bluuebunny/crossref_metadata_2025 huggingface dataset:
Perspectives of vitamin C upregulating regulatory T cells in the era of thrombopoietin receptor agonists for immune thrombocytopenia
Authors: Tsao Shiu Ying
Published: October 2022

Background

Immune thrombocytopenia (ITP) is a rare disorder involving excessive peripheral destruction of platelets and inadequate bone marrow platelet production due to autoimmune reactions against megakaryocytes. Diagnosis is usually by the exclusion of primary causes; its rarity would only permit trial and error therapy experience.

Historically, for ITP, oral ascorbic acid (AA) gave inconsistent results. However, unlike other nutrients, AA is found to have an exceptionally tight intestinal absorption restriction mandating intravenous delivery for any therapeutic purposes. Recently, as there is more pre‐clinical evidence of AA restoring regulatory T cells (Tregs) by robust demethylation, the historical oral route was likely to be the “bottle neck” restricting effective blood levels. During this era of thrombopoietin receptor agonists (TPO‐RAs), planned tapering is often required upon discontinuation but unplanned discontinuations, for example, due to side effects, are more problematic. Moreover, combinations with TPO‐RAs are currently being tried using steroids and rituximab except rituximab is inappropriate during pandemics. Notably, with the indirect (but prognostically relevant) action of TPO‐RAs on Tregs, boosting Treg functions by adding other Treg active agents, for example, steroids or AA, seems appropriate, especially if without added toxicity upon combining.

Conclusions

With updated pharmacokinetic concepts, it is timely to repeat AA clinical trials for ITP but using intravenous administration. Initially, this may be on compassionate grounds for its probable role as an adjunct to TPO‐RAs for unsuccessful tapering and, especially, for all unplanned discontinuations of TPO‐RAs. Such off‐label usage of AA is justified because of AA's robust pre‐clinical evidence on demethylation and initial clinical experience (despite the inappropriate administrative route). Moreover, moderate intravenous AA dosages have one of the best safety profiles, let alone its eminent affordability. Admittedly, after the initial clinical experience, more systematic trials on AA are required, especially for the most appropriate dosage range and its efficacy as monotherapy.
Symplectic model reduction methods for the Vlasov equation
Authors: Tyranowski Tomasz M. , Kraus Michael
Published: October 2022

Particle‐based simulations of the Vlasov equation typically require a large number of particles, which leads to a high‐dimensional system of ordinary differential equations. Solving such systems is computationally very expensive, especially when simulations for many different values of input parameters are desired. In this work, we compare several model reduction techniques and demonstrate their applicability to numerical simulations of the Vlasov equation. The necessity of symplectic model reduction algorithms is illustrated with a simple numerical experiment.
Diagnostic tools for hyperpigmentation disorders in skin of color: An updated review
Authors: Pagan Angel D. , Mitchell Krystal , Yousif Jenna , Henry Michelle
Published: October 2022

Hyperpigmentation disorders are highly prevalent and disproportionately affect patients with skin of color. Studies suggest that over 65% of Black or African American patients haveexperienced at least one episode of hyperpigmentation due to skin damage or irritation. Notably, melasma and postinflammatory hyperpigmentation are the two most common forms of dyschromia in patients with skin of color. Additionally, otherconditionssuch as lichen planus and erythema dyschromicum perstans can have a more severe presentation and significant morbidity in this patient population. Thus, hyperpigmentation disorders can benefit greatly from prompt and accurate diagnosis that results in more precise management. In this review, we present the most updated information regarding dermoscopy, reflectance confocal, and conventional light microscopy in the diagnosis of hyperpigmentation disorders in skin of color. In addition, we summarize the benefits and pitfalls of some of these techniques, with a special emphasis on their accuracy and potential to assess favorable treatment outcomes. We also describe recent studies that have compared these diagnostic techniques across many disorders of hyperpigmentation and the practical findings that can be applied to everyday practice. We recognize that the cost of equipment, clinician training, and device availability are all critical factors when choosing the ideal diagnostic tool and provide varied approaches to improve accuracy. Today, diagnosing and treating hyperpigmentation skin conditions has become easier through technological advances. More reliable, noninvasive techniques such as dermoscopy and reflectance confocal microscopy show promise as adjuncts to guide laser and light therapies and monitor treatment response in dermatology clinics and clinical trials.
Consider accommodations options for Complex Post‐Traumatic Stress Disorder
Authors: Bedrossian Louise
Published: October 2022

Complex Post‐Traumatic Stress Disorder is a new diagnostic category in The International Classification of Diseases‐11 released by the global Word Health Organization on January 1, 2022.
Can age‐related changes in parental care modulate inbreeding depression? A test using the burying beetle, Nicrophorus orbicollis
Authors: Schrader Matthew , Hughes Parker , Jenkins Samuel , Kusher Ian , Lopez Jonathan , Oglesby Harriet , McGhee Katie E.
Published: October 2022

Parental care has been shown to reduce the magnitude of inbreeding depression in some species with facultative care. However, parents often vary in the quality or amount of care they provide to their offspring, and it is less clear whether this variation also impacts the magnitude of inbreeding depression. Here, we tested whether age‐related changes in parental care modulate the expression of inbreeding depression in the burying beetle, Nicrophorus orbicollis. Consistent with previous studies, we found that older parents produced larger broods of offspring than younger parents without sacrificing mean larval mass. Inbreeding depression was evident in several fitness‐related traits: brood size at dispersal, the proportion of the brood that survived to eclosion, and mean age at death were all reduced in inbred broods compared with outbred broods. Surprisingly, inbred offspring were heavier at dispersal than outbred offspring. This was likely due to reduced sibling competition in inbred broods. Despite evidence for age‐related changes in parental investment and the existence of inbreeding depression, there was no evidence that an interaction between the two influenced any of the traits we measured. Our results suggest that age‐related changes in parental care may be too slight to influence the expression of inbreeding depression.
A comparison of density estimation methods for monitoring marked and unmarked animal populations
Authors: Twining Joshua P. , McFarlane Claire , O'Meara Denise , O'Reilly Catherine , Reyne Marina , Montgomery W. Ian , Helyar Sarah , Tosh David G. , Augustine Ben C.
Published: October 2022

Effective monitoring of wildlife populations forms the foundation of modern‐day conservation biology. Without reliable estimates of population size, it is not possible to determine population trends, a key requirement in determining species status under international legislation. Carnivores are one of the more difficult taxonomic groups to monitor due to low population densities and elusive behavior. Here, we compare conventional live trapping and two more modern, noninvasive field methods of population estimation: genetic fingerprinting from hair tube sampling and camera trapping for the pine marten (Martes martes). We apply marked spatial capture–recapture (SCR) models to the genetic and live‐trapping data where individuals were identifiable, and unmarked SCR (uSCR), camera‐trap distance sampling (CT‐DS), and random encounter models (REMs) to the camera‐trap data where individual ID was not possible. All five approaches produced plausible and relatively consistent point estimates (0.49–1.20 individuals/km2) despite differences in precision, cost, and effort being apparent. Genetic fingerprinting produced the most precise estimate out of the two approaches for marked animal populations and had the key benefit of being noninvasive but was the most expensive of all the methods. Live trapping produced the highest point estimate while being cheapest, but the most labor intensive and least precise. The camera‐trapping methods for unmarked animal populations were the most time efficient and precise except uSCR with a moderately informative prior (uSCRm), which produced the second least precise density estimate of all the methods compared. The CT‐DS produced the most precise estimate of all the methods, followed by REM and then uSCR with a strongly informative prior (uSCRs). While choice of method of density estimation depends on objectives and funding constraints, as well as the species of interest, we demonstrate the importance of usinga prioriknowledge of target species and consideration of planned statistical analysis to produce appropriate experimental designs with critical consideration required regarding trap spacing and spatial extent. Such considerations broaden the comparability and applicability of these methods and will serve to provide key reference estimates for researchers, wildlife managers, and non‐governmental organizations involved in monitoring wildlife populations.
Modeling Contact Behavior of Multiparticles and Particle–Current Collector Contact in Porous Electrode
Authors: Wu Yang , Huang Pingyuan , Gao Li Ting , Guo Zhan-Sheng
Published: October 2022

There are various component contacts in porous electrodes, such as the direct contact between the active particles and the particle–current collector, during electrode manufacturing and lithium‐ion battery electrochemical cycles. Herein, an electrochemical–mechanical representative volume element model is developed to study the contact behavior of porous electrodes. For the direct contact behavior of multiple particles, stronger battery constraints and larger size differences enhance the reduction in Li‐ion concentration in the contact area of the active particles in the porous electrode and the contact stress in the porous electrode particles. For the contact between the active particles and current collector, the decrease in the elastic modulus of the current collector slightly increases the contact radius and significantly reduces the contact stress. By comparing the contact area and contact stress of the smooth and rough current collectors, the latter has a smaller contact area and larger contact stress when in contact with active particles. These findings provide insights into designing Li‐ion batteries from the perspective of contact stress to minimize the mechanical failure of porous electrodes.
Secure transmission in smart grid dynamic wide area network by exploiting full‐duplex jamming scheme
Authors: Odeyemi Kehinde Oluwasesan , Owolawi Pius Adewale , Olakanmi Oladayo Olufemi
Published: October 2022

This article studies a smart grid dynamic wide area network where a friendly jammer is proposed to enhance the secrecy of the network. In the network, the smart meter (SM) in each household communicates with the full‐duplex meter data control unit (FD‐MDCU) via a decode‐and‐forward data aggregation unit in the presence of an eavesdropper. To improve the security of the network, the FD‐MDCU transmits jammer signal which interfere with the eavesdropper. It is assumed that all the household are not sending data at the same time, thus Markov chain is employed to model the number of active SM. Thus, to evaluate the performance of the proposed network, the closed‐form expressions of connection outage probability (COP), security outage probability, and secrecy throughput metrics are obtained. Moreover, more insight about the network performance is provide by obtaining the COP asymptotic expression at high signal‐to‐noise ratio. Also, the accuracy of the derived expressions is justified by Monte‐Carlo simulations. Our findings demonstrate the impact of network and channel parameters on the network security performance.
Effects of organic and chemical nitrogen fertilization and postharvest treatments on the visual and nutritional quality of fresh‐cut celery (Apium graveolens L.) during storage
Authors: Babalar Mesbah , Daneshvar Hadiseh , Díaz‐Pérez Juan Carlos , Nambeesan Savithri , Tabrizi Leila , Delshad Mojtaba
Published: October 2022

The shelf life of horticultural commodities depends on pre‐ and postharvest factors, such as soil fertilization and postharvest handling. The current study aimed to evaluate fresh‐cut celery's postharvest quality as affected by the rate and type (organic and chemical) of nitrogen (N) fertilizer and postharvest treatments. Celery (‘Tall Utah’) crop was grown in a field in Karaj, Iran. The experimental design was a randomized complete block with three replications and seven preharvest (fertilizer), and five postharvest treatments. Organic fertilizers were vermicompost (VER) and bio‐organic fertilizer [farmyard and livestock manure plus Trichoderma harzianum (COM)]. Chemical fertilizers were urea (46% N) at high rate [322 kg·ha1 N (UREA_HIGH)], optimal rate [196 kg·ha−1 N (UREA_OPT)], and low rate [138 kg·ha−1 N (UREA_LOW)]; ammonium nitrate [35% N (AN)] at 196 kg·ha−1 N; and treatment without fertilization was used as a control. Postharvest treatments included plastic packaging (PP), hydrocooling (HC), blanching (B), and edible coating of psyllium seed mucilage (EC). After postharvest treatments, celery petioles were stored (0–2°C, 85%–90% RH) for 4 weeks and evaluated weekly for quality attributes. Organic fertilizers and UREA_LOW were the most effective treatments in reducing the changes in color, weight loss, titratable acidity (TA), pH, and total soluble solids (TSS) of fresh‐cut celery. Organic fertilizers enhanced the vitamin C content, total phenols, and antioxidant activity in celeries. As postharvest treatments, hydrocooling, plastic packaging, and blanching maintained chroma and hue values. Blanching had the greatest effect on the L* value. Hydrocooling increased celery's TA, TSS, and vitamin C content and reduced weight loss and pH during storage. Thus, celery quality was improved when grown under low or adequate N fertilization. Hydrocooling was an effective postharvest treatment for preserving fresh‐cut celery quality during storage.
Antioxidant and antimicrobial potential of water lily extracts and their effects on the quality of frozen Nile tilapia (Oreochromis niloticus) fillets
Authors: Dulal Md. Apon , Jahan Israt , Rasul Md. Golam , Islam Md. Rabiul , Khan Murshida , Shah A. K. M. Azad
Published: October 2022

This study was investigated to evaluate the antioxidant and antimicrobial potential of water lily extracts and their effects on the quality of Nile tilapia (Oreochromis niloticus) fillets during frozen storage (−18 ± 1°C). Antioxidant and antimicrobial activities of water lily extracts, and chemical, microbiological, and sensory qualities of fish fillets were assessed. Results showed that the highest total phenolic content (34.07 mg GAE/g) and total flavonoid content (32.67 mg QE/g extract) were found in the ethanolic extract and the lowest in water extract of water lily. The ethanolic extracts of water lily also exhibited the highest antioxidant capacities and antimicrobial activities than other hydroethanolic and water extracts. The water lily extracts‐treated fish fillets showed the highest potentiality in lowering the pH, total volatile basic nitrogen, and thiobarbituric acid reactive substances than the untreated fillets throughout the storage period. Moreover, ethanolic extracts of water lily exhibited comparatively higher efficacy in inhibiting bacterial growth in fish fillets than other extracts‐treated fillets. The ethanolic extracts‐treated fillets also showed better sensory attributes than hydroethanolic and control fillets. Therefore, ethanolic extract of water lily can be used as a natural preservative in enhancing the quality and prolonging the shelf life of Nile tilapia fillets during frozen storage.
The impact of price promotions on sales of unhealthy food and drink products in British retail stores
Authors: Watt Toby , Beckert Walter , Smith Richard , Cornelsen Laura
Published: October 2022

We study the health impact of food and beverage price promotion strategies—multi‐buy offers and price discounts, typically biased toward unhealthy product categories—in British consumer retail. We are the first to employ econometric models from the marketing literature to analyze the impact of price promotions with a focus on population health. Our dynamic, reduced form demand model incorporates endogenous inventory (stock piling), consumption rates imputed from repeat purchases and allows for unobserved household heterogeneity. We find that removing price discounts is more effective for reducing purchase volume compared to removing multi‐buy offers for 10 out of 12 food and drink groups, particularly those products for which price reduction is more common than multibuy. We find that price promotions induce consumption—and waste –through behavioral effects, associated with increased household inventory (stockpiling).
Deletion of adipocyte prohibitin 1 exacerbates high‐fat diet‐induced steatosis but not liver inflammation and fibrosis
Authors: Wang Xiaolin , Kim Seung‐Jin , Guan Yukun , Parker Richard , Rodrigues Robim M. , Feng Dechun , Lu Shelly C. , Gao Bin
Published: October 2022

Adipose tissue dysfunction is closely associated with the development and progression of nonalcoholic fatty liver disease (NAFLD). Recent studies have implied an important role of prohibitin‐1 (PHB1) in adipose tissue function. In the current study, we aimed to explore the function of adipocyte PHB1 in the development and progression of NAFLD. The PHB1 protein levels in adipose tissues were markedly decreased in mice fed a high‐fat diet (HFD) compared to those fed a chow diet. To explore the function of adipocyte PHB1 in the progression of NAFLD, mice with adipocyte‐specific (adipo) deletion of Phb1 (Phb1
adipo−/− mice) were generated. Notably, Phb1
adipo−/− mice did not develop obesity but displayed severe liver steatosis under HFD feeding. Compared to HFD‐fed wild‐type (WT) mice, HFD‐fed Phb1
adipo−/− mice displayed dramatically lower fat mass with significantly decreased levels of total adipose tissue inflammation, including macrophage and neutrophil number as well as the expression of inflammatory mediators. To our surprise, although liver steatosis in Phb1
adipo−/− mice was much more severe, liver inflammation and fibrosis were similar to WT mice after HFD feeding. RNA sequencing analyses revealed that the interferon pathway was markedly suppressed while the bone morphogenetic protein 2 pathway was significantly up‐regulated in the liver of HFD‐fed Phb1
adipo−/− mice compared with HFD‐fed WT mice. Conclusion: HFD‐fed Phb1
adipo−/− mice display a subtype of the lean NAFLD phenotype with severe hepatic steatosis despite low adipose mass. This subtype of the lean NAFLD phenotype has similar inflammation and fibrosis as obese NAFLD in HFD‐fed WT mice; this is partially due to reduced total adipose tissue inflammation and the hepatic interferon pathway.
Prevalence and risk factor of postoperative adhesions following repeated cesarean section: A prospective cohort study
Authors: Aboshama Rehab Abdelhamid , Taha Omima T. , Abdel Halim Hala Waheed , Elrehim Eman Ibrahim Abd , Kamal Shaimaa Hanafy Moustafa , ElSherbiny Ahmed Mohamed , Magdy Hagar Abdelgawad , Albayadi Eslam , Elsaid Rasha Ezzat , Abdelghany Amany Mohamed , Anan Mohamed A. , Abdelfattah Laila Ezzat
Published: October 2022

Objective

To evaluate the prevalence of intraperitoneal adhesions after repeated cesarean delivery and its associated personal and surgical risk factors.

Methods

This prospective cohort study was conducted at the delivery ward at Fayoum University Hospital from October 2020 to December 2021. Women were recruited according to predetermined inclusion and exclusion criteria. Eligible women were interviewed, and data were obtained for personal history, past surgical and obstetrical history, and data about the current delivery. Nair's scoring system was used to evaluate intraperitoneal adhesions. Postoperative data and complications were reported.

Results

Three hundred women were recruited. Moderate to severe adhesions occurred in 186 patients (62%). These patients had a significantly prolonged hospital stay and were delivered by expert surgeons (P < 0.001 and P = 0.008, respectively). The adhesion score correlated positively with patients' age (P < 0.001), parity (P < 0.001), interpregnancy interval (P = 0.033), duration of hospital admission either previously or in the current delivery (P = 0.001 and P < 0.001), time to ambulation (P < 0.001), time to intestinal movement (P < 0.001), operative time (P < 0.001), and surgeons' age and experience (both P = 0.015).

Conclusion

Adhesions led to increased maternal morbidity. Multiple contributing factors were significantly related to adhesions with multiple cesarean deliveries.
Does a Lingua Franca matter in bilateral international trade?
Authors: Su Li , Jung Hojin , Yang Mingzhuo
Published: October 2022

This article explores the impact of language proficiency on international trade by using panel data analysis. To do so, we construct a time‐variant test‐score‐based measure of common language. Controlling for the standard gravity model variables, we find strong empirical evidence that English proficiency promotes bilateral trade flows through facilitating direct communication. We confirm that this finding is robust even when we estimate its effects separately on goods and services trade flows at a disaggregated level. Furthermore, we show that institutional similarities between trading partners play a role that is similar to communication easiness in trade. Our study provides a policy implication for government support for attaining second language fluency.
Novel NRF2‐activated cancer treatments utilizing synthetic lethality
Authors: Baird Liam , Kensler Thomas W. , Yamamoto Masayuki
Published: October 2022

The KEAP1‐NRF2 pathway regulates the main inducible cellular response to oxidative and electrophilic stresses. Activating mutations in the KEAP1‐NRF2 pathway occur commonly in human cancer, where they contribute to the formation of aggressive tumours that are associated with a poor prognosis for patients. An important clinical feature of these tumours is their defiance to all current anti‐cancer treatment regimens, highlighting the need for the development of new therapeutic strategies to target NRF2‐activated cancers. In this review, we discuss the mechanisms through which acquired NRF2 hyperactivation can result in resistance of tumours to immune checkpoint inhibitor therapies in addition to classical chemotherapeutics, and propose with examples that using a synthetic lethal strategy mediated by NRF2‐target gene‐dependent bioactivation of prodrugs represents a promising strategy to specifically enhance toxicity to heretofore untreatable NRF2‐hyperactivated human tumours.
Sensitivity of coupled cluster electronic properties on the reference determinant: Can Kohn–Sham orbitals be more beneficial than Hartree–Fock orbitals?
Authors: Benedek Zsolt , Timár Paula , Szilvási Tibor , Barcza Gergely
Published: October 2022

Coupled cluster calculations are traditionally performed over Hartree–Fock reference orbitals (HF‐CC methodology). However, in the literature it has been repeatedly raised whether the use of a Kohn–Sham reference (KS‐CC methodology) might result in improved performance relative to HF‐CC. In the present study, we re‐examine the relation of HF‐CC and KS‐CC methods by comparing the results of widely applied truncated CC calculations (CCSD, CCSD(T), CCSDT) to the limit of full configuration interaction (FCI), which serves as an undebatable reference point of accuracy. Based on a series of CC calculations on diatoms and transition metal complexes, we demonstrate that no systematic improvement of coupled cluster electronic energies, densities and chemical reaction energies is expected when changing from HF to a KS reference. Nevertheless, fortuitous error cancellations might occasionally result in illusory improvement compared to HF‐CC. Altogether, the application of KS‐CC is not advantageous over HF‐CC, but it is also not unreasonable as the choice of reference has negligible influence on the results at sufficiently high CC levels. In addition, KS‐CC can be a particularly useful alternative if difficulties are encountered in HF or HF‐CC convergence. It is also notable that KS‐CC results are found to be practically independent of the chosen density functional, which implies that almost any KS‐CC method can be used in place of HF‐CC.
Ceftolozane/Tazobactam Probability of Target Attainment in Patients With Hospital‐Acquired or Ventilator‐Associated Bacterial Pneumonia
Authors: Gao Wei , Patel Yogesh T. , Zhang Zufei , Johnson Matthew G. , Fiedler‐Kelly Jill , Bruno Christopher J. , Rhee Elizabeth G. , Anda Carisa De , Feng Hwa‐Ping
Published: October 2022

Probability of target attainment (PTA) analyses were conducted to support the recommended ceftolozane/tazobactam dosing regimens, adjusted for renal function, in patients with hospital‐acquired/ventilator‐associated bacterial pneumonia (HABP/VABP). Previously published population pharmacokinetic models describing the disposition of ceftolozane and tazobactam in plasma and epithelial lining fluid (ELF) in patients with HABP/VABP were used to simulate ceftolozane and tazobactam concentration–time profiles in plasma and ELF over the course of 14 days. The simulations were conducted for patients with normal renal function and for patients receiving adjusted doses for mild, moderate, and severe renal impairment. PTA was calculated using established pharmacokinetic/pharmacodynamic targets for ceftolozane and tazobactam. Across renal function groups, plasma PTA was 100% for ceftolozane and >99% for tazobactam; ELF PTA was >99% for ceftolozane and >87% for tazobactam. These results provided support for the currently recommended ceftolozane/tazobactam dosing regimens for HABP/VABP, which were efficacious and well tolerated in the Ceftolozane–Tazobactam Versus Meropenem for Treatment of Nosocomial Pneumonia (ASPECT‐NP) trial.
Dentists of tomorrow 2022: An analysis of the results of the ADEA 2022 Survey of U.S. Dental School Seniors
Authors: Istrate Emilia C. , Cooper Betsy , West Karen P.
Published: October 2022

Purpose/Objectives

This study examines the journey of US dental schools’ predoctoral senior class of 2022, from the influences on and their motivations to pursue careers in dentistry, the aspects of their dental school experiences, plans upon graduation, and the investment in their careers.

Methods

The study is an analysis of the results of the American Dental Education Association (ADEA) Survey of Dental School Seniors, 2022 Graduating Class. Each year, ADEA surveys senior predoctoral students from the accredited US dental schools. Whenever feasible, the answers of the survey respondents from the 2022 class were compared with their 2017 counterparts and with the responses of 2022 predoctoral senior students of historically underrepresented race and ethnicity groups.

Results

The analysis revealed that 47% of the 2022 respondents decided to become a dentist before going to undergraduate college, more than the proportion of their 2017 colleagues (44%). When it comes to preparedness to practice dentistry, the responses indicated a high level of readiness to go into the profession. Nineteen percent of survey participants reported that the COVID‐19 pandemic affected their professional plans immediately after graduation. Between 2017 and 2022, the share of survey respondents who planned to join a private practice immediately after graduation increased from 48% to 53%. Almost a third of the 2022 respondents who planned to go into private practice immediately upon graduation intended to join a dental service organization. When accounting for inflation, the average education debt for students graduating with debt who responded to ADEA 2022 survey was 11% lower from what the 2017 respondents reported.

Conclusions

This study finds that some preferences changed from the 2017 cohort to the 2022 cohort toward deciding to go to dental school before college and joining a private practice upon graduation. Senior students responding to the ADEA survey in 2022 stated a high level of preparedness to practice dentistry. US dental schools pursued consistently their mission to educate, train, and graduate oral health professionals fully prepared to go into the profession.
Misdiagnosis of adult primary hemophagocytic lymphohistiocytosis as NK/T‐cell lymphoma: A case report
Authors: Kong Qi , Wang Jingshi , Zhang Yanlin , Hu Junxia , Yu Mingzhu , Wu Lin , Wang Zhao
Published: October 2022

We reported a case of a 19‐year‐old male patient with central nervous system symptoms as the main clinical manifestations, and multiple intracranial and abdominal occupying lesions visualized by imaging examinations, who was initially misdiagnosed as NK/T‐cell lymphoma but poorly responsive to the treatment. Finally, he was diagnosed as familial hemophagocytic lymphohistiocytosis type‐2 by genome sequencing, perforin test and pedigree study. The patient survived well after allogeneic hematopoietic stem cell transplantation. Central nervous system symptoms could be the main clinical manifestations in patients with primary hemophagocytic lymphohistiocytosis , whose early‐stage manifestations of blood system were usually atypical, easily leading to misdiagnosis. In clinical practice, primary hemophagocytic lymphohistiocytosis should be considered in patients with central nervous system symptoms and unknown causes. The combination of rapid immunological function test and genome sequencing contributes to the diagnosis of primary hemophagocytic lymphohistiocytosis.
Microvascular Dysfunction Associates With Outcomes in Hypertrophic Cardiomyopathy: Insights From the Intravoxel Incoherent MotionMRI
Authors: Xiang Xiaorui , Lin Xiaoqiang , Zhang Baoteng , Lin Chen , Lei Junqiang , Guo Shunlin , Zhao Shihua
Published: October 2022

Background

Although intravoxel incoherent motion (IVIM) MRI has emerged as an in vivo marker of tissue diffusion and perfusion, its prognostic value in patients with hypertrophic cardiomyopathy (HCM) remains unclear.

Purpose

To investigate whether IVIM‐MRI derived parameters are associated with outcomes in patients with HCM.

Study Type

Prospective cohort.

Subjects

A total of 112 patients (51.72 ± 17.13 years) with suspected or known HCM.

Field Strength/Sequence

Single‐shot echo planar IVIM imaging, balanced steady‐state free precession, and phase‐sensitive inversion‐recovery late gadolinium enhancement (LGE) sequences at 3 T.

Assessment

All patients were followed up of 29.3 ± 12.3 months for combined major adverse cardiac events (MACE) including cardiac death, aborted sudden death, heart transplantation, and rehospitalization for heart failure. The CVI42 imaging platform was used to assess morphological and functional MRI indices and to quantify LGE. The Body Diffusion Toolbox was used to derive pseudo diffusion (D*), water molecular diffusion (D) and perfusion fraction (f).

Statistical Tests

Univariable and stepwise multivariable Cox model analyses were used to investigate the association between variables and composite endpoints. Kaplan–Meier curves were constructed to assess event‐free survival, and the event rates were compared by the log‐rank test.

Results

A total of 19 patients reached endpoints. Patients with MACE showed a significantly impaired D* value, lower f value, and more extensive LGE than those without MACE (all,P < 0.05), while there was no significant difference in D value (P = 0.285). In the Cox regression models, D* value (hazard ratio [HR] 0.93; 95% CI: 0.88–0.98) and f value (HR 0.65; 95% CI: 0.45–0.92) were independent predictors for MACE. Moreover, in Kaplan–Meier survival analysis, the incidence of MACE was significantly higher in patients with decreased D* value and f value.

Conclusions

Impaired D* and f values derived from IVIM‐MRI are associated with adverse outcomes in patients with HCM.

Level of Evidence

2

Technical Efficacy Stage

2
The effect of surgical change to hip geometry on hip biomechanics after primary total hip arthroplasty
Authors: Bahl Jasvir S. , Arnold John B. , Saxby David J. , Taylor Mark , Solomon Lucian B. , Thewlis Dominic
Published: October 2022

The aim of this study was to determine the effect of surgical change to the acetabular offset and femoral offset on the abductor muscle and hip contact forces after primary total hip arthroplasty (THA) using computational methods. Thirty‐five patients undergoing primary THA were recruited. Patients underwent a computed tomography scan of their pelvis and hip, and underwent gait analysis pre‐ and 6‐months postoperatively. Surgically induced changes in acetabular and femoral offset were used to inform a musculoskeletal model to estimated abductor muscle and hip joint contact forces. Two experiments were performed: (1) influence of changes in hip geometry on hip biomechanics with preoperative kinematics; and (2) influence of changes in hip geometry on hip biomechanics with postoperative kinematics. Superior and medial placement of the hip centre of rotation during THA was most influential in reducing hip contact forces, predicting 63% of the variance (p < 0.001). When comparing the preoperative geometry and kinematics model, with postoperative geometry and kinematics, hip contact forces increased after surgery (0.68 BW, p = 0.001). Increasing the abductor lever arm reduced abductor muscle force by 28% (p < 0.001) and resultant hip contact force by 17% (0.6 BW, p = 0.003), with both preoperative and postoperative kinematics. Failure to increase abductor lever arm increased resultant hip contact force 11% (0.33 BW, p < 0.001). In conclusion, increasing the abductor lever arm provides a substantial biomechanical benefit to reduce hip abductor and resultant hip joint contact forces. The magnitude of this effect is equivalent to the average increase in hip contact force seen with improved gait from pre‐to post‐surgery.
Effect of implant length variations on stress shielding in proximal humeral replacement after tumor excision under torsion: Finite element study
Authors: Pareatumbee Pivatidevi , Zainul‐Abidin Suraya , Yew Andy , Chou Siaw M. , Howe Tet Sen , Koh Joyce S. B. , Tan Mann Hong
Published: October 2022

The proximal humerus is the most common site of occurrence of primary bone tumors in the upper limb. Endoprosthetic replacement is deemed as the preferred reconstructive option following primary resection of bone tumors. However, it has been also associated with complications such as stress shielding and aseptic loosening compromising prosthetic survival. Our objective was to conduct a finite element (FE) study to investigate the effect of varying endoprosthesis length on bone stresses as well as to quantify the extent of stress shielding across the bone length (BL) in a humerus‐prosthesis assembly for proximal humeral replacement after tumor excision thereby allowing us to identify the optimal implant length with best biomechanical performance. FE models of the intact humerus and humerus‐prosthesis assemblies were established where they were loaded at the elbow joint under torsion with the glenohumeral joint fixed to represent twisting. After dividing the bone into individual slices consisting of 5% BL, the maximum cortical and cancellous principal, von Mises and shear bone stresses were calculated. To measure the level of stress shielding, the percentage stress change from the intact state was evaluated across each slice. Similar stress patterns were observed between the intact state and shorter endoprosthesis compared to the longer endoprostheses. Our findings illustrated the possibility of stress shielding occurring under torsional forces with its effect increasing with implant lengthening. To conclude, we believe that using a shorter prosthesis may substantially diminish the risk of potential implant failure due to stress shielding.
Comparison of Geqingpi and Sihuaqingpi based on ultra‐high‐performance liquid chromatography‐tandem mass spectrometry combined with multivariate statistics, network pharmacology analysis, and molecular docking
Authors: Wang Yang , Cui Weiliang , Yang Chunguo , Wei Haifeng , Liu Qingzhi , Xiong Lewen , Li Huifen , Lin Yongqiang
Published: October 2022

Citri Reticulatae Pericarpium Viride is used in traditional Chinese medicine as Geqingpi and Sihuaqingpi varieties. We used the ultra‐high‐performance liquid chromatography‐quadrupole‐Exactive Orbitrap‐mass spectrometry method and high‐performance liquid chromatography‐triple quadrupole‐tandem mass spectrometry to analyze the chemical compounds in these varieties. Principal components analysis and orthogonal partial least squares discriminant analysis were used to analyze the quantitative results. Network pharmacology and molecular docking technology were used to forecast Citri Reticulatae Pericarpium Viride treatment mechanisms in irritable bowel syndrome. We identified 44 main compounds in Citri Reticulatae Pericarpium Viride. Compared to Sihuaqingpi, Geqingpi had higher narirutin, didymin, naringenin, and hesperetin, and lower hesperidin, isosinensetin, nobiletin, 3,5,6,7,8,3′,4′‐hexamethoxyflavone, tangeretin. Tangeretin, nobiletin, narirutin, didymin, and isosinensetin were the main compounds distinguishing Geqingpi from Sihuaqingpi. We found that the MAPK signaling pathway, which is closely related to irritable bowel syndrome, was an important target pathway. TP53, HRAS, MAPK1, AKT1, and EGFR were important targets in this pathway. Eriodictyol‐7‐O‐rutinoside, narirutin, limonin, and hesperidin showed a good binding ability to the five targets. Orientin, unique to Sihuaqingpi, bound well to TP53, MAPK1, AKT1, and EGFR, while rhoifolin bound well to TP53, HRAS, MAPK1, AKT1, and EGFR. Hesperetin, unique to Geqingpi, bound well to TP53, HRAS, and MAPK1, while naringenin bound well to HRAS. Hesperidin and didymin bound well to TP53, MAPK1, AKT1, and EGFR.
A liquid chromatography‐mass spectrometry untargeted urinary metabonomics combined with quantitative analysis of seven amino acids biomarkers on yaobitong capsule in the intervention of rheumatoid arthritis rats
Authors: Zhang Jing , Lu Qing , Xin Ling , Lou Yanwei , Xiao Wei , Wang Zhenzhong , Zhao Longshan , Xiong Zhili
Published: October 2022

Yaobitong capsule is a compound preparation of traditional Chinese medicine that has been widely applied in disease treatment. To insight into the therapeutic effects of the yaobitong capsule on rheumatoid arthritis and its mechanisms, a liquid chromatography‐mass spectrometry untargeted urine metabolomics method was established and validated, combined with the quantitative analysis of seven potential amino acid biomarkers in rat urine. The results showed that 35 potential biomarkers were found in untargeted metabonomics, which was related to amino acid metabolism, lipid metabolism, energy metabolism, and purine metabolism. Moreover, seven amino acid biomarkers, including proline, methionine, glutamic acid, histidine, lysine, cysteine, and glutamine, were further separated and quantified in multiple‐reaction monitoring with a positive ionization mode. Then the linearity, standard curves, accuracy, precision, limit of quantitation, recovery, stability, carryover, and matrix effect of the quantitative method were examined. Finally, the validated method was successfully applied to investigate the urine samples of the control group, adjuvant‐induced rheumatoid arthritis model group, yaobitong capsule‐treatment group, and positive control group in rats. The contents of seven amino acids in different groups showed significant differences. Consequently, our findings revealed that the yaobitong capsule exerted therapeutic effects on rheumatoid arthritis rats by maintaining amino acid homeostasis.
Nonlinear multidecadal trends in organic matter dynamics in Midwest reservoirs are a function of variable hydroclimate
Authors: Bhattacharya Ruchi , Jones John R. , Graham Jennifer L. , Obrecht Daniel V. , Thorpe Anthony P. , Harlan James D. , North Rebecca L.
Published: October 2022

Dissolved organic matter (DOM) and particulate organic matter (POM) can influence biogeochemical processes in aquatic systems. An understanding, however, of the source, composition, and processes driving inland reservoir organic matter (OM) cycling at a regional scale over the long term is currently unexplored. Here, we quantify decadal patterns (> 20 yr) of DOM quantity and composition and POM in 40 reservoirs in the midcontinent United States. We built 184 Random Forest models to identify how the relative influence of watershed characteristics and limnological parameters on OM dynamics may vary over time and in synchrony with hydroclimatic anomalies. The reservoir OM quantity and composition varied nonmonotonically through time and in contrast to lake browning observed in the northern hemisphere. Reservoir DOM composition switched from humic and aromatic during wet summers to aliphatic, potentially autochthonous DOM during particularly prolonged dry summers in the mid‐2000s. The shift in reservoir DOM quantity and composition could be attributed to the change in time‐varying control of watershed and limnological factors mediated by the hydroclimatic conditions. Watershed control (e.g., percent crops) was predominant during wet summers, while the effect of reservoir morphology (e.g., maximum depth) and water quality parameters (e.g., Secchi depth, chlorophyll a) were evident during dry summers. Thus, future predictions of drier conditions may promote “greening” with negative implications for reservoir water quality and treated drinking water. Considering the nonlinear nature of reservoir OM dynamics and its controls will help to better mitigate water quality issues in these constructed systems increasingly impacted by global changes.
Streaking artifact reduction for CBCT‐based synthetic CT generation in adaptive radiotherapy
Authors: Gao Liugang , Xie Kai , Sun Jiawei , Lin Tao , Sui Jianfeng , Yang Guanyu , Ni Xinye
Published: October 2022

Background

Cone‐beam computed tomography (CBCT) is widely used for daily image guidance in radiation therapy, enhancing the reproducibility of patient setup. However, its application in adaptive radiotherapy (ART) is limited by many imaging artifacts and inaccurate Hounsfield units (HUs). The correction of CBCT image is necessary and of great value for CBCT‐based ART.

Purpose

To explore the synthetic CT (sCT) generation from CBCT images of thorax and abdomen patients, which usually surfer from serious artifacts duo to organ state changes. In this study, a streaking artifact reduction network (SARN) is proposed to reduce artifacts and combine with cycleGAN to generate high‐quality sCT images from CBCT and achieve an accurate dose calculation.

Methods

The proposed SARN was trained in a self‐supervised manner. Artifact‐CT images were generated from planning CT by random deformation and projection replacement, and SARN was trained based on paired artifact—CT and CT images. The planning CT and CBCT images of 260 patients with cancer, including 120 thoracic and 140 abdominal CT scans, were used to train and evaluate neural networks. The CBCT images of another 12 patients in late treatment fractions, which contained large anatomy changes, were also tested by trained models. The trained models include commonly used U‐Net, cycleGAN, attention‐gated cycleGAN (cycAT), and cascade models combined SARN with cycleGAN or cycAT. The generated sCT images were compared in terms of image quality and dose calculation accuracy.

Results

The sCT images generated by SARN combined with cycleGAN and cycAT showed the best image quality, removed the most artifacts, and retained the normal anatomical structure. The SARN+cycleGAN performed best in streaking artifacts removal with the maximum percent integrity uniformity (PIUm) of 91.0% and minimum standard deviation (SD) of 35.4 HU for delineated artifact regions among all models. The mean absolute error (MAE) of CBCT images in the thorax and abdomen were 71.6 and 55.2 HU, respectively, using planning CT images after deformable registration as ground truth. Compared with CBCT, the thoracic and abdominal sCT images generated by each model had significantly improved image quality with smaller MAE (p< 0.05). The SARN+cycAT obtained the minimum MAEs of 42.5 HU in the thorax while SARN+cycleGAN got the minimum MAEs of 32.0 HU in the abdomen. The sCT generated by U‐Net had a remarkably lower anatomical structure accuracy compared with the other models. The thoracic and abdominal sCT images generated by SARN+cycleGAN showed optimal dose calculation accuracy with gamma passing rates (2 mm/2%) of 98.2% and 96.9%, respectively.

Conclusions

The proposed SARN can reduce serious streaking artifacts in CBCT images. The SARN combined with cycleGAN can generate high‐quality sCT images with fewer artifacts, high‐accuracy HU values, and accurate anatomical structures, thus providing reliable dose calculation in ART.
Typical value ranges and signal patterns in patients with neurogenic bladder: Quality control in urodynamics using an air‐charged catheter system
Authors: Deng Han , Liao Limin , Wu Juan , Li Xing , Pang Dongqing , Liu Qinggang , Wang Xuesheng , Li Xunhua , Liang Ya'nan , Zhou Zhonghan , Luo Runtian , He Panqi
Published: October 2022

Purpose

To establish typical value ranges (TVRs) of the air‐charged catheter (ACC) system, and analyze the typical signal patterns (TSPs) of cough under different bladder volumes for quality control of a urodynamic study using the ACC system.

Materials and Methods

The urodynamic traces of 1977 patients with neurogenic bladder (NB) were analyzed for intravesical pressure (pves), abdominal pressure (pabd), and detrusor pressure (pdet) in the cough test at our center from July 2017 to December 2021. The pdet cough signals were described and classified. The pdet cough signal patterns in different bladder volumes and postures were analyzed.

Results

The 50% range of the initial resting pves, pabd, and pdet in the supine and sitting positions were 7–15, 7–14, and 0–0 cmH2O, and 24–33, 24–33, and 0–0 cmH2O, respectively. The cough amplitudes for pves and pabd were similar in the 50% range, as follows: 10–27 and 8–25 cmH2O in the supine position, respectively; and 18–43 and 17–40 cmH2O in the sitting position, respectively. The cough amplitude of pves and pabd was not related to bladder volume (p > 0.05). The cough spikes of pdet were divided into three types: type I, in which pdet has a minimal change (<5 cmH2O); type II, a monophasic cough spike, in which could be a positive (IIa, ≥5 cmH2O) or negative spike (IIb, ≥5 cmH2O); and type III, a biphasic spike, in which could be a positive‐to‐negative biphasic (IIIa) or negative‐to‐positive spike (IIIb). Under different bladder volumes, the cough signals of pdet were all expressed as type I, II, or III, and the cough signals were unrelated to bladder volume (p > 0.05).

Conclusions

TVRs of the initial resting state in patients with NB were established to provide guidance for quantitative quality control of the ACC system. The TSPs of the pdet cough signal under different bladder volume and posture were described, which could be used for qualitative quality control of the ACC system.