bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychometric evaluation of the healthy aging activity engagement scale
Authors: Lu Tingting , Kong Linghui , Zhang Huijun
Published: October 2022

Objective

The aim of this study was to translate the Healthy Aging Activity Engagement Scale (HAAE) into Chinese and validate its psychometric properties in the middle-aged and elderly population.

Methods

A total of 424 middle-aged and elderly people were recruited from China's Jiangsu Province, Liaoning Province, Shandong Province, and Heilongjiang Province. Cronbach's α co-efficient, split-half reliability, and test-retest reliability were used to evaluate the reliability of the translated scale. Expert consultation was used to evaluate the content validity of the translated scale. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to evaluate the structural validity of the scale.

Results

The Cronbach's α co-efficient of the Chinese version of HAAE was 0.965 and the Cronbach's α co-efficient of the dimensions ranged from 0.898 to 0.957. The split-half reliability was 0.807, and the test-retest reliability was 0.850. The content validity index of the scale (S-CVI) was 0.969. A total of three common factors were extracted from the EFA. The CFA validated the explored 3-factor structure, and the indicators were fitted well (χ2/df = 1.393, comparative fit index = 0.982, goodness- of- fit index = 0.911. Tucker-Lewis Index = 0.981 and root mean square error of approximation = 0.030).

Conclusion

The translated Chinese version of HAAE had suitable reliability and validity in the middle-aged and elderly population. The translated scale will be used to evaluate the level of healthy aging among middle-aged and elderly people in Chinese mainland. Furthermore, it also can provide some health advice for clinical patients.
Analytical assays to evaluate enzymatic activity and screening of inhibitors for ornithine decarboxylase
Authors: Tinoco Luzineide W. , da Silva Santos Bruno Maia , Soares Jhones Matheus da Silva , Finelli Fernanda Gadini
Published: October 2022

Ornithine decarboxylase (ODC) catalyzes the decarboxylation of ornithine to produce putrescine, the first step in the metabolism of polyamines (putrescine, spermidine, and spermine), which are essential growth factors in eukaryotic cells. ODC is active as a homodimer and depends on pyridoxal 5′-phosphate (PLP) as a cofactor. An increase in the concentration of polyamines has been associated with carcinogenesis. Therefore, there is much interest in identifying inhibitors of this pathway as potential chemotherapeutic and chemopreventive agents. The best-known inhibitor of mammalian ODC is α-difluoromethylornithine (DFMO), a highly selective compound that alkylates Cys-360 (a residue of the ODC active site). Although DFMO was initially developed for the treatment of cancer, the World Health Organization recommends its use in combination with nifurtimox for the treatment of human African trypanosomiasis. Considering the importance of ODC as a promising target for the treatment of various types of cancer and other infectious diseases, choosing the right method for screening potential inhibitors can help to accelerate the discovery of new drugs. Several methods for the determination of ODC activity are found in the literature. Among these, we can mention analysis with radioactive markers, colorimetric assays using auxiliary enzymes to detect CO2 or H2O2 release, chromatographic separations with putrescine derivatization, mass spectrometry, and spectroscopic techniques. In this review, the main analysis methods used will be described, highlighting their advantages and disadvantages, as well as identifying the most promising methods for high-throughput screening.
ORP should not be used to estimate or compare concentrations of aqueous H2: An in silico analysis and narrative synopsis
Authors: LeBaron Tyler W. , Sharpe Randy
Published: October 2022

Oxidation reduction potential (ORP) has become a commonly used measurement to characterize functional beverages, specifically alkaline ionized water and hydrogen water. Numerous health benefits including antioxidant effects have been attributed to a negative ORP value. A greater negative ORP value is often incorrectly interpreted to mean a greater degree of health benefits and/or a high concentration of H2. Some hydrogen meters use the Nernst equation to calculate the concentration of H2 based on the measured ORP value. Unfortunately, due to the fundamental issues with the ORP meter, the calculated H2 value may be very inaccurate. Using the Nernst equation, we performed an in silico analysis of the ORP as a function of pH, temperature, and H2 concentration. Our analysis shows that a one unit increase in pH (e.g., 7–8) influences the ORP by as much as increasing the H2 concentration by 100 times (e.g., 1–100 mg/L). Similarly, at a saturated H2 concentration (1.57 mg/L) and pH 7, every ∆T of 20 °C changes the ORP by ≈ 30 mV. This is comparable to changing the H2 concentration by a factor of 10 (0.1 mg/L to 1 mg/L). Finally, to measure H2 within 0.1 mg/L, ORP meters need to have an accuracy of about 0.8 mV. However, ORP meters have an error range of at least ±10 mV, which corresponds to a potential error in measured H2 concentration of nearly 2 mg/L (≈125% error). This analysis shows that pH, temperature, and the intrinsic ORP errors can individually influence the ORP greater than the entire contribution of dissolved H2 within normally used ranges. In fact, this can easily result in a water sample with a greater negative ORP than another despite having significantly less H2. This makes it impossible to consistently determine if one water sample has more H2 than another water sample. Therefore, we can only conclude, based on a negative ORP reading, that, excluding the possibility of other reductive redox couples, some level of dissolved H2 is present in the water. Accordingly, ORP and ORP-based H2 meters are not recommended for testing or comparing the concentration of H2 in water. Experimental studies are warranted to determine if the ORP error is as great as or greater than what is predicted via this in silico analysis.
Mole crab-inspired vertical self-burrowing
Authors: Treers Laura K. , McInroe Benjamin , Full Robert J. , Stuart Hannah S.
Published: October 2022

We present EMBUR—EMerita BUrrowing Robot—the first legged robot inspired by the Pacific mole crab, Emerita analoga, capable of burrowing vertically downward. We choose Emerita analoga as a model organism for its rapid downward burrowing behaviors, as it is four times as fast as the most rapid bivalve mollusk. Vertical burrowing in granular media is a challenging endeavor due to the tendency for the media to create upwards resistive forces on an intruder, even during purely horizontal motions. Our robot is capable of vertically burrowing its body in granular substrate primarily through excavation using two leg pairs, which are functionally analogous to groupings of leg pairs of the mole crab. We implement a novel leg mechanism with a sweeping trajectory, using compliant fabric to enable an anisotropic force response. The maximum resistive force during the power stroke is 6.4 times that of the return stroke. We compare robot body pitch and spatial trajectories with results from biomechanical studies of the mole crabs. We characterize the sensitivity of the robot to initial depth, body pitch and leg pose, and propose bounds on initial conditions which predict various burrowing failure modes. Parametric studies utilizing Granular Resistive Force Theory inform our understanding of robot behavior in response to leg phasing and orientation. Not only does this robotic platform represent the first robophysical model of vertical mole crab-inspired burrowing, it is also one of the first legged, primarily excavative small-scale burrowing agents.
Ambient ageism: Exploring ageism in acoustic representations of older adults in AgeTech advertisements
Authors: Graham Megan E.
Published: October 2022

Ageing-in-place environments are increasingly marked by ambient digital technologies designed to keep older adults safe while they live independently at home. These AgeTech companies market their products by constructing imagined visual and aural worlds of the smart home, usually deploying ageist representations of ageing and older adults. The advertisements are multimodal, and while what is seen on screen is often considered most important in a visuo-centric western culture, scholars have argued that it is what audiences hear that has the greatest impact. The acoustic domain of AgeTech advertisements and its relationship to ageism in marketing has not yet been explored. Accordingly, this paper will address this gap by following Van Leeuwen's framework for critical analysis of musical discourse to explore what AgeTech companies say about ageing, older adults, and ageing-in-place technologies using sound in an illustrative set of smart home advertisements for ageing-in-place. The paper will discuss how music, voice, and sound are semiotic resources that are used to construct stereotypical (both negative and positive) portrayals of older adults, reinforce the narrative of “technology as saviour,” and trouble the private/public boundaries of the ageing-in-place smart home.
A novel integrated angioscope-laser system for atherosclerotic carotid artery occlusion: Feasibility and techniques
Authors: Zhang Boqian , Zhang Guiyun
Published: October 2022

Introduction

Atherosclerotic extracranial carotid artery stenosis accounts for about 20%–30% of all strokes, which is one of the leading causes of adult morbidity and mortality. Although carotid endarterectomy (CEA) is still the mainly operational manner for atherosclerotic carotid artery stenosis/occlusion (ACAS/ACAO), and carotid angioplasty and stenting (CAS) have been used as an alternative, both CEA and CAS have limitations of their own, such as extensive invasiveness and in-stent restenosis.

Methods

In this study we established a novel interventional system in vitro to take advantage of both CEA and CAS. Twenty consecutive carotid atherosclerotic plaques were harvested from the patients who underwent CEA. The plaques were randomized into two groups and inserted into the pruned and sutured descending aortas of the swine in vitro. The ZebraScope™ was modified with a protective device on its flexible tip, so that the plaque could be dissected from the wall of parent carotid artery and ablated completely without damage to the carotid artery. The holmium:YAG (Ho:YAG) and thulium fiber laser (TFL) generators were alternately used when needed.

Results

All the carotid atherosclerotic plaques were completely ablated by Ho:YAG laser and/or TFL. The Ho:YAG laser was more effective for the atherosclerotic plaques with severe calcification, while the TFL was more suitable for those with moderate calcification. There were still some thermal injury spots on the inner wall of the parent carotid artery caused by the laser in the non-protected group B. In the protected group A, on the contrary, there was no even a thermal injury spot was found on the relevant location except for one sample. The difference of ablating duration was statistically significant between group A (36.5 ± 4.79 min) and group B (63.4 ± 6.55 min) (P < 0.01).

Conclusion

According to our knowledge, this is the first attempt to ablate carotid atherosclerotic plaques assisted by the ZebraScope™ in vitro. The protective and dissecting device on the tip of the angioscope makes it safe and visible when the ablation is performed to carotid atherosclerotic plaques. The Ho:YAG laser and TFL are effective and safe for ablating the plaque in vitro.
Analysis of the Influence of the Moment the Internationalization Process Begins on the Internationalization Intensity of Family and Nonfamily Businesses: An Approach Using a Tobit Model
Authors: Varas-Fuente Oscar Javier , Arguedas-Sanz Raquel , Rodrigo-Moya Beatriz
Published: October 2022

The specific characteristics of family businesses as well as the internationalization path followed can influence the intensity of the internationalization process. Many studies have analyzed how family character can influence the internationalization process of family businesses, and the results obtained have not been conclusive. Nevertheless, previous research has not sufficiently addressed the influence that the moment of initiation of the internationalization process has on the levels of internationalization achieved. Based on the behavioral agency model, the unique set of business resources (familiness), and the socioemotional wealth (SEW) perspective, this study examines, the internationalization intensity of family and nonfamily businesses in two defined groups (early internationalization and internationalization from the local market). Likewise, the effect that the entry of the second generation has on the internationalization of these companies is analyzed. To perform this analysis, Tobit regression models are estimated from a data set of panel data from the Spanish Survey on Business Strategies for small and medium-sized Spanish family businesses from 2005 to 2016, finding that family ownership and management have a negative influence on the intensity of exports, regardless of the path of internationalization followed, and that the entry of new generations has a positive relationship with the level of internationalization of these businesses. Finally, implications of the findings for research and management are discussed.
The Cranial Morphology of the Black-Footed Ferret: A Comparison of Wild and Captive Specimens
Authors: Antonelli Tyler , Leischner Carissa L. , Hartstone-Rose Adam
Published: October 2022

The black-footed ferret (Mustela nigripes), a North American mustelid species, was once found abundantly throughout the Midwest until the extreme decline in prairie dogs (Cynomys spp.), the black-footed ferret’s primary food source, brought the species to near-extinction. Subsequently, the Black-Footed Ferret Recovery Program was created in the 1980s with a goal of bringing all remaining individuals of the species into captivity in order to breed the species back to a sustainable population level for successful reintroduction into the wild. While many components of the ferrets’ health were accounted for while in captivity—especially those affecting fecundity—this study aims to assess the effects that captivity may have had on their cranial morphology, something that has not been widely studied in the species. In a previous study, we showed that the captive ferrets had significant oral health problems, and here we aim to document how the captive diet also affected their skull shape. For this study, 23 cranial measurements were taken on the skulls of 271 adult black-footed ferrets and 53 specimens of two closely related species. Skulls were divided based on sex, species, captivity status and phase of captivity and compared for all measurements using stepwise discriminant analysis as well as principal component analysis derived from the combined variables. We found that there are significant differences between captive and wild specimens, some of which are larger than interspecific variation, and that a diet change in the captive specimens likely helped decrease some of these differences. The results suggest that captivity can cause unnatural cranial development and that diet likely has a major impact on cranial morphology.
Phytoestrogens: A Review of Their Impacts on Reproductive Physiology and Other Effects upon Grazing Livestock
Authors: Wyse Jessica , Latif Sajid , Gurusinghe Saliya , McCormick Jeffrey , Weston Leslie A. , Stephen Cyril P.
Published: October 2022

Legume crops and pastures have a high economic value in Australia. However, legume species commonly used for grazing enterprises have been identified to produce high concentrations of phytoestrogens. These compounds are heterocyclic phenolic, and are similar in structure to the mammalian estrogen, 17β-estradiol. The biological activity of the various phytoestrogen types; isoflavones, lignans and coumestans, are species-specific, although at concentrations of 25 mg/kg of dry matter each of the phytoestrogen types affect reproductive functions in grazing livestock. The impacts upon fertility in grazing livestock such as cattle and sheep, vary greatly over length of exposure time, age and health of animal and the stress stimuli the plant is exposed to. More recently, research into the other effects that phytoestrogens may have upon metabolism, immune capacity and growth and performance of grazing livestock has been conducted. Potential new benefits for using these phytoestrogens, such as daidzein and genistein, have been identified by observing the stimulation of production in lymphocytes and other antibody cells. Numerous isoflavones have also been recognized to promote protein synthesis, increase the lean meat ratio, and increase weight gain in cattle and sheep. In Australia, the high economic value of legumes as pasture crops in sheep and cattle production enterprises requires proactive management strategies to mitigate risk associated with potential loss of fertility associated with inclusion of pasture legumes as forages for grazing livestock.
Ultrasonography and Infrared Thermography as a Comparative Diagnostic Tool to Clinical Examination to Determine Udder Health in Sows
Authors: Spiegel Sebastian , Spiegel Florian , Luepke Matthias , Wendt Michael , von Altrock Alexandra
Published: October 2022

The aim of the study was to examine whether the use of infrared thermography and ultrasonography can complement or replace the clinical examination of the sows’ mammary glands for pathological alterations. Sows of different parities with inconspicuous udders on palpation before and after birth (n = 35) and sows at the time of weaning (n = 107) were examined. Thermal images were taken from both sides of the udder, while ultrasound pictures were taken from four sides of the respective mammary glands. Within three weeks before birth, a statistically significant increase in the average surface temperature of the glands of about 1.54 °C and of the thickness of the parenchyma of about 1.39 cm could be observed. After weaning, in 10.3% of the examined sows, roundish hyperechogenic nodules were detected sonographically in the glands´ parenchyma. The average skin temperature above the nodules was 1.24 °C lower compared to the total skin area of the altered complex. However, scratches on the udder skin showed similar temperature changes. In two sows, the nodules remained undetected during the clinical examination. Therefore, sonography seems to be superior compared to clinical and thermographic investigations, although it proved to be very time-consuming.
Urban Birds as Antimicrobial Resistance Sentinels: White Storks Showed Higher Multidrug-Resistant Escherichia coli Levels Than Seagulls in Central Spain
Authors: Martín-Maldonado Bárbara , Rodríguez-Alcázar Pablo , Fernández-Novo Aitor , González Fernando , Pastor Natalia , López Irene , Suárez Laura , Moraleda Virginia , Aranaz Alicia
Published: October 2022

The presence of AMR bacteria in the human–animal–environmental interface is a clear example of the One Health medicine. Several studies evidence the presence of resistant bacteria in wildlife, which can be used as a good indicator of anthropization level on the ecosystem. The fast increase in AMR in the environment in the last decade has been led by several factors as globalization and migration. Migratory birds can travel hundreds of kilometers and disseminate pathogens and AMR through different regions or even continents. The aim of this study was to compare the level of AMR in three migratory bird species: Ciconia ciconia, Larus fuscus and Chroicocephalus ridibundus. For this purpose, commensal Escherichia coli has been considered a useful indicator for AMR studies. After E. coli isolation from individual cloacal swabs, antimicrobial susceptibility tests were performed by the disk-diffusion method, including 17 different antibiotics. A total of 63.2% of gulls had resistant strains, in contrast to 31.6% of white storks. Out of all the resistant strains, 38.9% were considered multi-drug resistant (50% of white storks and 30% of seagulls). The antibiotic classes with the highest rate of AMR were betalactamics, quinolones and tetracyclines, the most commonly used antibiotic in human and veterinary medicine in Spain.
A Surveillance Video Real-Time Object Detection System Based on Edge-Cloud Cooperation in Airport Apron
Authors: Lyu Zonglei , Luo Jia
Published: October 2022

Airport apron carries a lot of preparations for flight operation, and the advancement of its various tasks is of great significance to the flight operation. In order to build a more intelligent and easy-to-deploy airport apron operation analysis guarantee system, it is necessary to study a low-cost, fast, and real-time object detection scheme. In this article, a real-time object detection solution based on edge cloud system for airport apron operation surveillance video is proposed, which includes lightweight detection model Edge-YOLO, edge video detection acceleration strategy, and a cloud-based detection results verification mechanism. Edge-YOLO reduces the amounts of parameters and computational complexity by using model lightweight technology, which can achieve better detection speed performance on edge-end embedded devices with weak computing power, and adds an attention mechanism to compensate for accuracy loss. Edge video detection acceleration strategy achieves further detection acceleration for Edge-YOLO by utilizing the motion information of objects in the video to achieve real-time detection. Cloud-based detection results verification mechanism verifies and corrects the detection results generated by the edge through a multi-level intervention mechanism to improve the accuracy of the detection results. Through this solution, we can achieve reliable and real-time monitoring of airport apron video on edge devices with the support of a small amount of cloud computing power.
Long-Term Warming and Nitrogen Addition Regulate Responses of Dark Respiration and Net Photosynthesis in Boreal Bog Plants to Short-Term Increases in CO2 and Temperature
Authors: Le Thuong Ba , Wu Jianghua , Gong Yu , Dinh Mai-Van
Published: October 2022

Boreal bog plants adapted to cold and low available nutrient conditions might be strongly affected by global changes, including elevated CO2 (eCO2), warming (W), and increasing nitrogen (N) availability. Here, we examined responses of dark respiration (Rd) and net photosynthesis (Anet) in four dominant bog plants to five levels of short-term increases in both CO2 and temperature (CTI); and the effects of long-term (6 years) W and N addition on these responses. Results indicated that CTI increased Rd; meanwhile, the increase of these environmental variables decreased Anet in all these boreal bog plants. Long-term nitrogen addition simulated the increases of Rd and decreases of Anet in Trichophorum cespitosum. Long-term warming mitigated the increases of Rd in Andromeda glaucophylla and Gaylussacia bigeloviana, and the decrease of Anet in Gaylussacia bigeloviana. These findings highlight the importance of long-term warming and nitrogen addition in regulating responses of boreal bog plants to short-term CTI, suggesting the necessity to investigate the long-term effects of these environmental changes when projecting responses of boreal bog vegetation to global changes.
Climatology of O/N2 Variations at Low- and Mid-Latitudes during Solar Cycles 23 and 24
Authors: Khan Jahanzeb , Younas Waqar , Khan Majid , Amory-Mazaudier Christine
Published: October 2022

We present a study concerning the thermospheric O/N2 variations for the period 2002 to 2020, using the measurements of global ultraviolet imager (GUVI) onboard TIMED satellite. In this regard, monthly averaged O/N2 was computed—using the five quietest days of the month—at low- and mid-latitudes. To find the longitudinal dependence of thermospheric variations, the analysis is further extended to different longitudinal sectors, namely Asia, Africa, and America. We found that the latitudinal and longitudinal O/N2 variations follow the solar activity. These variations, during a high solar activity in northern winter, are found to be always much greater than southern winter and northern summer. The latitudinal and longitudinal variations of O/N2 at low- and mid-latitudes in December solstice are observed to be higher than June solstice counterparts in the northern hemisphere. We also computed the amplitudes of annual and semiannual variations using the bandpass filters. The former variations of O/N2 for low-latitudes do not follow the solar activity in the southern hemisphere. Moreover, these variations are stronger for mid-latitudes as compared with low-latitude regions. Similarly, the annual variations in Asian and African sectors of southern hemisphere do not follow the solar cycle (SC) trends. In the northern hemisphere, the variations are stronger during a solar maximum than in the southern counterpart. The observed semiannual variations are in-phase for both hemispheres; moreover, the corresponding amplitude remains almost the same at low- and mid-latitudes, while the semiannual variations for low-latitudes, and corresponding longitudinal regions, are stronger during a high solar activity. These variations, for mid-latitudes, in African, northern Asian, and southern American sectors do not follow the SC activity.
Study of SOC Estimation by the Ampere-Hour Integral Method with Capacity Correction Based on LSTM
Authors: Zhang Xin , Hou Jiawei , Wang Zekun , Jiang Yueqiu
Published: October 2022

The estimation of the state of charge (SOC) of a battery’s power is one of the key technologies in a battery management system (BMS). As a common SOC estimation method, the traditional ampere-hour integral method regards the actual capacity of the battery, which is constantly changed by the usage conditions and environment, as a constant for calculation, which may cause errors in the results of SOC estimation. Considering the above problems, this paper proposes an improved ampere-hour integral method based on the Long Short-Term Memory (LSTM) network model. The LSTM network model is used to obtain the actual battery capacity variation, replacing the fixed value of battery capacity in the traditional ampere-hour integral method and optimizing the traditional ampere-hour integral method to improve the accuracy of the SOC estimation method. The experimental results show that the errors of the results obtained by the improved ampere-hour integral method for the SOC estimation are all less than 10%, which proves that the proposed design method is feasible and effective.
Biophysical Stimulation in Delayed Fracture Healing of Hand Phalanx: A Radiographic Evaluation
Authors: De Francesco Francesco , Gravina Pasquale , Varagona Stefano , Setti Stefania , Gigante Antonio , Riccio Michele
Published: October 2022

Phalangeal fractures are common events among the upper limbs accounting for 10% of all human body fractures. Fracture complete healing process may persevere several months or years. Most phalangeal fractures present favorable union within 3 to 6 weeks. In the literature, biophysical stimulation has yielded favorable outcomes in the treatment of hand fractures. A survey involving hospitals in the US reported the use of biophysical stimulation (72%) in relation to nonhealing fractures at three months after trauma. A noninvasive procedure such as biophysical stimulation may be preferential prior to consideration of invasive procedures. In this retrospective study, we analyzed 80 phalangeal fractures, 43 of which did not show any radiographic sign of healing 30 days after surgery; on radiograms, we calculated radiographic data and the total active motion (TAM) for clinical comparison. All radiographic images were evaluated using Adobe Photoshop CS3 (version 10.0, Adobe Systems Inc., San Jose, CA, USA). We calculated the index of relative bone healing each month after surgery starting from 30 days, which was considered as T1, and followed up for a total of 6 months after stimulation (T6) with better results in stimulated groups. We concluded that prompt administration of biophysical stimulation supports fracture healing and yields an important improvement in the union rate compared with nontreatment. Above all, our patients experienced less injury-related distress between the fracture and repair period, which consequently reduced immobilization time, envisaging an early rehabilitation interval, with a better patient hand outcome.
Adalimumab Originator vs. Biosimilar in Hidradenitis Suppurativa: A Multicentric Retrospective Study
Authors: Burlando Martina , Fabbrocini Gabriella , Marasca Claudio , Dapavo Paolo , Chiricozzi Andrea , Malvaso Dalma , Dini Valentina , Campanati Anna , Offidani Annamaria , Dattola Annunziata , Caro Raffaele Dante Caposiena , Bianchi Luca , Venturini Marina , Gisondi Paolo , Guarneri Claudio , Malara Giovanna , Trifirò Caterina , Malagoli Piergiorigio , Fargnoli Maria Concetta , Piaserico Stefano , Carmisciano Luca , Castelli Riccardo , Parodi Aurora
Published: October 2022

This study aimed to compare adalimumab originator vs. biosimilar in HS patients, and to evaluate the effect of a switch to a biosimilar, or a switch back to the originator, in terms of treatment ineffectiveness. Patients with a diagnosis of HS were enrolled from 14 Italian sites. Treatment ineffectiveness was measured using Hurley score. The major analyses were 1) comparison between the two treatment groups (non-switcher analysis), and 2) the cross-over trend of Hurley score between treatment switchers (switcher analysis). Cox and Poisson regression models were used to compare the treatment ineffectiveness between groups. A total of 326 patients were divided into four groups: 171 (52.5%) taking originator; 61 (18.7%) patients taking biosimilar; 66 (20.2%) switchers; 28 (8.6%) switchers from originator to biosimilar and switched. A greater loss of efficacy was observed in the group allocated to the biosimilar than the originator group. The switcher analysis showed an effectiveness loss in the biosimilar compared to the originator. These results seem to indicate that a switch from one drug to the other may lead to a greater risk of inefficacy. A return to the previous treatment also does not ensure efficaciousness.
Early Clinical Remission Is a Predictor of Long-Term Remission with the Use of Vedolizumab for Ulcerative Colitis
Authors: Haga Keiichi , Shibuya Tomoyoshi , Osada Taro , Sato Shunsuke , Fukuo Yuka , Kobayashi Osamu , Yamada Toshio , Asaoka Daisuke , Ito Kentaro , Nomura Kei , Haraikawa Mayuko , Nomura Osamu , Fukushima Hirofumi , Murakami Takashi , Ishikawa Dai , Hojo Mariko , Nagahara Akihito
Published: October 2022

Vedolizumab (VDZ) is an α4β7 integrin-antibody used to manage refractory ulcerative colitis (UC). This retrospective multicenter study aimed to identify predictors of efficacy or the time points when evaluation of VDZ therapy for UC would be most useful. We compiled data on 87 patients with moderate to severe active UC that was treated with VDZ. Overall clinical remission (CR) rates at 6 weeks and 52 weeks after VDZ administration were 44.4% (bio-naïve 44.2%, bio-failure 44.8%) and 52.8% (bio-naïve 53.5%, bio-failure 51.7%) respectively. Also, 83.3% (bio-naïve 81.3%, bio-failure 85.7%) of patients achieved mucosal healing at week 52. Among patients with a CR at week 52, 73.3% had a CR at week 6. In contrast, of patients who discontinued VDZ, 82.4% had not reached a CR at week 6. Our study demonstrated that VDZ was effective in a large percentage of UC patients, with a high mucosal healing rate even after prior biological exposures. This suggests that VDZ can be a treatment option even in bio-failure cases. Additionally, it was considered that early CR can predict long-term remission and that week 6 can be a helpful evaluation point for treatment decisions when using VDZ for UC.
Autologous Adipose Tissue vs. Platelet-Rich Plasma for Treatment of Knee Osteoarthritis
Authors: Gupta Ashim
Published: October 2022

Osteoarthritis (OA) is a tremendously widespread joint ailment, typically affecting large weight-bearing joints and influencing over 30 million individuals in the United States, with the anticipated number of patients to reach 67 million by 2030 [...]
An Asymmetric Microfluidic/Chitosan Device for Sustained Drug Release in Guided Bone Regeneration Applications
Authors: Shi Xin , Ma Beibei , Chen Hongyu , Tan Wei , Ma Shiqing , Zhu Guorui
Published: October 2022

One of the major challenges of guided bone regeneration (GBR) is infections caused by pathogen colonization at wound sites. In this paper, an asymmetric microfluidic/chitosan device was developed to release drugs to inhibit infections and to ensure that guided bone regeneration can be realized. The microfluidic technique was introduced into the GBR membrane for the first time, which demonstrated more controllable drug release, more flexible clinical use and had a lower cost compared with surface treatments and embedded nanoparticles. Based on the theory of diffusion and Fick’s first law, the contact area and concentration gradient were adjusted to realize sustained drug release. The standard deviation of minocycline release over 5 days was only 12.7%, which was lower than the joint effect of porous chitosan discs and nanospheres. The in vitro experiments against E. coli and Streptococcus mutans showed the excellent antibacterial performance of the device (>95%). The in vitro experiments for fibroblasts at the microfluidic side and osteoblasts at the chitosan side showed the satisfactory biocompatibility and the ability of the device to enhance bone regeneration. Therefore, this microfluidic/chitosan device is a promising therapeutic approach to prevent infection and guide bone regeneration.
Aptamer against Aflatoxin B1 Obtained by SELEX and Applied in Detection
Authors: Yang Chung-Hsuan , Tsai Ching-Hsiu
Published: October 2022

Aflatoxins, especially aflatoxin B1 (AFB1), are the most prevalent mycotoxins in nature. They contaminate various crops and cause global food and feed safety concerns. Therefore, a simple, rapid, sensitive, and specific AFB1 detection tool is urgently needed. Aptamers generated by SELEX technology can specifically bind the desired targets with high affinity. The broad range of targets expands the scope of applications for aptamers. We used an AFB1-immobilized magnetic nanoparticle for SELEX to select AFB1-specific aptamers. One aptamer, fl−2CS1, revealed a dissociation constant (Kd = 2.5 μM) with AFB1 determined by isothermal titration calorimetry. Furthermore, no interaction was shown with other toxins (AFB2, AFG1, AFG2, OTA, and FB1). According to structural prediction and analysis, we identified a short version of the AFB1-specific aptamer, fl−2CS1/core, with a minimum length of 39-mer used in the AFB1-aptasensor system by real-time qPCR. The aptasensor showed a broad range of detection from 50 ppt to 50 ppb with an accuracy of 90% in the spiked peanut extract samples. With the application of the AFB1-aptasensor we have constructed, a wide range detection tool with high accuracy might be developed as a point-of-care testing tool in agriculture.
Paper-Based Screen-Printed Ionic-Liquid/Graphene Electrode Integrated with Prussian Blue/MXene Nanocomposites Enabled Electrochemical Detection for Glucose Sensing
Authors: Niamsi Wisanu , Larpant Nutcha , Kalambate Pramod K. , Primpray Vitsarut , Karuwan Chanpen , Rodthongkum Nadnudda , Laiwattanapaisal Wanida
Published: October 2022

As glucose biosensors play an important role in glycemic control, which can prevent the diabetic complications, the development of a glucose sensing platform is still in needed. Herein, the first proposal on the in-house fabricated paper-based screen-printed ionic liquid/graphene electrode (SPIL-GE) modified with MXene (Ti3C2Tx), prussian blue (PB), glucose oxidase (GOx), and Nafion is reported. The concentration of PB/Ti3C2Tx was optimized and the optimal detection potential of PB/Ti3C2Tx/GOx/Nafion/SPIL-GE is −0.05 V. The performance of PB/Ti3C2Tx/GOx/Nafion modified SPIL-GE was characterized by cyclic voltammetry and chronoamperometry technique. This paper-based platform integrated with nanomaterial composites were realized for glucose in the range of 0.0–15.0 mM with the correlation coefficient R2 = 0.9937. The limit of detection method and limit of quantification were 24.5 μM and 81.7 μM, respectively. In the method comparison, this PB/Ti3C2Tx/GOx/Nafion/SPIL-GE exhibits a good correlation with the reference hexokinase method. This novel glucose sensing platform can potentially be used for the good practice to enhance the sensitivity and open the opportunity to develop paper-based electroanalytical devices.
Postoperative Delirium in Neurosurgical Patients: Recent Insights into the Pathogenesis
Authors: Xu Yinuo , Ma Qianquan , Du Haiming , Yang Chenlong , Lin Guozhong
Published: October 2022

Postoperative delirium (POD) is a complication characterized by disturbances in attention, awareness, and cognitive function that occur shortly after surgery or emergence from anesthesia. Since it occurs prevalently in neurosurgical patients and poses great threats to the well-being of patients, much emphasis is placed on POD in neurosurgical units. However, there are intricate theories about its pathogenesis and limited pharmacological interventions for POD. In this study, we review the recent insights into its pathogenesis, mainly based on studies within five years, and the five dominant pathological theories that account for the development of POD, with the intention of furthering our understanding and boosting its clinical management.
Identifying Tissue- and Cohort-Specific RNA Regulatory Modules in Cancer Cells Using Multitask Learning
Authors: Mokhtaridoost Milad , Maass Philipp G. , Gönen Mehmet
Published: October 2022

MicroRNA (miRNA) alterations significantly impact the formation and progression of human cancers. miRNAs interact with messenger RNAs (mRNAs) to facilitate degradation or translational repression. Thus, identifying miRNA–mRNA regulatory modules in cohorts of primary tumor tissues are fundamental for understanding the biology of tumor heterogeneity and precise diagnosis and treatment. We established a multitask learning sparse regularized factor regression (MSRFR) method to determine key tissue- and cohort-specific miRNA–mRNA regulatory modules from expression profiles of tumors. MSRFR simultaneously models the sparse relationship between miRNAs and mRNAs and extracts tissue- and cohort-specific miRNA–mRNA regulatory modules separately. We tested the model’s ability to determine cohort-specific regulatory modules of multiple cancer cohorts from the same tissue and their underlying tissue-specific regulatory modules by extracting similarities between cancer cohorts (i.e., blood, kidney, and lung). We also detected tissue-specific and cohort-specific signatures in the corresponding regulatory modules by comparing our findings from various other tissues. We show that MSRFR effectively determines cancer-related miRNAs in cohort-specific regulatory modules, distinguishes tissue- and cohort-specific regulatory modules from each other, and extracts tissue-specific information from different cohorts of disease-related tissue. Our findings indicate that the MSRFR model can support current efforts in precision medicine to define tumor-specific miRNA–mRNA signatures.
Roles of Chromatin Remodelling and Molecular Heterogeneity in Therapy Resistance in Glioblastoma
Authors: Chen Huey-Miin , Nikolic Ana , Singhal Divya , Gallo Marco
Published: October 2022

Cancer stem cells (CSCs) represent a therapy-resistant reservoir in glioblastoma (GBM). It is now becoming clear that epigenetic and chromatin remodelling programs link the stemlike behaviour of CSCs to their treatment resistance. New evidence indicates that the epigenome of GBM cells is shaped by intrinsic and extrinsic factors, including their genetic makeup, their interactions and communication with other neoplastic and non-neoplastic cells, including immune cells, and their metabolic niche. In this review, we explore how all these factors contribute to epigenomic heterogeneity in a tumour and the selection of therapy-resistant cells. Lastly, we discuss current and emerging experimental platforms aimed at precisely understanding the epigenetic mechanisms of therapy resistance that ultimately lead to tumour relapse. Given the growing arsenal of drugs that target epigenetic enzymes, our review addresses promising preclinical and clinical applications of epidrugs to treat GBM, and possible mechanisms of resistance that need to be overcome.
A Multi-Centre Study to Risk Stratify Colorectal Polyp Surveillance Patients Utilising Volatile Organic Compounds and Faecal Immunochemical Test
Authors: Chandrapalan Subashini , Khasawneh Farah , Singh Baljit , Lewis Stephen , Turvill James , Persaud Krishna , Arasaradnam Ramesh P.
Published: October 2022

(1) Background: The service capacity for colonoscopy remains constrained, and while efforts are being made to recover elective services, polyp surveillance remains a challenge. (2) Methods: This is a multi-centre study recruiting patients already on polyp surveillance. Stool and urine samples were collected for the faecal immunochemical test (FIT) and volatile organic compounds (VOC) analysis, and all participants then underwent surveillance colonoscopy. (3) Results: The sensitivity and specificity of VOC for the detection of a high-risk finding ((≥2 premalignant polyps including ≥1 advanced polyp or ≥5 premalignant polyps) were 0.94 (95% CI, 0.88 to 0.98) and 0.69 (95% CI, 0.64 to 0.75) respectively. For FIT, the sensitivity was (≥10 µg of haemoglobin (Hb) / g faeces) 0.54 (95% CI, 0.43 to 0.65) and the specificity was 0.79 (95% CI, 0.73 to 0.84). The probability reduction for having a high-risk finding following both negative VOC and FIT will be 24% if both tests are applied sequentially. (4) Conclusion: The diagnostic performance of VOC is superior to FIT for the detection of a high-risk finding. The performance further improves when VOC is applied together with FIT sequentially (VOC first and then FIT). VOC alone or the combination of VOC and FIT can be used as a triage tool for patients awaiting colonoscopy within a polyp surveillance population, especially in resource-constrained healthcare systems.
Clinical Trends in Management of Locally Advanced ESCC: Real-World Evidence from a Large Single-Center Cohort Study
Authors: Jeon Yeong Jeong , Yoo Junsang , Cho Jong Ho , Shim Young Mog
Published: October 2022

Neoadjuvant chemoradiation followed by surgery (NCRT+S) has been widely applied to patients with locally advanced esophageal squamous cell carcinoma (ESCC); however, treatment trends and their survival outcomes in a real-world clinical setting are poorly understood. This study aimed to analyze real-world evidence to understand treatment patterns and outcomes for patients with ESCC. We analyzed the treatment pattern and 5-year overall survival (5yOS) by synthesizing the individuals’ general characteristics, cancer information, and treatment records extracted from the Clinical Data Warehouse from 1994 to 2018. Of a total of 2151 patients, most patients received upfront surgery and 5yOS was 36.8% (31.4–43.1%). From 2003 to 2012, the use of NCRT increased, and 5yOS was improved to 42.2% (38.8–45.7%). Notably, after 2013, the proportion of NCRT+S markedly increased up to >50% of patients: 5yOS was much improved to 56.3% (53.2–59.6%). With regard to treatment, patients with NCRT+S had the most favorable 5yOS of 58.1% (53–63.7%), although that for patients with upfront surgery was 48.6% (45.9–51.5%, p < 0.001). Moreover, patients who received adjuvant therapy after surgery had better OS than those with surgery alone (58.4% (52.7–64.7%) vs. 47.3% (44.1–50.7%), p < 0.001). This analysis of real-world data demonstrated a significantly improved survival outcome for locally advanced ESCC over time since NCRT prior to surgery had been routinely applied. We revealed that NCRT+S was the most effective treatment for locally advanced ESCC and that adjuvant chemotherapy may be an encouraging therapeutic option for patients with positive nodes after upfront surgery.
Prognostic Value of Circulating Tumor DNA (ctDNA) in Oncogene-Driven NSCLC: Current Knowledge and Future Perspectives
Authors: Zografos Eleni , Dimitrakopoulos Foteinos-Ioannis , Koutras Angelos
Published: October 2022

As we enter an unprecedented era of personalized medicine, molecular targeted therapies have the potential to induce improved survival outcome in patients with non-small cell lung cancer (NSCLC). However, a significant percentage of oncogene-driven NSCLC patients will relapse even after definitive treatment, whereas chronic and durable response to targeted therapies is a less common event in advanced-stage lung cancer. This phenomenon could be attributed to minimal residual disease (MRD), defined as a population of disseminated tumor cells that survive during the course or after treatment, eventually leading to recurrence and limiting patient survival. Circulating tumor DNA (ctDNA) is a powerful biomarker for MRD detection and monitoring and is a non-invasive approach of treating cancer, and especially NSCLC, based on a real-time assessment of the tumor genomic landscape. In this review, we present the key findings of studies that have used ctDNA with regard to its prognostic value and in respect to the most common druggable driver mutations of genes in NSCLC, such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), rearranged during transfection (RET), Kirsten rat sarcoma virus (KRAS), B-Raf proto-oncogene (BRAF), and mesenchymal epithelial transition factor receptor (MET).
Multi- and Transgenerational Effects of Environmental Toxicants on Mammalian Reproduction
Authors: Rebuzzini Paola , Fabozzi Gemma , Cimadomo Danilo , Ubaldi Filippo Maria , Rienzi Laura , Zuccotti Maurizio , Garagna Silvia
Published: October 2022

Environmental toxicants (ETs) are an exogenous chemical group diffused in the environment that contaminate food, water, air and soil, and through the food chain, they bioaccumulate into the organisms. In mammals, the exposure to ETs can affect both male and female fertility and their reproductive health through complex alterations that impact both gametogeneses, among other processes. In humans, direct exposure to ETs concurs to the declining of fertility, and its transmission across generations has been recently proposed. However, multi- and transgenerational inheritances of ET reprotoxicity have only been demonstrated in animals. Here, we review recent studies performed on laboratory model animals investigating the effects of ETs, such as BPA, phthalates, pesticides and persistent contaminants, on the reproductive system transmitted through generations. This includes multigenerational effects, where exposure to the compounds cannot be excluded, and transgenerational effects in unexposed animals. Additionally, we report on epigenetic mechanisms, such as DNA methylation, histone tails and noncoding RNAs, which may play a mechanistic role in a nongenetic transmission of environmental information exposure through the germline across generations.