bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of Nitrogen Spirocycles in a Tandem Co(III)‐catalyzed C−H Activation/Dipolar Cycloaddition Reaction
Authors: Brześkiewicz Jakub , Loska Rafał
Published: October 2023

Complex spirocyclic isoindolines and pyrrolidines are formed in a tandem process involving Co(III)‐catalyzed dienylation of cyclic C‐aryl nitrones with 2,3‐butadien‐1‐ol carbonates, followed by intramolecular 1,3‐dipolar cycloaddition. The nitrone moiety serves both as a directing group for the C(aryl)−H activation and the dipole in the cycloaddition step. High regioselectivity of the fused vs. bridged product can be obtained by adjusting the reaction temperature. Reactions with substituted allenic substrates provide heterocycles with additional stereocenters usually with complete diastereoselectivity. The reaction products were readily transformed further into other complex nitrogen‐containing spirocyclic systems.
Teilautomatisierte Generierung von digitalen Infrastrukturmodellen mittels Multi‐Datenfusion
Authors: Jäkel Jan‐Iwo , Gölzhäuser Peter , Schmitt Annette , Bange Justine , Klemt‐Albert Katharina , Reiterer Alexander , Marx Steffen
Published: October 2023

Die Eisenbahninfrastruktur besitzt eine hohe Signifikanz für Wirtschaft und Gesellschaft. Das Durchschnittsalter der Eisenbahnbrücken in Deutschland liegt bei etwa 75 Jahren. Entsprechend ist auch die Bestandsdokumentation der Bauwerke historisch bzw. veraltet. Für den Anlagenbetreiber stellt die Inventarisierung, Aktualisierung und Bereitstellung von mehr als 4,6 Millionen Bestandsplänen eine enorme Herausforderung dar. Zudem benötigt die Generation von digitalen Modellen der Brückenbauwerke viele Ressourcen. Diese Faktoren stellen ein gravierendes Problem für ein qualitatives und effizientes Erhaltungsmanagement dar. Im Rahmen des Forschungsprojekts mdfBIM wird eine teilautomatisierte Methode zur Erstellung objektbasierter digitaler Modelle von Bestandsbrücken mittels Multi‐Datenfusion entwickelt. Für diese Methode wird ein ganzheitliches Prozessmodell erarbeitet und die Möglichkeiten einer teilautomatisierten Datenaufnahme und ‐verarbeitung hin zu einem BIM‐Modell als zentrale Datenbasis eruiert. Die Validierung des Ansatzes erfolgt anschließend an einem realen Demonstrator. Der Beitrag zeigt, wie ein teilautomatisierter Ansatz zur Digitalisierung von Bestandsbrückenbauwerken und die Schaffung einer einheitlichen Datengrundlage für das Instandhaltungsmanagement erfolgreich umgesetzt worden sind.
Primary care framework needed for preterm infant monitoring: AAP
Authors: Knopf Alison
Published: October 2023

Preterm birth and its complications are the leading causes of neonatal illnesses and deaths in the United States; the American Academy of Pediatrics (AAP) is calling for a primary care framework (pediatricians) to help monitor these babies. Early identification of neurodevelopmental conditions for children who graduated from the neonatal intensive care unit is critical, according to a report from the American Academy of Pediatrics (AAP), which encourages primary care pediatricians to take a more critical role in the long‐term, timely, and coordinated care needed by high‐risk infants during their early childhood years.
Rethinking ADHD in girls: Recent advances
Authors: Walters Anne S.
Published: October 2023

I recently did a media interview related to an earlier CABL commentary (Walters, 2018) focused on the underdiagnosis of ADHD in girls, prompting me to look at the recent research on the topic. Interestingly, the journalist I spoke with shared an article that noted the rising numbers of women ages 23–29 years and 30–34 years diagnosed with ADHD. Although still a relatively small percentage compared to female children, this percentage has almost doubled from 2020–2022 (Russell et al., 2023). In addition, the percentage of males versus females of any age diagnosed with ADHD increased from males being 133% more likely to be diagnosed in 2010 to females 28% more likely in 2022 (Russell et al., 2023).
Listeria monocytogenes bacteremia developed during treatment of COVID‐19
Authors: Yamamoto Jin , Nakamoto Keitaro , Shimasaki Teppei , Kurai Daisuke , Saraya Takeshi , Ishii Haruyuki
Published: October 2023

Key Clinical Message

Listeria monocytogenes is an important pathogen in older patients and immunosuppressed patients, often causing bacteremia. Complications resulting from infections other than COVID‐19 must also be considered during COVID‐19 treatment.
Two anti‐Prelog NAD‐Dependent Alcohol Dehydrogenases with Broad Substrate Scope and Excellent Enantioselectivity
Authors: Damian Matteo , Mutti Francesco G.
Published: October 2023

Enantiomerically pure alcohols are important to produce active pharmaceutical ingredients, agrochemicals and fine chemicals. Herein, we explored the substrate scope and chemo‐ and enantioselectivity of two NAD‐dependent anti‐Prelog alcohol dehydrogenases from Candida maris (Cm‐ADH) and Pichia finlandica (Pf‐ADH) in the asymmetric reduction of ketones. The ADHs were tested for the reduction of acetophenone with NADH that was recycled using a formate dehydrogenase and sodium formate. Cm‐ADH and Pf‐ADH performed best at 30 °C and at around pH 7 and pH 6, respectively. Pf‐ADH operated well at 50 mM acetophenone concentration, while Cm‐ADH was limited to 10 mM. Regarding the substrate scope, linear‐chain alkyl ketones were efficiently reduced (up to 98 % conversion), while branched and cyclic ketones gave lower conversions (up to 60 %). Aryl‐aliphatic ketones showed variable levels of conversion (<1–79 %), while α,β‐unsaturated and heteroaromatic ketones exhibited good to excellent conversions. In most of the cases, the enantiomeric excess was >99 %. Aliphatic and aryl‐aliphatic aldehydes were converted with up to >99 % conversion. A scale‐up experiment with Pf‐ADH using acetophenone as substrate led to 73 % isolated yield and >99 % ee (R).

This work contributes to filling the gap in biocatalytic asymmetric synthesis of chiral alcohols by introducing two NAD‐dependent ADHs with anti‐Prelog selectivity.
Impact of Grain Size and Grain Nature in Thin‐Film Solar Cells
Authors: Prabu R. Thandaiah , Malathi S. R. , Kumar Rajnish , Alkhalidi Huda S. , Kumar Atul
Published: October 2023

Herein, a theoretical investigation is conducted on grain‐size inhomogeneity's impact and grain boundaries’ (GBs’) electrical nature in thin‐film solar cells. Using the Matthiessen rule, grain‐size‐dependent mobility is derived in polycrystalline material. The obtained grain‐size‐dependent mobility values are fed into the Poisson solver to calculate device performance. The severity of grain sizes in the lower region determines how grain size affects the photovoltaic performance by grain‐size‐dependent efficiency simulation. Low grain sizes become critical, especially for low‐thickness absorbers. The second aspect of the study assesses potential variation at GBs to reveal the impact of the electrical properties of GBs. Evidence shows that the acceptor defects at GB are benign for device performance, causing upward band bending at the GB and acting as electron barriers. Device performance is adversely affected by donor defects at GBs due to downward band bending. As summarized in the findings, the polycrystallinity‐induced cause–effect relationships of grains are likely to interest solar cell researchers.
Chrysosplenol D can inhibit the growth of prostate cancer by inducing reactive oxygen species and autophagy
Authors: Zhang Haoyu , You Zhixin , Li Yilei , Gao Cheng , Wang Yuhao , Zhang Xiaoxiang
Published: October 2023

Objective

To uncover the effects of chrysosplenol D (CHD) on the progression of prostate cancer in vitro as well as in mice.

Methods

DU145 and PC‐3 cells were treated with increasing doses of CHD for 24, 48, or 72 h. Cell Counting Kit‐8 (CCK‐8) and colony formation assays were conducted to confirm the effects of CHD on cell viability. Flow cytometry (FCM) and immunostaining assays showed the effects of CHD on cell apoptosis and oxidative stress. Immunoblot was performed to detect the effects of CHD on autophagy. Besides, tumor growth assays were conducted to confirm the role of CHD in tumor growth in mice. GraphPad 6.0 was used for statistical analysis. All data were represented as mean ± SD. p < .05 and the significant difference was indicated by an asterisk.

Results

CHD suppressed the viability of prostate cancer cells in CCK‐8 assays, decreased colony number in colony formation assays, and induced cell apoptosis in FCM and immunostaining assays. CHD also restrained the oxidative stress with a decreased 2′‐7′‐dichlorofluorescein diacetate staining intensity. CHD restrained the autophagy of prostate cancer cells, as well as suppressed tumor growth in mice.

Conclusion

CHD could serve as a drug for prostate cancer.
Estimating seasonal Pacific geoduck clam Panopea generosa show-factors from long-term observation
Authors: Hajas Wayne , Atkins Mike
Published: October 2023

Objective

The geoduck show-factor is the probability an individual geoduck is detectable to a diver during a stock assessment survey. It is one of the values used to estimate the abundance of geoducks. This paper presents estimates of show-factor according to data collected during 21 approximately monthly surveys over a 32-month period. The new estimates are compared against other long-term studies of show-factor and against estimates made from shorter term (approximately daily surveys over a period of approximately 1 week) studies.

Methods

Data were collected from three plots near Marina Island, British Columbia, and three novel methods were used for the analysis. Two of the methods estimate show-factors at the time of data collection, while the third method treats show-factor as a function of the time of year. All three methods generate probabilistic results.

Result

Each method of show-factor analysis indicated a strong seasonal effect. Show-factors were highest from March to June and lowest from October to December. The difference between the high and low show-factors was at least a factor of two. The three methods generated estimates of show-factor that are generally lower than the values previously used as part of stock assessment on the coast of British Columbia.

Conclusion

If this difference between long- and short-term show-factor can be generalized to the many commercial beds on the coast of British Columbia, the abundance of geoducks has been underestimated and the fishery is even more cautious than currently believed. As of yet, long-term data have not been collected on a coastwide basis and conclusions cannot be more definitive.
Fighting for survival: Analyzing strategic trends in arts advocacy
Authors: Meagher Trevor , Bezboruah Karabi , Suh Jiwon
Published: October 2023

American arts organizations are locked in a continuous fight for their survival as a result of their demanding operational contexts. Virtually every arts organization engages in some form of formal or informal advocacy in order to raise public awareness and secure financial support or political goodwill. While there are almost as many different advocacy strategies as there are arts organizations, studies that trace changes in strategic employment over time are rare, as advocates are typically focused on present issues and the immediate future. This research seeks to address this knowledge gap. Through a systematic review of over 260 scholarly sources, editorials, blogs, think pieces, and miscellaneous other pro‐arts arguments, this article identifies five main arguments for supporting the arts that have been commonly used by arts advocates since the inception of the National Endowment for the Arts. This article presents a theoretical typology that is useful for understanding these arguments and the thematic connections between them. It concludes with a discussion of general trends towards strategic isomorphism and research sophistication among these strategies, then offers avenues for future research that may assist arts advocates with evaluating strategies' success so as to improve their future effectiveness.
Persistence of pulmonary hypertension in patients undergoing ventricular assist devices and orthotopic heart transplantation
Authors: Rajaratnam Arun , El‐Swais Ameen , McTiernan Charles , Thoma Floyd W. , Baghal Moaaz O. , Raffensperger Kristen , Chang Chung‐Chou H. , Hickey Gavin W. , Shah Faraaz A. , Al Ghouleh Imad
Published: October 2023

Pulmonary hypertension (PH) is common in advanced heart failure and often improves quickly after left ventricular assist device (VAD) implantation or orthotopic heart transplantation (OHT), but long‐term effects and outcomes are not well‐described. This study evaluated PH persistence after VAD as destination therapy (VAD‐DT), bridge to transplant (VAD‐OHT), or OHT‐alone. The study constituted a retrospective review of patients who underwent VAD‐DT (n = 164), VAD‐OHT (n = 111), or OHT‐alone (n = 138) at a single tertiary‐care center. Right heart catheterization (RHC) data was collected pre‐, post‐intervention (VAD and/or OHT), and 1‐year from final intervention (latest‐RHC) to evaluate the longitudinal hemodynamic course of right ventricular function and pulmonary vasculature. PH (Group II and Group I) definitions were adapted from expert guidelines. All groups showed significant improvements in mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP), cardiac output, and pulmonary vascular resistance (PVR) at each RHC with greatest improvement at post‐intervention RHC (post‐VAD or post‐OHT). PH was reduced from 98% to 26% in VAD‐OHT, 92%−49% in VAD‐DT, and 76%−28% in OHT‐alone from preintervention to latest‐RHC. At latest‐RHC mPAP remained elevated in all groups despite normalization of PAWP and PVR. VAD‐supported patients exhibited suppressed pulmonary artery pulsatility index (PaPi < 3.7) with improvement only posttransplant at latest‐RHC. Posttransplant patients with PH at latest‐RHC (n = 60) exhibited lower survival (HR: 2.1 [95% CI: 1.3−3.4], p < 0.001). Despite an overall significant improvement in pulmonary pressures and PH proportion, a notable subset of patients exhibited PH post‐intervention. Post‐intervention PH was associated with lower posttransplant survival.
A novel condition‐based maintenance policy considering imperfect switching for warm standby systems
Authors: Qi Faqun , Wang Yunke , Wang Xisha , Wu Yao
Published: October 2023

This paper proposes a novel condition‐based maintenance model for a two‐component warm standby system considering an imperfect switching policy. Unlike the conventional models, joint optimization of preventive and failure switching strategies is investigated. The standby component can be switched preventively when the component reaches the preventive maintenance (PM) threshold before the online one fails. The failure switching is triggered when the online component reaches the corrective maintenance (CM) threshold. In addition, the switching mechanism between the two components is related to the order fulfillment rate. The optimal PM threshold and order fulfillment rate can be derived by minimizing the long‐term average cost rate. A numerical example is provided to demonstrate the robustness of the decision model under different scenarios through sensitivity analysis. Ultimately, the effectiveness of the proposed model in this article was verified by comparing the models.
Falsche ,,Hirntod‘‘-Feststellung in Deutschland
Authors: Beckmann Rainer
Published: October 2023

Der sogenannte ,,Hirntod‘‘ ist in Deutschland als Todeszeichen weitgehend anerkannt. Seine Feststellung
anhand von Richtlinien der Bundesärztekammer gilt als sicher. Der Fall einer abgebrochenen ,,Hirntod‘‘-Feststellung
aus dem Jahr 2014 zeigt jedoch, dass die damals geltenden Richtlinien korrekturbedürftig waren. Eine
genauere Überprüfung der aktuellen Regeln zur Feststellung des ,,Hirntodes‘‘ ergibt, dass auch
sie Mängel und Ungereimtheiten enthalten. Insbesondere verstoßen die Richtlinien gegen die Begründungspflicht
gem. §16 Abs. 2 S. 2 TPG.
Bioactive molecules from terrestrial and seafood resources in hypertension treatment: focus on molecular mechanisms and targeted therapies
Authors: Islam Md. Rezaul , Dhar Puja Sutro , Akash Shopnil , Syed Sabeena Hussain , Gupta Jeetendra Kumar , Gandla Kumaraswamy , Akter Muniya , Rauf Abdur , Hemeg Hassan A. , Anwar Yasir , Aljohny Bassam Oudh , Wilairatana Polrat
Published: October 2023

Hypertension (HTN), a complex cardiovascular disease (CVD), significantly impacts global health, prompting a growing interest in complementary and alternative therapeutic approaches. This review article seeks to provide an up-to-date and thorough summary of modern therapeutic techniques for treating HTN, with an emphasis on the molecular mechanisms of action found in substances found in plants, herbs, and seafood. Bioactive molecules have been a significant source of novel therapeutics and are crucial in developing and testing new HTN remedies. Recent advances in science have made it possible to understand the complex molecular mechanisms underlying blood pressure (BP)-regulating effects of these natural substances better. Polyphenols, flavonoids, alkaloids, and peptides are examples of bioactive compounds that have demonstrated promise in influencing several pathways involved in regulating vascular tone, reducing oxidative stress (OS), reducing inflammation, and improving endothelial function. The article explains the vasodilatory, diuretic, and renin–angiotensin–aldosterone system (RAAS) modifying properties of vital plants such as garlic and olive leaf. Phytochemicals from plants are the primary in traditional drug development as models for novel antihypertensive drugs, providing diverse strategies to combat HTN due to their biological actions. The review also discusses the functions of calcium channel blockers originating from natural sources, angiotensin-converting enzyme (ACE) inhibitors, and nitric oxide (NO) donors. Including seafood components in this study demonstrates the increased interest in using bioactive chemicals originating from marine sources to treat HTN. Omega-3 fatty acids, peptides, and minerals obtained from seafood sources have anti-inflammatory, vasodilatory, and antioxidant properties that improve vascular health and control BP. Overall, we discussed the multiple functions of bioactive molecules and seafood components in the treatment of HTN.
Improving community health volunteers’ knowledge on cervical cancer using dialogue-based training in rural Kisumu County
Authors: Ochomo Edwin Onyango , Masinde David , Ouma Collins
Published: October 2023

Background

The global burden of cervical cancer continue to rise with the low- and middle-income countries bearing the greatest burden. East Africa recorded about 54560 cases and 36497 deaths attributed to cervical cancer in 2020 with 5236 cases and 3211 deaths being reported annually. This high burden can be attributed to low screening rates and late diagnosis, which lead to undesirable outcomes. Kenya still has low screening rates with only 16.4% of the eligible women screened against the WHO target of 70% by 2030. Kisumu has a lower screening rate of about 5.7% according to KHIS 2019 data. This low screening rate is due to lack of proper community health education. We evaluated the effectiveness of dialogue-based training in improving community health volunteers’ (CHV) knowledge on cervical cancer in Nyando.

Methods

The study adopted a pre-and-post, longitudinal study design. The CHVs knowledge was assessed before and after the training. We calculated the proportion net change in the number of CHVs with improved knowledge after the intervention. Statistical significance was assessed at p ≤ 0.05.

Results

The pre-test mean score was 30.1%, this improved to 53.4% at post-test following the dialogue-based training of the CHVs. The knowledge on the various aspects: risk factors (p < 0.0001), signs and symptoms (p < 0.0001) and screening (p < 0.0001) significantly improved at the post-test following the dialogue-based training. The overall score also significantly improved (p < 0.0001) following the training among the CHVs. Occupation (p < 0.0001) was found to be significantly associated with knowledge on cervical cancer.

Conclusion

The CHVs’ knowledge was inadequate but significantly improved following the dialogue-based training.
Orientations de facilitation pour soutenir l’application de l’Algo dans les services de soutien à domicile des personnes aînées
Authors: Ruest Mélanie , Guay Manon
Published: October 2023

Comment soutenir le déploiement de connaissances coconstruites par des personnes cliniciennes, gestionnaires ou chercheures? Ce thème est abordé à partir de l’étude de l’application de l’Algo, un algorithme clinique décisionnel conçu pour la sélection des aides techniques visant à faciliter l’hygiène corporelle des personnes aînées vivant à domicile. L’objectif de cette note sur les politiques et les pratiques est de présenter les orientations de facilitation dégagées à la suite d’un devis mixte multiphases (2015–2019) mis en œuvre dans les services de soutien à domicile au Québec (Canada). Les orientations de facilitation centrée sur la tâche et holistique sont présentées en fonction des stades d’utilisation de l’Algo, afin de soutenir les personnes cliniciennes, gestionnaires et chercheures dans la poursuite de son application auprès des personnes aînées. De plus, cette note illustre l’apport des devis mixtes à la conduite et à la compréhension de l’application des connaissances coconstruites.
ATP1A1/BCL2L1 predicts the response of myelomonocytic and monocytic acute myeloid leukemia to cardiac glycosides
Authors: Cerella Claudia , Gajulapalli Sruthi Reddy , Lorant Anne , Gerard Deborah , Muller Florian , Lee Yejin , Kim Kyung Rok , Han Byung Woo , Christov Christo , Récher Christian , Sarry Jean-Emmanuel , Dicato Mario , Diederich Marc
Published: October 2023

Myelomonocytic and monocytic acute myeloid leukemia (AML) subtypes are intrinsically resistant to venetoclax-based regimens. Identifying targetable vulnerabilities would limit resistance and relapse. We previously documented the synergism of venetoclax and cardiac glycoside (CG) combination in AML. Despite preclinical evidence, the repurposing of cardiac glycosides (CGs) in cancer therapy remained unsuccessful due to a lack of predictive biomarkers. We report that the ex vivo response of AML patient blasts and the in vitro sensitivity of established cell lines to the hemi-synthetic CG UNBS1450 correlates with the ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1)/BCL2 like 1 (BCL2L1) expression ratio. Publicly available AML datasets identify myelomonocytic/monocytic differentiation as the most robust prognostic feature, along with core-binding factor subunit beta (CBFB), lysine methyltransferase 2A (KMT2A) rearrangements, and missense Fms-related receptor tyrosine kinase 3 (FLT3) mutations. Mechanistically, BCL2L1 protects from cell death commitment induced by the CG-mediated stepwise triggering of ionic perturbation, protein synthesis inhibition, and MCL1 downregulation. In vivo, CGs showed an overall tolerable profile while impacting tumor growth with an effect ranging from tumor growth inhibition to regression. These findings suggest a predictive marker for CG repurposing in specific AML subtypes.
Monolithic full-color active-matrix micro-LED micro-display using InGaN/AlGaInP heterogeneous integration
Authors: Qi Longheng , Li Peian , Zhang Xu , Wong Ka Ming , Lau Kei May
Published: October 2023

A prototype of full-color active-matrix micro-light-emitting diode (micro-LED) micro-display with a pixel density of 391 pixel per inch (ppi) using InGaN/AlGaInP heterogeneous integration is demonstrated. InGaN blue/green dual-color micro-LED arrays realized on a single metal organic chemical vapor deposition (MOCVD)-grown GaN-on-Si epiwafer and AlGaInP red micro-LED arrays are both monolithically fabricated, followed by the integration with a common complementary metal oxide semiconductor (CMOS) backplane via flip-chip bonding technology to form a double-layer thin-film display structure. Full-color images with decent color gamut and brightness are successfully displayed through the fine adjustment of driving current densities of RGB subpixels. This full-color display combines the advantages of high quantum efficiency of InGaN material on blue/green light and AlGaInP material on red light through heterogeneous integration and high pixel density through monolithic fabrication approach, demonstrating the feasibility and prospects of high brightness, good color performance, and high-resolution micro-LED micro-displays in future metaverse applications.
Miniature integrated spectrometers towards high-performance and cost-effective
Authors: Sun Haoxuan , Zhou Yicheng , Li Liang
Published: October 2023

The conjugated mode of bound states in a continuum is integrated as a narrowband wavelength extraction unit. A low-cost and easy-to-prepare strategy, using solution-processable semiconductors, has been demonstrated to form a new platform for on-chip spectral analysis.
Spatiotemporal mode-locking and dissipative solitons in multimode fiber lasers
Authors: Cao Bo , Gao Chenxin , Liu Kewei , Xiao Xiaosheng , Yang Changxi , Bao Chengying
Published: October 2023

Multimode fiber (MMF) lasers are emerging as a remarkable testbed to study nonlinear spatiotemporal physics with potential applications spanning from high energy pulse generation, precision measurement to nonlinear microscopy. The underlying mechanism for the generation of ultrashort pulses, which can be understood as a spatiotempoal dissipative soliton (STDS), in the nonlinear multimode resonators is the spatiotemporal mode-locking (STML) with simultaneous synchronization of temporal and spatial modes. In this review, we first introduce the general principles of STML, with an emphasize on the STML dynamics with large intermode dispersion. Then, we present the recent progress of STML, including measurement techniques for STML, exotic nonlinear dynamics of STDS, and mode field engineering in MMF lasers. We conclude by outlining some perspectives that may advance STML in the near future.
Findings from the Indonesian family life survey on patterns and factors associated with multimorbidity
Authors: Griselda Meliana , Alfian Sofa D. , Wicaksono Imam A. , Wawruch Martin , Abdulah Rizky
Published: October 2023

The prevalence of multimorbidity tends to increase with age, but it is now also reported in the middle-aged population, which has a negative impact on healthcare systems and health outcomes. This study aims to analyze the patterns and factors associated with multimorbidity in Indonesia. This national cross-sectional population-based survey used publicly available data from the Indonesian Family Life Survey (IFLS-5) for 2014 among middle-aged (40–59 years old) and elderly (≥ 60 years old) respondents. Information on all chronic diseases was assessed using a self-reported questionnaire. Sociodemographic and health-related behavioral factors were obtained from self-reported data. Binary logistic regression analysis was used to identify the factors associated with multimorbidity. Adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were reported. The study recruited 11,867 respondents. The prevalence of multimorbidity was 18.6% (95% CI 17.9–19.3) with which 15.6% among middle age (95% CI 14.95–16.25) and 24.9% among the elderly (95% CI 24.12–25.68). Hypertension was the most commonly reported disease (23.2%) in all combinations of multimorbidity and among all age groups. Socio-demographic factors: elderly (AOR: 1.66; 95% CI 1.46–1.89), female (AOR: 1.42; 95% CI 1.20–1.69), living in the urban area (AOR: 1.22; 95% CI 1.09–1.38), higher educational level (AOR: 2.49; 95% CI 1.91–3.26), unemployed (AOR: 1.63; 95% CI 1.44–1.84), and higher economic level (AOR: 1.41; 95% CI 1.18–1.68) were associated with multimorbidity. Poor health behavior factors: being former smokers (AOR: 2.03; 95% CI 1.65–2.51) and obesity (AOR: 1.53; 95% CI 1.35–1.75) were also associated with multimorbidity. The prevalence of multimorbidity in the middle-aged and elderly population in Indonesia is relatively high, particularly in populations with poor health behaviors. Therefore, healthcare professionals should integrate more patient-specific factors when designing and implementing tailored interventions to manage multimorbidity in Indonesia.
Antibody response and soluble mediator profile in the first six months following acute SARS-CoV-2 infection
Authors: Corsini Camila A , Filgueiras Priscilla S , Almeida Nathalie BF , Miranda Daniel AP de , Gomes Sarah VC , Lourenço Adelina Junia , Bicalho Cecilia MF , Assis Jessica V de , Amorim Raquel NH , Silva Raphael A , Vilela Raquel VR , Lima Tulio M , Abreu Daniel PB de , Alvim Renata GF , Castilho Leda R , Martins-Filho Olindo A , Otta Dayane A , Grenfell Rafaella FQ
Published: October 2023

The COVID-19 pandemic has caused a severe global health and economic crisis, with significant consequences for human mortality and morbidity. Therefore, there is an urgent need for more studies on the immune response to SARS-CoV-2 infection, both to enhance its effectiveness and prevent its deleterious effects. This study presents the chronology of antibodies during six months after infection in hospitalized patients and the kinetics of serum soluble mediators of the cellular response triggered by SARS-CoV-2. Samples and clinical data from 330 patients hospitalized at the Hospital da Baleia in Belo Horizonte, Brazil, who were suspected of having COVID-19, were collected at the time of hospitalization and during 6 months after infection. The immune response was analyzed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. There was a significant difference in IgM specific antibody titers from the 7th to 60th days after infection between COVID-19 negative and positive patients. Soon after 60 days after infection, antibody levels started to reduce, becoming similar to the antibody levels of the COVID-19 negative patients. IgG specific antibodies started to be detectable after 9 days of infection and antibody levels were comparatively higher in positive patients as soon as after 7 days. Furthermore, IgG levels remained higher in these patients during the complete period of 180 days after infection. The study observed similar antibody profiles between different patient groups. The soluble systemic biomarkers evaluated showed a decrease during the six months after hospitalization, except for CCL11, CXCL8, CCL3, CCL4, CCL5, IL-6, IFN-g, IL-17, IL-5, FGF-basic, PDGF, VEGF, G-CSF, and GM-CSF. The results indicate that IgM antibodies are more prominent in the early stages of infection, while IgG antibodies persist for a longer period. Additionally, the study identified that patients with COVID-19 have elevated levels of biomarkers after symptom onset, which decrease over time.
Distinguishing fanged frogs (Limnonectes) species (Amphibia: Anura: Dicroglossidae), from Thailand using high resolution melting analysis
Authors: Suwannapoom Chatmongkon , Osathanunkul Maslin
Published: October 2023

Morphologically, species of fanged frogs (Limnonectes) are exceedingly similar, making it difficult to distinguish them within the complex. In Thailand, it has been difficult to distinguish between the sympatric species L. bannaensis and L. taylori, particularly among tadpoles, adolescents, and adult females. A precise identification contributes to a greater understanding of biodiversity, particularly for assessing distributions and population dynamics. Therefore, a novel approach is required. The objective of this study was to develop a high resolution melting analysis (HRM) for the rapid and accurate identification of six species of Limnonectes of the L. kuhlii complex found in Thailand, particularly the two sympatric fanged frogs. Here, HRM assays using 16S rRNA mitochondrial primers were designed and developed. There was as much as a 25.3% variation in the nucleotide sequence of the fragment amplified by HRM16S primers among the six species of Limnonectes. Prior to conducting an in vitro HRM, the DNA sequences were used in a simulation HRM, uMELT Quartz, to predict the melting curve for each species of Limnonectes. There were discrepancies between the predicted melting curves of each species generated by the programme. Consequently, in vitro HRM tests were conducted. The obtained melting curve and Tm values were consistent with those predicted, albeit with a slightly different Tm value and a more distinct melting curve. All evaluated species of Limnonectes could be easily distinguished from one another by comparing the melting curve shapes. The HRM assay was then used to confirm the species of 18 Limnonectes samples in comparison to the reference samples (confidence interval > 90%). In addition, the results of HRM were consistent with those of experts who used morphological analysis to identify species. The HRM was found to be useful, and therefore the method would also contribute to future ecological and systematic studies on the target species.
Quantifying hierarchy and prestige in US ballet academies as social predictors of career success
Authors: Herrera-Guzmán Yessica , Gates Alexander J. , Candia Cristian , Barabási Albert-László
Published: October 2023

In the recent decade, we have seen major progress in quantifying the behaviors and the impact of scientists, resulting in a quantitative toolset capable of monitoring and predicting the career patterns of the profession. It is unclear, however, if this toolset applies to other creative domains beyond the sciences. In particular, while performance in the arts has long been difficult to quantify objectively, research suggests that professional networks and prestige of affiliations play a similar role to those observed in science, hence they can reveal patterns underlying successful careers. To test this hypothesis, here we focus on ballet, as it allows us to investigate in a quantitative fashion the interplay of individual performance, institutional prestige, and network effects. We analyze data on competition outcomes from 6363 ballet students affiliated with 1603 schools in the United States, who participated in the Youth America Grand Prix (YAGP) between 2000 and 2021. Through multiple logit models and matching experiments, we provide evidence that schools’ strategic network position bridging between communities captures social prestige and predicts the placement of students into jobs in ballet companies. This work reveals the importance of institutional prestige on career success in ballet and showcases the potential of network science approaches to provide quantitative viewpoints for the professional development of careers beyond science.
Reference induces biases in late visual processing
Authors: Su Yannan , Wachtler Thomas , Shi Zhuanghua
Published: October 2023

How we perceive a visual stimulus can be influenced by its surrounding context. For example, the presence of a reference skews the perception of a similar feature in a stimulus, a phenomenon called reference repulsion. Ongoing research so far remains inconclusive regarding the stage of visual information processing where such repulsion occurs. We examined the influence of a reference on late visual processing. We measured the repulsion effect caused by an orientation reference presented after an orientation ensemble stimulus. The participants’ reported orientations were significantly biased away from the post-stimulus reference, displaying typical characteristics of reference repulsion. Moreover, explicit discrimination choices between the reference and the stimulus influenced the magnitudes of repulsion effects, which can be explained by an encoding-decoding model that differentiates the re-weighting of sensory representations in implicit and explicit processes. These results support the notion that reference repulsion may arise at a late decision-related stage of visual processing, where different sensory decoding strategies are employed depending on the specific task.
Longitudinal x-ray based lung function measurement for monitoring Nintedanib treatment response in a mouse model of lung fibrosis
Authors: Khan Amara , Markus M. Andrea , Svetlove Angelika , Hülsmann Swen , Alves Frauke , Dullin Christian
Published: October 2023

Lung fibrosis (LF) is a chronic progressive, incurable, and debilitating condition of the lung, which is associated with different lung disease. Treatment options are still sparse. Nintedanib, an oral tyrosine kinase inhibitor, significantly slows the LF progression. However, there is a strong need of further research and the development of novel therapies. In this study, we used a correlative set-up that combines X-ray based lung function (XLF) with microCT and whole body plethysmography (WBP) for a comprehensive functional and structural evaluation of lung fibrosis (LF) as well as for monitoring response to orally administered Nintedanib in the mouse model of bleomycin induced LF. The decline in lung function as early as one week after intratracheal bleomycin instillation was reliably detected by XLF, revealing the lowest decay rate in the LF mice compared to healthy ones. Simultaneously performed microCT and WBP measurements corroborated XLF findings by exhibiting reduced lung volume $$V^{insp}_{\mu CT}$$

V

μ
C
T

insp

and tidal volume $$TV_{WBP}$$

T

V

WBP

. In LF mice XLF also revealed profound improvement in lung function one week after Nintedanib treatment. This positive response to Nintedanib therapy was further substantiated by microCT and WBP measurements which also showed significantly improved $$V^{insp}_{\mu CT}$$

V

μ
C
T

insp

and $$TV_{WBP}$$

T

V

WBP

in the Nintedanib treated mice. By comparing the XLF data to structural features assessing the extent of fibrosis obtained by ex-vivo high-resolution synchrotron radiation-based imaging and classical histology we demonstrate that: (1) a simple low dose x-ray measurement like XLF is sensitive enough to pick up treatment response, (2) Nintedanib treatment successfully improved lung function in a bleomycin induced LF mouse model and (3) differences between the fully restored lung function and the partially reduced fibrotic burden compared to healthy and untreated mice. The presented analysis pipeline underlines the importance of a combined functional and anatomical readout to reliably measure treatment response and could easily be adapted to other preclinical lung disease models.
Antioxidant and α-glucosidase inhibitory activities of compound isolated from Stachytarpheta jamaicensis (L) Vahl. leaves
Authors: Fatmawati Sri , Auwaliyah Fithrotul , Yuliana  , Hasanah Nur , Putri Devi Anggraini , Kainama Healthy , Choudhary Muhammad Iqbal
Published: October 2023

Stachytarpheta jamaicensis is one of the folk medicines used for the treatment of diabetes in Ambon, Indonesia, but there are limited studies on the bioactivities of its constituents. This study aims to assess the antioxidant and antidiabetic activities of four extracts of S. jamaicensis leaves extracted using several solvents. Bioassay guided fractionation on each extract establishes for exploring S. jamaicensis leaves active compounds. The antioxidant was evaluated using the DPPH and ABTS methods, while the α-glucosidase inhibitory was carried out in vitro assay. The results showed that the methanol extract of S. jamaicensis leaves displays inhibition of DPPH, ABTS and α-glucosidase activity compared to other solvent extracts. Furthermore, 6β-hydroxyipolamiide was successfully isolated from the methanol extract of S. jamicensis leaves which was reported to have α-glucosidase inhibitory activity with an IC50 of 539.17 μg/mL. Based on the results, S. jamaicensis could be recommended as an antioxidant and antidiabetic agent.
Head trauma analysis of laboratory reconstructed headers using 1966 Slazenger Challenge and 2018 Telstar 18 soccer balls
Authors: Ferdousi Jasmine , Post Andrew , Karton Clara , Doelle Klara , Gilchrist Michael D. , Hoshizaki T. Blaine
Published: October 2023

Retired soccer players are presenting with early onset neurodegenerative diseases, potentially from heading the ball. It has been proposed that the older composition of soccer balls places higher strains on brain tissues. The purpose of this research was to compare the dynamic head response and brain tissue strain of laboratory reconstructed headers using replicas of the 1966 Slazenger Challenge and 2018 Telstar 18 World Cup soccer balls. Head-to-ball impacts were physically conducted in the laboratory by impacting a Hybrid III head form at three locations and four velocities using dry and wet soccer ball conditions, and computational simulation was used to measure the resulting brain tissue strain. This research showed that few significant differences were found in head dynamic response and maximum principal strain between the dry 1966 and 2018 balls during reconstructed soccer headers. Headers using the wet 1966 soccer ball resulted in higher head form responses at low-velocity headers and lower head responses as velocities increased. This study demonstrates that under dry conditions, soccer ball construction does not have a significant effect on head and brain response during headers reconstructed in the laboratory. Although ball construction didn’t show a notable effect, this study revealed that heading the ball, comparable to goalkeeper kicks and punts at 22 m/s, led to maximum principal strains exceeding the 50% likelihood of injury risk threshold. This has implications for the potential risks associated with repetitive heading in soccer for current athletes.
Investigation of nano- and microdomains formed by ceramide 1 phosphate in lipid bilayers
Authors: Drabik Dominik , Drab Mitja , Penič Samo , Iglič Aleš , Czogalla Aleksander
Published: October 2023

Biological membranes are renowned for their intricate complexity, with the formation of membrane domains being pivotal to the successful execution of numerous cellular processes. However, due to their nanoscale characteristics, these domains are often understudied, as the experimental techniques required for quantitative investigation present significant challenges. In this study we employ spot-variation z-scan fluorescence correlation spectroscopy (svzFCS) tailored for artificial lipid vesicles of varying composition and combine this approach with high-resolution imaging. This method has been harnessed to examine the lipid-segregation behavior of distinct types of ceramide-1-phosphate (C1P), a crucial class of signaling molecules, within these membranes. Moreover, we provide a quantitative portrayal of the lipid membranes studied and the domains induced by C1P at both nano and microscales. Given the lack of definitive conclusions from the experimental data obtained, it was supplemented with comprehensive in silico studies—including the analysis of diffusion coefficient via molecular dynamics and domain populations via Monte Carlo simulations. This approach enhanced our insight into the dynamic behavior of these molecules within model lipid membranes, confirming that nano- and microdomains can co-exist in lipid vesicles.
The amphiregulin/EGFR axis has limited contribution in controlling autoimmune diabetes
Authors: Raugh Arielle , Jing Yi , Bettini Matthew L. , Bettini Maria
Published: October 2023

Conventional immunosuppressive functions of CD4+Foxp3+ regulatory T cells (Tregs) in type 1 diabetes (T1D) pathogenesis have been well described, but whether Tregs have additional non-immunological functions supporting tissue homeostasis in pancreatic islets is unknown. Within the last decade novel tissue repair functions have been ascribed to Tregs. One function is production of the epidermal growth factor receptor (EGFR) ligand, amphiregulin, which promotes tissue repair in response to inflammatory or mechanical tissue injury. However, whether such pathways are engaged during autoimmune diabetes and promote tissue repair is undetermined. Previously, we observed that upregulation of amphiregulin at the transcriptional level was associated with functional Treg populations in the non-obese diabetic (NOD) mouse model of T1D. From this we postulated that amphiregulin promoted islet tissue repair and slowed the progression of diabetes in NOD mice. Here, we report that islet-infiltrating Tregs have increased capacity to produce amphiregulin, and that both Tregs and beta cells express EGFR. Moreover, we show that amphiregulin can directly modulate mediators of endoplasmic reticulum stress in beta cells. Despite this, NOD amphiregulin deficient mice showed no acceleration of spontaneous autoimmune diabetes. Taken together, the data suggest that the ability for amphiregulin to affect the progression of autoimmune diabetes is limited.
Contextual fear memory impairment in Angelman syndrome model mice is associated with altered transcriptional responses
Authors: Su Wenyue , Liu Yan , Lam Aileen , Hao Xiaoning , Baudry Michel , Bi Xiaoning
Published: October 2023

Angelman syndrome (AS) is a rare neurogenetic disorder caused by UBE3A deficiency and characterized by severe developmental delay, cognitive impairment, and motor dysfunction. In the present study, we performed RNA-seq on hippocampal samples from both wildtype (WT) and AS male mice, with or without contextual fear memory recall. There were 281 recall-associated differentially expressed genes (DEGs) in WT mice and 268 DEGs in AS mice, with 129 shared by the two genotypes. Gene ontology analysis showed that extracellular matrix and stimulation-induced response genes were prominently enriched in recall-associated DEGs in WT mice, while nuclear acid metabolism and tissue development genes were highly enriched in those from AS mice. Further analyses showed that the 129 shared DEGs belonged to nuclear acid metabolism and tissue development genes. Unique recall DEGs in WT mice were enriched in biological processes critical for synaptic plasticity and learning and memory, including the extracellular matrix network clustered around fibronectin 1 and collagens. In contrast, AS-specific DEGs were not enriched in any known pathways. These results suggest that memory recall in AS mice, while altering the transcriptome, fails to recruit memory-associated transcriptional programs, which could be responsible for the memory impairment in AS mice.
Seven chromatin regulators as immune cell infiltration characteristics, potential diagnostic biomarkers and drugs prediction in hepatocellular carcinoma
Authors: Chai Jin-wen , Hu Xi-wen , Zhang Miao-miao , Dong Yu-na
Published: October 2023

Treatment is challenging due to the heterogeneity of hepatocellular carcinoma (HCC). Chromatin regulators (CRs) are important in epigenetics and are closely associated with HCC. We obtained HCC-related expression data and relevant clinical data from The Cancer Genome Atlas (TCGA) databases. Then, we crossed the differentially expressed genes (DEGs), immune-related genes and CRs to obtain immune-related chromatin regulators differentially expressed genes (IRCR DEGs). Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to select the prognostic gene and construct a risk model for predicting prognosis in HCC, followed by a correlation analysis of risk scores with clinical characteristics. Finally, we also carried out immune microenvironment analysis and drug sensitivity analysis, the correlation between risk score and clinical characteristics was analyzed. In addition, we carried out immune microenvironment analysis and drug sensitivity analysis. Functional analysis suggested that IRCR DEGs was mainly enriched in chromatin-related biological processes. We identified and validated PPARGC1A, DUSP1, APOBEC3A, AIRE, HDAC11, HMGB2 and APOBEC3B as prognostic biomarkers for the risk model construction. The model was also related to immune cell infiltration, and the expression of CD48, CTLA4, HHLA2, TNFSF9 and TNFSF15 was higher in high-risk group. HCC patients in the high-risk group were more sensitive to Axitinib, Docetaxel, Erlotinib, and Metformin. In this study, we construct a prognostic model of immune-associated chromatin regulators, which provides new ideas and research directions for the accurate treatment of HCC.