bluuebunny/crossref_metadata_2025 huggingface dataset:
DANet: Temporal Action Localization with Double Attention
Authors: Sun Jianing , Wu Xuan , Xiao Yubin , Wu Chunguo , Liang Yanchun , Liang Yi , Wang Liupu , Zhou You
Published: June 2023

Temporal action localization (TAL) aims to predict action instance categories in videos and identify their start and end times. However, existing Transformer-based backbones focus only on global or local features, resulting in the loss of information. In addition, both global and local self-attention mechanisms tend to average embeddings, thereby reducing the preservation of critical features. To solve these two problems better, we propose two kinds of attention mechanisms, namely multi-headed local self-attention (MLSA) and max-average pooling attention (MA) to extract simultaneously local and global features. In MA, max-pooling is used to select the most critical information from local clip embeddings instead of averaging embeddings, and average-pooling is used to aggregate global features. We use MLSA for modeling local temporal context. In addition, to enhance collaboration between MA and MLSA, we propose the double attention block (DABlock), comprising MA and MLSA. Finally, we propose the final network double attention network (DANet), composed of DABlocks and other advanced blocks. To evaluate DANet’s performance, we conduct extensive experiments for the TAL task. Experimental results demonstrate that DANet outperforms the other state-of-the-art models on all datasets. Finally, ablation studies demonstrate the effectiveness of the proposed MLSA and MA. Compared with structures using backbone with convolution and global Transformer, DABlock consisting of MLSA and MA has a superior performance, achieving an 8% and 0.5% improvement on overall average mAP, respectively.
Glycerol Carbonate Solventless Synthesis Using Ethylene Carbonate, Glycerol and a Tunisian Smectite Clay: Activity, Stability and Kinetic Studies
Authors: Snoussi Yosra , Escanciano Itziar A. , Serafini Mariana Alvarez , Besbes Neji , Bolivar Juan M. , Ladero Miguel
Published: June 2023

Biodiesel is nowadays added in 5–10% v/v to diesel, and its production involves the parallel creation of a vast glycerol amount as a by-product. Despite its many applications, there is a surplus of glycerol (Gly) that has boosted the search for new applications of this compound, now transformed into an industrial synthesis intermediate or platform chemical. Its transcarbonation is a type of reaction that occurs under mild conditions, using weak or moderate basic catalysts, and allows the parallel production of glycols of industrial interest with high selectivity, such as ethylene glycol. In this research, we have studied the activity of a Tunisian clay rich in inorganic carbonates that give it a weak basic character. The raw clay (RC) has been fully characterized by XRD, FTIR, SEM-EDS and nitrogen porosimetry. Subsequently, it has been employed as a catalyst to react glycerol (G) with ethylene carbonate (EC) to obtain glycerol carbonate (GC) and ethylene glycol (EG). The main operating variables and their effects on glycerol conversion and initial reaction rate were analyzed: catalyst concentration (2–6% w/w glycerol), reagent molar ratio (EC:G 1.5:1 to 3:1), and temperature (80–110 °C). Then, an appropriate kinetic model was selected from the results obtained under various reaction conditions, including the total deactivation of order 1 of the catalyst. The kinetic constant activation energy in this reaction using Tunisian smectite was found to be around 183.3 kJ·mol−1. In the second phase of the investigation, we explored the reuse of smectite using the kinetic model to appreciate the effect of cycle-to-cycle deactivation. It can be seen that the kinetic constant of the main reaction generally decreases with the number of cycles at low temperature and goes through a maximum at high operating temperature, while the deactivation constant increases with the number of catalytic cycles. The catalyst shows more stability, in general, at higher temperatures.
Effectiveness of a Priority Management Scheme of Living Modified Organism Re-Collection Areas in Natural Environments of South Korea
Authors: Lim Hye Song , Yoon A-Mi , Kim Il Ryong , Choi Wonkyun , Jung Young Jun , Lee Sunghyeon , Lee Jung Ro
Published: June 2023

Since 2009, the Ministry of Environment and the National Institute of Ecology in South Korea have been conducting a living modified organism (LMO) monitoring and post-management project in natural environments to prevent the unintentional release and spread of LMOs to natural ecosystems. The project surveyed six administrative districts of South Korea from 2009 to 2013 and collected 1960 LMO suspicious samples from 1850 monitoring sites. As a result, 113 LMOs were identified at 65 sites and removed for post-management. An analysis of the five-year LMO monitoring results showed that LMOs were re-collected in 38.4% of the 65 areas where they were initially collected. This result led to the establishment of a new LMO management system in 2014, with priority given to areas where LMOs had been re-collected twice or more within the last five years. Intensive surveys and post-management were conducted four times a year in these priority management areas. The results confirmed that the novel management system for LMO priority areas effectively prevented the continuous collection of LMOs in the same areas. In conclusion, establishing a safety management system for priority management areas, intensive surveys, and post-management efforts are crucial for protecting natural ecosystems from the putative risks of unintentionally released LMOs.
Locating Infectious Sources Using Bluetooth System of Smart Devices
Authors: Qin Hongli , Guo Tao , Han Yunan
Published: June 2023

Infectious diseases, such as COVID-19, may have a significant impact on human daily life and social activities. One effective method to prevent and control the spread of such diseases is to accurately locate the sources of infection and limit the possible exposure to the virus. This paper presents a method, system, big data storage and analysis to control the infection based on Bluetooth technology. GPS and Bluetooth positioning are combined to track the movement trajectory of each person with a smart device, locally store the location information and close contacts, as well as periodically update it on the cloud platform. Based on the related algorithms of big data, this method can provide personal and regional risk levels, providing an alarm function which can be triggered by being close enough to a high-risk area or if the infected person’s risk level is greater than the set threshold within the Bluetooth interconnection range. The system can provide a wealth of data on the location of infection sources and close contacts, offering valuable technical support for rapid and efficient epidemic prevention and control.
Development of Artificial Intelligence-Based Dual-Energy Subtraction for Chest Radiography
Authors: Yamazaki Asumi , Koshida Akane , Tanaka Toshimitsu , Seki Masashi , Ishida Takayuki
Published: June 2023

Recently, some facilities have utilized the dual-energy subtraction (DES) technique for chest radiography to increase pulmonary lesion detectability. However, the availability of the technique is limited to certain facilities, in addition to other limitations, such as increased noise in high-energy images and motion artifacts with the one-shot and two-shot methods, respectively. The aim of this study was to develop artificial intelligence-based DES (AI–DES) technology for chest radiography to overcome these limitations. Using a trained pix2pix model on clinically acquired chest radiograph pairs, we successfully converted 130 kV images into virtual 60 kV images that closely resemble the real images. The averaged peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) between virtual and real 60 kV images were 33.8 dB and 0.984, respectively. We also achieved the production of soft-tissue- and bone-enhanced images using a weighted image subtraction process with the virtual 60 kV images. The soft-tissue-enhanced images exhibited sufficient bone suppression, particularly within lung fields. Although the bone-enhanced images contained artifacts on and around the lower thoracic and lumbar spines, superior sharpness and noise characteristics were presented. The main contribution of our development is its ability to provide selectively enhanced images for specific tissues using only high-energy images obtained via routine chest radiography. This suggests the potential to improve the detectability of pulmonary lesions while addressing challenges associated with the existing DES technique. However, further improvements are necessary to improve the image quality.
Characterization of Raindrop Size Distribution over Santa Clara Valley
Authors: Quinn Nathan , Chiao Sen
Published: June 2023

This study presents a year-long (January 2019–April 2020) analysis of the Z–R relationship and drop size distribution (DSD) scaling parameters for size, concentration, and shape of rain events over Santa Clara Valley, CA. External influences were analyzed based on synoptic variability and seasons. For the former, 850 hPa winds were separated into groups based on direction and magnitude. Results show that greater drop size, lower concentration, and larger shape parameters for spring, while winter and fall showed smaller drop sizes, higher concentrations, and smaller shape parameters. For synoptic variability, southeasterly-to-southwesterly flow was associated with larger drop sizes, larger concentrations, and smaller shape parameters relative to northwesterly flow. Differences in the DSD scaling parameter values and Z–R relationship were also observed between strong and weak low-level flow. The results of this study suggest that it is beneficial to derive specific microphysical relationships based on seasons and different synoptic events to improve radar rain rate retrieval algorithms using the Z–R relationship.
Intraseasonal Variation in the Mesosphere Observed by the Mengcheng Meteor Radar from 2015 to 2020
Authors: Tang Yihuan , Hao Xiaojing , Qiu Shican , Cheng Wenhan , Yang Chengyun , Wu Jianfei
Published: June 2023

The intraseasonal oscillations (30–100 days, ISO) in the MLT (mesosphere and lower thermosphere) horizontal wind are investigated based on observations from the Mengcheng meteor radar. There is a clear seasonal variation in ISO in the horizontal wind at 80 km, which is strongest during the winter and weakest during the summer. At 100 km, ISO occurs throughout most of the year except winter, and there are significant differences in periods and amplitudes from year to year. From 2015 to 2016, ISOs with periods of 40–60 days were present in the 100 km horizontal wind, whereas none were simultaneously observed in the 80 km horizontal wind. Cross wavelets were used to study the relationship between ISO in the MLT region and ISO in the lower atmosphere. Some of the ISO activity is linked to tropospheric tropical convective activity, but the ISO connections with that in tropospheric convection are not consistent in the upper mesosphere and in the lower thermosphere.
Characteristics of Marine Heatwaves in the Indonesian Waters during the PDO, ENSO, and IOD Phases and Their Relationships to Net Surface Heat Flux
Authors: Beliyana Erlin , Ningsih Nining Sari , Gunawan Sekar Ramdanira , Tarya Ayi
Published: June 2023

We conducted an investigation into the characteristics of marine heatwaves (MHWs) in Indonesian waters, aiming to understand the underlying mechanisms responsible for their formation, particularly the ones generated by net surface heat flux. To accomplish this, we utilized remote sensing data from the National Oceanic and Atmospheric Administration and the European Centre for Medium-Range Weather Forecasts. The dataset covered a 40-year period (1982–2021) encompassing both warm (1982–2007) and cold (2008–2021) phases of the Pacific Decadal Oscillation (PDO). Statistical analysis methods were employed to process the data. Our study reveals significant findings regarding MHWs in Indonesian waters. We observed the highest average frequency and maximum intensity of MHWs, occurring approximately 2–3 times a year and exceeding 1.5 °C, respectively, during the warm phase of PDO (with El Niño events occurring more frequently than La Niña). Conversely, the longest durations of MHWs in Indonesian waters were recorded during the cold phase of PDO (with La Niña events occurring more frequently than El Niño), spanning approximately 7–15 days. We identified local forcing in the form of net surface heat flux as the primary driver of MHW frequency and maximum intensity. During the warm phase of PDO, the net surface heat flux was notably higher, primarily due to increased shortwave radiation (heat gain) and reduced latent heat flux (heat loss) through the evaporation process. These factors collectively contributed to maintaining warmer ocean temperatures. Moreover, our study provides valuable insights into the interannual variability of MHWs through the application of composite calculations. We discovered a strong correlation between the occurrence of El Niño and positive Indian Ocean Dipole (IOD) events during the warm PDO phase and the highest frequency and maximum intensity of MHWs, with approximately 2.52 events and 1.54 °C, respectively. In contrast, we found that MHWs with the longest durations were closely linked to La Niña and negative IOD events during the cold PDO phase, lasting approximately 10.90 days. These findings highlight the complex interplay between climate phenomena and MHW characteristics, further deepening our understanding of their dynamics.
Settlement of a Foundation on an Unsaturated Sandy Base Taking Vibrocreep into Account
Authors: Ter-Martirosyan Armen Z. , Shebunyaev Alexander N. , Sobolev Evgeny S.
Published: June 2023

Dynamic loading causes (1) a substantial change in the strength and deformation parameters of sandy soil and (2) excessive viscoplastic deformation. The goal of this study is to create a new analytical solution to the problem of the settlement of (1) the foundation that is the source of dynamic loading, and (2) a nearby foundation, taking into account the rheological properties of sandy soil subjected to vibration, given that these rheological properties depend on shear stresses. The proposed solution allows the progress of deformation over time to be described. The present paper states and provides an analytical solution for the problem of evaluating the settlement of a single foundation that transmits static and dynamic harmonic pressure to the base. The authors also analyze the settlement of another foundation located at some distance from the transmitting foundation. The second foundation transmits static pressure to the base. The dependence of the viscosity coefficient on the shear stress intensity and vibration intensity, as well as the vibrocreep decay over time, are based on the exponential and homographic dependencies previously identified by two of the authors (A.Z. Ter-Martirosyan and E.S. Sobolev). The solution to the problem is obtained by numerical integration in the Mathcad program of an analytical expression for nonlinear viscoplastic deformations. As a result of the research, the authors have found that the dynamic viscoplastic component makes the greatest contribution to foundation settlement. The settlement of the transmitting foundation increases along with increasing static and dynamic pressure transmitted to the base. The settlement of the nearby foundation increases when the pressure increases under the foundation, but it reduces when static pressure from the transmitting foundation, the depth of the foundation, and the distance between the foundations increase. General analytical dependencies obtained by the authors comply with the results of laboratory and field experiments performed by other researchers. These dependencies can be used to predict the settlement of foundations in whose unsaturated sandy bases mechanical vibrations propagate.
The Recursive Structures of Manin Symbols over Q, Cusps and Elliptic Points on X0 (N)
Authors: Wang Sanmin
Published: June 2023

Firstly, we present a more explicit formulation of the complete system D(N) of representatives of Manin’s symbols over Q, which was initially given by Shimura. Then, we establish a bijection between D(M)×D(N) and D(MN) for (M,N)=1, which reveals a recursive structure between Manin’s symbols of different levels. Based on Manin’s complete system Π(N) of representatives of cusps on X0(N) and Cremona’s characterization of the equivalence between cusps, we establish a bijection between a subset C(N) of D(N) and Π(N), and then establish a bijection between C(M)×C(N) and C(MN) for (M,N)=1. We also provide a recursive structure for elliptical points on X0(N). Based on these recursive structures, we obtain recursive algorithms for constructing Manin symbols over Q, cusps, and elliptical points on X0(N). This may give rise to more efficient algorithms for modular elliptic curves. As direct corollaries of these recursive structures, we present a recursive version of the genus formula and prove constructively formulas of the numbers of D(N), cusps, and elliptic points on X0(N).
Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions
Authors: Ścibior Agnieszka , Aureliano Manuel , Holder Alvin A. , Llopis Juan
Published: June 2023

In the present Special Issue on “Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions”, an attempt has been made to include reports updating our knowledge of elements considered to be potential candidates for therapeutic applications and certain metal-containing species, which are extensively being examined towards their potential biomedical use due to their specific physicochemical properties [...]
ALM Therapy Promotes Functional and Histologic Regeneration of Traumatized Peripheral Skeletal Muscle
Authors: Hoeger Nina Sarah , Mittlmeier Thomas , Vollmar Brigitte , Stratos Ioannis , Dobson Geoffrey P. , Rotter Robert
Published: June 2023

Skeletal muscle trauma is a common injury with a range of severity. Adenosine, lidocaine and Mg2+ (ALM) is a protective solution and improves tissue perfusion and coagulopathy. Male Wistar rats were anesthetized and subjected to standardized skeletal muscle trauma of the left soleus muscle with the protection of the neurovascular structures. Seventy animals were randomly assigned to saline control or ALM. Immediately after trauma, a bolus of ALM solution was applied intravenously, followed by a one-hour infusion. After 1, 4, 7, 14 and 42 days, the biomechanical regenerative capacity was examined using incomplete tetanic force and tetany, and immunohistochemistry was used to examine for proliferation and apoptosis characteristics. Biomechanical force development showed a significant increase following ALM therapy for incomplete tetanic force and tetany on days 4 and 7. In addition, the histological evaluation showed a significant increase in proliferative BrdU-positive cells with ALM therapy on days 1 and 14. Ki67 histology also detected significantly more proliferative cells on days 1, 4, 7, 14 and 42 in ALM-treated animals. Furthermore, a simultaneous decrease in the number of apoptotic cells was observed using the TUNEL method. ALM solution showed significant superiority in biomechanical force development and also a significant positive effect on cell proliferation in traumatized skeletal muscle tissue and reduced apoptosis.
The Ubiquitin-Proteasome System Participates in Sperm Surface Subproteome Remodeling during Boar Sperm Capacitation
Authors: Zigo Michal , Kerns Karl , Sutovsky Peter
Published: June 2023

Sperm capacitation is a complex process endowing biological and biochemical changes to a spermatozoon for a successful encounter with an oocyte. The present study focused on the role of the ubiquitin–proteasome system (UPS) in the remodeling of the sperm surface subproteome. The sperm surface subproteome from non-capacitated and in vitro capacitated (IVC) porcine spermatozoa, with and without proteasomal inhibition, was selectively isolated. The purified sperm surface subproteome was analyzed using high-resolution, quantitative liquid chromatography–mass spectrometry (LC-MS) in four replicates. We identified 1680 HUGO annotated proteins, out of which we found 91 to be at least 1.5× less abundant (p < 0.05) and 141 to be at least 1.5× more abundant (p < 0.05) on the surface of IVC spermatozoa. These proteins were associated with sperm capacitation, hyperactivation, metabolism, acrosomal exocytosis, and fertilization. Abundances of 14 proteins were found to be significantly different (p < 0.05), exceeding a 1.5-fold abundance between the proteasomally inhibited (100 µM MG132) and vehicle control (0.2% ethanol) groups. The proteins NIF3L1, CSE1L, NDUFB7, PGLS, PPP4C, STK39, and TPRG1L were found to be more abundant; while BPHL, GSN, GSPT1, PFDN4, STYXL1, TIMM10, and UBXN4 were found to be less abundant in proteasomally inhibited IVC spermatozoa. Despite the UPS having a narrow range of targets, it modulated sperm metabolism and binding by regulating susceptible surface proteins. Changes in CSE1L, PFDN4, and STK39 during in vitro capacitation were confirmed using immunocytochemistry, image-based flow cytometry, and Western blotting. The results confirmed the active participation of the UPS in the extensive sperm surface proteome remodeling that occurs during boar sperm capacitation. This work will help us to identify new pharmacological mechanisms to positively or negatively modulate sperm fertilizing ability in food animals and humans.
Emerging Extracellular Molecular Targets for Innovative Pharmacological Approaches to Resistant Mtb Infection
Authors: Italia Alice , Shaik Mohammed Monsoor , Peri Francesco
Published: June 2023

Emerging pharmacological strategies that target major virulence factors of antibiotic-resistant Mycobacterium tuberculosis (Mtb) are presented and discussed. This review is divided into three parts corresponding to structures and functions important for Mtb pathogenicity: the cell wall, the lipoarabinomannan, and the secretory proteins. Within the cell wall, we further focus on three biopolymeric sub-components: mycolic acids, arabinogalactan, and peptidoglycan. We present a comprehensive overview of drugs and drug candidates that target cell walls, envelopes, and secretory systems. An understanding at a molecular level of Mtb pathogenesis is provided, and potential future directions in therapeutic strategies are suggested to access new drugs to combat the growing global threat of antibiotic-resistant Mtb infection.
Identification of the Stapled α-Helical Peptide ATSP-7041 as a Substrate and Strong Inhibitor of OATP1B1 In Vitro
Authors: Ishikawa Rika , Saito Kosuke , Misawa Takashi , Demizu Yosuke , Saito Yoshiro
Published: June 2023

ATSP-7041, a stapled α-helical peptide that inhibits murine double minute-2 (MDM2) and MDMX activities, is a promising modality targeting protein–protein interactions. As peptides of molecular weights over 1000 Da are not usually evaluated, data on the drug–drug interaction (DDI) potential of stapled α-helical peptides remain scarce. Here, we evaluate the interaction of ATSP-7041 with hepatic cytochrome P450s (CYPs; CYP1A2, CYP2C9, CYP2C19, CYP3A4, and CYP2D6) and transporters (organic anion transporting polypeptides (OATPs; OATP1B1 and OATP1B3), P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP)). ATSP-7041 demonstrated negligible metabolism in human liver S9 fraction and a limited inhibition of CYP activities in yeast microsomes or S9 fractions. On the contrary, a substantial uptake by OATPs in HEK 293 cells, a strong inhibition of OATP activities in the cells, and an inhibition of P-gp and BCRP activities in reversed membrane vesicles were observed for ATSP-7041. A recent report describes that ALRN-6924, an ATSP-7041 analog, inhibited OATP activities in vivo; therefore, we focused on the interaction between ATSP-7041 and OATP1B1 to demonstrate that ATSP-7041, as a higher molecular weight stapled peptide, is a substrate and strong inhibitor of OATP1B1 activity. Our findings demonstrated the possibility of transporter-mediated DDI potential by high molecular weight stapled peptides and the necessity of their evaluation for drug development.
Heterogenous Genetic, Clinical, and Imaging Features in Patients with Neuronal Intranuclear Inclusion Disease Carrying NOTCH2NLC Repeat Expansion
Authors: Fitrah Yusran Ady , Higuchi Yo , Hara Norikazu , Tokutake Takayoshi , Kanazawa Masato , Sanpei Kazuhiro , Taneda Tomone , Nakajima Akihiko , Koide Shin , Tsuboguchi Shintaro , Watanabe Midori , Fukumoto Junki , Ando Shoichiro , Sato Tomoe , Iwafuchi Yohei , Sato Aki , Hayashi Hideki , Ishiguro Takanobu , Takeda Hayato , Takahashi Toshiaki , Fukuhara Nobuyoshi , Kasuga Kensaku , Miyashita Akinori , Onodera Osamu , Ikeuchi Takeshi
Published: June 2023

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder that is caused by the abnormal expansion of non-coding trinucleotide GGC repeats in NOTCH2NLC. NIID is clinically characterized by a broad spectrum of clinical presentations. To date, the relationship between expanded repeat lengths and clinical phenotype in patients with NIID remains unclear. Thus, we aimed to clarify the genetic and clinical spectrum and their association in patients with NIID. For this purpose, we genetically analyzed Japanese patients with adult-onset NIID with characteristic clinical and neuroimaging findings. Trinucleotide repeat expansions of NOTCH2NLC were examined by repeat-primed and amplicon-length PCR. In addition, long-read sequencing was performed to determine repeat size and sequence. The expanded GGC repeats ranging from 94 to 361 in NOTCH2NLC were found in all 15 patients. Two patients carried biallelic repeat expansions. There were marked heterogenous clinical and imaging features in NIID patients. Patients presenting with cerebellar ataxia or urinary dysfunction had a significantly larger GGC repeat size than those without. This significant association disappeared when these parameters were compared with the total trinucleotide repeat number. ARWMC score was significantly higher in patients who had a non-glycine-type trinucleotide interruption within expanded poly-glycine motifs than in those with a pure poly-glycine expansion. These results suggested that the repeat length and sequence in NOTCH2NLC may partly modify some clinical and imaging features of NIID.
Is It Time for a Paradigm Shift in the Treatment of Schizophrenia? The Use of Inflammation-Reducing and Neuroprotective Drugs—A Review
Authors: Messina Antonino , Concerto Carmen , Rodolico Alessandro , Petralia Antonino , Caraci Filippo , Signorelli Maria Salvina
Published: June 2023

Comprehending the pathogenesis of schizophrenia represents a challenge for global mental health. To date, although it is evident that alterations in dopaminergic, serotonergic, and glutamatergic neurotransmission underlie the clinical expressiveness of the disease, neuronal disconnections represent only an epiphenomenon. In recent years, several clinical studies have converged on the hypothesis of microglia hyperactivation and a consequent neuroinflammatory state as a pathogenic substrate of schizophrenia. Prenatal, perinatal, and postnatal factors can cause microglia to switch from M2 anti-inflammatory to M1 pro-inflammatory states. A continuous mild neuroinflammatory state progressively leads to neuronal loss, a reduction in dendritic spines, and myelin degeneration. The augmentation of drugs that reduce neuroinflammation to antipsychotics could be an effective therapeutic modality in managing schizophrenia. This review will consider studies in which drugs with anti-inflammatory and neuroprotective properties have been used in addition to antipsychotic treatment in patients with schizophrenia.
Lifelong Fitness in Ambulatory Children and Adolescents with Cerebral Palsy II: Influencing the Trajectory
Authors: Duff Susan V. , Kimbel Justine D. , Grant-Beuttler Marybeth , Sukal-Moulton Theresa , Moreau Noelle G. , Friel Kathleen M.
Published: June 2023

Physical activity of at least moderate intensity in all children contributes to higher levels of physical and psychological health. While essential, children with cerebral palsy (CP) often lack the physical capacity, resources, and knowledge to engage in physical activity at a sufficient intensity to optimize health and well-being. Low levels of physical activity place them at risk for declining fitness and health, contributing to a sedentary lifestyle. From this perspective, we describe a framework to foster a lifelong trajectory of fitness in ambulatory children with CP (GMFCS I–III) as they progress into adolescence and adulthood, implemented in conjunction with a training program to augment bone and muscle health. First, we recommend that altering the fitness trajectory of children with CP will require the use of methods to drive behavioral change prior to adolescence. Second, to promote behavior change, we suggest embedding lifestyle intervention into fitness programming while including meaningful activities and peer socialization to foster self-directed habit formation. If the inclusion of lifestyle intervention to drive behavior change is embedded into fitness programs and found to be effective, it may guide the delivery of targeted programming and community implementation. Participation in comprehensive programming could alter the long-term trajectory of musculoskeletal health while fostering strong self-efficacy in persons with CP.
Tradition and Innovation in Construction Project Management
Authors: Ke Yongjian , Zhang Jingxiao , Philbin Simon P.
Published: June 2023

Construction project management is a multidimensional discipline that requires meticulous consideration of various critical aspects, including cost, quality, schedule requirements, as well as social and environmental impacts, and broader stakeholder interests [...]
Lymphatic Mapping in Colon Cancer Depending on Injection Time and Tracing Agent: A Systematic Review and Meta-Analysis of Prospective Designed Studies
Authors: Lucas Katharina , Melling Nathaniel , Giannou Anastasios D. , Reeh Matthias , Mann Oliver , Hackert Thilo , Izbicki Jakob R. , Perez Daniel , Grass Julia K.
Published: June 2023

An optimized lymph node yield leads to better survival in colon cancer, but extended lymphadenectomy is not associated with survival benefits. Lymphatic mapping shows several colon cancers feature aberrant drainage pathways inducing local recurrence when not resected. Currently, different protocols exist for lymphatic mapping procedures. This meta-analysis assessed which protocol has the best capacity to detect tumor-draining and possibly metastatic lymph nodes. A systematic review was conducted according to PRISMA guidelines, including prospective trials with in vivo tracer application. The risk of bias was evaluated using the QUADAS-2 tool. Traced lymph nodes, total resected lymph nodes, and aberrant drainage detection rate were analyzed. Fifty-eight studies met the inclusion criteria, of which 42 searched for aberrant drainage. While a preoperative tracer injection significantly increased the traced lymph node rates compared to intraoperative tracing (30.1% (15.4, 47.3) vs. 14.1% (11.9, 16.5), p = 0.03), no effect was shown for the tracer used (p = 0.740) or the application sites comparing submucosal and subserosal injection (22.9% (14.1, 33.1) vs. 14.3% (12.1, 16.8), p = 0.07). Preoperative tracer injection resulted in a significantly higher rate of detected aberrant lymph nodes compared to intraoperative injection (26.3% [95% CI 11.5, 44.0] vs. 2.5% [95% CI 0.8, 4.7], p < 0.001). Analyzing 112 individual patient datasets from eight studies revealed a significant impact on aberrant drainage detection for injection timing, favoring preoperative over intraoperative injection (OR 0.050 [95% CI 0.010–0.176], p < 0.001) while indocyanine green presented itself as the superior tracer (OR 0.127 [95% CI 0.018–0.528], p = 0.012). Optimized lymphatic mapping techniques result in significantly higher detection of aberrant lymphatic drainage patterns and thus enable a personalized approach to reducing local recurrence.
Repurposing of Chronically Used Drugs in Cancer Therapy: A Chance to Grasp
Authors: Hijazi Mohamad Ali , Gessner André , El-Najjar Nahed
Published: June 2023

Despite the advancement in drug discovery for cancer therapy, drug repurposing remains an exceptional opportunistic strategy. This approach offers many advantages (faster, safer, and cheaper drugs) typically needed to overcome increased challenges, i.e., side effects, resistance, and costs associated with cancer therapy. However, not all drug classes suit a patient’s condition or long-time use. For that, repurposing chronically used medications is more appealing. This review highlights the importance of repurposing anti-diabetic and anti-hypertensive drugs in the global fight against human malignancies. Extensive searches of all available evidence (up to 30 March 2023) on the anti-cancer activities of anti-diabetic and anti-hypertensive agents are obtained from multiple resources (PubMed, Google Scholar, ClinicalTrials.gov, Drug Bank database, ReDo database, and the National Institutes of Health). Interestingly, more than 92 clinical trials are evaluating the anti-cancer activity of 14 anti-diabetic and anti-hypertensive drugs against more than 15 cancer types. Moreover, some of these agents have reached Phase IV evaluations, suggesting promising official release as anti-cancer medications. This comprehensive review provides current updates on different anti-diabetic and anti-hypertensive classes possessing anti-cancer activities with the available evidence about their mechanism(s) and stage of development and evaluation. Hence, it serves researchers and clinicians interested in anti-cancer drug discovery and cancer management.
Tumorigenesis in Inflammatory Bowel Disease: Microbiota-Environment Interconnections
Authors: Mignini Irene , Ainora Maria Elena , Di Francesco Silvino , Galasso Linda , Gasbarrini Antonio , Zocco Maria Assunta
Published: June 2023

Colo-rectal cancer (CRC) is undoubtedly one of the most severe complications of inflammatory bowel diseases (IBD). While sporadic CRC develops from a typical adenoma-carcinoma sequence, IBD-related CRC follows different and less understood pathways and its pathophysiological mechanisms were not completely elucidated. In contrast to chronic inflammation, which is nowadays a well-recognised drive towards neoplastic transformation in IBD, only recently was gut microbiota demonstrated to interfere with both inflammation processes and immune-mediated anticancer surveillance. Moreover, the role of microbiota appears particularly complex and intriguing when also considering its multifaceted interactions with multiple environmental stimuli, notably chronic pathologies such as diabetes and obesity, lifestyle (diet, smoking) and vitamin intake. In this review, we presented a comprehensive overview on current evidence of the influence of gut microbiota on IBD-related CRC, in particular its mutual interconnections with the environment.
Taxifolin Inhibits Breast Cancer Growth by Facilitating CD8+ T Cell Infiltration and Inducing a Novel Set of Genes including Potential Tumor Suppressor Genes in 1q21.3
Authors: Lin Xiaozeng , Dong Ying , Gu Yan , Kapoor Anil , Peng Jingyi , Su Yingying , Wei Fengxiang , Wang Yanjun , Yang Chengzhi , Gill Armaan , Neira Sandra Vega , Tang Damu
Published: June 2023

Taxifolin inhibits breast cancer (BC) via novel mechanisms. In a syngeneic mouse BC model, taxifolin suppressed 4T-1 cell-derived allografts. RNA-seq of 4T-1 tumors identified 36 differentially expressed genes (DEGs) upregulated by taxifolin. Among their human homologues, 19, 7, and 2 genes were downregulated in BCs, high-proliferative BCs, and BCs with high-fatality risks, respectively. Three genes were established as tumor suppressors and eight were novel to BC, including HNRN, KPRP, CRCT1, and FLG2. These four genes exhibit tumor suppressive actions and reside in 1q21.3, a locus amplified in 70% recurrent BCs, revealing a unique vulnerability of primary and recurrent BCs with 1q21.3 amplification with respect to taxifolin. Furthermore, the 36 DEGs formed a multiple gene panel (DEG36) that effectively stratified the fatality risk in luminal, HER2+, and triple-negative (TN) equivalent BCs in two large cohorts: the METABRIC and TCGA datasets. 4T-1 cells model human TNBC cells. The DEG36 most robustly predicted the poor prognosis of TNBCs and associated it with the infiltration of CD8+ T, NK, macrophages, and Th2 cells. Of note, taxifolin increased the CD8+ T cell content in 4T-1 tumors. The DEG36 is a novel and effective prognostic biomarker of BCs, particularly TNBCs, and can be used to assess the BC-associated immunosuppressive microenvironment.
Spatial Transcriptomics Identifies Expression Signatures Specific to Lacrimal Gland Adenoid Cystic Carcinoma Cells
Authors: Moeyersoms Acadia H. M. , Gallo Ryan A. , Zhang Michelle G. , Stathias Vasileios , Maeng Michelle M. , Owens Dawn , Abou Khzam Rayan , Sayegh Yoseph , Maza Cynthia , Dubovy Sander R. , Tse David T. , Pelaez Daniel
Published: June 2023

Although primary tumors of the lacrimal gland are rare, adenoid cystic carcinoma (ACC) is the most common and lethal epithelial lacrimal gland malignancy. Traditional management of lacrimal gland adenoid cystic carcinoma (LGACC) involves the removal of the eye and surrounding socket contents, followed by chemoradiation. Even with this radical treatment, the 10-year survival rate for LGACC is 20% given the propensity for recurrence and metastasis. Due to the rarity of LGACC, its pathobiology is not well-understood, leading to difficulties in diagnosis, treatment, and effective management. Here, we integrate bulk RNA sequencing (RNA-seq) and spatial transcriptomics to identify a specific LGACC gene signature that can inform novel targeted therapies. Of the 3499 differentially expressed genes identified by bulk RNA-seq, the results of our spatial transcriptomic analysis reveal 15 upregulated and 12 downregulated genes that specifically arise from LGACC cells, whereas fibroblasts, reactive fibrotic tissue, and nervous and skeletal muscle account for the remaining bulk RNA-seq signature. In light of the analysis, we identified a transitional state cell or stem cell cluster. The results of the pathway analysis identified the upregulation of PI3K-Akt signaling, IL-17 signaling, and multiple other cancer pathways. This study provides insights into the molecular and cellular landscape of LGACC, which can inform new, targeted therapies to improve patient outcomes.
Prediction of Prostate Cancer Biochemical and Clinical Recurrence Is Improved by IHC-Assisted Grading Using Appl1, Sortilin and Syndecan-1
Authors: Logan Jessica M. , Hopkins Ashley M. , Martini Carmela , Sorvina Alexandra , Tewari Prerna , Prabhakaran Sarita , Huzzell Chelsea , Johnson Ian R. D. , Hickey Shane M. , Ung Ben S.-Y. , Lazniewska Joanna , Brooks Robert D. , Moore Courtney R. , Caruso Maria C. , Karageorgos Litsa , Martin Cara M. , O’Toole Sharon , Bogue Edgerton Laura , Ward Mark P. , Bates Mark , Selemidis Stavros , Esterman Adrian , Heffernan Sheena , Keegan Helen , Ní Mhaolcatha Sarah , O’Connor Roisin , Malone Victoria , Carter Marguerite , Ryan Katie , Clarke Andres , Brady Nathan , Klebe Sonja , Samaratunga Hemamali , Delahunt Brett , Sorich Michael J. , Moretti Kim , Butler Lisa M. , O’Leary John J. , Brooks Douglas A.
Published: June 2023

Gleason scoring is used within a five-tier risk stratification system to guide therapeutic decisions for patients with prostate cancer. This study aimed to compare the predictive performance of routine H&E or biomarker-assisted ISUP (International Society of Urological Pathology) grade grouping for assessing the risk of biochemical recurrence (BCR) and clinical recurrence (CR) in patients with prostate cancer. This retrospective study was an assessment of 114 men with prostate cancer who provided radical prostatectomy samples to the Australian Prostate Cancer Bioresource between 2006 and 2014. The prediction of CR was the primary outcome (median time to CR 79.8 months), and BCR was assessed as a secondary outcome (median time to BCR 41.7 months). The associations of (1) H&E ISUP grade groups and (2) modified ISUP grade groups informed by the Appl1, Sortilin and Syndecan-1 immunohistochemistry (IHC) labelling were modelled with BCR and CR using Cox proportional hazard approaches. IHC-assisted grading was more predictive than H&E for BCR (C-statistic 0.63 vs. 0.59) and CR (C-statistic 0.71 vs. 0.66). On adjusted analysis, IHC-assisted ISUP grading was independently associated with both outcome measures. IHC-assisted ISUP grading using the biomarker panel was an independent predictor of individual BCR and CR. Prospective studies are needed to further validate this biomarker technology and to define BCR and CR associations in real-world cohorts.
Personalized [177Lu]Lutetium-PSMA Therapy for Patients with Pre-Treated Castration-Resistant Prostate Cancer: A Single Institution Experience from a Comprehensive Cancer Centre
Authors: Thaiss Wolfgang , Zengerling Friedemann , Friedrich Julia , Hechler Veronika , Grunert Michael , Bolenz Christian , Wiegel Thomas , Beer Ambros J. , Prasad Vikas
Published: June 2023

Castration resistant prostate cancer (CRPC) is characterized by an aggressive biological behavior with a relatively short survival time, especially in progressive tumors pretreated with new hormonal agents and taxane chemotherapy. [177Lu]-Lutetium-PSMA (Lu-PSMA) treatment has proven efficacy in these patients. However, around 30% of the CRPC patients do not benefit from Lu-PSMA treatment, and little is known about predictive factors for treatment success if Lu-PSMA is offered in an individualized approach based on clinical and laboratory features. In this monocentric retrospective study, 86 CRPC patients receiving Lu-PSMA treatment were evaluated. The focus of the study was to describe clinical factors at baseline and during early treatment that are related to overall survival (OS). In addition, PSMA PET/CT-, PSA-response, and safety and tolerability (CTCAE adverse event reporting) were assessed. Efficacy endpoints were calculated using stratified Kaplan–Meier methods and Cox regression models. Mean applied dose was 17.7 GBq (mean 5.3 ± 1.1 GBq per cycle) with an average of 3.6 (range 1–8) therapy cycles. Patients were followed up for a mean of 12.4 months (range 1–39). The median OS was 15 months (95% CI 12.8–17.2). The best overall response rate in patients assessed with PSMA PET/CT and PSA response was 27.9%, and 50.0% had at least stable disease. Nine patients had a ≥grade 3 adverse event with anemia being the most frequent adverse event. Positive predictors for prolonged OS from baseline parameters were pre-treatment hemoglobin level of ≥10 g/dL and a lower PSA values at treatment start, while the presence of visceral or liver metastases were not significantly associated with worse prognoses in this cohort. With careful patient selection, an individualized Lu-PSMA treatment approach is feasible and patients with dose-limiting factors or visceral metastases should be included in prospective trials.
Predicting Chemotherapy Benefit across Different Races in Early-Stage Breast Cancer Patients Using the Oncotype DX Score
Authors: Shaw Vikram R. , Amos Christopher I. , Cheng Chao
Published: June 2023

Background: Oncotype DX assay, a multigene molecular test, has been widely used to stratify relapse risk and guide chemotherapy treatment in breast cancer. However, the optimal threshold of the Oncotype DX score in predicting chemotherapy benefit and its racial variation has not been investigated. Methods: In this study, we apply a random forest survival model to the SEER-Oncotype cohort data (Surveillance, Epidemiology, and End Results with Oncotype DX test information for breast cancer patients) and determine chemotherapy benefit thresholds in early-stage, estrogen-receptor-positive (ER+), and HER2-negative (HER2−) patients of different races. Results: Our results indicate that early-stage ER+, HER2−, and LN−/LN+ patients may benefit from receiving chemotherapy at a lower Oncotype DX score than current guidelines (Recurrence Score, RS > 25 or RS > 30) suggest. According to the estimated chemotherapy sensitivity thresholds from our models, 2.05–2.72-fold more lymph-node-negative (LN−) and 2.08–5.02-fold more lymph-node-positive (LN+) patients who may not currently be recommended for chemotherapy by their Oncotype DX test result may actually have the potential to benefit from chemotherapy. Furthermore, our models indicate a racial difference in chemotherapy benefit: white, black, and Asian women with early-stage ER+/LN− tumors benefit from chemotherapy when their Oncotype DX scores are greater than 19.9, 37.2, and 18.0, respectively. Conclusions: Our study provides a method for calibrating multigene molecular tests to help guide treatment decisions in racially and ethnically diverse patients with cancer. Specifically, we identify key chemotherapy sensitivity thresholds for the Oncotype DX recurrence score test in breast cancer patients and provide evidence that certain patients may benefit from receiving chemotherapy at a lower threshold than the current clinical guidelines suggest.
A β-Arrestin 2-Biased Dopamine Receptor Type 2 (DRD2) Agonist Is More Efficacious Than Cabergoline in Reducing Cell Proliferation in PRL-Secreting but Not in Non-Functioning Pituitary Tumor Cells
Authors: Di Muro Genesio , Mangili Federica , Esposito Emanuela , Barbieri Anna Maria , Catalano Rosa , Treppiedi Donatella , Marra Giusy , Nozza Emma , Lania Andrea G. A. , Ferrante Emanuele , Locatelli Marco , Arosio Maura , Peverelli Erika , Mantovani Giovanna
Published: June 2023

The molecular events underlying the variable effectiveness of dopamine receptor type 2 (DRD2) agonists in pituitary neuroendocrine tumors (PitNETs) are not known. Besides the canonical pathway induced by DRD2 coupling with Gi proteins, the β-arrestin 2 pathway contributes to DRD2′s antimitotic effects in PRL- and NF-PitNETs. A promising pharmacological strategy is the use of DRD2-biased agonists that selectively activate only one of these two pathways. The aim of the present study was to compare the effects of two biased DRD2 ligands, selectively activating the G protein (MLS1547) or β-arrestin 2 (UNC9994) pathway, with unbiased DRD2 agonist cabergoline in PRL- and NF-PitNET cells. In rat tumoral pituitary PRL-secreting MMQ cells, UNC9994 reduced cell proliferation with a greater efficacy compared to cabergoline (−40.2 ± 20.4% vs. −21 ± 10.9%, p < 0.05), whereas the G-protein-biased agonist induced only a slight reduction. β-arrestin 2 silencing, but not pertussis toxin treatment, reverted UNC9994 and cabergoline’s antiproliferative effects. In a cabergoline-resistant PRL-PitNET primary culture, UNC9994 inhibited cell proliferation and PRL release. In contrast, in NF-PitNET primary cultures (n = 23), biased agonists did not show better antiproliferative effects than cabergoline. In conclusion, the preferential activation of the β-arrestin 2 pathway by UNC9994 improves DRD2-mediated antiproliferative effects in PRL-PitNETs, suggesting a new pharmacological approach for resistant or poorly responsive tumors.