bluuebunny/crossref_metadata_2025 huggingface dataset:
FIGURE 4 from Identification of an Imidazopyridine-based Compound as an Oral Selective Estrogen Receptor Degrader for Breast Cancer Therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Gräßle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina A. , Fuhr Olaf , Munuganti Ravi S. N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C. B.
Published: July 2023

X15695 stabilizes p53. Western blot analysis of p53 in extracts of MCF-7 (A) and T47D (B) cells treated with vehicle or the indicated concentrations of X15695 for 48 hours. Anti-β-actin antibody was used for the loading control (same as it appears in Fig. 3A and B). Quantitative RT-PCR of p53 expression in MCF-7 (C) and T47D (D) cells after treatment with vehicle (DMSO) or the indicated concentrations of X15695 for 48 hours. The results are the mean ± SEM (n = 3; ns, nonsignificant). E, Western blot analysis of p53 in extracts of MCF-7 cells treated with 0.5 μmol/L MG132 in the presence and absence of 1 μmol/L X15695 for 48 hours. Anti-β-actin antibody was used for the loading control. F, Quantification of the p53 protein band intensities relative to the intensity of the β-actin signal. The results are the means ± SEM (n = 3; *, P ≤ 0.05; ns, nonsignificant result). Western blot analysis of MDM2 levels in extracts of MCF-7 (G) and T47D (H) cells after treatment with the indicated concentration of X15695 for 48 hours. Anti-β-actin antibody was used for determination of equal protein level. The protein band intensities were quantified and presented below. Measurement of DCF fluorescence in MCF-7 (I) and T47D (J) cells treated with the indicated concentrations of X15695 or DMSO for 48 hours. The signals were normalized to DNA content of the samples measured after Hoechst 33258 staining. The results are the mean ± SEM (n = 3; ***, P ≤ 0.001; ****, P ≤ 0.0001). K, Reduced H2DCF-DA oxidation assay showing the effect of NAC on ROS production in MCF-7 cells treated with X15695 for 48 hours. Results represent the mean H2DCF-DA oxidation normalized to DNA content (n = 1 with 6 technical replicates). L, Western blots of lysates of MCF-7 cells treated with the indicated concentrations of NAC 1 hour prior to treatment with 1 μmol/L X15695 or DMSO for 48 hours. Expression of p53 was monitored using anti-p53 antibody and anti-β-actin antibody was used as a protein loading control. M and N, Immunofluorescence images showing p53 localization in MCF-7 and T47D cells treated with vehicle (DMSO) and 1 μmol/L X15695 for the indicated time periods. For staining, anti-p53 antibody was used followed by goat anti-mouse IgG, Alexa Fluor 488 antibody – green) and DAPI (magenta; M) or Alexa Fluor 488 antibody – red) and DAPI (light blue; N).
FIGURE 3 from Identification of an Imidazopyridine-based Compound as an Oral Selective Estrogen Receptor Degrader for Breast Cancer Therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Gräßle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina A. , Fuhr Olaf , Munuganti Ravi S. N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C. B.
Published: July 2023

X15695 destabilizes ERα. Western blot analysis of ERα in extracts of MCF-7 (A) and T47D (B) cells after treatment with vehicle or the indicated concentrations of X15695 for 48 hours. Anti-β-actin antibody was used for protein loading control. The protein samples used to determine the expression level of ERα were also used for the determination of p53 levels in Fig. 4A and B. Therefore, the β-actin control levels in these experiments are identical. Representative immunofluorescent staining carried out on hormone starved MCF-7 cells (C) treated with 100 nmol/L or 1 μmol/L X15695 in the presence and absence of 10 nmol/L E2 for 16 hours and T47D cells (D) treated with 1 μmol/L X15695 for 16 hours in full medium without hormone depletion. Staining was performed with anti-ERα antibody followed by goat anti-mouse IgG, Alexa Fluor 488 (green) and by DAPI (magenta). Fluorescence images were taken at 20×3 magnification. E, Western blot analysis of ERα in extracts of MCF-7 cells treated with vehicle or X15695 (1 μmol/L) for 24 hours followed by treatment with 100 μg/mL cycloheximide. The reaction was termination at the indicated timepoints. Anti-β-actin antibody was used to determine equal protein loading. F, Protein signals were quantified and presented in percentages as the signal of ERα relative to the β-actin signal. The value at timepoint zero of cycloheximide treatment was set to 100%. The values are the means ± SEM, n = 3; **, P ≤ 0.01.
FIGURE 1 from Identification of an Imidazopyridine-based Compound as an Oral Selective Estrogen Receptor Degrader for Breast Cancer Therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Gräßle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina A. , Fuhr Olaf , Munuganti Ravi S. N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C. B.
Published: July 2023

Imidazopyridine structures for inhibition of prostate and breast cancer proliferation. A, Comparison of benzothiazole and imidazopyridine scaffolds. B, Chemical structures of the benzothiazole A4B17 and six imidazopyridines that potently inhibit clonal expansion of ER+ and AR+ breast and prostate cancer cells. C, Chemical structures showing the structure of different imidazopyridine derivatives. D, Crystal structures of X15695, X15696, and X19168.
A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer
Authors: Nguyen Vina P. , Campbell Katie M. , Nowicki Theodore S. , Elumalai Nila , Medina Egmidio , Baselga-Carretero Ignacio , DiNome Maggie L. , Chang Helena R. , Oseguera Denise K. , Ribas Antoni , Glaspy John A.
Published: July 2023

Purpose:

Neoadjuvant combination immune checkpoint blockade and intralesional oncolytic virotherapy have the potential to activate antitumor responses in patients with breast cancer.

Experimental Design:

Eligibility for this pilot phase I trial included patients with localized HER2-negative breast cancer who received systemic nivolumab and ipilimumab and intratumor talimogene laherparepvec (T-VEC; NCT04185311). The primary objective was to evaluate the safety and adverse event profile of immunotherapy combined with T-VEC in patients with localized, HER2-negative breast cancer.

Results:

Six patients were enrolled, 4 having relapses after prior neoadjuvant chemotherapy and 2 who were previously untreated. Toxicities included 1 patient having grade 3 hypotension and type 1 diabetes mellitus, 3 patients with hypothyroidism, and all patients having constitutional symptoms known to be associated with the administration of T-VEC. One patient had a pathologic complete response, 3 patients had pathologic partial responses, 1 showed no significant response, and 1 had disease progression. Biopsies demonstrated increased immune cell infiltration in samples from patients who responded to therapy.

Conclusions:

This triple immunotherapy regimen provided responses in patients with advanced or relapsed HER2-negative breast cancer, at the expense of long-term toxicities.

Significance:

Systemic immune checkpoint blockade with a programmed death receptor 1 and a CTL antigen-4 blocking antibody, combined with intralesional oncolytic virotherapy, is a chemotherapy-free combination aimed at inducing an antitumor immune response locally and systemic immunity.
Equipamentos básicos para as bibliotecas da USP: (Cadernos de Estudos SIBIUSP N.4)
Authors:   Universidade de São Paulo. Sistema Integrado de Bibliotecas. Departamento Técnico, Krzyzanowski Rosaly Favero , Barone Ana Maria ,   Universidade de São Paulo. Sistema Integrado de Bibliotecas. Departamento Técnico, Ferracin, Ana Maria ,   Universidade de São Paulo. Sistema Integrado de Bibliotecas. Departamento Técnico, Sturlini Raquel Maria Giancolli ,   Universidade de São Paulo. Sistema Integrado de Bibliotecas. Departamento Técnic, Pasquarelli Maria Luiza Rigo ,   Universidade de São Paulo. Sistema Integrado de Bibliotecas. Departamento Técnico
Published: July 2023

Em 1987, o Fundo de Construção da USP (FUNDUSP) solicitou ao Departamento Técnico do Sisitema Integrado de Bibliotecas um estudo sobre os equipamentos essenciais ao funcionamento das bibliotecas da USP. Esta obra apresenta a metodologia utilizada para o levantamento dos equipamentos e suas especificações, além da forma de seleção de empresas especializadas, baseada em análises dos aspectos imprescindíveis quanto à funcionalidade e adequação dos equipamentos ao ambiente das bibliotecas.
Os Lusíadas na Rússia: entrevista com Olga Ovtcharenko
Authors: Oliveira Rafael Tsukamoto , Vassoler Mariana Barbieri
Published: July 2023

Olga Ovtcharenko é tradutora e pesquisadora das literaturas russa e portuguesa. Graduou-se em 1976 pela Universidade Estatal de Moscou, também conhecida como Lomonóssov, na Faculdade de Letras onde posteriormente lecionou, entre os anos 80-90. Entre os anos de 1984 e 87, lecionou língua e literatura russa na Universidade de Coimbra, em Portugal. Atua principalmente nas áreas de teoria literária do século XX, de história das literaturas portuguesa e russa, e de literatura comparada. Desde o fim dos anos 90, Ovtcharenko tem se dedicado à tradução de uma série de clássicos da literatura portuguesa inéditos para o público russo, tais como Os Lusíadas de Camões, Eurico, o Presbítero de Alexandre Herculano, Viagens na minha terra de Almeida Garrett, entre outros, além da extensa produção de artigos e comentários acerca do tema; é também colaboradora do Centro Interuniversitário de Estudos Camonianos da Universidade de Coimbra.
Um poeta em anos de prosa
Authors: Silva André Souza da
Published: July 2023

Depois de mais de duas décadas de carreira literária, Valter Hugo Mãe põe-se a relembrar a infância em Contra mim (2020), seu primeiro livro de memórias. Publicada no Brasil em 2020, a obra galardoada com o Prêmio da Associação Portuguesa de Escritores (APE) apresenta ao leitor um panorama da infância e adolescência do escritor, desde cedo envolto nos problemas mais profundos do Portugal onde cresceu. O livro é também uma forma de nos debruçarmos sobre os temas que o consagraram como romancista, além de fazer com que revisitemos sua poesia, embora esta seja menos conhecida pelo leitor brasileiro.
O primeiro contato dos portugueses com a Índia: estudo comparativo entre Os Lusíadas e alguns relatos históricos quinhentistas
Authors: Davees C. J.
Published: July 2023

O presente artigo visa comparar a epopeia de Luis de Camões com a matéria histórica que forneceu base aos Cantos VII e VIII do poema, seções essas que retratam os acontecimentos mais decisivos da Expansão Ultramarina portuguesa. O objetivo deste artigo é estudar as fontes históricas que cobrem as primeiras interações portuguesas com a Índia.
Leucoagaricus subtropicus sp. nov. (Agaricaceae) from Anhui Province, China
Authors: YANG YU , XIAO YUAN-PIN , LUO XIA , GONG YIN-PING , WANG SHUAI , YANG MENG-MENG , TAO YING-YING
Published: July 2023

Leucoagaricus subtropicus sp. nov., a new species of lepiotaceous fungi, is described from Anhui Province, China. Phylogenetic analyses based on combined sequence data from ITS and LSU indicated that it forms clusters within the Leucoagaricus. Moreover, morpho-anatomical analyses provided further confirmation of its distinctiveness. This novel taxon is mainly recognized by its medium-size, brownish-red fibrous scales in pileus with darker in the middle, greyish red to blood-red when bruised, brownish-orange droplets on base stipe, polymorphic cheilocystidia. The observed morphological and molecular phylogenetic differences clearly distinguish our species from all previously known species of Leucoagaricus, confirming its novelty. The new species is described, illustrated, and compared to species with similar characteristics.
The identity of Synotis borii (Asteraceae-Senecioneae)
Authors: XU YING , SINGH HARSH , TANG MING
Published: July 2023

Our critical examination of ample material including the type specimen and our study of the protologue convinced us that Synotis borii is not different from S. saluenensis and therefore should be synonymized with the latter.
Recollection and new data on the distribution of Aeschynanthus elmeri (Gesneriaceae) from the island of Mindanao, Southern Philippines
Authors: NAIVE MARK ARCEBAL K.
Published: July 2023

Recent fieldwork within Zamboanga peninsula revealed the recollection of the poorly known Philippine endemic Gesneriaceae species, Aeschynanthus elmeri. The name is herein lectotypified and a detailed description based on our recent collections, comparison to its closely similar species, ecology, updated geographical distribution information and a provisional IUCN conservation assessment is provided below.
Discriminant Analysis for Severe Storm Environments in South-Central Brazil
Authors: dos Santos Letícia O. , Nascimento Ernani L. , Allen John T.
Published: July 2023

Severe storms produce hazardous weather phenomena, such as large hail, damaging winds, and tornadoes. However, relationships between convective parameters and confirmed severe weather occurrences are poorly quantified in south-central Brazil. This study explores severe weather reports and measurements from newly available datasets. Hail, damaging wind, and tornado reports are sourced from the PREVOTS project from June 2018 to December 2021, while measurements of convectively induced wind gusts from 1996 to 2019 are obtained from METAR reports and from Brazil’s operational network of automated weather stations. Proximal convective parameters were computed from ERA5 reanalysis for these reports and used to perform a discriminant analysis using mixed-layer CAPE and deep-layer shear (DLS). Compared to other regions, thermodynamic parameters associated with severe weather episodes exhibit lower magnitudes in south-central Brazil. DLS displays better performance in distinguishing different types of hazardous weather, but does not discriminate well between distinct severity levels. To address the sensitivity of the discriminant analysis to distinct environmental regimes and hazard types, five different discriminants are assessed. These include discriminants for any severe storm, severe hail only, severe wind gust only, and all environments but broken into “high” and “low” CAPE regimes. The best performance of the discriminant analysis is found for the “high” CAPE regime, followed by the severe wind regime. All discriminants demonstrate that DLS plays a more important role in conditioning Brazilian severe storm environments than other regions, confirming the need to ensure that parameters and discriminants are tuned to local severe weather conditions.
Impact of Working Capital Management on Profitability: A Studyof the Select Indian Pharmaceutical Companies
Authors: Mahalwala Rachna , Ahuja Girish
Published: July 2023

The smooth running of business operations demands an efficient management of working capital by properly managing the inventory, accounts receivables and accounts payables of the business. This helps companies not only fulfil their short-term financial commitments but also boost their earnings. Therefore, the present study aims at verifying the impact of working capital management on the profitability of the companies under pharmaceutical industry in India. For empirical analysis, the data of 618 pharmaceutical companies is taken over a period of seven years from 2014–2015 to 2020–2021 and multivariate panel data regression technique is applied on data for estimating the results. The findings of the study validate that the profitability of companies is significantly influenced by working capital management. These findings will provide an insight to corporate managers and owners of pharmaceutical companies in deciding appropriate working capital strategy.
The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesis
Authors: Yang Tao , Hei Renyi , Li Xiaosong , Ma Tianhua , Shen Yifen , Liu Chao , He Wen , Zhu Lin , Gu Yongchun , Hu Yanping , Wei Wenbin , Shen Yihang
Published: July 2023

Background

Sebaceous glands (SGs) synthesize and secret sebum to protect and moisturize the dermal system via the complicated endocrine modulation. Dysfunction of SG are usually implicated in a number of dermal and inflammatory diseases. However, the molecular mechanism behind the differentiation, development and proliferation of SGs is far away to fully understand.

Methods

Herein, the rat volar and mammary tissues with abundant SGs from female SD rats with (post-natal day (PND)-35) and without puberty onset (PND-25) were arrested, and conducted RNA sequencing. The protein complex of Neuropeptide Y receptor Y2 (NPY2R)/NPY5R/Nuclear factor of activated T cells 1 (NFATc1) was performed by immunoprecipitation, mass spectrum and gel filtration. Genome-wide occupancy of NFATc1 was measured by chromatin immunoprecipitation sequencing. Target proteins’ expression and localization was detected by western blot and immunofluorescence.

Results

NPY2R gene was significantly up-regulated in volar and mammary SGs of PND-25. A special protein complex of NPY2R/NPY5R/NFATc1 in PND-25. NFATc1 was dephosphorylated and activated, then localized into nucleus to exert as a transcription factor in volar SGs of PND-35. NFATc1 was especially binding at enhancer regions to facilitate the distal SG and sebum related genes’ transcription. Dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) contributed to NFATc1 phosphorylation in PND-25, and inactivated of DYRK1A resulted in NFATc1 dephosphorylation and nuclear localization in PND-35.

Conclusions

Our findings unmask the new role of NPY2R/NFATc1/DYRK1A in pubertal SG, and are of benefit to advanced understanding the molecular mechanism of SGs’ function after puberty, and provide some theoretical basis for the treatment of acne vulgaris from the perspective of hormone regulation.

Graphical Abstract
Critical review of the default values used in the environmental impact assessment of biocidal products applied in livestock production systems
Authors: Steinhoff-Wagner Julia , Mateus-Vargas Rafael Hernán , Haupt Ruth , Heinemann Céline
Published: July 2023

Background

The default values in the models used for environmental risk assessment are mostly more than a decade old. Market developments, structural and legal changes lead to adaptions of animal husbandry and manure management during this time. The scope of this research project was the critical review with regard to the topicality and plausibility of the default values for the assessment of insecticides/larvicides and disinfectants in stables, which are mentioned in the relevant emission scenario documents (Joint Research Centre, Institute for Health and Consumer Protection, Raffael B, Van de Plassche E (2012) Emission scenario document for product type 3: veterinary hygiene biocidal products. Publications Office. 10.2788/29747; OECD (2006) Emission Scenario Document for Product Type 18 No.14 Emission Scenario Document for Insecticides for Stables and Manure Storage Systems”, ENV/JM/MONO(2006)4), supplemented by the draft of Addendum 1 (European Chemicals Acd 1999 agency (ECHA) (draft recommendation of 2021). Addendum to OECD SERIES ON EMISSION SCENARIO DOCUMENTS, Number 14: Emission Scenario Document for Insecticides for Stables and Manure Storage Systems, ENV/JM/MONO(2006)4 Version 1.2).

Results

Several default values used in the current emission scenario documents (ESDs) were identified as outdated such as the housing scenarios for laying hens. It should be evaluated if outside climate housing was already covered by the existing scenarios or requires the addition of a new one. Additionally, the lack of valid data regarding for instance biocide application and biodegradation data, may also have an impact on the predicted environmental concentration (PEC).

Conclusions

Based on the results of the present study an update of the ESDs is suggested.
Which aspects facilitate the adherence of patients with low back pain to physiotherapy? A Delphi study
Authors: Alt Andreas , Luomajoki Hannu , Luedtke Kerstin
Published: July 2023

Background

The effectiveness of physiotherapy to reduce low back pain depends on patient adherence to treatment. Facilitators and barriers to patient adherence are multifactorial and include patient and therapist-related factors. This Delphi study aimed to identify an expert consensus on aspects facilitating the adherence of patients with back pain to physiotherapy.

Method

International experts were invited to participate in a three-round standard Delphi survey. The survey contained 49 items (32 original and 17 suggested by experts) which were rated on 5-point Likert scales. The items were assigned to six domains. The consensus level was defined as 60%.

Results

Of 38 invited experts, 15 followed the invitation and completed all three rounds. A positive consensus was reached on 62% of the 49 proposed items to facilitate adherence. The highest consensus was achieved in the domains “Influence of biopsychosocial factors” (89%) and “Influence of cooperation between physiotherapists and patients” (79%). Additional important domains were the “Influence of competencies of physiotherapists” (71%) and “Interdisciplinary congruence” (78%). “Administration aspects” and the “Use of digital tools” did not reach expert consensus.

Conclusions

Biopsychosocial factors, therapeutic skills, and patient-physiotherapist collaboration should be considered in physiotherapy practice to facilitate adherence in patients with LBP. Future studies should prospectively evaluate the effectiveness of individual or combined identified aspects for their influence on patient adherence in longitudinal study designs.
Intravenous application of tranexamic acid in intramedullary nailing for the treatment of geriatric intertrochanteric fractures: a systematic review and meta-analysis
Authors: Zhang Jiakai , Fan Xiaoyuan , Zheng Yi , Wu Junlong , Yuan Xinhua
Published: July 2023

Background

Meta-analyses on the use of tranexamic acid (TXA) in intertrochanteric fractures have shown inconsistent results due to variations in inclusion criteria and clinical heterogeneity. To address these limitations, we conducted a rigorous analysis of recent randomized controlled trials (RCTs) with strict inclusion criteria. The aim of this study was to objectively evaluate the effects and safety of intravenous TXA administration in the treatment of geriatric intertrochanteric femoral fractures with intramedullary nailing.

Methods

PubMed, Embase, and the Cochrane Library were searched for RCTs published from the database inception to August 2022. The date of total blood loss (TBL), intra-operative blood loss (IBL), hidden blood loss (HBL), transfusion rate, transfusion units, thromboembolic events, and mortality were extracted. Review Manager 5.3 was used for the analysis.

Results

A total of six RCTs involving 689 patients were included. Meta-analyses indicated that TXA can significantly reduce TBL (WMD = -232.82; 95% CI -312.81 to -152.84; p < 0.00001), IBL (WMD = -36.33; 95% CI -51.38 to -21.28; p < 0.00001), HBL (WMD = -189.23; 95% CI -274.92 to -103.54; p < 0.0001), transfusion rate (RR = 0.53; 95% CI 0.33 to 0.85; p = 0.008), and transfusion units (WMD = -0.58; 95% CI -0.75 to -0.41; p < 0.01). No increase in thromboembolic events rate (RR = 0.75; 95% CI 0.38 to 1.50; p = 0.42) and mortality (RR = 1.36; 95% CI 0.61 to 3.04; p = 0.45) was observed.

Conclusions

Our meta-analysis provides robust evidence supporting the efficacy and safety of intravenous TXA administration in treating geriatric intertrochanteric femoral fractures with intramedullary nailing. TXA significantly reduces blood loss and transfusion requirements without increasing the risk of thromboembolic events or mortality.
Association between impulsivity and cognitive capacity decrease is mediated by smartphone addiction, academic procrastination, bedtime procrastination, sleep insufficiency and daytime fatigue among medical students: a path analysis
Authors: Hamvai Csaba , Kiss Hedvig , Vörös Henrietta , Fitzpatrick Kevin M. , Vargha András , Pikó Bettina F.
Published: July 2023

Background

Medical students are at high risk for sleep disturbance. One possible cause of their sleeping problem is impulsivity. We aim to investigate the possible mediators between medical students’ impulsivity and sleep outcomes. Thus, we developed and investigated a model where the predictors were attentional, non-planning, and motor impulsivity subtraits. In the final model, subjective cognitive capacity decrease was the outcome variable. In light of previous findings, academic procrastination, smartphone addiction, and bedtime procrastination were considered important mediators as well as two variables of poor sleep, sleeping insufficiency, and daytime fatigue.

Methods

Medical students (N = 211; ageM = 22.15 years; ageSD = 3.47 years; 71.6% women) were recruited to complete an online survey comprised of demographics (age, gender), self-administered scales (Abbreviated Impulsiveness Scale, Bedtime Procrastination Scale, Abbreviated Impulsiveness Scale, Academic Procrastination Scale-Short Form) and questions on tiredness, daily fatigue and subjective cognitive capacity decrease. Correlation and path analyses were implemented to examine hypothesized relationships between the variables.

Results

Both attentional impulsivity (β = 0.33, p < .001) and non-planning impulsivity (β = -0.19, p < .01) had a direct relationship with cognitive capacity decrease. Attentional impulsivity was also associated with decreased cognitive capacity with a serial mediation effect via smartphone addiction, academic procrastination, bedtime procrastination, sleep insufficiency and fatigue (estimate = 0.017, p < .01). The indirect link between non-planning impulsivity and cognitive capacity decrease was mediated by academic procrastination, bedtime procrastination, sleep insufficiency and fatigue (estimate = 0.011, p < .01).

Conclusions

Inability to stay focused and plan tasks effectively (directly and indirectly) predicts poor sleep outcomes. This relationship is mediated by excessive smartphone use, academic procrastination, and bedtime procrastination. Our findings are relevant in light of self-regulatory learning, which is crucial in medical education. This is a recursive cycle of planning, emotion regulation, proper strategy selection and self-monitoring. Future interventions addressing attentional and non-planning impulsivity, problematic smartphone use, academic procrastination, and in turn, bedtime procrastination might make this routine more effective. In the conclusion section, practical implications of the results are discussed.
Operationalising masculinities in theories and practices of gender-transformative health interventions: a scoping review
Authors: Zielke Julia , Batram-Zantvoort Stephanie , Razum Oliver , Miani Céline
Published: July 2023

Gender-transformative health interventions that involve men and boys are gaining global reach, adaptability to specific geographical, population and epidemiological contexts, public endorsement, and conceptual sophistication. However, the ways in which masculinities are conceptualised and operationalised in theory and practice across these interventions remains unclear. The purpose of this scoping review is to map intervention studies that conceptually grapple with masculinities and analyse: a) how the concept of masculinities is adapted and operationalised in gender-transformative interventions, with respect to intervention population and context, b) what the relationship between the concept of masculinities and its wider theoretical embedding is, and c) on which levels transformation can be observed when working with ‘masculinities’.

We conducted a search in APA Psych Articles, APA PsycINFO, and CINAHL via EBSCO, MedLine, PubMed, and Web of Sciences (December 2021) looking for peer-reviewed studies on gender-transformative health interventions which engaged with masculinities conceptually. There were no restrictions regarding language, publication date, or geography. Forty-two articles were included in this review. Our abductive analysis finds that ‘hegemonic masculinities’ is a central concept in almost all included studies. This shows how the concept is adaptable to a range of different intervention contexts. The review further identifies five theoretical approaches, that help operationalise masculinities on an analytical level: feminist framework, affect theory, critical pedagogy, theories of social change, and ecological approaches. Lastly, this review draws out six levels on which transformation can be observed in the intervention outcomes: relational level, symbolic level, material level, affective level, cognitive-behavioural level, and community-structural level. The discussion underlines that processes and practices of (gender) transformation also require engagement with theories of transformation more widely and advocates for theoretical pluralism. Lastly, implications for practice, including preventative, ecological and community-based care models, are drawn out.
Peptide aptamer-based time-resolved fluoroimmunoassay for CHIKV diagnosis
Authors: Liu Tonggong , Gao Cheng , Wang Jingzhe , Song Jianning , Chen Xi , Chen Hongfang , Zhao Xiaona , Tang Huanwen , Gu Dayong
Published: July 2023

Background

Chikungunya virus (CHIKV) and Dengue virus (DENV) have similar clinical symptoms, which often induce misdiagnoses. Therefore, an antigen detection diagnostic system that can clearly identify these two viruses is desirable.

Methods

In this study, we developed a novel peptide with high affinity and specificity to CHIKV, and further constructed peptide aptamer-based TRFIA assay to efficiently detect CHIKV. Peptide aptamer B2 (ITPQSSTTEAEL) and B3 (DTQGSNWI) were obtained through computer-aided design and selected as CHIKV-specific peptide aptamers based on their high binding affinity, strong hydrogen bonding, and RMSD of molecular docking. Then, a sandwich-Time-Resolved Fluoroimmunoassay (TRFIA) was successfully constructed for the detection of the interaction between peptide aptamers and viruses.

Results

When using B2 as the detection element, highly specific detection of CHIKV E2 was achieved with detection limits of 8.5 ng/ml in PBS solution. Variation coefficient between inter-assay showed the disturbances received from the detection of clinical fluid specimens (including serum and urine), were also within acceptable limits. The detection limits for 10-fold dilution serum and urine were 57.8 ng/mL and 147.3 ng/mL, respectively. The fluorescent signal intensity exhibited a good linear correlation with E2 protein concentration in the range of 0-1000 ng/mL, indicating the potential for quantitative detection of E2 protein.

Conclusions

These results demonstrate that the construction of peptide aptamers with high affinity and specificity provides an excellent method for rapid diagnostic element screening, and the developed peptide aptamer B2 contributed to better detection of CHIKV viral particles compared to traditional antibodies.
Analysis of Incentive Policies and Initiatives on Orphan Drug Development in China: Challenges, Reforms and Implications
Authors: Zhao Zhiyao , Pei Zhongyang , Hu Anxia , Zhang Yuhui , Chen Jing
Published: July 2023

Objectives

Rare diseases are a global public health issue with a more pressing situation in China. Unfortunately, the relevant research and development in this country are still in its infancy, leading to limited drug accessibility. In view of this, the Chinese government has taken a series of countermeasures to promote orphan drug R&D in recent years, which has presented encouraging results. This paper aims to review incentive policies and funding initiatives formulated by the Chinese government and examine their implications on orphan drug R&D.

Methods

Policies targeting orphan drug R&D during 2012–2022 were retrieved from the relevant official websites, categorized into different themes and analyzed for the contents. Data on government funding, drug approval, clinical trial approval and orphan drug designation were collected through internet search to analyze the implications of those incentive policies and initiatives on orphan drug R&D in China.

Results

A total of 20 relevant policy documents were identified and five major themes were revealed through content analysis, including national strategy, expedited approval, safety and efficacy requirements, data protection and technical support. The government input in orphan drug R&D has witnessed a steady annual increase. Driven by those incentives, the numbers of orphan drugs approved for marketing and drug candidates entering clinical studies are increasing year by year, and more domestic pharmaceutical companies are actively involved in the R&D of orphan drugs.

Conclusions

Orphan drug development in China is growing rapidly under the stimulation of incentive regulatory policies and more investment in researches. China is working toward a more standardized and comprehensive rare disease ecosystem. However, there are still some challenges, such as the lack of sufficient financial support and the call for systematic legislation on rare diseases, to be addressed for future success.
Current state of rare disease registries and databases in Australia: a scoping review
Authors: Ruseckaite Rasa , Mudunna Chethana , Caruso Marisa , Helwani Falak , Millis Nicole , Lacaze Paul , Ahern Susannah
Published: July 2023

Background

Rare diseases (RDs) affect approximately 8% of all people or > 400 million people globally. The Australian Government’s National Strategic Action Plan for Rare Diseases has identified the need for a national, coordinated, and systematic approach to the collection and use of RD data, including registries. Rare disease registries (RDRs) are established for epidemiological, quality improvement and research purposes, and they are critical infrastructure for clinical trials. The aim of this scoping review was to review literature on the current state of RDRs in Australia; to describe how they are funded; what data they collect; and their impact on patient outcomes.

Methods

We conducted a literature search on MEDLINE, EMBASE, CINAHL and PsychINFO databases, in addition to Google Scholar and grey literature. Dissertations, government reports, randomised control trials, conference proceedings, conference posters and meeting abstracts were also included. Articles were excluded if they did not discuss RDs or if they were written in a language other than English. Studies were assessed on demographic and clinical patient characteristics, procedure or treatment type and health-related quality of life captured by RDRs or databases that have been established to date.

Results

Seventy-four RDRs were identified; 19 were global registries in which Australians participated, 24 were Australian-only registries, 10 were Australia and New Zealand based, and five were Australian jurisdiction-based registries. Sixteen “umbrella” registries collected data on several different conditions, which included some RDs, and thirteen RDRs stored rare cancer-specific information. Most RDRs and databases captured similar types of information related to patient characteristics, comorbidities and other clinical features, procedure or treatment type and health-related quality of life measures. We found considerable heterogeneity among existing RDRs in Australia, especially with regards to data collection, scope and quality of registries, suggesting a national coordinated approach to RDRs is required.

Conclusion

This scoping review highlights the current state of Australian RDRs, identifying several important gaps and opportunities for improvement through national coordination and increased investment.
Health Literacy predicts incident foot ulcers after 4 years – the SHELLED cohort study
Authors: Chen Pamela , Callisaya Michele , Wills Karen , Greenaway Timothy , Winzenberg Tania
Published: July 2023

Aims/hypothesis

To determine whether health literacy is associated with an index diabetes‐related foot ulcer (DFU).

Methods

The SHELLED Study is a 4‐year prospective study of people with diabetes aged over 40 with no history of DFU. The primary outcome was development of a first foot ulcer. Health Literacy was measured using the short form Test of Functional Health Literacy in Adults (s‐TOFHLA) and nine domains of the Health Literacy Questionnaire (HLQ).

Results

Of 222 participants, 191 (86.0%) completed the study, of whom 13 (5.9%) developed an incident ulcer. In multivariable models, every unit increase in S‐TOFHLA was associated with a reduced odds of foot ulcer development by 6% (OR 0.94, 95% CI 0.88 to 0.99). Better scores on two HLQ domains reduced the odds of foot ulcer (actively managing my health (OR 0.23, 95% CI 0.08 to 0.65) and understanding health information well enough to know what to do (OR 0.39, 95% CI 0.19 to 0.78). This was independent of baseline risk for foot disease.

Conclusions/interpretation

These data provide novel evidence that health literacy is an important clinical risk factor for index foot ulceration. This is an area of potential focus for research and development of educational programs or policy aimed at reducing development of incident foot ulceration.
Synergistic bactericidal effects of carvone and β-lactams against Xanthomonas campestris pv. vesicatoria
Authors: Kim Jeong Yoon , Kim Ju Yeon , Park Jae Yeon , Kim Jin-Seong , Seo Min-Kyung , Shin Min-Kyoung , Kim Jin-Hyo
Published: July 2023

Xanthomonas campestris pv. vesicatoria (Xcv) causes brown spots on the leaves, stems, and fruits of plants, called bacterial leaf scorch (BLS). For the control of pathogens, antibiotics have been used frequently, and they can develop the resistance. In this study, the bactericidal and synergistic effects of caraway oil and its main components against the pathogen (Xcv) were investigated. The tested caraway oil consisted of 58.4% of carvone and 31.1% of limonene. The minimum inhibitory concentration (MIC) of caraway oil and carvone was the same as 125 μg mL−1, and the minimum bactericidal concentration (MBC) was 1000 μg mL−1 for caraway oil and 500 μg mL−1 for carvone, while limonene showed no inhibition below 1000 μg ml−1. In the growth of Xcv, carvone treatment over 31.3 μg mL−1 inhibited dose-dependently, and the bactericidal effect showed after 18 h more than 250 μg mL−1; It was agreed with the release of intracellular components over 250 μg mL−1, especially. Furthermore, carvone damaged the plasmid DNA of Xcv, and it would be the reason for the bactericidal activity. The synergistic effect of carvone was found with β-lactams selectively; the fractional inhibitory concentration (FIC) indexes of carvone with ampicillin or amoxicillin were below 0.5, and the mixture of carvone (125 μg mL−1) and ampicillin (500 μg mL−1) showed the bactericidal activity as well.
The association between the thyroid feedback quantile-based index and serum uric acid in U.S. adults
Authors: Xie Haitao , Li Ning , Zhou Guowei , He Zhiyuan , Xu Xiaoqing , Liu Qian , Wang Haiyan , Han Jie , Shen Le , Yu Peng , Chen Jiandong , Chen Xiaohu
Published: July 2023

Objectives

Previous studies have shown that there may be a positive correlation between serum uric acid levels and hyperthyroidism. However, the relationship between thyroid function and serum uric acid in healthy people is unclear. This study analyzed the relationship between impaired thyroid hormone sensitivity and serum uric acid levels, and presented them in quantitative form.

Research design and methods

This is a cross-sectional study of 4460 adults (male: 2300; female: 2160) who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2010. Parameters representing central sensitivity to thyroid hormones were calculated as: thyroid feedback quantile-based index (TFQIFT4), thyroid stimulating hormone index (TSHI), and total thyroxine (T4) resistance index (TT4RI); Peripheral sensitivity to thyroid hormone was evaluated by FT3/FT4 ratio. In addition, we have innovated total triiodothyronine (T3) resistance index (TT3RI) and TFQIFT3 indexes based on FT3 and TSH. Multiple linear regression models were used to evaluate the correlation between thyroid resistance index and serum uric acid, and the results were presented graphically as smooth curve fittings.

Results

Higher levels of serum uric acid were associated with decreased sensitivity to thyroid hormones in euthyroid individuals. In conjunction with an increase in the thyroid hormone sensitivity index value, uric acid levels gradually increased as well. Furthermore, we found a segmented relationship between TT3RI and serum uric acid changes. The saturation and threshold analyses indicated that 18.85 was the turning point (logarithmic likelihood ratio test = 0.036). When TT3RI < 18.85, the relationship between serum uric acid and TT3RI was not significant [β(95% CI) 0.47 (− 0.05, 1.00), P = 0.077], but when TT3RI > 18.85, there was a significant rise in serum uric acid with an increase in TT3RI [β(95% CI) 3.94 (0.94, 6.95), P = 0.010]. A further finding of the interaction test was that impaired thyroid hormone sensitivity and uric acid changes vary among different age groups and BMI levels.

Conclusions

Decreased sensitivity to thyroid hormones was associated with high levels of serum uric acid in people with normal thyroid function. The interaction test shows that different age groups and BMI groups impact the association between impaired thyroid hormone sensitivity and serum uric acid. Furthermore, smooth curve fitting revealed a segmental relationship between TT3RI and serum uric acid levels.
Multidisciplinary recommendations for the management of CAR-T recipients in the post-COVID-19 pandemic era
Authors: Zhang Tingting , Tian Weiwei , Wei Shuang , Lu Xinyi , An Jing , He Shaolong , Zhao Jie , Gao Zhilin , Li Li , Lian Ke , Zhou Qiang , Zhang Huilai , Wang Liang , Su Liping , Kang Huicong , Niu Ting , Zhao Ailin , Pan Jing , Cai Qingqing , Xu Zhenshu , Chen Wenming , Jing Hongmei , Li Peng , Zhao Wanhong , Cao Yang , Mi Jianqing , Chen Tao , Chen Yuan , Zou Ping , Lukacs-Kornek Veronika , Kurts Christian , Li Jian , Liu Xiansheng , Mei Qi , Zhang Yicheng , Wei Jia
Published: July 2023

The outbreak of coronavirus disease 2019 (COVID-19) posed an unprecedented challenge on public health systems. Despite the measures put in place to contain it, COVID-19 is likely to continue experiencing sporadic outbreaks for some time, and individuals will remain susceptible to recurrent infections. Chimeric antigen receptor (CAR)-T recipients are characterized by durable B-cell aplasia, hypogammaglobulinemia and loss of T-cell diversity, which lead to an increased proportion of severe/critical cases and a high mortality rate after COVID-19 infection. Thus, treatment decisions have become much more complex and require greater caution when considering CAR T-cell immunotherapy. Hence, we reviewed the current understanding of COVID-19 and reported clinical experience in the management of COVID-19 and CAR-T therapy. After a panel discussion, we proposed a rational procedure pertaining to CAR-T recipients with the aim of maximizing the benefit of CAR-T therapy in the post COVID-19 pandemic era.
Inflammatory biomarkers of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in 563 severe OSA patients before and after surgery
Authors: Lin Chung-Wei , Lin Pei-Wen , Chiu Li-Wen , Chai Han-Tan , Chang Chun-Tuan , Friedman Michael , Salapatas Anna M. , Rahavi-Ezabadi Sara , Lin Hsin-Ching
Published: July 2023

Background

Evidence has proved that high neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were risk factors for cardiovascular comorbidities. The alterations of NLR and PLR following obstructive sleep apnea (OSA) treatment were under studied and thus should be investigated. This study aimed to evaluate the changes of inflammatory biomarkers including NLR and PLR in severe OSA patients after surgical interventions of the upper airway, and their relationships with improvements in polysomnographic (PSG) parameters.

Methods

This retrospective cohort study included 563 consecutive severe OSA patients at a tertiary academic medical center who received OSA surgery, as well as underwent pre- and post-operative polysomnographic (PSG) examinations and blood tests. The changes of major PSG estimates, NLR, and PLR before and at least 3 months after OSA surgery were analyzed using paired t-tests with subgroup analyses. Pearson's correlations were performed to discover which PSG parameter contributed to the improvement of the values.

Results

After OSA surgery, the major PSG estimates, NLR and PLR dropped significantly in the overall population. In those with a higher preoperative NLR (pre-operative NLR≧3) and PLR (pre-operative PLR≧150), the mean (SD) difference of NLR (− 0.8 [1.6], 95% CI − 1.5 to − 0.2) and PLR (− 41.6 [40], 95% CI − 52.8 to − 30.5) were even more substantial. The changes of the “apnea, longest ( r = 0.298, P = .037)” and “hypopnea, longest ( r = 0.321, P = .026)” were found significantly related to the improvement of PLR.

Conclusion

NLR and PLR did significantly drop in severe OSA patients following OSA surgery, and this could be related to the alterations of sleep indices. The findings could possess clinical importance for severe OSA patients after OSA surgeries in reducing possible OSA-associated cardiovascular comorbidities.
Metabolomics reveals the effects producing region and fermentation stage on substance conversion in cigar tobacco leaf
Authors: Zhang Guanghai , Yao Heng , Zhao Gaokun , Wu Yuping , Xia Huachan , Li Yongping , Kong Guanghui
Published: July 2023

Background

The quality of cigar tobacco leaves was closely related to fermentation. To investigate the substance changes in cigar tobacco leaves during their fermentation, metabolomics was determined at different fermentation stages. In this study, the metabolic profile among different regions and fermentation periods of cigar tobacco leaf were evaluated.

Results

A total of 1103 metabolites were identified in cigar tobacco leaf samples. A total of 293, 105 and 199 metabolites showed differential accumulation in the cigar tobacco leaf among different regions (PEF0 vs. LCF0, PEF0 vs. DHF0, PEF0 vs. YXF0) and 216, 242, 220, 227 and 198 metabolites showed differential accumulation in the different fermentation (LCF0 vs. LCF1, LCF0 vs. LCF2, LCF0 vs. LCF3, LCF0 vs. LCF4, LCF0 vs. LCF5). The main upregulated compounds were flavonoids, phenolic acids and lignans and coumarins, and the main downregulated compounds were organic acids, phenolic acids and amino acids and derivatives in the fermentation comparison group.

Conclusions

These results provide valuable information for accurately grasping the end time of fermentation and improve efficiency of cigar tobacco leaf fermentation.

Graphical Abstract