bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of correlation between CD44, radiotherapy response, and survival rate in patients with advanced stage of head and neck squamous cell carcinoma (HNSCC)
Authors: Dubey Parul , Gupta Rajeev , Mishra Anupam , Kumar Vijay , Bhadauria Smrati , Bhatt Madan Lal Brahma
Published: March 2022

Purpose

Cancer stem cells (CSCs) constitute a distinctive subpopulation of cancer cells that are competent in tumor initiation, invasion, recurrence, and resistance to chemoradiotherapy. CD44, a hyaluronic acid (HA) receptor has been considered as a potential CSC marker in head and neck cancer. The purpose of this study is to evaluate the correlation between CD44 and clinicopathological parameters, treatment response, survival, and recurrence.

Methods

The CD44 expression was examined by immunohistochemistry (IHC) in 90 samples of head and neck squamous cell carcinoma (HNSCC) confirmed patients. The expression of CD44 and its association with clinicopathological parameters, treatment response, and survival was determined.

Results

In all HNSCC patient samples, CD44 was expressed consistently at different intensities. Tumor size (p < 0.001), stage (p < 0.001), and treatment response (p < 0.001) showed statistically significant association with CD44 expression. Alcohol and CD44 were observed as independent predictors of response to radiotherapy using multivariate ordinal logistic regression analysis. Analysis of 2‐year overall survival (OS) showed that CD44 expression (p = 0.02), tumor size (p = 0.001), lymph node status (p < 0.001), stage (p < 0.001), and grade (p = 0.007) were significantly associated with OS. Using Cox regression analysis, lymph node status (p = 0.001), grade (p < 0.001), recurrence (p < 0.001), and CD44 expression (p = 0.003) were found to be potential independent predictors of OS.

Conclusion

Our findings suggest that CD44 contributes to resistance to radiotherapy and poor OS. The results also suggest that except for CD44 there could be other factors such as lymph node metastasis, grade, and alcohol which should be investigated as potential targets for therapy.
Improved risk scoring systems for colorectal cancer screening in Shanghai, China
Authors: Wu Wei‐Miao , Gu Kai , Yang Yi‐Hui , Bao Ping‐Ping , Gong Yang‐Ming , Shi Yan , Xu Wang‐Hong , Fu Chen
Published: March 2022

Background

An optimal risk‐scoring system enables more targeted offers for colonoscopy in colorectal cancer (CRC) screening. This analysis aims to develop and validate scoring systems using parametric and non‐parametric methods for average‐risk populations.

Methods

Screening data of 807,695 subjects and 2806 detected cases in the first‐round CRC screening program in Shanghai were used to develop risk‐predictive models and scoring systems using logistic‐regression (LR) and artificial‐neural‐network (ANN) methods. Performance of established scoring systems was evaluated using area under the receiver operating characteristic curve (AUC), calibration, sensitivity, specificity, number of high‐risk individuals and potential detection rates of CRC.

Results

Age, sex, CRC in first‐degree relatives, chronic diarrhoea, mucus or bloody stool, history of any cancer and faecal‐immunochemical‐test (FIT) results were identified as predictors for the presence of CRC. The AUC of LR‐based system was 0.642 when using risk factors only in derivation set, and increased to 0.774 by further incorporating one‐sample FIT results, and to 0.808 by including two‐sample FIT results, while those for ANN‐based systems were 0.639, 0.763 and 0.805, respectively. Better calibrations were observed for the LR‐based systems than the ANN‐based ones. Compared with the currently used initial tests, parallel use of FIT with LR‐based systems resulted in improved specificities, less demands for colonoscopy and higher detection rates of CRC, while parallel use of FIT with ANN‐based systems had higher sensitivities; incorporating FIT in the scoring systems further increased specificities, decreased colonoscopy demands and improved detection rates of CRC.

Conclusions

Our results indicate the potentials of LR‐based scoring systems incorporating one‐ or two‐sample FIT results for CRC mass screening. External validation is warranted for scaling‐up implementation in the Chinese population.
Female case with misdiagnosis of hemophilia A who underwent total knee arthroplasty: A case report
Authors: Bari Alireza , Mansouritorghabeh Hassan
Published: March 2022

A female was diagnosed with hemophilia A. She had undergone bilateral total knee arthroplasty. She had a history of numerous hemorrhages including hemarthrosis. After further investigations, the diagnosis of von Willebrand disease type 2N was confirmed. The differential diagnoses for hemophilia A include von Willebrand disease, rare bleeding disorders, and severe platelet disorders.
Ru on N‐doped Carbon for the Selective Hydrogenolysis of Sugars and Sugar Alcohols
Authors: Beine Anna Katharina , Ludovicy Jil , Chai Jiachun , Hofmann Jan P. , Glotzbach Christoph , Hausoul Peter J. C. , Palkovits Regina
Published: March 2022

Glycols are accessible via metal‐catalyzed hydrogenolysis of sugar alcohols such as xylitol obtained from hemicellulose. Ru‐based catalysts are highly active but also catalyze side‐reactions such as decarbonylation and deoxygenation. To achieve high selectivity, these reactions need to be suppressed. In our study, we introduce heteroatom doped carbon materials as catalyst supports providing high selectivity. Heteroatom doping with nitrogen and oxygen was achieved by treating activated carbon with HNO3, NH3 and H2 or carbonization of organic precursors. For all N‐doped materials a high glycol selectivity of
80 % for sorbitol and xylitol and 44 % for xylose and glucose was reached. XPS analysis confirms the presence of different nitrogen species at the carbon surface and varying ligand effects for oxygen and nitrogen. Oxygen has an electron withdrawing effect on ruthenium and leads to a decreased activity. Nitrogen has weaker electron withdrawing properties, resulting in an enhanced selectivity.
An Intermetallic CaFe6Ge6 Approach to Unprecedented Ca−Fe−O Electrocatalyst for Efficient Alkaline Oxygen Evolution Reaction
Authors: Yang Hongyuan , Hausmann J. Niklas , Hlukhyy Viktor , Braun Thomas , Laun Konstantin , Zebger Ingo , Driess Matthias , Menezes Prashanth W.
Published: March 2022

Based on the low‐cost and relatively high catalytic activity, considerable efforts have been devoted towards developing redox‐active transition metal (TM)‐oxygen electrocatalysts for the alkaline oxygen evolution reaction (OER) while the role of redox‐inactive alkaline earth metals has often been neglected in OER. Herein, for the first time, we developed a novel ternary intermetallic CaFe6Ge6 precatalyst, whose surface rapidly transforms into a porous ultrathin Ca−Fe−O heteroshell structure during alkaline OER through the oxidative leaching of surficial Ge. Benefiting from synergistic effects, this highly efficient OER‐active material with distinct Ca−Fe−O layers has a large electrochemical surface area and more exposed active Fe sites than a Ca‐free FeOx phase. Also, the presence of Ca in Ca−Fe−O is responsible for the enhanced transport and activation of hydroxyls and related OER reaction intermediate as unequivocally illustrated by a combination of quasi in‐situ Raman spectroscopy and various ex‐situ methods.
Participation and losses in multi‐level marketing: Evidence from a Federal Trade Commission settlement
Authors: Bäckman Claes , Hanspal Tobin
Published: March 2022

More than 20 million Americans are affiliated with multi‐level marketing firms (MLMs), but there is little empirical evidence on who participates in this controversial part of today's labor market. We link data on 350,000 individuals cited in an Federal Trade Commission settlement with one of the largest MLMs to detailed county‐level information. We find that the share of refund claimants is greater in areas with higher median income and where women are absent from the labor market, suggesting value in flexible work. However, check amount, a proxy for losses, are correlated with higher inequality and lower social capital, suggesting that the pitfalls accrue to vulnerable groups.
Structures and Reactivities of Cocrystals Involving Diboronic Acids and Bipyridines: In Situ Linker Reaction and 1D‐to‐2D Dimensionality Change via Crystal‐to‐Crystal Photodimerization
Authors: Guadalupe Vasquez‐Ríos  María , Campillo‐Alvarado Gonzalo , Swenson Dale C. , Höpfl Herbert , MacGillivray Leonard R.
Published: March 2022

Cocrystallizations of diboronic acids [1,3‐benzenediboronic acid (1,3‐bdba), 1,4‐benzenediboronic acid (1,4‐bdba) and 4,4’‐biphenyldiboronic acid (4,4’‐bphdba)] and bipyridines [1,2‐bis(4‐pyridyl)ethylene (bpe) and 1,2‐bis(4‐pyridyl)ethane (bpeta)] generated the hydrogen‐bonded 1 : 2 cocrystals [(1,4‐bdba)(bpe)2] (1), [(1,4‐bdba)(bpeta)2] (2), [(1,3‐bdba)(bpe)2(H2O)2] (3) and [(1,3‐bdba)(bpeta)2(H2O)] (4), wherein 1,3‐bdba involved hydrated assemblies. The linear extended 4,4’‐bphdba exhibited the formation of 1 : 1 cocrystals [(4,4'‐bphdba)(bpe)] (5) and [(4,4'‐bphdba‐me)(bpeta)] (6). For 6, a hemiester was generated by an in‐situ linker transformation. Single‐crystal X‐ray diffraction revealed all structures to be sustained by B(O)−H⋅⋅⋅N, B(O)−H⋅⋅⋅O, Ow−H⋅⋅⋅O, Ow−H⋅⋅⋅N, C−H⋅⋅⋅O, C−H⋅⋅⋅N, π⋅⋅⋅π, and C−H⋅⋅⋅π interactions. The cocrystals comprise 1D, 2D, and 3D hydrogen‐bonded frameworks with components that display reactivities upon cocrystal formation and within the solids. In 1 and 3, the C=C bonds of the bpe molecules undergo a [2+2] photodimerization. UV radiation of each compound resulted in quantitative conversion of bpe into cyclobutane tpcb. The reactivity involving 1 occurred via 1D‐to‐2D single‐crystal‐to‐single‐crystal (SCSC) transformation. Our work supports the feasibility of the diboronic acids as formidable structural and reactivity building blocks for cocrystal construction.
Performance analysis of disease diagnostic system using IoMT and real‐time data analytics
Authors: Yıldırım Emre , Çalhan Ali , Cicioğlu Murtaza
Published: March 2022

In this article, the Internet of Medical Things (IoMT) framework based on Apache Spark big data processing technology is proposed for real‐time analysis of health data obtained from wireless body area networks (WBANs), which is one of the most important components of IoMT. The proposed framework consists of four layers: data source, data collection, data analytics and visualization. In addition, the proposed IoMT framework is presented with two different disease prediction scenarios, diabetes and heart disease. Diabetes and heart disease prediction processes are carried out using the random forest (RF), logistic regression (LR) and support vector machine (SVM) algorithms belonging to the Apache Spark machine learning library (MLlib). The analysis of health data generated in WBANs takes place in real‐time in the Apache Spark‐based data analytics layer. In this study, the performances of MLlib algorithms in the real‐time model developed for heart and diabetes disease are examined. The SVM algorithm with an accuracy rate of 93.33% for heart disease and the LR algorithm with an accuracy rate of 78.89% for diabetes are found to provide the best performances.
Antipsychotics prescribed for one in three children at clinical high risk for psychosis
Authors: Knopf Alison
Published: March 2022

In an editorial in the March issue of the Journal of the American Academy of Child and Adolescent Psychiatry, researchers focus on what they admit is a “delicate, complex, and often divisive issue” — prescribing antipsychotics for children and adolescents who have conditions which carry an “established higher risk of imminent development of an overt psychotic state.” This risk, known as clinical high risk for psychosis (CHR‐P), is not the same as, for example, a genetic risk. It is specifically related to the DSM‐5 attenuated psychosis syndrome (APS) which falls below the severity threshold for a diagnosis of schizophrenia and other psychotic disorders.
COVID‐19 linked to decreases in ED or hospital encounters for self‐harm or overdose
Authors: Knopf Alison
Published: March 2022

The initial 15 months of COVID‐19 were associated with a decline in hospital care for overdose or self‐harm in adolescents and young adults, according to a study conducted in Ontario.
Integrating Bimetal Alloy into N‐Doped Carbon Nanotubes@Nanowires Superstructure for Zn‐Air Batteries
Authors: Xu Chen , Niu Yanli , Gong Shuaiqi , Liu Xuan , Xu Mingze , Liu Tao , Chen Zuofeng
Published: March 2022

Exploring bifunctional oxygen electrocatalysts with low cost and high performance is critical to the development of rechargeable zinc‐air batteries, but it still remains a huge challenge. In this work, a “coordination construction‐pyrolysis/self‐catalyzed growth” approach was employed to fabricate branches@trunks‐like, N‐doped carbon nanotubes@nanowires superstructure with uniformly incorporated CoFe alloy nanoparticles (CoFe@CNTs‐NWs). The rational design of such hierarchical architecture could effectively enlarge the exposure of active sites, modulate their electronic structure, and assist the electron transfer and mass diffusion, thus benefiting both ORR and OER. The resultant CoFe@CNTs‐NWs displayed prominent bifunctional electrocatalytic activity and stability with a minimized oxygen overpotential of 0.71 V. When used as a cathode for zinc‐air batteries, it provided a high peak power density of 131 mW cm−2 and remarkable charge‐discharge stability for at least 400 cycles (130 h). This study presents a successful demonstration for optimizing the electrocatalytic performance by elaborate nanostructure and carbon matrix hybridization with simultaneous modulation of electronic structure, thus providing a new avenue to the rational design of transition metal‐based oxygen electrocatalysts.
Scaling‐down biopharmaceutical production processes via a single multi‐compartment bioreactor (SMCB)
Authors: Gaugler Lena , Mast Yannic , Fitschen Jürgen , Hofmann Sebastian , Schlüter Michael , Takors Ralf
Published: March 2022

Biopharmaceutical production processes often use mammalian cells in bioreactors larger than 10,000 L, where gradients of shear stress, substrate, dissolved oxygen and carbon dioxide, and pH are likely to occur. As former tissue cells, producer cell lines such as Chinese hamster ovary (CHO) cells sensitively respond to these mixing heterogeneities, resulting in related scenarios being mimicked in scale‐down reactors. However, commonly applied multi‐compartment approaches comprising multiple reactors impose a biasing shear stress caused by pumping. The latter can be prevented using the single multi‐compartment bioreactor (SMCB) presented here. The exchange area provided by a disc mounted between the upper and lower compartments in a stirred bioreactor was found to be an essential design parameter. Mimicking the mixing power input at a large scale on a small scale allowed the installation of similar mixing times in the SMCB. The particularities of the disc geometry may also be considered, finally leading to a converged decision tree. The work flow identifies a sharply contoured operational field comprising disc designs and power input to install the same mixing times on a large scale in the SMCB without the additional shear stress caused by pumping. The design principle holds true for both nongassed and gassed systems.
Performance‐based design of tall‐coupled cross‐laminated timber wall building
Authors: Teweldebrhan Biniam Tekle , Tesfamariam Solomon
Published: March 2022

Growing demand in sustainable high‐rise timber structures is satisfied by proposing innovative structural systems that enhance the building's stiffness, strength, and energy‐dissipation capacity. This study propose and develop the performance‐based design (PBD) guideline for balloon type cross‐laminated timber (CLT) coupled wall (CLT‐CW) structure. In this system, the CLT shear‐walls are connected with energy dissipation coupling beams that comprise shear‐links and in return reduce the seismic demand of the system. To facilitate the desired rocking deformation mode of CLT shear‐wall panels, buckling‐restrained brace (BRB) hold‐downs are used. Utility of the proposed system and design is applied on a 20‐story balloon CLT‐CW system. To investigate the effect of coupling ratio () on the behavior of the system, five values (10%–50%) are used. Nonlinear and incremental dynamic analyses (IDAs) are performed using suitable set of 30 ground motion (GM) records that reflects the seismicity of Vancouver, Canada. Fragility curves are developed and compared considering both the collapse and non‐collapse limit states. The results show that, for a given CLT‐CW system, a system with higher value exhibits better seismic performance.
Urinary free cortisol and childhood maltreatments in eating disorder patients: New evidence for an ecophenotype subgroup
Authors: Meneguzzo Paolo , Mancini Cecilia , Terlizzi Samira , Sales Chiara , Francesconi Maria Federica , Todisco Patrizia
Published: March 2022

Introduction

Increasing neurobiological evidence has suggested the presence of a specific ecophenotype in people with eating disorders (EDs) linked to early maltreatment. Urinary‐free cortisol could strengthen the data and show specific relationships between maltreated subtypes and the hormonal profiles of patients with EDs. This study aims to evaluate the presence of different urinary cortisol in drug‐free patients in the acute phase of the disorder and its relationship with childhood maltreatment.

Methods

A sample of 78 female patients with ED is included in the study. Childhood maltreatment history and 24‐h urinary free cortisol (24‐h UFC) are evaluated at a specialised ED ward admission.

Results

Patients with a maltreatment history show more blunted 24‐h UFC levels than peers without childhood maltreatment (p = 0.001). Regression analysis showed that child abuse is a predictor of the reduction of 24‐h UFC (p < 0.001), with physical abuse (p = 0.011) and sexual abuse (p = 0.050) that could have a more specific impact than other maltreatment subtypes.

Discussion

Childhood maltreatment should be evaluated in ED patients due to its biological impact on the hormonal stress axis, which could impair the ability of patients to respond to standardized ED treatment.
Pulse injection simulation based on the coupling of transient flow in tubing and fracture propagation in reservoirs
Authors: Zhu Ge , Dong Shimin , Ma Biao
Published: March 2022

Pulse injection can reduce the maximum operating pressure at the wellhead, which is conducive to solving the operational difficulties caused by the high breakdown pressure. The new injection mode causes a transient fluid flow in the tubing, and it interacts with the initiation and propagation of hydraulic fractures. However, there is still a lack of theoretical models to consider the above factors so that its mechanism cannot be explained. In this study, the transient flow model in the tubing was first established. Subsequently, the fracture propagation model was completed based on particle flow code (PFC). Moreover, the transient flow model was embedded into the PFC simulation software via its code script FISH. Finally, their coupled simulation model was established. Based on this model, the effects of injection flow rates on the fluid pressure in the tubing and the initiation and propagation of hydraulic fractures were discussed. Furthermore, the influence of parameters in the pulse injection scheme on the maximum wellhead pressure was studied by the orthogonal design method. The results show that with the increase of the injection flow rate, the fluid pressurization rate in the tubing and the fracture propagation rate both raise, which also causes a significant increase of the maximum wellhead pressure. Compared with a stable injection mode, pulse injection can evidently reduce the maximum wellhead pressure. The influence degree of each parameter on the maximum wellhead pressure in the pulse scheme is as follows: t2 > Δq > Δt4 > Δt5 > Δt3. The research results of this paper have guiding significance for the engineering application and parameter design of pulse injection hydraulic fracturing.
A novel method for estimating connectivity‐based parcellation of the human brain from diffusion MRI: Application to an aging cohort
Authors: Coelho Ana , Magalhães Ricardo , Moreira Pedro S. , Amorim Liliana , Portugal‐Nunes Carlos , Castanho Teresa , Santos Nadine Correia , Sousa Nuno , Fernandes Henrique M.
Published: March 2022

Connectivity‐based parcellation (CBP) methods are used to define homogenous and biologically meaningful parcels or nodes—the foundations of brain network fingerprinting—by grouping voxels with similar patterns of brain connectivity. However, we still lack a gold standard method and the use of CBPs to study the aging brain remains scarce. Our study proposes a novel CBP method from diffusion MRI data and shows its potential to produce a more accurate characterization of the longitudinal alterations in brain network topology occurring in aging. For this, we constructed whole‐brain connectivity maps from diffusion MRI data of two datasets: an aging cohort evaluated at two timepoints (mean interval time: 52.8 ± 7.24 months) and a normative adult cohort—MGH‐HCP. State‐of‐the‐art clustering techniques were used to identify the best performing technique. Furthermore, we developed a new metric (connectivity homogeneity fingerprint [CHF]) to evaluate the success of the final CBP in improving regional/global structural connectivity homogeneity. Our results show that our method successfully generates highly homogeneous parcels, as described by the significantly larger CHF score of the resulting parcellation, when compared to the original. Additionally, we demonstrated that the developed parcellation provides a robust anatomical framework to assess longitudinal changes in the aging brain. Our results reveal that aging is characterized by a reorganization of the brain's structural network involving the decrease of intra‐hemispheric, increase of inter‐hemispheric connectivity, and topological rearrangement. Overall, this study proposes a new methodology to perform accurate and robust evaluations of CBP of the human brain.
Using child‐friendly movie stimuli to study the development of face, place, and object regions from age 3 to 12 years
Authors: Kamps Frederik S. , Richardson Hilary , Murty N. Apurva Ratan , Kanwisher Nancy , Saxe Rebecca
Published: March 2022

Scanning young children while they watch short, engaging, commercially‐produced movies has emerged as a promising approach for increasing data retention and quality. Movie stimuli also evoke a richer variety of cognitive processes than traditional experiments, allowing the study of multiple aspects of brain development simultaneously. However, because these stimuli are uncontrolled, it is unclear how effectively distinct profiles of brain activity can be distinguished from the resulting data. Here we develop an approach for identifying multiple distinct subject‐specific Regions of Interest (ssROIs) using fMRI data collected during movie‐viewing. We focused on the test case of higher‐level visual regions selective for faces, scenes, and objects. Adults (N = 13) were scanned while viewing a 5.6‐min child‐friendly movie, as well as a traditional localizer experiment with blocks of faces, scenes, and objects. We found that just 2.7 min of movie data could identify subject‐specific face, scene, and object regions. While successful, movie‐defined ssROIS still showed weaker domain selectivity than traditional ssROIs. Having validated our approach in adults, we then used the same methods on movie data collected from 3 to 12‐year‐old children (N = 122). Movie response timecourses in 3‐year‐old children's face, scene, and object regions were already significantly and specifically predicted by timecourses from the corresponding regions in adults. We also found evidence of continued developmental change, particularly in the face‐selective posterior superior temporal sulcus. Taken together, our results reveal both early maturity and functional change in face, scene, and object regions, and more broadly highlight the promise of short, child‐friendly movies for developmental cognitive neuroscience.
COVID‐19 associated EBV reactivation and effects of ganciclovir treatment
Authors: Meng Mei , Zhang Sheng , Dong Xuan , Sun Wenqing , Deng Yunfeng , Li Wenzhe , Li Ranran , Annane Djillali , Wu Zhixiong , Chen Dechang
Published: March 2022

Background

Systemic reactivation of Epstein–Barr virus (EBV) may occur in novel coronavirus disease 2019 (COVID‐19) caused by the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). However, the clinical consequences of EBV reactivation remain uncertain.

Methods

In this retrospective study, we screened 1314 patients with confirmed COVID‐19 who died or were discharged between January 1, 2020 and March 12, 2020, in Wuhan Infectious Disease Hospital, Wuhan, China. Patients who had complete data for EBV serology and cytomegalovirus (CMV) serology were eligible. Serum levels of viral capsid antigen (VCA)‐immunoglobulin G (IgG), Epstein–Barr nuclear antigen‐IgG, VCA‐IgM, early antigen (EA)‐IgG, CMV‐IgG, and CMV‐IgM were compared between survivors and nonsurvivors. Dynamic changes of laboratory tests and outcomes were compared in patients with and without ganciclovir treatment. We used 1:1 matching based on age, gender, and illness severity to balance baseline characteristics.

Results

EBV reactivation was present in 55 of 217 patients. EBV reactivation was associated with age (57.91 [13.19] vs. 50.28 [12.66] years, p < .001), female gender (31 [56%] vs. 60 [37%], p = .02). Patients with EBV reactivation have statistically nonsignificant higher mortality rate (12 [22%] vs. 18 [11%], p = .08). EA‐IgG levels were significantly higher in nonsurvivors than in survivors (median difference: −0.00005, 95% confidence interval, CI [−3.10, 0.00], p = .05). As compared to patients with COVID‐19 who did not receive ganciclovir therapy, ganciclovir‐treated patients had improved survival rate (0.98, 95% CI [0.95, 1.00] vs. 0.88, 95% CI [0.81, 0.95], p = .01). Hemoglobin (p < .001) and prealbumin (p = .02) levels were significantly higher in ganciclovir‐treated patients.

Conclusion

A high proportion of COVID‐19 patients had EBV reactivation that may be associated with an increased risk of death. Whether treatment with ganciclovir may decrease the mortality of COVID‐19 patients complicated with EBV reactivation warrants to be addressed in a placebo‐controlled randomized trial in the future.
The effects of taxes and stock repurchases on domestic and multinational companies’ debt levels
Authors: Liu Hanni
Published: March 2022

In past decades, corporate debt levels have risen to historical highs and remained elevated. This study examines one of the key reasons that caused the high debt levels––income taxes. Specifically, this study contrasts the effects of tax planning on corporate debt levels in domestic companies (DCs) and multinational companies (MNCs) in the United States. It also explores how stock repurchase enhances such effects. The findings show that the association between debts and the outcomes of tax of planning is stronger in DCs than in MNCs. This suggests that DCs are more likely to use debt tax shields than MNCs. In addition, compared to tax‐efficient DCs, tax‐efficient MNCs are more likely to borrow in order to repurchase stock, resulting high debt levels. Moreover, the study provides evidence that the credit rating adjusts DCs’ and MNCs’ credit ratings when they raise debts to repurchase stocks.
Clinical value of serum JKAP in acute ischemic stroke patients
Authors: Zhang Jianli , Yang Jing , Hu Jingchun , Zhao Weiwei
Published: March 2022

Background

Jun N‐terminal kinase pathway‐associated phosphatase (JKAP) regulates neuronal function, T helper (Th) 1/2/17 cell differentiation, and inflammatory process, but its clinical role in acute ischemic stroke (AIS) patients remains unclear. Hence, this study intended to evaluate JKAP level and its relationship with disease severity, Th1, 2, 17 secreted cytokines, adhesion molecules, and prognosis of AIS patients.

Methods

Serum JKAP of 122 AIS patients and 50 controls was detected by ELISA. For AIS patients only, Th1, 2, 17 secreted cytokines IFN‐γ, IL‐4, IL‐17; TNF‐α, ICAM‐1, and VCAM‐1 were also detected by ELISA.

Results

JKAP was decreased in AIS patients compared with controls (46.350 (interquartile range (IQR): 34.250–59.875) pg/ml vs. 84.500 (IQR: 63.175–113.275) pg/ml, p < 0.001), which could distinguish AIS patients from controls (area under curve (AUC): 0.810, 95% confidence interval (CI): 0.732–0.888). In AIS patients, JKAP negatively linked with the National Institutes of Health Stroke Scale (NIHSS) score (rs = −0.342, p < 0.001); besides, it was positively related to IL‐4 (rs = 0.213, p = 0.018) and negatively associated with IL‐17 (rs = −0.270, p = 0.003) but not related to IFN‐γ (rs = −0.146, p = 0.109). Furthermore, elevated JKAP associated with declined TNF‐α (rs = −0.219, p = 0.015) and ICAM‐1 (rs = −0.235, p = 0.009) but not related to VCAM‐1 (rs = −0.156, p = 0.085). Besides, declined JKAP was linked with 2‐year recurrence (p = 0.027) and 3‐year recurrence (p = 0.010) in AIS patients; while JKAP was not related to 1‐year recurrence or death risk (both p > 0.050).

Conclusion

JKAP may sever as a candidate prognostic biomarker in AIS patients, indicating its potency for AIS management.
The application of certified reference materials for clinical mass spectrometry
Authors: Lingxiao Shen , Jinfei Ma , Qingqing Yang , Pengyun Liu , Huafen Liu
Published: March 2022

Background

In the application process of clinical mass spectrometry, there are difficulties such as standardization, low degree of automation, complex instruments, and high requirements for operations, which will affect the accuracy and comparability of results. Reference materials are one of the major approaches to achieve measurement accuracy and metrological comparability.

Methods

Based on the problems of reference materials in clinical mass spectrometry, the precautions for the use of reference materials are summarized in the aspects of measurement method validation, calibrator usage, and quality control in this article. Additionally, combined with the previous experience of the author's laboratory, the operation mode and acceptance criteria of the new calibration solution lot replacement were formulated to ensure the continuous comparability of the measurement system.

Conclusion

Carefully understand and correctly regulate the use and management of reference materials to ensure the accuracy of test results, thereby improving the comparability and consistency of results between laboratories.
Abnormal expression of histone acetylases in CD8+ T cells of patients with severe aplastic anemia
Authors: Qi Weiwei , Zhang Yu , Wang Yachen , Wang Huaquan , Fu Rong , Shao Zonghong
Published: March 2022

Introduction

We aimed to investigate the balance between the mRNA levels of histone acetyltransferases (HATs) and histone deacetylases (HDACs) in CD8+ T cells of patients with severe aplastic anemia (SAA).

Methods

Twenty untreated SAA patients, 18 remission SAA patients (R‐SAA), and 22 normal controls were evaluated. The mRNA expression levels of HATs, HDACs, and IFNG in CD8+ T cells were measured by real‐time quantitative reverse transcription polymerase chain reaction.

Results

Histone acetylase EP300 and CREBBP mRNA levels were significantly elevated in CD8+ T cells of SAA patients compared with the normal controls (both p < 0.05). No significant differences were observed in HDAC1 and HDAC7 mRNA between SAA patients and the normal controls. There was an obvious positive correlation between IFNG and EP300 (r = 0.5126, p < 0.01), and CREBBP (r = 0.4663, p < 0.05), respectively, in SAA and R‐SAA patients. In addition, EP300 and CREBBP mRNA levels were clearly correlated with clinical parameters of peripheral blood and bone marrow in those patients.

Conclusion

Our findings suggest that EP300 and CREBBP are increased in CD8+ T cells of SAA patients and are correlated with disease severity. The imbalances in HATs and HDACs may play a role in activating CD8+ T cells to promote the immune pathogenesis of SAA.
Barriers, support, and resilience of prospective first‐in‐family university students: Australian high school educators' perspective
Authors: Pires Charmian M. , Chapin Laurie A.
Published: March 2022

First‐in‐family (FiF) university students—or first generation students—are recognised to have disadvantages and lack social and cultural capital compared with non‐FiF students. The challenges FiF students encounter at university are well understood, however, their journey begins while still in high school. We call this high school cohort prospective FiF (PFiF) students and young people whose parents never attended university. This qualitative study explored the perspectives of 10 high school educators from Melbourne, Australia about the barriers and supports PFiF students encounter as they navigate the path to university. Participants identified that family inexperience, unsupportive attitudes at home and at school, lack of financial capacity and invisibility represented barriers. However, participants also explained that PFiF students can be resilient and motivated, especially when combined with appropriate support from schools, family, and university programmes. The findings highlight the challenges for PFiF and bring much‐needed attention to their challenges and needs in the early transition to higher education.
Virtual aids and students’ performance with haptic simulation in implantology
Authors: Vincent Marin , Giess Renaud , Balthazard Rémy , Tran Nguyen , Mortier Éric , Joseph David
Published: March 2022

Objetives

This study aims to validate that haptic simulator assistance could improve drilling ability in implantology and that the repetition of training session could highlight a learning curve.

Methods

This work was carried out with 88 first‐year dental students. After randomization, students were divided into two groups. Group 1 was assigned to prepare an implant site for a left first mandibular molar (36) on haptic simulator with assistance provided by simulator. Group 2 had to perform the same exercise without assistance. Whatever the group, the maximum time for each reparation was restricted to 5 min. An interval of 1 week was done between each session. For each test, different objective parameters provided by the simulator were recorded and analyzed.

Results

This study showed that the presence of virtual aids led to quickly obtain better results, and the training led to gradually acquire sufficient competence to do without virtual aids.

Conclusion

By associating virtual assistance and repetition, the student will acquire more quickly the skills allowing to carry out his clinical gestures in real conditions.
How aerobic exercise improves executive function in ADHD children: A resting‐state fMRI study
Authors: Jiang Kaihua , Xu Yue , Li Yamin , Li Lin , Yang Mingmei , Xue Peng
Published: March 2022

The aim of the study is to explore the functional magnetic resonance imaging (fMRI) characteristics of the improvement in executive function by aerobic exercise in children with attention deficit hyperactivity disorder (ADHD). Seventeen children with ADHD were selected for 8 weeks of rope skipping aerobic training, and fMRI findings and executive function were examined before and after training. Regional homogeneity (ReHo) and degree centrality (DC) indexes were used in fMRI analysis, whereas the flanker task was used to test executive function. A paired t test was used to compare the fMRI indexes and response time of executive function before and after training. After aerobic exercise, the brain regions in which the ReHo value of ADHD children significantly increased included the left middle frontal gyrus and the right superior frontal gyrus; the brain region in which the DC value increased was the right posterior cingulate cortex. The flanker task response time decreased significantly (P < 0.05, after correction) after aerobic exercise. The study findings support the hypothesis that aerobic exercise can improve the executive function of ADHD children, and the brain mechanism involved is mainly related to the enhancement of spontaneous prefrontal lobe activity.
Effectiveness of angiotensin converting enzyme inhibitors in preventing pneumonia: A systematic review and meta‐analysis
Authors: Tsunoda Hideki , Okami Yukiko , Honda Yuki , Shiroshita Akihiro , Kataoka Yuki , Tsujimoto Yasushi , Matsumura Kazuhiro
Published: March 2022

We performed a systematic review and meta‐analysis to re‐evaluate the effectiveness of angiotensin‐converting enzyme inhibitors (ACE‐I) in the reduction of pneumonia risk. We searched relevant publications in five databases. All studies included patients older than 18 years, who had used ACE‐I as an intervention, and had assessed pneumonia. Seven RCTs (n = 8704) and 38 observational studies (n = 1,705,030) were included. The overall risk of bias was high. ACE‐I‐treated patients were associated with a slightly lower risk of pneumonia, both from pooled estimates of RCTs [pooled odds ratio (OR), 0.75; 95% confidence interval (CI), 0.62–0.90; low certainty of evidence] and observational studies (pooled OR, 0.85; 95% CI, 0.78–0.92; very low certainty of evidence). Considering the small effect size of ACE‐I in preventing pneumonia and the low quality of the evidence, routine use of ACE‐I for pneumonia prevention is not recommended.
Prolonged fecal shedding of SARS‐CoV‐2 in a young immunocompetent COVID‐19 patient: A case report and literature overview
Authors: Xiao Fang , Wan Peiqi , Wei Qiuling , Wei Guiyang , Yu Yanhong
Published: March 2022

Clinicians are facing several challenges in tackling coronavirus disease 2019 (COVID‐19); one issue is prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) RNA. Here, we describe a case of SARS‐CoV‐2 infection in a young immunocompetent patient with a virological course lasting for 71 days. Following antiviral treatment, but no additional glucocorticoid or interferon therapy, the patient recovered from COVID‐19 pneumonia (moderate). Detection of viral RNA via throat swabs showed negative results. However, the viral RNA reappeared and persisted in stool samples for an additional 27 days, while the patient remained asymptomatic and exhibited no abnormal signs. This case indicates that SARS‐CoV‐2 can result in a prolonged fecal RNA shedding, even in an immunocompetent patient with zero exposure to immunosuppressive therapies.
Comparison of extraction‐based and elution‐based polymerase chain reaction testing, and automated and rapid antigen testing for the diagnosis of severe acute respiratory syndrome coronavirus 2
Authors: Yoshioka Nori , Deguchi Matsuo , Hagiya Hideharu , Kagita Masanori , Tsukamoto Hiroko , Takao Miyuki , Yoshida Hisao , Hamaguchi Shigeto , Maeda Ikuhiro , Hidaka Yoh , Tomono Kazunori
Published: March 2022

We aimed to compare the differences in testing performance of extraction‐based polymerase chain reaction (PCR) assays, elution‐based direct PCR assay, and rapid antigen detection tests for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). We used nasopharyngeal swab samples of patients with coronavirus disease 2019 (COVID‐19). We used the MagNA Pure 24 System (Roche Diagnostics K.K.) or magLEAD 12gC (Precision System Science Co., Ltd.) for RNA extraction, mixed the concentrates with either the LightMix Modular SARS‐CoV PCR mixture (Roche Diagnostics K.K.) or Takara SARS‐CoV‐2 direct PCR detection kit (Takara Bio Inc.), and amplified it using COBAS® z480 (Roche Diagnostics K.K.). For elution‐based PCR, we directly applied clinical samples to the Takara SARS‐CoV‐2 direct PCR detection kit before the same amplification step. Additionally, we performed Espline SARS‐CoV‐2 (Fuji Rebio Co., Ltd.) for rapid diagnostic test (RDT), and used Lumipulse SARS‐CoV‐2 antigen (Fuji Rebio Co., Ltd.) and Elecsys SARS‐CoV‐2 antigen (Roche Diagnostics K.K.) for automated antigen tests (ATs). Extraction‐based and elution‐based PCR tests detected the virus up to 214–216 and 210 times dilution, respectively. ATs remained positive up to 24–26 times dilution, while RDT became negative after 22 dilutions. For 153 positive samples, positivity rates of the extraction‐based PCR assay were 85.6% to 98.0%, while that of the elution‐based PCR assay was 73.2%. Based on the RNA concentration process, extraction‐based PCR assays were superior to elution‐based direct PCR assays for detecting SARS‐CoV‐2.
Bacterial overgrowth assessment and treatment among pediatric intestinal rehabilitation and nutrition support providers: An international survey of clinical practice patterns
Authors: Namjoshi Shweta S. , Galloway David , Herdes Rachel E. , Talathi Saurabh , Ding Victoria Y. , Mezoff Ethan A.
Published: March 2022

Background

Small bowel bacterial overgrowth (SBBO) is a common, but difficult to diagnose and treat, problem in pediatric short bowel syndrome (SBS). Lack of clinical consensus criteria and unknown sensitivity and specificity of bedside diagnosis makes research on this potential SBS disease modifier challenging. The objective of this research was to describe clinical care of SBBO among international intestinal rehabilitation and nutrition support (IR&NS) providers treating patients with SBS.

Methods

A secure, confidential, international, electronic survey of IR&NS practitioners was conducted between March 2021 and May 2021. All analyses were conducted in the R statistical computing framework, version 4.0.

Results

Sixty percent of respondents agreed and 0% strongly disagreed that abdominal pain, distension, emesis, diarrhea, and malodorous stool, were attributable to SBBO. No more than 20% of respondents strongly agreed and no more than 40% agreed that any sign or symptom was specific for SBBO. For a first‐time diagnosis, 31 practitioners agreed with use of a 7‐day course of a single antibiotic, with a majority citing grade 5 evidence to inform their decisions (case series, uncontrolled studies, or expert opinion). The most common first antibiotic used to treat a new onset SBBO was metronidazole, and rifaximin was the second most commonly used. One hundred percent of respondents reported they would consider a consensus algorithm for SBBO, even if the algorithm may be divergent from their current practice.

Conclusion

SBBO practice varies widely among experienced IR&NS providers. Development of a clinical consensus algorithm may help standardize care to improve research and care of this complex problem and to identify risks and benefits of chronic antibiotic use in SBS.
Investigation into theanti‐inflammatoryproperties of metformin in intervertebral disc cells
Authors: Ramanathan Rahul , Firdous Ayesha , Dong Qing , Wang Dong , Lee Joon , Vo Nam , Sowa Gwendolyn
Published: March 2022

Introduction

Intervertebral disc degeneration (IDD) is closely related to heightened inflammation in the annulus fibrosis (AF) and nucleus pulposus (NP) cells in the intervertebral disc. An imbalanced matrix homeostasis has been shown to contribute to disc degeneration and associated discogenic low back pain. Metformin, a diabetes medication, has been noted to exhibit anti‐inflammatory properties through upregulation of the AMPK pathway, leading to various anti‐inflammatory‐related responses in hepatocytes. However, it is still unclear how metformin influences disc cellular response to inflammatory stress and the corresponding mechanism. Hence, the objective of this study is to elucidate the effects of metformin on expression of key pro‐inflammatory, catabolic, and anabolic factors within rat AF cells in response to inflammatory stimulation and mechanical tensile stress.

Methods

Five Fischer 344 rats were sacrificed and their spines isolated. AF cells were cultured and plated in flexible silicone membrane‐based six‐well plates. Wells were split into eight groups and subjected to metformin, IL‐1β, mechanical stretch, and combined treatments. Relative gene expressions of MMP‐13, COX‐2, iNOS, AGC, and Col1 were assessed with quantitative real‐time polymerase chain reaction (qRT‐PCR), and downstream prostaglandin E2(PGE2) production was quantified with enzyme‐linked immunosorbent assay (ELISA). NF‐kB nuclear translocation was also quantified.

Results

Metformin in the presence of the combined stress treatments (M + IL/S) significantly increased Col1, COX‐2, and MMP‐13 gene expression, decreased PGE2 production compared to IL/S conditions alone. Metformin treatment of cultured rat annulus fibrosus cells significantly reduced the nuclear translocation of NF‐κB after 4 h of IL‐1β treatment from 43.1% in case of IL‐1β treatment down to 26.2% in the case of metformin + IL‐1β treatment.

Discussion

The lack of metformin‐mediated suppression of inflammatory response in the nonstretch groups indicates that metformin may be enacting its effects through a stretch‐dependent manner. These results suggest a foundation for pursuing further research into metformin's potential role as an anti‐inflammatory agent for curtailing intervertebral disc degeneration.
Incomplete autophagy: Trouble is a friend
Authors: Zhang Qiang , Cao Shijie , Qiu Feng , Kang Ning
Published: March 2022

Incomplete autophagy is an impaired self‐eating process of intracellular macromolecules and organelles in which accumulated autophagosomes do not fuse with lysosomes for degradation, resulting in the blockage of autophagic flux. In this review, we summarized the literature over the past decade describing incomplete autophagy, and found that different from the double‐edged sword effect of general autophagy on promoting cell survival or death, incomplete autophagy plays a crucial role in disrupting cellular homeostasis, and promotes only cell death. What matters is that incomplete autophagy is closely relevant to the pathogenesis and progression of various human diseases, which, meanwhile, intimately linking to the pharmacologic and toxicologic effects of several compounds. Here, we comprehensively reviewed the latest progress of incomplete autophagy on molecular mechanisms and signaling pathways. Moreover, implications of incomplete autophagy for pharmacotherapy are also discussed, which has great relevance for our understanding of the distinctive role of incomplete autophagy in cellular physiology and disease. Consequently, targeting incomplete autophagy may contribute to the development of novel generation therapeutic agents for diverse human diseases.
An effective numerical simulation for solving a class of Fokker–Planck equations using Laguerre wavelet method
Authors: Srinivasa Kumbinarasaiah , Rezazadeh Hadi , Adel Waleed
Published: March 2022

This work presents a fast and efficient approach for solving the Fokker–Planck equation via the Laguerre wavelet collocation method. Properties of the Laguerre wavelet are presented, along with the Laguerre basis to reduce the problems into systems of either linear or nonlinear algebraic equations. This system is then solved to find the unknown coefficients. A convergent analysis for the proposed scheme is explained through theorems. Several numerical examples are presented to demonstrate the applicability and accuracy of the method to a wide variety of similar problems. The results are compared to other methods through graphs and tables.
On properties of aggregated regularized systems of equations for a homogeneous multicomponent gas mixture
Authors: Zlotnik Alexander , Fedchenko Anna
Published: March 2022

Two aggregated regularized systems of equations for a multicomponent homogeneous gas mixture are considered. An entropy balance equation with a non‐negative entropy production is derived for them in the presence of diffusion fluxes. The existence, uniqueness andL2‐dissipativity of weak solutions to an initial‐boundary value problem for the systems linearized on a constant solution are established. The Petrovskii parabolicity and the local in time classical unique solvability of the Cauchy problem are also proved for the aggregated systems themselves.