bluuebunny/crossref_metadata_2025 huggingface dataset:
Formulation and assessment of chickpea pulao using fenugreek seeds and Indian rennet to improve blood glycemic levels
Authors: Arooj Misha , Ahmed Zaheer , Khalid Nauman , Suleria Hafiz A. R.
Published: March 2024

Diabetes is becoming a significant health concern in Asia, where the prevalence has reached alarming levels. An important contributing factor is the consumption of high‐carbohydrate foods, including rice, bread, etc. These high‐carbohydrate foods pose a major risk to public health due to their impact on postprandial hyperglycemia. This research aimed to formulate a chickpea pulao (cooked Indian–Pakistani rice dish) and to evaluate its effects on postprandial blood glucose levels in type 2 diabetic individuals. Antioxidant potential and total phenolic contents of herbs at different concentrations (1, 3, 5, 7, and 9%) were measured through DPPH and Folin Ciocalteu assays. The antidiabetic potential was tested by α‐amylase and α‐glucosidase inhibition assays. After sensory evaluation, the best‐chosen concentration was used to formulate the chickpea pulao. The study trial was advertised under “DP trial,” and 12 participants were recruited. A single‐blind randomized cross‐over trial was conducted for 3 weeks with a one‐week wash‐over time in between. Participants' preprandial and postprandial blood glucose levels were recorded for control and intervention recipes. Results indicated that both fenugreek seeds (FS) and Indian rennet (IR) showed good antioxidant and hypoglycemic activity (p = .000) in raw and boiled extracts. For DPPH, the IC50 values of unboiled and boiled combined (FS + IR) extracts were calculated as 7.4% and 8.02%, respectively. Similarly, for α‐amylase, the IC50 values of combined IR and FS unboiled and boiled extracts were 6.58% and 6.83%, and for α‐glucosidase inhibition assay, the values were measured as 14.98% and 16.24%. The single‐blind randomized cross‐over trial showed that consuming the intervention recipe significantly reduced postprandial hyperglycemia (p = .000) in type 2 diabetic participants. The intervention recipe decreased hyperglycemia by approximately 15% daily compared to the control recipe. Incorporation of hypoglycemic herbs into dietary patterns can work as an adjunct therapy for diabetes management, especially in populations with a high prevalence of this disease.
The use of a SOX10 reporter toward ameliorating oligodendrocyte lineage differentiation from human induced pluripotent stem cells
Authors: Piscopo Valerio E. C. , Chapleau Alexandra , Blaszczyk Gabriela J. , Sirois Julien , You Zhipeng , Soubannier Vincent , Chen Carol X.‐Q. , Bernard Geneviève , Antel Jack P. , Durcan Thomas M.
Published: March 2024

Oligodendrocytes (OLs) are key players in the central nervous system, critical for the formation and maintenance of the myelin sheaths insulating axons, ensuring efficient neuronal communication. In the last decade, the use of human induced pluripotent stem cells (iPSCs) has become essential for recapitulating and understanding the differentiation and role of OLs in vitro. Current methods include overexpression of transcription factors for rapid OL generation, neglecting the complexity of OL lineage development. Alternatively, growth factor‐based protocols offer physiological relevance but struggle with efficiency and cell heterogeneity. To address these issues, we created a novel SOX10‐P2A‐mOrange iPSC reporter line to track and purify oligodendrocyte precursor cells. Using this reporter cell line, we analyzed an existing differentiation protocol and shed light on the origin of glial cell heterogeneity. Additionally, we have modified the differentiation protocol, toward enhancing reproducibility, efficiency, and terminal maturity. Our approach not only advances OL biology but also holds promise to accelerate research and translational work with iPSC‐derived OLs.
Sex‐specific neuropsychological correlates of apathy and depression across neurodegenerative disorders
Authors: Kapustin Daniel , Tumati Shankar , Wong Melissa , Herrmann Nathan , Dixon Roger A. , Seitz Dallas , Rapoport Mark J. , Lanctôt Krista L.
Published: March 2024

Background

Apathy and depression are common neuropsychiatric symptoms across neurodegenerative disorders and are associated with impairment in several cognitive domains, yet little is known about the influence of sex on these relationships.

Objectives

We examined the relationship between these symptoms with neuropsychological performance across a combined cohort with mild or major neurodegenerative disorders, then evaluated the impact of sex.

Design, Setting and Participants

We conducted a cohort analysis of participants in the COMPASS‐ND study with mild cognitive impairment (MCI), vascular MCI, Alzheimer's disease, mixed dementia, Parkinson's disease, frontotemporal dementia, and cognitively unimpaired (CU) controls.

Measurements

Participants with neurodegenerative disease and CU controls were stratified by the presence (severity ≥1 on Neuropsychiatric Inventory Questionnaire) of either depressive symptoms alone, apathy symptoms alone, both symptoms, or neither. A neuropsychological battery evaluated executive function, verbal fluency, verbal learning, working memory, and visuospatial reasoning. Analysis of covariance was used to assess group differences with age, sex, and education as covariates.

Results

Groups included depressive symptoms only (n = 70), apathy symptoms only (n = 52), both (n = 68), or neither (n = 262). The apathy and depression + apathy groups performed worse than the neither group on tests of working memory (t(312) = −2.4, p = 0.02 and t(328) = −3.8, p = 0.001, respectively) and visuospatial reasoning (t(301) = −2.3, p = 0.02 and t(321) = −2.6, p = 0.01, respectively). The depression, apathy, and depression + apathy groups demonstrated a similar degree of impairment on tests of executive function, processing speed, verbal fluency, and verbal learning when compared to participants without apathy or depression. Sex‐stratified analyses revealed that compared to the male neither group, the male apathy and depression + apathy groups were impaired broadly across all cognitive domains except for working memory. Females with depression alone showed deficits on tests of executive function (t(166) = 2.4, p = 0.01) and verbal learning (t(167) = −4.3, p = 0.001) compared to the female neither group.

Conclusions

This study demonstrated that in neurodegenerative diseases, apathy with or without depression in males was associated with broad cognitive impairments. In females, depression was associated with deficits in executive function and verbal learning. These findings highlight the importance of effectively treating apathy and depression across the spectrum of neurodegenerative disorders with the goal of optimizing neuropsychological outcomes.
Accuracy and efficacy of ultrasound‐guided puncture (vs. computed tomography‐guided) in cervical medial branch blocks for cervicogenic pain: A randomized controlled study
Authors: Tian Jie , Li Xin‐Yan , Yin Yan , Zhao Nan , Xiao Hong , Liu Hui
Published: March 2024

Cervical medial branch block (CMBB) has been recognized as an effective treatment for cervicogenic pain. Previous studies mostly used ultrasound‐guided out‐of‐plane puncture for CMBB, while this prospective study was designed to investigate the efficacy of ultrasound‐guided in‐plane puncture, specifically focusing on the new target of CMBB for cervical pain. This study includes two parts: the accuracy study (N = 15, CMBB was completed by ultrasound and confirmed by computed tomography [CT], in which a good distribution percentage of the analgesic solution was observed) and the efficacy study (N = 40, CMBB was completed by ultrasound or CT, while the proportion of pain relief (numerical rating scale) decrease by more than 50% postoperatively was analyzed). The results showed that the good distribution percentage of the analgesic solution was 97.8%. Furthermore, in the early period (30 min and 2 h postoperatively), the proportion of patients with pain relief was lower in the ultrasound group than that in the CT group, especially at 2 h postoperatively (52% vs. 94%). However, at 24 h postoperatively and later, the proportion of patients with pain relief gradually stabilized to about 60%–70%, and lasted for about 2 weeks to 1 month. Therefore, the new target for CMBB, guided by ultrasound in‐plane, offers high visibility and accuracy. A single CMBB performed under ultrasound guidance resulted in pain relief comparable to that of a CT‐guided procedure (1 day to 1 month postoperatively). This study indicated that CMBB guided by ultrasound in‐plane could be regarded as a promising approach for treatment of cervicogenic pain.
Metal‐to‐insulator transition in oxide semimetals by anion doping
Authors: Hong Haitao , Zhang Huimin , Lin Shan , Dhas Jeffrey A. , Paudel Binod , Xu Shuai , Chen Shengru , Cui Ting , Fan Yiyan , Rong Dongke , Jin Qiao , Zhu Zihua , Du Yingge , Chambers Scott A. , Ge Chen , Wang Can , Zhang Qinghua , Wang Le , Jin Kui‐juan , Dong Shuai , Guo Er‐Jia
Published: March 2024

Oxide semimetals exhibiting both nontrivial topological characteristics stand as exemplary parent compounds and multiple degrees of freedom, offering a promise for the realization of novel electronic states. In this work, we report the structural and transport phase transition in an oxide semimetal, SrNbO3, achieved through effective anion doping. Notably, the resistivity increased by more than three orders of magnitude at room temperature upon nitrogen‐doping. The extent of electronic modulation in SrNbO3 is strongly correlated with misfit strain, underscoring its phase instability to both chemical doping and crystallographic symmetry variations. Using first‐principles calculations, we discern that elevating the level of nitrogen doping induces an upward shift in the conductive bands of SrNbO3−δNδ. Consequently, a transition from a metallic state to an insulating state becomes apparent as the nitrogen concentration reaches a threshold of 1/3. This investigation shows effective anion engineering in oxide semimetals, offering pathways for manipulating their physical properties.
Assays on 3D tumor spheroids for exploring the light dosimetry of photodynamic effects under different gaseous conditions
Authors: Li Yuewu , Yang Tianyi , Liu Sijia , Chen Chunxiao , Qian Zhiyu , Yang Yamin
Published: March 2024

The multifaceted nature of photodynamic therapy (PDT) requires a throughout evaluation of a multitude of parameters when devising preclinical protocols. In this study, we constructed MCF‐7 human breast tumor spheroid assays to infer PDT irradiation doses at four gradient levels for violet light at 408 nm and red light at 625 nm under normal and hypoxic oxygen conditions. The compacted three‐dimensional (3D) tumor models conferred PDT resistance as compared to monolayer cultures due to heterogenous distribution of photosensitizers along with the presence of internal hypoxic region. Cell viability results indicated that the violet light was more efficient to kill cells in the spheroids under normal oxygen conditions, while cells exposed to the hypoxic microenvironment exhibited minimal PDT‐induced death. The combination of 3D tumor spheroid assays and the multiparametric screening platform presented a solid framework for assessing PDT efficacy across a wide range of different physiological conditions and therapeutic regimes.
Global level of methylation in the sea lamprey (jawless vertebrate) genome is intermediate between invertebrate and jawed vertebrate genomes
Authors: Zhang Zhao , Liu Gangbiao , Zhou Zhan , Su Zhixi , Gu Xun
Published: March 2024

In eukaryotes, cytosine methylation is a primary heritable epigenetic modification of the genome that regulates many cellular processes. In invertebrate, methylated cytosine generally located on specific genomic elements (e.g., gene bodies and silenced repetitive elements) to show a “mosaic” pattern. While in jawed vertebrate (teleost and tetrapod), highly methylated cytosine located genome‐wide but only absence at regulatory regions (e.g., promoter and enhancer). Many studies imply that the evolution of DNA methylation reprogramming may have helped the transition from invertebrates to jawed vertebrates, but the detail remains largely elusive. In this study, we used the whole‐genome bisulfite‐sequencing technology to investigate the genome‐wide methylation in three tissues (heart, muscle, and sperm) from the sea lamprey, an extant agnathan (jawless) vertebrate. Strikingly, we found that the methylation level of the sea lamprey is very similar to that in sea urchin (a deuterostome) and sea squirt (a chordate) invertebrates. In sum, the global pattern in sea lamprey is intermediate methylation level (around 30%), that is higher than methylation level in the genomes of pre‐bilaterians and protostomes (1%−10%), but lower than methylation level appeared in jawed vertebrates (around 70%, teleost and tetrapod). We anticipate that, in addition to genetic dynamics such as genome duplications, epigenetic dynamics such as global methylation reprograming was also orchestrated toward the emergence and evolution of vertebrates.
Facilitators and barriers to community pharmacy PrEP delivery: a scoping review
Authors: Harrison China , Family Hannah , Kesten Joanna , Denford Sarah , Scott Anne , Dawson Sarah , Scott Jenny , Sabin Caroline , Copping Joanna , Harryman Lindsey , Cochrane Sarah , Horwood Jeremy
Published: March 2024

Introduction

Pre‐exposure prophylaxis (PrEP) is an effective medication to reduce the risk of acquiring HIV. PrEP is available free of charge in the UK from sexual health clinics. Expanding PrEP delivery to community pharmacies holds promise and aligns with UK government goals to eliminate new cases of HIV by 2030. The aim of this scoping review was to describe the existing evidence about the barriers to and facilitators of community pharmacy oral PrEP delivery, for pharmacists and pharmacy clients, as aligned with the Capacity Opportunity, Motivation Behaviour (COM‐B) Model.

Methods

Five bibliographic and five review databases were searched from inception to August 2023. Literature of any study design was included if it discussed barriers and facilitators of community pharmacy PrEP delivery. Trial registrations, protocols and news articles were excluded.

Results

A total of 649 records were identified, 73 full texts were reviewed and 56 met the inclusion criteria, predominantly from high‐income/westernized settings. Most of the included literature was original research (55%), from the United States (77%) conducted during or after the year 2020 (63%). Barriers to PrEP delivery for pharmacists included lack of knowledge, training and skills (capability), not having the necessary facilities (opportunity), concern about the costs of PrEP and believing that PrEP use could lead to risk behaviours and sexually transmitted infections (motivation). Facilitators included staff training (capability), time, the right facilities (opportunity), believing PrEP could be a source of profit and could reduce new HIV acquisitions (motivation). For clients, barriers included a lack of PrEP awareness (capability), pharmacy facilities (opportunity) and not considering pharmacists as healthcare providers (motivation). Facilitators included awareness of PrEP and pharmacist's training to deliver it (capability), the accessibility of pharmacies (opportunity) and having an interest in PrEP (motivation).

Discussion

To effectively enhance oral PrEP delivery in UK community pharmacies, the identified barriers and facilitators should be explored for UK relevance, addressed and leveraged at the pharmacy team, client and care pathway level.

Conclusions

By comprehensively considering all aspects of the COM‐B framework, community pharmacies could become crucial providers in expanding PrEP accessibility, contributing significantly to HIV prevention efforts.
Affectional and gender minority student experiences in CACREP‐accredited counseling programs at conservative Christian institutions: A call for change
Authors: Tis Matt
Published: March 2024

This study explored the experiences of affectional and gender minority students at CACREP accredited counseling programs housed within conservative Christian institutions (CCIs) and the damage caused by the discriminatory environments there. The results highlight the opportunity and responsibility that CCIs have to both protect these vulnerable student populations and provide models for them as well as the need for the counseling field to align the expectations of practitioners with the expectations placed upon training programs.
Coronavirus HKU1 infection and development of pediatric acute liver failure with immune dysregulation phenotype
Authors: Ajmera Arun , Pernicone Peter Joseph , Patel Nishant , Benabe Stefany Hernandez
Published: March 2024

Pediatric acute liver failure is a rare but serious complication of Coronavirus infections. Our patient is a previously healthy 8‐year‐old male who presented with acute liver failure in the setting of human coronavirus HKU1 (HCoV‐HKU1) infection while asymptomatic from a respiratory perspective. During the hospital course, he developed acute hepatic encephalopathy and was listed for liver transplantation, but fortunately recovered remaining status 7 (inactive) on the transplant list. With a negative diagnostic evaluation other than his viral infection and hyperdense CD8 T‐cells on liver immunohistochemical staining, pediatric acute liver failure (PALF) immune dysregulation phenotype was diagnosed.
Governing at a distance to change corporate social responsibility discourse: Navigating through institutions and actors
Authors: Yeröz Huriye , Karatas‐Ozkan Mine , Yamak Sibel
Published: March 2024

In this paper, we demonstrate what influences the evolution of Corporate Social Responsibility (CSR) debates. Using the idea of ‘governing at a distance’ (Rose & Miller, 1992) from the Foucauldian governmentality perspective, we identify the mechanisms behind CSR's context‐based evolution. Examining 72 academic texts on CSR from the 1940s to the 2000s, we find that spatial political contexts and power interests shape CSR. We argue that CSR discourse is linked to governing systems and was part of a post‐WWII restructuring to support capitalism against communism in the global order. Our study reveals that academic journals and scholars introduced American CSR concepts to Turkish academia through strong ties to institutions like Harvard Business School and the Ford Foundation, influencing the emergence and change of CSR over time. Changes in CSR discourse are contextually embedded and politically laden with its emergence having a strong governmentality dimension for which academics (through their texts, academic acumen, and affiliated institutions) play a key role as intermediaries governing at a distance. While the critical perspective emphasizes the issues of coercion and contestations, our paper suggests the importance of cooperation and concerted efforts in shaping the global construction of CSR. We have demonstrated the nuanced interplay between the local and global governance of business and academic associations, challenging the perceived rigidity of their boundaries.
Role of pea protein isolate in modulating pea starch digestibility: insights from physicochemical and microstructural analysis
Authors: Kuang Jiwei , Yang Xijuan , Xu Ke , Zheng Wancai , Dang Bin
Published: March 2024

BACKGROUND

Understanding the interactions between protein and starch is crucial in revealing the mechanisms by which protein influences starch digestibility. The present study investigated the impact of different contents of pea protein isolate (PPI) on the physicochemical properties and digestibility of pea starch (PS).

RESULTS

The results demonstrated that as the content of PPI increased from 0% to 12%, and the digestion of PS decreased by 12.3%. Rheological analysis indicated that PPI primarily interacted with molecular chains of PS through hydrogen bonds. Increasing the content of PPI resulted in a 30.6% decrease in the hardness of the composite gels, accompanied by a 10% reduction in the short‐ordered structure of PS. This hindered the formation of molecular aggregation and resulted in a loose and disordered gel network structure. The microstructure confirmed that the attachment of PPI to PS served as a physical barrier, impeding starch digestibility.

CONCLUSION

In summary, the primary mechanism by which PPI inhibited PS digestion involved steric hindrance exerted by PPI and its interaction with PS via hydrogen bonds. These findings contribute to a better understanding of the interaction mechanisms between PS and PPI and offer insights for the optimal utilization of pea resources. © 2024 Society of Chemical Industry.
Intradiscal administration of autologous platelet‐rich plasma in patients with Modic type 1 associated low back pain: A prospective pilot study
Authors: Kawabata Soya , Nagai Sota , Ito Kei , Takeda Hiroki , Ikeda Daiki , Kawano Yusuke , Kaneko Shinjiro , Shiraishi Yukako , Sano Yuichiro , Ohno Yoshiharu , Fujita Nobuyuki
Published: March 2024

Background

Various treatments for chronic low back pain (LBP) have been reported; among them, platelet‐rich plasma (PRP) as a regenerative medicine has attracted much attention. Although Modic type 1 change (MC1) is associated with LBP, no treatment has been established so far. In addition, no studies have administered PRP to intervertebral discs (IVDs) in patients with LBP, targeting MC1 only. Thus, the purpose of this study was to determine the safety and efficacy of PRP administration to the IVDs in patients with MC1 experiencing LBP.

Methods

PRP was injected intradiscally to 10 patients with MC1 experiencing LBP. Patients were followed prospectively for up to 24 weeks after primary administration. Physical condition, laboratory data, and lumbar x‐ray images were evaluated for safety assessment. Furthermore, to evaluate the effectiveness of PRP, patient‐reported outcomes were considered. In addition, changes in MC1 were assessed using magnetic resonance imaging (MRI).

Results

There were no adverse events in the laboratory data or lumbar X‐ray images after administration. The mean visual analog scale, which was 70.0 ± 13.3 before the treatment, significantly decreased 1 week after PRP administration and was 39.0 ± 28.8 at the last observation. Oswestry disability index and Roland Morris disability questionnaire scores promptly improved after treatment, and both improved significantly 24 weeks after PRP administration. Follow‐up MRI 24 weeks after treatment showed a significant decrease in the mean high‐signal intensity of fat‐suppressed T2‐weighted imaging from 10.1 to 7.90 mm2 compared with that before PRP administration.

Conclusions

The safety and efficacy of PRP administration to the IVDs of patients with MC1 experiencing LBP were identified. Post‐treatment MRI suggested improvement in inflammation, speculating that PRP suppressed inflammation and consequently relieved the patient's symptoms. Despite the small number of patients, this treatment is promising for patients with MC1 experiencing LBP. The study protocol has been reviewed and approved by the Certified Committee for Regenerative Medicine and the Japanese Ministry of Health, Labor and Welfare (Japan Registry of Clinical Trials [jRCT] No. jRCTb042210159).
Heralded Entanglement Distribution Between Two Spin‐Wave Memories Using Temporally Multiplexed Scheme
Authors: Wang Minjie , Jiao Haole , Lu Jiajin , Fan Wenxin , Yang Zhifang , Xi Mengqi , Li Shujing , Wang Hai
Published: March 2024

The elementary link, which is formed by entanglement between two remote atomic ensembles, is a fundamental component of Duan–Lukin–Cirac–Zoller (DLCZ) quantum repeater. For practical realization of quantum repeaters, it is required that entanglement between two atomic‐ensemble‐based memories can be generated with high rates and retrieved with high efficiencies. However, so far, such quantum‐repeater links remain challenge in experiments. Here, heralded entanglement distribution between atomic‐ensemble‐based memories is demonstrated via temporally multiplexed scheme. A train of 12 write pulses in time is applied to a cloud of cold atoms along different directions, which generates temporally multiplexed pairs of Stokes photons and spin waves via DLCZ processes. The Stokes fields propagating in the two spatial modes, which are paired with two spin waves are combined to perform a single‐photon Bell‐state measurement. A successful detection projects the two spin waves into a single‐excitation entanglement, which represents entanglement distribution in an elementary link. Compared with single‐mode storage scheme, the temporally multiplexed scheme gives rise to a 11.8‐fold increase in entanglement generation rate. By using cavity‐enhanced scheme, spin waves stored in the atoms are retrieved on demand and the retrieval efficiencies are up to 70%, which is beneficial for the subsequent entanglement swapping between adjacent links.
Large‐Range Beam Steering through Dynamic Manipulation of Topological Charges
Authors: Zhang Kong , Zhang Guanjie , Chen Xinghong , Sang Yungang , Mao Yifei
Published: March 2024

Dynamic tuning of light properties by external stimuli is at the core of various applications such as electro‐optical modulators, beam steering, and spatial light modulators. The conventional mechanism involves fine‐tuning the eigenmode of an optical system through adjusting the effective refractive index. However, the weak nonlinearity results in low modulation efficiency, leading to devices with poor performance and large size. Polarization topological charge is a significant concept that has facilitated the development of innovative optical devices like low‐threshold lasers and vortex generators. But the devices reported so far are static in nature. Here, a method for dynamically controlling light by actively manipulating the evolution of topological charges in momentum space is first presented. By switching between integer and half‐integer states of topological charges, the device's radiation properties undergo a significant transformation. The beam direction can be tuned up to 160°, which, to the best of the authors' knowledge, is the largest tuning angle among similar beam steering devices. Furthermore, the device demonstrates high radiation efficiency while maintaining a compact device size. This light controlling method can be applied in various fields, including optical communication, tunable lasers, and light detection and ranging.
Real‐Time Jones Matrix Synthesis by Compact Polarization Inline Holographic Microscopy
Authors: Liu Hanzi , R.V Vinu , Chen Kaiquan , Liao Dongyang , Chen Ziyang , Pu Jixiong
Published: March 2024

The Jones matrix is a powerful quantitative tool for polarimetric imaging and characterization, where the matrix elements represent the intrinsic optical properties of the anisotropic objects on interaction with the polarized light. Most of the state‐of‐the‐art single‐shot Jones‐matrix imaging techniques rely on interferometric methods, which makes the design complex with the use of large number of polarization optics and produces space‐bandwidth limitations. The simultaneous extraction of Jones matrix elements with a compact system design is still a technical challenge in view of its potential applications in biomedical and real‐time characterization scenarios. In this paper, the imaging features of the in‐line holography are exploited to develop a compact polarization in‐line holography (PIH) system capable of single‐shot extraction of Jones‐matrix elements. The technique achieves simultaneous orthogonal polarization state generation and corresponding polarization multiplexed in‐line hologram detection by utilizing a compact polarization geometry. The imaging compatibility and measurement accuracy of the method is experimentally validated by the real‐time synthesis of Jones‐matrix elements corresponding to custom designed polarization sensitive samples and standard birefringent resolution target. Furthermore, to demonstrate the application of the system in dynamic imaging, the transient polarization changes of a custom‐designed parallel nematic liquid crystal display (LCD) are investigated.
Randomized Phase I Trial of the α‐Synuclein Antibody Lu AF82422
Authors: Buur Louise , Wiedemann Jonas , Larsen Frank , Ben Alaya‐Fourati Fayrouz , Kallunki Pekka , Ditlevsen Dorte Kornerup , Sørensen Mette Høgh , Meulien Didier
Published: March 2024

Background

Immunotherapy targeting pathological α‐synuclein (α‐syn) species is a promising strategy for slowing disease progression in neurodegenerative synucleinopathies, including Parkinson's disease (PD).

Objective

The aim was to evaluate the safety, tolerability, pharmacokinetics, and target engagement of ascending doses of Lu AF82422.

Methods

In this first‐in‐human study (NCT03611569), healthy participants (18–55 years, cohort A) and patients with PD (40–80 years, Hoehn and Yahr stage ≤3, cohort B) were enrolled in ascending‐dose cohorts and randomly assigned to receive single intravenous infusions of Lu AF82422 (cohorts A1–A6: 75, 225, 750, 2250 4500, and 9000 mg, respectively; cohorts B1 and B2: 2250 and 9000 mg, respectively) or placebo. Participants were monitored during a 12‐week observational period.

Results

Overall, single intravenous infusions of Lu AF82422 were safe and well tolerated, and no serious adverse events (AE) were observed; the most common AEs were related to the study on lumbar punctures, headache, and common infections. Lu AF82422 concentrations (in plasma and cerebrospinal fluid [CSF]) increased in a dose‐proportional manner with no observable differences between cohorts; mean plasma half‐life was 700 h. Plasma concentrations of Lu AF82422 had an immediate, concentration‐dependent lowering effect on the plasma concentration of free α‐syn and on the ratio of free to total α‐syn in all cohorts and lowered the free‐to‐total α‐syn ratio in CSF in the high‐dose PD cohort.

Conclusions

The safety and pharmacokinetic profile of Lu AF82422 were appropriate for further clinical development, and results indicated peripheral target engagement. The central target engagement observed in participants with PD indicates that the doses of Lu AF82422 tested may provide CSF concentrations sufficient to target aggregated forms of α‐syn. © 2024 H. Lundbeck A/S. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Multilayered neural network for power series‐based approximation of fractional delay differential equations
Authors: Kumar Manoj , Kumar Sandeep , Kumar Kranti , Goswami Pranay
Published: March 2024

This paper trains a multilayered neural network (MLNN) for solving fractional delay differential equations (FDDEs), including nonlinear and singular types. The proposed methodology involves replacing the unknown functions in the equations with a truncated power series expansion. Subsequently, a collection of algebraic equations is solved utilizing an iterative minimization technique that leverages the capabilities of the MLNN architecture. The outcomes demonstrate that the MLNN architecture provides the required accuracy and strong stability compared to several numerical methods.
Stabilization of string–beam–string transmission systems with localized frictional damping and delay
Authors: Hao Jianghao , Wang Yue
Published: March 2024

In this paper, we consider two string–beam–string boundary transmission problems with localized frictional damping and delay. The first transmission problem is that the frictional damping and delay are in the left string equation and the right string equation is thermoelastic. The second transmission problem is that the damping and the delay are both only acting on the middle beam equation. Using the semigroup theory, we get the existence and the uniqueness of solution under suitable assumptions on the weight of the damping and the weight of the delay. Furthermore, we prove that the first transmission problem is exponentially stable and the second transmission problem is polynomially stable using the frequency domain method and the multiplier techniques.
An introductory review of swarm technology for spacecraft on‐orbit servicing
Authors: Asri El Ghali , Zhu Zheng H.
Published: March 2024

This review paper presents a comprehensive evaluation and forward‐looking perspective on the underexplored topic of servicing target objects using spacecraft swarms. Such targets can be known or unknown, cooperative or uncooperative, and pose significant challenges in modern space operations due to their inherent complexity and unpredictability. Successfully servicing space objects is vital for active debris removal and broader on‐orbit servicing tasks such as satellite maintenance, repair, refueling, orbital assembly, and construction. Significant effort has been invested in the literature to explore the servicing of targets using a single spacecraft. Given its advantages and benefits, this paper expands the discussion to encompass a swarm approach to the problem. This review covers various single‐spacecraft approaches and presents a critical examination of the existing, although limited, body of work dedicated to servicing orbital objects using multiple spacecraft. The focus is also broadened to include some influential studies concerning the characterization, capture, and manipulation of physical objects by general multiagent systems, a subject with significant parallels to the core interest of this manuscript. Furthermore, this article also delves into the realm of simultaneous localization and mapping, highlighting its application within close‐proximity operations in space, especially when dealing with unknown uncooperative targets. Special attention is paid to the benefits that this field can receive from distributed multiagent architectures. Finally, an exploration of the promising field of swarm robotics is presented, with an emphasis on its potential to revolutionize the servicing of orbital target objects. Concurrently, a survey of general research directly engaging swarms in the orbital context is conducted. This review aims to bridge the knowledge gap and stimulate further research in the underexplored domain of servicing space targets with spacecraft swarms.
The maximum principle for optimal control of mean‐field FBSDE driving by Teugels martingales with terminal state constraints
Authors: Huang Zhen , Wang Ying , Lin Xiangyun
Published: March 2024

This article studies the problem of optimal control with state constraints for mean‐field type stochastic systems, which is governed by a fully coupled forward‐backward stochastic differential equation with Teugels martingales. In this system, the coefficients contain not only the state processes but also its expectation value, and the cost function is of mean‐field type as well. We use an equivalent backward formulation to deal with the terminal state constraint, and then we obtain a stochastic maximum principle by Ekeland's variational principle. In addition, we discuss a stochastic linear‐quadratic control problem with state constraints.
Advanced polymeric dendrimers in the management of Alzheimer's disease
Authors: Kapare Harshad S. , Pawar Ranjitsinh , Neve Vrushali , Bhalchim Vrushali , Giram Prabhanjan S.
Published: March 2024

In recent years, advanced polymeric dendrimers have emerged as a promising avenue for AD management. Dendrimers are highly branched, three‐dimensional macromolecules with precise nanoarchitectures, making them ideal candidates for the delivery of therapeutic agents and diagnostic tools. Their unique properties, such as well‐defined size, multifunctionality, and controlled surface chemistry, allow for the design of targeted and highly efficient drug delivery systems and diagnostic probes. This review aims to provide a comprehensive overview of the potential applications of advanced polymeric dendrimers in the management of Alzheimer's disease. We explored their role in drug delivery, diagnostics, and other therapeutic interventions for AD. Additionally, we will delve into the challenges and opportunities in utilizing dendrimers as a key player in the battle against this devastating disease. The review will begin by discussing the current state of Alzheimer's disease, including its pathological features, clinical manifestations, and existing treatment strategies. It will then transition to an in‐depth examination of polymeric dendrimers, highlighting their structural characteristics, synthesis methods, and biocompatibility. Subsequently, the review will delve into the various ways in which dendrimers can be tailored for AD management, including drug encapsulation and delivery, enhanced blood–brain barrier penetration, and targeted diagnostic imaging. Furthermore, we explored the potential benefits of dendrimer‐based therapies, such as improved drug efficacy, reduced side effects, and enhanced patient compliance. The review will also address the challenges associated with dendrimer‐based approaches, including toxicity concerns, regulatory hurdles, and the need for rigorous clinical evaluation.
Prenatal phenotype of a homozygous nonsense MPDZ variant in a fetus with severe congenital hydrocephalus
Authors: Vanden Eynde Nathalie , Van den Mooter Eve , Vantroys Elise , De Schutter Elke , Leus Astrid , Keymolen Kathelijn , Dimitrov Boyan , van Berkel Kim
Published: March 2024

The fetal phenotype of MPDZ‐associated congenital hydrocephalus type 2 with or without brain or eye anomalies (HYC2) (OMIM 615219) is not well described in the literature. The present case shows not previously published clinical fetal features that are detected during routine second trimester ultrasound screening at 21 weeks of gestation such as bilateral ventriculomegaly, lean cavum septum pellucidum, suspicion of hypoplastic corpus callosum, and suspicion of gyration disorder with normal fossa posterior. Combination of clinical features and a gene panel for congenital malformation syndromes detected a homozygous, likely pathogenic nonsense variant in the MPDZ gene. HYC2 is a rare autosomal recessive disorder with prenatal onset. Clinical presentation is highly variable, varying from stillbirth and severe neurodevelopmental problems with death in infancy to adult patients. Other reported associated congenital anomalies are mainly heart defects and ophthalmologic abnormalities. The present case so far is the first prenatally well described case of HYC2 in an ongoing pregnancy.
Eliminating first trimester combined testing: Consequences for early detection of significant fetal anomalies
Authors: Lugthart M. A. , Heinrich H. , Ertugrul I. , Nsiah‐Asare E. N. , van de Kamp K. , Linskens I. H. , van Maarle M. C. , van Leeuwen E. , Pajkrt E.
Published: March 2024

Objective

To determine whether implementation of cell‐free DNA (cfDNA) testing for aneuploidy as a first‐tier test and subsequent abolition of first trimester combined testing (FCT) affected the first trimester detection (<14 weeks) of certain fetal anomalies.

Methods

We performed a geographical cohort study in two Fetal Medicine Units between 2011 and 2020, including 705 fetuses with prenatally detected severe brain, abdominal wall and congenital heart defects. Cases were divided into two groups: before (n = 396) and after (n = 309) cfDNA introduction. The primary outcome was the first trimester detection rate (<14 weeks) overall and for non‐chromosomal anomalies solely.

Results

Overall, gastroschisis, AVSD and HLHS were detected more often in the first trimester in the before group compared to the after group, respectively 54.5% versus 18.5% (p = 0.004), 45.9% versus 26.9% (p = 0.008) and 30% versus 3.4% (p = 0.005). After exclusion of chromosomal anomalies identifiable through cfDNA testing, the detection of AVSD remained higher in the before group (43.3% vs. 9.5%, p = 0.02), leading to a possible earlier gestation at termination. The termination of pregnancy (TOP) rate did not differ among the groups. In the after group, referrals for suspected anomalies following a dating scan between 11 and 14 weeks significantly increased from 17.4% to 29.1% (p < 0.001).

Conclusion

This study underscores the value of a scan dedicated to fetal anatomy in the first trimester as we observed a decline in the early detection of certain fetal anomalies (detectable in the first trimester) subsequent to the abolition of FCT.
Uptake rate of carrier screening among consanguineous couples
Authors: Ricca Julianne , Brandt Justin S. , Jacob Natalie , Ashkinadze Elena
Published: March 2024

Objective

To quantify the uptake rates of Carrier Screening (CS) in consanguineous couples and compare this rate to that of non‐consanguineous couples.

Methods

We performed a matched case control study of 82 consanguineous couples seen at Rutgers‐Robert Wood Johnson Medical school who were offered carrier screening between January 1, 2012 and October 10, 2022. We then matched each consanguineous female patient to a non‐consanguineous female control patient who was also offered CS at the time of their genetic counseling appointment. A 2 × 2 contingency table analysis was used to compare rates of acceptance and declination between the consanguineous and non‐consanguineous groups.

Results

The overall acceptance rate among consanguineous couples was 82.9%, whereas the overall acceptance rate among non‐consanguineous couples was 56.1%. After statistical analysis, consanguineous couples were significantly more likely to accept CS as compared to non‐consanguineous couples (OR = 3.801, 95% CI; p < 0.0001). We also report the carrier couple rates and individual carrier statistics between these two groups.

Conclusion

This study supports the idea that consanguineous couples are more likely to pursue CS and have a higher carrier couple yield.
The longitudinal relationship between self‐compassion and cancer patients' unmet supportive care needs
Authors: Yu Yunlei , Li Yanze , Zhao Jiang , Yao Juntao , Duan Yaokun , Shao Yufei , Xie Juan , Zhu Lei
Published: March 2024

Objectives

Unmet supportive care needs are associated with psychological symptoms such as depression and anxiety. However, so far, few studies have explored the protective psychological factors of unmet needs. Therefore, this study intends to explore the protective effect of self‐compassion on unmet needs of Chinese cancer patients and to examine the predictive role of self‐compassion on these needs during treatment.

Methods

A longitudinal study was performed at Shaanxi Provincial Cancer Hospital in Xi'an, China. A total of 153 heterogeneous cancer patients were assessed after the first diagnosis (T1), at the beginning (T2) and end (T3) of medical treatment. Hierarchical linear regression analyses were used to examine the research questions.

Results

Cross‐sectional regression analyses showed that self‐compassion at T1 was significantly related to psychological needs at T1. Negative self‐compassion at T1 was significantly related to total unmet needs, psychological needs, health system, and information and sexual needs. Longitudinal regression analyses showed that self‐compassion at T1 significantly predicted total unmet needs; health system and information (HSI) needs at T2, psychological needs at T3, and negative self‐compassion at T1 significantly predicted total unmet needs, HSI needs, physical needs, and patient care needs at T2 when controlling for unmet needs at T1. Positive self‐compassion was not a predictor of unmet needs.

Conclusions

Self‐compassion can be a protective factor of unmet needs in cancer patients. Future intervention studies should focus on improving the overall level of self‐compassion and reducing the level of negative self‐compassion in cancer patients to reduce patients' unmet needs.
The effect of a couple‐based posttraumatic growth intervention in supporting couples coping with colorectal cancer: A randomized controlled study
Authors: Wang Zhiming , Chen Xuan , Zhou Junrui , Lin Chunyan , Zhao Jie , Li Qiuping
Published: March 2024

Objectives

To promote posttraumatic growth (PTG) in colorectal cancer (CRC) couples, a couple‐based PTG intervention was conducted, and the intervention had previously proved be feasible in CRC couples. The current study was conducted to validate the effects of intervention in CRC couples.

Method

This is a randomized controlled study that included 174 CRC couples. All participants were randomized to either the intervention (usual care plus 5‐week PTG intervention, n = 87) or the control group (usual care, n = 87). Data were collected from CRC couple dyads at baseline and immediately post‐intervention periods. Primary outcome refers to positive changes, and secondary outcomes include marital satisfaction, quality of life (QOL), and anxiety and depression. Multilevel modeling was applied to analyze the intervention effects.

Results

Participants in the program showed increased PTG, marital satisfaction, and QOL both physically and mentally, and decreased levels of anxiety and depression over time. And spousal caregivers showed greater improvement in marital satisfaction and physical QOL compared with patients. In addition, significant intervention effects were shown in the participants' benefit finding, physical health and depressive symptoms.

Conclusion

The study confirmed the effect of the PTG intervention on CRC couples' benefit finding, physical health and depressive symptoms. However, this study only measured outcome variables at two time‐points. Future studies should add follow‐up assessments to evaluate long‐term effects of the intervention in CRC couples.

Registration number

ChiCTR2300067809.
Wound microenvironment‐responsive peptide hydrogel with multifunctionalities for accelerating wound healing
Authors: Dong Weimiao , Yang Haihong , Liu Min , Mei Leixia , Han Jun
Published: March 2024

The fabrication of wound microenvironment‐responsive peptide hydrogels with hemostatic ability, antibacterial activity, and wound healing potential remains a challenge. Herein, we constructed a multifunctional dressing by inducing the self‐assembly of a peptide (Pep‐1) and water‐soluble new methylene blue (NMB) through electrostatic interaction. The self‐assembly mechanism was demonstrated using a combination of transmission electron microscopy, circular dichroism spectrum, fluorescence spectrum, Zeta potential, and rheological analysis. The Pep‐1/NMB hydrogel also exhibited a faster drug release rate in wound acidic environment. Furthermore, when Pep‐1/NMB was exposed to a 635 nm laser, its antibacterial ratios increased sharply to 95.3%, indicating remarkably improved antibacterial effects. The findings from the blood coagulation and hemostasis assay indicated that Pep‐1/NMB effectively enhanced the speed of blood clotting in vitro and efficiently controlled hemorrhage in a mouse liver hemorrhage model. Meanwhile, hemolytic and cytotoxicity evaluation revealed that the hydrogel had excellent hemocompatibility and cytocompatibility. Finally, the findings from the wound healing studies and H&E staining indicated that the Pep‐1/NMB hydrogel had a significant impact on cell migration and wound repair. The results indicated that wound microenvironment‐responsive Pep‐1/NMB hydrogel had significant potential as a highly effective wound dressing platform, offering rapid hemostasis, antibacterial, and wound healing acceleration properties.