bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling the tau puzzle: a review of mechanistic targets and therapeutic interventions to prevent tau pathology in Alzheimer’s disease
Authors: Kammula Sachin , Tripathi Sulagna , Wang Ning , Dawson Valina L. , Dawson Ted M. , Mao Xiaobo
Published: October 2023

Alzheimer’s disease (AD) is a prevalent neurodegenerative disease characterized by irreversible neural degeneration and cognitive decline. The prion-like propagation of the β-amyloid (Aβ) and tau proteins leads to the formation of protein plaques and, subsequently, neuronal dysfunction, contributing significantly to AD pathogenesis. Although effective AD treatments remain elusive, targeting tau protein aggregation has emerged as a promising therapeutic approach. However, recent anti-tau antibody trials have shown limited success in improving cognition, underscoring the need for a more advanced, multifaceted approach to address multiple mechanisms of tau pathology. This review examines the role of tau protein in the context of AD, with a particular focus on potential therapeutic interventions. Emphasis is placed on the modulation of tau protein expression, tau post-translational modifications and aggregation, receptor-mediated uptake and extracellular release pathways, neural inflammatory response pathways, intercellular organelle exchange, mitochondrial function, microtubule stability, and nuclear factor expression as critical intervention points. Despite the challenges faced in ongoing anti-tau clinical efforts, a comprehensive strategy targeting multiple pathways involved in tau pathology, by using either combinations of existing drugs or novel multitarget drugs, holds promise. By gaining a deeper understanding of the complex mechanisms underlying tau pathology, researchers can develop innovative therapeutic strategies to combat AD.
Essential tremor and ageing
Authors: Niemann Nicki , Shill Holly A.
Published: October 2023

Essential Tremor (ET) is a very common neurological condition that increases with age. Tremor progresses in severity and body distribution with aging. Patients with ET may develop clinical signs of cerebellar dysfunction. Other neurological signs may be seen as well, but their association with ET has not been fully solidified. Pathological changes in the cerebellum are seen with ET, although describing ET as a neurodegenerative disease is still premature. Links to other neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease can be seen but may simply reflect co-incidental co-morbidities of aging.
TINJAUAN PUSTAKA SISTEMATIS: PREDIKSI PRESTASI BELAJAR PESERTA DIDIK DENGAN ALGORITMA PEMBELAJARAN MESIN
Authors: Rajagukguk Sabar Aritonang
Published: October 2023

Penggunaan data profil dan capaian pemelajaran peserta didik dengan pembelajaran mesin untuk memprediksi prestasi belajar peserta didik akan memberi kontribusi penting bagi penyusunan strategi yang tepat dalam peningkatan prestasi belajar. Artikel ini menampilkan tinjauan pustaka sistematis (systematic literature review) terhadap 15 artikel penelitian yang mengimplementasikan algoritma pembelajaran mesin untuk memprediksi prestasi belajar peserta didik. Hasilnya adalah pembelajaran mesin relevan digunakan dalam memprediksi prestasi belajar peserta didik; sementara empat algoritma yang paling sering digunakan untuk memprediksi prestasi belajar peserta didik adalah ANN, Naïve Bayes, Logistic Regression, SVM dan Decision Tree. Temuan lain adalah bahwa pemangku kepentingan yang paling mendapat manfaat dari penelitian sejenis adalah lembaga pendidikan, dan jenis algoritma pembelajaran mesin yang paling banyak digunakan adalah jenis algoritma untuk klasifikasi.
First scientific research on common bottlenose dolphins in the Calabrian (Italy) Ionian Sea
Authors: Menniti Maria Assunta , Vella Adriana , Alessi Jessica
Published: October 2023

Bottlenose dolphins (Tursiops truncatus) suffer from multiple anthropogenic pressures due to their habitat preference in coastal waters. As this vulnerable species is protected under the European Habitats Directive and various other conventions (Bern, Barcelona, Bonn) and agreements (ACCOBAMS), it requires MPAs (such as SCIs—Sites of Community Importance and SACs—Special Areas of Conservation) for their protection. Bottlenose dolphin research carried out in the stretch of the Southern Ionian Sea, between Brancaleone and Botricello, has reduced the gap in knowledge about the presence and distribution of cetacean species in this region. The first year-long study, in 2019, was developed through the regional operational program 2014–2020, 6.5.a.1-sub-action 2 “Conserving, restoring and protecting habitats and species of the Natura 2000”. The project involved a multi-action approach including scientific field research, citizen science in order to increase the knowledge and awareness regarding the marine environment and dolphins’ conservation, and removal of the marine litter in the SAC Fondali di Stalettì in order to reduce the negative impact these could have on the health of the bottlenose dolphins (entrapment in abandoned fishing ghost nets, plastic ingestion, etc.). Preliminary results on the presence and distribution of bottlenose dolphins scientifically investigated year-round are presented here. Similar scientific studies are necessary for cetacean protection providing necessary knowledge for the institution of marine protected areas (MPAs) and monitoring for effective conservation of marine mammals.
Rethinking Human and Machine Intelligence through Kant, Wittgenstein, and Gödel
Authors: Lee Jae Jeong
Published: October 2023

This paper proposes a new metaphysical framework for distinguishing between human and machine intelligence. By drawing an analogy from Kant’s incongruent counterparts, it posits two deterministic worlds -- one comprising a human agent and the other comprising a machine agent. Using ideas from Wittgenstein and Gödel, the paper defines “deterministic knowledge” and investigates how this knowledge is processed differently in those worlds. By postulating the distinctiveness of human intelligence, this paper addresses what it refers to as “the vantage point problem” – namely, how to make a qualitative distinction between the determinist and the universe where the determinist belongs.
Quality Assessment of Condensate Water Generating from Air Conditioning Units
Authors: Khan Mohammad Osman
Published: October 2023

The increasing demand for water resources in urban areas, such as Bangladesh, due to population growth is a significant concern. One potential solution under consideration is the use of air conditioning (AC) condensate water. A study conducted at the European University of Bangladesh (EUB) focused on assessing the quality and quantity of AC condensate water from various systems. The results indicate that the collected water generally adhered to the quality standards established for drinking and household use in Bangladesh. Parameters such as pH (averaging 6.8), turbidity (1.08 NTU), total dissolved solids (TDS) (averaging 219 mg/L), iron content (0 mg/L), alkalinity (averaging 41.67 mg/L), arsenic (0 mg/L), chemical oxygen demand (COD) (averaging 3.67 mg/L), biochemical oxygen demand (BOD) (averaging 1.33 mg/L), chloride content (averaging 30.77 mg/L), and other factors were evaluated. Moreover, the AC units at EUB, varying in cooling capacity (1 ton, 2 tons, and 4 tons), produced substantial monthly volumes of 96, 177, and 354 liters of condensate water, respectively. This underscores the potential of AC condensate water as a valuable resource for addressing urban water scarcity. As a result, there is a pressing need for local decision-makers and policymakers to establish well-defined guidelines for the effective utilization of AC condensate water to mitigate water scarcity issues in urban areas.
Rare Bipolaris Species Fungal Periprosthetic Hip Infection in an Immunocompetent Host
Authors: Tummala Sailesh V. , Lin Eugenia , Mujahed Tala , Beauchamp Christopher P. , Blair Janis E. , Goulding Krista A.
Published: October 2023

Case:

We present a case report of a 64-year-old man who developed a rare Bipolaris species fungal periprosthetic joint infection (PJI) after revision arthroplasty for complications associated with a metal-on-metal total hip arthroplasty. The patient underwent a 2-stage debridement with antibiotic bead placement and implant retention, along with chronic antifungal suppression. At the 2-year follow-up, the patient remained asymptomatic.

Conclusion:

Fungal PJI with filamentous fungi such as Bipolaris species is a rare clinical entity. This case report highlights the clinical presentation and management of this rare condition.
Surgical Management of Recurrent Plexiform Neurofibroma in a Pediatric Patient with Severe Cervical Kyphotic Deformity: A Case Report
Authors: Jung Solji , Kang Dongho , Kim Donghwan , Lee Sang Hyub
Published: October 2023

Approximately 50% of patients with neurofibromatosis type 1 (NF1) develop orthopedic complications, and spinal deformities are common manifestations. Cervical kyphosis is comparatively rare in NF1; however, it results in spinal cord compression associated with paralysis and respiratory dysfunction, requiring surgical correction. Pediatric patients with NF1 usually have small and defective pedicles or lateral masses, and surgery with a single approach is limited to ensure sufficient spinal cord decompression and deformity correction. However, no reliable treatment guidelines are available for this challenging condition. This case report presents a 7-year-old patient with NF1 who had severe cervical kyphosis with intradural extramedullary neurofibromas. The tumors were removed before correcting the deformity to decompress the spinal cord and reduce the risk of spinal cord injury. Moreover, we effectively corrected and stabilized the kyphosis using the anterior-posterior-anterior approach.
Valorisation of prawn carapace waste by Exiguobacterium sp GM010 for pilot scale pigment production and its safety efficacy in Wistar rats
Authors: Mekalaa Krishna Prashanth , Peddha Muthukumar , DHALE MOHAN
Published: October 2023

Purpose
Utilisation of prawn carapace hydrolysate by Exiguobacterium sp GM010 for the growth and bioactive pigment production as fermentative substrate. To produce the pigment in pilot scale, the culture conditions were optimized and safety efficacy studies of the pigment were evaluated for commercial application in food and nutraceutical industries.
Methods
Exiguobacterium sp GM010 was grown in prawn carapace (biowaste) hydrolysate as fermentative substrate in a 10L medium using a 15L capacity fermentor. Based on our previous studies, fermentation parameters were set (pH 8.0, 30˚C, five days) by varying the aeration (0.5 to 3.0L min− 1). The pigment produced was quantitatively and qualitatively analysed in comparison with pigment produced in lab scale fermentation. Both acute (OECD 423) and sub-acute (OECD 427) toxicity studies were performed to determine its safety efficacy.
Results
The biomass and pigment extract yield were 28.76 ± 1.78 and 0.82 ± 0.04 g/L, respectively, at 1.5 L of aeration and higher than other aeration concentrations. The UV-visible spectrum of pigment extract revealed the absorption peak at 357, 466, and 491nm. The colour distribution of pigment was in the yellowish-orange region of the CIE Lab spectrum. Similar qualitative and quantitative pigment characteristics were observed in the fermentor and flask. The acute and sub-acute toxicity of the pigment extract confirmed no significant changes in feed intake, body weight (bw) gain and relative vital organ weight in Wistar rats. Similarly, no significant changes in biochemical and haematological parameters at 250, 500 and 1000 mg kg− 1 bw confirmed no sign of toxicity. Histopathological examination of all the vital organs was regular. Serum biochemistry results of the treated and control groups have shown insignificant changes.
Conclusion
Prawn carapace hydrolysate can be valorised on a pilot scale to produce Exiguobacterium sp GM010 pigment. Further, the pigments so produced were found to be non-toxic to Wistar rats, indicating its potential use as food additives and nutraceuticals.
Interaction-aware 3D Molecular Generative Framework for Generalizable Structure-based Drug Design
Authors: Kim Woo Youn , Zhung Wonho , Kim Hyeongwoo
Published: October 2023

Deep generative modeling has a strong potential to accelerate drug design. However, existing generative models often face challenges in generalization due to limited data, leading to less innovative designs and unfavorable interactions with target proteins. To address these issues, we propose an interaction-aware 3D molecular generative framework with its conditional generative model named DeepICL. By leveraging the universal nature of protein-ligand interactions, our model can achieve a generalizable structure-based drug design even with a small experimental dataset. Our framework's generalization ability is comprehensively assessed by analyzing generated ligands for unseen targets in terms of binding pose stability, affinity, geometric patterns, diversity, and novelty. The successful design of mutant-selective inhibitors further manifests the impact of our interaction-aware conditional generation approach in real-world applications.
Environmental Impact Assessment of Steel Reinforcing Bar Manufacturing Process from Scrap Materials by applying Life Cycle Assessment Method: A Case Study on the Ethiopian Metal Industries
Authors: Fente Tefera Eniyew , Tsegaw Assefa Asmare
Published: October 2023

A clear understanding of the major environmental impacts of steelmaking from scraps, as well as potential solutions involving a circular economy paradigm, is essential. This study is conducted to pave the way for using life cycle assessment (LCA) to have sustainable development and effective resource management by evaluating the environmental impacts of the steel rebar manufacturing process using secondary resources. This is a cradle-to-gate LCA that includes scrap collection and sorting, transportation, melting, continuous casting, billet reheating, and reinforcing bar rolling. Inventory data is acquired as primary data from the factory and secondary data from the SIMAPRO-integrated eco-event database. All of the analyses in this LCA were conducted using the Recipe midpoint and endpoint impact assessment techniques taking one-ton reinforcing bar production as reference flow. The global warming potential created during the manufacturing process is recorded as 467 kgCO2 eq in the environmental impact report. By moving hot billet directly to the rolling mill and using an efficient transportation system, the environmental impact of global warming potential can be reduced nearly 50%.
Twenty-six years of phytoplankton pigments reveal a circumpolar Class Divide around the Southern Ocean
Authors: Hayward Alexander , Pinkerton Matt , Wright Simon , Gutierrez-Rodriguez Andres , Law Cliff
Published: October 2023

Regional taxonomic variation of phytoplankton communities in the Southern Ocean remains largely uncharacterised despite the distinct trophic and biogeochemical roles of different taxa in anthropogenic carbon uptake, biogeochemical processes, and the support of fisheries. We analysed 26 years of pigment data (14,824 publicly available samples between 32°S and the Antarctic coast) from over 50 oceanographic voyages (1996 – 2022), using the phytoclass software, representing the largest analysis of Southern Ocean phytoplankton pigments to date. The analysis showed that the Antarctic Polar Front (APF) separates phytoplankton communities between diatom and haptophyte domination, confirming a biological analogue to the recognised Biogeochemical Divide in regional carbon dioxide flux and global export production. Furthermore¸ community composition was remarkably similar south of the APF despite significant spatial variation in biomass. These insights into the geospatial distribution of phytoplankton community composition will improve modelling and projection of future change in ecosystems, carbon and nutrient dynamics in the Southern Ocean.
Comparison of the effect of dexmedetomidine intrathecal injection and intravenous infusion on subarachnoid blockade during knee arthroscopy procedures
Authors: Liu Shujiao , Sun Yaorui , Wang Yewen , Sun Chao , Zhang Quanyi
Published: October 2023

Background: Comparison of whether intrathecal dexmedetomidine prolongs spinal anesthesia-associated sensorimotor blockade more than intravenous infusion during knee arthroscopy procedures performed under subarachnoid block.
Methods: Ninety patients aged 18-75 years, ASA class I-II, who underwent knee arthroscopy between October 2022 and April 2023 were randomized into intrathecal、intravenous and control groups.Subjects received three modes of administration: an intrathecal group (2ml of 1% ropivacaine + 5μg of dexmedetomidine，with saline pumped intravenously at a dose of 0.5μg/kg/h), an intravenous group (intrathecal 2ml of 1% ropivacaine +1ml of 0.9% saline, with dexmedetomidine pumped intravenously at a dose of 0.5μg/kg/h), and a control group (intrathecal 2ml of 1% ropivacaine + 1ml of 0.9% saline, with saline pumped intravenously at a dose of 0.5μg/kg/h). Total analgesic duration, duration of sensory and motor blockade, Ramsay sedation score, Visual Analogue Score (VAS) at different postoperative time points, and occurrence of adverse effects were recorded.
Results：The total analgesia duration was significantly longer in the intrathecal group than in the intravenous and control groups (352.13±51.70min VS 273.47±62.57min VS 241.41±59.22min，P<0.001).The duration of sensory block was shorter in the intrathecal group than in the intravenous and control groups (4 [3-4]min VS 5 [4-5]min VS 5 [4-5]min；P<0.001);the duration of motor block was shorter in the intrathecal group than in the intravenous group and the control group (5 [4-5]min VS 5 [5-6]min VS 6[5.5-7]min；P<0.001).Sedation scores were higher in the intravenous group than in the intrathecal and control groups (P < 0.001). At 5 hours postoperatively, the VAS score in the intrathecal group was smaller than that in the intravenous and control groups (P<0.001). At 24 hours postoperatively, the VAS score in the intrathecal group was smaller than that in the control group (P < 0.001). In addition, the incidence of bradycardia was significantly higher in the intravenous group than in the intrathecal and control groups (30%, 6.5%, and 3.4%, respectively; P=0.018，P=0.007).
Conclusions：Intrathecal administration of dexmedetomidine did prolong the total analgesia duration, as well as accelerate the onset of sensory-motor blockade compared with intravenous pumping, and did not result in any hemodynamic instability or other adverse events at the doses studied.
Trial registration:This single-center, prospective, RCT has completed the registration of the Chinese Clinical Trial Center at 26/09/2023 with the registration number ChiCTR2300076170.
Interface states of metal‒oxide‒semiconductor devices based on aligned carbon nanotube arrays
Authors: Zhang Zhiyong , Liu Yifan , Ding Sujuan , Li Weili , Zhang Zirui , Pan Zipeng , Ze Yumeng , Gao Bing , Zhang Yanning , Jin Chuanhong , Peng Lian-Mao
Published: October 2023

A deep understanding of the interface states in metal-oxide-semiconductor (MOS) structures is the premise of improving the gate stack quality, which sets the foundation for building field-effect transistors (FETs) with high performance and high reliability. Although MOSFETs built on aligned semiconducting carbon nanotube (A-CNT) arrays have been considered ideal energy-efficient successors to commercial silicon (Si) transistors, research on the interface states of A-CNT MOS devices, let alone their optimization, is lacking. Here, we fabricate MOS capacitors based on an A-CNT array with a well-designed layout and accurately measure the capacitance-voltage and conductance-voltage (C-V and G-V) data. Then, the gate electrostatics and the physical origins of interface states are systematically analysed and revealed. In particular, targeted improvement of gate dielectric growth in the A-CNT MOS device contributes to suppressing the interface state density (Dit) to 6.1 × 1011 cm-2eV-1, which is a record for CNT- or low-dimensional semiconductors-based MOSFETs, boosting a record transconductance (gm) of 2.42 mS/μm and an on-off ratio of 105. Further decreasing Dit below 1×1011 cm-2eV-1 is necessary for A-CNT MOSFETs to achieve the expected high energy efficiency and high reliability.
GPATCH11 variants cause mis-splicing and early-onset retinal dystrophy with neurological impairment
Authors: Perrault Isabelle , Zanetti Andrea , Fares-Taie Lucas , Amiel Jeanne , Roger Jerome , Audo Isabelle , Robert Matthieu , David Pierre , Jung Vincent , GOUDIN Nicolas , Guerrera Ida , Moriceau Stéphanie , Amana Danielle , Boddaert Nathalie , Briault Sylvain , Bruel Ange-Line , Gitiaux Cyril , Kaminska Karolina , Philip-Sarles Nicole , Quinodoz Mathieu , Santos Christina , Santos Luisa Coutinho , Sigaudy Sabine , Sá Mariana Soeiro e , Sousa Ana Berta , Thauvin Christel , Kaplan Josseline , Rivolta Carlo , Rozet Jean-Michel
Published: October 2023

Spliceosome and ciliary dysfunctions can lead to remarkably similar clinical syndromes. Studying ten individuals with retinal dystrophy, neurological involvement, and skeletal abnormalities, suggestive of both spliceosomopathies and ciliopathies, we involved GPATCH11, a lesser-known GPATCH-domain-containing regulators of RNA metabolism. To elucidate GPATCH11 function, we employed fibroblasts from unaffected individuals and patients carrying a recurring mutation specifically removing the main part of the GPATCH-domain while preserving other domains. Additionally, we generated a mouse model replicating the patient's genetic defect, exhibiting behavioural abnormalities and retinal dystrophy. Our findings revealed GPATCH11 unique subcellular localization, marked as foci staining pattern and a diffuse presence in the nucleoplasm, alongside its centrosomal localization, indicating roles in RNA and cilia metabolism. We show dysregulation of U4 snRNA in patient cells and dysregulation in both gene expression and spliceosome activity within the mutant mouse retina, impacting key processes such as photoreceptor light responses, RNA regulation, and primary cilia-associated metabolism. These results highlight GPATCH11 roles in RNA metabolism, spliceosome regulation, and potential ciliary involvement. They underscore its significance in maintaining proper gene expression, contributing to retinal, neurological, and skeletal functions. Our research also demonstrates how studying rare genetic disorders can reveal broader gene functions, providing insights into GPATCH11 multifaceted roles.
Functionalized MXene Ink Enables Environmentally Stable Printed Electronics
Authors: Park Soo-Jin , Ko Tae Yun , Ye Heqing , Murali G. , Lee Seul-Yi , Park Young Ho , Lee Jihoon , Lee Juyun , Yun Dong-Jin , Gogotsi Yury , Kim Seon Joon , Kim Se , Jeong Yong Jin , In Insik
Published: October 2023

Establishing dependable, cost-effective electrical connections is vital for enhancing device performance and shrinking electronic circuits. MXenes, renowned for their remarkable electrical conductivity and high breakdown voltage offer great promise as contact materials in microelectronics. However, their hydrophilic surfaces, susceptible to environmental degradation, and poor stability in organic solvents, have restricted their electronic applications. Thus, we’ve harnessed the electrohydrodynamic (EHD) printing for fully solution-processed thin-film transistors (TFTs). These TFTs employ alkylated 3,4-dihydroxy-L-phenylalanine functionalized Ti3C2Tx (AD-MXene) as source, drain, and gate electrodes. AD-MXene excels in EHD printing due to its outstanding dispersion stability in ethanol and sustained high electrical conductivity, surpassing traditional vacuum-deposited gold and aluminum electrodes. It enhances the environmental stability of TFTs, enabling integration into complex systems such as engineering logic gates (NOT, NAND, and NOR) and one-transistor-one-memory cells. This advance highlights ligand-functionalized MXenes’ significant potential in printed electrical contacts and paves the way for environmentally robust MXene-based electronics (MXetronics).
Pushing the thinness and transparency limit of silver films for flexible optoelectronic devices via an ion-beam thinning-back process
Authors: Duan Huigao , Ma Dongxu , Ji Ming , Yi Hongbo , Fan Fu , Feng Bo , Chen Yiqin
Published: October 2023

Silver (Ag) films thinner than 10 nm are ideal candidates for transparent conductors for flexible optoelectronic devices due to their merits of a low sheet resistance (Rs), high transparency and excellent flexibility performance. Further reducing the Ag film thickness theoretically allows higher transparency but in practice leads to reduced transparency and drastically increased sheet resistance because the ultrathin film tends to be noncontinuous and unsmooth. Herein, we developed a thinning-back process to address this dilemma, in which Ag film is first deposited to a larger thickness with high continuity and then thinned back to a reduced thickness with an ultrasmooth surface, both implemented by a flood ion beam. Contributed by the slight implantation of silver atoms into the substrate during the ion-beam sputtering deposition process, high-quality Ag films with a thinned thickness down to 4.5 nm can be obtained with atomic-level surface roughness due to the implantation-induced pinning effect. Enabled by the reduced thickness, high continuity and improved smoothness, the obtained ultrathin Ag films exhibit excellent visible transparency and comparable electrical conductivity to commercial indium tin oxide (ITO). Especially, the ultrasmooth surface allows the lowest optical haze among all existing transparent conductors. As a flexible transparent conductor, the ultrathin Ag films demonstrate outstanding mechanical flexibility due to the ductility of Ag metal. Considering the overall performance of the obtained ultrathin Ag films, this ion-beam-based process presents a promising solution towards the best possible transparent conductor with ultimate thinness and transparency for flexible optoelectronic devices.
Weather forecast using WRFg at 2 km resolution over two provinces in northwestern Panama
Authors: Batista Josue , Pinzon Reinhardt
Published: October 2023

In this paper, the 24- and 48-hour precipitation and temperature forecasts generated by dynamic downscaling (DDS) using the WRF-ARW (running on CPU) and AceCAST (running on GPU) models are analyzed for the western region of Panama (particularly in the provinces of Bocas del Toro and Chiriquí) during hurricanes ETA and IOTA. Various microphysics and cumulus parameterization schemes are used to generate rainfall forecasts with 11 and 2 km resolution, then these forecasts are compared against measurements from weather stations. The results indicate that under the ETA and IOTA events, the rainfall generated by BMJ microphysics scheme and Kain-Fritsch cumulus parameterization was the most similar to the observed rainfall data. On the other hand, it was found that the computation time of the forecasts obtained by AceCAST (GPU) was at least two times shorter than the WRF-ARW (CPU) model, thus using the computing power of GPUs to generate weather forecasts significantly reduces the issuance time of forecasts.
Simultaneous Learning against to Sequential Learning via Haptic Interaction
Authors: Saracbasi Ozge Ozlem , Harwin William , Kondo Toshiyuki , Hayashi Yoshikatsu
Published: October 2023

From a parent assisting to their child to use a spoon, to a physical therapist helping stroke patients to relearn walking, haptic assistance via haptic feedback plays an important role in skill learning. It is known that skill learning is associated with learning unknown dynamics within the interaction. For instance, while learning skills with a new partner under unknown environmental dynamics, humans are specifically exposed to two unknown dynamics: partner dynamics and environmental dynamics. Although recent studies have focused on skill learning mostly through adaptation to environmental dynamics or partner dynamics, much less is known about ’dual instability’. Is it possible to deal with dual instability? We developed a new paradigm in which we asked paired participants to control the joint cursor, representing the interaction dynamics e.g. partner, own self and environment. Note that the haptic device controls the joint cursor through two springs connected to cursors controlled by the paired participants, however, only the joint cursor was made visible. As the environmental dynamics exert the forces on the joint cursor, dual instability for the participants was realised. Under the cooperative task, we assessed whether one can learn to bring the joint cursor to the target with a partner. We examined skill learning under four conditions: (1) cooperative sequential learning, (2) simultaneous learning of partner and environmental dynamics, (3) individual sequential learning, (4) individual learning. Skill learning were quantified using time to target, trajectory smoothness and force. Experimental results suggested that if two-people interact actively (i.e. move the joint cursor together), there could be a separation of dual dynamics, which result in skill learning. The order of the unknown dynamics is not matter (e.g. sequential or simultaneous). There could be skill learning even though exposed to the most difficult condition, in simultaneous learning.
Mental Health App Boost My Mood (BMM) as Preventive Early Intervention for Adolescents With (Sub)clinical Depressive Symptoms
Authors: Willems Linda , Rasing Sanne P. A. , Heijs Dewi A. M. , Vermulst Ad A. , Huvenaars Mireille J. , Onrust Simone A. , Creemers Daan H. M.
Published: October 2023

Background
Depression is a common mental disorder. Detecting (sub)clinical depressive symptoms in adolescents at an early stage and offering a low-threshold early intervention can minimize the risk of serious and/or long-term depression. As such, a digital intervention can be a low-threshold preventive and early intervention. This study aims to examine whether the Boost My Mood (BMM)-app is a suitable preventive early intervention for adolescents with (sub)clinical depressive symptoms.
Methods
This naturalistic single-arm evaluation study (N = 50) was conducted in adolescents aged 16–21 with (sub)clinical depressive symptoms. Furthermore, the BMM-app was studied in relation to anxiety, worrying, stress, and sleeping problems. An exploratory objective was to determine whether positive expectations and social support are related to app use.
Results
The study showed a significant decrease in not only depressive symptoms, but also anxiety, worrying and stress while using the BMM-app. Sleeping problems did not significantly decrease over time while using the BMM-app. The degree of use of the BMM-app and telling significant others about using the BMM-app were both not related to a decrease in depressive symptoms. The BMM-app was used significantly more when the adolescent had told relatives about their depressive symptoms.
Conclusions
A digital intervention, such as the BMM-app, can be a low-threshold preventive and early intervention for adolescents with (sub)clinical depressive symptoms. Beneficial effects of the BMM-app were reported on depressive symptoms as well as other aspects of quality of life, such as anxiety, worrying, and stress. Whereas several factors may have played a role in the current findings on depressive symptoms, there are reasons to assume that part of the reduction in symptoms could be attributed to the BMM-app. Although no causality can be assumed, this study is a first step in the implementation of preventive apps in mental health care.
Adaptation of a standardized lifestyle intervention to maximize health outcomes in adolescent metabolic and bariatric surgery patients
Authors: Misserian Maral , Wheelington Alicia , King Rashon , Francis Jackson , Mathew M Sunil , Allicock Marlyn , Cartwright Bethany R. , Adewunmi Adejumoke , Chandrasekhar Aparajita , Polavarapu Dhatri , Barlow Sarah , Messiah Sarah E.
Published: October 2023

Background: Metabolic and bariatric surgery (MBS) is safe and efficacious in treating adolescents with severe obesity. Behavioral/lifestyle programs can support successful preparation for surgery and post-MBS weight loss, but no standardized lifestyle intervention exists for adolescents. Here we describe the process of developing and adapting the Diabetes Prevention Program Group Lifestyle Balance (DPP/GLB) curriculum to support adolescents pre- and post-MBS.
Methods: We collected both qualitative and quantitative data from a diverse group of adolescents (N=19, mean age 15.2 years, range 13-17, 76.0% female, 42.1% non-Hispanic Black, 42.1% non-Hispanic White, 15.8% Other, 59% Hispanic). Additionally, we included data from 13 parents, all of whom were mothers. These participants were recruited from an adolescent MBS program at Children’s Health System of Texas. In an online survey, we asked participants to rank their preferences and interests in DPP/GLB content topics. We complemented these results with in-depth interviews from a subset of 10 participants. This qualitative data triangulation informed the development of the TeenLYFT lifestyle intervention program, designed to support adolescents who were completing MBS. This program was adapted from the DPP/GLB, incorporating the social cognitive model (SCM) and the socioecological model (SEM) constructs to better cater to the needs of adolescent MBS patients.
Results: Adolescents’ top 3 ranked areas of content were: (1) steps to adopt better eating habits and healthier foods; (2) healthy ways to cope with stress; and (3) steps to stay motivated and manage self-defeating thoughts. Nearly all adolescent participants preferred online delivery of content (versus in-person). Mothers chose similar topics with the addition of information on eating healthy outside the home. Key themes from the adolescent qualitative interviews included familial support, body image and self-confidence, and comorbidities as key motivating factors in moving forward with MBS.
Conclusions: The feedback provided by both adolescents and parents informed the development of TeenLYFT, an online support intervention for adolescent MBS candidates. The adapted program may reinforce healthy behaviors and by involving parents, help create a supportive environment, increasing the likelihood of sustained behavior change. Understanding adolescent/parent needs to support weight management may also help healthcare providers improve long-term health outcomes for this patient population.
Down-regulated FDX1 inhibited the proliferation and migration of renal cell carcinoma cells
Authors: Bai Zhijie , Wang Chun , Zhang Mingpeng , Yang Yanjie , Liu Qian , Shang Zhiqun
Published: October 2023

Background
With the intensive study of cell death, a copper-related cell death mechanism has been uncovered that is different from other forms of cell death, which researchers have named cuproptosis. Ferredoxin1 (FDX1) is a key gene in cuproptosis. Available studies have shown that FDX1 expression is down-regulated in a variety of solid tumors and plays an inhibitory role in tumors. However, studies related to the role of FDX1 in renal cell carcinoma (RCC) and its mechanism are scarce and still need to be further explored.
Methods
Expression spectrum and clinical data obtained from TCGA were used to analyze the differential expression of FDX1 in various types of tumors, the relationship between FDX1 and different clinical features as well as patient survival and prognosis. Immunohistochemical staining experiments were used to verify the difference in FDX1 expression between RCC tissues and normal tissues. RT-qPCR and western blot were carried out to validate the expression of FDX1 between normal renal tubular epithelial cells and RCC cells at the mRNA and protein levels. The effects of FDX1 on the proliferation and migration ability of RCC cells were explored by CCK-8 and scratch assays. Finally, potential signaling pathways involved in FDX1 in RCC were analyzed via Gene Set Enrichment Analysis (GSEA)and subsequently validated using RT-qPCR.
Results
We found that FDX1 was lowly expressed in RCC tissues and cells, suggesting that FDX1 acts as a protective factor in RCC and that increased expression of FDX1 is favorable to the prognosis of patients. Tumor proliferation and invasive ability were inhibited after the expression of FDX1. In addition, GSEA analysis was significantly enriched in multiple signaling pathways including oxidative phosphorylation. RT-qPCR results indicated that the expression of some important genes in the oxidative phosphorylation pathway was also up-regulated after overexpression of FDX1 in RCC cells.
Conclusion
Low expression of FDX1 in RCC is associated with poor patient survival. Overexpression of FDX1 may be involved in inhibiting the proliferation and migration of RCC cells through the oxidative phosphorylation pathway.
New-Onset Atrial High-Rate Episodes in Left Bundle Branch Area Pacing Versus Right Ventricular Pacing for Patients With Atrioventricular Block
Authors: Zhang Shigeng , Yang Wen , Wang Shengchan , Cheng Yandi , Jiang Zhixin , zhou xiujuan , Shan qijun
Published: October 2023

Purpose
Left bundle branch area pacing (LBBAP) has demonstrated beneficial effects on clinical outcomes. Comparative data on the risk of atrial high-rate episodes (AHREs) between LBBAP and right ventricular pacing (RVP) are lacking. This study aimed to investigate whether LBBAP can reduce the risk of new-onset AHREs compared with RVP in patients with atrioventricular block (AVB).
Methods
A total of 175 consecutive AVB patients undergoing dual-chamber pacemaker implantation (LBBAP or RVP) and with no history of atrial fibrillation were enrolled. Propensity score matching for baseline characteristics yielded 43 matched pairs. The primary outcome was new-onset AHREs detected on scheduled device follow-up. Changes in echocardiographic measurements were also compared between groups.
Results
New-onset AHREs occurred in 42(24.0%) of all enrolled patients (follow-up 14.1 ± 7.5 months) and the incidence of new-onset AHREs in the LBBAP group was significantly lower than RVP (19.8% vs 34.7%, P = 0.039). After propensity score matching, LBBAP still resulted in significantly lower incidence of new-onset AHREs (11.6% vs 32.6%, P = 0.019), and a lower hazard ratio for new-onset AHREs compared with RVP (HR 0.274; 95% CI 0.113–0.692). At 1 year, LBBAP achieved preserved left ventricular ejection fraction (LVEF) (63.0 ± 3.2% to 63.1 ± 0.8%, P = 0.562), while RVP resulted in reduced LVEF (63.4 ± 4.9% to 60.5 ± 0.8%, P = 0.01). Changes in LVEF were significantly different between 2 groups {2.6% (0.2 to 5.0), P = 0.031}.
Conclusion
LBBAP demonstrated a reduced risk of new-onset AHREs compared with RVP in patients with AVB.
Non-invasive kidney diagnosis: A multimodal transformer system for diabetic nephropathy diagnosis via retinal imaging
Authors: Chen Xiangmei , Zheyi Dong , Wang Xiaofei , Pan Sai , Weng Taohan , Jiang Shuangshuang , Chen Xiao-Niao , Wang Qian , Li Ying , Wang Zonghua , Lin Wenwen , Li Liu , Jiang Lai , Li Shengxi , Deng Xin , Fu Yibing , Cheng Haimei , Cao Xueying , Yang Jian , Zhang Li , Yong Wang , Wu Jie , Tang Li , Chen Pu , Zhou Jianhui , Yu Xinyue , Yang Jin-Kui , He Yani , Lin Hong-Li , Geng Yanqiu , Li Jijun , Wang Liqiang , Xu Mai
Published: October 2023

It remains a formidable challenge to differentiate between diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) without resorting to kidney biopsy, resulting in missed opportunities for targeted interventions that may significantly alter the prognosis of NDRD. To reform the traditional biopsy-all diagnostic paradigm and avoid unnecessary biopsy, we developed a transformer-based deep learning (DL) system for detecting DN and NDRD upon non-invasive multi-modal data of fundus images and clinical characteristics. Our Trans-MUF achieved an AUC of 0.980 (95% CI: 0.979 to 0.980) over the internal retrospective set, and also had the superior eneralizability over a prospective dataset (AUC: 0.989, 95% CI: 0.987 to 0.990) and a multicenter, cross-machine and multi-operator dataset (AUC: 0.932, 95% CI: 0.931 to 0.939). On the other hand, the accuracy of antidiastole detection by nephrologists can be improved by 21%, through visualization assistance of the DL system. Therefore, this paper lays a foundation for automatically differentiating DN and NDRD without biopsy.
Regulation of multi-condensates miscibility is required for limiting transgenerational epigenetic inheritance
Authors: Wan Gang , Zhao Changfeng , Cai Shiyu , Ruona shi , Yang Shuhan , Huang Jing , Liang Yonglin , Lu Pu , Zhang Xiaofei , Kennedy Scott
Published: October 2023

Biomolecular condensates, such as nucleolus, stress granules/P bodies, and germ granules in Caenorhabditis elegans, are multiphase assemblages. However, the mechanisms underlying the formation of these multi-phase condensates and their significance remain poorly understood. Here, we demonstrate that the spatially ordered PZMS assemblage of germ granules in Caenorhabditis elegans is established hierarchically by three LOTUS domain proteins. Additionally, we identified a Z granules protein termed HERD-1 that prevents the mixing of P granules, Z granules, and Mutator foci. Surprisingly, loss of herd-1 leads to RNAi defect but paradoxically results in prolonged transgenerational epigenetic inheritance of RNAi for over 50 generations due to uncontrolled pUG RNAs-siRNAs cycles after PZM fusion. Moreover, ectopic recruitment of Mutator foci to P granules or Z granules closely mimics the phenotype observed in herd-1mutant. Our findings propose an assembly principle for multi-phase condensates and highlight the active maintenance of immiscibility between condensates by specific cellular machinery, which restrict transgenerational epigenetic inheritance.
Validation of the ROX index to predict high flow nasal cannula therapy treatment failure in infants with bronchiolitis
Authors: Cloney Kellie , Stevens Hannah , Foster Jennifer , Gallant Julien , Sandila Navjot , Verma Neeraj , Krmpotic Kristina
Published: October 2023

Purpose
High-flow nasal cannula (HFNC) therapy is commonly used to provide an intermediate level of respiratory support for infants with bronchiolitis. The ratio of SpO2/FiO2 to respiratory rate (ROX index) has previously been shown to aid in prediction of HFNC treatment failure in adults and children with diverse respiratory diseases. We aimed to evaluate the utility of the ROX index in predicting HFNC treatment failure in infants with bronchiolitis.
Methods
Retrospective analysis of previously well infants (< 1 year) hospitalized for bronchiolitis and initiated on HFNC as their primary modality of respiratory support.
Results
Of 64 infants (median age 70 days), 5 (7.8%) required intubation within 6 hours of HFNC initiation (median time to intubation 225 minutes; interquartile range 125–290 minutes). No between-group differences were observed with respect to sex, age, weight, respiratory syncytial virus infection status, presumed bacterial pneumonia, hospital unit of HFNC initiation, or respiratory parameters at initiation and 1 hour following. Compared to infants who were successfully treated with HFNC, infants who required intubation were initiated earlier in the course of their illness (3 days vs 4 days; p = 0.02). The ROX index did not demonstrate discriminatory ability at time of HFNC initiation (AUROC 0.6; p = 0.5) or 1 hour after initiation (AUROC 0.6; p = 0.6).
Conclusions
The ROX index at HFNC initiation and 1 hour did not predict early treatment failure in infants with bronchiolitis. Examination of a larger cohort of infants and greater number of treatment failures is required.
Comparative clinical study of phosphorous-necrosis and medical-related osteonecrosis of the jaws
Authors: Xie Rongju , Wang Weihong , Bian Longchun , Qian Yemei , Li Jingyi , Zhang Hongrong
Published: October 2023

Background: Phosphorous necrosis of the jaw (PNJ) shares similar clinical and pathological features to medical-related osteonecrosis of the jaw (MRONJ). This study aims to compare the similarities and differences between PNJ and medical-related osteonecrosis of the jaw (MRONJ) in terms of clinical and pathological features, and to provide a theoretical basis for the clinical diagnosis and management of PNJ.
Material and Methods: A retrospective analysis assessed clinical differences among 38 PNJ patients and 31 MRONJ patients diagnosed and treated between January 2009 and October 2022. Pathological alterations in bone tissue were assessed using EDS, H&E, Masson and TRAP staining on five specimens from both MRONJ and PNJ cases, and immunohistochemistry was used to determine the expression levels of OPG, RANKL, and Runx2. The mandibular coronoid process was removed from individuals with temporomandibular joint ankylosis as control.
Results: CBCT imaging indicated necrotic bone formation in block, strip, or plaque shapes. EDS analysis revealed that the calcium/phosphorus ratio in the bone tissue of PNJ and MRONJ was significantly lower than that of the control group (P<0.05). Additionally, staining indicated reduced osteoblast counts, disrupted bone trabecular structure, and decreased collagen fiber content in the bone tissues of PNJ and MRONJ. Immunohistochemistry revealed that RANKL expression was significantly lower in MRONJ compared to PNJ and control groups (P<0.05). Conversely, Runx2 expression was significantly higher in PNJ than in MRONJ and control groups (P<0.05), with no significant difference in OPG expression.
Conclusion: PNJ and MRONJ exhibit comparable clinical manifestations and pathological traits, although disparities may exist in their underlyingexhibit comparable clinical manifestations and pathological traits, although disparities may exist in their underlying molecular mechanisms.
Restricted Cubic Spline Model Analysis of the Association between Anal Fistula and Anorectal Abscess incidence and Body Mass Index
Authors: Ye Sangyu , Huang Zichen , Zheng Lihua , Shi Yuying , Zhi Congcong , Liu Ningyuan , Cheng Yicheng
Published: October 2023

Background
The epidemiological profile of anal fistula and anorectal abscess has not been well studied. Based on the results of a retrospective cross-sectional survey, we aimed to investigate the potential influential factors associated with anal fistula and anorectal abscess.
Methods
We conducted a retrospective analysis of patients between January 2017 and May 2022. A comprehensive questionnaire was designed to collect potential influential factors, all the participants were divided into patients with anal fistula or perianal abscess and healthy control group. Multiple logistic regression was used to identify factors in significant association with anal fistula and perianal abscess. Additionally, we combined restricted cubic spline regression to examine the dose-response relationship between factors and the risk of developing anal fistula or anorectal abscess.
Results
The present study included 1223 participants, with 275 anal fistulas, 184 anorectal abscesses, and 765 healthy controls. We found no statistically significant differences between patients and controls in basic information and preoperative assessment of life factors, except for body mass index. It was indicated that people with overweight or obesity were more prone to anal fistula or anorectal abscess than normal-weight individuals. The dose-response research indicated the J-shaped trend between the ascending BMI levels and the higher risk of suffering from anal fistula and anorectal abscess.
Conclusions
Our findings indicate that overweight and obesity are risk factors for anal fistula and anorectal abscess, which plays a role in the prevention of anorectal diseases. This provides some theoretical basis for clinicians to provide health education to their patients.