bluuebunny/crossref_metadata_2025 huggingface dataset:
The link between gut microbiome and Alzheimer's disease: From the perspective of new revised criteria for diagnosis and staging of Alzheimer's disease
Authors: Liang Yuan , Liu Congcong , Cheng Manman , Geng Lijie , Li Jing , Du Wenying , Song Minfang , Chen Nian , Yeleen Traore Aicha Noura , Song Li , Wang Xiaoni , Han Ying , Sheng Can
Published: June 2024

Over the past decades, accumulating evidence suggests that the gut microbiome exerts a key role in Alzheimer's disease (AD). The Alzheimer's Association Workgroup is updating the diagnostic criteria for AD, which changed the profiles and categorization of biomarkers from “AT(N)” to “ATNIVS.” Previously, most of studies focus on the correlation between the gut microbiome and amyloid beta deposition (“A”), the initial AD pathological feature triggering the “downstream” tauopathy and neurodegeneration. However, limited research investigated the interactions between the gut microbiome and other AD pathogenesis (“TNIVS”). In this review, we summarize current findings of the gut microbial characteristics in the whole spectrum of AD. Then, we describe the association of the gut microbiome with updated biomarker categories of AD pathogenesis. In addition, we outline the gut microbiome‐related therapeutic strategies for AD. Finally, we discuss current key issues of the gut microbiome research in the AD field and future research directions.

Highlights

The new revised criteria for Alzheimer's disease (AD) proposed by the Alzheimer's Association Workgroup have updated the profiles and categorization of biomarkers from “AT(N)” to “ATNIVS.”

The associations of the gut microbiome with updated biomarker categories of AD pathogenesis are described.

Current findings of the gut microbial characteristics in the whole spectrum of AD are summarized.

Therapeutic strategies for AD based on the gut microbiome are proposed.
Atroposelective Arene‐Forming Wittig Reaction by Phosphorus PIII/PV=O Redox Catalysis
Authors: Jana Kalipada , Zhao Zhengxing , Musies Janis , Sparr Christof
Published: June 2024

The Wittig reaction is renowned as exceptionally versatile method for converting a diversity of aldehydes and ketones into alkenes. Recently, strategies for chiral phosphine catalysis under PIII/PV=O redox cycling emerged to render this venerable transformation stereoselective. Herein, we describe that phosphine redox catalysis enables the enantioselective synthesis of pertinent biaryl atropisomers by means of a stereocontrolled arene‐forming Wittig reaction. Key to the process is the release of an endogenous base from readily accessible tert‐butyloxycarbonylated Morita–Baylis–Hillman adducts triggered by catalyst intramolecularization, permitting mild phosphine redox catalysis for atroposelective Wittig reactions. By this strategy, a broad diversity of biaryl atropisomers is obtained with up to 94 : 6 enantioselectivity.
Applying Machine Learning for Antibiotic Development and Prediction of Microbial Resistance
Authors: Panjla Apurva , Joshi Saurabh , Singh Geetanjali , Bamford Sarah E. , Mechler Adam , Verma Sandeep
Published: July 2024

Antimicrobial resistance (AMR) poses a serious threat to human health worldwide. It is now more challenging than ever to introduce a potent antibiotic to the market considering rapid emergence of antimicrobial resistance, surpassing the rate of antibiotic drug discovery. Hence, new approaches need to be developed to accelerate the rate of drug discovery process and meet the demands for new antibiotics, while reducing the cost of their development. Machine learning holds immense promise of becoming a useful tool, especially since in the last two decades, exponential growth has occurred in computational power and biological big data analytics. Recent advancements in machine learning algorithms for drug discovery have provided significant clues for potential antibiotic classes. Apart from discovery of new scaffolds, the machine learning protocols will significantly impact prediction of AMR patterns and drug metabolism. In this review, we outline power of machine learning in antibiotic drug discovery, metabolic fate, and AMR prediction to support researchers engaged and interested in this field.
Predefined‐time adaptive neural dynamic surface tracking control for high‐order nonlinear switched systems
Authors: Meng Zhu , Ma Jiawei , Wang Huanqing
Published: June 2024

In this article, the issue of adaptive predefined‐time control for high‐order switched systems is researched. Neural networks (NNs) are introduced to approximate the uncertain nonlinear functions. In particular, a novel predefined‐time convergence filter is proposed to refrain from the problem of repeated differentiation of virtual controllers. On the basis of the backstepping recursion technique and the common Lyapunov function (CLF) approach, a neural adaptive predefined‐time dynamic surface control (DSC) scheme is proposed that can demonstrate all the signals in closed‐loop systems are bounded and the tracking error can converge to a small area near zero within predefined time. The simulation results illustrate the effectiveness of the proposed control scheme.
Verformungsmonitoring von Brücken mittels berührungsloser Satellitenradarmessungen
Authors: Vorwagner Alois , Kwapisz Maciej , Leopold Philip , Ralbovsky Marian , Gutjahr Karl Heinz , Moser Thomas
Published: June 2024

Die Europäische Weltraumbehörde (ESA) stellte kürzlich freie Forschungssatellitendaten zur Verfügung. Damit sind auch Erdoberflächenverformungen berührungslos mittels Radarinterferometrie aus dem Weltraum bestimmbar. Gleichzeitig werden sensorlos viele Punkte erfasst und Zeitreihen gebildet. Die erzielte Genauigkeit, im Zentimeterbereich, reicht zwar für Messungen von Erdbewegungen aus, aber noch nicht für Bauwerke. In diesem Beitrag wird ein neues Verfahren für ein Verformungsmonitoring am Beispiel der Schottwienbrücke in Österreich demonstriert. Verwendet werden sowohl historisch aufgezeichnete Satellitendaten sowie Messdaten aus künstlich am Bauwerk angebrachten „Corner‐Reflektoren“, welche mit Fernerkundungsmethoden ausgewertet werden. Ein entwickeltes Modell kann die Bauwerktemperatur auf Basis von Netzwetterdaten sensorlos prognostizieren und zur Genauigkeitssteigerung die thermischen Brückenverformungen kompensieren. Die Jahresmessungen von 2022 zeigen im Vergleich zum Referenzsystem (digitale Schlauchwaage) eine Standardabweichung von 1,7 bis 3,0 mm sowohl mit künstlichen Corner‐Reflektoren als auch bei natürlichen Rückstreupunkten ohne Sensoren am Bauwerk. Somit können mit Satelliten gleichzeitig viele Brücken im Intervall von 6 Tagen erfasst und auch retrospektiv bis ins Jahr 2016 zurück ausgewertet werden. Bedingt durch die zeitverzögerte Prozessierung eignet sich ein Satellitenmonitoring derzeit gut für die Langzeitverformungsüberwachung von weitgespannten Brücken.
Temperature‐responsive hydrogel‐grafted vessel‐on‐a‐chip: Exploring cold‐induced endothelial injury
Authors: Shen Chong , Li Jiajie , She Wenqi , Liu Aiping , Meng Qin
Published: July 2024

Cold‐induced vasoconstriction is a significant contributor that leads to chilblains and hypothermia in humans. However, current animal models have limitations in replicating cold‐induced acral injury due to their low sensitivity to cold. Moreover, existing in vitro vascular chips composed of endothelial cells and perfusion systems lack temperature responsiveness, failing to simulate the vasoconstriction observed under cold stress. This study presents a novel approach where a microfluidic bioreactor of vessel‐on‐a‐chip was developed by grafting the inner microchannel surface of polydimethylsiloxane with a thermosensitive hydrogel skin composed of N‐isopropyl acrylamide and gelatin methacrylamide. With a lower critical solution temperature set at 30°C, the gel layer exhibited swelling at low temperatures, reducing the flow rate inside the channel by 10% when the temperature dropped from 37°C to 4°C. This well mimicked the blood stasis observed in capillary vessels in vivo. The vessel‐on‐a‐chip was further constructed by culturing endothelial cells on the surface of the thermosensitive hydrogel layer, and a perfused medium was introduced to the cells to provide a physiological shear stress. Notably, cold stimulation of the vessel‐on‐a‐chip led to cell necrosis, mitochondrial membrane potential (ΔΨm) collapse, cytoskeleton disaggregation, and increased levels of reactive oxygen species. In contrast, the static culture of endothelial cells showed limited response to cold exposure. By faithfully replicating cold‐induced endothelial injury, this groundbreaking thermosensitive vessel‐on‐a‐chip technology offers promising advancements in the study of cold‐induced cardiovascular diseases, including pathogenesis and therapeutic drug screening.
Adipogenic differentiation effect of human periodontal ligament stem cell initial cell density on autologous cells and human bone marrow stromal cells
Authors: Wang Jing , Gu Yingzhi , Sun Yaxi , Qiao Qingchen , Huang Xiaofeng , Yang Kai , Bai Yuxing
Published: June 2024

Stem cells demonstrate differentiation and regulatory functions. In this discussion, we will explore the impacts of cell culture density on stem cell proliferation, adipogenesis, and regulatory abilities. This study aimed to investigate the impact of the initial culture density of human periodontal ligament stem cells (hPDLSCs) on the adipogenic differentiation of autologous cells. Our findings indicate that the proliferation rate of hPDLSCs increased with increasing initial cell density (0.5–8 × 104 cells/cm2). After adipogenic differentiation induced by different initial cell densities of hPDLSC, we found that the mean adipose concentration and the expression levels of lipoprotein lipase (LPL), CCAAT/enhancer binding protein α (CEBPα), and peroxisome proliferator‐activated receptor γ (PPAR‐γ) genes all increased with increasing cell density. To investigate the regulatory role of hPDLSCs in the adipogenic differentiation of other cells, we used secreted exocrine vesicles derived from hPDLSCs cultivated at different initial cell densities of 50 μg/mL to induce the adipogenic differentiation of human bone marrow stromal cells. We also found that the mean adipose concentration and expression of LPL, CEBPα, and PPARγ genes increased with increasing cell density, with an optimal culture density of 8 × 104 cells/cm2. This study provides a foundation for the application of adipogenic differentiation in stem cells.
TCF12 induces ferroptosis by suppressing OTUB1‐mediated SLC7A11 deubiquitination to promote cisplatin sensitivity in oral squamous cell carcinoma
Authors: Liu Yanchun , Bai Qin , Pang Nan , Xue Jun
Published: July 2024

Chemotherapy resistance is a major obstacle to effective cancer treatment, and promotion of ferroptosis can suppress cisplatin resistance in tumor cells. TCF12 plays a suppressive role in oral squamous cell carcinoma (OSCC), but whether it participates in the regulation of cisplatin resistance by modulating ferroptosis remains unclear. Here, we found that TCF12 expression was decreased in OSCC cells compared with normal oral cells, and it was reduced in cisplatin (DDP)‐resistant OSCC cells compared with parental cells. Moreover, overexpression of TCF12 sensitized DDP‐resistant cells to DDP by promoting ferroptosis. Intriguingly, silencing TCF12 reversed the promotion effect of the ferroptosis activator RSL3 on ferroptosis and DDP sensitivity, and overexpressing TCF12 antagonized the effect of the ferroptosis inhibitor liproxstatin‐1 on ferroptosis and DDP resistance. Mechanically, TCF12 promoted ubiquitination of SLC7A11 and decreased SLC7A11 protein stability through transcriptional repression of OTUB1, thereby facilitating ferroptosis. Consistently, SLC7A11 overexpression neutralized the promotion effect of TCF12 on ferroptosis and DDP sensitivity. Additionally, upregulation of TCF12 hindered the growth of mouse OSCC xenografts and enhanced the DDP sensitivity of xenografts by inducing ferroptosis. In conclusion, TCF12 enhanced DDP sensitivity in OSCC cells by promoting ferroptosis, which was achieved through modulating SLC7A11 expression via transcriptional regulation of OTUB1.
Osteoking prevents bone loss and enhances osteoblastic bone formation by modulating the AGEs/IGF‐1/β‐catenin/OPG pathway in type 2 diabetic db/db mice
Authors: Yang Yi , Li Rong , Wang Peijin , Zhao Yulan , Li Jintao , Jiao Jianlin , Zheng Hong
Published: June 2024

Type 2 diabetic osteoporosis (T2DOP) is a skeletal metabolic syndrome characterized by impaired bone remodeling due to type 2 diabetes mellitus, and there are drawbacks in the present treatment. Osteoking (OK) is widely used for treating fractures and femoral head necrosis. However, OK is seldom reported in the field of T2DOP, and its role and mechanism of action need to be elucidated. Consequently, this study investigated whether OK improves bone remodeling and the mechanisms of diabetes‐induced injury. We used db/db mice as a T2DOP model and stimulated MC3T3‐E1 cells (osteoblast cell line) with high glucose (HG, 50 mM) and advanced glycation end products (AGEs, 100 µg/mL), respectively. The effect of OK on T2DOP was assessed using a combined 3‐point mechanical bending test, hematoxylin and eosin staining, and enzyme‐linked immunosorbent assay. The effect of OK on enhancing MC3T3‐E1 cell differentiation and mineralization under HG and AGEs conditions was assessed by an alkaline phosphatase activity assay and alizarin red S staining. The AGEs/insulin‐like growth factor‐1(IGF‐1)/β‐catenin/osteoprotegerin (OPG) pathway‐associated protein levels were assayed by western blot analysis and immunohistochemical staining. We found that OK reduced hyperglycemia, attenuated bone damage, repaired bone remodeling, increased tibial and femoral IGF‐1, β‐catenin, and OPG expression, and decreased receptor activator of nuclear kappa B ligand and receptor activator of nuclear kappa B expression in db/db mice. Moreover, OK promoted the differentiation and mineralization of MC3T3‐E1 cells under HG and AGEs conditions, respectively, and regulated the levels of AGEs/IGF‐1/β‐catenin/OPG pathway‐associated proteins. In conclusion, our results suggest that OK may lower blood glucose, alleviate bone damage, and attenuate T2DOP, in part through activation of the AGEs/IGF‐1/β‐catenin/OPG pathway.
Favipiravir‐induced bradycardia: A case report
Authors: Kashefizadeh Alireza , Ohadi Laya , Amiri Farbod , Abdolmaleki Maryam , Eslami Vahid , Jafari Fesharaki Mehrdad
Published: June 2024

Key Clinical Message

The purpose of this case report is to reveal one of the cardiovascular side effects of favipiravir, sinus bradycardia.

Favipiravir has emerged as a potential treatment for COVID‐19, with its antiviral properties showing promise in inhibiting viral replication. However, concerns regarding its safety profile, particularly its cardiac adverse effects, remain a subject of debate. We present the case of a 58‐year‐old man with a history of diabetes mellitus and chronic obstructive pulmonary disease who developed bradycardia following treatment with favipiravir for COVID‐19 pneumonia. Despite being asymptomatic, the patient exhibited sinus bradycardia, which resolved upon discontinuation of favipiravir. Favipiravir has been associated with QT prolongation and sinus bradycardia, though the exact mechanisms remain unclear. Our case adds to the growing body of evidence highlighting the potential cardiac complications of favipiravir therapy in COVID‐19 patients. Further research is warranted to clarify the underlying mechanisms and optimize patient management strategies. Clinicians should be cautious for cardiac adverse events when prescribing favipiravir for COVID‐19 treatment, especially in patients with preexisting cardiac conditions. Continued research is essential to ensure the safe and effective use of favipiravir in the management of COVID‐19.
An Overview of Carbon Dioxide Photo/Electrocatalyzed by Titanium Dioxide Catalyst
Authors: Wang Jiaman , Xiong Jing , Guo Hao , Wei Yuechang
Published: June 2024

This study provides a comprehensive review of recent advancements in photocatalytic and electrocatalytic carbon dioxide reduction using titanium dioxide catalysts. The basic concepts of light absorption, electron transport, and reduction processes are introduced in this paper, which also delves into the specifics of photocatalytic and electrocatalytic reduction of carbon dioxide. The paper highlights the key applications and benefits of titanium dioxide, including its strong stability, outstanding light absorption capacity, and good electron transport performance, in the photocatalytic and electrocatalytic reduction of carbon dioxide. Furthermore, it examines the impact of various surface modification techniques on catalytic performance, as well as the effects of various titanium dioxide catalyst forms on catalytic activity and selectivity in carbon dioxide reduction. The in‐depth analysis exhibit promising catalytic properties and hold significant potential for future advancements. However, some obstacles still need to be overcome, such as increasing catalytic activity and selectivity while minimizing energy dissipation. In order to improve catalytic performance and efficiency, future research should prioritize the optimization of structural design and surface modification techniques for catalysts. Additionally, the paper provides a scientific foundation for accomplishing sustainable carbon conversion, it also calls for additional experimental and theoretical research into the mechanism of action for titanium dioxide catalyst.
Insulin and Metformin are Associated With Reduced Risk of Amyotrophic Lateral Sclerosis
Authors: Lehrer Steven , Rheinstein Peter H.
Published: July 2024

Background

Type 2 diabetes (T2D), but not type 1, protected against amyotrophic lateral sclerosis (ALS). In T2D serum insulin is normal or elevated in the early stages. Type 1 diabetes, characterized by a total lack of insulin, is associated with an increased risk of ALS. The antidiabetic metformin also protects against ALS. Connexin 43 (Cx43), an astrocyte protein, operates as an open channel via which toxic substances from astrocytes reach motor neurons to cause ALS.

Methods

In the current study we analyzed FDA MedWatch data to determine whether insulin or metformin could reduce the risk of ALS. We performed in silico molecular docking studies and molecular dynamics simulation with Cx43 to determine if insulin or metformin dock within the Cx43 channel and can block it effectively, again reducing risk of ALS.

Results

In MedWatch, Insulin use is associated with a significantly reduced risk of ALS (Proportional Reporting Ratio 0.401). Metformin use is associated with a significantly reduced risk of ALS (PRR 0.567). The Human insulin heterodimer docked within center of the Cx43 channel, effectively blocking it. Molecular dynamics simulation showed that the block is highly stable and may be responsible for the protective effect of T2D on ALS. Metformin docks within the Cx43 channel, but the relatively small size of the metformin molecule may not allow it to obstruct the passage of toxic substances from astrocytes to motor neurons.

Conclusion

MedWatch data indicate that both insulin and metformin reduce risk of ALS. The results of our in silico docking study and molecular dynamics simulation corroborate our previous findings with Cx31. Insulin docks within the open hemichannel of hexameric Cx43, potentially blocking it. Molecular dynamics simulation showed that the block is stable and may be responsible for the protective effect of T2D and insulin on ALS.
2D‐MXene composite systems for effective photocatalytic degradation of pharmaceutical compounds
Authors: Gholap Vishwanath , Subash Alsha , Joseph Tharikha , Kandasubramanian Balasubramanian
Published: June 2024

The escalating incidence of chronic diseases and infections has driven an increase in the use of antibiotics, raising concerns regarding their disposal and presence in water sources. Antibiotic‐resistant genes (ARGs) can arise in bacteria and other microorganisms when antibiotics are present in the water. Human, plant, and animal physiological processes may be negatively impacted by extended exposure to these substances. Since MXenes are effective photocatalysts and adsorption agents, they have garnered a lot of attention in the wastewater treatment industry. While employing MXene alone typically yields inadequate results, it is advantageous to combine MXene with other materials to generate derivatives or composites. This comprehensive review meticulously examines MXene composites with various materials to enhance their photocatalytic prowess, unveiling composite systems capable of achieving an exceptional degradation efficiency of up to 99%, as exemplified by the UiO‐66/MXene composite and g‐C3N4/Ti3C2 MXene/black phosphorus heterojunction. Additionally, this paper provides critical insights into the intrinsic characteristics, synthesis methodologies, and performance efficiencies for these composites, thereby serving as an invaluable resource for researchers and practitioners in the field.
Design, analysis, and implementation of DC‐DC boost converter with new active snubber cell
Authors: Gecmez Hilal Sebnem , Ting Naim Suleyman , Sahin Yakup
Published: June 2024

In this paper, a new active snubber cell for DC‐DC boost converters is introduced for the purpose of soft switching. The introduced snubber cell ensures lossless turning‐on by zero‐voltage transition (ZVT) and turning‐off by zero‐voltage switching (ZVS) of the main switch. Besides, it enables turning‐on by ZVS and turning‐off by zero current switching (ZCS) of the main diode. None of the semiconductor power devices are subjected to extra voltage stress, and all of them operate by soft switching (SS). The converter can successfully maintain the SS even under light loads. Furthermore, the proposed converter structure is advantageous in terms of simplicity and low cost. The operating modes and theoretical analysis of the introduced converter are presented and it is validated using a prototype with a 500 W output power and at the 100 kHz switching frequency. Owing to the proposed active snubber cell, the converter efficiency is achieved as 97.2%.
REDD+ organisational arrangements and potential for sectoral integration: Evidence from Cameroon
Authors: Gakou‐Kakeu Josiane , Di Gregorio Monica , Paavola Jouni , Sonwa Denis Jean
Published: June 2024

The organisational arrangements of the Reducing Emissions from Deforestation and forest Degradation (REDD+) mechanism have been scrutinised for their capacity to support emissions reduction and promote local stakeholder participation. Yet, whether they facilitate REDD+ integration into land use sectors driving deforestation has received little attention. We assess the potential of the organisational arrangements of the Cameroonian REDD+ scheme to support sectoral integration. We draw on analysis of documentary material and conceptual literature on organisational structures for environmental integration, which distinguishes horizontal and vertical integration mechanisms with distinct features and potentials to foster integration. Our analysis reveals that the Cameroonian REDD+ scheme chaired by the environmental department and featuring a multisectoral steering committee aligns with horizontal integration. Such arrangements would infuse the REDD+ mechanism with the technical expertise of the leading department, but expose REDD+ integration to sectoral resistance and funding challenges because of the limited institutional leverage of the environmental department. The organisational reforms proposed by the national REDD+ strategy featuring the Prime Minister's leadership of the REDD+ process might enhance political support for REDD+ integration, but could expose REDD+ development to the vagaries of political shifts. We propose a hybrid organisational arrangement combining horizontal and vertical integration mechanisms, with the potential to minimise their respective weaknesses, maximise their strengths, and enhance REDD+ integration into land‐use sectors. We recommend further feasibility analyses into the applicability of the proposed arrangement to other settings.
Convenient Access to a N,N’‐bis(2,6‐terphenyl) Substituted N‐Heterocyclic Carbene
Authors: Twycross Daniel , Tan Justin , Davey Christopher J. , Leverett Anthony R. , Cole Marcus L. , McKay Alasdair I.
Published: June 2024

The efficient synthesis of a N,N’‐bis(2,6‐terphenyl) substituted N‐heterocyclic carbene (NHC) is reported. The gain in efficiency and total yield, compared to traditional synthesis, is the result of a high yielding and scalable double Suzuki coupling step, affording a 2,6‐terphenyl aniline, catalyzed by a Pd β‐diketiminate complex. A stereoelectronic study revealed the new NHC to be very similar to the only other N,N’‐bis(2,6‐terphenyl) substituted NHC. Application to the stabilization of Group 13 trihydrides gives acceptable outcomes but inferior to those observed when the bulky IPr* NHC is deployed.
Reconstructive Approach to the Regiospecific Synthesis of N9‐Alkylated Purines
Authors: Savateev Konstantin V. , Gazizov Denis A. , Slepukhin Pavel A. , Ulomsky Evgeniy N. , Rusinov Vladimir L.
Published: June 2024

A regiospecific synthesis of N9‐alkylated purines as novel acyclic nucleosides was developed. This approach is based on reconstructive methodology involving the construction of a target heterocyclic scaffold on a readily available 5‐aminotetrazole moiety, which is subsequently cleaved under reductive conditions due to azido‐tetrazole tautomerism. It appeared that the rate of reduction for the azide fragment in 6‐nitro‐7‐alkylaminotetrazolo[1,5‐a]pyrimidines is much greater than the rate of nitro group reduction. Treatment of these heterocycles with hydrogen over a palladium catalyst resulted in the formation of triaminopyrimidines in excellent yields through the reduction of both the azide and nitro group. Triaminopyrimidines were transformed into the desired N9‐alkylated purines, and an analog of the marketed drug penciclovir was synthesized by the developed method.
Chronic fatigue in the general population: Prevalence, natural course and associations with chronic pain (the HUNT pain study)
Authors: Glette Mari , Stiles Tore Charles , Woodhouse Astrid , Nilsen Tom Ivar Lund , Landmark Tormod
Published: June 2024

Background

Fatigue and pain are both prevalent and frequently co‐occur. No standard measure of fatigue exists, but most definitions include a continuum between high levels of energy and fatigue. There is limited knowledge about the course of fatigue in the general population and its association with functioning and other health outcomes. Our main aim was to identify trajectories of energy and fatigue in the general population and to investigate whether chronic pain is related to a negative prognosis of chronic fatigue.

Methods

Longitudinal latent class analysis was performed to classify 4771 individuals into trajectory groups based on five quarterly repeated measures.

Results

A five‐cluster solution was identified: ‘much energy’ (n = 1471, [31%]), ‘varying energy’ (n = 1445, [30%]), ‘some energy’ (n = 921, [19%]), ‘low energy’ [chronic moderate fatigue] (n = 852, [18%]) and ‘no energy’ [chronic severe fatigue] (n = 82, [2%]). Individuals with chronic moderate fatigue who reported chronic pain had reduced probability of improvement over the following 3 years (OR = 0.67, 95% CI [0.52, 0.88]).

Conclusions

Chronic fatigue is highly prevalent in the general population and a small proportion have chronic severe fatigue. When chronic pain co‐occurs with chronic fatigue, improvement of chronic fatigue is less likely, indicating that these symptoms may perpetuate each other.

Significance Statement

Understanding the close relationship between chronic pain and chronic fatigue is important as they both contribute to suffering and loss of functioning, may be related to the same underlying diseases, or in the absence of disease, may share common mechanisms. This study highlights the important role of chronic pain in relation to chronic fatigue, both by showing a strong association between the prevalence of the two conditions, and by showing that chronic pain is associated with a negative prognosis of chronic fatigue.
An external focus promotes motor learning of an aiming task in individuals with hearing impairments
Authors: Samadi Zahra , Abedanzadeh Rasool , Norouzi Ebrahim , Abdollahipour Reza
Published: June 2024

Research has shown that external relative to internal focus (IF) instructions may improve motor performance as well as cognitive function (e.g., attentional stability and task‐focus). The aim of the study was to examine the influence of attentional focus instructions on skill acquisition and learning of an aiming task in individuals with hearing impairments. The participants (N = 39, Mage = 17.87 ± 1.88 years) performed a bowling task with their dominant hand to knock down as many pins as possible. On day 1, they were randomly divided into three attentional focus groups; IF (focus on your throwing hand), external focus (EF) (focus on the pins), and control (no‐focus) instructions. Each participant performed 36 trials, divided into 3 blocks of 12 trials. Attentional focus instructions were given before each block, with a brief reminder provided after each 3 trials. On day 2, retention and transfer (further distance) tests were performed. Results showed that while there were no significant differences between groups in the pre‐test, the EF group outperformed both IF and control groups in retention and transfer tests. No significant difference was found between the control and IF. The findings suggest that the advantages of the external relative to the IF and no‐focus instructions may generalize to individuals with hearing impairments.
Improving Downstream Process Related Manufacturability Based on Protein Engineering—A Feasibility Study
Authors: Capito Florian , Wong Ting Hin , Faust Christine , Brand Kilian , Dittrich Werner , Sommerfeld Mark , Tiwari Garima , Langer Thomas
Published: June 2024

While bioactivity and a favorable safety profile for biotherapeutics is of utmost importance, manufacturability is also worth of consideration to ease the manufacturing process. Manufacturability in the scientific literature is mostly related to stability of formulated drug substances, with limited focus on downstream process‐related manufacturability, that is, how easily can a protein be purified. Process‐related impurities or biological impurities like viruses and host cell proteins (HCP) are present in the harvest which have mostly acid isoelectric points and need to be removed to ensure patient safety. Therefore, during molecule design, the surface charge of the target molecule should preferably differ sufficiently from the surface charge of the impurities to enable an efficient purification strategy. In this feasibility study, we evaluated the possibility of improving manufacturability by adapting the surface charge of the target protein. We generated several variants of a GLP1‐receptor‐agonist‐Fc‐domain‐FGF21‐fusion protein and demonstrated proof of concept exemplarily for an anion exchange chromatography step which then can be operated at high pH values with maximal product recovery allowing removal of HCP and viruses. Altering the surface charge distribution of biotherapeutic proteins can thus be useful allowing for an efficient manufacturing process for removing HCP and viruses, thereby reducing manufacturing costs.
Embracing Implementation Science to Enhance Fisheries and Aquatic Management and Conservation
Authors: Cooke Steven J. , Young Nathan , Alexander Steven , Kadykalo Andrew N. , Danylchuk Andy J. , Muir Andrew M. , Hinderer Julie L.M. , Cvitanovic Chris , Nguyen Vivian M.
Published: June 2024

The management and conservation of fisheries and aquatic resources are inherently applied activities. Therefore, when knowledge generated from research and monitoring, or knowledge that is held by practitioners and other actors (e.g., Indigenous elders, fishers), fails to inform those applied decisions, the persistent gap between knowledge and action is reinforced (i.e., the knowledge–action gap). In the healthcare realm, there has been immense growth in implementation science over the past decade or so with a goal of understanding and bridging the gap between knowledge and action and delivering on evidence-based decision making. Yet, within fisheries and aquatic sciences, the concept of implementation science has not received the same level of attention. We posit, therefore, that there is an urgent need to embrace implementation science to enhance fisheries and aquatic management and conservation. In this paper, we seek to describe what implementation science is and what it has to offer to the fisheries and aquatic science and management communities. For our context, we define implementation science as the scientific study of processes and approaches to promote the systematic uptake of research and monitoring findings and other evidence-based practices into routine practice and decision making to improve the effectiveness of fisheries management and aquatic conservation. We explore various frameworks for implementation science and consider them in the context of fisheries and aquatic science. Although there are barriers and challenges to putting implementation science into practice (e.g., lack of capacity for such work, lack of time to engage in reflection, lack of funding), there is also much in the way of opportunity and several examples of where such efforts are already underway. We conclude by highlighting the research needs related to implementation science in the fisheries and aquatic science realm that span methodological approaches, albeit a common theme is the need to involve practitioners (and other relevant actors) in the research. By introducing the concept and discipline of implementation science to the fisheries and aquatic science community, our hope is that we will inspire individuals and organizations to learn more about how implementation science can help deliver on the promise of evidence-based management and decision making and narrow the gap between research and practice.
Does college selectivity reduce obesity? A partial identification approach
Authors: Brunello Giorgio , Christelis Dimitris , Sanz‐de‐Galdeano Anna , Terskaya Anastasia
Published: June 2024

We use data from the National Longitudinal Study of Adolescent to Adult Health to investigate whether the quality of tertiary education ‐measured by college selectivity‐causally affects obesity prevalence in the medium run (by age 24–34) and in the longer run (about 10 years later). We use partial identification methods, which allow us, while relying on weak assumptions, to overcome the potential endogeneity of college selectivity as well as the potential violation of the stable unit treatment value assumption due to students interacting with each other, and to obtain informative identification regions for the average treatment effect of college selectivity on obesity. We find that attending a more selective college causally reduces obesity, both in the medium and in the longer run. We provide evidence that the mechanisms through which the impact of college selectivity on obesity operates include an increase in income, a reduction in physical inactivity and in the consumption of fast food and sweetened drinks.
Effects of atypical antipsychotics on serum asprosin level and other metabolic parameters in patients with schizophrenia
Authors: Amini Kiumarth , Motallebi Mohammad‐Javad , Bakhtiari Kimia , Hajmiri Minoo Sadat , Zamanirafe Maryam , Sharifikia Mahdis , Ranjbar Akram , Keshavarzi Amir , Mirjalili Mahtabalsadat , Mehrpooya Maryam
Published: June 2024

Background

In this cross‐sectional study, we compared fasting serum asprosin levels and metabolic parameters between patients receiving one of three atypical antipsychotics (olanzapine, risperidone, or aripiprazole) and healthy subjects.

Methods

The study population included 62 adult outpatients with schizophrenia and 22 healthy controls, matched for age and gender. Patients were in remission and had been on stable monotherapy with one of these atypical antipsychotics for over 6 months. Body Mass Index (BMI) and fasting serum levels of asprosin, glucose, HA1c, insulin, and lipid profile were compared across the investigated groups. Additionally, the number of participants meeting the insulin resistance criterion, defined as homeostasis model assessment for insulin resistance (HOMA‐IR) >2.5, as well as the number of participants with elevated BMI levels (men >27 kg/m2, women >25 kg/m2) were compared among the groups.

Results

We observed statistically significant differences in BMI and fasting serum levels of glucose, HA1c, insulin, triglyceride (TG), high‐density lipoprotein cholesterol, and asprosin among patients receiving olanzapine or risperidone, as compared to those receiving aripiprazole and healthy subjects. Patients on aripiprazole exhibited values comparable to healthy subjects, whereas those on risperidone or olanzapine showed significantly higher values, with the highest observed in the olanzapine group. Additionally, the prevalence of participants meeting the insulin resistance criterion and those with elevated BMI was also greater in individuals receiving olanzapine or risperidone compared to those on aripiprazole and healthy subjects. Serum asprosin levels showed a significant positive correlation with BMI and several metabolic parameters, including HbA1c, fasting insulin, HOMA‐IR, and TG. No significant differences were observed among the investigated groups in terms of serum levels of total cholesterol and low‐density lipoprotein cholesterol.

Conclusions

Our cross‐sectional study highlights the association between elevated asprosin levels, weight gain, and metabolic disorders in patients treated with olanzapine and risperidone. Given the bidirectional nature of the relationship between serum asprosin levels and these metabolic disturbances, further research is warranted to elucidate potential causative pathways.
Inundation dynamics in seasonally dry floodplain forests in southeastern Brazil
Authors: Meyer Oliveira Aline , van Meerveld Ilja , Gianasi Fernanda Moreira , Maciel Silva‐Sene André , Farrapo Camila Laís , de Carvalho Araújo Felipe , Oliveira Fernanda , Aparecido Silva Ferreira Leony , Carolina Arantes da Silva Lidiany , Gama Reis Miguel , Vieira Pompeu Patricia , Manoel dos Santos Rubens
Published: June 2024

Floodplains are one of the most threatened ecosystems. Even though the vegetation composition in floodplain forests is expected to reflect the variation in groundwater levels and flood duration and frequency, there is little field data on the inundation dynamics (e.g., the variability in flood duration and flood frequency), especially for the understudied seasonally dry tropics. This limits our understanding of these ecosystems and the mechanisms that cause the flooding. We, therefore, investigated six floodplain forests in the state of Minas Gerais in Brazil for 1.5 years (two wet seasons): Capivari, Jacaré, and Aiuruoca in the Rio Grande basin, and Jequitaí, Verde Grande, and Carinhanha in the São Francisco basin. These locations span a range of climates (humid subtropical to seasonal tropical) and biomes (Atlantic forest to Caatinga). At each location, we continuously measured water levels in five geomorphologically distinct eco‐units: marginal levee, lower terrace, higher terrace, lower plain, and higher plain, providing a unique hydrological dataset for these understudied regions. The levees and terraces were flooded for longer periods than the plains. Inundation of the terraces lasted around 40 days per year. The levees in the Rio Grande basin were flooded for shorter durations. In the São Francisco basin, the flooding of the levees lasted longer and the water level regime of the levees was more similar to that of the terraces. In the Rio Grande basin, flooding was most likely caused by rising groundwater levels (i.e., “flow pulse”) and flood pulses that caused overbank flooding. In the São Francisco basin, inundation was most likely caused by overbank flooding (i.e., “flood pulse”). These findings highlight the large variation in inundation dynamics across floodplain forests and are relevant to predict the impacts of changes in the flood regime due to climate change and other anthropogenic changes on floodplain forest functioning.
Federal economic data on local and regional food producers
Authors: Bauman Allison , Jablonski Becca B. R. , Yeh D. Adeline , Chenarides Lauren , Thilmany McFadden Dawn
Published: July 2024

US local and regional food systems (LRFS) garner significant support from the federal government. Congress has directed the US Department of Agriculture to collect data on farmers and ranchers that use these markets, but challenges remain. We provide information about the three national surveys that provide farm‐level data on sales through LRFS, including how questions have changed over time. We highlight the benefits and challenges of using each survey from scale/scope and producer implication perspectives and offer recommendations to improve the existing survey instruments to support enhanced economic understanding of the implications of local and regional food markets.
14‐3‐3 Family of Proteins: Biological Implications, Molecular Interactions, and Potential Intervention in Cancer, Virus and Neurodegeneration Disorders
Authors: Low Zheng Yao , Yip Ashley Jia Wen , Chan Alvin Man Lung , Choo Wee Sim
Published: July 2024

The 14‐3‐3 family of proteins are highly conserved acidic eukaryotic proteins (25–32 kDa) abundantly present in the body. Through numerous binding partners, the 14‐3‐3 is responsible for many essential cellular pathways, such as cell cycle regulation and gene transcription control. Hence, its dysregulation has been linked to the onset of critical illnesses such as cancers, neurodegenerative diseases and viral infections. Interestingly, explorative studies have revealed an inverse correlation of 14‐3‐3 protein in cancer and neurodegenerative diseases, and the direct manipulation of 14‐3‐3 by virus to enhance infection capacity has dramatically extended its significance. Of these, COVID‐19 has been linked to the 14‐3‐3 proteins by the interference of the SARS‐CoV‐2 nucleocapsid (N) protein during virion assembly. Given its predisposition towards multiple essential host signalling pathways, it is vital to understand the holistic interactions between the 14‐3‐3 protein to unravel its potential therapeutic unit in the future. As such, the general structure and properties of the 14‐3‐3 family of proteins, as well as their known biological functions and implications in cancer, neurodegeneration, and viruses, were covered in this review. Furthermore, the potential therapeutic target of 14‐3‐3 proteins in the associated diseases was discussed.
Loading thionine onto MXene enhances electron transfer and ultrasensitive electrochemical detection of H2O2
Authors: Dong Shaoqing , Sun Yue , Liu Teng , Wu Yongzheng , Song Wenxu , Zhou Qing
Published: June 2024

As an important reactive oxygen species (ROS) signal molecule in plant physiological regulation, H2O2 maintains cellular homeostasis through concentration regulation. It is worth paying attention to the concentration imbalance of H2O2 caused by various stresses, resulting in programed cell death or even developmental arrest in plants. To accurately quantify alterations in H2O2 concentration induced by these stress factors, and deeply understand the H2O2‐related physiological processes, a highly efficient hybrid electrode material of thionine@Ti3C2Tx (Th@MXene) composite was developed. MXene nanosheets not only performed as carriers with high specific surface area for loading Th but also contributed to the enhancement of electrical conductivity. Meanwhile, Th was uniformly loaded on the MXene surface, facilitating electron transport from the analyte to the modified electrode. Under the optimal detection conditions, the sensing electrode (Th@MXene/GCE) was employed to quantify H2O2 through Square‐wave Voltammetry signals with a good linear relationship (correlation coefficient is 0.9997), and a wide calibration range of the sensor was 0.1 to 10,000 nM. Above all, the detection limit can be as low as 34 pM, demonstrating excellent sensitivity. Additionally, the sensor exhibited repeatability in real samples, demonstrating exceptional practicality.
Arts and psychomotor therapies in personality disorder treatment: An appropriate therapeutic entrance to personal development: A commentary
Authors: Haeyen Suzanne , Dimaggio Giancarlo
Published: June 2024

Personality disorders (PD) are based not just on maladaptive ideas about self and others, they also are grounded on embodied patterns of behaviors and reactions to interpersonal stressors. There is growing interest in working with the body and through the body so to address automatisms that lead to suffering and dysfunctional social action. In this issue of the Journal of Clinical Psychology: In‐Session the use of art and psychomotor therapies for these patients was explored by seven different clinical perspectives. Patients described presented with different PD and associated symptoms. The arts and psychomotor therapies deployed in personality disorder treatment are: (visual) art therapy, music therapy, drama therapy, dance (movement) therapy, and psychomotor therapy making psychotherapeutic use of the different modalities: art, music, play, role‐play, performance, improvisation, dance, body awareness and movement. Interventions provide kinesthetic, sensory, perceptual, and symbolic opportunities to invite alternative modes of meaning‐making, accessing own needs and wishes, and communicating them to others. In this commentary we summarize some of the different topics covered by the clinical‐based papers, including working mechanisms of arts and psychomotor therapies, the importance of bottom‐up emotion regulation processes, how to treat trauma in the presence of a PD, how to integrate art and psychomotor therapies in a fine‐grained formulation and how to understand the process of change. Although there is a need for more empirical research, we hope this issue makes a solid case that clinicians can effectively include art and psychomotor therapies when treating the full range of PD.
IGF2 promotes the differentiation of chicken embryonic myoblast by regulating mitochondrial remodeling
Authors: Zhao Changbin , Hu Bowen , Zeng Xiaoyin , Zhang Ze , Luo Wen , Li Hongmei , Zhang Xiquan
Published: July 2024

Skeletal muscle is crucial for animal movement and posture maintenance, and it serves as a significant source of meat in the livestock and poultry industry. The number of muscle fibers differentiated from myoblast in the embryonic stage is one of the factors determining the content of skeletal muscle. Insulin‐like growth factor 2 (IGF2), a well‐known growth‐promoting hormone, is crucial for embryonic and skeletal muscle growth and development. However, the specific molecular mechanism underlying its impact on chicken embryonic myoblast differentiation remains unclear. To elucidate the molecular mechanism by which IGF2 regulates chicken myoblast differentiation, we manipulated IGF2 expression in chicken embryonic myoblast. The results demonstrated that IGF2 was upregulated during chicken skeletal muscle development and myoblast differentiation. On the one hand, we found that IGF2 promotes mitochondrial biogenesis through the PGC1/NRF1/TFAM pathway, thereby enhancing mitochondrial membrane potential, oxidative phosphorylation, and ATP synthesis during myoblast differentiation. This process is mediated by the PI3K/AKT pathway. On the other hand, IGF2 regulates BNIP3‐mediated mitophagy, clearing dysfunctional mitochondria. Collectively, our findings confirmed that IGF2 cooperatively regulates mitochondrial biogenesis and mitophagy to remodel the mitochondrial network and enhance mitochondrial function, ultimately promoting myoblast differentiation.