bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutation of RORγT reveals a role for Th17 cells in both injury and recovery from renal ischemia-reperfusion injury
Authors: Mehrotra Purvi , Ullah Md Mahbub , Collett Jason A. , Myers Sarah L. , Dwinell Melinda R. , Geurts Aron M. , Basile David P.
Published: September 2020

To investigate T helper type 17 (Th17) cells in the setting of acute kidney injury, the gene encoding the master regulator of Th17 cell differentiation, that is, RAR-related orphan receptor-γ (RORγT), was mutated in Lewis rats using CRISPR/Cas9 technology. In response to 40 min of bilateral renal ischemia-reperfusion (I/R), RAR-related orphan receptor C ( Rorc)−/− rats were resistant to injury relative to wild-type Rorc+/+ rats. This protection was associated with inhibition of IL-17 expression and reduced infiltration of CD4+ cells, CD8+ cells, B cells, and macrophages. To evaluate the effect of Th17 cells on repair, ischemia was increased to 50 min in Rorc−/− rats. This maneuver equalized the initial level of injury in Rorc−/− and Rorc+/+ rats 1 to 2 days post-I/R based on serum creatinine values. However, Rorc−/− rats, but not Rorc+/+ rats, failed to successfully recover renal function and had high mortality by 4 days post-I/R. Histological assessment of kidney tubules showed evidence of repair by day 4 post-I/R in Rorc+/+ rats but persistent necrosis and elevated cell proliferation in Rorc−/− rats. Adoptive transfer of CD4+ cells from the spleen of Rorc+/+ rats or supplementation of exogenous rIL-17 by an osmotic minipump improved renal function and survival of Rorc−/− rats following 50 min of I/R. This was associated with a relative decrease in the number of M1-type macrophages and a relative increase in the percentage of T regulatory cells. Taken together, these data suggest that Th17 cells have both a deleterious and a beneficial role in kidney injury and recovery, contributing to early postischemic injury and inflammation but also possibly being critical in the resolution of inflammation during kidney repair.
A mini-review of pharmacological strategies used to ameliorate polyuria associated with X-linked nephrogenic diabetes insipidus
Authors: Mortensen Line A. , Bistrup Claus , Jensen Boye L. , Hinrichs Gitte R.
Published: September 2020

Nephrogenic diabetes insipidus (NDI) is characterized by renal resistance to the antidiuretic hormone arginine vasopressin (AVP), which leads to polyuria, plasma hyperosmolarity, polydipsia, and impaired quality of living. Inherited forms are caused by X-linked loss-of-function mutations in the gene encoding the vasopressin 2 receptor (V2R) or autosomal recessive/dominant mutations in the gene encoding aquaporin 2 (AQP2). A common acquired form is lithium-induced NDI. AVP facilitates reabsorption of water through increased abundance and insertion of AQP2 in the apical membrane of principal cells in the collecting ducts. In X-linked NDI, V2R is dysfunctional, which leads to impaired water reabsorption. These patients have functional AQP2, and thus the challenge is to achieve AQP2 membrane insertion independently of V2R. The current treatment is symptomatic and is based on distally acting diuretics (thiazide or amiloride) and cyclooxygenase inhibitors (indomethacin). This mini-review covers published data from trials in preclinical in vivo models and a few human intervention studies to improve NDI by more causal approaches. Promising effects on NDI in preclinical studies have been demonstrated by the use of pharmacological approaches with secretin, Wnt5a, protein kinase A agonist, fluconazole, prostaglandin E2 EP2 and EP4 agonists, statins, metformin, and soluble prorenin receptor agonists. In patients, only casuistic reports have evaluated the effect of statins, phosphodiesterase inhibitors (rolipram and sildenafil), and the guanylate cyclase stimulator riociguat without amelioration of symptoms. It is concluded that there is currently no established intervention that causally improves symptoms or quality of life in patients with NDI. There is a need to collaborate to improve study quality and conduct formal trials.
High-resolution analysis of differential gene expression during skeletal muscle atrophy and programmed cell death
Authors: Tsuji Junko , Thomson Travis , Chan Elizabeth , Brown Christine K. , Oppenheimer Julia , Bigelow Carol , Dong Xianjun , Theurkauf William E. , Weng Zhiping , Schwartz Lawrence M.
Published: September 2020

Skeletal muscles can undergo atrophy and/or programmed cell death (PCD) during development or in response to a wide range of insults, including immobility, cachexia, and spinal cord injury. However, the protracted nature of atrophy and the presence of multiple cell types within the tissue complicate molecular analyses. One model that does not suffer from these limitations is the intersegmental muscle (ISM) of the tobacco hawkmoth Manduca sexta. Three days before the adult eclosion (emergence) at the end of metamorphosis, the ISMs initiate a nonpathological program of atrophy that results in a 40% loss of mass. The ISMs then generate the eclosion behavior and initiate a nonapoptotic PCD during the next 30 h. We have performed a comprehensive transcriptomics analysis of all mRNAs and microRNAs throughout ISM development to better understand the molecular mechanisms that mediate atrophy and death. Atrophy involves enhanced protein catabolism and reduced expression of the genes involved in respiration, adhesion, and the contractile apparatus. In contrast, PCD involves the induction of numerous proteases, DNA methylases, membrane transporters, ribosomes, and anaerobic metabolism. These changes in gene expression are largely repressed when insects are injected with the insect steroid hormone 20-hydroxyecdysone, which delays death. The expression of the death-associated proteins may be greatly enhanced by reductions in specific microRNAs that function to repress translation. This study not only provides fundamental new insights into basic developmental processes, it may also represent a powerful resource for identifying potential diagnostic markers and molecular targets for therapeutic intervention.
Computer-Aided Analysis of Multiple SARS-CoV-2 Therapeutic Targets: Identification of Potent Molecules from African Medicinal Plants
Authors: Iheagwam Franklyn Nonso , Rotimi Solomon Oladapo
Published: September 2020

The COVID-19 pandemic, which started in Wuhan, China, has spread rapidly over the world with no known antiviral therapy or vaccine. Interestingly, traditional Chinese medicine helped in flattening the pandemic curve in China. In this study, molecules from African medicinal plants were analysed as potential candidates against multiple SARS-CoV-2 therapeutic targets. Sixty-five molecules from the ZINC database subset (AfroDb Natural Products) were virtually screened with some reported repurposed therapeutics against six SARS-CoV-2 and two human targets. Molecular docking, druglikeness, absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the best hits were further simulated. Of the 65 compounds, only three, namely, 3-galloylcatechin, proanthocyanidin B1, and luteolin 7-galactoside found in almond (Terminalia catappa), grape (Vitis vinifera), and common verbena (Verbena officinalis), were able to bind to all eight targets better than the reported repurposed drugs. The findings suggest these molecules may play a role as therapeutic leads in tackling this pandemic due to their multitarget activity.
Ningdong Granule Upregulates the Striatal DA Transporter and Attenuates Stereotyped Behavior of Tourette Syndrome in Rats
Authors: Li Jijun , Guo Yi , Zhao Lin , Sun Kexing , Xi Guangjun , Li Zai-Wang
Published: September 2020

This study aimed to evaluate the possible mechanism of Ningdong granule (NDG) for the treatment of Tourette syndrome (TS). The rats with stereotyped behavior were established by microinjection with TS patients’ sera; then, the model rats were divided into NDG and haloperidol (Hal) group, and the nonmedication model rats were regarded as treatment control (TS group). The stereotyped behavior of the rats was recorded, the level of dopamine (DA) in striatum, and the content of homovanillic acid (HVA) in sera were tested, and dopamine transporter (DAT) expression was measured in the study. The experimental results showed that NDG effectively inhibited the stereotyped behavior (P < 0.01), decreased the levels of DA in the striatum (P < 0.05), increased the content of sera HVA (P < 0.01), and enhanced the protein and mRNA expression of DAT in the striatum (P < 0.01). Additionally, the results also revealed Hal could improve the stereotyped behavior as well but had no remarkable influence on DAT expression and DA metabolism. In conclusion, NDG attenuates stereotyped behavior, and its mechanism of action might be associated with the upregulation of DAT expression to regulate DA metabolism in the brain.
The Impact of Bioactive Surfaces in the Early Stages of Osseointegration: An In Vitro Comparative Study Evaluating the HAnano® and SLActive® Super Hydrophilic Surfaces
Authors: da Silva Rodrigo A. , da Silva Feltran Geórgia , Ferreira Marcel Rodrigues , Wood Patrícia Fretes , Bezerra Fabio , Zambuzzi Willian F.
Published: September 2020

There is an increased effort on developing novel and active surfaces in order to accelerate their osteointegration, such as nanosized crystalline hydroxyapatite coating (HAnano®). To better understand the biological behavior of osteoblasts grown on HAnano® surface, the set of data was compared with SLActive®, a hydrophilic sandblasted titanium surface. Methodologically, osteoblasts were seeded on both surfaces up to 72 hours, to allow evaluating cell adhesion, viability, and set of genes encoding proteins related with adhesion, proliferation, and differentiation. Our data shows HAnano® displays an interesting substrate to support cell adhesion with typical spread morphologic cells, while SLActive®‐adhering cells presented fusiform morphology. Our data shows that the cellular adhesion mechanism was accompanied with upexpression of integrin β1, Fak, and Src, favoring the assembling of focal adhesion platforms and coupling cell cycle progression (upmodulating of Cdk2, Cdk4, and Cdk6 genes) in response to HAnano®. Additionally, both bioactive surfaces promoted osteoblast differentiation stimulus, by activating Runx2, Osterix, and Alp genes. Although both surfaces promoted Rankl gene expression, Opg gene expression was higher in SLActive® and this difference reflected on the Rankl/Opg ratio. Finally, Caspase1 gene was significantly upmodulated in response to HAnano® and it suggests an involvement of the inflammasome complex. Collectively, this study provides enough evidences to support that the nanohydroxyapatite‐coated surface provides the necessary microenvironment to drive osteoblast performance on dental implants and these stages of osteogenesis are expected during the early stages of osseointegration.
Delayed 18F-FDG PET/CT Appearance of Urachal Adenocarcinomas
Authors: Xu Lian , Shi Yiping , Wang Yining , Zhou Xiang , Huang Gan , Chen Ruohua , Liu Jianjun
Published: September 2020

Background. Urachal carcinoma is a rare urological malignancy. Use of 18F-FDG PET/CT in urological oncology has developed slowly because of the urinary elimination of 18F-FDG. We investigated whether delayed postdiuretic 18F-FDG PET/CT could be used for diagnosing urachal carcinoma. Methods. This retrospective study included 6 patients who underwent delayed postdiuretic 18F-FDG PET/CT for the evaluation of urachal carcinoma. The delayed postdiuretic PET/CT parameters and clinical characteristics of urachal carcinoma were investigated. Results. There was no significant difference in the SUVmax between the primary tumors and the urine in the bladder before delayed diuresis (25.4 ± 19.5 vs. 42.9 ± 31.1, P=0.18). However, the SUVmax of the primary tumors was significantly higher than the SUVmax of urine after delayed diuresis (25.4 ± 19.5 vs. 3.5 ± 1.6, P=0.002). Diuretic 18F-FDG PET/CT was positive in all patients when compared with normal liver tissues or urine after delayed diuresis. The SUVmax, TLR, and TUR of the primary tumors were 25.4 (range: 7.2–58.9), 7.0 (range: 1.8–14.7), and 6.8 (range: 3.8–11.3), respectively. Delayed postdiuretic 18F-FDG PET/CT had a negative predictive value of 100% (5/5) for predicting lymph node metastasis. One patient received chemotherapy after radical resection of urachal carcinoma because 18F-FDG PET/CT found lung metastases, and one patient only received chemotherapy because PET/CT found peritoneal and skeletal metastases. Conclusions. Delayed postdiuretic 18F-FDG PET/CT is a useful tool for the preoperative evaluation of urachal carcinoma. 18F-FDG PET/CT may improve clinical decision making and management of urachal carcinomas.
Paraplegia due to Thoracic Mobile Schwannoma after Myelography
Authors: Honda Akira , Iizuka Yoichi , Mieda Tokue , Sonoda Hiroyuki , Ishiwata Sho , Kakuta Yohei , Tsunoda Daisuke , Takasawa Eiji , Tajika Tsuyoshi , Koshi Hiromi , Chikuda Hirotaka
Published: September 2020

Introduction. Spinal mobile tumors are very rare. We herein report a case of paraplegia caused by migration and incarceration of thoracic mobile schwannoma after myelography. Case Presentation. A 25-year-old man who had weakness and numbness in both his legs also had pain radiating to the back that was induced by back flexion or extension and jumping. Magnetic resonance imaging (MRI) showed an intradural extramedullary lesion at the T10 and T11 levels. Myelography was performed but discontinued due to his back and lower limb pain. Computed tomography after myelography revealed a rostrally migrated intradural mass with a discrepancy in the exact location in comparison to the MRI findings. He underwent a second lumbar puncture and drained the cerebrospinal fluid (CSF) to aid the spinal cord, because the symptoms gradually worsened and led to paraplegia. After the drainage of the CSF, his symptoms were immediately resolved. The day after myelography, he underwent complete resection of the tumor with the diagnosis of schwannoma. One year after the surgery, he had been working despite having hyperreflexia in his lower limbs with no weakness or sensory disturbance. Conclusion. Severe neurological deficits associated with spinal cord damage can occur due to migration of mobile tumors.
Efficiency of High and Standard b Value Diffusion-Weighted Magnetic Resonance Imaging in Grading of Gliomas
Authors: Al-Agha Mansour , Abushab Khaled , Quffa Khetam , Al-Agha Samy , Alajerami Yasser , Tabash Mohammed
Published: September 2020

Background. Glioma is the most common fatal malignant tumor of the CNS. Early detection of glioma grades based on diffusion-weighted imaging (DWI) properties is considered one of the most recent noninvasive promising tools in the assessment of glioma grade and could be helpful in monitoring patient prognosis and response to therapy. Aim. This study aimed to investigate the accuracy of DWI at both standard and high b values (b = 1000 s/mm2 and b = 3000 s/mm2) to distinguish high-grade glioma (HGG) from low-grade glioma (LGG) in clinical practice based on histopathological results. Materials and Methods. Twenty-three patients with glioma had DWI at l.5 T MR using two different b values (b = 1000 s/mm2 and b = 3000 s/mm2) at Al-Shifa Medical Complex after obtaining ethical and administrative approvals, and data were collected from March 2019 to March 2020. Minimum, maximum, and mean of apparent diffusion coefficient (ADC) values were measured through drawing region of interest (ROI) on a solid part at ADC maps. Data were analyzed by using the MedCalc analysis program, version 19.0.4, receiver operating characteristic (ROC) curve analysis was done, and optimal cutoff values for grading gliomas were determined. Sensitivity and specificity were also calculated. Results. The obtained results showed the ADCmean, ADCratio, ADCmax, and ADCmin were performed to differentiate between LGG and HGG at both standard and high b values. Moreover, ADC values were inversely proportional to glioma grade, and these differences are more obvious at high b value. Minimum ADC values using standard b value were 1.13 ± 0.17 × 10−3 mm2/s, 0.89 ± 0.85 × 10−3 mm2/s, and 0.82 ± 0.17 × 10−3 mm2/s for grades II, III, and IV, respectively. Concerning high b value, ADCmin values were 0.76 ± 0.07 × 10−3 mm2/s, 0.61 ± 0.01 × 10−3 mm2/s, and 0.48 ± 0.07 × 10−3 mm2/s for grades II, III, and IV, respectively. ADC values were inversely correlated with results of glioma grades, and the correlation was stronger at ADC3000 (r = −0.722, P≤0.001). The ADC3000 achieved the highest diagnostic accuracy with an area under the curve (AUC) of 0.618, 100% sensitivity, 85.7% specificity, and 85.7% accuracy for glioma grading at a cutoff point of ≤0.618 × 10−3 mm2/s. The high b value showed stronger agreement with histopathology compared with standard b value results (k = 0.89 and 0.79), respectively. Conclusion. The ADC values decrease with an increase in tumor cellularity. Meanwhile, high b value provides better tissue contrast by reflecting more tissue diffusivity. Therefore, ADC-derived parameters at high b value are more useful in the grading of glioma than those obtained at standard b value. They might be a better surrogate imaging sequence in the preoperative evaluation of gliomas.
Test Verification of Two-Stage Adaptive Delay Compensation Method for Real-Time Hybrid Simulation
Authors: Wang Zhen , Yan Xueqi , Ning Xizhan , Wu Bin
Published: September 2020

Real-time hybrid simulation (RTHS) is a versatile testing technique for performance evaluation of structures subjected to dynamic excitations. Research revealed that compensation for the delay induced by the dynamics of the loading system and other factors is a critical issue for obtaining reliable test results. Lately, a two-stage adaptive delay compensation (TADC) method was conceived and performed on the benchmark problem of RTHS. For this method, the main part of the system delay is coarsely compensated by the classic polynomial extrapolation (PE) method; the second stage represents a fine remedy for the remaining delay with adaptive compensation based on a discrete model of the loading system. As an extension of this study, this paper aims to further verify and reveal the performance of this method through real tests on a viscous damper specimen. In particular, loading tests with a swept signal and RTHS with sinusoidal and seismic excitations were carried out. Investigations show that the TADC method is endowed with smaller parameter variation ranges, simple yet effective initialization or a soft-start process, less dependence on initial parameter estimation accuracy, and best compensation performance.
Circulating Th1 and Th2 Subset Accumulation Kinetics in Septic Patients with Distinct Infection Sites: Pulmonary versus Nonpulmonary
Authors: Xue Ming , Tang Yuying , Liu Xu , Gu Mingyuan , Xie Jianfeng , Liu Ling , Huang Yingzi , Guo Fengmei , Yang Yi , Qiu Haibo
Published: September 2020

Background. Persistent peripheral CD4+T cell differentiation towards T helper (Th)2 rather than Th1 has been proved to be related to immunosuppression and poor prognosis in sepsis. However, it is unclear whether these circulating Th1 and Th2 subtype accumulations differed in septic populations of distinct infection sites and presented different associations with outcomes among patients with pulmonary versus nonpulmonary sepsis. Methods. From a secondary analysis of a prospective observational study, seventy-four previously immunocompetent patients with community-acquired severe sepsis within 24 hours upon onset were enrolled. Whole blood was collected on the admission day (D0), 3rd day (D3), and 7th day (D7). The patients were classified as pulmonary (n=52) and nonpulmonary sepsis (n=22). Circulating Th1 and Th2 populations were evaluated by flow cytometry, and clinical data related to disease severity and inflammatory response were collected. The associations of circulating Th1 and Th2 subset accumulations with distinct infection sites or outcomes within subgroups were explored. Results. Patients with pulmonary sepsis held similar disease severity and 28-day mortality with those of nonpulmonary sepsis. Of note is the finding that circulating Th2 levels on D7 (P=0.04) as well as Th2/Th1 on D3 (P=0.01) and D7 (P=0.04) were higher in the pulmonary sepsis compared with nonpulmonary sepsis while Th1 levels were lower on D0, D3, and D7 (P=0.01, <0.01, and =0.05, respectively). Compared to 28-day survivors, higher Th2/Th1 driven by increased Th2 were observed among 28-day nonsurvivors on D3 and D7 in both groups. The association between circulatory Th2 populations or Th2/Th1 and 28-day death was detected in pulmonary sepsis (P<0.05, HR>1), rather than nonpulmonary sepsis. Conclusions. Circulating Th2 accumulation was more apparent among pulmonary sepsis while nonpulmonary sepsis was characterized with the hyperactive circulating Th1 subset among previously immunocompetent patients. This finding suggested that circulating Th1 and Th2 subset accumulations vary in septic subgroups with different infection sites.
Immunological Evaluation for Personalized Interventions in Children with Tuberculosis: Should It Be Routinely Performed?
Authors: Carreto-Binaghi Laura E. , Juárez Esmeralda , Guzmán-Beltrán Silvia , Herrera María Teresa , Torres Martha , Alejandre Alejandro , Martínez-Orozco José Arturo , Becerril-Vargas Eduardo , Gonzalez Yolanda
Published: September 2020

Childhood tuberculosis (TB) is a significant public health problem and the ninth leading cause of death worldwide. Progression of Mycobacterium tuberculosis infection to active disease depends on mycobacterial virulence, environmental diversity, and host susceptibility and immune response. In children, malnutrition and immaturity of the immune system contribute to an inadequate immune response. Coinfections, though rarely described in TB, might be associated with host immune deficiencies. Here, we describe the immunological evaluation of eight pediatric patients infected with a member of the M. tuberculosis complex, most of them with concomitant pulmonary infections (bacteria, viruses, or fungi). We assessed the functionality of several innate immunity receptors, IL-12 receptor, and IFN-γ receptor, as well as the antioxidant levels (glutathione), which are essential mechanisms for fighting intracellular pathogens such as M. tuberculosis. This study is aimed at developing a thorough immunological evaluation of patients with TB and a coinfection.
Gingival Biopsy to Detect Mosaicism in Overgrowth Syndromes: Report of Two Cases of Megalencephaly-Capillary Malformation Syndrome with Periodontal Anomalies
Authors: Marty Mathieu , Bonnaud Carole , Jones Natalie , Longy Michel , Vaysse Frédéric , Bieth Eric , Bailleul-Forestier Isabelle
Published: September 2020

Background. Megalencephaly-capillary malformation (MCAP) is a rare overgrowth syndrome caused by postzygotic activating mutations in the PIK3CA gene. Aim. To illustrate the benefits of gingival biopsy in the genetic diagnosis of overgrowth syndromes. Design. Gingival biopsy was performed on a 13-year-old patient and a 16-year-old patient with MCAP and who suffered from periodontal disease. PIK3CA sequencing was performed on DNA extracted from gingival biopsies, blood, and saliva. Results. Pathogenic p.Glu365Lys and p.Glu545Asp PIK3CA mutations were found in the gingival biopsies with an allelic frequency of 22% and 35%, respectively, while they were undetectable in blood or saliva. The genetic diagnosis of MCAP through detection of PIK3CA somatic mosaicism in a periodontal biopsy is unprecedented. Conclusions. Considering the tissue distribution and level of somatic mosaicism for PIK3CA mutation, the composite embryologic origin of periodontium and its high fibroblast cell content make it an ideal target for molecular analysis in overgrowth syndromes, and multidisciplinary approach including paediatric dentists should be encouraged. In addition, our clinical findings suggest that periodontal disease is part of the MCAP phenotypic spectrum and should be systematically investigated.
Influence of Maximum Particle Diameter on the Mechanical Behavior of Soil‐Rock Mixtures
Authors: He Zhuoling , Zhang Junyun , Sun Tao
Published: September 2020

With the steady development of the development of the western region in China, the construction of mountain highways has developed rapidly, and the soil‐rock mixed filler, as an excellent filler, is widely used in the subgrade filling of mountain highways. Unlike ordinary fine‐grained soil, the source of the soil‐rock mixtures (S‐RMs) is not unique, and the particle size difference is large and the water content is not uniform, resulting in very complicated mechanical properties. But the current highway embankment codes are still mainly established on the fine‐grained soil. It is not fully applicable to soil‐rock filled embankment. Based on soil‐rock filled embankment engineering practice, this research uses a large‐scale direct shear test to research the mechanical characteristics of the S‐RMs with different maximum particle diameters. According to the large‐scale direct shear test of S‐RMs with different maximum particle diameters, the shear displacement vs shear stress curve, shear dilation, and strength characteristics with maximum particle diameter were analyzed. Results demonstrate that whether secondary hardening occurs mainly depends on the normal stress and the maximum particle diameter of the filler. At different maximum particle diameters, the horizontal displacement vs vertical displacement curves of the S‐RMs can be roughly divided into continuous shearing and beginning of shearing and quick dilation. And the shear strength increases with the increase of the maximum particle diameter. Moreover, the cohesion decreases first and then increases with the increase of the maximum particle diameter, and the internal friction angle increases with the increase of the maximum particle diameter. Therefore, some RBs with large particle diameter added to filler can effectively improve the shear strength of the S‐RMs, which may be valuable for realistic engineering.
Pregnancy and Lactation in a 67-Year-Old Elderly Gravida following Donor Oocyte In Vitro Fertilization
Authors: Magistrado Leila , Tolcher Mary C. , Suhag Anju , Zambare Sonal , Aagaard Kjersti M.
Published: September 2020

There is limited data on the anticipated perinatal course among gravidae in their sixth and seventh decades. Our objective was to describe the relatively uncomplicated prenatal, intrapartum, and postpartum course of a 67-year-old essential primigravida. Briefly, our patient conceived a singleton pregnancy via IVF with donor oocytes, then presented at 13 6/7 weeks of gestation to initiate prenatal care. Her medical history was significant for chronic hypertension, hyperlipidemia, and obesity. Her cardiac function was monitored throughout pregnancy, and she delivered at 36 1/7 weeks by cesarean for a decline in left ventricular function with mitral regurgitation. Her intrapartum and postpartum course was uncomplicated, and she was able to successfully breastfeed for six months and resume prepregnancy activity. For comparison, we analyzed deliveries among gravidae>45 years of age from our institutional obstetrical database (2011-2018). This case represents the eldest gravidae identified in the literature and illustrates the potential for a relatively uncomplicated perinatal course with successful lactation. This case may enable other providers to counsel elderly patients on anticipated outcomes inclusive of ability to breastfeed.
Statins Use and Outcome of Acute Ischemic Stroke Patients after Systemic Thrombolysis
Authors: Mowla Ashkan , Shah Harshit , Lail Navdeep Singh , Vaughn Caila B , Shirani Peyman , Sawyer Robert N.
Published: September 2020

Aim: The aim of this was to study the effects of statins and their intensity on symptomatic intracranial hemorrhage (sICH) and outcome after IV thrombolysis (IVT) for acute ischemic stroke (AIS). Methods: We retrospectively reviewed the medical records and cerebrovascular images of all the patients treated with IVT for AIS in our center in a 10-year period. Patients were further characterized as any statin users versus non-users on admission to the emergency department. Statins were categorized in high intensity or low intensity statin based on its propensity to reduce lower low-density cholesterol by ≥45% or <45%, respectively. Safety and discharge modified Rankin Score were compared between statin users versus non-users and also between high-intensity versus low-intensity groups. Results: A total of 834 patients received IVT for AIS in our center during a 10-year period. Multivariate models were adjusted for age, NIH Stroke Scale at admission, INR, and history of DM and atrial fibrillation. There was no association between odds of sICH and any statin use (OR = 0.52 [0.26–1.03], p = 0.06). In multivariate model, any statin use was not associated with odds of poor outcome (Table 4: OR = 1.01 [0.79–1.55], p = 0.57). There was no significant association between odds of sICH among patients on high-intensity statin compared to low intensity statin (multivariate model OR = 0.39 [0.11–1.40], p = 0.15). There was 47% reduced odds of poor outcome among patients on high-intensity statin as compared to low-intensity statin (OR = 0.53[0.32–0.88] p = 0.01). However, this significant association was lost in the multivariate model (OR = 0.60 [0.35–1.05], p = 0.07). Conclusion: Our study does not show any significant association between risk of sICH and poor outcome after IVT for patients on prior statin therapy. We also did not find significant association between the risk of sICH and poor outcome after IVT and the intensity of the stain used.
Use of Cadaveric Skin Graft for Staged Gastroschisis Repair in a Premature Infant
Authors: Labuz Daniel F. , Asch Morris J. , Buchmiller Terry L.
Published: September 2020

Gastroschisis is a congenital abdominal wall defect that, when simple, has excellent overall outcomes. However, morbidity increases with prematurity. A staged approach to closure is often needed until the infant can tolerate definitive repair. We demonstrate the novel use of cadaveric skin allograft as a defect patch, exploiting a tolerant neonatal immune system for long-term durable coverage. A 580-g, 26-week-gestation boy was born with gastroschisis. Primary closure was not possible, necessitating staged closure. After initial silo placement, neither the fascia nor the skin could be closed. Therefore, cadaveric skin was utilized for coverage: there was 100% take, no wound care needs, and no acute rejection. He was discharged at 4 months tolerating full feeds. At 6 months signs of rejection ultimately manifested, and he underwent uneventful elective graft excision and fascial closure. We offer this as a useful option for management of staged gastroschisis closure in an extremely premature infant.
Sensitization to Local Seafood Allergens in Adult Patients with Atopic Dermatitis in Malaysia
Authors: Lee Hock Leng , Tang Min Moon , Bakhtiar Mohammed Faizal , Mohamad Yadzir Zailatul Hani , Johar Asmah
Published: September 2020

Background: Seafood is an important source of nutrition in Asia. However, it was believed to cause or aggravate atopic dermatitis (AD). Objectives: We aim to determine relevant seafood sensitization among adults with AD and investigate cross-sensitization to aeroallergens. Methods: One hundred thirty-two adults with AD who were subjected to skin prick test (SPT) with 7 common local seafood allergens (anchovy, tuna, mackerel, squid, giant freshwater prawn, shrimp, and crab), house dust mites (HDMs), and cockroach were analyzed retrospectively. Results: The median age of the study subjects was 32 years (range 17–77 years) with a male to female ratio of 1:3. The mean duration of AD was 16 years. Eighty-two patients (62.2%) had other atopic conditions. Using SCORAD, 44.7% had mild, 42.4% moderate, and 12.9% severe disease. Eighty-six patients (65.2%) self-reported to have seafood allergy, with the main symptoms of transient pruritus and erythema within 2 h of ingestion. SPT revealed 51.5% of the patients were sensitized to at least 1 of the 7 seafood allergens. The relevant sensitization rate was 45.1%. Interestingly, 46% of those without a history of seafood allergy developed at least 1 positive reaction in the SPT. Prawn, shrimp, and crab were the 3 most frequently sensitized allergens. Nearly all patients (98.3%) who were sensitized to crustaceans were also sensitized to HDMs and/or cockroach. There was no significant correlation between a positive SPT to seafood with age, age of onset of AD, duration, and severity of AD, and the presence of other atopic diatheses. Conclusion: The relevant sensitization rate of local seafood among adults with AD was 45.1%.
Recurrence of Hepatocellular Carcinoma in Hepatitis C Virus (HCV) Liver Transplant Recipients Treated with Pretransplant Direct-Acting Antiviral (DAA) Therapy
Authors: Lim Nicholas , Singh Dupinder , Jackson Scott , Lake John R.
Published: September 2020

Background: Direct-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV). The impact of DAAs on recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains uncertain. Objective: We aimed to evaluate the risk of HCC recurrence in LT recipients cleared of HCV with DAAs at the time of LT compared to a control group of LT recipients who were viremic at the time of LT. Methods: The study was a single-center, retrospective cohort study of patients undergoing LT for HCV-related HCC from 2002 to 2017. We compared time to post-LT HCC recurrence in patients with a sustained virological response (SVR) from DAAs prior to LT (DAA group) to patients who were viremic at LT (HCV+ group) using Kaplan-Meier analysis. We performed a secondary analysis comparing post-LT HCC recurrence in the DAA group to LT recipients with SVR from interferon-based treatment prior to LT (IFN group). Results: One hundred fifty-one patients underwent LT for HCC related to HCV: 34 patients in DAA group, 95 patients in HCV+ group, and 22 in IFN group. Kaplan-Meier estimates of being HCC free were 96.2, 96.2, and 78.8% at 6, 12, and 24 months in DAA group, respectively, and 100, 98.6, and 95.8% at 6, 12, and 24 months in the HCV+ group, respectively; p = 0.08. There was no difference observed for HCC recurrence between the DAA and IFN groups. In a multivariate Cox proportional hazards model, DAA use increased the risk of post-LT HCC recurrence (HR 5.2, 95% CI 0.9–29.81, p = 0.07). Conclusions: A strong trend was observed on both Kaplan-Meier and multivariate analyses toward increased post-LT HCC recurrence in patients who achieved SVR prior to LT with DAAs compared to patients who were viremic at LT. Caution is required when considering pre-LT treatment of HCV with DAAs in patients with HCC.
Underutilization of Treatment for Black Adults With Apparent Treatment-Resistant Hypertension
Authors: Langford Aisha T. , Akinyelure Oluwasegun P. , Moore Tony L. , Howard George , Min Yuan-I , Hillegass William B. , Bress Adam P. , Tajeu Gabriel S. , Butler Mark , Jaeger Byron C. , Yano Yuichiro , Shimbo Daichi , Ogedegbe Gbenga , Calhoun David , Booth John N. , Muntner Paul
Published: September 2020

Resistant hypertension, defined as blood pressure levels above goal while taking ≥3 classes of antihypertensive medication or ≥4 classes regardless of blood pressure level, is associated with increased cardiovascular disease risk. The 2018 American Heart Association Scientific Statement on Resistant Hypertension recommends healthy lifestyle habits and thiazide-like diuretics and mineralocorticoid receptor antagonists for adults with resistant hypertension. The term apparent treatment-resistant hypertension (aTRH) is used when pseudoresistance cannot be excluded. We estimated the use of healthy lifestyle factors and recommended antihypertensive medication classes among US Black adults with aTRH. Data were pooled for Black participants in the JHS (Jackson Heart Study) in 2009 to 2013 (n=2496) and the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) in 2013 to 2016 (n=3786). Outcomes included lifestyle factors (not smoking, not consuming alcohol, ≥75 minutes of vigorous-intensity or ≥150 minutes of moderate or vigorous physical activity per week, and body mass index <25 kg/m
2
) and recommended antihypertensive medications (thiazide-like diuretics and mineralocorticoid receptor antagonists). Overall, 28.3% of participants who reported taking antihypertensive medication had aTRH. Among participants with aTRH, 14.5% and 1.2% had ideal levels of 3 and 4 of the lifestyle factors, respectively. Also, 5.9% of participants with aTRH reported taking a thiazide-like diuretic, and 9.8% reported taking a mineralocorticoid receptor antagonist. In conclusion, evidence-based lifestyle factors and recommended pharmacological treatment are underutilized in Black adults with aTRH. Increased use of lifestyle recommendations and antihypertensive medication classes specifically recommended for aTRH may improve blood pressure control and reduce cardiovascular disease–related morbidity and mortality among US Black adults.

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Is Endovascular Treatment Still Good for Ischemic Stroke in Real World?
Authors: Zhao Zixu , Zhang Jiarui , Jiang Xin , Wang Li , Yin Zixiao , Hall Michael , Wang Yang , Lai Lingfeng
Published: September 2020

Background and Purpose:

Although endovascular treatment (EVT) for acute ischemic stroke is classified as I evidence, outcomes after EVT in real-world practice appear to be less superior than those in randomized clinical trials (RCTs). Additionally, the effect of EVT is unclear compared with medical treatment (MT) for patients with mild symptoms defined by National Institutes of Health Stroke Scale score <6 or with severe symptoms defined by Alberta Stroke Program Early CT Score <6.

Methods:

Literatures were searched in big databases and major meetings from December 6, 2009, to December 6, 2019, including RCTs and observational studies comparing EVT against MT for patients with acute ischemic stroke. Observational studies were precategorized into 3 groups based on imaging data on admission: mild stroke group with National Institutes of Health Stroke Scale score <6, severe stroke group with Alberta Stroke Program Early CT Score <6 or ischemic core ≥50 mL, and normal stroke group for all others. Outcome was measured as modified Rankin Scale score of 0 to 2, mortality at 90 days, and symptomatic intracranial hemorrhage (sICH) at 24 hours.

Results:

Fifteen RCTs (n=3694) and 37 observational studies (n=9090) were included. EVT was associated with higher modified Rankin Scale 0 to 2 rate and lower mortality in RCTs and normal stroke group, whereas EVT was associated with higher sICH rate in normal stroke group, and no difference of sICH rate appeared between EVT and MT in RCTs. In severe stroke group, EVT was associated with higher modified Rankin Scale 0 to 2 rate and lower mortality, whereas no difference of sICH rate was found. In mild stroke group, there was no difference in modified Rankin Scale 0 to 2 rate between EVT and MT, whereas EVT was associated with higher mortality and sICH rate.

Conclusions:

Evidence from RCTs and observational studies supports the use of EVT as the first-line choice for eligible patients corresponding to the latest guideline. For patients with Alberta Stroke Program Early CT Score <6, EVT showed superiority over MT, also in line with the guidelines. On the contrary to the guideline, our data do not support EVT for patients with National Institutes of Health Stroke Scale score <6.
Musicking with Music-Generation Software in Virtutes Occultae
Authors: Brook Taylor
Published: September 2020

This article explores concepts of compositional meaning that arise from cocreative composing with music-generation software. Drawing from an analysis of the 2017 electroacoustic composition Virtutes Occultae, the composer discusses the implications of computer-generated music for the role of the composer. After an overview of how the music-generation software he developed contributed to the creation of Virtutes Occultae, the composer makes comparisons between his process and the use of generative commercial music software to create music, in order to draw distinctions between creating computer-generated music to extend aesthetic sensibilities and creating computer-generated music that iterates based on established commercial styles. Finally, the composer proposes future paths for further investigation involving the development of new musical styles through computer-generated music and reactive computer improvisation.
Sociosonic Interventions: Distributed Authorship in Socially Engaged Sound Practices
Authors: Rennie Tullis
Published: September 2020

How do creative sound practices function in the context of socially engaged art? Toward developing a practical methodology, this paper focuses on sound-led projects that stage socially engaged art practice in community settings, including some involving the author. Aesthetics, ethics and politics are employed as interrogative lenses for distributed creative processes. Methods for collaborative art-making that facilitate a balance between these lenses are discussed, with the author further arguing the necessity of artistic “disruption.” Such sociosonic interventions are demonstrated to occur most effectively when sound practices challenge the paradigm of unidirectional audial reproduction: rupturing traditional hierarchies of creator and listener.
Ceratolejeunea panamensis (Lejeuneaceae, Marchantiophyta), a new species from Panama

Authors: FOSSATTI IRIS , BASTOS CID JOSÉ PASSOS , BENÍTEZ ÁNGEL
Published: September 2020

Ceratolejeunea panamensis is described from Chiriquí province, Panama. The new species is distinguished from other species of the genus Ceratolejeunea by its numerous, scattered ocelli (6-20) in the leaf lobes and the very shortly bifid, reniform underleaves.
Do Obese Patients Present With More Advanced Breast Cancer?
Authors: Wang Melinda , Huang Julian , Chagpar Anees B.
Published: September 2020

Background

Obesity is a known risk factor for breast cancer development; however, it is unclear whether obesity is associated with more aggressive disease. We sought to determine the relationship between obesity and tumor characteristics in breast cancer patients.

Methods

Medical records of invasive breast cancer patients undergoing mastectomy at our institution between January 2010 and April 2018 were reviewed. Patients who had received neoadjuvant therapy were excluded. Patients were separated into obese (body mass index [BMI] ≥ 30 kg/m2) and nonobese (BMI < 30 kg/m2) categories and compared using nonparametric statistical analyses.

Results

Of the 415 patients in this cohort, 124 (29.9%) were obese. Obese patients were more likely to present with larger tumors (tumor size ≥ 2 cm: 53.2% vs 41.0%, P = .024) and more node-positive disease (46.8% vs 28.9%, P = .001). Controlling for confounders, obesity was independently associated with node-positive disease (odds ratio [OR] = 2.00; 95% CI 1.24-3.21, P = .004), but not with tumor size ≥ 2 cm (OR = 1.38; 95% CI 0.87-2.21, P = .174).

Conclusion

Obesity is associated with node-positive disease at presentation independent of other factors.
Post-acquisition Performance Analysis of Indian Target Firms: The Role of Deal Characteristics
Authors: Kapil Sheeba , Barick Gaurav
Published: September 2020

The aim of this article is to identify and determine various dimensions of deal characteristics affecting the post-acquisition performance of Indian target firms. Available researches have focussed on the stock market reaction as the indicator of target firm performance. Nonetheless, various determinants are found to affect the post-acquisition performance of target firms. Bearing that in mind, this article focusses on the significance of deal characteristics while assessing the performance of the Indian target firms post-acquisition. The article attempts to analyse the post-acquisition performance of target firms independent of the acquirer firm to get a more appropriate perception of their position.

The change model, generalised method of moments (GMM) model and the regression model has been employed to assess the changes in operating performance, analyse the importance of financial variables in post-acquisition performance and study the impact of deal characteristics in the post-acquisition performance of the Indian target firms. The outcomes reveal that there has been a significant difference in the improvement of targets depending on whether it has been taken over by a domestic acquirer or inbound acquirer.
How State Presence Leads to Civil Conflict
Authors: Ying Luwei
Published: September 2020

Political scientists and policy-makers have long argued that state weakness leads to civil conflict while enhancing state power helps prevent violence. Why, then, has increased state capacity worldwide recently coincided with more civil conflicts? This study argues that enhanced state presence at the sub-national level—a symptom of growing state capacity—may induce violent resistance from the established non-state powers such as local leaders and communities in the short term. Empirically, I conduct two analyses, one at the province level and the other at the ethnic group level. To measure state presence, I use accuracy of census data in the first analysis and global ground transportation data in the second analysis. Results demonstrate that increased state presence triggers civil conflict, particularly in the first five years of such increasing state presence, and this effect is stronger in remote and ethnically heterogeneous regions. Evidence also suggests that ethnic groups settled in peripheral regions are prominent resisters to state penetration. This paper thus expands prior understanding of the role of state power in civil conflicts.
Constitutional Scholars as Constitutional Actors
Authors: Lazarus Liora
Published: September 2020

This article explores the idea that constitutional scholars may be thought of as constitutional actors analogous to integrity institutions and examines the normative implications of conceiving of constitutional scholars in this way. One implication of such an analogy is to strengthen academic freedom and protect the integrity and independence of constitutional scholarship. Moreover, viewing constitutional scholars as constitutional actors also sharpens our understanding of the ethical obligations of constitutional scholarship: of ‘academic self-awareness’ and of ‘decisional’ and ‘institutional’ independence. This duty of independence may be equally important to the public standing, expert status and integrity of the constitutional law discipline in this highly politicised populist moment.
Coexistence of Basaloid Squamous Cell Carcinoma and Large Cell Neuroendocrine Carcinoma in the Larynx: A Case Report and Literature Review
Authors: Wang Sanchun , Fang Hongyan , Tong Weifang , Wang Hongyan , Teng Bo
Published: September 2020

Basaloid squamous cell carcinoma and large cell neuroendocrine carcinoma are not common in head and neck, these tumors rarely occur in the larynx but both have highly aggressive clinical behavior and a high mortality rate. The diagnosis is complicated by these tumors’ atypical clinical and pathological features. This case details a coexistence of basaloid squamous cell carcinoma and large cell neuroendocrine carcinoma of a woman in the larynx. The patient underwent endoscopy- and coblation-assisted transoral microsurgery to achieve hyoid horizontal epiglottidectomy and has no recurrence after 12 months of follow-up.