bluuebunny/crossref_metadata_2025 huggingface dataset:
Xenophobic Discrimination
Authors: Atrey Shreya
Published: July 2023

This article presents a general account of xenophobic discrimination in international law. It shows that the dominant grounds‐based approach to addressing xenophobic discrimination as either (i) racial discrimination or (ii) discrimination based on nationality or citizenship, fails to capture what is wrong about xenophobic discrimination. Likewise, the suggestion to address xenophobic discrimination via a dedicated ground like foreignness may also fail given the inherently intersectional character of foreignness as in turn constituted by other grounds. Instead, xenophobic discrimination can be understood as a sui generis category of discrimination which is not necessarily based on a particular ground, but which leads to the particular harm of disbelongingness or civic ostracisation which excludes people from participating in the social, political, economic and cultural life of the communities they find themselves in. The article thus makes three contributions: first, it proposes a shift away from a grounds‐based to a harm‐based approach to discrimination in international law; secondly, it delineates the nature of harm entailed in xenophobic discrimination; and thirdly, it shows why such harm should be treated as prima facie wrongful in international law.
Vaginal morphology and position associated with prolapse recurrence after vaginal surgery: A secondary analysis of the DEMAND study
Authors: Bowen Shaniel T. , Moalli Pamela A. , Abramowitch Steven D. , Luchristt Douglas H. , Meyer Isuzu , Rardin Charles R. , Harvie Heidi S. , Hahn Michael E. , Mazloomdoost Donna , Iyer Pooja , Carper Benjamin , Gantz Marie G. ,   for the NICHD Pelvic Floor Disorders Network
Published: July 2023

Objective

To identify vaginal morphology and position factors associated with prolapse recurrence following vaginal surgery.

Design

Secondary analysis of magnetic resonance images (MRI) of the Defining Mechanisms of Anterior Vaginal Wall Descent cross‐sectional study.

Setting

Eight clinical sites in the US Pelvic Floor Disorders Network.

Population or Sample

Women who underwent vaginal mesh hysteropexy (hysteropexy) with sacrospinous fixation or vaginal hysterectomy with uterosacral ligament suspension (hysterectomy) for uterovaginal prolapse between April 2013 and February 2015.

Methods

The MRI (rest, strain) obtained 30–42 months after surgery, or earlier for participants with recurrence who desired reoperation before 30 months, were analysed. MRI‐based prolapse recurrence was defined as prolapse beyond the hymen at strain on MRI. Vaginal segmentations (at rest) were used to create three‐dimensional models placed in a morphometry algorithm to quantify and compare vaginal morphology (angulation, dimensions) and position.

Main outcome measures

Vaginal angulation (upper, lower and upper–lower vaginal angles in the sagittal and coronal plane), dimensions (length, maximum transverse width, surface area, volume) and position (apex, mid‐vagina) at rest.

Results

Of the 82 women analysed, 12/41 (29%) in the hysteropexy group and 22/41 (54%) in the hysterectomy group had prolapse recurrence. After hysteropexy, women with recurrence had a more laterally deviated upper vagina (p = 0.02) at rest than women with successful surgery. After hysterectomy, women with recurrence had a more inferiorly (lower) positioned vaginal apex (p = 0.01) and mid‐vagina (p = 0.01) at rest than women with successful surgery.

Conclusions

Vaginal angulation and position were associated with prolapse recurrence and suggestive of vaginal support mechanisms related to surgical technique and potential unaddressed anatomical defects. Future prospective studies in women before and after prolapse surgery may distinguish these two factors.
Preconception maternal retinal arteriolar narrowing and fetal growth throughout pregnancy: A prospective cohort study
Authors: Li Ling‐Jun , Du Ruochen , Chan Jerry Kok Yen , Tan Kok Hian , Wong Tien Yin , Eriksson Johan G. , Su Lin Lin , Chong Yap Seng , Huang Zhongwei , Zhang Cuilin
Published: July 2023

Objective

To investigate the association between preconception maternal retinal arteriolar calibre and fetal growth.

Design, setting and population

A hospital‐based, prospective preconception cohort including 369 women with a singleton live birth.

Methods

We collected detailed information on sociodemographic status, pregnancy history and lifestyle, and performed retinal imaging at the preconception visit.

Main outcome measures

We retrieved medical records documenting fetal growth biometrics (e.g., abdominal circumference [AC], head circumference [HC], femur length [FL]) at 11–13, 18–21, 24–28, and 32–34 weeks throughout pregnancy. We then computed the z scores for all fetal growth biometrics from 14 weeks of gestation where data were available, referencing the INTERGROWTH‐21st fetal growth chart. We used a linear mixed model to estimate the association between maternal preconception retinal arteriolar calibre and fetal growth biometrics z scores throughout pregnancy, with random intercept accounting for repeated measures within individuals. We then performed a multivariable linear regression of maternal preconception retinal arteriolar calibre and z score changes for all fetal growth biometrics between 24–28 weeks and 32–34 weeks of gestation, after full adjustment.

Results

Maternal preconception generalised retinal arteriolar narrowing was consistently associated with a reduction in fetal AC z scores (−0.34; 95% CI −0.66 to −0.03) throughout pregnancy. In addition, women with preconception generalised retinal arteriolar narrowing tended to have significantly reduced z score changes in AC (−0.41; 95% CI −0.90 to −0.001) and fetal FL (−0.55; 95% CI −1.00 to −0.10) between 24–28 weeks and 32–34 weeks of gestation, respectively.

Conclusions

Our findings suggest that women with narrower preconception retinal arterioles had smaller fetuses, evidenced by reductions in AC and FL z score throughout pregnancy.
Disulfiram relieves severe acute pancreatitis by inhibiting GSDMD‐dependent NETs formation
Authors: Ling Xin , Nie Chi , Sheng Li Ping , Han Chao Qun , Ding Zhen
Published: July 2023

Objectives

Severe acute pancreatitis (SAP) is characterized by pancreatic and systemic inflammation and persistent organ failure. Neutrophil extracellular traps (NETs) are considered to play an important role in the development of SAP. We aimed to explore the effect of disulfiram (DSL), a newly developed anti‐inflammatory drug, on NETs in SAP.

Methods

A mouse model of SAP was induced by caerulein and lipopolysaccharide, and the mice were divided into the normal control group, the DSL group, the SAP group, and the SAP treated with 50 mg/kg (50DSLSAP) and 100 mg/kg DSL (100DSLSAP) groups, respectively. The severity of SAP was evaluated based on the morphological and biochemical changes. Gasdermin D (GSDMD) expression was evaluated in vivo and in vitro to verify the effect of DSL. Additionally, the expressions of NETs were also evaluated in vivo and in vitro in SAP with and without DSL treatment to explore the possible mechanism of DSL on SAP.

Results

Pancreatic inflammatory injury increased in the SAP group, which was alleviated by DSL. GSDMD, a protein related to the formation of NETs, increased in SAP. Expressions of NETs were also promoted in the in vivo SAP model and by phorbol myristate acetate (PMA) in vitro. Moreover, DSL inhibited the expressions of GSDMD and NETs in vivo. The results were further confirmed in the in vitro experiment.

Conclusions

NETs are highly associated with inflammatory injury in SAP. DSL inhibits NETs formation by downregulating GSDMD, which in turn relieves the inflammation of SAP. Our study may provide a possible therapeutic target for SAP.
Boundary experts: Science and politics in measuring the Sustainable Development Goals
Authors: Iversen Thor Olav
Published: July 2023

The Sustainable Development Goals (SDGs) purport to cleanly separate politics and technical matters, embodied by the political negotiation of goals and targets, and the technical creation of an indicator framework. This article analyses how this boundary between science and politics is managed in practice. The statisticians tasked with selecting indicators through the Inter‐agency and Expert Group on Sustainable Development Goal Indicators (IAEG‐SDGs) are seconded to a global process from national statistical offices. Boundary management requires acceptance of certain normative and political aspects of creating an indicator framework, such as claims to national relevance. Others, like overt national intervention, are however considered impermissible. Each statistician must manage their role as a boundary expert that experience irresolvable tensions due to representing specific countries while being mandated to propound scientific practices and norms. Building on this empirical inquiry, the article sketches out a new normative ideal for knowledge pluralism in the measurement of sustainable development. It argues that indicator processes would benefit from more pluralistic indicator bodies than the IAEG‐SDGs. Including diversified knowledge and perspectives from civil society and international organisations would explicate already existing political contestation. It would also contribute to capturing more of the complexities of sustainable development in future monitoring frameworks through consideration of a broader selection of methodologies.
Especies exóticas y nativas utilizadas por las poblaciones tradicionales de la estepa patagónica: Un enfoque basado en la redundancia y la versatilidad
Authors: Santoro Flávia Rosa , Arias Toledo Bárbara , Richeri Marina , Ladio Ana Haydeé
Published: July 2023

El modelo de redundancia utilitaria se ha utilizado para verificar indirectamente la resiliencia de los sistemas de conocimiento de plantas beneficiosas utilizados por las poblaciones locales. A partir de las bases de este modelo y de la hipótesis de la diversificación, podemos pensar que las especies exóticas pueden entrar en los sistemas socioecológicos para llenar vacíos y reducir la presión de uso sobre las especies nativas. En este estudio, queremos describir el panorama de la redundancia de especies de plantas utilizadas por tres poblaciones tradicionales de la estepa patagónica con fines medicinales, combustibles y comestibles. También comparamos la presión de uso y el grado de singularidad de las especies nativas y exóticas, utilizando la redundancia y la versatilidad como variables sustitutivas. Nuestros resultados muestran que, según la redundancia utilitaria, los sistemas de conocimiento de plantas de las tres comunidades parecen tener una capacidad de adaptación similar para proporcionar opciones de respuesta al cambio; por ejemplo, permitiendo que ciertos elementos compensen/sustituyan la pérdida de otros. Descubrimos que las especies nativas son las más singulares y pueden estar sometidas a una mayor presión de uso que las exóticas. Así pues, nuestros resultados apuntan a la importancia de conservar el ambiente nativo de la estepa patagónica para la supervivencia de las poblaciones tradicionales. Nuestro estudio puede servir para establecer especies botánicas prioritarias para la conservación en la estepa patagónica.
How hotel firm value fluctuates with alternative leveraging strategies
Authors: Chen Ying , Valenzuela Eric , Capener Don
Published: July 2023

This study empirically examines the impact of leverage and capital structure on firm value for the US hotel industry from 1991 to 2017. We find strong evidence that leverage positively relates to firm value for firms in the hotel industry. This relationship is most robust for hotel firms with low financial health, consistent with the theory that firms signal positive information through capital structure. We also find that the relationship between leverage and firm value was weakened during the financial crisis, particularly for firms close to financial distress. Our results suggest that hotel management, creditors, and investors should pay attention to the magnifying effect of leverage on firm performance and the impact of financial crises on the value of debt. This study's empirical results also support the idea that firms in the hotel industry signal to outside investors through debt.
The Second Displacement of Refugees: Urban Regeneration Against Commoning Practices in Belgrade's Waterfront
Authors: Tsavdaroglou Charalampos , Kaika Maria
Published: July 2023

We develop the concept of “second displacement” to symbolise the renewed forms of uprooting that refugees undergo in arrival cities in the name of urban regeneration. Focusing on the eviction of 2,000 refugees from a self‐organised settlement in Belgrade's old train station in order to redevelop the site as a luxurious “Waterfront” project, we show how the refugees’ commoning practices and claims for living space in city centres often come into direct conflict with public and private interests over urban regeneration and with imaginaries over who has the right to the city. Whilst most displacement literature focuses on state policies, we call attention to how the uprooting of refugees is often entangled with urban renewal plans and private investors’ interests. In Belgrade, the depiction of the refugees’ living spaces as “badlands” by the state, catalysed the formation of the rent gap that facilitated re‐allocation of rights to the city.
Development and evaluation of a kangaroo mother care implementation model in South Ethiopia
Authors: Tadele Henok , Kassa Dejene Hailu , Gebriel Fitsum W. , Bilal Selamawit Mengesha , Gedefaw Abel , Teshome Million , Kawza Aknaw , Wangoro Shemels , Muleta Mekonnen , Abebo Teshome Abuka , Asefa Anteneh , Astatkie Ayalew , Haji Yusuf , Alemayehu Akalewold , Aziz Khalid , Brune Thomas , Singhal Nalini , Worku Bogale , Tadesse Birkneh Tilahun
Published: July 2023

Aim

To develop a model for increasing the coverage of kangaroo mother care (KMC), which involved ≥8 h of skin‐to‐skin contact per day and exclusive breastfeeding, for small babies with birth weight < 2000 g in South Ethiopia.

Methods

A mixed methods study was conducted between June 2017 and January 2019 at four hospitals and their catchment areas. Iterative cycles of implementation, program learning and evaluation were used to optimise KMC implementation models. The study explored the community‐facility continuum of care and assessed the proportion of neonates with a birth weight less than 2000 g receiving effective KMC.

Results

Three KMC implementation models were tested with Model 2 being the final version. This model included enhanced identification of home births, improved referral linkages, immediate skin‐to‐skin care initiation in facilities and early contact after discharge. These improvements resulted in 86% coverage of effective facility‐based KMC initiation for eligible babies. The coverage was 81.5% at discharge and 57.5% 7 days after discharge. The mean age of babies at KMC initiation was 8.2 days (SD = 5.7).

Conclusion

The study found that the KMC implementation model was feasible and can lead to substantial population‐level KMC coverage for small babies.
Black box algorithms in mental health apps: An ethical reflection
Authors: Manríquez Roa Tania , Biller‐Andorno Nikola
Published: July 2023

Mental health apps bring unprecedented benefits and risks to individual and public health. A thorough evaluation of these apps involves considering two aspects that are often neglected: the algorithms they deploy and the functions they perform. We focus on mental health apps based on black box algorithms, explore their forms of opacity, discuss the implications derived from their opacity, and propose how to use their outcomes in mental healthcare, self‐care practices, and research. We argue that there is a relevant distinction between functions performed by algorithms in mental health apps, and we focus on the functions of analysis and generation of advice. When performing analytic functions, such as identifying patterns and making predictions concerning people's emotions, thoughts, and behaviors, black box algorithms can be better than other algorithms to provide information to identify early signs of relapse, support diagnostic processes, and improve research by generating outcomes that lead to a better understanding of mental health. However, when carrying out the function of providing mental health advice, black box algorithms have the potential to deliver unforeseen advice that may harm users. We argue that the outcomes of these apps may be trustworthy as a complementary source of information, but express caution about black box algorithms that give advice directly to users. To reap the benefits of mental health apps based on black box algorithms and avoid unintended consequences, we critically need to know whether these algorithms are fulfilling the function of providing mental health advice.
Identification of compounds that preferentially suppress the growth of T‐cell acute lymphoblastic leukemia‐derived cells
Authors: Miyashita Kazuya , Yagi Takuya , Kagaya Noritaka , Takechi Azusa , Nakata Chihiro , Kanda Risa , Nuriya Hideko , Tanegashima Kosuke , Hoyano Shota , Seki Fumiya , Yoshida Chihiro , Hachiro Yoshifumi , Higashi Tomoya , Kitada Nobuo , Toya Takashi , Kobayashi Takeshi , Najima Yuho , Goyama Susumu , Maki Shojiro A. , Kitamura Toshio , Doki Noriko , Shin‐ya Kazuo , Hara Takahiko
Published: July 2023

T‐cell acute lymphoblastic leukemia (T‐ALL) is one of the most frequently occurring cancers in children and is associated with a poor prognosis. Here, we performed large‐scale screening of natural compound libraries to identify potential drugs against T‐ALL. We identified three low‐molecular‐weight compounds (auxarconjugatin‐B, rumbrin, and lavendamycin) that inhibited the proliferation of the T‐ALL cell line CCRF‐CEM, but not that of the B lymphoma cell line Raji in a low concentration range. Among them, auxarconjugatin‐B and rumbrin commonly contained a polyenyl 3‐chloropyrrol in their chemical structure, therefore we chose auxarconjugatin‐B for further analyses. Auxarconjugatin‐B suppressed the in vitro growth of five human T‐ALL cell lines and two T‐ALL patient‐derived cells, but not that of adult T‐cell leukemia patient‐derived cells. Cultured normal T cells were several‐fold resistant to auxarconjugatin‐B. Auxarconjugatin‐B and its synthetic analogue Ra#37 depolarized the mitochondrial membrane potential of CCRF‐CEM cells within 3 h of treatment. These compounds are promising seeds for developing novel anti‐T‐ALL drugs.
Men, testosterone and Covid‐19
Authors: Groti Antonic Kristina , Antonic Blaz , Caliber Monica , Dhindsa Sandeep
Published: July 2023

Men have more severe Coronavirus disease 2019 (Covid‐19) outcomes and higher mortality rates than women, and it was suggested that testosterone levels might promote severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and Covid‐19 severity. However, clinical studies have not supported this theory. Studies have consistently shown that serum testosterone concentrations during acute Covid‐19 in men are inversely proportional to the inflammatory cytokines and severity of illness. It is likely that lower testosterone concentrations in this setting are a result of acute Covid‐19 illness on the hypothalamic–pituitary–testicular axis. Clinical trials that attempted to lower testosterone concentrations further or block androgen signaling acutely during Covid‐19 in men did not result in improved Covid‐19 outcomes. Additionally, pre‐existing male hypogonadism, diagnosed before Covid‐19 pandemic, was found to be a risk factor for hospitalization from Covid‐19. In this review, we also discuss the preclinical and mechanistic studies that have evaluated the role of androgens in SARS‐CoV‐2 infection and illness. Finally, long‐term consequences of Covid‐19 on male reproductive health are reviewed. SARS‐CoV‐2 virus is known to infiltrate testis and induce orchitis in men, but it is unclear if Covid‐19 leads to an increase in incidence of male hypogonadism.
Creating an appetite awareness and lifestyle modification intervention for Black women at risk for binge eating disorder: A pilot open trial
Authors: Goode Rachel W. , Bardone‐Cone Anna , Wilhoit‐Reeves Stephanie , Williams Lesley , Malian Hannah , Coan Danielle , Noem Taylor , Tate Deborah F.
Published: July 2023

Despite the availability of evidence‐based interventions to improve binge eating, Black women have some of the lowest rates of access to care for eating disorders. Innovation is needed to offer accessible and culturally relevant treatment options. To this end, using an open trial design, we investigated the feasibility and acceptability of a group‐based, appetite awareness training (AAT) + lifestyle modification (LM) programme in Black women at risk for BED in a primary care setting. Participants (n = 20) were Black women recruited from a family medicine centre affiliated with a local public university, and who reported at least two binge eating episodes in the last 28 days. Participants completed a 16‐session AAT + LM programme over 4 months. Key outcomes were objective binge eating (assessed by the EDE and the EDE‐Q), body dissatisfaction, and weight change, all assessed at baseline, four (post‐treatment) and 6 months (2‐month follow‐up). Ninety‐five percent of participants completed assessments at post‐treatment and attended nearly 60% of intervention sessions. Among completers (n = 19), body dissatisfaction and objective binge eating decreased from baseline to post‐treatment and this decrease was maintained at the 2‐month follow‐up. In exit interviews, participants reported programme satisfaction. Providing training in appetite awareness combined with lifestyle modification principles may be useful in the treatment of body dissatisfaction and binge eating among Black women.
A retrospective head‐to‐head comparison of the Lugano classification and PERCIST for FDG‐PET/CT response assessment in diffuse large B‐cell lymphoma
Authors: Nielsen Nicklas B. , Gerke Oke , Nielsen Anne L. , Juul‐Jensen Karen , Larsen Thomas S. , Møller Michael B. , Hildebrandt Malene G.
Published: July 2023

Background

Diffuse large B‐cell lymphoma (DLBCL) is the most common form of lymphoma. European guidelines recommend FDG‐PET/CT for staging and end of treatment (EOT) response assessment, mid‐treatment response assessment is optional. We compared the Lugano classification and PET Response Criteria In Solid Tumours (PERCIST) for FDG‐PET/CT response assessment in DLBCL head‐to‐head.

Methods

We retrospectively included patients with DLBCL who underwent first‐line R‐CHOP(‐like) therapy (2013−2020). Interim and EOT FDG‐PET/CT response were reevaluated using the Lugano classification and PERCIST. Response was dichotomized into complete metabolic response (CMR) versus non‐CMR (interim and EOT) and responders versus nonresponders (interim only). The cutoff for nonresponse at interim was a Deauville score of 5 (DS5) with the Lugano classification and a partial metabolic response with ≤66% reduction in SULpeak using PERCIST (PERCIST66).

Results

In multivariable Cox regression (N = 170), DS5 at interim, PERCIST66 at interim, non‐CMR at EOT with the Lugano classification and non‐CMR at EOT with PERCIST were predictive of progression‐free survival (PFS). The Lugano classification and PERCIST agreed perfectly at interim and EOT and with 98.4% for the identification of nonresponders at interim. The accuracy for predicting events within 2 years of diagnosis was 84.2% for DS‐5 at interim, 87.6% for PERCIST66 at interim, 86% for non‐CMR with the Lugano classification at EOT and 83.3% for non‐CMR with PERCIST at EOT.

Conclusion

The Lugano classification and PERCIST were equally predictive of PFS. Nonresponse at interim and non‐CMR at EOT were predictive of poor PFS with comparable accuracy for predicting events within 2 years.
Challenges in humanitarian response implementation: a large‐scale review of aid worker perspectives
Authors: Bollettino Vincenzo , Isely Rachel , Nyarko Godfred , Rudnicki Chloe , Rehmani Karima , Stoddard Hannah , Vinck Patrick
Published: July 2023

Aid workers offer important perspectives for understanding better the most pervasive challenges that arise when implementing emergency response programming in humanitarian settings. This large sample study provides a global review of these perspectives, derived from 4,679 applications to the National NGO Program on Humanitarian Leadership, in which aid workers were asked to respond to the following question: ‘What do you consider to be the biggest challenges in the implementation of emergency response programming in today's humanitarian settings?’. Through a qualitative coding process, the research team identified 14 major challenges that were prevalent across the applicants’ responses and cross‐tabulated these with their demographics. Coordination (30 per cent) and operating environment (29.5 per cent) were the most frequently reported. The study found a significant association between challenges identified and certain demographic variables. The results supplement a body of literature that is largely composed of small‐scale, context‐specific studies in which disaggre‐gation of data by demographics is not possible.
Relationship between the strain measures of left atrial function and heart failure worsening
Authors: Diomede Davide , Terazzi Erica , Diomede Nicolangelo , Alcidi Gianmarco , Pugliese Rosanna , Ioannoni Sara , Romano Matteo , Granatiero Michele , Di Terlizzi Vito , Correale Michele , Di Biase Matteo , Brunetti Natale Daniele , Iacoviello Massimo
Published: July 2023

Background

Two‐dimensional speckle tracking evaluation (2D‐STE) is a useful tool to evaluate the complexity of atrial function by the analysis of the different phases of atrial deformation and by the combination with Doppler measurements of diastolic function.

Aim of the study

To evaluate the role of the left atrial (LA) strain parameters to predict worsening chronic heart failure (CHF).

Methods

We enrolled outpatients affected by CHF referred to our heart failure unit. Each patient underwent a medical visit, an electrocardiogram (ECG), and an echocardiographic examination. LA function was assessed by 2D‐STE. The three phases of LA strain, that is, the reservoir (LAr), the conduit (LAcd), and the contraction (LAct)—were evaluated. Moreover, the ratio between E and LAr (E/LAr) and those between LAr and septal (LAr/Ees), lateral (LAr/Eel), and septal‐lateral (LAr/Eem) E/e’ were measured. During follow‐up, the events related to worsening of heart failure were evaluated.

Results

Two hundred eleven patients were enrolled. During a mean follow‐up of 14 ± 7 months, 37 patients showed at least one event related to heart failure worsening. At univariate Cox regression analysis, LAr, LAcd, LAct, E/LAr, LAr/Ees, LAr/Eel, and LAr/Eem were all associated with events related to heart failure worsening, but at multivariate regression analyses, only LAr (Hazard Ratio, HR: .95; 95% Confidence Interval, CI: .92–.99; p: .031), LAct (HR: 1.06; 95% CI: 1.01–1.12; p: .027), E/LAr (HR: 1.10; 95%CI: 1.0–1.16; p < .001), LAr/Ees (HR: .57; 95% CI: .37–.87; p: .010), and LAr/Eem (HR: .71; 95% CI: .53–.96; p: .026) remained significantly associated with the events. Finally, in a predictive model including the other relevant echocardiographic parameters LAr < 18%, LAct > −10.0%, LAr/Ees < 1.28, and E/LAr > 3.70 were associated with a statistically significant overall net reclassification improvement.

Conclusions

In CHF patients, the measure of the LA reservoir and contraction by 2D‐STE is independently associated with heart failure worsening, but the accuracy in predicting the events is even greater when the reservoir is combined with the Doppler measures of diastolic function.
Subclones with variants of uncertain clinical significance might contribute to ineffective hemopoiesis and leukemia predisposition
Authors: Giudice Valentina , Serio Bianca , Errichiello Santa , Ferrara Idalucia , Galdiero Alessandra , Bertolini Angela , Visconti Roberta , De Novellis Danilo , Guariglia Roberto , Luponio Serena , Morini Denise , Della Corte Anna Maria , Sessa Anna Maria , Verdesca Francesco , Langella Maddalena , Izzo Barbara , Selleri Carmine
Published: July 2023

Background

Splicing modifications, genomic instability, and hypomethylation are central mechanisms promoting myelodysplasia and acute myeloid leukemia (AML). In this real‐life retrospective study, to elucidate pathophysiology of clonal hemopoiesis in hematological malignancies, we investigated clinical significance of mutations in leukemia‐related genes of known pathogenetic significance and of variants of uncertain clinical significance (VUS) in a cohort of patients with MDS and AML.

Methods

A total of 59 consecutive subjects diagnosed with MDS, 48 with AML, and 17 with clonal cytopenia with unknown significance were screened for somatic mutations in AML‐related genes by next‐generation sequencing.

Results

We showed that TET2, SETBP1, ASXL1, EZH2, RUNX1, SRSF2, DNMT3A, and IDH1/2 were commonly mutated. MDS patients also showed a high genetic complexity, especially for SETBP1. Moreover, the presence of SETBP1 wild‐type or two or more simultaneous VUS variants identified a subgroup of AML and MDS patients with better outcome, while the presence of single SETBP1 VUS variant was related to a worse prognosis, regardless TET2 mutational status.

Conclusions

In conclusions, we linked both pathogenic and VUS variants in AML‐related genes to clonal hematopoiesis; therefore, we proposed to consider those variants as prognostic markers in leukemia and myelodysplasia. However, further studies in larger prospective cohorts are required to validate our results.
Is the cingulate island sign a marker for early dementia conversion in Parkinson's disease?
Authors: Chung Seok Jong , Kim Su Hong , Park Chan Wook , Lee Hye Sun , Kim Yun Joong , Lee Phil Hyu , Jeong Yong , Sohn Young H.
Published: July 2023

Background

To investigate whether the cingulate island sign (CIS) ratio (i.e., the ratio of regional uptake in the posterior cingulate cortex relative to the precuneus and cuneus on cerebral perfusion scans) is associated with early dementia conversion in Parkinson's disease (PD).

Methods

We enrolled 226 patients with newly diagnosed PD and 48 healthy controls who underwent dual‐phase 18F‐FP‐CIT PET scans. Patients with PD were classified into three groups according to the CIS ratio on early‐phase 18F‐FP‐CIT PET images: a PD group with CIS or high CIS ratios (PD‐CIS; n = 96), a PD group with inverse CIS or low CIS ratios (PD‐iCIS; n = 40), and a PD group consisting of the remaining patients with normal CIS ratios (PD‐nCIS; n = 90). We compared the risk of dementia conversion within a 5‐year time point between the groups.

Results

There were no significant differences in age, sex, education, or baseline cognitive function between the PD groups. The PD‐CIS group had higher Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and more severely decreased dopamine transporter availability in the putamen. The PD‐iCIS group had a smaller hippocampal volume compared with the other groups. The risk of dementia conversion in the PD‐CIS group did not differ from that in the PD‐iCIS and PD‐nCIS groups. Meanwhile, the PD‐iCIS group had a higher risk of dementia conversion than the PD‐nCIS group.

Conclusion

The results of this study suggest that inverse CIS, rather than CIS, is relevant to early dementia conversion in patients with PD.
Impact on carbamazepine usage and cutaneous adverse reactions before and after the reimbursement of HLA‐B*1502 genotyping in Taiwan, 2000–2017: A nationwide longitudinal study
Authors: Chang Bao‐Luen , Liu Jia‐Rou , Chang Shu‐Hao , See Lai‐Chu
Published: July 2023

Objective

The HLA‐B*1502 allele is strongly associated with carbamazepine (CBZ)‐induced Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in the Han Chinese population. This study investigated the impact of HLA‐B*1502 screening on CBZ utilization and rates of severe cutaneous allergic reactions (SCARs) and SJS/TEN over time in Taiwan, where screening for HLA‐B*1502 genotyping before prescribing CBZ was reimbursed in June 2010.

Methods

Using the Taiwan National Health Insurance Research Database, we analyzed 13 277 457 episodes of seeking treatment for epilepsy or neuralgia between 2000 and 2017. Episodes were categorized into quarters based on treatment time. Propensity score‐based stabilized weighting (PSSW) ensured well‐balanced covariates. The difference in 3‐month SCAR and SJS/TEN rates between phase 2 (2011–2017) and phase 1 (2000–2009) was examined using a one‐sample Z‐test. Pearson correlation coefficients assessed the association between screening rate, the number of CBZ users and nonusers, and SCAR and SJS/TEN rates after HLA‐B*1502 genotyping.

Results

CBZ prescriptions reduced from 7% (2000–2003) to 6% (2004–2010) and 4% (2011–2017). The screening rates of CBZ nonusers and CBZ users increased from 0%, .5% in 2011 to .8%, 16% in 2017, respectively. After PSSW, the mean 3‐month SCAR incidence rates (per 10 000 episodes) significantly decreased from phase 1 to phase 2 for CBZ users (6.91 vs. 3.09, p < .0001) and nonusers (1.96 vs. 1.65, p < .0001). SJS/TEN incidence rates (per 10 000 episodes) significantly decreased from phase 1 to phase 2 for CBZ users (2.94 vs. 1.93, p < .0001) but not for nonusers (.71 vs. .74, p = .1492). In phase 2, SCAR incidence rates were significantly and negatively correlated with the screening rate for both CBZ users (r = −.38, p = .0342) and nonusers (r = −.80, p < .001). No significant correlation was found between SJS/TEN incidence rates and screening rates.

Significance

Recognizing HLA‐B*1502 allele and avoiding CBZ therapy in HLA‐B*1502‐positive patients is critical for preventing CBZ‐induced severe adverse events.
Rafoxanide, a salicylanilide anthelmintic, interacts with human plasma protein transthyretin
Authors: Yokoyama Takeshi , Mizuguchi Mineyuki , Nabeshima Yuko , Nakagawa Yusuke , Okada Takuya , Toyooka Naoki , Kusaka Katsuhiro
Published: July 2023

Transthyretin (TTR) is a carrier protein for thyroid hormone thyroxine (T4) in plasma, placental cytosol, and cerebrospinal fluid. While the potential toxicity of small molecules that compete with T4 for binding to TTR should be carefully studied, these small molecules can also serve as anti‐ATTR amyloidosis drugs by stabilizing the TTR structure. Here, we demonstrated that rafoxanide, an EU‐approved anthelmintic drug for domesticated animals, binds to the T4‐binding site of TTR. An intrinsic fluorescence quenching assay showed that rafoxanide also binds to the thyroid hormone‐related proteins, including serum albumin and thyroid hormone receptor β. Rafoxanide strongly inhibited TTR amyloidogenesis in fibrillization assay, but the binding of rafoxanide to TTR was interfered with in human plasma, probably due to interactions with thyroid hormone‐related proteins. Protein crystallography provided clues for the optimization of binding affinity and selectivity. Our findings emphasize the importance of considering rafoxanide as both a possible thyroid‐disrupting chemical and a lead compound for the development of new ATTR amyloidosis inhibitors.
An equivalent cohesive zone model for a wide range of ductile and brittle adhesives
Authors: Noruzi Mohammad , Khoramishad Hadi
Published: July 2023

This paper aims to propose an equivalent trapezoidal traction–separation law (ET‐TSL) of the cohesive zone model applicable to a wide range of ductile and brittle adhesives using equivalent and fictitious material concepts. The ET‐TSL can reduce the analysis time and cost of complex problems without degrading the prediction accuracy. To experimentally validate the proposed ET‐TSL, double‐cantilever beam (DCB) samples were fabricated with glass fiber‐reinforced polymer substrates and a highly ductile adhesive and then tested. The fracture behavior of the specimens was modeled using the proposed ET‐TSL. Moreover, the accuracy and comprehensiveness of the proposed model were verified by employing the proposed ET‐TSL for different adhesive joints made of different adhesives ranging from brittle to ductile adhesives and different substrates found in the literature. It was found that the proposed ET‐TSL can provide reasonable accuracy in simulating the fracture response of different types of adhesive joints with brittle and ductile adhesives.
Didn’t I see these rocks in the movies? Yes, of course—they are the Vasquez Rocks
Authors: Painter Deborah
Published: July 2023

The Vasquez Rocks of Agua Dulce and Santa Clarita, California, USA have become associated with other planets or dimensions since the 1960s, when the popular American television programme Star Trek used them as dramatic backdrops in three episodes, ‘Arena’, ‘The Alternative Factor’ and ‘Friday's Child’. Today they are a popular visitor attraction, but what is their geological background?
Dried blood spot‐based host genome analysis technique targeting pathological associations with hepatitis B: Development and clinical application in the Cambodian population
Authors: Setoyama Hiroko , Nishida Nao , Nagashima Shintaro , Ko Ko , Yamazoe Taiji , Tanaka Yasuhito , Mizokami Masashi , Tanaka Junko , Kanto Tatsuya
Published: July 2023

Aim

Reports of patients with hepatitis B have highlighted associations between polymorphisms in the human leukocyte antigen (HLA)‐DPB1, CXCL13, and CXCR5 genes and disease pathology. Owing to its potential to contribute to the development of new diagnostic and therapeutic methods, we aimed to establish a reliable host genome analysis technique that can be used in countries with inadequate infrastructure.

Method

We compared multiple commercially available kits for dried blood spot (DBS)‐based sample collection to develop a basic DBS‐based host genome analysis technique. We then collected blood samples from Cambodian patients with hepatitis  B and performed single‐nucleotide polymorphism genotyping and HLA allele typing by the DBS system.

Result

We were able to perform single‐nucleotide polymorphism genotyping and HLA allele typing with host DNA samples obtained using a combination of a HemaSpot™ filter paper‐based device and a SMITEST® EX‐R&D DNA extraction kit. The accuracy of genotyping using samples obtained by this method was not inferior to one using samples obtained by venipuncture. In the Cambodian population, significant associations of HLA‐DPB1*04:01 with protection against chronic hepatitis B virus (HBV) infection, and HLA‐DPB1*05:01 and HLA‐DPB1*13:01 with susceptibility to chronic HBV infection were identified.

Conclusion

Based on the DBS system, we clarified the associations of HLA‐DPB1 alleles with chronic HBV infection in the Cambodian population for the first time. Because the DBS is a low‐cost, durable, transportable, and easy‐to‐handle modality, genetic analysis based on the DBS system is a feasible strategy for obtaining a deeper understanding of HBV epidemiology, especially in middle‐ or low‐income countries.
Predictions based on phylogeography and climatic niche modelling depict an uncertain future scenario for giant blister beetles (Berberomeloe, Meloidae) facing intensive greenhouse expansion and global warming
Authors: Sánchez‐Vialas Alberto , Calatayud‐Mascarell Arnau , Recuero Ernesto , Ruiz José L. , García‐París Mario
Published: July 2023

Large‐scale agricultural and tourism development are the main threats to biodiversity in south‐eastern Spain. Species with low dispersal abilities, such as some endemic insects from this region, are particularly vulnerable to fragmentation and loss of genetic and morphological diversity. Here, we studied the current and future threat of climate and land‐use change on the intraspecific diversity of one such group of endemics, the giant blister beetles of the Berberomeloe insignis species group.

Using a phylogeographic approach and morphometrics, we identified intraspecific variation within the B. insignis species group. These data were coupled with ecological niche modelling (ENM) to determine the effect of agricultural and climate change on the connectivity across phylogroups.

We identified a marked geographic structure within B. insignis, with the time to the most recent common ancestor (TMRCA) of the two main mtDNA clades dating back to 2.1 Ma. Cyto‐nuclear discordances found across parapatric populations suggest past events of genetic introgression. B. insignis presents a head pattern that is geographically structured and mostly congruent with the four mitochondrial lineages. In contrast, diversification within Berberomeloe tenebrosus is more recent, dating back to less than 1 Ma. Future ENMs highlight the role of mountains as potential refugia under a climate warming scenario but predict extinctions in the lowlands.

Based on our analyses, two lineages of B. insignis are threatened and should be urgently considered as independent conservation units, and their current geographic distribution areas protected to conserve, at the very least, a portion of the species' evolutionary heritage.
Government Expenditure on the Public Education System
Authors: Fu Chao , Ishimaru Shoya , Kennan John
Published: July 2023

We investigate equilibrium impacts of federal policies such as free‐college proposals, taking into account that human capital is cumulative and that state governments have resource constraints. In our model, a state government cares about household welfare and aggregate educational attainment. The government chooses income tax rates, per‐student expenditures on K‐12 and college education, college tuition, and the provision of other public goods. We estimate the model using U.S. data. Our simulations suggest that free‐college policies would decrease state expenditure on education. More students would obtain college degrees. Most households would “pay” for the free‐college policies through negative welfare effects.
Speaking anxiety and task complexity effects on second language speech
Authors: Mora Joan C. , Mora‐Plaza Ingrid , Bermejo Miranda Gonzalo
Published: July 2023

The association between speaking anxiety and L2 speech production, including L2 pronunciation, remains largely under‐researched, especially in relation to task complexity. The present study investigates the effect of task complexity on speaking anxiety and their impact on specific dimensions of L2 speech production: speaking fluency (speed, breakdown, and repair) and accuracy (grammar, lexis and pronunciation); and global assessments of L2 speaking performance: accentedness and comprehensibility. Forty‐two Spanish learners of English performed simple and complex versions of a monologic oral narrative task. The results indicated that task complexity affected learners’ anxiety levels and was detrimental to their L2 speaking fluency, pronunciation accuracy, and accentedness. Moreover, higher self‐perceived anxiety was associated with lower breakdown fluency and less lexico‐grammatical accuracy. Last, once the contributions of L2 proficiency and working memory were controlled for, anxiety accounted for a significant 13%–15% of variance in breakdown fluency.
Comparison of nutritional and trace element concentrations in some Sri Lankan traditional rice varieties
Authors: Kodikara Chamali , Vidanarachchi Janak K. , Nissanka Sarath P. , Bergquist Jonas , Pettersson Jean , Ubhayasekera Sarojini Jayantha Kumari A.
Published: July 2023

Recently, traditional rice cultivars have become more popular than new, enhanced rice varieties, with the main focus being on their health benefits. Few rice cultivars have been thoroughly studied to understand their nutritional and health benefits. Inductively coupled plasma atomic emission/mass spectroscopy methods were used to determine the concentrations of 24 key nutrients and trace elements in 104 traditional rice types (Oryza sativa L.) grown in Sri Lanka. Compared to the Codex Alimentarius provisional tolerable daily intake for 24 different elements, the concentrations of toxic elements such as As, Cd, Pb and Cr were significantly lower (P < 0.05), and most of the nutritional elemental concentrations were substantially higher (P < 0.05) in evaluated traditional rice varieties. Furthermore, Pb, Bi, B, K, Mg, S, Zn and Fe concentrations among traditional rice varieties were not substantially different (P > 0.05). Notably, several traditional rice varieties (i.e. Rathu Heenati, Pragathi Wee, Weda Heenati, etc.) contained significantly high levels of selenium (≈250 μg L−1 DM, P < 0.05), an important trace element that is deficient in the diets of 1 billion people globally.
Bone‐modifying agents are protective for symptomatic skeletal events in Radium‐223 treatment
Authors: Blas Leandro , Shiota Masaki , Matsumoto Takashi , Hori Yoshifumi , Nakamura Motonobu , Seki Narihito , Kuroiwa Kentaro , Yokomizo Akira , Morokuma Futoshi , Kiyoshima Keijiro , Eto Masatoshi
Published: July 2023

Introduction

Radium‐223 (Ra‐223) dichloride therapy increases overall survival and delays time to the first symptomatic skeletal event (SSE) in patients with castration‐resistant prostate cancer (CRPC) and bone metastases. Bone‐modifying agents (BMA) reduce SSE in patients with bone metastasis, but there is little information on their use with Ra‐223. This study aimed to investigate the effect of BMA on SSE in patients with bone metastatic CRPC treated with Ra‐223 in real‐world practice.

Methods

We included 73 patients treated with Ra‐223 from 10 institutions in Japan. Time to the first SSE was estimated using the Kaplan–Meier method and compared between groups using the log‐rank test. We used univariate analysis to ascertain the association between variables and SSE.

Results

During a median follow‐up of 12.7 months (interquartile range, 7–21.7), 12 (16.4%) patients presented SSE. Age and BMA use were different between men with and without SSE. The 1‐year SSE‐free survival rate from Ra‐223 treatment initiation was 82.4% (95% CI, 69.4%–90.2%). BMA use was associated with favorable SSE‐free survival (hazard risk, 0.23; 95% confidence interval, 0.061–0.85; p = 0.027). Two (4.7%) and seven (23.3%) patients presented symptomatic pathological bone fracture in groups with and without BMA use, respectively (p = 0.017).

Conclusion

This study stresses the importance of BMA use in patients with CRPC and bone metastases in Ra‐223 treatment.