bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnesium isoglycyrrhizinate prevents cadmium-induced activation of JNK and apoptotic hepatocyte death by reversing ROS-inactivated PP2A
Authors: Chen Xiaoling , Wang Xiaoxue , Yang Liu , Xu Hongjiang , Wu Yiqun , Wu Jialin , Chen Long , Xu Chong
Published: August 2021

Objectives

Cadmium (Cd) induces reactive oxygen species (ROS)-mediated hepatocyte apoptosis and consequential liver disorders. This study aimed to investigate the effect of magnesium isoglycyrrhizinate (MgIG) on Cd-induced hepatotoxicity.

Methods

L02 and AML-12 cells were used to study MgIG hepatoprotective effects. Cd-evoked apoptosis, ROS and protein phosphatase 2A (PP2A)/c-Jun N-terminal kinase (JNK) cascade disruption were analysed by cell viability assay, 6-diamidino-2-phenylindole (DAPI) and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, ROS imaging and Western blotting. Pharmacological and genetic approaches were used to explore the mechanisms.

Key findings

We show that MgIG attenuated Cd-evoked hepatocyte apoptosis by blocking JNK pathway. Pre-treatment with SP600125 or ectopic expression of dominant-negative c-Jun enhanced MgIG’s anti-apoptotic effects. Further investigation found that MgIG rescued Cd-inactivated PP2A. Inhibition of PP2A activity by okadaic acid attenuated the MgIG’s inhibition of the Cd-stimulated JNK pathway and apoptosis; in contrast, overexpression of PP2A strengthened the MgIG effects. In addition, MgIG blocked Cd-induced ROS generation. Eliminating ROS by N-acetyl-l-cysteine abrogated Cd-induced PP2A-JNK pathway disruption and concurrently reinforced MgIG-conferred protective effects, which could be further slightly strengthened by PP2A overexpression.

Conclusions

Our findings indicate that MgIG is a promising hepatoprotective agent for the prevention of Cd-induced hepatic injury by mitigating ROS-inactivated PP2A, thus preventing JNK activation and hepatocyte apoptosis.
Radio spectral properties of star-forming galaxies in the MIGHTEE-COSMOS field and their impact on the far-infrared-radio correlation
Authors: An Fangxia , Vaccari M , Smail Ian , Jarvis M J , Whittam I H , Hale C L , Jin S , Collier J D , Daddi E , Delhaize J , Frank B , Murphy E J , Prescott M , Sekhar S , Taylor A R , Ao Y , Knowles K , Marchetti L , Randriamampandry S M , Randriamanakoto Z
Published: August 2021

We study the radio spectral properties of 2094 star-forming galaxies (SFGs) by combining our early science data from the MeerKAT International GHz Tiered Extragalactic Exploration (MIGHTEE) survey with VLA, GMRT radio data, and rich ancillary data in the COSMOS field. These SFGs are selected at VLA 3 GHz, and their flux densities from MeerKAT 1.3 GHz and GMRT 325 MHz imaging data are extracted using the ‘superdeblending’ technique. The median radio spectral index is $\alpha _{\rm 1.3\, GHz}^{\rm 3\, GHz}=-0.80\pm 0.01$ without significant variation across the rest-frame frequencies ∼1.3–10 GHz, indicating radio spectra dominated by synchrotron radiation. On average, the radio spectrum at observer-frame 1.3–3 GHz slightly steepens with increasing stellar mass with a linear fitted slope of β = −0.08 ± 0.01, which could be explained by age-related synchrotron losses. Due to the sensitivity of GMRT 325 MHz data, we apply a further flux density cut at 3 GHz ($S_{\rm 3\, GHz}\ge 50\, \mu$Jy) and obtain a sample of 166 SFGs with measured flux densities at 325 MHz, 1.3 GHz, and 3 GHz. On average, the radio spectrum of SFGs flattens at low frequency with the median spectral indices of $\alpha ^{\rm 1.3\, GHz}_{\rm 325\, MHz}=-0.59^{+0.02}_{-0.03}$ and $\alpha ^{\rm 3.0\, GHz}_{\rm 1.3\, GHz}=-0.74^{+0.01}_{-0.02}$. At low frequency, our stacking analyses show that the radio spectrum also slightly steepens with increasing stellar mass. By comparing the far-infrared-radio correlations of SFGs based on different radio spectral indices, we find that adopting $\alpha _{\rm 1.3\, GHz}^{\rm 3\, GHz}$ for k-corrections will significantly underestimate the infrared-to-radio luminosity ratio (qIR) for >17 per cent of the SFGs with measured flux density at the three radio frequencies in our sample, because their radio spectra are significantly flatter at low frequency (0.33–1.3 GHz).
Morphine Equivalent Total Dosage as Predictor of Adverse Outcomes in Opioid Prescribing
Authors: Bonifonte Anthony , Merchant Rahim , Deppen Krisanna
Published: August 2021

Objective

The objective of this work was to develop a risk prediction model for opioid overdose and opioid use disorder for patients at first opioid prescription and compare the predictive accuracy of morphine equivalent total dosage with the predictive accuracy of daily dosage .

Design

Records from patients 18–79 years of age with opioid prescriptions between January 1, 2016, and June 30, 2019, no prior history of adverse outcomes, and no malignant cancer diagnoses were collected from the electronic health record system of a medium-sized central Ohio health care system (n = 219,276). A Cox proportional-hazards model was developed to predict the adverse outcomes of opioid overdose and opioid use disorder from patient sociodemographic, pharmacological, and clinical diagnosis factors.

Results

During the study time frame, 573 patients experienced overdoses, and 2,571 patients were diagnosed with opioid use disorder. Morphine equivalent total dosage of opioid prescriptions was identified as a stronger predictor of adverse outcomes (C = 0.797) than morphine equivalent daily dosage (C = 0.792), with the best predictions coming from a model that includes both predictors (C = 0.803). In the model with both daily and total dosage predictors, patients receiving a high total / low daily dosage experienced a higher risk (hazard ratio [HR] = 2.17) than those receiving a low total / high daily dosage (HR = 2.02). Those receiving a high total / high daily dosage experienced the greatest risk of all (HR = 3.09).

Conclusions

These findings demonstrate the value of including morphine equivalent total dosage as a predictor of adverse opioid outcomes and suggest that total dosage may be more strongly correlated with increased risk than daily dosage.
A Paratextual Battle: Mottos, Meaning and Conflict in Printed Journals 1709–1712
Authors: Readioff Corrina
Published: August 2021

Within studies of the influence upon eighteenth-century print culture of the Tatler (1709–1711) and the Spectator (1711–1712, 1714), little attention has been given to Addison and Steele’s innovative incorporation of a prefatory Latin or Greek quotation at the head of each issue. A unique feature at the time of the Tatler’s first publication, the initially unchanging motto quickly became a focus for attention, imitation and literary competition. When the rival journal the Female Tatler (1709–1710) appeared with similar paratextual adornment, the ensuing contest sparked a rapid intensification of the motto’s significance and function. This catalysed the development of issue-specific mottos, a technique that outlasted the Tatler print war to become involved in further political print contests until its ultimate adoption as a mark of genteel intellectualism in the Spectator. This article will examine the initial motivations for including a prefatory motto, exploring the unfolding conflict with the Female Tatler together with the way in which paratextual quotations were weaponized in this short, sharp rivalry. Further paratextual battles between the Examiner (1710–1711), Whig Examiner (1710) and Medley (1710–1711) will then be investigated, together with the Spectator’s use of the motto as a literary weapon to consolidate educational elitism in print culture.
Asset Pricing with Fading Memory
Authors: Nagel Stefan , Xu Zhengyang
Published: August 2021

Building on evidence that lifetime experiences shape individuals’ macroeconomic expectations, we study asset prices in an economy in which a representative agent learns with fading memory about unconditional mean endowment growth. With IID fundamentals, constant risk aversion, and memory decay calibrated to microdata, the model generates a high and strongly countercyclical objective equity premium, while the subjective equity premium is virtually constant. Consistent with this theory, experienced payout growth (a weighted average of past growth rates) is negatively related to future stock market excess returns and subjective expectations errors in surveys, and positively to analysts’ forecasts of long-run earnings growth.
Immunoglobulin G4–related disease and idiopathic multicentric Castleman’s disease: confusable immune-mediated disorders
Authors: Sasaki Takanori , Akiyama Mitsuhiro , Kaneko Yuko , Takeuchi Tsutomu
Published: August 2021

IgG4-related disease (IgG4-RD) and idiopathic multicentric Castleman’s disease (iMCD) are both rare systemic immune-mediated disorders. However, the pathogenesis differs markedly between the two diseases and differing therapeutic strategies are adopted: IgG4-RD is treated using a moderate dose of glucocorticoids or rituximab, while iMCD therapy involves an IL-6-targeted approach. Nonetheless, some clinical features of IgG4-RD and iMCD overlap, so differential diagnosis is sometimes difficult, even though the classification and diagnostic criteria of the diseases require careful exclusion of the other. The key findings in IgG4-RD are high IgG4:IgG ratio, allergic features and germinal centre expansion involving T follicular helper cells, while iMCD involves polyclonal antibody production (high IgA and IgM levels), sheet-like mature plasma cell proliferation and inflammatory features driven by IL-6. The distribution of organ involvement also provides important clues in both diseases. Particular attention should be given to differential diagnosis using combined clinical and/or pathological findings, because single features cannot distinguish IgG4-RD from iMCD. In the present review, we discuss the similarities and differences between IgG4-RD and iMCD, as well as how to distinguish the two diseases.
Macroevolutionary ecomorphology of the Carnivora skull: adaptations and constraints in the extant species
Authors: Meloro Carlo , Tamagnini Davide
Published: August 2021

The mammalian order Carnivora is characterized by a broad taxonomic and ecological diversity. By using a large sample of extant species, we tested the impact of ecological factors on carnivoran skull (cranium and mandible) morphology, taking advantage of a combined geometric morphometrics and comparative method approach. We implemented several evolutionary models to account for different tempo and mode of evolution in size and shape data. These models validated the association between skull morphology and diet at the interspecific scale. The functional distinction between pinniped (aquatic) and fissiped (mostly terrestrial) taxa was found valid only in mandible shape and cranial size. High levels of morphological disparity and evolutionary rates were identified in specialized dietary groups, and positive association between rates and disparity was found for skull size. Cranium and mandible showed consistent patterns of covariation that reflect constrained functional processes, which stabilize the ecomorphological evolution of Carnivora. Aquatic adaptations allowed carnivorans to invade and persist within novel regions of the mandibular morphospace. This ecological shift did not increase morphological disparity but occurred at a faster rate than in terrestrial species. Those species exhibit a stronger level of cranio-mandibular covariation due to constraints imposed by more demanding masticatory adaptations.
A Comparison of Paracervical Block Volumes Before Osmotic Dilator Placement
Authors: Shaw Kate A. , Lerma Klaira , Hughes Tayler , Hastings Charlotte , Fok Wing Kay , Blumenthal Paul D.
Published: August 2021

OBJECTIVE:

To evaluate whether a 12-mL paracervical block is noninferior to a 20-mL block in reducing pain with osmotic dilator insertion.

METHODS:

In this single-blinded noninferiority trial, we randomized individuals undergoing insertion of osmotic dilators before second-trimester abortion to receive either a 12-mL or 20-mL 1% lidocaine paracervical block. The primary outcome was pain immediately after insertion of osmotic dilators. Prespecified secondary outcomes included pain with paracervical block administration, overall pain, and side effects, with 88 participants being required for a noninferiority margin of 15 mm on a 100-mm visual analog scale assuming an SD of 28. We analyzed data using Wilcoxon rank sum, χ2, and t tests and performed analysis of variance to account for repeated measures. Secondary analysis included multivariable regression to explore potential confounders.

RESULTS:

From January 2018 to October 2020, of 232 eligible individuals, 174 were approached and 96 randomized (48 participants to each group); 91 were available for analysis (45: 12 mL, 46: 20 mL). Group demographics were similar, with a mean gestation of 21 weeks and four osmotic dilators placed. The 12-mL paracervical block was noninferior to the 20-mL paracervical block for pain with osmotic dilator insertion with a difference in means of −1.36 (95% CI −12.56 to 9.85) favoring 12 mL. Median pain scores after dilator placement were 47 mm (interquartile range 22–68) and 50 mm (interquartile range 27–67) in 12-mL compared with 20-mL paracervical block, respectively (P=.81). No difference was seen in median pain at baseline, with paracervical block administration, postprocedure or with overall pain or experience. At least one lidocaine-related side effect occurred in 4% of participants in the 12-mL group compared with 13% for those receiving 20 mL (P=.15), with metallic taste, ringing in ears, and lightheadedness being most common.

CONCLUSION:

A 12-mL paracervical block is noninferior to a 20-mL block for pain reduction with osmotic dilator insertion.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT03356145.
Abortion Access for Incarcerated People
Authors: Sufrin Carolyn , Jones Rachel K. , Beal Lauren , Mosher William D. , Bell Suzanne
Published: August 2021

OBJECTIVE:

To understand abortion incidence among incarcerated people and the relation to prison and jail pregnancy policies.

METHODS:

We collected abortion numbers and policy data from convenience sample of 22 state prison systems, all Federal Bureau of Prisons sites, and six county jails that voluntarily reported monthly, aggregate pregnancy outcomes for 12 months in 2016–2017. Sites also completed a baseline survey of institution characteristics and pregnancy policies, including abortion. We reported facility policies and abortion incidence according to state-level abortion characteristics.

RESULTS:

Only half of state prisons in the study allowed abortion in both the first and second trimesters, and 14% did not allow abortion at all. Of the 19 state prisons permitting abortion, two thirds required the incarcerated woman to pay. Four jails of the six study jails (67%) allowed abortions in the first and second trimesters, and 25% of those required the incarcerated woman to pay for the procedure. The three prisons and two jails that did not allow abortions were in states considered hostile to abortion access. In the state and federal prisons studied, 11 of the 816 pregnancies (1.3%) that ended during the study time period were abortions. Of the 224 pregnancies that ended at study jails, 33 were abortions (15%), with more than half of those (55%) occurring in the first trimester. The abortion ratio (proportion of pregnancies ending in abortion) was 1.4% for prisons and 18% for jails.

CONCLUSION:

Although some incarcerated individuals have abortions, many prisons and jails have restrictive policies surrounding abortion, either through self-payment requirements or explicit prohibition. Findings from this study should prompt further inquiry into abortion incidence in these settings and address interventions to ensure incarcerated people, in accordance with legal requirements and health equity, have access to abortion.
Contraceptive Provision and Quality Care Measures for Insured Individuals in Massachusetts Who Are Deaf or Hard of Hearing
Authors: Wu Justine P. , Zhang Jianying , McKee Michael , Akobirshoev Ilhom , McKee Kimberly S. , Mitra Monika
Published: August 2021

OBJECTIVE:

To evaluate contraceptive provision and contraceptive care quality measures for individuals who are deaf or hard of hearing and compare these outcomes to those individuals who are not.

METHODS:

We conducted a claims analysis with data from the 2014 Massachusetts All-Payer Claims Database. Among premenopausal enrollees aged 15–44, we determined provision of any contraception (yes or no) and provision by contraception type: prescription contraception (pills, patch, ring, injectables, or diaphragm), long-acting reversible contraceptive (LARC) devices, and permanent contraception (tubal sterilization). We compared these outcomes by deaf or hard-of-hearing status (yes or no). The odds of contraceptive provision were calculated with regression models adjusted for age, Medicaid insurance, a preventive health visit, and deaf or hard-of-hearing status. We calculated contraceptive care quality measures, per the U.S. Office of Population Health, as the percentage of enrollees who used: 1) LARC methods or 2) most effective or moderately effective methods (tubal sterilization, pills, patch, ring, injectables, or diaphragm).

RESULTS:

We identified 1,171,838 enrollees at risk for pregnancy; 13,400 (1.1%) were deaf or hard of hearing. Among individuals who were deaf or hard of hearing, 31.4% were provided contraception (23.5% prescription contraception, 5.4% LARC, 0.7% tubal sterilization). Individuals who were deaf or hard of hearing were less likely to receive prescription contraception (adjusted odds ratio 0.92, 95% CI 0.88–0.96) than individuals who were not deaf or hard of hearing. The percentage of individuals who were deaf or hard of hearing who received most effective or moderately effective methods was less than that for individuals who were not (24.2% vs 26.3%, P<.001). There were no differences in provision of LARC or permanent contraception by deaf and hard-of-hearing status.

CONCLUSION:

Individuals who were deaf or hard of hearing were less likely to receive prescription contraception than individuals who were not; factors underlying this pattern need to be examined. Provision of LARC or permanent contraception did not differ by deaf or hard-of-hearing status. These findings should be monitored and compared with data from states with different requirements for contraceptive coverage.
A Multivariable Predictive Model for Success of External Cephalic Version
Authors: Dahl Carly M. , Zhang Yue , Ong Janice X. , Yeh Chen , Son Moeun , Miller Emily S. , Roy Archana , Grobman William A.
Published: August 2021

OBJECTIVE:

To create a prediction model for external cephalic version (ECV) success using objective patient characteristics.

METHODS:

This retrospective study included pregnant individuals of at least 18 years of age with a nonanomalous, singleton gestation who underwent an ECV attempt between 2006 and 2016 at a single quaternary care hospital. Variables assessed included maternal age, height, weight, body mass index (BMI), parity, fetal sex, gestational age, estimated fetal weight, type of fetal malpresentation, placental location, and amniotic fluid volume. Univariable and multivariable logistic regression models were used to determine the association of patient characteristics with ECV success. Estimated odds ratios and corresponding 95% CIs were calculated for each variable, and backward elimination and bootstrapping were used to find a parsimonious model for ECV success with the highest discriminatory capacity (as determined by the area under the receiver operating characteristic curve [AUC]). This model was evaluated with a calibration curve across deciles of success.

RESULTS:

A total of 1,138 individuals underwent an ECV attempt and were included in this analysis. The overall ECV success frequency was 40.6%. Factors significantly associated with ECV success were maternal age, parity, placental location, estimated fetal weight, and type of fetal malpresentation. A final model with BMI, parity, placental location, and type of fetal malpresentation had the highest AUC (0.667 [95% CI 0.634–0.701]), resulted in good calibration, and is represented by the following equation: 1/[1+e-x] where x=1.1726–0.0314 (BMI)−0.9299 (nulliparity)+1.0218 (transverse or oblique presentation at ECV)−0.5113 (anterior placenta). An interactive version of this equation was created and can be accessed at www.ecvcalculator.com.

CONCLUSION:

A prediction model that estimates the probability of ECV success was created and internally validated. This model incorporates easily obtainable and objective patient factors known before ECV and may be used in decision making and patient counseling about ECV.
Staged Chest Wall Reconstruction for Radiation-induced Costochondritis
Authors: Kim Byeong Seok , Kim Hong Il , Kim Jong In , Park Jin Hyung , Yi Hyung Suk , Kim Yoon Soo , Kim Hyo Young
Published: August 2021

Costochondritis after breast reconstruction and radiation therapy is rarely reported. Moreover, it is difficult to diagnose using computed tomography and magnetic resonance imaging; as such, wound debridement and reconstruction must be performed in several stages. A 51-year-old woman was diagnosed with invasive cancer of the right breast, and she underwent nipple sparing mastectomy and direct-to-implant breast reconstruction in November 2007. Thirteen years later, in September 2020, she experienced pain and swelling on her right breast. Incisional drainage and implant removal were performed in another clinic; however, the infection was not controlled. An implant-induced infection was suspected, and debridement was performed to a level where fresh tissue appeared in the upper layer of the intercostal muscle. Antibiotics and open dressing were used for 10 days; however, yellowish debris was noted, and third to fifth ribs and costal cartilages turned dark brown. Radiation-induced costochondritis was diagnosed based on clinical findings from the intraoperative field, wound course, and cartilage biopsy. Radical chest wall resection and reconstruction was performed using Teflon (Dupont/Chemours, Wilmington, Del.) and latissimus dorsi musculocutaneous flap. The patient was discharged 2 weeks after surgery without any complications. Costochondritis should be clinically diagnosed while performing the first debridement in staged operation. Radical chest wall resection is essential with chest wall reconstruction using Teflon and a latissimus dorsi musculocutaneous flap.
Lower Extremity Salvage in the Setting of Bullous Pemphigoid Exacerbation: A Case Report
Authors: Pollock Samara E. , Rice Shauna M. , Ferree Sarah D. , Friedstat Jonathan , Eberlin Kyle , Kourosh Arianne S
Published: August 2021

Bullous pemphigoid is an autoimmune blistering disease where patients suffer from painful bullae, often covering large portions of the skin and requiring management with immune-suppression. Our case report of recurring bullous pemphigoid illustrates the importance of considering immunosuppressive perioperative management in patients with a history of autoimmune blistering even when the disease has been quiescent for some time. With multidisciplinary care and immune suppressive therapies in the perioperative period, a free flap complicated by recurrent bullous pemphigoid can be salvaged.
Management of Large Pediatric Wound Defects Using a Continuous External Tissue Expander
Authors: Choi Youna K. , Mehta Sagar T. , Luo Jessica , Siddiqi Faizi , Gociman Barbu
Published: August 2021

Both internal and external tissue expanders take advantage of the innate adaptive mechanisms the skin exerts in response to mechanical tension, known as the stress-relaxation phenomenon. Internal tissue expander use is time-consuming and can be complicated by infection and extrusion. In this case series, continuous external tissue expanders used to manage large pediatric wounds were assessed. Fourteen patients (ages: 4 days to 17 years) with large wounds underwent continuous external tissue expansion intraoperatively. The success of wound closure was assessed. In addition, the size of the patient’s wounds, duration of device application, and postoperative complications were evaluated. The continuous external tissue expander was applied to wound sizes ranging from 14.7 to 560 cm2 for 5 to 10 days until the wound was amenable for direct closure. In 11 of the 14 patients, delayed primary closure was achieved. The device significantly reduced the wound sizes of the remaining three cases (average 80% size reduction). There was no incidence of wound dehiscence or infection. This case series demonstrates the benefit of the continuous external tissue expansion in managing pediatric wounds that would not otherwise be amenable to primary closure. The method allows for timely closure with limited risk of infection or extrusion, and should be in the armamentarium of reconstructive plastic surgeons.
Short- to Medium-term Outcome of Prepectoral versus Subpectoral Direct-to-implant Reconstruction using Acellular Dermal Matrix
Authors: Mathew John
Published: August 2021

Background:

Subpectoral implant reconstruction (SIR) is associated with animation deformity and increased postoperative pain. The aim of our study was to compare the short- to medium-term outcome of prepectoral implant reconstruction (PIR) and SIR with acellular dermal matrix.

Methods:

A review of prospectively collected data of patients who underwent PIR and SIR using biological mesh by a single surgeon between Nov 2016 and Nov 2020 was done. Presentation, smoking history, BMI, bra size, radiology size, pathology data, mastectomy weight, implant volume, radiation treatment, and outcomes were analyzed. For intergroup comparisons, the data were analyzed using Pearson chi-square test and the Student t-test. P values of less than 0.05 were considered statistically significant.

Results:

Eighty-two patients had 109 implant reconstructions (85 PIR and 24 SIR). Median follow-up was 27 months (4–53). Twenty-five of PIR and six of SIR were risk reduction surgeries. Two groups were comparable except for significantly higher percentage of node positive (13/18, 72% versus 20/60, 33%; P = 0.003), Her 2-positive disease (7/18, 39% versus 9/60, 15%; P = 0.027), and radiotherapy (15/24, 63% versus 21/85, 25%; P = 0.001) in SIR. There was no statistically significant difference between the two groups with regard to hematoma, wound infection, red reaction, seroma needing aspiration, wound necrosis, and implant loss. Significantly more patients in the prepectoral group had rippling needing fat grafting (n = 13, 15% versus 0; P = 0.041) and significantly more patients in the subpectoral group had fat grafting for contour deformity (n = 6, 25% versus n = 6, 7%; P = 0.025).

Conclusion:

PIR is comparable to conventional SIR with regard to most of the complications.
What Should Be Done to Re-evaluate Cessation of Nucleos(t)ide Analog Therapy for Chronic Hepatitis B Infection?
Authors: Cheng Yongqian , Ji Yingjie , Duan Huijuan , Li Yuanyuan , Lau George , Wang Fu-Sheng
Published: August 2021

Anti-viral therapy with nucleos(t)ide analogs (NUCs) for chronic hepatitis B (CHB) is generally considered to be a long-term treatment. Relevant guidelines issued by Asian Pacific Association for the Study of the Liver, European Association for the Study of the Liver, and American Association for the Study of Liver Diseases have recently proposed requirements and standards for cessation of NUCs, but it remains unclear which proportion of CHB patients on long-term or prolonged treatment of NUCs will relapse after NUCs cessation. Recently, paradoxical increase in loss of hepatitis B surface antigen (HBsAg) with or without the development of anti-hepatitis B surface antibody has been observed in NUCs’ treated CHB patients with cessation of therapy. Hence, it is of great clinical relevance to identify CHB who might have been over-treated with NUCs and might even benefit HBsAg loss or seroconversion with cessation of therapy. To address these issues, our review comprehensively analyzed the data from recent clinical trials in which the antiviral efficacy in the long-term or prolonged treatment of NUCs and/or interferon-α for CHB patients were evaluated. Furthermore, the relevant problems and deficiencies existing in the study design of previous clinical studies were also described. To solve the unmet issues in the field, a prospective study with a large-enough sample size would be required to understand the related virologic and immunological markers that can accurately predict the outcome and prognosis of the CHB patients who stop the NUCs treatment. With the rapid advancement of antiviral drug development for CHB patients, the future ideal regimens should include multiple targets for antiviral drug therapy combined with efficient immune-modulatory therapy, which will help more CHB patients to obtain functional cure with NUCs cessation.
Diagnosis and Treatment Guidelines for Mesenchymal Stem Cell Therapy for Coronavirus Disease 2019 (Beijing, 2021)
Authors: Xu Ruonan , Shi Lei , Xie Wei-Fen , Xu Zhe , Meng Fan-Ping , Fu Jun-Liang , Yuan Xin , Huang Lei , Shi Ming , Li Yonggang , Li Yuanyuan , Yao Chen , Zhang Yu , Liu Zhongmin , Gao Chenyan , Wu Zhaohui , Meng Shufang , Han Weidong , Xiang Charlie , Wang Gui-Qiang , Li Taisheng , Wang Xiaoying , Sun Yunxia , Wu Zunyou , Zhang Wenhong , Zhao Chunhua , Hu Yu , Cheng Tao , Wei Yuquan , Zhou Qi , Wang Fu-Sheng
Published: August 2021

The coronavirus disease 2019 (COVID-19) can be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and has led to millions of deaths among more than 100 million infected people around the world according to the declaration from World Health Organization. Dysregulated immune response of both the innate and adaptive immune systems is subsistent on COVID-19 patients, of which the degree are associated with disease severity, lung damage and long term functional disability. Current treatment options have included antiretroviral drugs, anti-inflammatory factors, antibodies, immune checkpoint inhibitors, and convalescent plasma therapy. More recently, mesenchymal stem cell (MSC) therapy has been explored for the management and control of COVID-19, particularly with the aim of preventing or at least mitigating respiratory co-morbidities. Though the safety and efficacy of stem cell therapy have been validated in multiple phase I–III clinical trials, to date, no standardized stem cell preparation, administration dosage or interval, product QA/QC testing, storage, transportation, or disposal protocols have been established. The present paper proposes a systematic methodology that addresses all the foregoing process steps and evaluation criteria for the efficacious and safe administration of MSCs in the treatment of patients infected with COVID-19.
Effects of auditory or visual stimuli on gait in Parkinsonic patients: a systematic review
Authors: Trindade Marta F.D. , Viana Rui A.
Published: August 2021

Background:

External stimuli can improve gait performance in Parkinsons Disease (PD): auditory stimuli can increase velocity and visual stimuli may act at step length.

Objective:

To systematize the scientific evidence about the effects of auditory or visual stimuli on gait in patients with PD.

Methods:

From January 2016 to December 2018, a systematic literature research was conducted in the PubMed/Medline and Web of Science databases. Study designs considered were randomized controlled trials (RCTs) and observational studies, which evaluated the effects of auditory or visual stimuli on gait in PD. The methodological quality was assessed by the Critical Appraisal Skills Program.

Results:

Five articles were included with 232 participants and a methodological rank of mean of 10.3 on the cohort studies (n = 3), 8 on the case control studies (n = 1), and 6 on the RCTs (n = 1). Although 3 evaluated the effects of auditory stimuli on gait in PD, 2 analyzed those of visual stimuli. Based on these, it was verified a significant improvement of diverse gait parameters.

Conclusion:

The application of auditory or visual stimuli have beneficial effects on gait parameters. Further investigation is required.
Expression of Angiotensin II Receptor 2 in Microcystic Lymphatic Malformation
Authors: Siljee Sam Duro , Gower Alexandra , Brasch Helen Dian , Patel Josie , Bockett Nicholas , Itinteang Tinte , Tan Swee Thong
Published: August 2021

Objectives:

To investigate the presence of components of the renin-angiotensin system (RAS) on the embryonic stem cell (ESC)–like population in microcystic lymphatic malformation (mLM).

Methods:

mLM tissue samples from 18 patients underwent immunohistochemical staining for RAS components including angiotensinogen, renin, prorenin receptor (PRR), angiotensin-converting enzyme (ACE), ACE2, and angiotensin II receptor 2 (AT2R). Snap-frozen mLM tissues from 6 of the patients were used to confirm protein expression by western blotting for angiotensinogen, PRR, ACE, ACE2, and AT2R. Reverse transcription quantitative polymerase chain reaction was used to detect transcript expression of angiotensinogen, renin, PRR, ACE, ACE2, AT1R, and AT2R in 5 of the mLM tissue samples.

Results:

Immunohistochemical staining demonstrated expression of AT2R in all, and PRR in 1, while angiotensinogen, renin, ACE, and ACE2 were not observed in any of the 18 mLM samples. Western blotting showed expression of angiotensinogen, PRR, and ACE, but not ACE2 or AT2R in all 6 mLM tissue samples. Reverse transcription quantitative polymerase chain reaction demonstrated transcript expression of angiotensinogen, PRR, ACE, and ACE2 in all, AT1R in 4, AT2R in 2, and renin in 1 of the 5 mLM tissue samples. Immunofluorescence dual-staining in 2 mLM tissue samples demonstrated expression of AT2R on the OCT4+ cells.

Conclusion:

This study shows expression of angiotensinogen, PRR, ACE. ACE2, AT1R, and AT2R transcripts and AT2R protein, in mLM tissue samples, with AT2R localizing to the OCT4+ ESC-like population. This suggests the ESC-like population may be a novel therapeutic target by modulation of the RAS.
Association between fibromyalgia and cataract
Authors: Hu Wei-Syun , Lin Cheng-Li , Chen Tung-Sheng
Published: August 2021

This study was set to investigate whether fibromyalgia increased cataract risk.

Fibromyalgia patients were the case group and controls were people who never had a history of fibromyalgia. We estimated the hazard ratio of cataract by Cox proportional-hazards model. The adjusted hazard ratios were obtained by controlling variables of age, sex, and comorbidities. Stratification analysis was also performed to ensure the association of fibromyalgia and cataract.

We included 6949 participants in each groups. The incidence rate of cataract in patients with fibromyalgia (108.9 per 1000 person-years) was higher than that of control group (58.9 per 1000 person-years). The risk of cataract in fibromyalgia patients was 2.48 (95% confidence interval = 2.34–2.63) times higher than subjects without fibromyalgia.

Fibromyalgia is associated with higher risk of cataract.
A novel RNA binding protein-associated prognostic model to predict overall survival in hepatocellular carcinoma patients
Authors: Liu Ye , Liu Xiaohong , Gu Yang , Lu Haofeng
Published: August 2021

Hepatocellular carcinoma (HCC) is 1 of the deadliest malignancies worldwide. Despite significant advances in diagnosis and treatment, the mortality rate from HCC persists at a substantial level. Construction of a prognostic model that can reliably predict HCC patients’ overall survival is urgently needed.

Two RNA-seq dataset (the Cancer Genome Atlas and International Cancer Genome Consortium) and 1 microarray dataset (GSE14520) were included in our study. RNA-binding proteins (RBPs) in HCC patients was examined by differentially expressed genes analysis, functional enrichment analysis and protein-protein interaction network analysis. Subsequently, the Cancer Genome Atlas dataset was randomly divided into training and testing cohort with a prognostic model developed in the training cohort. In order to evaluate the prognostic value of the model, a comprehensive survival assessment was conducted.

Five RBPs (ribosomal protein L10-like, enhancer of zeste homolog 2 (EZH2), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A), zinc finger protein 239, interferon-induced protein with tetratricopeptide repeats 1) were used to construct the model. The model accurately predicted the prognosis of liver cancer patients in both the training cohort and validation cohort. HCC patients could be assigned into a high-risk group and a low-risk group by this model, and the overall survival of these 2 groups was significantly different (P 
< .05). Furthermore, the risk scores obtained by this model were highly correlated with immune cell infiltration.

The prognostic model helps to identify HCC patients at high risk of mortality, which optimizes decision-making for individualized treatment.
Combined radiotherapy and chemotherapy versus radiotherapy alone in elderly patients with nasopharyngeal carcinoma
Authors: Lu Yan , Hua Jianfeng , Yan Fengqin , Jiang Chuner , Piao Yongfeng , Ye Zhimin , Fu Zhenfu , Jiang Haitao , Wang Fangzheng , Jiang Yangming
Published: August 2021

Currently, the impact of chemotherapy (CT) on survival outcomes in elderly patients with nasopharyngeal carcinoma (NPC) receiving radiation therapy (RT) remains controversial. This retrospective study aims to investigate survival outcomes in a cohort of elderly NPC patients receiving RT alone or together with CT.

Clinical data on 529 NPC patients aged 65 years and older extracted from the Surveillance, Epidemiology, and End Results registry (2004–2015) was collected and retrospectively reviewed. In this cohort, 74 patients were treated with RT alone and 455 individuals received RT and CT. We used propensity score matching with a 1:3 ratio to identify correlations between patients based on 6 different variables. Kaplan–Meier analysis was used to evaluate overall (OS) and cancer-specific survival (CSS). The differences in OS and CSS between the 2 treatment groups were compared using the Log-rank test and Cox proportional hazards models.

The estimated 5-year OS and CSS rates for all patients were 49.5% and 59.3%, respectively. The combination of RT and CT provided longer OS than RT alone (53.7% vs 36.9%, P = .002), while no significant difference was observed in CSS (61.8% vs 51.7%, P = .074) between the 2 groups. Moreover, multivariate analysis demonstrated that the combination of CT and RT correlated favorably with OS and CSS. Subgroup analyses showed that the combination of RT and CT correlated better with both OS and CSS in patients with stage T3 or N2 or stage III.

Among NPC patients aged 65 years and older, treatment with RT and CT provided longer OS than RT alone. Furthermore, the combination of RT and CT showed a better correlation with OS and CSS in NPC patients with stage T3 or N2 or stage III.
PTEN Hamartoma Syndrome in a Child Presenting With Malrotation, Panintestinal Polyps, Severe Anemia, and Protein-Losing Enteropathy
Authors: Stoecklein Nicole , Ahmed Atif A. , Lawson Caitlin E. , Attard Thomas
Published: August 2021

PTEN hamartoma syndrome (PTEN-HS) is a rare syndrome including neurologic, neurodevelopmental, integumentary, endocrine, and gastrointestinal manifestations. Eosinophilic disorders of the gastrointestinal system are diverse group of disorders reported to be more common in PTEN-HS. Our patient had malrotation and obstruction in infancy and subsequently developed macrocephaly and a lipoma. She presented at 4 years of age with both iron deficiency anemia and hypoalbuminemia from protein-losing enteropathy. She went on to endoscopy, colonoscopy, and video capsule endoscopy showing gastric, small intestinal, and colonic polyps but with histology including both a mixed histologic characterization of the polyps as expected with PTEN-HS, along with eosinophilic esophagitis, gastric, duodenal, colonic and polyp eosinophilia. She improved with enteral nutritional support and budesonide. Intestinal malrotation is a previously unrecognized feature of PTEN-HS, in our patient protein-losing enteropathy may have resulted from polyposis or eosinophilic gastrointestinal disorder. Albeit rare, PTEN-HS represents an elusive differential diagnosis with a broad spectrum including gastrointestinal symptomatology. Our case report illustrates the overlap of clinical, endoscopic, and histologic findings that can complicate PTEN-HS.
Bowmanella yangjiangensis sp. nov. and Amphritea pacifica sp. nov., isolated from mariculture fishponds in China
Authors: Cai Zhipeng , Lu Huibin , Qian Youfeng , Chen Letian , Xu Meiying
Published: August 2021

Four Gram-stain-negative, catalase- and oxidase-positive, rod-shaped and motile strains (Y26, Y57T, ZJ14WT and RP18W) were isolated from mariculture fishponds in PR China. Comparisons based on 16S rRNA gene sequences showed that strains Y26 and Y57T share 16S rRNA gene sequence similarities in the range of 95.1−98.5 % with species of the genus

Bowmanella

, and strains ZJ14WT and RP18W share 16S rRNA gene sequence similarities in the range of 96.7 −98.8 % with species of the genus

Amphritea

, respectively. The genome sizes of strains Y26, Y57T, ZJ14WT and RP18W were about 4.85, 5.40, 4.70 and 4.70 Mbp with 49.5, 51.7, 51.2 and 51.3 mol% G+C content, respectively. The calculated pairwise OrthoANIu values among strains Y26, Y57T and species of the genus

Bowmanella

were in the range of 72.6−83.1 %, but the value between strains Y26 and Y57T was 96.2 %. The pairwise OrthoANIu values among strains ZJ14WT, RP18W and other species of the genus

Amphritea

were all less than 93.9 %, but the value between strains ZJ14WT and RP18W was 99.3 %. Q-8 was the major respiratory quinone of strains Y26, Y57T, ZJ14WT and RP18W, and the major fatty acids of these strains were all C16 : 1 ω7c, C16 : 0 and C18 : 1 ω7c. The predominant polar lipids of strains Y26 and Y57T included phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and phosphatidylinositol, but strains ZJ14WT and RP18W only contained phosphatidylethanolamine and phosphatidylglycerol. Combining phenotypic, biochemical and genotypic characteristics, strains Y26 and Y57T should belong to the same species and represent a novel member of the genus

Bowmanella

, and strains ZJ14WT and RP18W should belong to the same species and represent a novel member of the genus

Amphritea

, for which the names Bowmanella yangjiangensis sp. nov. (type strain Y57T=GDMCC 1.2180T=KCTC 82439T) and Amphritea pacifica sp. nov. (type strain ZJ14WT=GDMCC 1.2203T=KCTC 82438T) are proposed.
The genomic and transcriptional landscape of primary central nervous system lymphoma
Authors: Radke Josefine , Ishaque Naveed , Koll Randi , Gu Zuguang , Schumann Elisa , Sieverling Lina , Uhrig Sebastian , Hübschmann Daniel , Toprak Umut H. , López Cristina , Hostench Xavier Pastor , Borgoni Simone , Juraeva Dilafruz , Pritsch Fabienne , Paramasivam Nagarajan , Balasubramanian Gnana Prakash , Schlesner Matthias , Sahay Shashwat , Pehl Debora , Radbruch Helena , Osterloh Anja , Korfel Agnieszka , Misch Martin , Onken Julia , Faust Katharina , Vajkoczy Peter , Moskopp Dag , Wang Yawen , Jödicke Andreas , Trümper Lorenz , Anagnostopoulos Ioannis , Lenze Dido , Hummel Michael , Schmitt Clemens A. , Wiestler Otmar D. , Wolf Stephan , Unterberg Andreas , Eils Roland , Herold-Mende Christel , Brors Benedikt ,   ICGC MMML-Seq Consortium, Siebert Reiner , Wiemann Stefan , Heppner Frank L.
Published: August 2021

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Despite extensive research, the molecular alterations leading to PCNSL have not been fully elucidated. In order to provide a comprehensive description of the genomic and transcriptional landscape of PCNSL, we here performed whole-genome and transcriptome sequencing and integrative analysis of 51 lymphomas presenting in the CNS, including 42 EBV-negative PCNSL, 6 secondary CNS lymphomas (SCNSL) and 3 EBV+ CNSL and matched controls. The results were compared to an independent validation cohort of 31 FFPE CNSL specimens (PCNSL, n = 19; SCNSL, n = 9; EBV+ CNSL, n = 3) as well as 39 FL and 36 systemic DLBCL cases outside the CNS. Somatic genomic alterations in PCNSL mainly affect the JAK-STAT, NFkB, and B-cell receptor signaling pathways, with hallmark recurrent mutations includingMYD88L265P (67%) andCD79B(63%),CDKN2Adeletions (83%) and also non-coding RNA genes such asMALAT1(70%),NEAT(60%), andMIR142(80%). Kataegis events, which affected 15 of 50 identified driver genes and 21 of the top 50 mutated ncRNAs, played a decisive role in shaping the mutational repertoire of PCNSL. Compared to systemic DLBCL, PCNSLs exhibited significantly more focal deletions in 6p21 targeting the HLA-D locus that encodes for MHC class II molecules as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis (SBS1, ID1 and ID2) were significantly enriched in PCNSL (SBS1:p= 0.0027, ID1/ID2:p< 1×10−4). Furthermore,TERTgene expression was significantly higher in PCNSL compared to ABC-DLBCL (p= 0.027). Although PCNSL share many genetic alterations with systemic ABC-DLBCL in the same signaling pathways, transcriptome analysis clearly distinguished both into distinct molecular subtypes. EBV+ CNSL cases may be distinguished by lack of recurrent mutational hotspots apart from IG andHLA-DRBloci.
A Comparison of Aerosol Mitigation Strategies and Aerosol Persistence in Dental Environments
Authors: Choudhary Shruti , Durkin Michael J. , Stoeckel Daniel C. , Steinkamp Heidi M. , Thornhill Martin H. , Lockhart Peter B. , Babcock Hilary M. , Kwon Jennie H. , Liang Stephen Y. , Biswas Pratim
Published: August 2021

Objectives

To determine the impact of various aerosol mitigation interventions and establish duration of aerosol persistence in a variety of dental clinic configurations.

Methods

We performed aerosol measurement studies in endodontic, orthodontic, periodontic, pediatric, and general dentistry clinics. We used an optical aerosol spectrometer and wearable particulate matter sensors to measure real-time aerosol concentration from the vantage point of the dentist during routine care in a variety of clinic configurations (e.g, open bay, single room, partitioned operatories). We compared the impact of aerosol mitigation strategies [ventilation and high-volume evacuation (HVE)] and prevalence of particulate matter in the dental clinic environment before, during and after high-speed drilling, slow speed drilling and ultrasonic scaling procedures.

Results

Conical and ISOVAC® HVE were superior to standard tip evacuation for aerosol-generating procedures. When aerosols were detected in the environment, they were rapidly dispersed within minutes of completing the aerosol-generating procedure. Few aerosols were detected in dental clinics – regardless of configuration – when conical and ISOVAC® HVE were used.

Conclusions

Dentists should consider using conical or ISOVAC® HVE rather than standard tip evacuators to reduce aerosols generated during routine clinical practice. Furthermore, when such effective aerosol mitigation strategies are employed, dentists need not leave dental chairs fallow between patients as aerosols are rapidly dispersed.

Clinical Significance

ISOVAC® HVE is highly effective in reducing aerosol emissions, with adequate ventilation and HVE use, dental fallow time can be reduced to 5 minutes.