAN is a dynamic framework that simplifies the process of planning for sustainability of evidence-based interventions throughout the lifecyle of an intervention, taking into consideration the people that matter as well as the learning, adaptation, and nurturing involved with understanding and studying the interactions between interventions/innovations, practice settings, intervention fit, and the broader ecological contexts in which implementation occurs. We use case-study data from our ongoing pragmatic HIV implementation trial, the 4 Youth by Youth project, to detail the value and implications of why people learning, adapting, and nurturing HIV interventions implemented in resource-limited settings matter.

PLAN is designed to further the dialogue on ways research and practice teams can critically work to ensure the sustainability of their evidence-based interventions from the onset, particularly in settings and with populations limited with resources. It also illustrates how attention to sustainability from the beginning may foster actions necessary for sustained program → sustained benefits → sustained capacity → sustained value, but in the absence of early and active planning, none of this will occur. Ultimately, we hope to accelerate the sustainability of evidence-based HIV interventions, and making a PLAN at the bare minimum may ensure that the goals of continuing and maintaining desirable features of any evidence-based interventions can be realized.
The illegal trade in European eels: outsourcing, funding, and complex symbiotic-antithetical relationships
Authors: Alonso Aitor Ibáñez , van Uhm Daan P.
Published: March 2023

Whilst traditionally, the study of the illegal wildlife trade has been focused on species that consider the role of the Western world as a consumer or transit hub, the study of the illegal trade in European eels is a landmark opportunity to deem the role of Europe as a source area for wildlife trafficking. Based on a qualitative methods research design, this case study delves into the nature of the illegal trade in European eels. In the context of globalization, a global eel market developed at the same time as stocks decreased sharply. The process of criminalization of the trade and fishing of eels, in combination with criminogenic asymmetries, has been facilitating opportunities for crime groups. In the legal-illegal continuum, upper- and underworld actors interact along the chain from rivers to worldwide consumers. This constant interaction fuels the illegal trade by providing the underworld with vital elements for its continuity, such as protection, finance, or laundering. In particular, this research focusses on the different legal-illegal interactions by looking at outsourcing, funding and complex symbiotic-antithetical relationships.
Influence of cognitive reserve on neuropsychological performance in subjective cognitive decline and mild cognitive impairment older adults
Authors: López-Higes Ramón , Rubio-Valdehita Susana , Delgado-Losada María Luisa , López-Sanz David
Published: March 2023

The analysis of the relationships between cognitive reserve and different cognitive domains has become a matter of interest since it can help us detect deviations from the typical ageing process. The main objective of our study was to analyse a structural equation model representing cognitive reserve’s relationships with three cognitive domains (episodic memory, working memory, and sentence comprehension) in older adults with subjective cognitive decline and mild cognitive impairment patients, in a cross-sectional study. A total of 266 Spanish-speaking older adults, from 65 to 80 years old, voluntarily participated in the study. The assessment protocol includes questionnaires as well as screening and domain-specific tests, providing relevant information for the classification of participants in the two groups previously mentioned (n1 = 150 and n2 = 116). The proposed model presented metric and configural invariance as well as stability across groups, since the indices reflecting goodness-of-fit reach acceptable values. Our hypotheses are partially confirmed since cognitive reserve strongly influences working memory and it does moderately in sentence comprehension in both groups, but it hardly influences episodic memory in the subjective cognitive decline group, while both are inversely associated in the patients’ group. Working memory could be considered as a mechanism through which cognitive reserve exerts its protector role on other cognitive domains: on sentence comprehension in both groups, and on episodic memory in the subjective cognitive decline group. However, in mild cognitive impairments patients, cognitive reserve does no longer influence episodic memory via working memory in a significant manner.
Association between response to anti-PD-1 treatment and blood soluble PD-L1 and IL-8 changes in patients with NSCLC
Authors: Yi Ling , Wang Xiaojue , Fu Siyun , Yan Zhuohong , Ma Tianyu , Li Siqi , Wei Panjian , Zhang Hongtao , Wang Jinghui
Published: March 2023

In this study, we explored the dynamic changes in blood sPD-L1 and its clinical value during anti-PD-1 immunotherapy in non-small cell lung cancer (NSCLC) patients. First, we established a sandwich ELISA for functional sPD-L1 that can bind to PD-1 and has biological functions. By monitoring functional sPD-L1 in 39 NSCLC patients treated with anti-PD-1 antibodies, we found a positive correlation between baseline sPD-L1 and tissue PD-L1 (P = 0.0376, r = 0.3581), with patients with lymph node metastasis having higher sPD-L1 levels (P = 0.0037) than those without lymph node metastasis. Although baseline functional sPD-L1 and PFS did not correlate significantly in this study, changes in sPD-L1 in patients with different clinical responses showed different trends. Blood sPD-L1 increased in 93% of patients after two cycles of anti-PD-1 treatment (P = 0.0054); sPD-L1 in nonresponsive patients continued to increase (P = 0.0181), but sPD-L1 started to decline in responsive patients. Blood IL-8 levels were associated with tumor load, and when combined with IL-8, the evaluation accuracy of sPD-L1 improved to 86.4%. This study preliminarily shows that the combination of sPD-L1 and IL-8 is a convenient and effective method for monitoring and evaluating the effectiveness of anti-PD-1 immunotherapy in NSCLC patients.
Comparison of two high dose rate intracavitary brachytherapy regimens in treatment of cervical cancer: a preliminary report
Authors: Krishna Abhishek , Hasib AG , Fernandes Donald , Athiyamaan M. S. , Rao Sandesh , Shankar Sharaschandra , Ali Mohsina , Priyadarshini Hepsiba , Sophia Maria , Shridhar CH , George Seby , Babu Amrutha , Banerjee Sourjya , Sunny Johan , Srinivas Challapalli , Lobo Dilson
Published: March 2023

Background

To assess and compare the local control and toxicities between HDR Intracavitary Brachytherapy with 7.5 Gy and 9 Gy per fraction after EBRT in treatment of carcinoma cervix.

Methodology

A total of 180 patients were randomly assigned to 2 arms. Arm A received HDR intracavitary brachytherapy with a dose of 7.5 Gy per fraction, 1 fraction per week for 3 fractions and Arm B received 9 Gy per fraction, 1 fraction per week for 2 fractions. Patients were evaluated on follow up for assessment of local control and toxicities.

Results

The median follow up was 12 months (6–18 months). In arm A 89% of the patient had complete response and 11% had recurrence or metastasis. In arm B 93% of the patient had complete response and 7% had recurrence or metastasis. Grade 2/3 diarrhoea was seen in 4.4% of patients in Arm A and in 7.7% in Arm B. Grade 2/3 proctitis was seen in 3.3% of patients in 7.5 Gy arm and in 6.6% in 9 Gy arm. One patient in each arm had grade 1 haematuria. The overall duration of treatment was significant lower in Arm B compared to Arm A (59 days vs 68 days, p = 0.01).

Conclusion

The result of this clinical study shows that Intracavitary brachytherapy with a dose of 9 Gy per fraction is non inferior to other schedules in term of local control and does not result in increased toxicity.
Efficacy and selectivity of tumor-treating field therapy for triple-negative breast cancer cells via in-house delivery device
Authors: Smothers Austin R. , Henderson Jason R. , O’Connell John J. , Stenbeck Jonathan M. , Dean Delphine , Harvey Tyler G. , Booth Brian W.
Published: March 2023

Purpose

Triple-negative breast cancer continues to be one of the leading causes of death in women, making up 7% of all cancer deaths. Tumor-treating electric fields are low-energy, low-frequency oscillating electric fields that induce an anti-proliferative effect on mitotic cells in glioblastoma multiforme, non-small cell lung cancer, and ovarian cancer. Little is known about effects of tumor-treating fields on triple-negative breast cancer and known research for tumor-treating fields only utilizes low (< 3 V/cm) electric field intensities.

Methods

We have developed an in-house field delivery device capable of high levels of customization to explore a much wider variety of electric field and treatment parameters. Furthermore, we investigated the selectivity of tumor-treating field treatment between triple-negative breast cancer and human breast epithelial cells.

Results

Tumor-treating fields show greatest efficacy against triple-negative breast cancer cell lines between 1 and 3 V/cm electric field intensities while having little effect on epithelial cells.

Conclusion

These results provide a clear therapeutic window for tumor-treating field delivery to triple-negative breast cancer.
Modeling the Resilience of Power Distribution Systems Subjected to Extreme Winds Considering Tree Failures: An Integrated Framework
Authors: Hou Guangyang , Muraleetharan Kanthasamy K.
Published: March 2023

Overhead electrical power distribution systems (PDS) are very susceptible to extreme wind hazards. Power outages can cause catastrophic consequences, including economic losses, loss of critical services, and disruption to daily life. Therefore, it is very important to model the resilience of PDS against extreme winds to support disaster planning. While several frameworks currently exist to assess the resilience of PDS subjected to extreme winds, these frameworks do not systematically consider the tree-failure risk. In other words, there is no integrated framework that can simultaneously consider tree failures, PDS component failures induced by falling trees, resilience assessment, and evaluation of resilience enhancement with vegetation management. Therefore, this study proposed an integrated simulation framework to model the resilience of PDS against extreme winds, which includes tree fragility modeling, PDS fragility modeling, PDS component failure estimation, system performance evaluation, system restoration modeling, and resilience enhancement evaluation. The framework is demonstrated with a power distribution network in Oklahoma. The results show that the estimated system resilience will reduce if tree failures are considered. Crown thinning can effectively enhance the system’s resilience, but the effectiveness is affected by both wind speed and direction.
Generalized metabolic flux analysis framework provides mechanism-based predictions of ophthalmic complications in type 2 diabetes patients
Authors: Batagov Arsen , Dalan Rinkoo , Wu Andrew , Lai Wenbin , Tan Colin S. , Eisenhaber Frank
Published: March 2023

Chronic metabolic diseases arise from changes in metabolic fluxes through biomolecular pathways and gene networks accumulated over the lifetime of an individual. While clinical and biochemical profiles present just real-time snapshots of the patients’ health, efficient computation models of the pathological disturbance of biomolecular processes are required to achieve individualized mechanistic insights into disease progression. Here, we describe the Generalized metabolic flux analysis (GMFA) for addressing this gap. Suitably grouping individual metabolites/fluxes into pools simplifies the analysis of the resulting more coarse-grain network. We also map non-metabolic clinical modalities onto the network with additional edges. Instead of using the time coordinate, the system status (metabolite concentrations and fluxes) is quantified as function of a generalized extent variable (a coordinate in the space of generalized metabolites) that represents the system’s coordinate along its evolution path and evaluates the degree of change between any two states on that path. We applied GMFA to analyze Type 2 Diabetes Mellitus (T2DM) patients from two cohorts: EVAS (289 patients from Singapore) and NHANES (517) from the USA. Personalized systems biology models (digital twins) were constructed. We deduced disease dynamics from the individually parameterized metabolic network and predicted the evolution path of the metabolic health state. For each patient, we obtained an individual description of disease dynamics and predict an evolution path of the metabolic health state. Our predictive models achieve an ROC-AUC in the range 0.79–0.95 (sensitivity 80–92%, specificity 62–94%) in identifying phenotypes at the baseline and predicting future development of diabetic retinopathy and cataract progression among T2DM patients within 3 years from the baseline. The GMFA method is a step towards realizing the ultimate goal to develop practical predictive computational models for diagnostics based on systems biology. This tool has potential use in chronic disease management in medical practice.
Resveratrol and Dulaglutide ameliorate adiposity and liver dysfunction in rats with diet-induced metabolic syndrome: Role of SIRT-1 / adipokines / PPARγ and IGF-1
Authors: Shamardl Hanan Abdel Moneam A. , Ibrahim Noha A. , Merzeban Dina H. , Elamir Azza M. , Golam Rehab M. , Elsayed Asmaa M.
Published: March 2023

Background

Adiposity and non-alcoholic fatty liver disease (NAFLD) are common characteristics of metabolic syndrome (MS). Understanding the underlying pathogenesis is crucial for the development of new remedies. Resveratrol controls obesity and glycemic disorders in patients with MS.

Objectives

This study aimed to evaluate the effect of resveratrol and dulaglutide on adipose tissues and liver in rats with MS, declaring their possible mechanisms.

Methods

Rats allocated as Control, MS (induced by a high fat/ high sucrose diet for eight weeks), MS + Resveratrol (30 mg/kg/day orally), and MS + Dulaglutide (0.6 mg/kg twice weekly SC); drugs administration was in the last four weeks. Serum biochemical measurements were done. Liver and visceral fat were processed for biochemistry, histopathology, and immunohistochemistry.

Results

MS results demonstrated significantly increased systolic and diastolic blood pressure, anthropometric measurements, serum levels of alanine aminotransferase (ALT), glycemic indices, and lipids with decreased HDL-C. Tissue levels of leptin, malondialdehyde (MDA), and TNF-α reactivity significantly increased. Expression of adiponectin, PPARγ, and insulin growth factor-1 (IGF-1) decreased. Also, Western blotting mRNA gene expression of liver SIRT-1 was down-regulated. Resveratrol and dulaglutide significantly and effectively reversed MS complexity, ameliorating all findings, particularly NAFLD and adiposity-induced inflammation. Resveratrol significantly appears superior to dulaglutide regarding the effects on hemodynamics, lipids, adipokines, IGF-1 levels, and adipocyte size. Parallel, dulaglutide has more influence on glycemic control.

Conclusion

Protective effects of the drugs may be through correlations between SIRT-1/adipokines/IGF-1 and PPARγ, improving the cross-talk between insulin resistance, obesity markers, liver dysfunction, and TNF-α. Promising multi-beneficial therapies of resveratrol or dulaglutide in MS are recommended clinically for this purpose.

Graphical Abstract

Showing the Experimental Design
Interventions to Reduce Exposure to Synthetic Phenols and Phthalates from Dietary Intake and Personal Care Products: a Scoping Review
Authors: Yang Tiffany C. , Jovanovic Nicolas , Chong Felisha , Worcester Meegan , Sakhi Amrit K. , Thomsen Cathrine , Garlantézec Ronan , Chevrier Cécile , Jensen Génon , Cingotti Natacha , Casas Maribel , McEachan Rosemary RC , Vrijheid Martine , Philippat Claire
Published: March 2023

Purpose of Review

A scoping review was conducted to identify interventions that successfully alter biomarker concentrations of phenols, glycol ethers, and phthalates resulting from dietary intake and personal care product (PCPs) use.

Recent Findings

Twenty-six interventions in populations ranging from children to older adults were identified; 11 actively removed or replaced products, 9 provided products containing the chemicals being studied, and 6 were education-only based interventions. Twelve interventions manipulated only dietary intake with a focus on bisphenol A (BPA) and phthalates, 8 studies intervened only on PCPs use and focused on a wider range of chemicals including BPA, phthalates, triclosan, parabens, and ultraviolet absorbers, while 6 studies intervened on both diet and PCPs and focused on phthalates, parabens, and BPA and its alternatives. No studies assessed glycol ethers. All but five studies reported results in the expected direction, with interventions removing potential sources of exposures lowering EDC concentrations and interventions providing exposures increasing EDC concentrations. Short interventions lasting a few days were successful. Barriers to intervention success included participant compliance and unintentional contamination of products.

The identified interventions were generally successful but illustrated the influence of participant motivation, compliance, ease of intervention adherence, and the difficulty of fully removing exposures due their ubiquity and the difficulties of identifying “safer” replacement products. Policy which reduces or removes EDC in manufacturing and processing across multiple sectors, rather than individual behavior change, may have the greatest impact on population exposure.
An instance-based deep transfer learning method for quality identification of Longjing tea from multiple geographical origins
Authors: Zhang Cheng , Wang Jin , Yan Ting , Lu Xiaohui , Lu Guodong , Tang Xiaolin , Huang Bincheng
Published: March 2023

For practitioners, it is very crucial to realize accurate and automatic vision-based quality identification of Longjing tea. Due to the high similarity between classes, the classification accuracy of traditional image processing combined with machine learning algorithm is not satisfactory. High-performance deep learning methods require large amounts of annotated data, but collecting and labeling massive amounts of data is very time consuming and monotonous. To gain as much useful knowledge as possible from related tasks, an instance-based deep transfer learning method for the quality identification of Longjing tea is proposed. The method mainly consists of two steps: (i) The MobileNet V2 model is trained using the hybrid training dataset containing all labeled samples from source and target domains. The trained MobileNet V2 model is used as a feature extractor, and (ii) the extracted features are input into the proposed multiclass TrAdaBoost algorithm for training and identification. Longjing tea images from three geographical origins, West Lake, Qiantang, and Yuezhou, are collected, and the tea from each geographical origin contains four grades. The Longjing tea from West Lake is regarded as the source domain, which contains more labeled samples. The Longjing tea from the other two geographical origins contains only limited labeled samples, which are regarded as the target domain. Comparative experimental results show that the method with the best performance is the MobileNet V2 feature extractor trained with a hybrid training dataset combined with multiclass TrAdaBoost with linear support vector machine (SVM). The overall Longjing tea quality identification accuracy is 93.6% and 91.5% on the two target domain datasets, respectively. The proposed method can achieve accurate quality identification of Longjing tea with limited samples. It can provide some heuristics for designing image-based tea quality identification systems.
p-adic vertex operator algebras
Authors: Franc Cameron , Mason Geoffrey
Published: March 2023

We postulate axioms for a chiral half of a nonarchimedean 2-dimensional bosonic conformal field theory, that is, a vertex operator algebra in which a p-adic Banach space replaces the traditional Hilbert space. We study some consequences of our axioms leading to the construction of various examples, including p-adic commutative Banach rings and p-adic versions of the Virasoro, Heisenberg, and the Moonshine module vertex operator algebras. Serre p-adic modular forms occur naturally in some of these examples as limits of classical 1-point functions.