bluuebunny/crossref_metadata_2025 huggingface dataset:
Representation of Patients With Chronic Kidney Disease in Clinical Trials of Cardiovascular Disease Medications
Authors: Colombijn Julia M. T. , Idema Demy L. , van Beem Sanne , Blokland Anna Marthe , van der Braak Kim , Handoko M. Louis , in ’t Veld Linde F. Huis , Kaul Tabea , Kolagasigil-Akdemir Nurda , Kusters Mike P. T. , Meijvis Sabine C. A. , Oosting Ilse J. , Spijker Rene , Bots Michiel L. , Hooft Lotty , Verhaar Marianne C. , Vernooij Robin W. M.
Published: March 2024

Importance

Patients with chronic kidney disease (CKD) are at high risk for cardiovascular disease, but their systematic underrepresentation in cardiovascular randomized clinical trials (RCTs) limits the generation of appropriate evidence to guide cardiovascular risk management (CVRM).

Objective

To evaluate the underrepresentation of patients with CKD in cardiovascular RCTs, and to highlight evidence gaps in CVRM medications in this population.

Evidence Review

A systematic search was conducted in ClinicalTrials.gov from February 2000 through October 2021 for RCTs with full-text publications. If no full-text publications were found in ClinicalTrials.gov, MEDLINE, Embase, and Google Scholar were also searched. Eligible RCTs were those evaluating the effectiveness of antiplatelets, anticoagulants, blood pressure–lowering drugs, glucose-lowering drugs, or cholesterol-lowering drugs in adults with cardiovascular disease or cardiovascular risk factors. Trials with a sample size of fewer than 100 patients were excluded.

Findings

In total, 1194 RCTs involving 2 207 677 participants (mean [SD] age, 63 [6] years; 1 343 970 males [64%]) were included. Since 2000, the percentage of cardiovascular RCTs excluding patients with CKD has increased from 66% to 79% (74% overall [884 RCTs]). In 864 RCTs (72%), more patients were excluded than anticipated on safety grounds (63% [306] of trials required no dose adjustment, and 79% [561] required dose adjustment). In total, 158 RCTs (13%) reported results for patients with CKD separately (eg, in subgroup analyses). Significant evidence gaps exist in most CVRM interventions for patients with CKD, particularly for those with CKD stages 4 to 5. Twenty-three RCTs (2%) reported results for patients with an estimated glomerular filtration rate less than 30 mL/min/1.73 m2, 15 RCTs (1%) reported for patients receiving dialysis, and 1 RCT (0.1%) reported for recipients of kidney transplant.

Conclusions and Relevance

Results of this systematic review suggest that representation of patients with CKD in cardiovascular RCTs has not improved in the past 2 decades and that these RCTs excluded more patients with CKD than expected on safety grounds. Lack of reporting or underreporting of results for this patient population is associated with evidence gaps in the effectiveness of most CVRM medications in patients with all stages of CKD, particularly CKD stages 4 to 5.
Polarization-Sensitive OCT Imaging of Scleral Abnormalities in Eyes With High Myopia and Dome-Shaped Macula
Authors: Ohno-Matsui Kyoko , Igarashi-Yokoi Tae , Azuma Takeshi , Sugisawa Keigo , Xiong Jianping , Takahashi Tomonari , Uramoto Kengo , Kamoi Koju , Okamoto Michiaki , Banerjee Suchandra , Yamanari Masahiro
Published: March 2024

Importance

The relevance of visualizing scleral fiber orientation may offer insights into the pathogenesis of pathologic myopia, including dome-shaped maculopathy (DSM).

Objective

To investigate the orientation and density of scleral collagen fibers in highly myopic eyes with and without DSM by polarization-sensitive optical coherence tomography (PS-OCT).

Design, Setting, and Participants

This case series included patients with highly myopic eyes (defined as a refractive error ≥6 diopters or an axial length ≥26.5 mm) with and without a DSM examined at a single site in May and June 2019. Analysis was performed from September 2019 to October 2023.

Exposures

The PS-OCT was used to study the birefringence and optic axis of the scleral collagen fibers.

Main Outcomes and Measures

The orientation and optic axis of scleral fibers in inner and outer layers of highly myopic eyes were assessed, and the results were compared between eyes with and without a DSM.

Results

A total of 72 patients (51 [70.8%] female; mean [SD] age, 61.5 [12.8] years) were included, and 89 highly myopic eyes were examined (mean [SD] axial length, 30.4 [1.7] mm); 52 (58.4%) did not have a DSM and 37 (41.6%) had a DSM (10 bidirectional [27.0%] and 27 horizontal [73.0%]). Among the 52 eyes without DSM, the 13 eyes with simple high myopia had primarily inner sclera visible, displaying radially oriented fibers in optic axis images. In contrast, the entire thickness of the sclera was visible in 39 eyes with pathologic myopia. In these eyes, the optic axis images showed vertically oriented fibers within the outer sclera. Eyes presenting with both horizontal and bidirectional DSMs had clusters of fibers with low birefringence at the site of the DSM. In the optic axis images, horizontally or obliquely oriented scleral fibers were aggregated in the inner layer at the DSM. The vertical fibers located posterior to the inner fiber aggregation were not thickened and appeared thin compared with the surrounding areas.

Conclusions and Relevance

This study using PS-OCT revealed inner scleral fiber aggregation without outer scleral thickening at the site of the DSM in highly myopic eyes. Given the common occurrence of scleral pathologies, such as DSM, and staphylomas in eyes with pathologic myopia, recognizing these fiber patterns could be important. These insights may be relevant to developing targeted therapies to address scleral abnormalities early and, thus, mitigate potential damage to the overlying neural tissue.
Patient With Dysphonia
Authors: Ng Christina H. , Rahman Mobeen , Damrose Edward J.
Published: March 2024

A male individual in his 60s presented with a hoarse and weak voice and a history of follicular lymphoma with multiple relapses treated with an allogeneic stem cell transplant complicated by graft-vs-host disease treated with sirolimus and steroids. What is your diagnosis?
Design and Usability of an Open-Source, Low-Cost Flexible Laryngoscope for Resource-Limited Settings
Authors: Srinivasan Yashes , Shamritsky David , Bhatta Asmita , Chou Ellaine , Pham Trang , Sanghvi Yashi , Woolf Lily , Zhang Michael , Odigie Eseosa , Chidziva Clemence , Muganda Erasmus , Zimani Priscilla , de Faria Newton , Rameau Anaïs
Published: March 2024

Importance

Endoscopes are paramount to the practice of otolaryngology. To provide physicians in low-middle–income countries with adequate tools to treat otolaryngologic problems, it is necessary to create a low-cost sustainable option.

Objective

To describe the design and usability of an open-source, low-cost flexible laryngoscope that addresses the lack of affordable and accessible methods for otolaryngologic visualization in resource-limited settings.

Design, Setting, and Participants

This quality improvement study used a mixed-methods approach, including a technical description of device design as well as quantitative and qualitative survey evaluation of device usability. Engineering involved device design, sourcing or manufacturing individual components, fabricating a prototype, and iterative testing. Key assumptions and needs for the device were identified in collaboration with otolaryngologists in Zimbabwe, and designed and simulated by biomedical engineers in a US university laboratory. Board-certified otolaryngologists at a single US university hospital trialed a completed prototype on simulated airways between May 2023 and June 2023.

Main Outcomes and Measures

Technical details on the design of the device are provided. Otolaryngologist gave feedback on device characteristics, maneuverability, and visualization using the System Usability Scale, a customized Likert-scale questionnaire (5-point scale), and semistructured interviews.

Results

A functional prototype meeting requirements was completed consisting of a distal-chip camera, spring bending tip, handle housing the control mechanism and electronics, and flexible polyether block amide–coated silicone sheath housing the camera and control wires; an external monitor provided real-time visualization and ability to store data. A total of 14 otolaryngologists participated in the device review. The mean (SD) System Usability Scale score was 88.93 (10.08), suggesting excellent usability. The device was rated highly for ease of set up, physical attributes, image quality, and functionality.

Conclusions and Relevance

This quality improvement study described the design of a novel open-source low-cost flexible laryngoscope that external review with otolaryngologists suggests was usable and feasible in various resource-limited environments. Future work is needed to translate the model into a clinical setting.
A Rare Case of Sudden Massive Neck Tumor
Authors: Zhang Jianyong , Zhu Xin
Published: March 2024

A 23-year-old male patient sought evaluation at the vascular thyroid surgery clinic for a large neck tumor that appeared abruptly 10 days prior. What is your diagnosis?
Effect of Silver Content and T4 Treatment on the In Vitro Degradation Behavior of Gasar Porous Mg–Ag Alloy
Authors: Sun Daliang , Li Zaijiu , Jin Qinglin , Liu Mingzhao , Yang Xiuping , Sun Yikai
Published: March 2024

Mg–Ag alloy has potential as a material for bone tissue repair, but the faster degradation rate in vivo limits its use in medical applications. In this study, pure Mg and Mg99.5Ag0.5 alloy with a porous structure are prepared using the metal/gas eutectic unidirectional solidification method (Gasar process). The influence of introducing Ag on the degradation behavior of porous Mg99.5Ag0.5 and pure Mg is investigated. The addition of Ag increases the compressive strength and elastic modulus of the material. The corrosion resistance of as‐cast Mg99.5Ag0.5 alloy decreases due to localized aggregation of Ag in the alloys. Therefore, the T4 (solution treatment) is chosen for the Mg99.5Ag0.5 alloy. After T4 treatment, due to the uniform distribution of Ag atoms in the alloy, the corrosion behavior on the alloy surface is more uniform, and a denser Mg(OH)2 passivation layer is formed on the surface, which reduces the degradation rate of Mg99.5Ag0.5. Importantly, insoluble Ca–P compounds in the form of hydroxyapatite (HA) phases gradually grown on passivated layers of porous T4 Mg99.5Ag0.5 contribute to bone growth. This indicates the feasibility of using the T4 Gasar porous Mg99.5Ag0.5 alloy as a potential tissue engineering scaffold.
Flexible Mini‐Inductors with Ultra‐High Inductance Density Directly Cut from Soft Magnetic Amorphous Alloys by Femtosecond Laser
Authors: Chen Yanan , Zhang Yan , Wang Ji , Chen Zhihao , Cao Xiaowen , Han Fei , Zang Bowen , Xiang Mingliang , Huo Juntao , Zhang Wenwu , Wang Jun‐Qiang
Published: March 2024

Inductors are indispensable parts in power modules of electronic devices. With the rapid development of flexible and wearable electronic devices, developing flexible micro‐inductors with large energy storage has become an urgent task. In this research, a sophisticated femtosecond laser ablation technique is employed to craft circular spiral mini‐inductors via selective etching of soft magnetic amorphous alloy ribbons. Remarkably, while these inductors possess dimensions akin to human fingerprints, they demonstrate an impressively elevated inductance value of ≈1.15 µH at 1 MHz. The inductance density is ≈280–390 nH mm−2, which is ≈10 times larger than conventional circular spiral inductors and is attributed to the high permeability of the amorphous alloys. Furthermore, the inductors showcase commendable flexibility, marked by stellar elasticity and a bending endurance exceeding 2500 cycles, thanks to the amorphous alloys' superior elastic strain limit. When integrated with an LM2576‐3.3BT buck converter, the fabricated inductor achieved a peak power conversion efficiency nearing 70%. These findings underscore the potential of such flexible mini‐inductors in the landscape of flexible electronics.
Unveiling Confinement Engineering for Achieving High‐Performance Rechargeable Batteries
Authors: Lv Ruixin , Luo Chong , Liu Bingran , Hu Kaikai , Wang Ke , Zheng Longhong , Guo Yafei , Du Jiahao , Li Li , Wu Feng , Chen Renjie
Published: March 2024

The confinement effect, restricting materials within nano/sub‐nano spaces, has emerged as an innovative approach for fundamental research in diverse application fields, including chemical engineering, membrane separation, and catalysis. This confinement principle recently presents fresh perspectives on addressing critical challenges in rechargeable batteries. Within spatial confinement, novel microstructures and physiochemical properties have been raised to promote the battery performance. Nevertheless, few clear definitions and specific reviews are available to offer a comprehensive understanding and guide for utilizing the confinement effect in batteries. This review aims to fill this gap by primarily summarizing the categorization of confinement effects across various scales and dimensions within battery systems. Subsequently, the strategic design of confinement environments is proposed to address existing challenges in rechargeable batteries. These solutions involve the manipulation of the physicochemical properties of electrolytes, the regulation of electrochemical activity, and stability of electrodes, and insights into ion transfer mechanisms. Furthermore, specific perspectives are provided to deepen the foundational understanding of the confinement effect for achieving high‐performance rechargeable batteries. Overall, this review emphasizes the transformative potential of confinement effects in tailoring the microstructure and physiochemical properties of electrode materials, highlighting their crucial role in designing novel energy storage devices.
Synthesis of Benzo[e][1,3]thiazin‐4‐ones via PPh3‐Promoted Cyclization of Benzo[c][1,2]dithiol‐3‐ones and Amidines
Authors: Liu Xiaobing , Lv Wenxin , Dong Junjie , Liu Zekai , Hu Feng , Zhou Chuncheng , Zhou Yao
Published: March 2024

A phosphine‐mediated cyclization of benzo[c][1,2]dithiol‐3‐ones and amidines is demonstrated herein. Triphenylphosphine was harnessed as the activating reagent to facilitate the ring‐opening of benzo[c][1,2]dithiol‐3‐ones via S−S bond cleavage. This PPh3‐Promoted cyclization reaction of benzo[c][1,2]dithiol‐3‐ones enabled to forge a diverse array of 1,3‐benzothiazones in decent yields with wide substrate scope under mild conditions.
Postprandial nutrient dynamics and their implications for formulated feed development for the ornate spiny lobster (Panulirus ornatus)
Authors: Hammel Nathan , Cobcroft Jennifer M. , Nankervis Leo
Published: March 2024

Crustacean feeding morphology and postprandial nutrient processing is a highly size‐selective procedure. The digestive system of lobsters is predicated on grinding feed to a fine particle size before digestion. Therefore, fine pregrinding of raw materials may bypass the need for extensive grinding in the proventriculus and expedite digestive and absorptive processes. Panulirus ornatus juveniles (N = 56) were allocated to four feed groups (n = 14). Groups A, B and C were fed nutritionally identical feeds featuring raw materials ground to 1000 µm (Feed A), 500 µm (Feed B) and 200 µm (Feed C) while the fourth group (Group S) acted as a 24‐h nonfeeding baseline control group. Sequential postprandial haemolymph extractions were performed at 0.5, 1, 1.5, 2, 3.5, 5.5 and 24 h across treatment groups. Haemolymph samples were assessed and analysed for brix (%), total proteins (g L–1), glucose (mmol L–1) and cholesterol (mmol L–1). Brix was found to have significant positive correlations with all the haemolymph biochemical properties while no significant correlations were identified between individual lobster size and haemolymph properties. Analysis of deviance applied to mixed effects models did not identify significant differences in haemolymph properties across feed groups. Trends identified here are indicative of diurnal rhythm patterns, likely orchestrated by the release of the crustacean hyperglycaemic hormone (CHH) when anticipating a meal. Additionally, the use of brix values, may not be optimal for identifying postprandial trends, yet could remain a valid indicator of longer‐term nutritional status.
Aggregation and aging of nanoparticle–protein complexes at interfaces studied by evanescent‐light scattering microscopy
Authors: Liu Wei , Zhu Yuwei , Jiang Hang , Zhou Lidan , Li Yinan , Wu Jiahao , Han Jie , Yang Cheng , Jiang Jianzhong , Ngai To
Published: March 2024

Plasma protein‐induced aggregation of nanoparticles (NPs) is a crucial issue in many applications, such as drug delivery. Although great efforts have been made to investigate the protein adsorption kinetics or protein‐induced NPs coalescence in bulk solutions, limited evidence has been uncovered for interfacial circumstances. Diet, disease, medicine, or senility could thoroughly change interfacial physicochemical properties of the inner lining of blood vessels. Implants including stents and artificial heart valves also have varied and evolutionary interfaces. Hence, there is an urgent need to understand the mechanism behind the non‐specific protein adsorption and NP‐protein aggregation in such interfacial cases. Here, we use evanescent light scattering to observe polystyrene NPs‒fibrinogen aggregation at substrates with varying surface properties. A density‐fluctuation correlation function is utilized to reveal the relaxation dynamics of the aggregates. Both time‐resolved and spatial‐correlated evidence shows that the aging process of such soft materials is out‐of‐equilibrium, where the dynamics faster and slower than exponential can coexist in one single relaxation process. Besides, corona formation, inner stress, and interconnection together determine the microstructure, local adhesion, and structural relaxation of the aggregates, which can further correspond to the protein‐to‐NP ratio as well as the surface chemistry of NPs and substrates.
Precise molecular sieving using metal‐doped ultramicroporous carbon membranes for H2 separation
Authors: Zhao Guanran , Wang Kaixin , Fang Chuning , Wang Yixing , Wang Darui , Song Zhen , Lei Linfeng , Xu Zhi
Published: March 2024

Blue hydrogen produced from fossil fuels is recognized as a promising large‐scale technology for realizing the hydrogen economy. Membrane‐based separation is emerging as a viable alternative to traditional hydrogen purification technologies. Here, we present a facile strategy for fabricating carbon molecular sieve (CMS) hollow fiber membranes containing uniformly dispersed palladium (Pd) nanoparticles. The Pd nanoparticles, anchored in the carbon strands of CMS membranes, induced the carbon matrix toward a more ordered structure arrangement through a synergistic effect of entropy‐driven size exclusion and acceleration of graphitization. As a result, the doped Pd nanoparticles facilitated the formation of ultramicropores <3.3 Å in the CMS membranes, which enabled a precise molecular sieving ability between H2 and CO2 with H2/CO2 selectivity up to 247. Furthermore, the membrane presented good mixed gas separation performances and was stable for over 250 h under simulated harsh industrial conditions.
Confinement and phase engineering boosting 1T phase MoS2/carbon hybrid for high‐performance capacitive deionization
Authors: Zhang Yaning , Fan Shiyuan , Gong Siqi , Liu Huibin , Xu Huiting , Qi Junjie , Wang Honghai , Li Chunli , Peng Wenchao , Liu Jiapeng
Published: March 2024

Capacitive deionization (CDI) has attracted significant attention as a water treatment technology owing to its low cost, high efficiency, and eco‐friendliness. However, the unsatisfactory desalination performance of traditional electrode materials hinders the development of CDI. Herein, 1T‐MoS2/C hybrid microspheres are successfully fabricated through confinement and phase engineering strategies. The confinement effect of porous hollow carbon microspheres reduces the overgrowth and agglomeration of MoS2 nanosheets, which is beneficial for exposing more active sites and enhancing stability. Meanwhile, the 1T phase MoS2 displays high intrinsic conductivity and large interlayer spacing, which is conducive to rapid insertion/extraction of Na+. Consequently, 1T‐MoS2/C hybrid becomes a prospect electrode material for CDI, which showcases outstanding desalination capacity (48.1 mg/g at 1.2 V), eminent desalination rate as well as exceptional stability. Moreover, the desalination mechanisms are clarified through various characterizations and density functional theory calculations. This study provides new perspectives on designing high‐performance MoS2‐based CDI electrode materials.
High‐performance BCN‐C heterostructured electrocatalyst derived from covalent triazine frameworks for nitrogen reduction
Authors: Lin Wenwen , Lin Gaobo , Luo Qinlan , Song Weiyu , Chen Hao , Zhang Zihao , Li Jing , Fu Jie
Published: March 2024

Designing and synthesizing heterostructure‐based catalysis combining two‐dimensional (2D) materials has attracted enormous attention in materials chemistry, especially for electrocatalysis, due to their tunable electronic properties and structure. In this work, a boron carbon nitride (BCN)‐coupled carbon (BCN‐C) heterostructure with improved electronic performance was synthesized starting from C‐ and N‐enriched 2D covalent triazine frameworks (CTFs) via a simple thermal transformation process using NaBH4 as the B source. The characterizations results showed that the B released from NaBH4 reacted with N and C in CTF, forming the BCN‐C heterostructure coupling the BCN and carbon with a strong interfacial effect. The electrocatalytic NRR experiments and density functional theory (DFT) calculation revealed that the interfacial electronic properties and large numbers of active sites of the BCN‐C heterostructure benefited the NRR. The BCN‐C‐1 catalyst showed a high Faradaic efficiency of 27.8% and an NH3 yield of 4.3 μg h−1 mgcat.−1 in 0.1 M HCl electrolyte, owing to its high specific surface area (288 m2/g) with a large number of exposed active sites and the Mott–Schottky effect from the BCN‐C heterostructure. This work highlights the design and synthesis of metal‐free catalysts with high activity and selectivity and makes them excellent candidates for electrocatalytic applications.
Chronic myelomonocytic leukemia: 2024 update on diagnosis, risk stratification and management
Authors: Patnaik Mrinal M. , Tefferi Ayalew
Published: March 2024

Disease Overview

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, characterized by prominent monocytosis and an inherent risk for leukemic transformation (~15%–20% over 3–5 years).

Diagnosis

Newly revised diagnostic criteria include sustained (>3 months) peripheral blood (PB) monocytosis (≥0.5 × 109/L; monocytes ≥10% of leukocyte count), consistent bone marrow (BM) morphology, <20% BM or PB blasts (including promonocytes), and cytogenetic or molecular evidence of clonality. Cytogenetic abnormalities occur in ~30% of patients, while >95% harbor somatic mutations: TET2 (~60%), SRSF2 (~50%), ASXL1 (~40%), RAS pathway (~30%), and others. The presence of ASXL1 and DNMT3A mutations and absence of TET2 mutations negatively impact overall survival (ASXL1WT/TET2MT genotype being favorable).

Risk Stratification

Several risk models serve similar purposes in identifying high‐risk patients that are considered for allogeneic stem cell transplant (ASCT) earlier than later. Risk factors in the Mayo Molecular Model (MMM) include presence of truncating ASXL1 mutations, absolute monocyte count >10 × 109/L, hemoglobin <10 g/dL, platelet count <100 × 109/L, and the presence of circulating immature myeloid cells; the resulting 4‐tiered risk categorization includes high (≥3 risk factors), intermediate‐2 (2 risk factors), intermediate‐1 (1 risk factor), and low (no risk factors); the corresponding median survivals were 16, 31, 59, and 97 months. CMML is also classified as being “myeloproliferative (MP‐CMML)” or “myelodysplastic (MD‐CMML),” based on the presence or absence of leukocyte count of ≥13 × 109/L.

Treatment

ASCT is the only treatment modality that secures cure or long‐term survival and is appropriate for MMM high/intermediate‐2 risk disease. Drug therapy is currently not disease‐modifying and includes hydroxyurea and hypomethylating agents; a recent phase‐3 study (DACOTA) comparing hydroxyurea and decitabine, in high‐risk MP‐CMML, showed similar overall survival at 23.1 versus 18.4 months, respectively, despite response rates being higher for decitabine (56% vs. 31%).

Unique Disease Associations

These include systemic inflammatory autoimmune diseases, leukemia cutis and lysozyme‐induced nephropathy; the latter requires close monitoring of renal function during leukocytosis and is a potential indication for cytoreductive therapy.
2024 update on allogeneic hematopoietic stem cell transplant for myelofibrosis: A review of current data and applications on risk stratification and management
Authors: Ali Haris , Bacigalupo Andrea
Published: March 2024

Background

Allogeneic hemopoietic stem cell transplantation (HSCT) currently remains the only curative treatment for patients with myelofibrosis (MF). Transplant related mortality (TRM) and relapse, remain two significant complications which need to be addressed.

Aims

The aim of this manuscript is to review current available reports on changes which have recently occurred, to improve the outcome of MF patients undergoing an allogeneic HSCT.

Methods

Published papers were used to analyze different aspects of allogeneic HSCT.

Results

Changes and updates are provided on selection of patients, prognostic systems, managing splenomegaly, conditioning regimens, predicting transplant outcome, stem cell sources, stem cell donors, graft versus host disease (GvHD) prophylaxis, patients with blast phase, hematopoietic reconstitution, disease markers, donor chimerism, and treatment of relapse.

Conclusions

The review outlines new transplant platforms which are now available for patients with myelofibrosis, together with persisting problems, among which, older age combined with marrow fibrosis and an inflammatory disease. Relapse also requires aggressive monitoring of drivers mutations, and early cellular therapy.
Mortality in adults with sickle cell disease: Results from the sickle cell disease implementation consortium (SCDIC) registry
Authors: Njoku Franklin , Pugh Norma , Brambilla Donald , Kroner Barbara , Shah Nirmish , Treadwell Marsha , Gibson Robert , Hsu Lewis L. , Gordeuk Victor R. , Glassberg Jeffrey , Hankins Jane S. , Kutlar Abdullah , King Allison A. , Kanter Julie
Published: March 2024

The cause of death in people affected by sickle cell disease (SCD) is often challenging to define as prior studies have used retrospective or administrative data for analysis. We used a prospective longitudinal registry to assess mortality and clinical co‐morbidities among subjects enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. At enrollment, we collected the following data: patient‐reported demographics, SCD phenotype, baseline laboratory values, comorbidities, and current medications. Subjects were followed for a median of 4.7 years before the present analysis. The relationship of clinical co‐morbidities (at time of enrollment) to mortality was determined using survival analysis, adjusting for SCD phenotype and gender. There was a total of 2439 people with SCD enrolled in the SCDIC registry. One hundred and twenty‐eight participants (5%) died during the observation period (2017–2022). Six people died from trauma and were excluded from further analysis. Proximate cause of death was unwitnessed in 17% of the deaths, but commonest causes of death include cardiac (18%), acute chest or respiratory failure (11%), sudden unexplained death (8%). Enrollment characteristics of the individuals who died (n = 122) were compared to those of survivors (n = 2317). Several co‐morbidities at enrollment increased the odds of death on univariate analysis. All co‐morbidities were included in a multivariable model. After backward elimination, iron overload, pulmonary hypertension, and depression, remained statistically significant predictors of the risk of death. SCD reduces life expectancy. Improved comprehensive and supportive care to prevent end‐organ damage and address comorbidities is needed for this population.
Taking the risk. A systematic review of ethical reasons and moral arguments in the clinical use of polygenic risk scores
Authors: Andreoli Lara , Peeters Hilde , Van Steen Kristel , Dierickx Kris
Published: March 2024

Debates about the prospective clinical use of polygenic risk scores (PRS) have grown considerably in the last years. The potential benefits of PRS to improve patient care at individual and population levels have been extensively underlined. Nonetheless, the use of PRS in clinical contexts presents a number of unresolved ethical challenges and consequent normative gaps that hinder their optimal implementation. Here, we conducted a systematic review of reasons of the normative literature discussing ethical issues and moral arguments related to the use of PRS for the prevention and treatment of common complex diseases. In total, we have included and analyzed 34 records, spanning from 2013 to 2023. The findings have been organized in three major themes: in the first theme, we consider the potential harms of PRS to individuals and their kin. In the theme “Threats to health equity,” we consider ethical concerns of social relevance, with a focus on justice issues. Finally, the theme “Towards best practices” collects a series of research priorities and provisional recommendations to be considered for an optimal clinical translation of PRS. We conclude that the use of PRS in clinical care reinvigorates old debates in matters of health justice; however, open questions, regarding best practices in clinical counseling, suggest that the ethical considerations applicable in monogenic settings will not be sufficient to face PRS emerging challenges.
Enhancing fracture toughness of carbon fiber/epoxy composites using polyphenylene ether as a modifier
Authors: Veeramani Naveen , Devine Machar , Quinn James A. , Alapati Arun Kumar , Bolluk Alp , Ray Dipa
Published: March 2024

In this study, carbon fiber/epoxy composites (CFRP) were fabricated by vacuum‐assisted resin infusion molding (VARIM) with polyphenylene ether (PPE) as a toughening agent. The PPE contained hydroxyl end groups that facilitated chemical bonding with epoxy during curing. PPE was incorporated into the epoxy matrix by dissolution, and spreading in the interlaminar regions. The presence of PPE as a toughener exhibited significant improvement in the Mode‐I fracture toughness of the composites. The CFRP samples, which were toughened with 5 wt.% and 10 wt.% PPE, showed about 191% to 380% enhancement, respectively, in the critical energy release rate (GIC) compared to the unmodified sample. Dynamic mechanical analysis (DMA) showed about a 6°C increase in the glass transition temperature of the toughened composites, which is an interesting aspect of this work. These results indicate the potential of using PPE as a toughening agent in CFRP composites.
The Sima de los Huesos thorax and lumbar spine: Selected traits and state‐of‐the‐art
Authors: Gómez‐Olivencia Asier , Arsuaga Juan Luis
Published: March 2024

Information on the evolution of the thorax and lumbar spine in the genus Homo is hampered by a limited fossil record due to the inherent fragility of vertebrae and ribs. Neandertals show significant metric and morphological differences in these two anatomical regions, when compared to Homo sapiens. Thus, the important fossil record from the Middle Pleistocene site of Sima de los Huesos (SH) not only offers important information on the evolution of these anatomical regions within the Neandertal lineage but also provides important clues to understand the evolution of these regions at the genus level. We present the current knowledge of the costal skeleton, and the thoracic and lumbar spine anatomy of the hominins found in Sima de los Huesos compared to that of Neandertals and modern humans. The current SH fossil record comprises 738 vertebral specimens representing a minimum of 70 cervical, 95 thoracic and 47 lumbar vertebrae, 652 rib fragments representing a minimum of 118 ribs, and 26 sternal fragments representing 4 sterna. The SH hominins exhibit a morphological pattern in their thorax and lumbar spine more similar to that of Neandertals than to that of H. sapiens, which is consistent with the phylogenetic position of these hominins. However, there are some differences between the SH hominins and Neandertals in these anatomical regions, primarily in the orientation of the lumbar transverse processes and in the robusticity of the second ribs. The presence of some but not all of the suite of Neandertal‐derived features is consistent with the pattern found in the cranium and other postcranial regions of this population.
Recent Advances of Chiral Isolated and Small Organic Molecules: Structure and Properties for Circularly Polarized Luminescence
Authors: Zhang Tingwei , Zhang Yue , He Zhiyuan , Yang Tingjun , Hu Xu , Zhu Tengfei , Zhang Yanfeng , Tang Yuhai , Jiao Jiao
Published: March 2024

This paper explores recent advancements in the field of circularly polarized luminescence (CPL) exhibited by small and isolated organic molecules. The development and application of small CPL molecule are systematically reviewed through eight different chiral skeleton sections. Investigating the intricate interplay between molecular structure and CPL properties, the paper aims at providing and enlighting novel strategies for CPL‐based applications.
Caregiver and youth inter‐rater assessment agreement in autism spectrum disorder, developmental coordination disorder, and typical development
Authors: Shipkova Michelle , Butera Christiana D. , Flores Genesis D. , Kilroy Emily , Jayashankar Aditya , Harrison Laura , Cermak Sharon A. , Aziz‐Zadeh Lisa
Published: March 2024

Youth diagnosed with autism spectrum disorder (ASD) and those with developmental coordination disorder (DCD) are at heightened risk for co‐occurring mental health diagnoses, especially anxiety and attention‐deficit/hyperactivity disorder (ADHD). However, caregiver‐child agreement on presence of related symptoms in populations with neurodevelopmental conditions is not well understood. Here, we examine the extent to which 37 ASD, 26 DCD, and 40 typically developing children and their caregivers agree on the degree of the child's symptoms of anxiety and ADHD. All caregiver‐child dyads completed the Screen for Child Anxiety Related Emotional Disorders and Conners 3 ADHD Index. Across groups, intraclass correlations indicated generally poor agreement on anxiety and ADHD symptomatology. Although youth generally reported greater internalizing symptoms (i.e., anxiety), caregivers tended to report more observable externalizing behaviors (i.e., ADHD). Together, the results of this study support the need for a multi‐informant approach in assessments of anxiety and ADHD in youth with neurodevelopmental disorders.
A novel graphene oxide‐based fluorescence method for detection of urine glycosaminoglycans
Authors: Kösoğlu Ceren Bakır , Dede Süreyya , Karakuş Emine , Erdoğmuş Ali , Keskin Bahadır , Önal Hasan
Published: March 2024

Glycosaminoglycans (GAGs) serve as a biomarker for mucopolysaccharidoses disease. In this study, a novel fluorometric method was developed to measure total GAGs in urine. Graphene oxide (GO) and rhodamine B (RhB), a cationic fluorescent dye, were employed in the development of the method. RhB attaches to the GO surface via electrostatic attraction, leading to the quenching of its fluorescence upon the establishment of the RhB–GO complex. However, the presence of GAGs prompts a resurgence of intense fluorescence. The linear range of the method is between 5.00 and 70.00 mg/L. The total GAG levels of urine samples analyzed using the method agree with the results of the biochemistry analysis laboratory (65.85 and 79.18 mg/L; 73.30 ± 1.76 and 72.21 ± 2.21). The method is simple, accurate, and sensitive and may be used for both first‐step diagnosis of the mucopolysaccharidoses and detection of individual GAGs for studies of GAG‐related research and other biological applications.
The HMGB1–RAGE axis in nucleus accumbens facilitates cocaine‐induced conditioned place preference via modulating microglial activation
Authors: Ye Jian , Gao Shuang‐Qi , Liu Zi‐Cun , Chen Xi , He Jin‐Gang , Hu Zhuang‐Li
Published: March 2024

Introduction

Repeated exposure to cocaine induces microglial activation. Cocaine exposure also induces a release of high mobility group box‐1 (HMGB1) from neurons into the extracellular space in the nucleus accumbens (NAc). HMGB1 is an important late inflammatory mediator of microglial activation. However, whether the secretion of HMGB1 acts on microglia or contributes to cocaine addiction is largely unknown.

Methods

Rats were trained by intraperitoneal cocaine administration and cocaine‐induced conditioned place preference (CPP). Expression of HMGB1 was regulated by viral vectors. Activation of microglia was inhibited by minocycline. Interaction of HMGB1 and the receptor for advanced glycation end products (RAGE) was disrupted by peptide.

Results

Cocaine injection facilitated HMGB1 signaling, together with the delayed activation of microglia concurrently in the NAc. Furthermore, the inhibition of HMGB1 or microglia activation attenuated cocaine‐induced CPP. Box A, a specific antagonist to interrupt the interaction of HMGB1 and RAGE, abolished the expression of cocaine reward memory. Meanwhile, the inhibition of HMGB1–RAGE interaction suppressed cocaine‐induced microglial activation, as well as the consolidation of cocaine‐induced memory.

Conclusion

All above results suggest that the neural HMGB1 induces activation of microglia through RAGE, which contributes to the consolidation of cocaine reward memory. These findings offer HMGB1–RAGE axis as a new target for the treatment of drug addiction.
The effects of standard and modified LSVT BIG therapy protocols on balance and gait in Parkinson's disease: A randomized controlled trial
Authors: Eldemir Sefa , Eldemir Kader , Saygili Fettah , Ozkul Cagla , Yilmaz Rezzak , Akbostancı Muhittin Cenk , Guclu‐Gunduz Arzu
Published: March 2024

Background

Lee Silverman voice treatment (LSVT) BIG is an exercise program developed for patients with Parkinson's disease (PwPD), consisting of sets of exercises performed for 4 consecutive days a week for 4 weeks. However, the standard protocol suggests a treatment frequency difficult to follow for most patients who have difficulties reaching rehabilitation clinics. Our aim was to compare the standard LSVT BIG protocol with a modified LSVT (m‐LSVT) BIG protocol (twice a week in the clinic for 4 weeks and twice a week at home for 4 weeks).

Methods

In this randomized controlled trial, 16 PwPD (aged 18–80 years, Hoehn and Yahr stages I–III) were recruited into two groups. The LSVT group received standard LSVT BIG training (four times per week for 4 weeks at the clinic). The other group was given m‐LSVT BIG exercises, but unlike the LSVT group, the m‐LSVT group exercised twice a week at the clinic and twice a week at home for 4 weeks. The Berg Balance Scale was used to assess functional balance. Biodex Balance System was used to assess laboratory balance measures. Timed Up and Go test and G‐Walk sensor system were used to assess functional mobility and spatiotemporal gait analysis.

Results

Significant group‐by‐time interactions on the eyes open‐firm surface score of the modified clinical test of sensory integration of balance (F = 10.138, p = .007) and gait cycle symmetry index (F = 10.470, p = .010) were found to be in favor of the LSVT group. Additionally, post hoc analyses revealed that both groups significantly improved postural stability, gait speed, motor symptoms, and functional mobility (p < .05).

Conclusion

The results revealed the beneficial effects of the modified protocol on balance and gait in PwPD, as well as the superiority of the standard LSVT BIG protocol. The m‐LSVT BIG protocol may be an effective intervention method, especially for PwPD who have difficulty adapting to the treatment frequency of the standard protocol.
Medically unexplained symptoms are common in women in tertiary neurological healthcare center: A survey cohort study of persons investigated for suspected multiple sclerosis
Authors: Novakova Lenka , Hedström Anna Karin , Axelsson Markus , Brandt Anne Frandsen , Alfredsson Lars , Olsson Tomas , Lycke Jan
Published: March 2024

Background

A significant proportion of individuals with suspicious onset of multiple sclerosis (MS) does not fulfill the diagnostic criteria. Although some receive other diagnoses, many remain undiagnosed and lack healthcare follow‐up. This study aimed to characterize persons with undetermined diagnosis (PwUD) through a questionnaire.

Methods

Incident cases with suspected MS were consecutively admitted to a tertiary neurological healthcare center in a prospective cohort study. Those who remained undiagnosed after 40 months (mean, range 31–52) were considered PwUD. They completed a modified questionnaire, previously used in a population‐based case‐control study of incident MS cases. Their responses were compared with two control cohorts, persons with MS (PwMS) and healthy controls, randomly selected from national registries, matched by age, gender, and area of residence.

Results

Out of 271 patients with suspected MS onset, 72 (20.3%) were PwUD with a female majority (79%). The response rate was 83% and 39% reported persisting MS‐like symptoms. Compared to controls (n = 548) and PwMS (n = 277), fewer PwUD were currently smoking (p = .4 and p = .03), consumed less alcohol (p = .04 and p = .01), and had children (p = .02 and p = .002). PwUD reported occurrence of other autoimmune disease in 29%, higher compared to PwMS and controls (p < .001 and p < .001).

Conclusions

UD is common among persons investigated for suspected MS, in particular among female parents. Our data suggest that PwUD can be characterized as nonsmokers with low alcohol consumption and a higher prevalence of autoimmune disease, in particular thyroid disease.
Genetic causal association between physical activities and epilepsy: A Mendelian randomization study
Authors: Li Peihong , Li Jiaxin , Xiao Zheng , Sheng Dandan , Liu Weiping , Xiao Bo , Zhou Luo
Published: March 2024

Background

Despite numerous investigations into the relationship between physical activities (PA) and epilepsy, the causal effects remain contentious. Thus, we conducted a two‐sample Mendelian randomization (MR) study to assess the potential causality.

Methods

Single‐nucleotide polymorphisms (SNPs) predisposed to self‐reported moderate and vigorous physical activities (MPA and VPA) and overall acceleration average (OAA) calculated through wrist‐worn accelerometers were selected as exposure instrumental variables. Five subtypes of epilepsy, including all epilepsy, focal epilepsy and generalized epilepsy (with or without each other), focal epilepsy‐strict definition and generalized epilepsy‐strict definition (without overlap), were chosen as the outcomes. The MR study utilized the inverse‐variance weighted (IVW) method as the primary analytical tool, supplemented by MR‐Egger, simple mode, weighted mode, and weighted median methods. Cochran's Q and MR‐Egger intercept tests were employed to assess heterogeneity and pleiotropy, while MR pleiotropy residual sum and outlier and leave‐one‐out analyses were conducted to identify potential SNP outliers.

Results

The study indicated that OAA was genetically linked to a decreased risk of both focal epilepsy (OR = 0.812, 95% CI: 0.687–0.960, p = .015, IVW) and focal epilepsy‐strict definition (OR = 0.732, 95% CI: 0.596–0.900, p = .003, IVW; OR = 0.749, 95% CI: 0.573−0.979, p = .035, Weighted median). Genetically predicted MPA and VPA did not exhibit a causal association with all epilepsy or its subtypes (p>.05). No evidence of heterogeneity, pleiotropy, or SNP outlier was observed.

Conclusions

Our findings suggested that PA with accelerometer monitoring may potentially reduce the risk of focal epilepsy, while there is no evidence supporting causal association between self‐reported MPA or VPA and either focal or generalized epilepsy.
Management of a pure uterine corpus rhabdomyosarcoma in a postmenopausal patient: A rare case report and review of the literature
Authors: Lugata John , Smith Caleigh , Mrosso Onesmo , Rwenyagila Doris , Shao Baraka , Mremi Alex
Published: March 2024

Key Clinical Message

Rhabdomyosarcoma of the female genital tract often involves the vagina and cervix. It usually occurs in infants and children. Such tumors are uncommon in the uterus, especially in adults. Treatment options are based on studies of younger individuals.

Rhabdomyosarcoma (RMS) is a malignant mesenchymal neoplasm with a tendency to differentiate into skeletal muscle cells. RMS is an aggressive tumor that tends to develop in children and younger patients. A vast majority of genital tract RMSs occur in the vagina and cervix. Such tumors rarely occur in adults. Usually, these tumors either occur as a component of a biphasic uterine tumor (carcinosarcoma or adenosarcoma) or can be a pure heterologous tumor. Pure uterine RMSs are extremely rare in adult patients and difficult to diagnose. Accurate diagnosis of these tumors depends on precise histopathological evaluation. The present report describes a rare case of embryonal RMS of the uterus in a postmenopausal female and explores the most recent literature. The aim is to strengthen the existing literature and aid clinicians in the management of similar cases. A 64‐year‐old postmenopausal female presented with a history of abdominal pain associated with abdominal distension, per vaginal bleeding, and foul‐smelling discharge for 6 months. A transabdominal ultrasound revealed a bulky uterus with a well‐circumscribed heterogeneous lesion. Histopathology confirmed the diagnosis of high‐grade embryonal RMS within the corpus region of the uterus. A total abdominal hysterectomy with bilateral salpingo‐oophorectomy was performed, followed by adjuvant chemotherapy to prevent relapse of the disease. Six months after oncological care has passed, the patient remains symptoms‐free without evidence of recurrence or metastasis.
The skin as a window to the gut: A case of carcinoid syndrome
Authors: Costa Catarina Alves , Lopes Tânia , Rodrigues Ana Patrícia , Lamas Nuno Jorge , Cruz Célia
Published: March 2024

Key Clinical Message

Neuroendocrine tumors (NETs) are a group of uncommon neoplasms derived from enterochromaffin or Kulchitsky cells (that secrete serotonin or other molecules into the bloodstream), which can manifest with symptoms of hormonal overproduction, namely carcinoid syndrome (CS). This can be the presenting feature in patients with advanced disease. We report the case of a 66‐year‐old woman presenting with chronic diarrhea, facial venous telangiectasia and elevated urinary 5‐hydrocyindoleacetic acid levels. A 68‐Ga DOTATOC PET/CT scan revealed an ileal mass and lesions consistent with liver, ovary and bone metastasis. A liver biopsy confirmed the diagnosis of well‐differentiated NET G1. Therapy with somatostatin analogs achieved symptom control, but the liver disease progressed and the patient passed away after 2 years of follow‐up. The challenge of diagnosing CS resides in its heterogeneous manifestations, which may range from mild to life‐threatening conditions. In this case, the cutaneous findings of venous telangiectasia strongly pointed to the correct diagnosis. Treatment can also be difficult due to refractory symptoms and inevitable progression of disease, highlighting the importance of early detection and thorough disease staging.