bluuebunny/crossref_metadata_2025 huggingface dataset:
Overview of Clomiphene Citrate Use in Male Hypogonadism and Infertility
Authors: Câmara Lucas Caseri
Published: December 2024

Clomiphene Citrate (CC) has been widely used in medicine since the 1970s, primarily as a Selective Estrogen Receptor Modulator (SERM) for female ovulation induction. However, its off-label use in men has gained traction, particularly for the treatment of hypogonadotropic hypogonadism and idiopathic infertility. CC’s mechanism of action, which increases gonadotropin-releasing hormone (GnRH) secretion and subsequently elevates luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, offers a unique advantage by preserving the hypothalamic-pituitary-gonadal axis and maintaining fertility.
This article presents evidence supporting CC’s efficacy and safety in these contexts, summarizing data from systematic reviews, meta-analyses, and retrospective studies. In hypogonadotropic men, CC has been shown to significantly improve total and free testosterone levels, gonadotropin concentrations, and hypogonadism symptoms, while avoiding common complications of testosterone replacement therapy (TRT), such as secondary polycythemia. CC also demonstrated favorable outcomes in seminal parameters, including sperm concentration and motility, as well as improved pregnancy rates in idiopathic infertility cases.
Adverse effects reported with CC use include reduced energy, mood instability, and occasional visual disturbances, most of which are mild and reversible. Long-term safety data are reassuring, with rare severe adverse events such as thrombotic complications. Studies comparing CC to TRT indicate a lower risk of hematological and prostate-related complications, underscoring its safety profile.
While the evidence supports CC as a viable alternative or adjunct to TRT in specific patient populations, further research is needed to refine treatment protocols, assess long-term outcomes, and explore biofunctional sperm parameters. Overall, CC represents a promising, cost-effective therapeutic option for addressing male hypogonadism and infertility, with its integration into clinical practice guided by careful patient selection and ongoing monitoring.
Effect of Unmanned Aerial Vehicle Sprayed Herbicides on the Soil Properties and Nutrient Availability in Rabi Groundnut
Authors: Mudigiri Chandana , T. RamPrakash , B. Padmaja , G Jayasree , P.C. Latha
Published: December 2024

Herbicides are normally applied by manually operated knapsack sprayers, which are laborious, uneven and prone to human mistakes. Unmanned aerial vehicles (UAVs) are a promising agricultural spraying alternative to manual operation. Drone herbicide spraying was compared to knapsack sprayers in this study. A two year field experiment was conducted at Regional Agriculture Research Station, Research Farm, Palem, Nagarkurnool, Telangana during rabi 2022-23 and 2023-24. A ready-mix post emergence herbicide with combination of Imazethapyr 3.75% + propaquizafop 2.5% ME was applied to groundnut at 20-25 DAS. The experiment consisted of 12 treatments viz., 75% recommended dose (RD), 100% RD and 125% RD which were applied with drone using 20 and 40 L ha-1 spray fluid and sprayed from 2.0 and 2.5 m height from canopy, Checks (5) were also maintained (manual spray of 75% RD,100%RD and 125% RD, weedy check and weed free) in the experiment for comparative evaluation of drone applied and manually applied herbicides. Experiment was laid out in 3X2X2 FRBD and replicated thrice. Results of the experiment showed that application of different doses of ready mix herbicide did not significantly influence the soil physical and chemical properties observed after harvest of the crop. Similarly, the available macro-nutrient status was also not significantly influenced by drone sprayed herbicide application compared to manual spraying using knapsack sprayer.
Diversity and Characterization of Bacillus thuringiensis Strains and Cry Gene Variability in Agro-Ecological Zones of Mali
Authors: Kassogué Adounigna , Kamissoko Oumou , Dao Sognan , Diallo Kangaye Amadou , Fané Rokiatou , Coulibaly Moctar , Bagayoko Mamadou Wéléba , Traoré Atia , Babana Amadou Hamadoun
Published: December 2024

Aims: This study aimed to identify the diversity of : Bacillus thuringiensis (Bt) strains in soils from different agro-ecological zones of Mali.
Study Design: Location and duration of the study: The work was carried out in Bamako, at LaboREM-Biotech located on the Badalabougou hill.
Methodology: Soil samples were collected in the different agro-ecological zones of Mali, specifically in the localities of Bougouni, Nièna, Sikasso, Koutiala, Ségou, Faya (classified forest) and Baguinéda. To properly carry out this activity, bacteria were isolated from soil samples. The different isolates obtained from the Luria Bertani (LB) agar culture medium were identified and characterized according to their macroscopic and microscopic aspects and their metabolic profile. After biochemical characterization, the different strains selected underwent molecular characterization by PCR using specific primers for the identification of Cry genes.
Results: In this study, seventy-two bacterial strains with a characteristic appearance of Bt were isolated. Sixty-nine (69) strains were identified as Bt after biochemical characterization of the selected isolates. Results of the PCR analysis showed that: among the Bt strains analyzed, sixty-two strains contained at least of the Cry1, Cry4, Cry10, Cry11, Cry24 and Cry32 genes and form 05 large groups with high diversity. Seven Bt strains selected did not code for any of the Cry genes sought.
Conclusion: Sixty-nine Bt strains were isolated in the different agroecological zones of Mali studied. These strains were used to strengthen the Bt bank already present at LaboREM-Biotech. This study shows the existence of a strong diversity of Bts in the agroecological zones studied and provides an overview of the diversity of cry genes carried by these strains and their importance in various fields.
Complexities in Assessing Health Risks of Anabolic Steroid Abuse
Authors: Câmara Lucas Caseri
Published: December 2024

The misuse of anabolic androgenic steroids (AAS) has been linked to a broad spectrum of adverse effects, ranging from mild symptoms like acne and gynecomastia to severe health risks, including cardiovascular complications. However, establishing causality for these outcomes is hindered by significant methodological limitations in many studies, which often rely on case reports, uncontrolled cohorts, or retrospective analyses. Additionally, numerous confounding factors complicate the interpretation of results, such as the use of counterfeit or adulterated drugs, excessive dosing, prolonged use, polypharmacy, and the absence of medical oversight.
This letter raises critical considerations for analyzing the health effects of AAS misuse, emphasizing the need to account for pre-existing health conditions, drug quality, dosing regimens, and concurrent substance use. Factors such as the duration of supraphysiological dosing, lifetime exposure, and whether users were monitored by healthcare professionals are crucial in evaluating risks. The chaotic and uncontrolled context of AAS abuse, often marked by high doses and the simultaneous use of legal and illegal substances, presents significant challenges to identifying specific causal relationships.
While the dangers of prolonged, unsupervised AAS misuse are well-documented, attributing precise causality to AAS in adverse health events remains complex. This discussion underscores the importance of robust methodologies and critical evaluation in future research to better understand the health risks associated with AAS and to mitigate potential harm.
Does motivation predict return to work? A longitudinal analysis
Authors: Vanovenberghe Charlotte , Du Bois Marc , Lauwerier Emelien , Van den Broeck Anja
Published: November 2021

Objectives

Motivation for return to work (RTW) reflects the degree of willingness to resume work activities and has been shown to be a crucial factor in long-term work disability. The satisfaction of basic psychological needs and motivation as described by the Self-Determination Theory (SDT) yield associations with outcomes such as quality of life and job satisfaction. The current study is the first study to examine whether motivation and basic psychological needs are predictive for RTW outcomes at 1-year follow-up.

Methods

About 349 people with a work disability (mean = 131.32 days off work) participated in this observational longitudinal research. Quality of motivation (MAWS) and basic psychological need satisfaction and frustration (BPNSFS) were measured at baseline. At 12-month follow-up, differences in RTW were assessed in terms of (1) time until RTW, (2) partial RTW, (3) relapse within 12 months, (4) work disability longer than 12 months. Binary logistic and cox regression analyses were used.

Results

Controlled motivation regarding the former job was related to shorter time until RTW. Autonomous motivation and amotivation did not seem predictive for RTW variables. The frustration of the basic needs was related to a longer work disability, need satisfaction was not related to the RTW variables. No significant predictors for relapse and partial RTW were found.

Conclusions

The frustration of basic psychological needs was predictive for a longer work disability. Controlled motivation on the other hand predicted faster RTW, which was an unexpected direction. SDT seems to have predictive value, yet underlying mechanisms remain unclear.
Translation Control by Proteins
Authors: Goldman Emanuel
Published: November 2021

Translation control by proteins refers to the process by which protein synthesis of specific products is regulated by external
trans
‐acting proteins, often by repression and sometimes autoregulatory on the messenger ribonucleic acid (mRNA) encoding the very protein being synthesised, and also by activation in some systems. Not within the scope of this article are global regulatory systems, such as stabilising or destabilising proteins that affect eukaryotic mRNA lifetimes, or translation factors that affect protein synthesis in general. Information on these subjects may be found elsewhere in this encyclopaedia.

Key Concepts

Mechanisms discussed involve specific interactions between
trans
‐acting regulator proteins and
cis
‐acting mRNAs.

Major consequences of this interaction include repression or activation of translation.

These interactions may also lead to RNA stabilisation or destabilisation and to altered RNA superstructure.

Each system employs these interactions for unique biological purposes, such as autoregulation.

One application of these interactions is in preparing a template for replication.

These interactions may also include targeting mRNA to a specific subcellular localisation.

A sensor system for iron concentrations based on these interactions is explained.

Protein–mRNA interactions may confer tight control on expression of otherwise potentially harmful products.

They also can adjust levels of synthesis to meet the needs of the system.

These interactions have also led to the development of important biotechnology and research tools, including SELEX and three‐hybrid systems.
Control Charts for Batch Processes
Authors: Qiu Peihua , Yi Fan
Published: November 2021

Applying control charts successfully to batch processes requires the recognition of some distinguishing features of batch processing versus single‐unit processing. Traditional control charts can be modified for use in batch‐processing practice of statistical process control (SPC); however, entirely different control chart methods and practices will often be required. This article reviews the common features of batch processing and the data available to control chart practitioners from typical batch processes and suggests alternatives to standard control charts for effective process monitoring and control.
An adaptive fuzzy sliding‐mode control for regenerative braking system of electric vehicles
Authors: Mei Peng , Karimi Hamid Reza , Yang Shichun , Xu Bin , Huang Cong
Published: November 2021

This article proposes a novel fuzzy sliding‐mode control scheme under an adaptive control strategy for energy management mechanism in electric vehicles that are subject to a regenerative braking system. The effectiveness of the fuzzy logic controller is to adjust the sliding mode parameters according to the slip ratio tracking error between the optimal slip ratio and the actual slip ratio. Specifically, the proposed torque distribution strategy can integrate the best battery condition and energy recovery efficiency under the practical constraints through this control method by fixing the pneumatic braking torque and motor torque. Finally, an electric vehicle model is established in the Simulink environment to verify the applicability of the proposed control algorithm.
Hydrogels and Hydrogel Nanocomposites: Enhancing Healthcare through Human and Environmental Treatment
Authors: Gutierrez Angela M. , Frazar Erin Molly , X. Klaus Maria Victoria , Paul Pranto , Hilt J. Zach
Published: November 2021

Humans are constantly exposed to exogenous chemicals throughout their life, which can lead to a multitude of negative health impacts. Advanced materials can play a key role in preventing or mitigating these impacts through a wide variety of applications. The tunable properties of hydrogels and hydrogel nanocomposites (e.g., swelling behavior, biocompatibility, stimuli responsiveness, functionality, etc.) have deemed them ideal platforms for removal of environmental contaminants, detoxification, and reduction of body burden from exogenous chemical exposures for prevention of disease initiation, and advanced treatment of chronic diseases, including cancer, diabetes, and cardiovascular disease. In this review, three main junctures where the use of hydrogel and hydrogel nanocomposite materials can intervene to positively impact human health are highlighted: 1) preventing exposures to environmental contaminants, 2) prophylactic treatments to prevent chronic disease initiation, and 3) treating chronic diseases after they have developed.
A Glutathione Activatable Photosensitizer for Combined Photodynamic and Gas Therapy under Red Light Irradiation
Authors: Wang Ran , Xia Xiang , Yang Yanjun , Rong Xiang , Liu Ting , Su Zehou , Zeng Xiaolong , Du Jianjun , Fan Jiangli , Sun Wen , Peng Xiaojun
Published: November 2021

Although photodynamic therapy (PDT) is a promising approach for cancer therapy, most existing photosensitizers lack selectivity for tumor cells and the overexpressed glutathione (GSH) in tumor cells reduces the PDT efficiency. Therefore, designing photosensitizers that can be selectively activated within tumor cells and combine PDT with other therapeutic modalities represents a route for precise and efficient anticancer treatment. Herein, an organic activatable photosensitizer, CyI‐DNBS, bearing 2,4‐dinitrobenzenesulfonate (DNBS) as the cage group is reported. CyI‐DNBS can be uptaken by cancer cells after which the cage group is selectively removed by the intracellular GSH, resulting in the generation of SO2 for gas therapy. The reaction also releases the activated photosensitizer, CyI‐OH, that can produce singlet oxygen (1O2) under red light irradiation. Therefore, CyI‐DNBS targets cancer cells for both photodynamic and SO2 gas therapy treatments. The activatable photosensitizer provides a new approach for PDT and SO2 gas synergistic therapy and demonstrates excellent anticancer effect in vivo.
Unusual Site‐Selective Doping in Layered Cathode Strengthens Electrostatic Cohesion of Alkali‐Metal Layer for Practicable Sodium‐Ion Full Cell
Authors: Peng Bo , Chen Yanxu , Wang Feng , Sun Zhihao , Zhao Liping , Zhang Xiaolei , Wang Wentao , Zhang Genqiang
Published: November 2021

P2‐type Na0.67Ni0.33Mn0.67O2 is a dominant cathode material for sodium‐ion batteries due to its high theoretical capacity and energy density. However, charging P2‐type Na0.67Ni0.33Mn0.67O2 to voltages higher than 4.2 V (vs. Na+/Na) can induce detrimental structural transformation and severe capacity fading. Herein, stable cycling and moisture resistancy of Na0.67Ni0.33Mn0.67O2 at 4.35 V (vs. Na+/Na) are achieved through dual‐site doping with Cu ion at transition metal site (2a) and unusual Zn ion at Na site (2d) for the first time. The Cu ion doping in 2a site stabilizes the metal layer, while more importantly, the unusual alkali‐metal site doping by Zn ion serves as O2‐Zn2+O2‐ “pillar” for enhancing electrostatic cohesion between two adjacent transition metal layers, preventing the crack of active material along the a–b‐plane and restraining the generation of O2 phase upon deep desodiation. This unique dual‐site‐doped [Na0.67Zn0.05]Ni0.18Cu0.1Mn0.67O2 cathode exhibits a prominent cyclability with 80.6% capacity retention over 2000 cycles at an ultrahigh rate of 10C, demonstrating its great potential for practical applications. Impressively, the full cell devices with [Na0.67Zn0.05]Ni0.18Cu0.1Mn0.67O2 and commercial hard carbon as cathode and anode, respectively, can deliver a high energy density of 217.9 Wh kg‐1 and excellent cycle life over 1000 cycles.
Polarized Emission of Lanthanide Metal–Organic Framework (Ln‐MOF) Crystals for High‐Capacity Photonic Barcodes
Authors: Pei Ke , Wu Jie , Zhao Mei , Feng Xin , Li Yuan , Ma Ying , Li Huiqiao , Zhai Tianyou
Published: November 2021

Photonic barcodes hold great promise for applications in information storage and data encryption. However, the spectroscopic encoding of lanthanide‐based photonic barcodes reported thus far is exclusively manipulated by sophisticated external stimuli or spatially resolved lanthanide heterostructures, and still suffers from small coding space and low coding capacity. Herein, a facile approach to design high‐capacity photonic barcodes through manipulating the polarized emission of Eu3+ metal–organic framework is proposed. Thanks to the highly anisotropic crystal structure and low‐symmetry energy level splitting of Eu3+, the large degree of polarization (≈0.96) enables not only color‐tunable emission but also abundant well‐resolved sub‐barcodes. Such polarization‐sensitive emission of the crystals provides a smart encoding strategy to realize polarization‐covert sub‐barcodes, which can be further integrated into a large coding library of photonic barcodes toward high‐capacity data storage and advanced anti‐counterfeiting applications.
Modification of the Magnetic and Electronic Properties of the Graphene‐Ni(111) Interface via Halogens Intercalation
Authors: Zhou Yong , Ovcharenko Roman , Paulus Beate , Dedkov Yuriy , Voloshina Elena
Published: November 2021

Electronic decoupling of graphene from metallic and semiconducting substrates via intercalation of different species is one of the widely used approaches in studies of graphene. In the present work, the modification of the electronic and magnetic properties of graphene on ferromagnetic Ni(111) layer via intercalation of halogen atoms (X = F, Cl, Br) is studied using the state‐of‐the‐art density‐functional theory approach. It is found that in all gr/X/Ni(111) intercalation systems, a graphene layer is fully electronically decoupled from the ferromagnetic substrate; however, different kind (electron or hole) and level of doping can be achieved. Despite the extremely small magnetic moment of C‐atoms in graphene observed after halogens intercalation, the sizeable spin‐splitting up to 35 meV for the linearly dispersing graphene π bands is found. The obtained theoretical data bring new ideas on the formation of the graphene‐ferromagnet interfaces where spin polarized free‐standing graphene layer can be formed with the possible application of these systems in electronics and spintronics.
SARS‐CoV‐2 N Protein Induces Acute Kidney Injury via Smad3‐Dependent G1 Cell Cycle Arrest Mechanism
Authors: Wang Wenbiao , Chen Junzhe , Hu Dingwen , Pan Pan , Liang Liying , Wu Wenjing , Tang Ying , Huang Xiao R. , Yu Xueqing , Wu Jianguo , Lan Hui Y.
Published: November 2021

COVID‐19 is infected by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and can cause severe multiple organ injury and death. Kidney is one of major target organs of COVID‐19 and acute kidney injury (AKI) is common in critically ill COVID‐19 patients. However, mechanisms through which COVID‐19 causes AKI remain largely unknown and treatment remains unspecific and ineffective. Here, the authors report that normal kidney‐specifically overexpressing SARS‐CoV‐2 N develops AKI, which worsens in mice under ischemic condition. Mechanistically, it is uncovered that SARS‐CoV‐2 N‐induced AKI is Smad3‐dependent as SARS‐CoV‐2 N protein can interact with Smad3 and enhance TGF‐β/Smad3 signaling to cause tubular epithelial cell death and AKI via the G1 cell cycle arrest mechanism. This is further confirmed in Smad3 knockout mice and cells in which deletion of Smad3 protects against SARS‐CoV‐2 N protein‐induced cell death and AKI in vivo and in vitro. Most significantly, it is also found that targeting Smad3 with a Smad3 pharmacological inhibitor is able to inhibit SARS‐CoV‐2 N‐induced AKI. In conclusion, the authors identify that SARS‐CoV‐2 N protein is a key mediator for AKI and induces AKI via the Smad3‐dependent G1 cell cycle arrest mechanism. Targeting Smad3 may represent as a novel therapy for COVID‐19‐asscoaited AKI.
Synthesis of Stable Nonaromatic Fluorenonephyrin Macrocycle
Authors: Giri Deeksha , Yadav Bharti , Sinha Avisikta , Ravikanth Mangalampalli
Published: November 2021

A new derivative of our recently reported nonaromatic fluorenophyrin 5 named fluorenonephyrin 6 was synthesized over a sequence of six steps starting with commercially available fluorene as precursor. Our attempts to direct oxidation of 5 to 6 were not successful. Hence, we synthesized 2,7‐bis(phenyl(1H‐pyrrol‐2‐yl)methyl)‐9‐fluorenone (fluorenone tripyrrane) in five simple steps from fluorene, and condensed it with pentafluorobenzaldehyde under mild acidic conditions in CH2Cl2 followed by oxidation with DDQ and chromatographic purification to afford fluorenonephyrin (9%). 6 was characterized and studied by HR‐MS, 1D and 2D NMR spectroscopy, absorption, electrochemical and DFT/TD‐DFT techniques. The DFT studies revealed that 6 was more distorted than 5 and that introduction of C=O in the macrocyclic core remarkably distorts the pyrrole rings of the dipyrrin unit from the mean plane of macrocyclic framework. The macrocycle showed a band at around 390 nm and a broad band at around 650 nm. The redox properties indicated that the macrocycle was highly electron‐deficient in nature. TD‐DFT studies were in accordance with the experimental observations.
Where do we stand with the covariation framework in primate societies?
Authors: Thierry Bernard
Published: November 2021

Comparative study of the social systems of macaques has revealed correlated variations between species in multiple social traits such as the asymmetry of dominance relationships, preferential treatment of kin, patterns of aggression and reconciliation, modes of socialization, and access to food resources. Macaques can be classified on a scale of four categories of social styles, ranging from the least to the most tolerant species. This led to the development of the covariation framework, which addresses the constraints responsible for the linkages between social traits, and their consequences on the evolution of primate social systems. Decades of research have provided a wealth of information that supports, complements, expands, or challenges the covariation framework. In this article, I review this body of knowledge and consider covariation in its two aspects, that is, as a pattern and as a hypothesis. I first consider the extent to which social styles can be invariant, the strength of correlations between traits, and the possible extension of the framework to nonhuman primates other than macaques. I then discuss how to formulate hypotheses, identify sources of linkage between traits, make predictions about the effects of social constraints, assess the tolerance dimension of social styles, and consider the breaking of linkages between traits. Whereas socioecological studies aim to understand how adaptation to the ecological environment determines the shape of social systems, the covariation framework is a complementary research program that seeks to unravel the internal processes that restrict or channel change in social behavior.
Synthesis and characterization of 1,3‐butadiene‐containing hyperbranched conjugated polymers as a selective chemosensors for Fe3+ ions
Authors: Chen Qi , Luo Chuxin , Ma Qi , Yan Xueyang , Cai Xuediao
Published: November 2021

Hyperbranched conjugated polymers (P1, P2 and P3) containing different aryl groups appended with carboxylic ester groups were synthesized by metal‐free catalyzed polymerization via A2 + B3 type monomers. These as‐prepared polymers can be dissolved well in common organic solvents and have good thermal stability. These polymers were investigated as fluorescence chemosensor for the detection of biologically important metal ion Fe3+. The corresponding Stern‐Volmer constants (Ksv) of P1, P2 and P3 were 3.99 × 104 M−1, 5.15 × 104 M−1 and 3.99 × 104 M−1, respectively. The detection limits of 1.203 × 10−7 M for P1, 8.487 × 10−7 M for P2 and 7.158 × 10−6 M for P3 were achieved. In addition, the water‐soluble hyperbranched conjugated polymers were obtained by hydrolysis of neutral polymer P1, P2 and P3. The ability of water‐soluble polymers to detect Fe3+ ion in an aqueous solution was investigated in this work. The results demonstrated that the different aryl moieties in backbone of hyperbranched polymers mainly affected their energy band instead of their selective detection of Fe3+ ions. All the polymers were highly sensitive and selective toward Fe3+ ions in organic solvents and aqueous solution, indicating that these polymers could be used as fluorescence chemosensor for Fe3+ ions in real time.
Distributed liquid crystal reflectivity control device network for momentum wheel unloading
Authors: Ji Haoran , Huang Di , Yang Zhibo , Li Zhihui
Published: November 2021

Momentum wheels are widely used in spacecraft attitude control. However, in the space far‐away from the Earth, it is difficult for the wheels to realize unloading to maintain their control ability because of the dependance of fuel. Reflectivity control devices (RCDs) become a possible solution for fuel‐free space attitude control by generating controllable solar radiation pressure (SRP) torque. However, the control ability of RCDs is limited because the torques they produce are rather small. To combine the advantages of both the momentum wheels and the RCDs, in this paper, an attitude control scheme utilizing momentum wheels as actuators and an RCD network for unloading is proposed. Firstly, the physical composition, force model, torque model, and principles of the distributed RCD network are given. After that, a stable and reliable unloading control method based on the envelope analysis is provided. Also, a three‐axis stabilized solar sail is utilized as an example to show to control system design. Numerical simulation proved that the momentum unloading for wheels can be realized safely and efficiently.
Performance limits of network delay systems based on bandwidth and packet loss constraints
Authors: Hu Xiao , Zhan Xisheng , Wu Jie , Yan Huaicheng
Published: November 2021

In this work, we study the error limits of the network delay systems in terms of bandwidth and packet loss. The tracking error index of networked delay systems is identified by the tracking error energy. The error limits of the network delay systems are achieved by the spectral decomposition and partial decomposition techniques. The results of this work show that the tracking error limits are relevant to the inherent characteristics of the provided object (non‐minimum phase zero, time delay, and unstable pole). In addition, the packet loss, channel noise, and bandwidth also determine the error limits of the network delay systems. The simulation results show that the theory presented is valid.
Eye gaze as a biomarker in the recognition of autism spectrum disorder using virtual reality and machine learning: A proof of concept for diagnosis
Authors: Alcañiz Mariano , Chicchi‐Giglioli Irene Alice , Carrasco‐Ribelles Lucía A. , Marín‐Morales Javier , Minissi Maria Eleonora , Teruel‐García Gonzalo , Sirera Marian , Abad Luis
Published: November 2021

The core symptoms of autism spectrum disorder (ASD) mainly relate to social communication and interactions. ASD assessment involves expert observations in neutral settings, which introduces limitations and biases related to lack of objectivity and does not capture performance in real‐world settings. To overcome these limitations, advances in technologies (e.g., virtual reality) and sensors (e.g., eye‐tracking tools) have been used to create realistic simulated environments and track eye movements, enriching assessments with more objective data than can be obtained via traditional measures. This study aimed to distinguish between autistic and typically developing children using visual attention behaviors through an eye‐tracking paradigm in a virtual environment as a measure of attunement to and extraction of socially relevant information. The 55 children participated. Autistic children presented a higher number of frames, both overall and per scenario, and showed higher visual preferences for adults over children, as well as specific preferences for adults' rather than children's faces on which looked more at bodies. A set of multivariate supervised machine learning models were developed using recursive feature selection to recognize ASD based on extracted eye gaze features. The models achieved up to 86% accuracy (sensitivity = 91%) in recognizing autistic children. Our results should be taken as preliminary due to the relatively small sample size and the lack of an external replication dataset. However, to our knowledge, this constitutes a first proof of concept in the combined use of virtual reality, eye‐tracking tools, and machine learning for ASD recognition.

Lay Summary

Core symptoms in children with ASD involve social communication and interaction. ASD assessment includes expert observations in neutral settings, which show limitations and biases related to lack of objectivity and do not capture performance in real settings. To overcome these limitations, this work aimed to distinguish between autistic and typically developing children in visual attention behaviors through an eye‐tracking paradigm in a virtual environment as a measure of attunement to, and extraction of, socially relevant information.
Synthesis and characterisation of quantum dots coupled to mycolic acids as a water‐soluble fluorescent probe for potential lateral flow detection of antibodies and diagnosis of tuberculosis
Authors: Kabwe Kapambwe P. , Nsibande Sifiso A. , Lemmer Yolandy , Pilcher Lynne A. , Forbes Patricia B. C.
Published: November 2021

This work explores the potential use of cadmium‐based quantum dots (QDs) coupled to mycolic acids (MAs) as a fluorescent probe to detect anti‐MA antibodies which are biomarkers for tuberculosis (TB). The use of free MAs as antigens for the serodiagnosis of TB is known but has not been developed into a point of care test. This study focuses on the synthesis, solubility, and lateral flow of QDs coupled to MAs. Water‐soluble CdSe/ZnS QDs capped with l‐cysteine were synthesised and covalently coupled to MAs via amide linkages to form a water‐soluble fluorescent probe: MA‐CdSe/ZnS QDs. The MA‐CdSe/ZnS QDs showed broad absorption bands and coupling, confirmed by the presence of amide bonds in the Fourier‐transform infrared (FTIR) spectrum, resulting in a blue shift in fluorescence. Powder X‐ray diffraction (XRD) revealed a shift and increase in the number of peaks for MA‐CdSe/ZnS QDs relative to the L‐cys‐CdSe/ZnS QDs, suggesting that coupling changed the crystal structure. The average particle size of MA‐CdSe/ZnS QDs was ~3.0 nm. Visual paper‐based lateral flow of MA‐CdSe/ZnS QDs was achieved on strips of nitrocellulose membrane with both water and membrane blocking solution eluents. The highly fluorescent MA‐CdSe/ZnS QDs showed good water solubility and lateral flow, which are important properties for fluorescence sensing applications.
Real‐world prognostic factors for survival among treated patients with metastatic pancreatic ductal adenocarcinoma
Authors: Yu Kenneth H. , Ozer Muhammet , Cockrum Paul , Surinach Andy , Wang Shu , Chu Bong Chul
Published: November 2021

Background

Many real‐world studies of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) are restricted to single centers, limiting the generalizability of their insights. This study aimed to identify important population‐based predictors for survival in patients diagnosed with mPDAC in a broader setting.

Methods

Data between 1 January 2017 and 31 December 2019 were extracted from the Flatiron Health EHR database. Treatment‐specific predictive models were generated for patients treated with first‐line gemcitabine+nab­paclitaxel (GNP), FOLFIRINOX, gemcitabine monotherapy (gem‐mono), and second‐line liposomal irinotecan‐based regimens. The holdout method was used for cross‐validation. Age at diagnosis, sex, BMI, smoking status, and ECOG performance score were included in all models with additional demographic, clinical characteristics, and hematological function assessed for inclusion.

Results

Of the 3625 patients, 43% received GNP, 26% received FOLFIRINOX, 7% received gem‐mono, and 23% received other regimens; 40% (n = 1448) advanced to the second line. Among all first‐line patients, the following were included in the final model: prior surgery, white blood cell (WBC) counts, serum albumin (SA), liver function tests (LFTs), serum bilirubin, serum carbohydrate antigen 19–9, and ascites. Models for patients receiving specific therapies differed from the overall model, GNP (ascites removed), FOLFIRINOX (stage at initial diagnosis added), and gem‐mono (LFTs omitted). Alkaline phosphatase (ALP), SA, and WBC counts were important predictors of survival among patients treated with second‐line liposomal irinotecan. Across all regimens, the strongest predictors of survival were ECOG score, SA, and ALP.

Conclusions

In this real‐world study of patients with mPDAC, important population prognostic factors of survival were identified in a large cohort of patients receiving systemic treatment.
Convenient Immobilization of α‐L‐Rhamnosidase on Cerium‐based Metal‐Organic Frameworks Nanoparticles for Enhanced Enzymatic Activity and Recyclability
Authors: Peng Lingling , Tan Wansen , Lu Yuting , Yao Ayan , Zheng Dayuan , Li Le , Xiao Jingran , Li Lijun , Li Qingbiao , Zhou Shu‐feng , Zhan Guowu
Published: November 2021

The α‐L‐Rhamnosidase (Rha) is a useful glycoside hydrolase for selectively hydrolyzing the terminal L‐rhamnose residues in flavonoids, being vital to food and pharmaceutical industries. However, Rha suffers from low recyclability and poor stability in harsh environments. Herein, we explored five typical metal‐organic frameworks (MOFs) as porous carriers to immobilize Rha, and the activities of the resultant Rha@MOF composites were compared with the free enzyme. The locations of the enzyme in MOFs were proved by a series of characterization techniques. It was found that Rha@Ce‐BTC (with enzyme immobilization efficiency of 23 % and enzyme loading content of 8.8 %) showed the highest enzymatic activity. The immobilized Rha@Ce‐BTC showed 80 % residual activity after five consecutive cycles, suggesting a limited leaching effect. Also, Rha@Ce‐BTC manifested markedly enhanced enzyme‐substrate affinity and catalytic efficiency compared to free Rha, as supported by Michaelis‐Menten kinetic studies. Accordingly, the Ce‐BTC would be an appealing carrier for enzyme immobilization, and the as‐designed enzyme/Ce‐BTC composites are promising candidates for industrial use with remarkably high activity, recyclability, and storage stability.
Linear childhood discoid lupus erythematosus along a Blaschko's line of the arm
Authors: Toyama Tetsuo , Miyagawa Takuya , Sato Shinichi , Asano Yoshihide
Published: November 2021

Linear childhood discoid lupus erythematosus (DLE) is a rare variant of DLE with a linear distribution that preferentially occurs on the face and scalp of children. We report a rare case of linear childhood DLE on the Blaschko's line of his left upper arm of a 7‐year‐old Japanese boy with 4‐year history of the disease. He was positive for anti‐single‐stranded DNA antibodies, but still showed no systemic symptoms during the 3‐year follow‐up period. We reviewed previous reports on linear childhood DLE and found that patients with nonfacial/nonscalp skin lesions are significantly more likely to be positive for autoantibodies.
Effect of Activation Process on the Performance of ZIF‐8 Membrane for Propylene/Propane Separation
Authors: Ma Qiang , Wang Xu , Feng Shengwei , Jin Hua , Mo Kai , Li Yanshuo
Published: November 2021

Fine‐tuning the interior structure of porous materials is desirable for altering the gas transport characteristic. An activation‐induced structure manipulation strategy is reported here to act on ZIF‐8 membranes for C3H6/C3H8 separation. Notably, after treatment with methanol, acetonitrile and chloroform, the amount of embedded N,N‐dimethylacetamide (DMAc) molecules within ZIF‐8 cavity is about 0.8, 1.2 and 3.8 molecules per cage, respectively. The increased amount of DMAc results in enhanced thermodynamic adsorption selectivity of ZIF‐8 for C3H6/C3H8, which is highly constructive to the separation ability of corresponding ZIF‐8 membranes. Typically, the ZIF‐8 membranes activated with methanol, acetonitrile and chloroform demonstrate C3H6 permeance of 1.5 · 10−8, 8.5 · 10−9 and 4.3 · 10−9 mol m−2s−1Pa−1, and C3H6/C3H8 separation factors of 52, 92 and 192, respectively.
Ultrasonic Spray Pyrolysis‐assisted Fabrication of Ultrathin CuWO4 Films with Improved Photoelectrochemical Performance
Authors: Duan Xiaoyu , Xu Chong , El Nahrawy Amany M. , Chen Jing , Zhu Zhiqiang , Wang Jianmin , Liang Qinghua , Cao Feng
Published: November 2021

CuWO4 is a promising n‐type oxide semiconductor for photoelectrochemical (PEC) applications due to the suitable band gap and good photochemical stability. An easy and large‐scale fabrication of ultrathin CuWO4 films with improved PEC performance is highly desired for future practical application but still challenging. Considering that the ultrasonic spray pyrolysis approach is a low‐cost and scalable technique for fabricating films with controllable thickness, we here report the controllable fabrication of ultrathin CuWO4 films with improved PEC performance by an automatic ultrasonic spray pyrolysis method. The effects of different tungsten sources and film thickness on the PEC performance of the resultant CuWO4 film were studied in detail. We find that the ultrathin CuWO4 film prepared from the ammonium metatungstate with a thickness of 2.16 μm shows the best PEC performance of 41 μA cm−2 at 1.23 V vs.RHE for water oxidation under visible light irradiation. We also explored the different charge transfer mechanism and PEC performance of the resultant CuWO4 films under back and front illumination.
Outcomes of pediatric acute myeloid leukemia treatment in Western Kenya
Authors: van Weelderen Romy E. , Njuguna Festus , Klein Kim , Mostert Saskia , Langat Sandra , Vik Terry A. , Olbara Gilbert , Kipng'etich Martha , Kaspers Gertjan J. L.
Published: November 2021

Background

Pediatric acute myeloid leukemia (AML) is a challenging disease to treat in low‐ and middle‐income countries (LMICs). Literature suggests that survival in LMICs is poorer compared with survival in high‐income countries (HICs).

Aims

This study evaluates the outcomes of Kenyan children with AML and the impact of sociodemographic and clinical characteristics on outcome.

Methods and Results

A retrospective medical records study was performed at Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya, between January 2010 and December 2018. Sociodemographic and clinical characteristics, and treatment outcomes were evaluated. Chemotherapy included two “3 + 7” induction courses with doxorubicin and cytarabine and two “3 + 5” consolidation courses with etoposide and cytarabine. Supportive care included antimicrobial prophylaxis with cotrimoxazole and fluconazole, and blood products, if available. Seventy‐three children with AML were included. The median duration of symptoms before admission at MTRH was 1 month. The median time from admission at MTRH to diagnosis was 6 days and to the start of AML treatment 16 days. Out of the 55 children who were started on chemotherapy, 18 (33%) achieved complete remission, of whom 10 (56%) relapsed. The abandonment rate was 22% and the early death rate was 46%. The 2‐year probabilities of event‐free survival and overall survival were 4% and 7%, respectively. None of the sociodemographic and clinical characteristics were significantly associated with outcome.

Conclusion

Survival of Kenyan children with AML is dismal and considerably lower compared with survival in HICs. Strategies to improve survival should be put in place including better supportive care, optimization of the treatment protocol, and reduction of the abandonment rate and time lag to diagnosis with sooner start of treatment.
Evaluation of the Pharmacokinetic Interaction and Safety of Ubrogepant Coadministered With Esomeprazole Magnesium
Authors: Boinpally Ramesh , Lu Kaifeng
Published: November 2021

Ubrogepant is a calcitonin gene–related peptide receptor antagonist for the acute treatment of migraine. Esomeprazole magnesium increases intragastric pH, which may affect oral ubrogepant absorption. This open‐label, nonrandomized, crossover trial evaluated esomeprazole magnesium's impact on the pharmacokinetics and safety of coadministered ubrogepant in healthy adults. Participants received ubrogepant 100 mg on day 1, esomeprazole magnesium 40 mg on days 9 to 13, and ubrogepant 100 mg with esomeprazole magnesium 40 mg on day 14. No effect on ubrogepant pharmacokinetics was concluded if 90% confidence intervals of geometric mean ratios were within 80% to 125% for comparison of pharmacokinetic parameters between ubrogepant + esomeprazole magnesium versus ubrogepant alone. Thirty participants enrolled (mean age, 31.7 years; 53.3% males). Ubrogepant peak plasma concentration (Cmax) decreased 23%, time to Cmax increased by 1.5 hours, and area under the plasma concentration‐time curve was reduced by ≈10% when coadministered with esomeprazole magnesium versus ubrogepant alone. The 90% confidence interval of the geometric mean ratio for Cmax did not fall within the 80% to 125% equivalence range, but the decrease was not considered clinically meaningful. Esomeprazole magnesium coadministered with ubrogepant did not increase the incidence rate of treatment‐emergent adverse events, and interactions between the medications are likely to have limited clinical relevance.
Hierarchical community‐discovery algorithm combining core nodes and three‐order structure model
Authors: Lei Guo , Sheng Yang , Shaozi Li , Qingshou Wu
Published: November 2021

A community structure in a complex network often exhibits hierarchical characteristics. Current hierarchical community‐discovery algorithms generally consider a single node as a community during the initial stage. This approach leads to over‐fine clustering granularity, too‐deep clustering levels, and other issues. Therefore, this article proposes a hierarchical community‐discovery algorithm that combines the core nodes and the three‐order structure model. Between neighboring nodes, there is a first‐order structure. The core node is identified based on its influence, and the similarity between the core node and its neighboring nodes is defined as the second‐order structure. The nodes satisfying the second‐order structure are then formed into a friend circle. The similarity between friend circles is defined as the third‐order structure. According to this structure, the friend circles are construed as a hierarchical clustering tree (HCT) where one HCT represents a community. The HCT built by this algorithm has relatively fewer levels and exhibits a flat feature. Experimental results on both artificial and real networks show that the algorithm performs well on various indicators. Additionally, the algorithm exhibits near‐linear time complexity.
Cortisol in early childhood moderates the association between family routines and observed affective balance in children from low‐income backgrounds
Authors: Lo Sharon L. , Riley Hurley O. , Sturza Julie , Vazquez Delia M. , Rosenblum Katherine , Kaciroti Niko , Lumeng Julie C. , Miller Alison L.
Published: November 2021

The study of emotion regulation often addresses control of negative emotion. Researchers have proposed that affective balance is an indicator of emotion regulation that incorporates the role of positive emotion in the context of negative emotional experiences. Environmental and individual factors, such as family processes and biological stress regulation, are known to shape emotion regulation. The present study investigated whether child diurnal cortisol, an indicator of biological stress regulation, moderated the association between family routines and observed affective balance. Children (N = 222; M age = 4.70 years, SD = 0.60) from low‐income households provided saliva samples to measure diurnal cortisol and completed a behavioral task designed to elicit negative emotions. Affective balance was defined as the difference score between the proportion of positive and negative emotional expressions displayed during the task. A higher affective balance score indicated greater positive compared with negative emotional displays. Simple slope analyses indicated that for children with a low morning cortisol intercept, more frequent family routines were associated with more affective balance. This pattern was not observed in children with average or high morning cortisol. Positive family routines may play an important role in shaping affective balance among children with disrupted cortisol levels from low‐income backgrounds.
Sexually dichromatic hybrids between two monochromatic duck species, the Chiloé wigeon and the Philippine duck
Authors: Ottenburghs Jente , Harteman Jan
Published: November 2021

Captive bird hybrids can provide important data on certain traits, such as hybrid viability and fertility. In this paper, we describe four hybrids between the Chiloé wigeon (Anas sibilatrix) and the Philippine duck (Anas luzonica). These two species diverged about 13 million years ago and are found on different continents, making the occurrence of wild hybrids extremely unlikely. Hence, these captive hybrids provide a unique opportunity to learn more about the outcome of hybridization between these highly divergent species. One pair of hybrids mated and produced six unfertilized eggs, suggesting that hybrids between these species are infertile. Morphologically, the hybrids were slightly larger than the parental species, but had intermediate bill lengths. With regard to plumage patterns, the hybrids displayed characteristics of both parental species: Males developed the iridescent green head pattern of the Chiloé wigeon, whereas the females showed the dark crown and eye stripe of the Philippine duck. Interestingly, Chiloé wigeon and Philippine duck are both sexually monochromatic whereas the hybrids showed clear sexual dimorphism. These hybrids can thus lead to novel insights into the genetic and developmental basis of sexual mono‐ and dichromatism in ducks.