bluuebunny/crossref_metadata_2025 huggingface dataset:
Pretreatment body mass index predicts survival among patients administered nivolumab monotherapy for pretreated non‐small cell lung cancer
Authors: Imai Hisao , Naito Erika , Yamaguchi Ou , Hashimoto Kosuke , Iemura Hidetoshi , Miura Yu , Shiono Ayako , Mouri Atsuto , Kaira Kyoichi , Kobayashi Kunihiko , Kagamu Hiroshi
Published: April 2022

Background

Biomarker assessments for nivolumab monotherapy efficacy in previously treated patients with non‐small cell lung cancer (NSCLC) remain unclear. We evaluated whether body mass index (BMI) and Glasgow prognostic score (GPS) are useful for assessing the efficacy of nivolumab alone as a second‐line treatment in patients with pretreated NSCLC.

Methods

Data of 99 patients treated with second‐line nivolumab monotherapy for NSCLC between January 2016 and December 2019 were evaluated for prognostic values of BMI and GPS to assess their usefulness in predicting progression‐free survival (PFS) and overall survival (OS).

Results

The Eastern Cooperative Oncology Group‐performance status (PS) independently predicted the second‐line nivolumab monotherapeutic effect; good PS (0–1) correlated with significantly longer PFS (4.3 vs. 1.9 months, log‐rank; p = 0.0004) and OS (17.7 vs. 4.6 months, log‐rank; p < 0.0001) than poor PS. BMI independently predicted survival, with high BMI (≥22.1 kg/m2) associated with significantly longer OS (19.1 vs. 8.5 months, log‐rank; p = 0.0023) than low BMI (<22.1 kg/m2). However, GPS showed no significant difference for PFS or OS.

Conclusion

Among patients with NSCLC treated with nivolumab monotherapy as second‐line treatment, PS was significantly correlated with both PFS and OS and BMI with OS. Thus, BMI could be a useful predictor of survival in these patients.
Real‐world evidence of cisplatin versus carboplatin in patients with locally advanced nasopharyngeal carcinoma receiving concurrent chemoradiotherapy: A multicenter analysis
Authors: Dechaphunkul Arunee , Danchaivijitr Pongwut , Jiratrachu Rungarun , Dechaphunkul Tanadech , Sookthon Chatsuda , Jiarpinitnun Chuleeporn , Paoin Chatchanok , Setakornnukul Jiraporn , Suktitipat Bhoom , Pattaranutaporn Poompis , Ngamphaiboon Nuttapong
Published: April 2022

Background

Though concurrent chemoradiotherapy (CCRT) with cisplatin remains a standard of care for patients with locally advanced nasopharyngeal carcinoma (LA‐NPC), carboplatin has alternatively been used without sufficient supportive evidences. Thus, we evaluated an efficacy and tolerability of carboplatin CCRT compared with cisplatin in LA‐NPC patients.

Methods

Patients with LA‐NPC treated with CCRT were identified through the Thai multicenter head and neck cancer database. Patient tolerability and survival were analyzed and compared between regimens. Survivals were calculated by using the Kaplan–Meier method, and compared by the log‐rank test. A p‐value of <0.05 was considered statistically significant.

Results

A total of 135 of 980 patients (13.8%) were treated with carboplatin. Patients treated with carboplatin were significantly associated with older age (p < 0.001), smoking (p = 0.003), more comorbidity (p = 0.014), kidney disease (p = 0.016), and lower baseline creatinine clearance (p < 0.001). Intensity‐modulated radiation therapy was used significantly more in the cisplatin group than carboplatin group (p < 0.001). Patients who received carboplatin were associated with delay (p = 0.049) and hospitalization (p = 0.006), whereas cisplatin CCRT had more dose reduction (p = 0.001). Patients treated with cisplatin had CCRT interruption from grade 3–4 mucositis (p = 0.019) more than carboplatin, whereas carboplatin had more grade 3–4 thrombocytopenia (p < 0.001). The 5‐year overall survival (OS) of patients treated with cisplatin and carboplatin was 59% and 49%, respectively (p = 0.128). Cisplatin or carboplatin CCRT was not a significant predictor for OS and locoregional recurrence‐free survival in multivariate analysis.

Conclusions

Carboplatin CCRT provided acceptable efficacy and tolerability profiles in real‐world practice. Carboplatin should be considered as an alternative regimen, particularly in cisplatin‐ineligible patients with LA‐NPC treated with CCRT.
How can SMEs effectively embed environmental sustainability? Evidence on the relationships between cognitive frames, life cycle management and organizational learning process
Authors: Bianchi Guia , Testa Francesco
Published: April 2022

Cognitive frames help companies make sense of the intrinsic tensions of sustainability issues and influence how they respond to calls for sustainability over time. Yet, cognitive frames have been investigated as a static feature and previous studies have overlooked the evolutionary dynamics that can lead an organization to change its own frame. This study observes the evolution of life cycle management implementation through the theory of cognitive frames. We conducted a longitudinal multiple case study of 10 SMEs involved in a European‐funded project. Over a three‐year period we examined how cognitive approaches to sustainability issues changed according to different learning mindsets. A total of three cognitive frames and two learning mindsets were revealed from the analysis, thus providing two important contributions. First, cognitive frames are not static in time, but can change to give more importance to the environmental sustainability of a life cycle. Second, the type of learning mindsets that managers in SMEs share can trigger changes in organizational cognitive frames.
An Alternative Metric for Evaluating the Potential Patient Benefit of Response-Adaptive Randomization Procedures
Authors: Proper Jennifer , Murray Thomas A.
Published: April 2022

When planning a two-arm group sequential clinical trial with a binary primary outcome that has severe implications for quality of life (e.g., mortality), investigators may strive to find the design that maximizes in-trial patient benefit. In such cases, Bayesian response-adaptive randomization (BRAR) is often considered because it can alter the allocation ratio throughout the trial in favor of the treatment that is currently performing better. Although previous studies have recommended using fixed randomization over BRAR based on patient benefit metrics calculated from the realized trial sample size, these previous comparisons have been limited by failures to hold type I and II error rates constant across designs or consider the impacts on all individuals directly affected by the design choice. In this paper, we propose a metric for comparing designs with the same type I and II error rates that reflects expected outcomes among individuals who would participate in the trial if enrollment is open when they become eligible. We demonstrate how to use the proposed metric to guide the choice of design in the context of two recent trials in persons suffering out of hospital cardiac arrest. Using computer simulation, we demonstrate that various implementations of group sequential BRAR offer modest improvements with respect to the proposed metric relative to conventional group sequential monitoring alone.
Inflammatory Waldenström's macroglobulinaemia: A French monocentric retrospective study of 67 patients
Authors: Elessa Dikelele , Debureaux Pierre‐Edouard , Villesuzanne Camille , Davi Frederic , Bravetti Clotilde , Harel Stephanie , Talbot Alexis , Oksenhendler Eric , Malphettes Marion , Thieblemont Catherine , Moatti Hannah , Maarek Odile , Arnulf Bertrand , Royer Bruno
Published: April 2022

Waldenström's macroglobulinaemia (WM) is a B‐cell neoplasm resulting from bone marrow lymphoplasmacytic infiltration and monoclonal IgM secretion. Some patients present concomitant inflammatory syndrome attributed to the disease activity; we named this syndrome inflammatory WM (IWM). We retrospectively analysed all WM patients seen in a single tertiary referral centre from January 2007 to May 2021, and after excluding aetiologies for the inflammatory syndrome using a pertinent blood workup, including C‐reactive protein (CRP), and imaging, we identified 67 (28%) IWM, 166 (68%) non‐IWM, and nine (4%) WM with inflammatory syndrome of unknown origin. At treatment initiation, IWM patients had more severe anaemia (median Hb 90 vs 99 g/l; p < 0.01), higher platelet count (median 245 vs 196 × 109/l; p < 0.01) and comparable serum IgM level (median 24.9 vs 23.0 g/l; p = 0.28). A positive correlation was found between inflammatory and haematological responses (minimal response or better) (odds ratio 32.08; 95% confidence interval 8.80–98.03; p < 0.001). Overall survivals (OS) were similar (median OS: 17 vs 20 years; p = 0.11) but time to next treatment (TNT) was significantly shorter for IWM (TNT1: 1.6 vs 4.8 years, p < 0.0001). IWM mostly shared the same presentation and outcome as WM without inflammatory syndrome.
Chronic liver diseases: From development to novel pharmacological therapies: IUPHAR Review 37
Authors: Borrello Maria Teresa , Mann Derek
Published: April 2022

Chronic liver diseases comprise a broad spectrum of burdensome diseases that still lack effective pharmacological therapies. Our research group focuses on fibrosis, which is a major precursor of liver cirrhosis. Fibrosis consists in a progressive disturbance of liver sinusoidal architecture characterised by connective tissue deposition as a reparative response to tissue injury. Multifactorial events and several types of cells participate in fibrosis initiation and progression, and the process still needs to be completely understood. The development of experimental models of liver fibrosis alongside the identification of critical factors progressing fibrosis to cirrhosis will facilitate the development of more effective therapeutic approaches for such condition. This review provides an overlook of the main process leading to hepatic fibrosis and therapeutic approaches that have emerged from a deep knowledge of the molecular regulation of fibrogenesis in the liver.

LINKED ARTICLES

This article is part of a themed issue on Translational Advances in Fibrosis as a Therapeutic Target. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.22/issuetoc
Glycolytic oscillations in HeLa cervical cancer cell spheroids
Authors: Amemiya Takashi , Shibata Kenichi , Takahashi Junpei , Watanabe Masatoshi , Nakata Satoshi , Nakamura Kazuyuki , Yamaguchi Tomohiko
Published: April 2022

Previous studies have unravelled glycolytic oscillations in cancer cells, such as HeLa cervical and DU145 prostate cancer cells, using a monolayer culture system. Here, we demonstrate glycolytic oscillations in HeLa cervical cancer cell spheroids. Experiments revealed that a small number of HeLa cells in spheroids exhibited heterogeneous oscillations with a higher frequency than those in monolayers. Model analyses and our previous experiments indicated that the higher frequencies of oscillations in spheroids were mostly due to the increase in glycolytic enzyme activity in the cells, and to the decrease in glucose concentration by diffusional transport of glucose from the surface to inside the spheroids, as well as the increase in cell density through spheroid formation. These results and our previous studies imply that more malignant cancer cells tend to exhibit glycolytic oscillations with higher frequencies than less malignant cells. Adjacent cells in spheroids oscillated within a 10% difference in frequency, but did not synchronize with each other. This suggests that weak cell‐to‐cell interactions might exist among HeLa cells connected with cadherins in the spheroid microenvironment; however, the interactions were not strong enough to induce synchronization of glycolytic oscillations.
Stocking in inland food fisheries of South and Southeast Asia: issues, risks, and rewards
Authors: Arthur Robert Ian , Valbo‐Jørgensen John , Lorenzen Kai , Kelkar Nachiket
Published: April 2022

Inland fisheries in South and Southeast Asia represent important sources of food, and many are extensively stocked. Stocking often catalyses wider changes in inland fisheries is considered in this context. Stocking can be beneficial, providing additional sources of food, incentives to manage, and income‐generating opportunities. However, there are also identifiable risks: stocking can be used to avoid or ignore addressing reasons underlying the degradation of inland fisheries and economic development, tenure arrangements, and culture technologies involved in stocking can combine to transform the very nature of inland fisheries. These transformations can degrade environments and alter the nature and distribution of benefits, potentially marginalising and impoverishing fishers. There is consequently a need to consider and assess more explicitly in advance the implications of stocking for the nature and distribution of social and environmental costs and benefits, and the risks related to access to, and availability of, food.
Labour market integration of FRY refugees in Sweden vs. Denmark
Authors: Andersson Joona Pernilla , Datta Gupta Nabanita
Published: April 2022

We compare the long‐run labour market integration of the Former Republic of Yugoslavia (FRY) refugees who arrived in the 1990s to the Scandinavian countries in the settings of Sweden and Denmark, respectively. These otherwise similar countries faced different economic conditions at the time of arrival and over the observation period. They also differed in terms of the restrictiveness of asylum policies and in attitudes towards immigration. Using register data from Statistics Sweden and Statistics Denmark, we show that FRY refugees, in both child and adult generations at arrival, are better integrated 12–15 years later in Sweden than in Denmark, even though Sweden experienced a higher level of unemployment than Denmark throughout the period. Our findings suggest that asylum policies promoting early labour market entry and early exposure to a host country's schooling system, as well as access to disability pension and social assistance, are important factors affecting refugee labour market integration.
The impact of using vacuum and isomaltulose as an osmotic agent on mass exchange during osmotic dehydration and their effects on qualitative parameters of strawberries
Authors: Macedo Leandro Levate , Corrêa Jefferson Luiz Gomes , Vimercati Wallaf Costa , da Silva Araújo Cintia
Published: April 2022

The impregnation of isomaltulose is an interesting strategy for the enrichment of strawberries since it is a carbohydrate with low glycemic and cariogenic indexes. The osmotic enrichment of strawberries with isomaltulose was performed considering the vacuum pulse in the first 0, 10, and 20 min in a total process time of 300 min, at 25°C. The tested solution concentrations were 25% and 35% (w w−1) of isomaltulose. The kinetics of solid gain, water loss, moisture content, and weight reduction were obtained. The fresh and final products had some physical and nutritional parameters evaluated. Osmotic processes resulted in a reduction of moisture content, water activity (aw), acidity, total anthocyanins and phenolic contents and antioxidant capacity, increased pH, influenced colorimetric parameters and caused shrinkage of the samples. The higher impregnation of isomaltulose was obtained with the vacuum pulse, which was 82% higher than the osmotic process without the vacuum pulse. The atmospheric process resulted in higher bioactive compounds levels and lower shrinkage and lower total color difference. Therefore, the 35% solution and use of vacuum were recommended when the objective was to maximize mass exchanges, while the 25% solution and without vacuum pulse were indicated for higher retention of strawberry bioactive compounds. The time of vacuum application at the beginning of the osmotic dehydration process and the use of osmotic solutions of different concentrations can result in different rates of dehydration and impregnation of isomaltulose in the strawberry and can influence important qualitative parameters. The evaluation of these factors helps in the optimization of the production of osmo‐dehydrated strawberries, increasing the process efficiency and the preservation of product quality.

Practical Applications

The time of vacuum application at the beginning of the osmotic dehydration process and the use of osmotic solutions of different concentrations can result in different rates of dehydration and impregnation of isomaltulose in the strawberry and can influence important qualitative parameters. The evaluation of these factors helps in the optimization of the production of osmo‐dehydrated strawberries, increasing the process efficiency and the preservation of product quality.
Hirayama disease: Nosological classification and neuroimaging clues for diagnosis
Authors: Iacono Salvatore , Di Stefano Vincenzo , Gagliardo Andrea , Cannella Roberto , Virzì Valentina , Pagano Sonia , Lupica Antonino , Romano Marcello , Brighina Filippo
Published: April 2022

Hirayama disease (HD) is a rare, benign, and nonprogressive motor neuron disease (MND) affecting the upper limbs. It usually presents with weakness and amyotrophy in a single upper extremity with an insidious onset between adolescence and the third decade of life. Since its description in 1959, HD has been known under several names and eponyms in Europe and in Asian countries probably due to its heterogeneous clinical features. Thus, the unclear nosological classification makes challenging the differential diagnosis between HD and other neuromuscular conditions, such as MNDs. However, apart from the nosological difficulties and the lack of evidence‐based guideline for diagnosis, the neuroimaging is the mainstay for the diagnosis of HD. Indeed, the specific findings on cervical flexion MRI usually lead to a prompt diagnosis. Here, we reviewed the nosological classifications of HD and its neuroimaging features. Also, we report a case of a 18‐year‐old boy who presented to our Clinic complaining of muscle weakness of the left distal upper limb without other neurological signs. The cervical MRI, in the neutral position, revealed a high T2 signal intensity in the C5‐C7 cervical myelomeres as well as the loss of cervical lordosis, whereas, during neck flexion, it showed the anterior displacement of the posterior dura ad the post‐gadolinium T1‐weighted imaging enhancement of the posterior epidural plexus. These findings are typical for HD allowing the diagnosis as well as the differential diagnosis from other neuromuscular diseases.
Reassessing North Eastern Atlantic‐Mediterranean species of Trapania (Mollusca, Nudibranchia)
Authors: Paz‐Sedano Sofía , Martín Álvarez José Francisco , Gosliner Terrence M. , Pola Marta
Published: April 2022

Trapania is the second largest genus belonging to the family Goniodorididae, of which most of the species are reported from Indo‐Pacific waters. To date, there are nine species of Trapania distributed along the temperate coasts of the East Atlantic Ocean and Mediterranean Sea: Trapania fusca, Trapania graeffei, Trapania hispalensis, Trapania lineata, Trapania maculata, Trapania orteai, Trapania pallida, Trapania sanctipetrensis and Trapania tartanella. However, the validity of some of these species has been problematic due to uncertain taxonomic characteristics used for the differentiation of the species. The genus Trapania has a very uniformly external morphology and very similar internal anatomy. As a consequence, the features most commonly used to differentiate species have been the colour pattern of the body and the morphology of the radula. In the present study, we perform a morphological and molecular revision of the East Atlantic‐Mediterranean species of the genus Trapania. Morphological analyses include dissections and scanning electron microscope photographs of radulae, labial cuticles and penises. Molecular work includes phylogenetic, species delimitation and haplotype network analyses. Our results bring doubt on the taxonomic characteristics used so far, suggesting that the richness of the North Eastern Atlantic‐Mediterranean species has been overestimated. Trapania hispalensis, T. lineata and T. pallida are shown to belong to the same taxa, with Trapania lineata as senior synonym.
Reductive site-selective atypical
C
,
Z
-type/N2-C2 cleavage allows C-terminal protein amidation
Authors: Mollner Tim A. , Giltrap Andrew M. , Zeng Yibo , Demyanenko Yana , Buchanan Charles , Oehlrich Daniel , Baldwin Andrew J. , Anthony Daniel C. , Mohammed Shabaz , Davis Benjamin G.
Published: April 2022

Biomolecule environments can enhance chemistries with the potential to mediate and modulate self-modification (e.g., self-cleavage). While these enhanced modes are found in certain biomolecules (e.g., RNA ribozymes), it is more rare in proteins. Targeted proteolytic cleavage is vital to physiology, biotechnology, and even emerging therapy. Yet, purely chemically induced methods for the site-selective cleavage of proteins remain scarce. Here, as a proof of principle, we designed and tested a system intended to combine protein-enhanced chemistry with tag modification to enable synthetic reductive protein chemistries promoted by diboron. This reductively driven, single-electron chemistry now enables an operationally simple, site-selective cleavage protocol for proteins directed to readily accessible dehydroalanine (Dha) residues as tags under aqueous conditions and in cell lysates. In this way, a mild, efficient, enzyme-free method now allows not only precise chemical proteolysis but also simultaneous use in the removal of affinity tags and/or protein-terminus editing to create altered N- and C-termini such as protein amidation (─CONH
2
).
Primary poorly differentiated carcinoma of the vagina with focal neuroendocrine differentiation: a tumour with aggressive behaviour
Authors: Mai Yi-Fan , Chan I-San , Lai Chiung-Ru , Chen Yi-Jen
Published: April 2022

Primary vaginal neuroendocrine tumours are extremely rare but aggressive. We report a case of primary poorly differentiated vaginal carcinoma with focal neuroendocrine differentiation. The clinical stage was cT3N1M0, FIGO stage III. The patient received six cycles of cisplatin-based concurrent chemoradiation therapy (CCRT) followed by six cycles of adjuvant chemotherapy (IEP protocol: ifosfomide, epirubicin and cisplatin). Pelvic MRI scans obtained after treatment completion revealed no residual tumour in the vagina. However, the patient experienced severe dyspnoea 2 months later. Chest X-ray revealed a reticulonodular interstitial pattern over bilateral lungs with suspicion of lymphangitic carcinomatosis. Further chest, abdominal and pelvic CT scans showed bilateral lung metastases with multiple mediastinal, left lower neck and left axilla, intra-abdominal and pelvic lymphadenopathies. For this rare tumour, cisplatin-based CCRT followed by IEP protocol adjuvant chemotherapy may have a limited treatment effect. Further studies are necessary to provide more information on clinical management.
Resampling to address inequities in predictive modeling of suicide deaths
Authors: Reeves Majerle , Bhat Harish S , Goldman-Mellor Sidra
Published: April 2022

Objective

Improve methodology for equitable suicide death prediction when using sensitive predictors, such as race/ethnicity, for machine learning and statistical methods.

Methods

Train predictive models, logistic regression, naive Bayes, gradient boosting (XGBoost) and random forests, using three resampling techniques (Blind, Separate, Equity) on emergency department (ED) administrative patient records. The Blind method resamples without considering racial/ethnic group. Comparatively, the Separate method trains disjoint models for each group and the Equity method builds a training set that is balanced both by racial/ethnic group and by class.

Results

Using the Blind method, performance range of the models’ sensitivity for predicting suicide death between racial/ethnic groups (a measure of prediction inequity) was 0.47 for logistic regression, 0.37 for naive Bayes, 0.56 for XGBoost and 0.58 for random forest. By building separate models for different racial/ethnic groups or using the equity method on the training set, we decreased the range in performance to 0.16, 0.13, 0.19, 0.20 with Separate method, and 0.14, 0.12, 0.24, 0.13 for Equity method, respectively. XGBoost had the highest overall area under the curve (AUC), ranging from 0.69 to 0.79.

Discussion

We increased performance equity between different racial/ethnic groups and show that imbalanced training sets lead to models with poor predictive equity. These methods have comparable AUC scores to other work in the field, using only single ED administrative record data.

Conclusion

We propose two methods to improve equity of suicide death prediction among different racial/ethnic groups. These methods may be applied to other sensitive characteristics to improve equity in machine learning with healthcare applications.
Developing a simulation-based learning model for acute medical education during COVID-19 pandemic with Simulation via Instant Messaging – Birmingham Advance (SIMBA)
Authors: Wallett Lucy , Chen Wentin , Thomas Lucretia , Blaggan Parisha , Ooi Emma , Zhou Dengyi , Hanania Thia , Ng Cai Ying , Evans Nia , Morgan Georgia , Allison Issy , Pan Carina Synn Cuen , Ponniah Gobeka , Radcliffe Eloise , Sheikh Jameela , Khashaba Alya , Hebbar Meghnaa , Delson Dwi , Reddy-Koanu Vinay , Ayuk John , Packer Gregory , Akufo-Tetteh Emily , Davitadze Meri , Melson Eka , Kempegowda Punith
Published: April 2022

Simulation-based learning (SBL) is well-established in medical education and has gained popularity, particularly during the COVID-19 pandemic when in-person teaching is infeasible. SBL replicates real-life scenarios and provides a fully immersive yet safe learning environment to develop clinical competency. Simulation via Instant Messaging – Birmingham Advance (SIMBA) is an exemplar of SBL, which we previously showed to be effective in endocrinology and diabetes. Previous studies reported the efficacy of SBL in acute medicine. We studied SIMBA as a learning intervention for healthcare professionals interested in acute medicine and defined our aims using the Kirkpatrick model: (i) develop an SBL tool to improve case management; (ii) evaluate experiences and confidence before and after; and (iii) compare efficacy across training levels.

Three sessions were conducted, each representing a PDSA cycle (Plan-Do-Study-Act), consisting of four cases and advertised to healthcare professionals at our hospital and social media. Moderators facilitated progression through 25 min simulations and adopted patient and clinical roles as appropriate. Consultants chaired discussion sessions using relevant guidelines. Presimulation and postsimulation questionnaires evaluated self-reported confidence, feedback and intended changes to clinical practice.

Improvements were observed in self-reported confidence managing simulated cases across all sessions. Of participants, 93.3% found SIMBA applicable to clinical practice, while 89.3% and 88.0% felt SIMBA aided personal and professional development, respectively. Interestingly, 68.0% preferred SIMBA to traditional teaching methods. Following participant feedback, more challenging cases were included, and we extended the time for simulation and discussion. The transcripts were amended to facilitate more participant-moderator interaction representing clinical practice. In addition, we refined participant recruitment over the three sessions. In cycle 1, we advertised incentives: participation counted towards teaching requirements, certificates and feedback. To rectify the reduction in participants in cycle 2, we implemented new advertisement methods in cycle 3, including on-site posters, reminder emails and recruitment of the defence deanery cohort.
Fibroblast growth factor 21 improves lipopolysaccharide-induced pulmonary microvascular endothelial cell dysfunction and inflammatory response through SIRT1-mediated NF-κB deacetylation
Authors: Zhou Xuemei , Wang Xinhua , Lu Lidong , Deng Minchao , Shi Xinglei
Published: April 2022

Pneumonia is a common infectious disease of the respiratory system in children. It often leads to death in children by causing acute lung injury. Fibroblast growth factor 21 (FGF21) is a peptide hormone that plays an important role in the regulation of energy homeostasis. This study aimed to investigate the role of FGF21 in alleviating the lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cell (HPMEC) injury, as well as the underlying mechanism. The expression of sirtuin 1 (SIRT1), NF-κB p65, Ac-NF-κB p65, apoptosis-related proteins, tight junction proteins and adhesion molecules in HPMECs were analyzed by Western blotting. The viability and apoptosis of HPMECs were detected by CCK-8 and TUNEL assays. Lactate dehydrogenase level and levels of inflammatory factors were respectively determined by assay kits. The mRNA expression of adhesion molecules in HPMECs was analyzed by RT-qPCR. As a result, SIRT1 expression was decreased and the expression of NF-κB p65 and Ac-NF-κB p65 were increased in LPS-induced HPMECs, which were reversed by recombinant FGF21 (rFGF21). rFGF21 increased the viability and inhibited the apoptosis, inflammatory response, permeability, and release of cell adhesion molecules of LPS-induced HPMECs. In addition, EX527 as SIRT1 inhibitor could reverse the effect of rFGF21 on LPS-induced HPMECs. In conclusion, FGF21 improved LPS-induced HPMEC dysfunction and inflammatory response through SIRT1-mediated NF-κB deacetylation.
Neutrino–(anti)neutrino forward scattering potential for massive neutrinos at low energies
Authors: Neto P. Dedin , Kemp E.
Published: April 2022

In this work, we calculate the expression for the potential due to neutrino–(anti)neutrino forward scattering at low energies [Formula: see text] for ultra-relativistic massive neutrinos [Formula: see text], a representative regime within astrophysical scenarios. There is a broadly used expression for this potential in the literature, which, however, lacks an explicit derivation from basic principles of quantum field theory. Therefore, this paper has an intention to guide the reader through the steps and concepts to derive this potential, trying to be clear and pedagogical. Moreover, we used a rigorous approach concerning the massive nature of the neutrinos, using massive quantized neutrino fields throughout the entire process, while the usual approach is to consider massless neutrino fields at the interaction. In this context, we explicitly show the validity of the massless neutrino fields approximation at the ultra-relativistic regime, as expected. As the last step, we connect the potential expression to the density matrix formalism, which is a usual framework for works considering neutrino–neutrino interactions. We also discuss some theoretical details through the paper such as the normal ordering of quantum operators and the implications of massive fields in the neutrino state at its production.
Energy transitions and half-life determinations of 47Sc isotopes from photonuclear reaction on Ti target
Authors: Koçak Gökhan , Akkoyun Serkan , Boztosun İsmail , Dapo Haris
Published: April 2022

For the activation of the target nucleus, bremsstrahlung photons generated in a medical linear accelerator can be used. Due to particle separation energy limitations for low photon energies in the giant resonance region ([Formula: see text]18[Formula: see text]MeV), the reaction exit channels are restricted to the ejection of one or two particles only. Thus, the gamma spectrum is relatively clear, and the use of ancillary detectors coupled to HPGe is not highly needed. In this study, the bremsstrahlung photons have been used for the activation of the titanium target. [Formula: see text]Sc isotopes are observed from the natural titanium target via photo-proton reactions. Decay radiations from the isotopes and half-life of [Formula: see text]Sc which is from the most abundant natural titanium have been determined consistent with the literature values.
Investigation on Ultrasound Long Bone Fracture Imaging Using the Migration Method
Authors: Kanyana Ruth , Olaniyan Ademola Olatide , Uzorka Afam
Published: April 2022

Ultrasound imaging plays a critical role in diagnostics in biomedicine because of its safety, nature, and low cost. Conventional ultrasound systems form images using a focused beam during transmission and dynamic focusing during the reception. The area under examination can be simultaneously insonified using a plane wave, which allows for ultrafast data capture rates but lowers image quality. The resultant image can be improved by coherent plane-wave compounding, in which numerous plane waves are released at different angles to produce distinct image datasets that are then blended to improve the final composite image. This study used the Fourier-domain technique for coherent plane-wave compounding image reconstruction from the image produced by conventional ultrasound to investigate the quality of the image produced compared to the X-ray image. To establish the merits and limitations of this approach, the researchers provided quantitative comparisons with the images obtained by the X-ray machine. The evaluation results are based on the peak signal-to-noise ratio (PSNR), mean, and variance. The results obtained showed that the migration method can precisely image the cortical bone fracture and offer good contrast between the bone tissue and the subcutaneous tissues.
A methodical survey of mathematical model-based control techniques based on open and closed loop control approach for diabetes management
Authors: Sharma Ankit , Singh Harendra Pal , Nilam
Published: April 2022

Disturbance of blood sugar level is controlled through well-known biomechanical feedback loops: high levels of glucose in blood facilitate to release insulin from the pancreas which accelerates the absorption rate of cellular glucose. Low glucose levels encourage to release pancreatic glucagon which induces glycogen breakdown to glucose in the liver. These bio-control systems do not function properly in diabetic patients. Though the control of disease seems intuitively easy, in real life, due to many differences in structure by diet and fasting, exercise, medications, patient’s profile and other stressors, it is not that easy. The mathematical models of the glucose-insulin regulatory system follow the patient’s physiological conditions which make it difficult to identify and estimate all the model parameters. In this paper, we have given a systematic literature review on mathematical models of the diabetic patients, and various kinds of disease control techniques through the development of open and closed loop insulin deliver command system and optimization of exogenous insulin rate. It demonstrates the open and closed loop type model-based control strategies underlying the assumptions of the concerned models. The combination of mathematical model with control strategies such as genetic algorithm (GA), neural network (NN), sliding mode controller (SMC), model predictive controller (MPC), and fuzzy logic control (FLC) has been considered, which provides an overview of this area, highlighting the control profile over the diabetic model with promising clinical results, outlining key challenges, and identifying needs for the future research. Also, the significance of these control algorithms has been discussed in the presence of the noises, the controller’s robustness and various other disturbances. It provides substantial information on diabetes management through various control techniques.
Acupuncture Effect Assessment in APP/PS1 Transgenic Mice: On Regulating Learning-Memory Abilities, Gut Microbiota, and Microbial Metabolites
Authors: Yang Bo , He Min , Chen Xinhua , Sun Mengmeng , Pan Ting , Xu Xiaohong , Zhang Xuesong , Gong Qing , Zhao Ye , Jin Ziqi , Cheng Zedong
Published: April 2022

Alzheimer’s disease (AD) is a brain illness that affects learning and memory capacities over time. In recent investigations, acupuncture has been shown to be an effective alternative treatment for AD. We investigated the effect of acupuncture on learning and memory abilities using a water maze in APP/PS1 transgenic mice. The amounts of Aβ and tau protein in mice’s hippocampal tissue were determined using Western blot. The levels of IL-1β, IL-10, LPS and TNF-α in mice’s serum were measured using ELISA. The variations of gut microbiota in mice’s feces were determined using the 16SrDNA technique, and the metabolites were examined using a untargeted metabolomics methodology. The results showed that acupuncture treatment improved mice’s learning and memory abilities substantially. Acupuncture therapy regulated the Aβ and tau protein concentration as well as the levels of IL-10 and LPS. Acupuncture treatment influenced the mouse microbiota and metabolites and had been linked to six biochemical pathways. This study adds to our understanding of the effect of acupuncture on AD and opens the door to further research into the alterations of intestinal bacteria in the presence of AD.
Delayed Presentation of Gastric Volvulus with Gastric Outlet Obstruction after Laparoscopic Sleeve Gastrectomy
Authors: Batayyah Esam , Yaseen Waed , Althobaiti Shatha
Published: April 2022

Background. Globally among bariatric procedures, SG popularity has grown significantly. New complications arise as a result of the rapid growth in the numbers of LSG. Once SG has been performed, the stomach is left with no fixations along the entire greater curvature, which may predispose to volvulus. Case Report. The 44-year-old patient had laparoscopic sleeve gastrectomy 2 years and 6 months before presentation in our emergent department complaining of episodic intolerance to oral intake for 3 months before presentation. Gastrografin swallow study showed gastric outlet obstruction. The patient was taken to the operation room for laparoscopic exploration, gastric untwisting. Conclusion. This case highlights a rare complication of SG which has been inconsistently addressed in the literature. Awareness of such complications would help surgeons to widen their differential diagnosis of postoperative sleeve gastrectomy early complications to manage them effectively. The video of the procedure showing the intraoperative finding can be accessed at.
Synthesis and Diuretic Activity of Substituted 1,3,4-Thiadiazoles
Authors: Ergena Asrat , Rajeshwar Yerra , Solomon Gebremedhin
Published: April 2022

1,3,4-Thiadiazole nuclease, a 5-membered heterocyclic ring system containing two nitrogen and one sulfur atoms in addition to carbon atoms, is compound that showed promising results in the process of searching new diuretic agents. In this study, seven 5- and 2-thioate derivatives of 1, 3, 4-thiadiazoles were synthesized by substitution reaction using acetone as solvent and K2CO3 as a base. The compounds ware then characterized by using IR and NMR spectroscopy. The diuretic activity of the compounds was evaluated on Swiss albino mice by measuring urine volume, urinary pH, and urinary Na+, K+, and Cl−. The result showed increase in urinary excretion of both water and electrolytes. 5-Methyl-substituted derivatives of 1, 3, 4-thiadiazoles showed significant increase in excretion of both water and electrolytes when they are compared to both negative control and 5-amino-substituted derivatives. The highest diuretic activity (0.82) was recorded for para-nitro-substituted benzene ring at 2-thioate group of 5-methyl-1, 3, 4-thiadiazole, while the least (0.56) was recorded for propanethioate group at 2nd position and amine group at 5th position of 1, 3, 4-thiadiazole. The finding of the present study showed that all the compounds have diuretic activity and 5-methyl derivatives of 1, 3, 4-thiadiazoles exhibited significant diuretic activity.
The Interaction of Internet Fun Design Resources Based on the Network Communication System
Authors: Min Xiaojie
Published: April 2022

The interactive function of the Internet is the basis of all data transmission. The functions of Internet products are becoming more and more complex, and the amount of information they carry also increases dramatically. People and products mainly interact with products through the product interface, and the operation of the interface becomes more and more complex and more important. With the help of the interactive function of the Internet, various “Internet +” businesses are carried out in an orderly manner. The realization of Internet functions also requires user-centric interactive design. This puts higher demands on the fun of Internet interaction. This article aims to study the interaction of interesting design resources on the Internet, so as to make the Internet interaction more interesting. This article proposes to add interesting elements to the interactive functions of the Internet on the basis of the network communication system and stimulate the user’s feelings from many aspects such as actions, pictures, sounds, and colors, so as to make the users feel psychologically happy and trigger. The experimental results in this paper show that fun interaction design can enhance user experience by 20%.
Simultaneous Integrated Boost Volumetric Modulated Arc Therapy for Rectal Cancer: Long-Term Results after Protocol-Based Treatment
Authors: Lee Dong Soo , Oh Seong-Taek , Ahn Chang-Hyeok , Lee Jaeim , Lee Kil-Yong , Chae Hiun Suk , Kim Sung Soo , Kim Sang Woo , Seo Kyung Jin
Published: April 2022

Background. Volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) is an advanced form of radiotherapy (RT) technology. The purpose of this study was to report long-term treatment outcomes in patients with locally advanced rectal cancer undergoing VMAT-SIB based concurrent chemoradiotherapy (CRT). Methods. Between January 2016 and January 2018, a total of 22 patients with operable stage II-III rectal adenocarcinoma were recruited for the pre-designed VMAT-SIB RT protocol. All patients underwent standard diagnostic and staging work-up. The RT target volumes included the following areas: PTV1 = mesorectum that contained gross tumors and enlarged lymph node regions and PTV2 = mesorectum and regional lymphatics from L4-5/S1 to 3-4 cm below the tumor or levator ani muscle, excluding PTV1. The VMAT-SIB dose prescription was as follows: PTV1 = 52.5 Gy/daily 2.1 Gy/25 fractions, PTV2 = 45 Gy/daily 1.8 Gy/25 fractions. Results. The mean age of the study population was 64 (range, 18-84) years, and 15 (68.2%) patients were male. Radical operation (total mesorectal excision) was performed by either low anterior resection, ultralow anterior resection, or abdominal perineal resection. All five (22.7%) of the patients with confirmed increasing serum carcinoembryonic antigen (CEA) level at diagnosis showed normalization of serum CEA level after the planned treatment. Among 20 patients who underwent preoperative CRT and surgery, tumor down staging in T- and N-stages was achieved in 10 patients (50%) and 13 patients (65%), respectively, with 20% of ypT0/Tis. With a median follow-up of 54.2 (range, 22.6-61.1) months, the 5-year disease-free survival, overall survival, and local control rates were 64.6%, 81.8%, and 84.4%, respectively. Five patients developed distant metastasis and one developed local recurrence as a first event. Two cases with anastomosis site leakage, three with adhesive ileus, and two with abscess formation were observed during postoperative periods. Conclusions. The current VMAT-SIB-based CRT protocol provided acceptable treatment and toxicity outcomes.
Novel Algorithms for Solving a System of Absolute Value Variational Inequalities
Authors: Batool Safeera , Noor Muhammad Aslam , Ahmad Riaz , Khan Ilyas , Andualem Mulugeta
Published: April 2022

The goal of this paper is to study a new system of a class of variational inequalities termed as absolute value variational inequalities. Absolute value variational inequalities present a rational, pragmatic, and novel framework for investigating a wide range of equilibrium problems that arise in a variety of disciplines. We first develop a system of absolute value auxiliary variational inequalities to calculate the approximate solution of the system of absolute variational inequalities, and then by employing the projection technique, we prove the existence of solutions of the system of absolute value auxiliary variational inequalities. By utilizing an auxiliary principle and the existence result, we propose several new iterative algorithms for solving the system of absolute value auxiliary variational inequalities in the frame of four different operators. Furthermore, the convergence of the proposed algorithms is investigated in a thorough manner. The efficiency and supremacy of the proposed schemes is exhibited through some special cases of the system of absolute value variational inequalities and an illustrative example. The results presented in this paper are more general and rehash a number of some previously published findings in this field.
New Iterative Method for Solving a Coupled System of Fractional‐Order Drinfeld–Sokolov–Wilson (FDSW) and Fractional Shallow Water (FSW) Equations
Authors: Ali Nasir , Yassen Mansour F. , Asiri Saeed Ahmed , Nawaz Rashid , Zada Laiq , Alam Mohammad Mahtab , Sene Ndolane
Published: April 2022

In this study, the new iterative method has been applied to a coupled system of fractional‐order Drinfeld–Sokolov–Wilson (FDSW) and fractional shallow water (FSW) equations. The fractional‐order derivatives are taken in the Caputo sense whose order is between 0 and 1. The suggested method is capable to handle the FDEs without any transformation and discretization. The obtained results have been compared with the exact solution and with the q‐homotopy analysis transform method. The outcomes show the efficiency and effectiveness of NIM by comparing through tables and graphs.
Optimal Online Service Strategy and Price Decision in Omnichannel Retail
Authors: Ji Guojun , Fu Tianyu , Chen Jiguang , Tan Kim Hua
Published: April 2022

As a new emerging sales promotion tool, various types of online services are increasingly adopted by firms to improve consumers’ satisfaction and then increase profit. This paper simulates a two-echelon supply chain where a supplier sells the product through an offline or online retailer. Online channel is characterised by direct selling and reselling. We consider three online service strategies: no online service and preemptive and reactive online service. Several results are obtained. We find that investing in online services can benefit all players in most scenarios more than no-service scenario. In the direct selling case, the offline retailer benefits the most from the reactive service strategy due to the webrooming effect, whereas the supplier performance is best in the preemptive service strategy. However, in the reselling case, we find that the supplier and the online and offline retailers benefit the most from reactive service strategy. Furthermore, we compare the prices and service levels of the three strategies and find that the webrooming effect coefficient can affect the optimal wholesale price, retail prices, and online service level. Finally, the findings indicate that the supplier’s choice of the two cases depends on the fixed cost of the online channel.