bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances in drug delivery applications of modified bacterial cellulose-based materials
Authors: Liang Shuya
Published: August 2023

Bacterial cellulose (BC) is generated by certain species of bacteria and comprises polysaccharides with unique physical, chemical, and mechanical characteristics. Due to its outstanding biocompatibility, high purity, excellent mechanical strength, high water absorption, and highly porous structure, bacterial cellulose has been recently investigated for biomedical application. However, the pure form of bacterial cellulose is hardly used as a biomedical material due to some of its inherent shortcomings. To extend its applications in drug delivery, modifications of native bacterial cellulose are widely used to improve its properties. Usually, bacterial cellulose modifications can be carried out by physical, chemical, and biological methods. In this review, a brief introduction to bacterial cellulose and its production and fabrication is first given, followed by up-to-date and in-depth discussions of modification. Finally, we focus on the potential applications of bacterial cellulose as a drug delivery system.
Analytical approaches for the evaluation of data deficient simulated leachable compounds in ENDS products: a case study
Authors: Smith Cameron , Lyndon Matthew , Jeong Lena , Lehman Danielle , Jameson J. Brian , Chevva Harish , Ayala-Fierro Felix , Cook David , Carter Karen , Oldham Michael , Gillman I. Gene
Published: August 2023

Leachable investigations are routinely undertaken across a range of sectors (e.g., pharmaceuticals, medical devices, etc.) to determine whether chemicals from a container closure system transfer into a product under normal conditions of use. For Electronic Nicotine Delivery Systems (ENDS) the container closure system includes all materials in contact with the e-liquid that is aerosolized and subsequently inhaled by the user. Currently, there is no guidance for conducting leachable studies for ENDS products, however, there are relevant guidance documents for orally inhaled drug products that can be applied to an ENDS container closure system. We present a case study of the analytical investigation of two leachable compounds identified in simulated leachable studies using aged JUULpods filled with unflavored e-liquid (PG/VG/nicotine/benzoic acid). Both compounds had limited toxicological information and were considered data deficient. A qualitative analysis of the aerosol collected from aged commercial JUULpods (Virginia Tobacco and Menthol), using a similar analytical method (LC-MS/MS) used in the simulated leachable studies, showed no trace or detectable levels of either leachable compound. Therefore, this qualitative analysis did not provide semi-quantitative values for the data-deficient leachable compounds necessary to support toxicological risk assessment. Further, no commercial authentic standards or reasonable synthetic route were available due to the molecular size and structural complexity of the compounds. Instead, method limits were established using an alternative approach to standard ICH guidelines. The experimentally determined method limit of quantitation, using spiked samples of simulated leachable e-liquid, provided conservative semi-quantitative values for each data deficient leachable compound in the aerosol that enabled a transfer efficiency from e-liquid to aerosol to be estimated. The transfer efficiency of each leachable compound was experimentally determined to be less than 3% based on the limit of quantitation, which then could be used to define a relevant exposure limit for the toxicological risk assessment. This work details a novel analytical approach for determining the transfer efficiency of data deficient leachable compounds from ENDS container closure systems into the ENDS aerosol to support toxicological health risk assessments.
Biofabrication of novel silver and zinc oxide nanoparticles from Fusarium solani IOR 825 and their potential application in agriculture as biocontrol agents of phytopathogens, and seed germination and seedling growth promoters
Authors: Trzcińska-Wencel Joanna , Wypij Magdalena , Terzyk Artur P. , Rai Mahendra , Golińska Patrycja
Published: August 2023

Introduction: Plant pathogenic microorganisms adversely affect the growth and yield of crops, which consequently leads to losses in food production. Metal-based nanoparticles (MNPs) can be a remedy to solve this problem.

Methods: Novel silver nanoparticles (AgNPs) and zinc oxide nanoparticles (ZnONPs) were biosynthesized from Fusarium solani IOR 825 and characterized using Dynamic Light Scattering (DLS), Fourier Transform Infrared (FTIR) spectroscopy, Transmission Electron Microscopy (TEM), X-ray diffraction (XRD) and measurement of Zeta potential. Antibacterial activity of NPs was evaluated against four plant pathogenic strains by determination of the minimum inhibitory (MIC) and biocidal concentrations (MBC). Micro-broth dilution method and poisoned food technique were used to assess antifungal activity of NPs against a set of plant pathogens. Effect of nanopriming with both types of MNPs on maize seed germination and seedlings growth was evaluated at a concentration range of 1–256 μg mL-1.

Results: Mycosynthesis of MNPs provided small (8.27 nm), spherical and stable (zeta potential of −17.08 mV) AgNPs with good crystallinity. Similarly, ZnONPs synthesized by using two different methods (ZnONPs(1) and ZnONPs(2)) were larger in size (117.79 and 175.12 nm, respectively) with Zeta potential at −9.39 and −21.81 mV, respectively. The FTIR spectra showed the functional groups (hydroxyl, amino, and carboxyl) of the capping molecules on the surface of MNPs. The values of MIC and MBC of AgNPs against bacteria ranged from 8 to 256 μg mL-1 and from 512 to 1024 μg mL-1, respectively. Both types of ZnONPs displayed antibacterial activity at 256–1024 μg mL-1 (MIC) and 512–2048 μg mL-1 (MBC), but in the concentration range tested, they revealed no activity against Pectobacterium carotovorum. Moreover, AgNPs and ZnONPs inhibited the mycelial growth of Alternaria alternata, Fusarium culmorum, Fusarium oxysporum, Phoma lingam, and Sclerotinia sclerotiorum. MIC and MFC values of AgNPs ranged from 16–128 and 16–2048 μg mL -1, respectively. ZnONPs showed antifungal activity with MIC and MFC values of 128–2048 μg mL-1 and 256–2048 μg mL-1, respectively. The AgNPs at a concentration of ≥32 μg mL-1 revealed sterilization effect on maize seeds while ZnONPs demonstrated stimulatory effect on seedlings growth at concentrations of ≥16 μg mL-1 by improving the fresh and dry biomass production by 24% and 18%–19%, respectively.

Discussion: AgNPs and ZnONPs mycosynthesized from F. solani IOR 825 could be applied in agriculture to prevent the spread of pathogens. However, further toxicity assays should be performed before field evaluation. In view of the potential of ZnONPs to stimulate plant growth, they could be crucial in increasing crop production from the perspective of current food assurance problems.
A study of deep learning algorithm usage in predicting building loss ratio due to typhoons: the case of southern part of the Korean Peninsula
Authors: Kim Ji-Myong , Bae Junseo , Adhikari Manik Das , Yum Sang-Guk
Published: August 2023

The goal of this study is to suggest an approach to predict building loss due to typhoons using a deep learning algorithm. Due to the influence of climate change, the frequency and severity of typhoons gradually increase and cause exponential destruction of building. Therefore, related industries and the government are focusing their efforts on research and model development to quantify precisely the damage caused by typhoons. However, advancement in the accuracy of prediction is still needed, and the introduction of new technology, obtained due to the fourth revolution, is necessary. Therefore, this study proposed a framework for developing a model based on a deep neural network (DNN) algorithm for predicting losses to buildings caused by typhoons. The developed DNN model was tested and verified by calculating mean absolute error (MAE), root mean square error (RMSE) and coefficient of determination (R2). In addition, to further verify the robustness of the model, the applicability of the framework proposed in this study was verified through comparative verification with the conventional multi-regression model. The results and framework of this study will contribute to the present understanding by suggesting a deep learning method to predict the loss of buildings due to typhoons. It will also provide management strategies to related workers such as insurance companies and facility managers.
Why Central Asia’s Mushiston is not a source for the Late Bronze Age tin ingots from the Uluburun shipwreck
Authors: Berger Daniel , Kaniuth Kai , Brügmann Gerhard , Pernicka Ernst
Published: August 2023

Tin was a crucial commodity in prehistory to produce bronze, and knowledge of the origins of this metal is important for understanding cultural relations and the complexity and extent of trade. However, many aspects of the provenance of tin are still not resolved. A recent study inScience Advances8(48) examined the historically significant tin ingots from the Uluburun shipwreck, which are key to the economy and long-distance trade of tin in the Late Bronze Age Mediterranean and beyond. Isotopic and chemical data of the objects was collected, from which a tin origin from Central Asia, particularly Mushiston in Tajikistan, and Anatolia was reconstructed. The study thereby proposed a solution to the long-standing riddle of tin provenance via scientific reasoning and comparative data. While this avenue of investigation is intriguing, this article maintains that the authors’ arguments do not support their far-reaching conclusions. Instead, it emphasises the similarities with Late and Middle Bronze Age tin ingots from Israel and Britain, and alternatively suggests a common origin of part of the Uluburun cargo with these items. South-west England is considered a very likely source region, but other tin ingots of the Uluburun wreck could also originate from Afghanistan and perhaps somewhere else.
Appraisal of geothermal potentials of some parts of the Abakaliki Anticlinorium and adjoining areas (Southeast Nigeria) using magnetic data
Authors: Eldosouky Ahmed M. , Ekwok Stephen E. , Ben Ubong C. , Ulem Christian A. , Abdelrahman Kamal , Gomez-Ortiz David , Akpan Anthony E. , George Anthony Michael , Pham Luan Thanh
Published: August 2023

The Abakaliki Anticlinorium and its adjoining areas were appraised with the object of delineating high geothermal potential zones. Spectral depth analysis involving an improved centroid technique was used to analyze high-quality magnetic data. The obtained geothermal parameters were gridded to map various geothermal features within the investigated area. The obtained results varied from 4.99–9.35 km, 2.31–6.15 km, 6.11–16.28 km, 35.63°C–94.93°C/km, and 89.07–237.32 mW/m2 for centroid depth, top depth, Curie point depth, geothermal gradient, and heat flow values, respectively. The delineated semioval structure in the central zone of the investigated region characterized by a shallow Curie point depth (< 8.5 km) correlates with the location of the high-heat flow (>191.0 mW/m2) and geothermal gradient (>74.0°C/km) region. The high geothermal potential of the region is triggered by the massive post-rift tectonic event of the Santonian period related to the Abakaliki Anticlinorium. Further geophysical exploration programs should be carried out before exploitation activities at anomalous geothermal regions.
Teaching and learning innovations for distance learning in the digital era: a literature review
Authors: Li Kam Cheong , Wong Billy T. M. , Chan Hon Tung
Published: August 2023

This paper presents a review study on teaching and learning innovations (TLIs) for distance learning in higher education, which involves substantial use of technology in its practice. The study covers 247 publications that were published from 2017 to 2022 and collected from Scopus to analyze the patterns and trends of TLIs for distance learning in higher education. The results show four main types of TLIs: educational technologies, teaching and learning approaches and activities, teaching and learning programs, and assessment approaches and activities. They also reveal seven major pedagogical patterns in the TLIs, covering the learning of science through online laboratories, virtual and augmented reality, multimedia, gaming, collaboration, tasks/projects, and blended/hybrid/flipped learning. These findings suggest implications for distance learning, covering the use of online laboratories in science courses, promotion of virtual and augmented-based distance learning, encouragement of development, implementation, and the study of pedagogical approaches to distance learning, as well as the increase in interactivity in multimedia-based distance learning.
Research on power system fault prediction based on GA-CNN-BiGRU
Authors: Zhang Daohua , Jin Xinxin , Shi Piao
Published: August 2023

Introduction: This paper proposes a power system fault prediction method that utilizes a GA-CNN-BiGRU model. The model combines a genetic algorithm (GA), a convolutional neural network (CNN), and a bi-directional gated recurrent unit network Bidirectional Gated Recurrent Unit to accurately predict and analyze power system faults.

Methods: The proposed model employs a genetic algorithm for structural search and parameter tuning, optimizing the model structure. The CNN is used for feature extraction, while the bi-directional gated recurrent unit network is used for sequence modeling. This approach captures the correlations and dependencies in time series data and effectively improves the prediction accuracy and generalization ability of the model.

Results and Discussion: Experimental validation shows that the proposed method outperforms traditional and other deep learning-based methods on multiple data sets in terms of prediction accuracy and generalization ability. The method can effectively predict and analyze power system faults, providing crucial support and aid for the operation and management of power systems.
Recent advances in the effective removal of hazardous pollutants from wastewater by using nanomaterials—A review
Authors: Chahar Mamta , Khaturia Sarita , Singh Har Lal , Solanki Vijendra Singh , Agarwal Neha , Sahoo Dipak Kumar , Yadav Virendra Kumar , Patel Ashish
Published: August 2023

Environmental nanotechnology has developed rapidly over the past few decades due to the fast advancement of nanotechnology and nanomaterials (NMs). Due to their nanoscale size, NMs are receiving immense attention in research and development worldwide. Their nano size has led to better catalysis, high reactivity, and high adsorption capacity. In wastewater treatment, nanotechnology has significant potential to improve the performance and efficiency of water decontamination; more effectively, it provides a sustainable way to keep water supplies safe. Numerous studies have found that removing harmful components from wastewater by employing nanoparticles in conjunction with various treatment methods is effective. The purpose of the current investigation is to conduct a review of the envisioned applications of various NMs in the treatment of wastewater. These NMs include carbonaceous NMs, metal-containing nanoparticles, and nanocomposites, all of which will be reviewed and highlighted in depth.
Projections of flood regime changes over the upper-middle Huaihe River Basin in China based on CMIP6 models
Authors: Bian Guodong , Zhang Jianyun , Song Mingming , Qian Xin , Guan Tiesheng , Wang Guoqing
Published: August 2023

Introduction: Climate change alters the hydrological cycle to different extents, in particular the intensification of extreme precipitation and floods, which has garnered more attention as a significant scientific issue in the last few decades. The last Coupled Model Inter-comparison Project 6 (CMIP6) was designed with new shared socioeconomic pathways (SSPs) to combine socioeconomic development with greenhouse gas emissions to project future climate.

Method: In this study, we used 22 global climate models (GCMs) from CMIP6 to investigate future variations in extreme precipitation and temperature under SSP2-4.5 and SSP5-8.5 scenarios over the upper-middle Huaihe River Basin (UMHRB). Then, the modified Xinanjiang model integrating the flood control module was driven to obtain projections of the daily streamflow and to evaluate the future variations in flood regimes.

Results: The results show that 1) the characteristics of future extreme precipitation, such as the average intensity and amount of annual precipitation and extreme precipitation, are projected to increase, and the average, maximum, and minimum temperature values also display substantial increasing trends in the future over the UMHRB; 2) warmer climate will lead to a more severe flood magnitude under the SSP5-8.5 scenario in the far future (2071–2100) over the UMHRB. The results of the multi-model ensemble show that the annual maximum flood peaks (15-day flood volumes) of Wangjiaba and Wujiadu stations are projected to increase by 46.4% (43.1%) and 45.4% (51.1%), respectively, in the far future (2071–2100) under the SSP5-8.5 scenario; and 3) variations in the flood frequency tend to resemble variations in flood magnitude, and the return period of the design flood will obviously decrease under future climate scenarios. For instance, in the far future, under SSP5-8.5 scenarios, the return period of the design flood with a 100-year return period will become 38 years and 31 years for Wangjiaba and Wujiadu stations, respectively.

Discussion: The study enhances a more realistic understanding that the occurrence of future extreme precipitation and floods is projected to be more frequent and severe, thereby resulting in an urgent imperative to develop pertinent adaptation strategies to enhance social resilience toward the warming climate.
The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases
Authors: Navarro-Compán Victoria , Puig Luis , Vidal Silvia , Ramírez Julio , Llamas-Velasco Mar , Fernández-Carballido Cristina , Almodóvar Raquel , Pinto José Antonio , Galíndez-Aguirregoikoa Eva , Zarco Pedro , Joven Beatriz , Gratacós Jordi , Juanola Xavier , Blanco Ricardo , Arias-Santiago Salvador , Sanz Sanz Jesús , Queiro Rubén , Cañete Juan D.
Published: August 2023

Interleukin-17 family (IL-17s) comprises six structurally related members (IL-17A to IL-17F); sequence homology is highest between IL-17A and IL-17F, displaying certain overlapping functions. In general, IL-17A and IL-17F play important roles in chronic inflammation and autoimmunity, controlling bacterial and fungal infections, and signaling mainly through activation of the nuclear factor-kappa B (NF-κB) pathway. The role of IL-17A and IL-17F has been established in chronic immune-mediated inflammatory diseases (IMIDs), such as psoriasis (PsO), psoriatic arthritis (PsA), axial spondylarthritis (axSpA), hidradenitis suppurativa (HS), inflammatory bowel disease (IBD), multiple sclerosis (MS), and asthma. CD4+ helper T cells (Th17) activated by IL-23 are well-studied sources of IL-17A and IL-17F. However, other cellular subtypes can also produce IL-17A and IL-17F, including gamma delta (γδ) T cells, alpha beta (αβ) T cells, type 3 innate lymphoid cells (ILC3), natural killer T cells (NKT), or mucosal associated invariant T cells (MAIT). Interestingly, the production of IL-17A and IL-17F by innate and innate-like lymphocytes can take place in an IL-23 independent manner in addition to IL-23 classical pathway. This would explain the limitations of the inhibition of IL-23 in the treatment of patients with certain rheumatic immune-mediated conditions such as axSpA. Despite their coincident functions, IL-17A and IL-17F contribute independently to chronic tissue inflammation having somehow non-redundant roles. Although IL-17A has been more widely studied, both IL-17A and IL-17F are overexpressed in PsO, PsA, axSpA and HS. Therefore, dual inhibition of IL-17A and IL-17F could provide better outcomes than IL-23 or IL-17A blockade.
Toxicopathic effects of waterborne Cd in sole juveniles, a prospective pollution monitoring sentinel for estuarine ecosystems
Authors: Briaudeau Tifanie , Guerrero-Limón Gustavo , Zorita Izaskun , Marigómez Ionan , Izagirre Urtzi
Published: August 2023

Introduction

Estuarine ecosystems are under high anthropogenic pressure and receive a wide Q7 variety of contaminants, including metals. They can remain trapped in estuarine sediments at high concentrations for long periods but eventually they can be released to the overlying water and become toxic for the resident benthic biota. As a consequence, biomonitoring programs surveying the health status of estuaries and coastal areas count with benthic species for the assessment of health disturbances in these specific ecosystems. The present investigation aims at recognizing toxicopathic effects elicited in estuarine life stages of the benthic fish Solea senegalensis on exposure to waterborne Cd, a model compound for metal contamination.

Methods

Biological responses to metal exposure were assessed based on the application of a “biomarker + histopathology” approach. Two-year old sole juveniles were exposed to various concentrations of waterborne Cd for 3 and 7 days (Control; Low Cd: 1 µg/l; Mid Cd: 10 µg/l and High Cd: 1000 µg/l). Liver samples were collected for chemical analysis at day 7. Biological samples were collected at days 3 and 7 for biochemical (brain and liver), histochemical (liver) and histopathological analysis (liver, gills and gonad).

Results

Brain acetyl cholinesterase was inhibited after 7 days exposure, indicating neurotoxic effects on exposure to 1000 µg Cd/l. Hepatic catalase and glutathione-Stransferase were induced at day 3 and inhibited at day 7, which suggests a bell-shaped response. A dose-dependent lysosomal membrane destabilization in hepatocytes was recorded at day 7. In parallel, histopathological lesions in gills, liver and gonad were more frequent at day 7 in soles exposed to high Cd concentrations.

Discussion

Overall, the “biomarker + histopathology” approach revealed that waterborne Cd causes toxicopathic effects in sole juveniles upon exposure to environmentally relevant concentrations (10 µg Cd/l). The effects were clearly time dependent, and thus it is conceivable that more severe biological effects would be elicited by these low concentrations of Cd at longer exposure periods. Therefore, biomarkers and histopathology in combination provide early-warning indications of altered health status after waterborne Cd exposure in sole juveniles, a prospective sentinel for biological effects assessment of metal contamination in pollution monitoring programs in estuaries and coastal areas.
Emergence of the subtropical sea urchin Centrostephanus rodgersii as a threat to kelp forest ecosystems in northern New Zealand
Authors: Balemi Celia A. , Shears Nick T.
Published: August 2023

Marine protected areas have long been proposed as a key tool to restore lost food web interactions and increase the resilience of ecosystems to climate change impacts. However, a changing climate can result in the arrival of new species or differentially affect native species, which can alter ecosystem dynamics and make it difficult to predict how ecosystems will respond to protection. The long-spined sea urchin Centrostephanus rodgersii is a well-known range extender with large impacts on kelp forest ecosystems, yet its response to warming and long-term marine protection has not been examined within its native range. We examine long-term trends in C. rodgersii and the endemic sea urchin Evechinus chloroticus following no-take protection within the Poor Knights Islands Marine Reserve, in northeastern Aotearoa New Zealand, from 1999-2022, and compare with population trends at an unprotected island group. Within the marine reserve, E. chloroticus decreased in density, became more cryptic, and urchin barrens associated with this species largely disappeared, whereas in fished areas, populations and extent of barrens remained stable. This differing response between the reserve and fished location is consistent with a top-down effect and greater abundance of predatory fish in the reserve. In contrast, the subtropical sea urchin C. rodgersii increased in abundance by 9.3 times in the Poor Knights Island Marine Reserve and 4.3 times at the fished location, with areas of urchin barrens associated with this species developing at both locations. This increase coincides with substantial warming over the monitoring period (0.25°C decade-1) and low numbers of key predators (rock lobster) at both reserve and fished locations. This highlights the emerging threat of C. rodgersii to rocky reefs in the region and how marine protection alone may not increase resilience to this threat. This suggests multifaceted management approaches are needed to mitigate the impacts of emerging pest species and increase the resilience of temperate reef ecosystems in a warming climate.
Nitrogen-enriched activated carbon derived from plant biomasses: a review on reaction mechanism and applications in wastewater treatment
Authors: Bumajdad Ali , Khan Mohammad Jakir Hossain , Lukaszewicz Jerzy P.
Published: August 2023

As a key kind of evolving carbonaceous adsorbent, nitrogen-enriched activated carbon has drawn a lot of focus due to its better physiochemical ability to eliminate an extensive range of wastewaters contaminants under severe conditions. Its environment-friendly character is one more reason behind this focus. Nitrogen also has immense effect on activated carbon structures’ pollutants adsorption capability; therefore, it is an area of interest. Reports concerning the reaction pathway of C-N (carbon-nitrogen) bond creation on AC surface are limited. Determining such mechanisms is challenging but critical to understand bond characteristics after carbonization. Moreover, it is vital to ascertain real-time kinetics concerning adsorption phenomena in liquid phase. Such a latest trend indicates that regulated nitrogen uses for carbonaceous substances having a biomass-based origin can provide the desired morphological characteristics produced through interconnections, production of enclosed holes, enhanced surface area, better adsorption ability, and many other benefits in contrast to conventional carbon-based substances. This review points out the developments in the main processes to introduce nitrogen atoms into the carbon matrix by utilizing different N-comprising chemical compounds. The nitrogen enrichment processes, reaction mechanisms and effects of nitrogen incorporation on the plant biomass-derived activated carbons (NEACs) are presented in brief. On the basis of their established physicochemical attributes, the adsorption performances of different biomass-derived NEACs have also been dealt with. More significantly, the review covers the technical issues in the present phase, topical trends, research gaps, economic viability along with a technical alignment recommendation to address the prevailing disadvantages.
Central retinal vein occlusion in young population: risk factors and outcomes
Authors: Berguig Jordan , Abdelmassih Youssef , Azar Georges , Lafolie Justine , Alonso Anne Sophie , Bonnin Sophie , Vasseur Vivien , Mauget-Faysse Martine
Published: August 2023

Objective

To evaluate the risk factors and outcomes of central retinal vein occlusion (CRVO) in young patients (< 40 years).

Methods

In this retrospective monocentric case series, we included young patients (<40 years) with CRVO. Patients’ medical files were analyzed focusing on demographic characteristics, suspected risk factors, ophthalmic work-up, visual acuity (VA), treatment, and outcomes.

Results

A total of 54 eyes of 52 patients were included. Central retinal vein occlusion was considered idiopathic in 13 patients (25%). The main risk factors identified were ocular hypertension (20.4%), inflammation (20.4%), high blood pressure (14.8%), and coagulation abnormality (11.1%). Final VA was lower in patients with high blood pressure and inflammation when compared to patients with no risk factor (p = 0.03 and 0.04, respectively). Intravitreal injections were needed in 23 eyes (42.6%) and 19 eyes (35.2%) received panretinal photocoagulation treatment.

Conclusion

Central retinal vein occlusion is frequently associated with risk factors in young patients (75% of patients). In addition to the usual factors found in older patients, such as ocular hypertension and high blood pressure, coagulation abnormality and inflammation were also among the risk factors identified. Young patients with CRVO should be evaluated for the presence of risk factors and patients with high blood pressure or inflammatory findings should be followed carefully since they have a worse outcome.
Assessing cardiorespiratory interactions via lagged joint symbolic dynamics during spontaneous and controlled breathing
Authors: Cairo Beatrice , Bari Vlasta , Gelpi Francesca , De Maria Beatrice , Porta Alberto
Published: August 2023

Introduction: Joint symbolic analysis (JSA) can be utilized to describe interactions between time series while accounting for time scales and nonlinear features. JSA is based on the computation of the rate of occurrence of joint patterns built after symbolization. Lagged JSA (LJSA) is obtained from the more classical JSA by introducing a delay/lead between patterns built over the two series and combined to form the joint scheme, thus monitoring coordinated patterns at different lags.

Methods: In the present study, we applied LJSA for the assessment of cardiorespiratory coupling (CRC) from heart period (HP) variability and respiratory activity (R) in 19 healthy subjects (age: 27–35 years; 8 males, 11 females) during spontaneous breathing (SB) and controlled breathing (CB). The R rate of CB was selected to be indistinguishable from that of SB, namely, 15 breaths·minute−1 (CB15), or slower than SB, namely, 10 breaths·minute−1 (CB10), but in both cases, very rapid interactions between heart rate and R were known to be present. The ability of the LJSA approach to follow variations of the coupling strength was tested over a unidirectionally or bidirectionally coupled stochastic process and using surrogate data to test the null hypothesis of uncoupling.

Results: We found that: i) the analysis of surrogate data proved that HP and R were significantly coupled in any experimental condition, and coupling was not more likely to occur at a specific time lag; ii) CB10 reduced CRC strength at the fastest time scales while increasing that at intermediate time scales, thus leaving the overall CRC strength unvaried; iii) despite exhibiting similar R rates and respiratory sinus arrhythmia, SB and CB15 induced different cardiorespiratory interactions; iv) no dominant temporal scheme was observed with relevant contributions of HP patterns either leading or lagging R.

Discussion: LJSA is a useful methodology to explore HP–R dynamic interactions while accounting for time shifts and scales.
Cranial nerve involvement among COVID-19 survivors
Authors: Heidari Mohammad Eghbal , Nazemi Pershang , Feizabad Elham , Beiranvand Farzaneh , Afzali Mahdieh
Published: August 2023

Introduction

COVID-19 was first reported in November 2019 in China and rapidly spread across the globe. COVID-19 causes neurologic symptoms and complications, which may persist even after recovery in patients. The objective of this research was to determine the involvement of cranial nerves in COVID-19 survivors.

Method

This was a retrospective study. The study was conducted between March and July of 2022. The analysis included 98 patients with a certain positive polymerase chain reaction. SPSS software version 19 was utilized for data analysis.

Results

The average age of the participants was 40.47 years (8.81). The olfactory nerve was found to be the most frequently involved cranial nerve (36.7%). Over 20% of participants had a taste disorder. The findings from the regression analysis indicated that lung involvement and age have a direct and significant relationship with cranial nerve involvement and can serve as its predictors (p = 0.001).

Conclusion

It seems that cranial nerve involvement was sustained in COVID-19 patients who survived. In addition, elderly patients and patients with severe illnesses were more likely to show cranial symptoms. It is necessary to monitor COVID-19 survivors for neurological symptoms.
Distinct neuroanatomical and neuropsychological features of Down syndrome compared to related neurodevelopmental disorders: a systematic review
Authors: Hamadelseed Osama , Chan Mike K. S. , Wong Michelle B. F. , Skutella Thomas
Published: August 2023

Objectives

We critically review research findings on the unique changes in brain structure and cognitive function characteristic of Down syndrome (DS) and summarize the similarities and differences with other neurodevelopmental disorders such as Williams syndrome, 22q11.2 deletion syndrome, and fragile X syndrome.

Methods

We conducted a meta-analysis and systematic literature review of 84 studies identified by searching PubMed, Google Scholar, and Web of Science from 1977 to October 2022. This review focuses on the following issues: (1) specific neuroanatomic and histopathological features of DS as revealed by autopsy and modern neuroimaging modalities, (2) language and memory deficits in DS, (3) the relationships between these neuroanatomical and neuropsychological features, and (4) neuroanatomic and neuropsychological differences between DS and related neurodevelopmental syndromes.

Results

Numerous post-mortem and morphometric neuroimaging investigations of individuals with DS have reported complex changes in regional brain volumes, most notably in the hippocampal formation, temporal lobe, frontal lobe, parietal lobe, and cerebellum. Moreover, neuropsychological assessments have revealed deficits in language development, emotional regulation, and memory that reflect these structural changes and are more severe than expected from general cognitive dysfunction. Individuals with DS also show relative preservation of multiple cognitive, linguistic, and social domains compared to normally developed controls and individuals with other neurodevelopmental disorders. However, all these neurodevelopment disorders exhibit substantial heterogeneity among individuals.

Conclusion

People with Down syndrome demonstrate unique neurodevelopmental abnormalities but cannot be regarded as a homogenous group. A comprehensive evaluation of individual intellectual skills is essential for all individuals with neurodevelopment disorders to develop personalized care programs.
The time is ripe for the renaissance of autism treatments: evidence from clinical practitioners
Authors: Torres Elizabeth B. , Twerski Goldie , Varkey Hannah , Rai Richa , Elsayed Mona , Katz Miriam Tirtza , Tarlowe Jillian
Published: August 2023

Introduction

Recent changes in diagnostics criteria have contributed to the broadening of the autism spectrum disorders and left clinicians ill-equipped to treat the highly heterogeneous spectrum that now includes toddlers and children with sensory and motor issues.

Methods

To uncover the clinicians’ critical needs in the autism space, we conducted surveys designed collaboratively with the clinicians themselves. Board Certified Behavioral Analysts (BCBAs) and developmental model (DM) clinicians obtained permission from their accrediting boards and designed surveys to assess needs and preferences in their corresponding fields.

Results

92.6% of BCBAs are open to diversified treatment combining aspects of multiple disciplines; 82.7% of DMs also favor this diversification with 21.8% valuing BCBA-input and 40.6% neurologists-input; 85.9% of BCBAs and 85.3% of DMs advocate the use of wearables to objectively track nuanced behaviors in social exchange; 76.9% of BCBAs and 57.0% DMs feel they would benefit from augmenting their knowledge about the nervous systems of Autism (neuroscience research) to enhance treatment and planning programs; 50.0% of BCBAs feel they can benefit for more training to teach parents.

Discussion

Two complementary philosophies are converging to a more collaborative, integrative approach favoring scalable digital technologies and neuroscience. Autism practitioners seem ready to embrace the Digital-Neuroscience Revolutions under a new cooperative model.
Clinicopathological and prognostic significance of heat shock proteins in hepatocellular carcinoma: a systematic review and meta-analysis
Authors: Xiang Dan , Jiang Mengdan , Chen Ya , Liu Chengjiang , Li Leilei
Published: August 2023

Background

Overexpression of heat shock proteins (HSPs) has been observed in a wide range of human tumors, and there is an increasing evidence demonstrated that HSPs play a key role in tumor progression. Several studies were conducted to explore the clinicopathological characteristics and prognostic value of HSPs in hepatocellular carcinoma (HCC), but the results remain controversial. To address this gap, we conducted a systematic review and meta-analysis.

Methods

The eligible literature was obtained from PubMed, Cochrane library, Web of science, Embase, Chinese National Knowledge Infrastructure and Wan Fang databases. We used the odds ratio (OR) and hazard ratio (HR) as the suitable parameters to assess the clinicopathological features and prognostic value of HSPs in HCC patients.

Results

The meta-analysis results showed that HSPs expression was associated with overall survival (OS) of HCC patients (HR = 1.61, 95%CI = 1.22-2.13, P=0.001, I2 = 62.7%). In addition, the pooled results suggested that HSPs expression was significantly correlated with tumor differentiation (OR = 1.33, 95%CI = 1.08-1.65, P = 0.907), vascular invasion (OR = 1.31, 95%CI = 1.02-1.69, P = 0.921) and lymphatic metastasis (OR=1.98, 95%CI= 1.70-2.31, P = 0.740). Meanwhile, the subgroup analysis showed a significant correlation between the expression of HSP27 (HR=1.69, 95%CI = 1.24-2.31, P = 0.674) and HSP90α (HR=2.03, 95%CI = 1.73-2.40, P = 0.743) with OS of HCC patients.

Conclusions

Our meta-analysis confirms that HSPs expression is closely associated with a worse prognosis in HCC patients, and may be directly involved in tumor differentiation and distant metastasis. In addition, the subgroup analysis results demonstrate that the expression of HSP27 and HSP90α can be served as potential prognostic predictors of HCC.
Long-term complete response with third-line PARP inhibitor after immunotherapy in a patient with triple-negative breast cancer: a case report
Authors: Caputo Roberta , Pagliuca Martina , Pensabene Matilde , Parola Sara , De Laurentiis Michelino
Published: August 2023

While standard treatment has shown efficacy in patients with breast cancer gene (BRCA) mutations, recurrence rates are high and additional effective therapies are needed. Olaparib, a poly adenosine diphosphate–ribose polymerase (PARP) inhibitor, approved for the treatment of metastatic germline BRCA1/BRCA2 breast cancer (BC), has demonstrated evidence of a progression-free survival (PFS) benefit, good safety profile, and improved quality of life compared with standard chemotherapy. We here describe the case of a patient with BRCA1 mutated advanced BC and a long history of response to chemotherapy and immunotherapy who received systemic treatment with olaparib. First diagnosed in March 2011 at the age of 38 years with early-stage BC of the right breast, she underwent quadrantectomy plus ipsilateral axillary lymphadenectomy and adjuvant treatments with chemotherapy regimen containing 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by radiotherapy. Five years later, following a contralateral nodule detection leading to left breast quadrantectomy, she received adjuvant systemic treatment with docetaxel plus cyclophosphamide and radiotherapy. Gene testing showed a germline BRCA1 deleterious variant, and she underwent bilateral prophylactic mastectomy and oophorectomy. One year later, skin metastasis and bone infiltrations were detected, and she was started on first-line systemic treatment. The patient was enrolled in the IMpassion131 trial (investigating atezolizumab addition to paclitaxel) but unblinding showed that she was randomized in the placebo arm. She received second-line systemic therapy with LAG525 plus carboplatin (CLAG525B2101 trial) resulting in a PFS of 14 months. At disease progression, she was eligible for systemic third-line therapy with olaparib (300 mg twice daily) and had a complete response after 6 months of therapy and a PFS of 40 months at the time of writing. To the best of our knowledge, this is the first report of a complete response following treatment with third-line systemic olaparib in a long-responding patient and relatively good tolerability and quality of life, pre-treated with both chemotherapy and immunotherapy.
Orlistat exerts anti-obesity and anti-tumorigenic effects in a transgenic mouse model of endometrial cancer
Authors: Xu Guangxu , Zhao Ziyi , Wysham Weiya Z. , Roque Dario R. , Fang Ziwei , Sun Wenchuan , Yin Yajie , Deng Boer , Shen Xiaochang , Zhou Chunxiao , Bae-Jump Victoria
Published: August 2023

Introduction

Among all cancers, endometrial cancer is most strongly associated with obesity, with more than 65% of endometrial cancers attributable to obesity and being overweight. Fatty acid synthase (FAS), a key lipogenic enzyme, is expressed in endometrial cancer tumors and is associated with a worse prognosis for this disease. Orlistat, an FAS inhibitor, is an FDA-approved weight loss medication that has demonstrated anti-tumor activity in a variety of preclinical cancer models.

Methods

In this study, the Lkb1fl/flp53fl/fl mouse model of endometroid endometrial cancer was exposed to three diet interventions, including a high fat diet (obese), a low fat diet (lean) and switch from a high fat to a low fat diet, and then exposed to orlistat or placebo.

Results

The mice fed a high-fat diet had significantly increased body weight and tumor weight compared to mice fed a low-fat diet. Switching from a high-fat diet to a low fat diet led to a reduction in mouse weight and suppressed tumor growth, as compared to both the high fat diet and low fat diet groups. Orlistat effectively decreased body weight in obese mice and inhibited tumor growth in obese, lean, and the high fat diet switch to low fat diet mouse groups through induction of apoptosis. Orlistat also showed anti-proliferative activity in nine of 11 primary cultures of human endometrial cancer.

Discussion

Our findings provide strong evidence that dietary intervention and orlistat have anti-tumor activity in vivo and supports further investigation of orlistat in combination with dietary interventions for the prevention and treatment of endometrial cancer.
Case Report: A case of complete response to entrectinib in NTRK fusion gene-positive parotid gland cancer
Authors: Moriyama Etsuko , Nagasu Sachiko , Tanaka Toshimitsu , Shimotsuura Yasutaka , Ono Takeharu , Umeno Hirohito , Akiba Jun , Kawahara Akihiko , Fujita Fumihiko , Kawaguchi Takumi , Miwa Keisuke
Published: August 2023

Introduction

Expression of the NTRK gene is rare in solid tumors but is highly prevalent in salivary gland secretory carcinomas. Here, we report a case of a complete response to entrectinib in a patient with NTRK fusion gene-positive parotid carcinoma.

Case description

The patient was a 44-year-old man who underwent total left parotidectomy and left cervical lymph node dissection for a left parotid tumor at 24 years of age. The histopathological diagnosis was mammary analog secretory carcinoma. Postoperatively, the patient received only radiation therapy. Sixteen years after the surgery, the patient became aware of a mass in the left parotid region. A close examination revealed local recurrence and multiple cervical lymph node metastases. S-1 monotherapy was started as chemotherapy but was discontinued 3 years later because of disease progression. As there was no standard treatment, a comprehensive genomic profiling test using a next-generation sequencer was performed, and the ETV6-NTRK3 fusion gene was identified. Entrectinib, an NTRK inhibitor, was immediately administered at a dose of 600 mg/day. The local recurrence rapidly shrank grossly from the beginning of treatment, and a complete response was observed 6 months later. However, creatinine levels exhibited an increase at week 68 of treatment; consequently, entrectinib dosage was lowered to 400 mg/day, leading to an immediate improvement in creatinine levels. Entrectinib was associated with additional side effects, including dysgeusia, fatigue, dizziness, and weight gain, all of which were also alleviated by the reduction in entrectinib dose. Thirty months after treatment initiation, the patient maintained a complete response and continued to receive entrectinib.

Conclusion

The NTRK fusion gene should always be checked in the presence of salivary gland secretory carcinoma.
Gentiopicroside modulates glucose homeostasis in high-fat-diet and streptozotocin-induced type 2 diabetic mice
Authors: Wang Xing , Long Dongmei , Hu Xianghong , Guo Nan
Published: August 2023

Gluconeogenesis is closely related to the occurrence and development of type 2 diabetes mellitus (T2DM). Gentiopicroside (GPS) is the main active secoiridoid glycoside in Gentiana manshurica Kitagawa, which can improve chronic complications associated with diabetes and regulate glucose metabolism. However, the effects and potential mechanisms by which GPS affects T2DM understudied and poorly understood. In this study, we systematically explored the pharmacological effects of GPS on T2DM induced by a high-fat diet (HFD) and streptozotocin (STZ) as well as explored its related mechanisms. The results showed that GPS supplementation discernibly decreased blood glucose levels, food intake and water consumption, ameliorated glucose intolerance, abnormal pyruvate tolerance, insulin resistance and dyslipidemia. Furthermore, GPS discernibly ameliorated pathological morphological abnormalities of the liver and pancreas, reduced hepatic steatosis and maintain the balance between α-cells and β-cells in pancreas. Moreover, GPS significantly inhibited gluconeogenesis, as evidenced by the suppressed protein expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase) in the liver. Additionally, the results of Western blot analysis revealed that GPS increased p-PI3K, p-AKT, and p-FOXO1 expression levels, and decreased FOXO1 expression at protein level in the liver. Furthermore, the results of the immunostaining and Western blot analysis demonstrated that GPS supplementation increased the expression of zonula occludens-1 (ZO-1) and occludin in the ileum. Collectively, these results indicate that GPS may inhibit hepatic gluconeogenesis by regulating the PI3K/AKT/FOXO1 signaling pathway and maintain intestinal barrier integrity, and ultimately improve T2DM. Together, these findings indicate that GPS is a potential candidate drug for the prevention and treatment of T2DM, and the results of our study will provide experimental basis for further exploration of the possibility of GPS as a therapeutic agent for T2DM.