bluuebunny/crossref_metadata_2025 huggingface dataset:
Conserved helical motifs in the IKZF1 disordered region mediate NuRD interaction and transcriptional repression
Authors: Zhang Tianyi , Wang Yi-Fang , Montoya Alex , Patrascan Ilinca , Nebioglu Nehir , Pallikonda Husayn A. , Georgieva Radina , King James W. D. , Kramer Holger B. , Shliaha Pavel V. , Rueda David S. , Merkenschlager Matthias
Published: October 2024

The transcription factor (TF) Ikaros zinc finger 1 (IKZF1) is essential for B-cell development, and recurrently mutated in human B-cell acute lymphoblastic leukemia (B-ALL). IKZF1 has been ascribed both activating and repressive functions via interactions with coactivator and corepressor complexes, but the relative abundance of IKZF1-associated coregulators and their contribution to IKZF1-mediated gene regulation are not well understood. To address this, we performed an unbiased identification of IKZF1-interacting proteins in pre-B cells and found that IKZF1 interacts overwhelmingly with corepressors and heterochromatin-associated proteins. Time-resolved analysis of transcription and chromatin state identified transcriptional repression as the immediate response to IKZF1 induction. Transcriptional repression preceded transcriptional activation by several hours, manifesting as a decrease in the fraction of transcriptional bursts at the single-molecule level. Repression was accompanied by a rapid loss of chromatin accessibility and reduced levels of histone H3 lysine 27 acetylation (H3K27ac), particularly at enhancers. We identified highly conserved helical motifs within the intrinsically disordered region of IKZF1 that mediate its association with the nucleosome remodeling and deacetylase (NuRD) corepressor complex through critical “KRK” residues that bind the NuRD subunit retinoblastoma binding protein 4 (RBBP4), a mechanism shared with the TFs FOG1, BCL11A, and SALL4. Functional characterization reveals that this region is necessary for the efficient silencing of target genes and antiproliferative functions of IKZF1 in B-ALL.
Siltuximab for chimeric antigen receptor T-cell therapy–related CRS and ICANS: a multicenter retrospective analysis
Authors: Bajwa Amneet , Zhao Qiuhong , Geer Marcus , Lin Chenyu , Westholder James , Maakaron Joseph , Ghosh Monalisa , Frame David , Galal Ahmed , Tossey Justin , Ahmed Nausheen , Bezerra Evandro , Denlinger Nathan , de Lima Marcos , Epperla Narendranath , Caimi Paolo , Voorhees Timothy
Published: October 2024

Chimeric antigen receptor T-cell (CAR-T) therapies are effective in many hematologic malignancies; however, adverse events including cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) can affect a significant number of patients. Those who develop refractory CRS or ICANS have few treatment options. Siltuximab, a monoclonal antibody binding circulating interleukin-6, has been proposed to have clinical activity in both CRS and ICANS. We conducted a multicenter retrospective analysis of siltuximab treatment for CRS and ICANS after CAR-T therapy in a real-world cohort from 6 academic centers. Fifty-four patients were evaluated. Sixteen patients had CRS previously treated with tocilizumab and 17 patients had ICANS previously treated with steroids. Of the patients with CRS at the time of siltuximab, 75% had improvement in CRS grade. Of the patients with ICANS at the time of siltuximab, 60% had improvement in ICANS grade. To our knowledge, this is the largest cohort of patients treated with siltuximab for CRS and/or ICANS after CAR-T therapies. Siltuximab appeared to be effective for both CRS and ICANS, including previously treated toxicities. These data support the use of siltuximab in CRS and ICANS as well as provide rationale for future prospective studies.
Impact of arm position compared to tourniquet and general anesthesia on peripheral vein width in supine adult patients: a prospective, monocentric, cross-sectional study
Authors: Berger Christian , Brandhorst Philipp , Asen Elena , Grallert Sven , Treskatsch Sascha , Weigeldt Moritz
Published: October 2024

Background

IV access is a commonly performed procedure that is often taught based on tradition rather than evidence. The effect of arm retroflexion on vein width, either alone or in combination with a tourniquet or general anesthesia (GA), remains unclear. In this case, the sonographically measured vein width is a surrogate parameter for the success of the puncture.

Methods

Prospective, cross-sectional study involving 57 patients scheduled for surgery in general anesthesia. We analyzed the impact of arm retroflexion, tourniquet, general anesthesia, and their combinations on the antebrachial veins in supine patients by ultrasound. Measurements were taken awake and during general anesthesia, each with and without the application of a tourniquet, and in three different arm positions (0°, 30°, and max° retroflexion) each. Data are presented as median and interquartile range [IQR].

Results

Tourniquet application (AT) had the greatest single effect on Cubital vein outer diameter compared to the baseline value of all measures (3.9 mm [3.4–5.1]; 4.8 mm [4.1–5.7], P = 0.001, r = 0.515). This effect was surpassed by the combination of AT and GA (5.1 mm [4.6–6.6], P = 0.001, r = 0.889). In contrast, retroflexion alone did not result in an increase at either 30° (4.2 mm [3.7–5.1], p = 1.0, r = 0.12) or max° (4.2 mm [3.6–4.9], p = 0.72, r = 0.23). With GA and AT, no further enlargement was measurable by 30° (5.4 mm [4.6–6.6], p = 1.0, r = 0.15) or max° (5.4 mm [4.6–6.6], p = 1.0, r = 0.07) retroflexion compared to GA-AT-0° (5.1 mm [4.6–6.6], p = 1.0, r = 0.15).

Conclusions

This study provides evidence that retroflexion of the arm in supine patients, whether alone or in addition to a tourniquet or general anesthesia, does not have any additional effect on vein width as a surrogate parameter for successful IV success. It shows for the first time that general anesthesia effectively increases vein diameter.

Trial registration

DRKS00029603 (date of registration 07.07.2022).
Kidney function, uric acid, and risk of atrial fibrillation: experience from the AMORIS cohort
Authors: Ding Mozhu , Schmidt-Mende Katharina , Carrero Juan-Jesus , Engström Gunnar , Hammar Niklas , Modig Karin
Published: October 2024

Background

Uric acid closely relates to both kidney disease and atrial fibrillation (AF), yet the extent to which it influences the kidney-AF association remains uncertain. We examined the relationship between kidney function and risk of AF, accounting for uric acid levels.

Methods

A total of 308,509 individuals in the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) cohort were included and their serum creatinine and uric acid were measured during 1985–1996. Ten-year incident AF was identified via linkage with the national registers. Glomerular filtration rate (eGFR) (ml/min/1.73 m2) was calculated with the 2009 Chronic Kidney Disease Epidemiology Collaboration equation. Hyperuricemia was defined as > 420 µmol/L for men and > 360 µmol/L for women.

Results

Over a mean follow-up of 9.4 years, 10,007 (3.2%) incident AF cases occurred. After adjusting for age, sex, cardiovascular diseases, total cholesterol, triglycerides, and glucose, individuals with low eGFR (< 30 and 30–59 ml/min/1.73 m2 ) had a higher risk of AF compared to those with normal eGFR (60–89) (hazard ratio (HR) = 1.72, 95% confidence interval (CI):1.29–2.30; HR = 1.10, 95% CI: 1.03–1.18, respectively). After further adjusting for uric acid levels, the association disappeared (HR = 0.97, 95% CI: 0.72–1.30; HR = 0.93, 95% CI: 0.86-1.00, respectively). When stratifying by hyperuricemia yes/no, eGFR < 30 ml/min/1.73 m2 was associated with higher AF risk in a small group of individuals without hyperuricemia (HR = 2.58, 95% CI: 1.64–4.07).

Conclusion

Uric acid largely accounted for the relationship between eGFR and AF in this study. However, in individuals without hyperuricemia, eGFR in the lowest range (< 30 ml/min/1.73 m2) was still associated with increased risk of AF.
Interpersonal symptoms in adolescence depression across Asian and European regions: a network approach
Authors: Cheung H. N. , Asgarabad M. Habibi , Ho W. S. , Zibetti M. R. , Li S. T. K. , Stella W. Y. Chan , Williams J. M.
Published: October 2024

Background

Major Depressive Disorder (MDD) poses a significant global health challenge, with symptom presentation potentially varying between adolescents and adults. Adolescence is a critical period marked by heightened vulnerability to interpersonal stresses, yet the impact of these stresses on the structure of depressive symptoms is not well understood. Recognizing the cultural nuances in how depression manifests among adolescents is crucial. To this end, this paper employs a network analysis approach, utilizing a comprehensive symptom checklist from the Multidimensional Depression Assessment Scale (MDAS). Our study investigates the role of interpersonal symptoms within the broader cluster of emotional, cognitive, and somatic symptoms and explores variations in adolescent groups in four Asian and European regions.

Methods

We recruited a diverse sample of 6,348 adolescents aged 12 to 18 from Hong Kong, Taiwan, the UK, China, and the Netherlands using the Qualtrics platform. Employing the Gaussian Graphical Model, we established a network model of depressive symptoms as measured by the MDAS, segregating the sample into Asian and European regions to examine the interconnections between them. The study focused on identifying central symptom nodes and comparing the network structures between the two groups.

Results

The analysis identified feeling worthless, low energy, being a burden to others, and low mood as central symptoms of depression. Notably, there were significant differences in the connections between depressive symptoms among Asian (Hong Kong, China and Taiwan) and European (UK and the Netherlands) adolescents, highlighting cultural variations in how interpersonal symptoms interact with emotional, cognitive, and somatic symptoms.

Conclusion

This study is pioneering in applying network analysis to include interpersonal symptoms in examining depression among a diverse adolescent population. It demonstrates that interpersonal symptoms are integral to the central features of depressive symptoms. Furthermore, our findings suggest that, compared to their UK and Dutch peers, interpersonal symptoms in Asian adolescents are uniquely connected to other symptom clusters, reflecting distinct cultural patterns. Limitations: The study engaged a broad community sample; however, future research could benefit from including a larger sample size to allow for a more detailed analysis of a greater number of symptom nodes.
Attitudes and perceptions of Thai medical students regarding artificial intelligence in radiology and medicine
Authors: Angkurawaranon Salita , Inmutto Nakarin , Bannangkoon Kittipitch , Wonghan Surapat , Kham-ai Thanawat , Khumma Porched , Daengpisut Kanvijit , Thabarsa Phattanun , Angkurawaranon Chaisiri
Published: October 2024

Introduction

Artificial Intelligence (AI) has made a profound impact on the medical sector, particularly in radiology. The integration of AI knowledge into medical education is essential to equip future healthcare professionals with the skills needed to effectively leverage these advancements in their practices. Despite its significance, many medical schools have yet to incorporate AI into their curricula. This study aims to assess the attitudes of medical students in Thailand toward AI and its application in radiology, with the objective of better planning for its inclusion.

Methods

Between February and June 2022, we conducted a survey in two Thai medical schools: Chiang Mai University in Northern Thailand and Prince of Songkla University in Southern Thailand. We employed 5-point Likert scale questions (ranging from strongly agree to strongly disagree) to evaluate students’ opinions on three main aspects: (1) their understanding of AI, (2) the inclusion of AI in their medical education, and (3) the potential impact of AI on medicine and radiology.

Results

Our findings revealed that merely 31% of medical students perceived to have a basic understanding of AI. Nevertheless, nearly all students (93.6%) recognized the value of AI training for their careers and strongly advocated for its inclusion in the medical school curriculum. Furthermore, those students who had a better understanding of AI were more likely to believe that AI would revolutionize the field of radiology (p = 0.02), making it more captivating and impactful (p = 0.04).

Conclusion

Our study highlights a noticeable gap in the understanding of AI among medical students in Thailand and its practical applications in healthcare. However, the overwhelming consensus among these students is their readiness to embrace the incorporation of AI training into their medical education. This enthusiasm holds the promise of enhancing AI adoption, ultimately leading to an improvement in the standard of healthcare services in Thailand, aligning with the country’s healthcare vision.
Diet quality in young adulthood and sleep at midlife: a prospective analysis in the Bogalusa Heart Study
Authors: Potts Kaitlin S. , Gustat Jeanette , Wallace Maeve E. , Ley Sylvia H. , Qi Lu , Bazzano Lydia A.
Published: October 2024

Background

Diet and sleep are both established risk factors for cardiometabolic diseases. Prior evidence suggests a potential link between these behaviors, though longitudinal evidence for how diet associates with sleep is scarce. This study aimed to determine the prospective association between diet quality in young adulthood and multiple sleep outcomes at midlife in the Bogalusa Heart Study (BHS).

Methods

This prospective study included 593 BHS subjects with dietary assessment at the 2001–2002 visit and sleep questionnaire responses from the 2013–2016 visit, after an average of 12.7 years (baseline mean age: 36 years, 36% male, 70%/30% White and Black persons). A culturally tailored, validated food frequency questionnaire assessed usual diet. Diet quality was measured with the Alternate Healthy Eating Index (AHEI) 2010, the Healthy Eating Index (HEI) 2015, and the alternate Mediterranean (aMed) dietary score. Robust Poisson regression with log-link function estimated risk ratios (RR) for insomnia symptoms, high sleep apnea score, and having a healthy sleep pattern by quintile and per standard deviation (SD) increase in dietary patterns. Models adjusted for potential confounders including multi-level socioeconomic factors, depression, and body mass index. Trends across quintiles and effect modification by sex, race, and education were tested.

Results

Higher diet quality in young adulthood, measured by both AHEI and HEI, was associated with lower probability of having insomnia symptoms at midlife. In the adjusted model, each SD-increase in AHEI (7.8 points; 7% of score range) conferred 15% lower probability of insomnia symptoms at follow-up (RR [95% confidence interval CI]: 0.85 [0.77, 0.93]), those in Q5 of AHEI had 0.54 times the probability as those in Q1 (95% CI: 0.39, 0.75), and there was a significant trend across quintiles (trend p = 0.001). There were no significant associations between young adult diet quality and having a high sleep apnea risk or a healthy sleep pattern at follow-up.

Conclusions

A healthy diet was associated with a lower probability of future insomnia symptoms. If replicated, these findings could have implications for chronic disease prevention strategies incorporating the lifestyle behaviors of sleep and diet.
World Health Organization repository of systematic reviews on interventions in environment, climate change and health: a new resource for decision makers, intervention implementers, and researchers
Authors: Shrikhande Shreya , Wolf Jennyfer , Vert Cristina , Egorova Alexandra , Neira Maria , Prüss Annette
Published: October 2024

To facilitate the use of the mounting evidence on how human health is inextricably linked to the health of the planet and the urgent need for measures against the escalating triple planetary crisis, the WHO has developed a repository of systematic reviews on interventions in the area of environment, climate change and health (ECH). This commentary introduces the repository, describes its rationale and development, and points to potential future evolutions. The repository aims to provide a user-friendly tool for quickly finding systematic reviews and meta-analyses on specific ECH topics. The spreadsheet includes details on each systematic review, such as population, intervention type, control group, outcomes, and location, among other information. This supports effective assessment of the available evidence, potentially informing policy decisions across various sectors. The repository is a resource for anyone interested in the interlinkages between health and environment and is also targeted at decision makers, intervention implementers and researchers in order to identify priority issues and support evidence-based action. Furthermore, it can be used to identify areas in need of greater research. Additionally, systematic reviews of intervention effectiveness are often used for setting general guidelines and standards, for choosing the most promising intervention in a certain situation and for calculating the disease burden attributable to a specific environmental risk.
Significant individual variation in cardiac-cycle-linked cerebrospinal fluid production following subarachnoid hemorrhage
Authors: Eide Per Kristian , Undseth Ragnhild Marie , Gjertsen Øyvind , Valnes Lars Magnus , Ringstad Geir , Lindstrøm Erika Kristina
Published: October 2024

Background

Spontaneous subarachnoid hemorrhage (SAH) often results in altered cerebrospinal fluid (CSF) flow and secondary hydrocephalus, yet the mechanisms behind these phenomena remain poorly understood. This study aimed to elucidate the impact of SAH on individual CSF flow patterns and their association with secondary hydrocephalus.

Methods

In patients who had experienced SAH, changes in CSF flow were assessed using cardiac-gated phase-contrast magnetic resonance imaging (PC-MRI) at the Sylvian aqueduct and cranio-cervical junction (CCJ). Within these regions of interest, volumetric CSF flow was determined for every pixel and net CSF flow volume and direction calculated. The presence of acute or chronic hydrocephalus was deemed from ventriculomegaly and need of CSF diversion. For comparison, we included healthy subjects and patients examined for different CSF diseases.

Results

Twenty-four SAH patients were enrolled, revealing a heterogeneous array of CSF flow alterations at the Sylvian aqueduct. The cardiac-cycle-linked CSF net flow in Sylvian aqueduct differed from the traditional figures of ventricular CSF production about 0.30–0.40 mL/min. In 15 out of 24 patients (62.5%), net CSF flow was retrograde from the fourth to the third and lateral ventricles, while it was upward at the cranio-cervical junction in 2 out of 2 patients (100%). The diverse CSF flow metrics did not distinguish between individuals with acute or chronic secondary hydrocephalus. In comparison, 4/4 healthy subjects showed antegrade net CSF flow in the Sylvian aqueduct and net upward CSF flow in CCJ. These net CSF flow measures also showed interindividual variability among other patients with CSF diseases.

Conclusions

There is considerable inter-individual variation in net CSF flow rates following SAH. Net CSF flow in the Sylvian aqueduct differs markedly from the traditional ventricular CSF production rates of 0.30–0.40 mL/min in SAH patients, but less so in healthy subjects. Furthermore, the cardiac-cycle-linked net CSF flow rates in Sylvian aqueduct and CCJ suggest an important role of extra-ventricular CSF production.
Incidence, predictability, and outcomes of systemic venous congestion following a fluid challenge in initially fluid-tolerant preload-responders after cardiac surgery: a pilot trial
Authors: Morosanu Bianca , Balan Cosmin , Boros Cristian , Dazzi Federico , Wong Adrian , Corradi Francesco , Bubenek-Turconi Serban-Ion
Published: October 2024

Background

Fluid administration has traditionally focused on preload responsiveness (PR). However, preventing fluid intolerance, particularly due to systemic venous congestion (VC), is equally important. This study evaluated the incidence and predictability of VC following a 7 ml/kg crystalloid infusion in fluid-tolerant preload-responders and its association with adverse outcomes.

Methods

This single-center, prospective, observational study (May 2023–July 2024) included 40 consecutive patients who were mechanically ventilated within 6 h of intensive care unit (ICU) admission after elective open-heart surgery and had acute circulatory failure. Patients were eligible if they were both fluid-tolerant and preload-responsive. PR was defined as a ≥ 12% increase in left-ventricular outflow tract velocity time integral (LVOT-VTI) 1 min after a passive leg raising (PLR) test. VC was defined by a portal vein pulsatility index (PVPI) ≥ 50%. Patients received a 7 ml/kg Ringer’s Lactate infusion over 10 min. The primary outcome was the incidence of VC 2 min post-infusion (early-VC). Secondary outcomes included VC at 20 min, the incidence of acute kidney injury (AKI) and severe AKI at 7 days, and ICU length of stay (LOS).

Results

45% of patients developed early-VC, with VC persisting in only 5% at 20 min. One-third of patients developed AKI, with 17.5% progressing to severe AKI. The median ICU LOS was 4 days. Patients with early-VC had significantly higher central venous pressure, lower mean perfusion pressure, worse baseline right ventricular function, and a higher incidence of severe AKI. While LVOT-VTI returned to baseline by 20 min in both groups, PVPI remained elevated in early-VC patients (p < 0.001). The LVOT-VTI versus PVPI regression line showed similar slopes (p = 0.755) but different intercepts (p < 0.001), indicating that, despite fluid tolerance and PR at baseline, early-VC patients had reduced right ventricular diastolic reserve (RVDR). Post-PLR PVPI predicted early-VC with an area under the curve of 0.998, using a threshold of 44.3% (p < 0.001).

Conclusion

Post-PLR PVPI effectively predicts fluid-induced early-VC in fluid-tolerant preload-responders, identifying those with poor RVDR. Its use can guide fluid management in cardiac surgery patients, helping to prevent unnecessary fluid administration and associated complications.

Trial Registration: NCT06440772. Registered 30 May 2024. Retrospectively registered.
Golgiphagy: a novel selective autophagy to the fore
Authors: Chen Yifei , Wu Yihui , Tian Xianyan , Shao Genbao , Lin Qiong , Sun Aiqin
Published: October 2024

The Golgi apparatus is the central hub of the cellular endocrine pathway and plays a crucial role in processing, transporting, and sorting proteins and lipids. Simultaneously, it is a highly dynamic organelle susceptible to degradation or fragmentation under various physiological or pathological conditions, potentially contributing to the development of numerous human diseases. Autophagy serves as a vital pathway for eukaryotes to manage intracellular and extracellular stress and maintain homeostasis by targeting damaged or redundant organelles for removal. Recent research has revealed that autophagy mechanisms can specifically degrade Golgi components, known as Golgiphagy. This review summarizes recent findings on Golgiphagy while also addressing unanswered questions regarding its mechanisms and regulation, aiming to advance our understanding of the role of Golgiphagy in human disease.
Insights into the length and breadth of methodologies harnessed to study human telomeres
Authors: Coulter Tiernan , Hill Claire , McKnight Amy Jayne
Published: October 2024

Telomeres are protective structures at the end of eukaryotic chromosomes that are strongly implicated in ageing and ill health. They attrition upon every cellular reproductive cycle. Evidence suggests that short telomeres trigger DNA damage responses that lead to cellular senescence. Accurate methods for measuring telomeres are required to fully investigate the roles that shortening telomeres play in the biology of disease and human ageing. The last two decades have brought forth several techniques that are used for measuring telomeres. This editorial highlights strengths and limitations of traditional and emerging techniques, guiding researchers to choose the most appropriate methodology for their research needs. These methods include Quantitative Polymerase Chain Reaction (qPCR), Omega qPCR (Ω-qPCR), Terminal Restriction Fragment analysis (TRF), Single Telomere Absolute-length Rapid (STAR) assays, Single TElomere Length Analysis (STELA), TElomere Shortest Length Assays (TESLA), Telomere Combing Assays (TCA), and Long-Read Telomere Sequencing. Challenges include replicating telomere measurement within and across cohorts, measuring the length of telomeres on individual chromosomes, and standardised reporting for publications. Areas of current and future focus have been highlighted, with recent methodical advancements, such as long-read sequencing, providing significant scope to study telomeres at an individual chromosome level.
Controls of low injectivity caused by interaction of reservoir and clogging processes in a sedimentary geothermal aquifer (Mezőberény, Hungary)
Authors: Markó Ábel , Brehme Maren , Pedretti Daniele , Zimmermann Günter , Huenges Ernst
Published: October 2024

Low injectivity is often experienced in geothermal doublets installed in sandstone reservoirs. This even led to a shutdown of the Mezőberény (Hungary) geothermal site. An on-site campaign was carried out in January 2021 to prepare a stimulation aiming to enhance the transmissivity of the sedimentary reservoir and the near-wellbore zone of this site. Previous studies have concluded that insufficient injectivity may be linked to a high skin effect in the near well-bore zone and pore clogging in combination with the low net sandstone content of the fluvio-deltaic reservoir. A chemical soft stimulation based on the injection of hydrochloric acid (HCl) was successfully used to unclog and recover the well injectivity. Despite such empirical evidence, the geochemical mechanisms leading to both, detrimental formation of clogging and the HCl-driven transmissivity restoration, have not yet been elucidated. This work presents the results of a novel analysis aiming at (a) predicting the dominant type of clogging forming in the near-well bore zone; (b) quantifying the drop in hydraulic conductivity as clogging occurs; and (c) supporting the optimization of the HCl dosage during the chemical soft stimulation. The study is supported by new experimental datasets never presented before from the Mezőberény site and a geochemical model set-up simulating the main mechanisms involved in the clogging and unclogging processes. It is concluded that the biofilm formation was the dominant, while the precipitation of calcite and amorphous ferrihydrite—later reduced to magnetite by microbes—was the secondary clogging mechanism: In the long-term (yearly scale) simulating the hydraulic conductivity showed a decline with forming scales; therefore, biofilm was presumably responsible for the experienced rapid (1 month) clogging. When modelling the chemical stimulation, the estimated amount of precipitated minerals was dissolved already with 2.5 mol of HCl per liter of water (~ 10 m/m%). Therefore, the 20 m/m% of HCl chosen during the field campaign might had a beneficial effect dissolving the potentially higher amount of scaling and/or the carbonate minerals of the matrix near the wellbore. Overall, it is concluded that the chemical and the microbial analyses together with the geochemical model were critical to tailor the remediation attempts and to propose further development or reconstruction of the surface system before going into operation to prevent recurrent impairments. Our findings highlight the importance of interactions of various clogging mechanisms with each other as well as with the reservoir processes and provide approaches to tackle the issue of injectivity drop by characterizing and quantifying their effects.
Multi-hazard risk assessment analysis in La Palma: an approach for risk mitigation
Authors: Martín-Raya Nerea , Díaz-Pacheco Jaime , López-Díez Abel
Published: October 2024

Background

La Palma, like many regions of the world, may be affected by various hazards, with different levels of susceptibility, which have a greater or lesser impact on society. In this context, a multi-risk approached model capable of estimating the total risk faced by the territory is required, considering the different hazards to which it is exposed (floods, earthquakes, volcanic eruptions and landslides) and the different conditions of vulnerability of both the population and the exposed assets.

Methods

The methodology employed in this study has been referred to as "multilayer single hazard", which consists of the aggregation or superposition of hazards located in the same space. As usual, the identification of the individual hazard of each one of them was carried out using heterogeneous methods, which is why an index is proposed to homogenize the hazards and make them comparable with each other. On the other hand, the model also integrates a prototype to evaluate vulnerability from a multiple perspective (vulnerability by hazard) and shows the aggregated information in maps at a medium representation scale (definition of 250 m).

Results

The risk integration results show that 5% of the island is at high risk levels. Simultaneously, the south of the island is presented as the area that shows the highest risk by combining a high hazard, especially related to volcanic hazards, and a high exposure, as it is home to a significant volume of population.

Conclusions

The proposed methodology is also interesting because it can be replicated in other areas of study.
“Like two peas in a pod?” Homogamous personalities, education, and union dissolution
Authors: Hofmann Elias , Krapf Sandra
Published: October 2024

This paper examines the association between the level of similarity in the “Big Five” personality traits of the partners in different-sex couples and their risk of union dissolution. Prior research has mainly focused on homogamy in socio-economic, demographic, and cultural characteristics, such as age, education, employment, and religion. The few studies on the effects of homogamy in the personalities of the partners on separation find mixed results. We extend on this by analysing the moderating effect of education. Using data from the German Socio-Economic Panel (SOEP) for the 2005–2019 period, we follow 3958 coresidential couples and observe 534 separations. Personality is measured via the “Big Five” personality traits. We estimate discrete-time event history models for union dissolution. In addition to reporting the main effects, we calculate interactions between personality and the level of education of the partners. Our results indicate that greater dissimilarity with regard to the personality trait “openness” is associated with a higher probability to separate. However, analysing interaction effects reveals that this is relevant mainly among medium educated men. Moreover, persons with high education seem to be less likely to separate if they are dissimilar from their partner in their level of “extraversion”. These findings suggest that relationship dynamics differ across educational groups.
The integrated Mexican nation-state building in the 20th century
Authors: Zhang Qingren
Published: October 2024

Since gaining independence in the early 19th century, Mexico embarked on a path toward building a nation-state. In criticizing the evolutionism that promotes white supremacy, Mexican society has embarked on a journey of introspection, delving into the essence of its indigenous national character. Following the Mexican Revolution at the turn of the 20th century, a nationalism advocating for integration was firmly established. The Institutional Revolutionary Party (PRI) government incorporated the principles of national integration into the broader building of the nation-state. On the one hand, it affirmed the crucial role of indigenous peoples and their cultures, tracing the origins of the Mexican nation-state back to these roots. On the other hand, the promotion of unified education, coupled with the implementation of a land-centered state corporatist system, aimed to achieve the integration and governance of Indigenous peoples, thereby incorporating them into the nation-building process and ultimately facilitating the integration of the nation-state. While the PRI government’s integration efforts led to tendencies towards marginalization and assimilation of indigenous peoples, alongside insufficient attention to their rights and political participation, it fundamentally changed the historically unrecognized status of indigenous communities since the colonial era. These efforts primarily addressed the issues that had challenged Mexican social development concerning indigenous peoples since the colonial era, contributing to maintaining national stability over an extended period.
Ultrasound-guided cryoablation of early breast cancer: safety, technical efficacy, patients’ satisfaction, and outcome prediction with MRI/CEM: a pilot case-control study
Authors: Galati Francesca , Pasculli Marcella , Maroncelli Roberto , Rizzo Veronica , Moffa Giuliana , Cerbelli Bruna , d’Amati Giulia , Catalano Carlo , Pediconi Federica
Published: October 2024

Background

This pilot prospective study aimed to evaluate ultrasound-guided cryoablation of breast cancer (BC) by assessing: (i) technical efficacy as the presence of necrosis in surgical specimens and rate of complete tumor ablation; (ii) safety as incidence and severity of complications; and (iii) patients’ satisfaction using a dedicated questionnaire. In addition, (iv) we tested the capability of magnetic resonance imaging (MRI) or contrast-enhanced mammography (CEM) to predict cryoablation efficacy.

Methods

From 07/2022 to 01/2023, we enrolled 20 patients with early-stage BC scheduled for breast surgery. Ten of them, with a cryo-feasible cancer location, were sent to cryoablation (cryo-group) and ten to routine surgical practice (control group). Both groups underwent surgery and were asked to answer a satisfaction questionnaire.

Results

Of eleven patients screened for cryoablation, only one refused to be treated at another hospital (acceptance rate 10/11, 91%). Surgery was quadrantectomy in 19 cases and mastectomy in 1. In the cryo-group, the procedure was completed and steatonecrosis was observed in 10/10 cases, with complete tumor ablation in nine of them. The post-procedural status was evaluated with MRI in five patients, with CEM in four patients, and with ultrasound in one patient who refused MRI and CEM. MRI or CEM correctly predicted complete cryoablation in eight patients and incomplete cryoablation in one patient. Patients in both groups did not have serious complications and responded positively to satisfaction questionnaires.

Conclusion

Ultrasound-guided cryoablation of early-stage BC is well accepted by patients, effective, and safe. MRI and CEM were able to predict the procedure's technical efficacy.

Trial registration

https://clinicaltrials.gov/study/NCT05727813 updated February 14, 2023.

Relevance statement

Our pilot study showed that ultrasound-guided cryoablation is a promising nonsurgical alternative for treating early-stage BC.

Key Points

Ultrasound-guided cryoablation was effective and safe in early BC patients.

The procedure was well-tolerated, with low morbidity and high patient satisfaction.

MRI and CEM predicted cryoablation efficacy, in accordance with histopathologic findings.

Cryoablation can be considered a potential alternative to surgery in selected patients.

Graphical Abstract
Quantitative ultrasound assessment of fatty infiltration of the rotator cuff muscles using backscatter coefficient
Authors: Toto-Brocchi Marco , Wu Yuanshan , Jerban Saeed , Han Aiguo , Andre Michael , Shah Sameer B. , Chang Eric Y.
Published: October 2024

Background

To prospectively evaluate ultrasound backscatter coefficients (BSCs) of the supraspinatus and infraspinatus muscles and compare with Goutallier classification on magnetic resonance imaging (MRI).

Methods

Fifty-six participants had shoulder MRI exams and ultrasound exams of the supraspinatus and infraspinatus muscles. Goutallier MRI grades were determined and BSCs were measured. Group means were compared and the strength of relationships between the measures were determined. Using binarized Goutallier groups (0–2 versus 3–4), areas under the receiver operating characteristic curves (AUROCs) were calculated. The nearest integer cutoff value was determined using Youden’s index.

Results

BSC values were significantly different among most Goutallier grades for the supraspinatus and infraspinatus muscles (both p < 0.001). Strong correlations were found between the BSC values and Goutallier grades for the supraspinatus (τb = 0.72, p < 0.001) and infraspinatus (τb = 0.79, p < 0.001) muscles. BSC showed excellent performance for classification of the binarized groups (0–2 versus 3–4) for both supraspinatus (AUROC = 0.98, p < 0.0001) and infraspinatus (AUROC = 0.98, p < 0.0001) muscles. Using a cutoff BSC value of −17 dB, sensitivity, specificity, and accuracy for severe fatty infiltration were 87.0%, 90.0%, and 87.5% for the supraspinatus muscle, and 93.6%, 87.5%, and 92.7% for the infraspinatus muscle.

Conclusion

BSC can be applied to the rotator cuff muscles for assessment of fatty infiltration. For both the supraspinatus and infraspinatus muscles, BSC values significantly increased with higher Goutallier grades and showed strong performance in distinguishing low versus high Goutallier grades.

Relevance statement

Fatty infiltration of the rotator cuff muscles can be quantified using BSC values, which are higher with increasing Goutallier grades.

Key Points

Ultrasound BSC measurements are reliable for the quantification of muscle fatty infiltration.

BCS values increased with higher Goutallier MRI grades.

BCS values demonstrated high performance for distinguishing muscle fatty infiltration groups.

Graphical Abstract
The impact of sex differences on stroke risk factors and 3-month outcomes in patients receiving thrombolytic therapy for acute ischemic stroke
Authors: Khedr Eman M. , Abo-Elfetoh Noha , Hasan Asmaa M. , Nasreldein Ahmed , Haridy Nourelhoda A.
Published: October 2024

Background

Acute ischemic stroke (AIS) is a major public health issue, and women have a disproportionate share of stroke-related disability and mortality, which is poorly understood. This study aimed to determine the effect of sex differences on AIS treated by thrombolysis using recombinant tissue plasminogen activator (rTPA). The study included 134 AIS patients eligible for rTPA. Risk factors, clinical presentation, thrombolysis response, complications, and outcomes were recorded. The outcomes were measured using the National Institute of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) 3 months after stroke. The incidence of intracranial haemorrhage was also determined.

Results

Among 134 AIS patients treated with rTPA (59% male, 41% female), females had higher rates of hypertension (67.3% versus 49.4%, p = 0.040) and atrial fibrillation (AF) (12.7% versus 2.5%, p = 0.020), while smoking was more prevalent in males (31.6% versus 0%, p < 0.0001). Cardioembolism was more frequent in females than in males (23.6% versus 6.3%, p = 0.004). Females also had shorter onset-to-door (110.7 ± 63 versus 131.1 ± 50.2 min, p = 0.035) and onset-to-needle times (151.6 ± 66.5 versus 173.7 ± 50.6 min, p = 0.046). Both sexes showed significant improvements in NIHSS (males: 11.58 ± 3.7 to 6.05 ± 5.6; females: 11.64 ± 4.7 to 6.9 ± 5.9; p < 0.0001) and mRS scores (males: 3.34 ± 1.05 to 2.03 ± 2; females: 3.53 ± 1 to 2.02 ± 2; p < 0.0001) over 3 months, with no significant differences between sexes. Predictors of poor outcome (mRS 3–6) differed: diabetes mellitus (DM) (OR 7.79, p = 0.002) and longer door-to-needle time (OR 1.04, p = 0.008) for males, and hemorrhage (OR 9.41, p = 0.048) for females. Hemorrhage predicted mortality in males (OR 27.08, p < 0.0001), while AF was associated with increased mortality in females (OR 8.06, p = 0.024).

Conclusions

This study revealed sex-specific differences in AIS risk factors, aetiology, and rTPA treatment timelines, although post-treatment improvements were comparable between sexes. Notably, outcome predictors and mortality factors differed by sex. These findings emphasize the need for sex-specific considerations in AIS management and risk assessment.
RNA silencing is activated by N gene-mediated hypersensitive response and plays a key role in local and systemic virus resistance
Authors: Li Wenjing , Yu Ru , Liu Wenjuan , Zhang Hong , Ren Chengyang , Zhang Yan , Ma Haoran , Zhu Changxiang , Liu Hongmei
Published: October 2024

In plants, recognition between resistance gene (R) and virus induces a local hypersensitive response (HR), which is accompanied by systemic acquired resistance (SAR). The dominant resistance gene N in tobacco confers resistance to tobacco mosaic virus (TMV) at both locally inoculated tissues and systemically infected tissues. However, the mechanisms underlying HR- and SAR-mediated viral inhibition are not fully revealed. In this study, we find that Nicotiana glutinosa RNA-binding protein (NgRBP) is an RNA silencing suppressor which enhances TMV-triggered HR. Stronger HR could result in stronger local and systemic RNA silencing as well as SAR. Enhanced RNA silencing in the systemically infected leaves induced by the NgRBP gene is compromised by transient expression of NahG. These results indicate that RNA silencing is activated by HR and plays a crucial role in local and systemic virus resistance. Our results reveal a crosstalk between N gene-mediated virus resistance and RNA silencing which would deepen our understanding of the established HR and SAR models.
Outcomes of left atrial appendage closure versus oral anticoagulant therapy in patients with atrial fibrillation: an updated meta-analysis of randomized control trials
Authors: Pramana Ketut Angga Aditya Putra , Cahyani Ni Gusti Ayu Made Sintya Dwi , Pintaningrum Yusra , Rahmat Basuki
Published: October 2024

Background

The purpose of this study is to compare the clinical results of Left Atrial Appendage Closure (LAAC) and oral anticoagulation (OAC) in individuals with AF.

Methods

For randomized controlled trials (RCTs) comparing the clinical results of OAC to LAAC in patients with atrial fibrillation (AF), we searched PubMed, ScienceDirect, and Cochrane. The included publications were subjected to meta-analyses using Review Manager v5.4.

Results

In comparison to OAC, LAAC was linked with a decreased incidence of all stroke (OR 0.68; 95% CI 0.55–0.84; p = 0.0004). LAAC was also linked to a decreased risk of hemorrhagic stroke (OR 0.20, 95% CI 0.07–0.55; p = 0.002). There is no statistically significant difference between the two groups in terms of ischemic stroke (OR 1.05; 95% CI 0.59–1.84; p = 0.88) or systemic embolization (OR 1.02; 95% CI 0.42–2.46; p = 0.97).

Conclusions

According to our meta-analysis, the LAAC was less likely than the OAC to have a complete or hemorrhagic stroke. For the two groups, however, there was no difference in the risk of ischemic stroke or systemic embolization.
Champions to enhance implementation of clinical and community-based interventions in cancer: a scoping review
Authors: Astorino Nicola Joseph , Nataliansyah M. Muska , Lopez-Olivo Maria A. , Adegboyega Adebola , Hirko Kelly A. , Chichester Lou-Anne R. , Nock Nora L. , Ginex Pamela , Christy Shannon M. , Levett Paul
Published: October 2024

Background

Champions are integral across research in cancer, yet studies exploring their roles are limited and have produced mixed results. The current review examines and synthesizes descriptions of how champions emerged and the types of activities they most often performed. By examining evidence from across the translational research continuum, this scoping review aims to characterize the role of champions and strategies that facilitate their involvement in the implementation of cancer care interventions in both clinical and community-based settings.

Methods

This scoping review was designed and implemented in compliance with PRISMA-ScR. The review focused on peer-reviewed articles in English-language journals. We searched five databases: PubMed (including MEDLINE), Scopus (including EMBASE), CINAHL, PsycINFO, and the Cochrane Library. Articles published from 1971 to 2022 were included. Two members of the team reviewed in duplicate each article and then a single member of the team extracted the data in Covidence, with a second member comparing the extraction to the original article. Qualitative and quantitative data were extracted and then synthesized. These data were used to summarize core champion activities and implementation strategies and to characterize barriers and facilitators to using champions in research.

Results

A total of 74 articles were included in the review. The qualitative synthesis highlighted facilitators and barriers to the effective use of champions. Facilitators included consideration of an individual’s characteristics when identifying champions, time spent planning for the specific responsibilities of champions, working within a supportive environment, and identifying champions embedded in the target setting. Major barriers included constrained time, low self-efficacy among champions, inadequate training, high turnover rates of champions, and a lack of buy-in from organizational leadership toward the intervention. Champions also were mostly assigned their roles, had varied core activities, and used complementary strategies to empower their target populations. Champions’ most frequent core activities include facilitation, outreach/promotion, and recruitment of participants into studies.

Conclusions

Champions were used in research of many cancer types and often serve similar roles regardless of where they are located within the translational research process. Despite their critical role, evidence is lacking on the impact of champions specifically on outcomes of many of the research studies that include them. Future research is needed to understand the nuances of champion-driven approaches across diverse cancer care settings.
The potential of xanthotoxin in the treatment of cognitive disorders: current insights and future perspectives
Authors: Agarwal Uma , Pannu Arzoo , Tonk Rajiv Kumar , Jaiswal Puja , Jain Kajal
Published: October 2024

Background

The prevalence of cognitive diseases, including Alzheimer’s disease and other forms of dementia, poses a significant global health challenge due to the limited availability of effective therapeutic options. Recent years have witnessed a growing emphasis in research on the exploration of natural compounds and their derivatives as prospective therapeutic agents for cognitive impairments.

Main body Xanthotoxin, a furanocoumarin compound derived from botanical sources, exhibits promising therapeutic promise in several neurological conditions such as depression, neuronal inflammation, Alzheimer’s disease, vascular cognitive impairment, epilepsy, and Parkinson’s disease. This potential stems from its notable neuroprotective, antioxidant, and anti-inflammatory characteristics. The present study offers a comprehensive examination of the acquisition of XAT from both natural sources and synthetic means. It delves into the significance of XAT in the treatment of cognitive disorders and delineates potential avenues for future research in the domain of XAT and cognitive disorders.

Conclusion

Ongoing research and advancements in the field of XAT have the potential to enhance its use as a potent therapeutic intervention for cognitive impairments, consequently enhancing the holistic welfare of those afflicted by these incapacitating disorders.