bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexural behavior of two-layer reinforced concrete slab with hollow cores
Authors: Eisa Ahmed S. , Aboul-Nour Louay A. , El-Ghamry Asmaa , Zeleňáková Martina , Katunský Dušan
Published: February 2024

Flexural behavior of a concrete slab system with an optimal weight-to-strength ratio comprising layered and hollow-core slab structures was investigated using two-layered slabs with hollow cores (LS/HCS). Six slabs with dimensions of 180, 450, and 1600 mm were tested experimentally and numerically using ANSYS software. Each layered slab comprises a 90-mm-thick lightweight concrete bottom layer and a 90-mm-thick high-strength concrete top layer. Three parameters were studied: core diameter (58, 86, and 110 mm), reinforcement ratio (0.37%, 0.53%, 0.95%), and treatment type (bonding agent, nails). Treatment types were analyzed via push-out testing; both nails and agents connected the slabs with sufficient bond strength. A control slab with 86-mm core diameter, shear-span-to-effective-depth ratio of 4, reinforcement ratio of 0.53%, and agent material was used. Concrete, steel bars, and loading support plates were modeled using SOLID65, LINK180, and SOLID185 elements, respectively. Analytical results were validated experimentally. A parametric study analyzed other parameters affecting LS/HCS behavior, including compressive strength, opening numbers, core shape, applied loading type, added top steel reinforcement, slab type, and slab height. Core diameter reduction, increased reinforcement ratios, and using nails enhanced the failure load. The LS/HCS gives an optimum weight-to-strength ratio with a 33.672% reduction compared with solid slabs.
Pregnancy- and parenting-related barriers to receiving medication for opioid use disorder: A multi-paneled qualitative study of women in treatment, women who terminated treatment, and the professionals who serve them
Authors: Apsley Hannah B , Brant Kristina , Brothers Sarah , Harrison Eric , Skogseth Emma , Schwartz Robert P , Jones Abenaa A
Published: February 2024

Background:

Women face unique barriers when seeking treatment for substance use disorders, often related to pregnancy and parenting.

Objectives:

This study adds to the extant literature by elucidating the pregnancy- and parenting-related barriers women face when initiating or continuing medication for opioid use disorder, specifically.

Design:

This study is based on qualitative semi-structured interviews.

Methods:

Three subgroups participated in semi-structured interviews regarding their experiences (N = 42): women with current or past opioid use disorders who have used or were presently using medication for opioid use disorder, professionals working in substance use disorder treatment programs, and criminal justice professionals.

Results:

Three parenting-related subthemes were identified: (1) insufficient access to childcare to navigate appointments and meetings, (2) fear of losing custody of, or access to, one’s children, and (3) prioritizing one’s children’s needs before one’s own. Three subthemes were identified with regard to pregnancy as a barrier: (1) hesitancy among physicians to prescribe medication for opioid use disorder for pregnant patients, (2) limited access to resources in rural areas, and (3) difficulty navigating a complex, decentralized health system.

Conclusion:

Systemic changes are needed to reduce pregnant and parenting women’s barriers to seeking medication for opioid use disorder. These include improved childcare support at both in-patient and outpatient treatment programs, which would assuage women’s barriers related to childcare, as well as their fears of losing access to their children if they spend time away from their children for treatment. An additional systemic improvement that may reduce barriers for these women is access to comprehensive, integrated care for their prenatal care, postpartum care, pediatric appointments, and appropriate substance use disorder treatment.
No pupillometric evidence for effortful proactive control in the proportion-congruent Stroop paradigm
Authors: Hasshim Nabil , Carruthers Molly , Ferrand Ludovic , Augustinova Maria , Parris Benjamin A
Published: February 2024

Cognitive control is the ability to allocate attention away from stimuli that are irrelevant to achieving a goal, towards stimuli that are. When conflict is anticipated, attention is biased in a global, top-down manner called proactive control and this effortful type of cognitive control is engaged before stimulus onset. The list-wise congruency proportion (LWPC) effect, where the Stroop congruency effect is reduced when there are more incongruent than congruent trials compared to vice versa, has been viewed as one of the prime signatures of this type of cognitive control. However, there has been recent debate about the extent to which this effect should be attributed to proactive control instead of alternative explanations such as simpler associative learning or reactive control. Thus, by using pupillometry (i.e., an indicator of cognitive effort), the present study investigated the extent to which LWPC effects result from effortful proactive control. Experiment 1 employed a classic proportion congruency manipulation, while Experiment 2 replaced congruent trials with neutral trials to control for potential effects of associative learning. While in line with past findings, proportion congruency effects were obtained in response times of both experiments and pupillometry showed both proportion congruency and Stroop effects after stimulus onset, no differences in pupil sizes were found during the preparatory phase. Therefore, these results do not support the idea that the observed LWPC effects are due to participants engaging in effortful proactive control.
“What will you do after?”: Lessons from Academia and the World Beyond
Authors: Madan Christopher R
Published: February 2024

Determining post-PhD career options is a challenge for many Psychology PhD graduates. Here I provide a comprehensive overview of the diverse career trajectories available to graduates, drawing from interviews with 53 PhD graduates conducted as part of the two-volume Academia and the World Beyond book series. From these, I conducted a hierarchical qualitative classification to categorise and characterise potential career paths. The findings reveal a spectrum of opportunities, from traditional academic roles to “academic adjacent” and “skill-transfer” careers. This work underscores the versatility of Psychology doctoral training, providing skills that can support a wide array of career possibilities. The results serve as a guide for current and prospective PhD students—and their mentors—emphasising the variety of professional contexts where doctoral training is beneficial.
Cerebral pulsatility in relation with various imaging markers of cerebral small vessel disease: a longitudinal community-based study
Authors: Zhong Weiyi , Xia Yiwei , Ying Yunqing , Wang Yi , Yang Lumeng , Liang Xiaoniu , Zhao Qianhua , Wu Jianjun , Liang Zonghui , Wang Xiaoxiao , Cheng Xin , Ding Ding , Dong Qiang
Published: February 2024

Background:

Cerebral pulsatility is thought to reflect arterial stiffness and downstream microvascular resistance. Although previous studies indicated cerebral pulsatility might closely relate to development of cerebral small vessel disease (SVD), yet evidence remain controversial and longitudinal data are rare.

Objective:

We aimed to explore relationships of cerebral pulsatility with severity and progression of various SVD imaging markers among the community-dwelling elderly.

Design:

A longitudinal cohort study.

Methods:

As part of the prospective community-based Shanghai Aging Study cohort, dementia- and stroke-free elderly were recruited for baseline assessment of cerebral pulsatility and SVD severity during 2010–2011 and traced for SVD progression during 2016–2017. Cerebral pulsatility was quantified for both anterior and posterior circulation with transcranial Doppler ultrasound. SVD imaging markers were measured with brain magnetic resonance imaging (MRI) including white matter hyperintensities (WMHs), enlarged perivascular spaces (ePVS), lacunes, and microbleeds. The cross-sectional and longitudinal relationships between cerebral pulsatility and SVD were analyzed by univariable and multivariable regression models.

Results:

Totally, 188 eligible subjects were included at baseline and out of them, 100 (53.19%) returned for a 7-year follow-up. At baseline, increased pulsatility of posterior circulation was independently associated with more periventricular WMH (PWMH) and ePVS in basal ganglia (BG-ePVS) but not with other SVD markers. Longitudinally, higher posterior pulsatility predicted greater PWMH progression in participants with hypertension (β = 2.694, standard error [SE] = 1.112, p = 0.020), whereas pulsatility of anterior circulation was shown to prevent BG-ePVS progression among followed-up elderly (β = −6.737, SE = 2.685, p = 0.012). However, no significant relationship was found between cerebral pulsatility and burden of lacunes or cerebral microbleeds.

Conclusion:

Higher pulsatility of posterior circulation could worsen PWMH progression, especially for participants with hypertension. But for development of ePVS, increased cerebral pulsatility could play a compensatory role among several healthy elderly. The distinct relationships between cerebral pulsatility and various SVD markers emphasized the importance of individualized SVD management.
Eomesodermin-expressing CD4+ Th cells and association with pregnancy in multiple sclerosis
Authors: Faissner Simon , Bongert Marielena , Trendelenburg Paulina , Thiel Sandra , Yamamura Takashi , Hellwig Kerstin , Gold Ralf
Published: February 2024

Background:

Pregnancy in patients with multiple sclerosis (MS) is accompanied by a decline of relapse activity with increased risk of relapses 3 months post-partum, for unknown reasons. Eomesodermin+ T-helper cells (Eomes+ Th cells) are known to mediate neuroinflammation and disease progression in MS and are induced by prolactin-secreting cells.

Objectives:

Here, investigated immune cell alterations and the pathophysiological role of Eomes+ Th cells for disease activity during pregnancy and post-partum in MS.

Methods:

We enrolled n = 81 pregnant patients with relapsing-remitting MS (RRMS), n = 27 post-partum RRMS and n = 26 female RRMS control patients under the umbrella of the German Multiple Sclerosis and Pregnancy Registry. Clinical data were collected and immune cell alterations were analysed using flow cytometry.

Results:

While CD3+CD4+ Th cells were unaffected, CD3+CD8+ cytotoxic T-cells were elevated post-partum ( p = 0.02) with reduced B-cell frequencies ( p = 0.01) compared to non-pregnant RRMS patients. NK cells were elevated during first trimester ( p = 0.02) compared to the third trimester. Frequencies of Eomes+ Th and Eomes+ Tc cells did not differ. There was no correlation of prolactin release and expression of Eomes+ Th cells. However, Eomes+ Th cells correlated with lower frequencies of regulatory T-cells during second ( r = −0.42; p < 0.05) and third trimester ( r = −0.37; p < 0.05). Moreover, Eomes+ Th cells correlated with frequencies of B-cells during third trimester ( r = 0.54; p = 0.02). Frequencies of Eomes+ Th cells were not associated with the number of relapses before pregnancy, during pregnancy or post-partum. However, Eomes+ Th cells strongly correlated with disability post-partum as assessed using the EDSS ( r = 0.52; p = 0.009).

Discussion:

Pregnancy in MS is associated with robust immunological alterations. Eomes+ Th cells are capable of inducing immune cell alterations during the course of pregnancy, most evident during the second and third trimester as shown with a correlation of reduced Treg cells and a significant increase of B-cells. Importantly, Eomes+ Th cells correlate with disability post-partum. In summary, during late pregnancy in MS an inflammatory, cytotoxic and dysregulated immunological environment is primed gaining function post-delivery. This may be responsible for post-partum disability accumulation.
Investigation of the Effect of 70 Potential Interferents on Measurement Results of Two Blood Glucose Monitoring Systems
Authors: Baumstark Annette , Pleus Stefan , Mende Jochen , Jendrike Nina , Tesar Martina , Schauer Sebastian , Sugiyama Takayuki , Aoki Takashi , Sugiura Mako , Freckmann Guido , Haug Cornelia
Published: February 2024

Background:

Reliable blood glucose (BG) measurements are important for people with diabetes to manage their therapy as well as in point-of-care testing (POCT) performed by health care professionals to monitor BG of patients or even to diagnose diabetes. Among other factors, endogenous and exogenous substances present in blood samples can impact the measurement results. To ensure and prove that blood glucose monitoring systems (BGMSs) are robust in terms of potential interferents, manufacturers have to perform extensive evaluations.

Method:

An interference screening test was performed for three reagent system lots of a POCT system and of a BGMS for self-monitoring of BG. A paired-difference approach based on ISO 15197:2013 and CLSI guideline EP07 was used with venous whole blood samples at two different glucose concentrations. Seventy potential interferents expected to be common in people with diabetes were evaluated.

Results:

The interference effects were determined as normalized biases between test samples and corresponding control samples. For 69 of the 70 investigated potential interferents, both systems met the predefined acceptance criteria, with the normalized biases falling within ±10 mg/dL or ±10% at glucose concentrations ≤100 mg/dL or >100 mg/dL, respectively, for each of the three evaluated reagent system lots.

Conclusions:

The BGMS investigated in this study were found to be robust with respect to the 70 evaluated potential interferents. Interference effects were observed only for N-Acetyl-L-cysteine. Extensive evaluations of potential interfering factors can make an important contribution to ensure reliability of BGMS.
Digital Diaspora Activism at the Margins: Unfolding Rohingya Diaspora Interactions on Facebook (2017–2022)
Authors: Ansar Anas , Maitra Julian
Published: February 2024

This study maps the Rohingya diaspora’s digital engagement on Facebook and explores how their participation has transformed over the years. Using the CrowdTangle analytics platform, this mixed-methods study presents the Rohingya community’s collective engagement on Facebook across six years, from January 2017 to December 2022. It comprises 47 Rohingya diaspora FB pages that published 34,905 posts and received nearly 8 million user interactions. Revealing their yearly transformation in interactions on Facebook, this study uncovers their contextual embodiment—within the increasingly complex and ever-changing regional and global socio-political landscape. Three key insights emerged from our findings. First, memories of loss, suffering, and longing for home intertwine in Rohingya transnational digital connectivity. In this remembrance process, Arakan (Rakhine) remains the place of reference and the center of gravity in their multi-layered identity formation and political mobilization. Second, as a gateway to seek global attention and articulate their political grievances, Rohingyas compose a coherent, unified, and human rights-based discourse on Facebook. Through such framing, they create an oppositional consciousness, drawing positive attention to their plight and the injustice they have endured for decades. Third, Islam, Muslim solidarity, and the narrative of Muslim victimhood emerge as indisputable markers in their identity (re)construction and manifesting political resistance. Anchoring on Islam, they build bridges between the scattered diaspora members and transcend their local struggle to the global audience, cementing the nexus between their Muslim identity and discrimination by the Buddhist-majority Myanmar government.
Association of Burnout With Primary Care Clinician Perception of Team-Based Scheduling Support
Authors: Funk Kylee A. , Stillman Martin , Wang Qi , Manser Sarah Turcotte , Rogers Elizabeth A.
Published: February 2024

Introduction:

Primary care clinician burnout is pervasive and detrimental. How components of teamwork and clinic culture might contribute to burnout remains unsettled.

Objective:

To examine associations between primary care clinician perceptions of specific components of teamwork and of organizational culture, and perceived stress and burnout.

Methods:

Cross-sectional survey study of primary care clinicians from 5 county health system clinics. Measures: Perceptions of teamwork related to coordination of care, and clinic provision of chronic disease self-management support; values alignment and workplace equity; and demographics.

Data Analysis:

Descriptive statistics and Spearman’s correlations to examine associations, controlling for clinic and examining response variability by clinic.

Results:

Of 72 clinicians, 64% were female and 32% non-white. About 56% had worked at least 4 years and half worked 5 to 6 half days/week or more in their clinic. Clinicians who reported having someone on the clinician’s care team routinely schedule follow-up appointments for patients with complex chronic illnesses reported lower stress and burnout. Those who perceived greater values alignment with their clinic and greater personal and employee equitable treatment had lower stress and burnout.

Conclusions:

Teamwork among clinicians and non-clinical staff, a component of teamwork that is not well-considered in current literature, could be an important piece of the puzzle to decrease the persistent and challenging issue of stress and burnout among primary care clinicians.
The Development and Validation of a Scale to Assess Perception of Physical Education Among University Students in China
Authors: Qin Ling , King Yan Ho Walter , Xie Yangyang , Wang Jiudan , Cheng Liangliang , Liu Zhaoxia , Pan Lei , Khoo Selina
Published: February 2024

This study aimed to develop and test a University Students’ Perceptions of Physical Education (PE) Scale. The study was conducted in three phases in a southwestern city in China from December 2021 to October 2022. In Phase 1, an item pool was constructed based on a literature review and semi-structured interviews. In Phase 2, expert evaluations and university student interviews were conducted to evaluate the content validity of the questionnaire. In Phase 3, a cross-sectional study was administered to university students. Composite reliability (CR) and average variance extracted (AVE) for internal consistency and test-retest reliability analyses were calculated for the stability reliability analysis. The validity evaluations included content, construct, and discriminant validity and an invariance test. The developed scale comprises 20 items covering six domains: habituated behavior in physical activity, self-efficacy in PE, attitude and experience in PE, skills and knowledge, classroom climate, and facilities, equipment and norms. Each domain’s CR and AVE values exceeded 0.7 and 0.5, respectively. The statistical indices of the final model were chi-square (χ2) = 458.227, degrees of freedom ( df) = 155, Comparative Fit Index = 0.957, Tucker–Lewis Index = 0.947, standardized root mean square residual = 0.061, and root mean square error of approximation = 0.066, supporting the reliability and viability of the scale. A scientific process was adopted in constructing the University Students’ Perceptions of PE Scale. High validity and reliability scores indicate the suitability of using this scale for further research.
A Green Surprise: Bilateral Bilious Pleural Effusion Secondary to Esophageal Rupture—A Case Report
Authors: Ravikumar Diviya Bharathi , Sivasubramanian Barath Prashanth , Dominic Savio Francis Vino , Gunendran Tharajan , Shekar Saketh Palasamudram
Published: February 2024

Bilothorax, an exudative pleural effusion due to the accumulation of bile. It is also called cholethorax or thoracobilia and was initially reported in 1971. Here, we report a rare case of an elderly male presenting with bilateral bilothorax due to esophageal rupture. A 78-year-old man with multiple medical ailments presented to the emergency room (ER) with a severe episode of vomiting accompanied by a popping sound, respiratory distress, and right sided chest pain. The patient had tachycardia, BP of 101/89 mm Hg, and tachypnea. Computed tomography scan of the chest and abdomen revealed air adjacent to the esophagus, suggesting perforation, atelectasis of right lung, and bilateral pleural effusion (R > L). However, an esophagram did not reveal any perforation. Right-sided chest tube drained dark green bilious fluid. The day after admission, he experienced hemodynamic compromise and hypoxemia requiring intubation, along with fluids and inotropes support. Diagnosis of bilateral bilothorax complicated by hypoxemic respiratory failure with septic shock was made. Cultures were drawn, and empiric antibiotics were started. Nuclear hepatobiliary scan (HIDA) was performed to rule out a hepatobiliary fistula. Results showed reflux activity in the stomach, and distal esophageal leak was identified. Gastrojejunal stenting was performed. However, after prolonged intubation, the family decided on terminal extubation, and he died while receiving hospice care. This case highlights the rarity of bilateral bilothorax, where the HIDA scan played a crucial role in identifying an esophageal leak as the underlying cause, despite normal esophagram results. This condition necessitates prompt diagnosis and aggressive therapeutic interventions.
Auditory Spatial Bisection of Blind and Normally Sighted Individuals in Free Field and Virtual Acoustics
Authors: Goicke Stefanie , Denk Florian , Jürgens Tim
Published: February 2024

Sound localization is an important ability in everyday life. This study investigates the influence of vision and presentation mode on auditory spatial bisection performance. Subjects were asked to identify the smaller perceived distance between three consecutive stimuli that were either presented via loudspeakers (free field) or via headphones after convolution with generic head-related impulse responses (binaural reproduction). Thirteen azimuthal sound incidence angles on a circular arc segment of ±24° at a radius of 3 m were included in three regions of space (front, rear, and laterally left). Twenty normally sighted (measured both sighted and blindfolded) and eight blind persons participated. Results showed no significant differences with respect to visual condition, but strong effects of sound direction and presentation mode. Psychometric functions were steepest in frontal space and indicated median spatial bisection thresholds of 11°–14°. Thresholds increased significantly in rear (11°–17°) and laterally left (20°–28°) space in free field. Individual pinna and torso cues, as available only in free field presentation, improved the performance of all participants compared to binaural reproduction. Especially in rear space, auditory spatial bisection thresholds were three to four times higher (i.e., poorer) using binaural reproduction than in free field. The results underline the importance of individual auditory spatial cues for spatial bisection, irrespective of access to vision, which indicates that vision may not be strictly necessary to calibrate allocentric spatial hearing.
Resistance Training on an Outdoor Exercise Structure Improves Lower-Body Relative Strength in Older Adults
Authors: Leadbetter Brianna , Sénéchal Martin , Seaman Ken , Bouchard Danielle R.
Published: February 2024

Improving relative strength is important for maintaining functionality with age, and outdoor exercise structures could be useful to facilitate this. A total of 29 adults aged 65+ participated in a non-randomized crossover study with a 6-week control followed by a 6-week resistance training intervention on an outdoor exercise structure (3x/week). Relative strength (predicted maximal leg press/lower body lean mass [Dual-energy X-ray Absorptiometry]) and physical function variables were measured at baseline, post-control, and post-intervention. Represented as median (25th–75th), lower body relative strength improved from 7.91 (7.01–9.35) post-control to 8.50 (7.99–9.72) post-intervention ( p = .002) in study completers ( n = 17). Maximum leg press ( p = .002), 30-second chair stand ( p  < .001), one-leg stance ( p = .011), and maximum chest press ( p = .009) also improved significantly during the intervention. There were no significant changes in aerobic activity, grip strength, lean mass, or muscle power. This study demonstrates that there could be potential relative strength benefits associated with the use of outdoor exercise structures in older adults.
What is the role of activism in air pollution politics? Understanding policy change in Poland
Authors: Maltby Tomas , Birch Sarah , Fagan Adam , Subašić Mate
Published: February 2024

There has been growing awareness across the world of the negative health effects of air pollution. Poland is the European country that is worst affected by this problem, and the Polish government has in recent years adopted a number of measures designed to reduce coal use. This paper explores the role of civil society activism in this shift, investigating the extent to which local activists played a catalytic role in shaping popular awareness of air pollution and accounting for policy developments in this area. We draw on individual-level data from two Eurobarometer surveys together with qualitative data from a series of original elite interviews and the analysis of related policy documents, and we find little evidence that activism was a driver of variations in local popular awareness of air pollution, but support for the supposition that activism played a major role in shaping policy change at local level.
RNASeq Analysis for Accurate Identification of Fusion Partners in Tumor Specific Translocations Detected by Standard FISH Probes in Hematologic Malignancies
Authors: Koduru Prasad , Chen Weina , Fuda Franklin , Kaur Gurbakhash , Awan Farrukh , John Samuel , Garcia Rolando , Gagan Jeffrey
Published: February 2024

Background:

Fluorescence labeled DNA probes and in situ hybridization methods had shorter turn round time for results revolutionized their clinical application. Signals obtained from these probes are highly specific, yet they can produce fusion signals not necessarily representing fusion of actual genes due to other genes included in the probe design. In this study we evaluated discordance between cytogenetic, FISH and RNAseq results in 3 different patients with hematologic malignancies and illustrated the need to perform next generation sequencing (NGS) or RNASeq to accurately interpret FISH results.

Methods:

Bone marrow or peripheral blood karyotypes and FISH were performed to detect recurring translocations associated with hematologic malignancies in clinical samples routinely referred to our clinical cytogenetics laboratory. When required, NGS was performed on DNA and RNA libraries to detect somatic alterations and gene fusions in some of these specimens. Discordance in results between these methods is further evaluated.

Results:

For a patient with plasma cell leukemia standard FGFR3 / IGH dual fusion FISH assay detected fusion that was interpreted as FGFR3-positive leukemia, whereas NGS/RNASeq detected NSD2::IGH. For a pediatric acute lymphoblastic leukemia patient, a genetic diagnosis of PDGFRB-positive ALL was rendered because the PDGFRB break-apart probe detected clonal rearrangement, whereas NGS detected MEF2D::CSF1R. A MYC-positive B-prolymphocytic leukemia was rendered for another patient with a cytogenetically identified t(8;14) and MYC::IGH by FISH, whereas NGS detected a novel PVT1::RCOR1 not previously reported.

Conclusions:

These are 3 cases in a series of several other concordant results, nevertheless, elucidate limitations when interpreting FISH results in clinical applications, particularly when other genes are included in probe design. In addition, when the observed FISH signals are atypical, this study illustrates the necessity to perform complementary laboratory assays, such as NGS and/or RNASeq, to accurately identify fusion genes in tumorigenic translocations.
An Effective Earned Value Management System (EVMS) is a Team Sport
Authors: Aramali Vartenie , Gibson G. Edward , Asmar Mounir El , Sanboskani Hala
Published: February 2024

We present a novel framework to assess 27 earned value management system (EVMS) environment factors and investigate their impact on project performance. A study of the EVMS literature, a survey of practitioners, and focus group meetings with 36 EVMS industry and government experts, supported the development of the framework. Focus groups involving 80 practitioners refined and tested it. We analyzed performance data from 35 completed projects/programs representing over US$21.8 billion in total cost; a project demonstrating a positive environment could save up to 25% in cost versus baseline. Practitioners can develop an effective EVMS environment by following the provided guidance.
How I treat the co-occurrence of venous and arterial thromboembolism: anticoagulation, antiplatelet therapy, or both?
Authors: May Jori E. , Moll Stephan
Published: February 2024

Arterial and venous thromboses are classically considered distinct disease states, with arterial thrombosis mediated predominantly by platelets and therefore, treated with antiplatelet therapy, and venous thrombosis mediated by the plasmatic coagulation system and treated with anticoagulation. However, co-occurrence of arterial and venous events is common, and there is increasing evidence of shared risk factors and pathophysiologic overlap. This presents a management challenge: does the patient with venous and arterial thrombosis, require anticoagulation, antiplatelet therapy, or both? Herein, we present a structured approach to the evaluation and management of patients with venous thrombosis who are also at risk for or have a history of an arterial thromboembolic event. We emphasize the importance of defining the indications for antithrombotic therapy, as well as the evaluation of factors that influence both thrombotic and bleeding risk, including disorder-specific and patient-specific factors, as well as the inherent risk balance of antithrombotic therapy regimens. We illustrate this approach in 4 cases, discussing the unique considerations and recent updates in the management of venous thrombosis, acute noncardioembolic ischemic stroke, coronary artery disease and acute myocardial infarction, and peripheral artery disease after revascularization.
The influence of voxelotor on cerebral blood flow and oxygen extraction in pediatric sickle cell disease
Authors: Brothers Rowan O. , Turrentine Katherine B. , Akbar Mariam , Triplett Sydney , Zhao Hongting , Urner Tara M. , Goldman-Yassen Adam , Jones Richard A. , Knight-Scott Jack , Milla Sarah S. , Bai Shasha , Tang Amy , Brown R. Clark , Buckley Erin M.
Published: February 2024

Voxelotor is an inhibitor of sickle hemoglobin polymerization that is used to treat sickle cell disease. Although voxelotor has been shown to improve anemia, the clinical benefit on the brain remains to be determined. This study quantified the cerebral hemodynamic effects of voxelotor in children with sickle cell anemia (SCA) using noninvasive diffuse optical spectroscopies. Specifically, frequency-domain near-infrared spectroscopy combined with diffuse correlation spectroscopy were used to noninvasively assess regional oxygen extraction fraction (OEF), cerebral blood volume, and an index of cerebral blood flow (CBFi). Estimates of CBFi were first validated against arterial spin–labeled magnetic resonance imaging (ASL-MRI) in 8 children with SCA aged 8 to 18 years. CBFi was significantly positively correlated with ASL-MRI–measured blood flow (R2 = 0.651; P = .015). Next, a single-center, open-label pilot study was completed in 8 children with SCA aged 4 to 17 years on voxelotor, monitored before treatment initiation and at 4, 8, and 12 weeks (NCT05018728). By 4 weeks, both OEF and CBFi significantly decreased, and these decreases persisted to 12 weeks (both P < .05). Decreases in CBFi were significantly correlated with increases in blood hemoglobin (Hb) concentration (P = .025), whereas the correlation between decreases in OEF and increases in Hb trended toward significance (P = .12). Given that previous work has shown that oxygen extraction and blood flow are elevated in pediatric SCA compared with controls, these results suggest that voxelotor may reduce cerebral hemodynamic impairments. This trial was registered at www.ClinicalTrials.gov as #NCT05018728.
How I treat ETP-ALL in children
Authors: Summers Ryan J. , Teachey David T. , Hunger Stephen P.
Published: February 2024

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a unique subtype of immature T-cell ALL that was initially associated with a dramatically inferior prognosis compared with non-ETP T-cell ALL (Not-ETP) when it was first described in 2009. Analyses of larger patient cohorts treated with more contemporary regimens, however, have shown minimal survival differences between ETP and Not-ETP. In this manuscript, we use representative cases to explore therapeutic advances and address common clinical questions regarding the management of children, adolescents, and young adults with ETP-ALL. We describe our recommended treatment approach for a child or adolescent with newly diagnosed ETP-ALL, with an emphasis on the prognostic significance of induction failure and detectable minimal residual disease and the role of hematopoietic stem cell transplant in first remission. We discuss the interplay between the ETP immunophenotype and genomic markers of immaturity in T-cell ALL. Finally, we review novel therapeutic approaches that should be considered when managing relapsed or refractory ETP-ALL.
Distinct regulatory networks control toxin gene expression in elapid and viperid snakes
Authors: Modahl Cassandra M. , Han Summer Xia , van Thiel Jory , Vaz Candida , Dunstan Nathan L. , Frietze Seth , Jackson Timothy N. W. , Mackessy Stephen P. , Kini R. Manjunatha
Published: February 2024

Background

Venom systems are ideal models to study genetic regulatory mechanisms that underpin evolutionary novelty. Snake venom glands are thought to share a common origin, but there are major distinctions between venom toxins from the medically significant snake families Elapidae and Viperidae, and toxin gene regulatory investigations in elapid snakes have been limited. Here, we used high-throughput RNA-sequencing to profile gene expression and microRNAs between active (milked) and resting (unmilked) venom glands in an elapid (Eastern Brown Snake, Pseudonaja textilis), in addition to comparative genomics, to identify cis- and trans-acting regulation of venom production in an elapid in comparison to viperids (Crotalus viridis and C. tigris).

Results

Although there is conservation in high-level mechanistic pathways regulating venom production (unfolded protein response, Notch signaling and cholesterol homeostasis), there are differences in the regulation of histone methylation enzymes, transcription factors, and microRNAs in venom glands from these two snake families. Histone methyltransferases and transcription factor (TF) specificity protein 1 (Sp1) were highly upregulated in the milked elapid venom gland in comparison to the viperids, whereas nuclear factor I (NFI) TFs were upregulated after viperid venom milking. Sp1 and NFI cis-regulatory elements were common to toxin gene promoter regions, but many unique elements were also present between elapid and viperid toxins. The presence of Sp1 binding sites across multiple elapid toxin gene promoter regions that have been experimentally determined to regulate expression, in addition to upregulation of Sp1 after venom milking, suggests this transcription factor is involved in elapid toxin expression. microRNA profiles were distinctive between milked and unmilked venom glands for both snake families, and microRNAs were predicted to target a diversity of toxin transcripts in the elapid P. textilis venom gland, but only snake venom metalloproteinase transcripts in the viperid C. viridis venom gland. These results suggest differences in toxin gene posttranscriptional regulation between the elapid P. textilis and viperid C. viridis.

Conclusions

Our comparative transcriptomic and genomic analyses between toxin genes and isoforms in elapid and viperid snakes suggests independent toxin regulation between these two snake families, demonstrating multiple different regulatory mechanisms underpin a venomous phenotype.
Unique properties of titanium dioxide quantum dots assisted regulation of growth and biochemical parameters of Hibiscus sabdariffa plants
Authors: Abdelhameed Reda E. , Abdalla Hanan , Ibrahim Manar A.
Published: February 2024

Owing to the uniqueness of quantum dots (QDs) as a potential nanomaterial for agricultural application, hence in the present study, titanium dioxide quantum dots (TiO2 QDs) were successfully synthesized via sol-gel technique and the physico-chemical properties of the prepared TiO2 QDs were analyzed. Based on the results, the TiO2 QDs showed the presence of anatase phase of TiO2. TEM examination revealed spherical QDs morphology with an average size of 7.69 ± 1.22 nm. The large zeta potential value (-20.9 ± 2.3 mV) indicate greater stability of the prepared TiO2 QDs in aqueous solutions. Moreover, in this work, the application of TiO2 QDs on Hibiscus sabdariffa plants was conducted, where H. sabdariffa plants were foliar sprayed twice a week in the early morning with different concentrations of TiO2 QDs (0, 2, 5, 10, 15 and 30 ppm) to evaluate their influence on these plants in terms of morphological indexes and biochemical parameters. The results exhibited an increasing impact of the different used concentrations of TiO2 QDs on morphological indexes, such as fresh weight, dry weight, shoot length, root length, and leaf number, and physio-biochemical parameters like chlorophyll a, chlorophyll b, carotenoid contents, total pigments and total phenolic contents. Remarkably, the most prominent result was recorded at 15 ppm TiO2 QDs where plant height, total protein and enzymatic antioxidants like catalase and peroxidase were noted to increase by 47.6, 20.5, 29.5 and 38.3%, respectively compared to control. Therefore, foliar spraying with TiO2 QDs positively serves as an effective strategy for inducing optimistic effects in H. sabdariffa plants.
Impact of body mass index on long-term outcomes in patients undergoing percutaneous coronary intervention stratified by diabetes mellitus: a retrospective cohort study
Authors: Rao Chongyou , Zhong Qin , Wu Rilige , Li Zongren , Duan Yongjie , Zhou You , Wang Chi , Chen Xu , Wang Ruiqing , He Kunlun
Published: February 2024

Background

Patients with diabetes mellitus (DM) caused by obesity have increased in recent years. The impact of obesity on long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) with or without DM remains unclear.

Methods

We retrospectively analysed data from 1918 patients who underwent PCI. Patients were categorized into four groups based on body mass index (BMI, normal weight: BMI < 25 kg/m2; overweight and obese: BMI ≥ 25 kg/m2) and DM status (presence or absence). The primary endpoint was the occurrence of major adverse cardiac and cerebrovascular events (MACCE; defined as all-cause death, myocardial infarction, stroke, and unplanned repeat revascularization).

Results

During a median follow-up of 7.0 years, no significant differences in MACCE, myocardial infarction, or stroke were observed among the four groups. Overweight and obese individuals exhibited lower all-cause mortality rates compared with normal-weight patients (without DM: hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.37 to 0.78; with DM: HR: 0.57, 95% CI: 0.38 to 0.86). In non-diabetic patients, the overweight and obese group demonstrated a higher risk of unplanned repeat revascularization than the normal-weight group (HR:1.23, 95% CI:1.03 to 1.46). After multivariable adjustment, overweight and obesity were not significantly associated with MACCE, all-cause death, myocardial infarction, stroke, or unplanned repeat revascularization in patients with and without diabetes undergoing PCI.

Conclusion

Overweight and obesity did not demonstrate a significant protective effect on long-term outcomes in patients with and without diabetes undergoing PCI.
How do quantitative studies involving people with dementia report experiences of standardised data collection? A narrative synthesis of NIHR published studies
Authors: Gridley Kate , Baxter Kate , Birks Yvonne
Published: February 2024

Background

People with dementia are routinely included as research participants in trials and other quantitative studies in which they are invited to respond to standardised measures. This paper reviews the reporting of standardised data collection from people with dementia in reports published in the National Institute for Health and Care Research (NIHR) Journals Library. The aim was to understand how the administration of standardised, self-report measures with people with dementia is reported in NIHR monographs and what could be learnt from this about the feasibility and acceptability of data collection approaches for future studies.

Methods

This was a systematic review with narrative synthesis. Broad search terms (Dementia OR Alzheimer*) were used to search the NIHR Journals Library website in December 2021. All studies that used (or intended to use) standardised measures to collect research data directly from people with dementia were eligible for inclusion. Information was extracted (where reported) on the process of data collection, dementia severity, levels of missing data and the experiences and reflections of those involved.

Results

Searches returned 42 records, from which 17 reports were assessed as eligible for inclusion, containing 22 studies. Response rates from participants with dementia in these studies varied considerably and appeared to be related to dementia severity and place of residence. Little information was reported on the process of data collection or the reasons for missing data, and most studies did not report the experiences of participants or those administering the measures. However, there was an indication from two studies that standardised data collection could provoke emotional distress in some participants with dementia.

Conclusions

Through this review we identified both variation in levels of missing data and gaps in reporting which make it difficult to ascertain the reasons for this variation. We also identified potential risks to the well-being of participants with dementia which may be associated with the content of standardised measures and the context of data collection. Open reporting of and reflection upon data collection processes and the experiences of people involved is essential to ensure both the success of future data collection and the wellbeing of study participants.

Trial registration

Registered with Research on Research https://ror-hub.org/study/2905/.
Comparing Bayesian hierarchical meta-regression methods and evaluating the influence of priors for evaluations of surrogate endpoints on heterogeneous collections of clinical trials
Authors: Collier Willem , Haaland Benjamin , Inker Lesley A. , Heerspink Hiddo J.L. , Greene Tom
Published: February 2024

Background

Surrogate endpoints, such as those of interest in chronic kidney disease (CKD), are often evaluated using Bayesian meta-regression. Trials used for the analysis can evaluate a variety of interventions for different sub-classifications of disease, which can introduce two additional goals in the analysis. The first is to infer the quality of the surrogate within specific trial subgroups defined by disease or intervention classes. The second is to generate more targeted subgroup-specific predictions of treatment effects on the clinical endpoint.

Methods

Using real data from a collection of CKD trials and a simulation study, we contrasted surrogate endpoint evaluations under different hierarchical Bayesian approaches. Each approach we considered induces different assumptions regarding the relatedness (exchangeability) of trials within and between subgroups. These include partial-pooling approaches, which allow subgroup-specific meta-regressions and, yet, facilitate data adaptive information sharing across subgroups to potentially improve inferential precision. Because partial-pooling models come with additional parameters relative to a standard approach assuming one meta-regression for the entire set of studies, we performed analyses to understand the impact of the parameterization and priors with the overall goals of comparing precision in estimates of subgroup-specific meta-regression parameters and predictive performance.

Results

In the analyses considered, partial-pooling approaches to surrogate endpoint evaluation improved accuracy of estimation of subgroup-specific meta-regression parameters relative to fitting separate models within subgroups. A random rather than fixed effects approach led to reduced bias in estimation of meta-regression parameters and in prediction in subgroups where the surrogate was strong. Finally, we found that subgroup-specific meta-regression posteriors were robust to use of constrained priors under the partial-pooling approach, and that use of constrained priors could facilitate more precise prediction for clinical effects in trials of a subgroup not available for the initial surrogacy evaluation.

Conclusion

Partial-pooling modeling strategies should be considered for surrogate endpoint evaluation on collections of heterogeneous studies. Fitting these models comes with additional complexity related to choosing priors. Constrained priors should be considered when using partial-pooling models when the goal is to predict the treatment effect on the clinical endpoint.