bluuebunny/crossref_metadata_2025 huggingface dataset:
Liver Injury in Liver Transplant Recipients With Coronavirus Disease 2019 (COVID‐19): U.S. Multicenter Experience
Authors: Rabiee Atoosa , Sadowski Brett , Adeniji Nia , Perumalswami Ponni V. , Nguyen Veronica , Moghe Akshata , Latt Nyan L. , Kumar Sonal , Aloman Costica , Catana Andreea M. , Bloom Patricia P. , Chavin Kenneth D. , Carr Rotonya M. , Dunn Winston , Chen Vincent L. , Aby Elizabeth S. , Debes Jose D. , Dhanasekaran Renumathy ,   on behalf of the COLD Consortium
Published: September 2020

Background and Aims

Coronavirus disease 2019 (COVID‐19) is associated with liver injury, but the prevalence and patterns of liver injury in liver transplantation (LT) recipients with COVID‐19 are open for study.

Approach and Results

We conducted a multicenter study in the United States of 112 adult LT recipients with COVID‐19. Median age was 61 years (interquartile range, 20), 54.5% (n = 61) were male, and 39.3% (n = 44) Hispanic. Mortality rate was 22.3% (n = 25); 72.3% (n = 81) were hospitalized and 26.8% (n = 30) admitted to the intensive care unit (ICU). Analysis of peak values of alanine aminotransferase (ALT) during COVID‐19 showed moderate liver injury (ALT 2‐5× upper limit of normal [ULN]) in 22.2% (n = 18) and severe liver injury (ALT > 5× ULN) in 12.3% (n = 10). Compared to age‐ and sex‐matched nontransplant patients with chronic liver disease and COVID‐19 (n = 375), incidence of acute liver injury was lower in LT recipients (47.5% vs. 34.6%; P = 0.037). Variables associated with liver injury in LT recipients were younger age (P = 0.009; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.20‐3.54), Hispanic ethnicity (P = 0.011; OR, 6.01; 95% CI, 1.51‐23.9), metabolic syndrome (P = 0.016; OR, 5.87; 95% CI, 1.38‐24.99), vasopressor use (P = 0.018; OR, 7.34; 95% CI, 1.39‐38.52), and antibiotic use (P = 0.046; OR, 6.93; 95% CI, 1.04‐46.26). Reduction in immunosuppression (49.4%) was not associated with liver injury (P = 0.156) or mortality (P = 0.084). Liver injury during COVID‐19 was significantly associated with mortality (P = 0.007; OR, 6.91; 95% CI, 1.68‐28.48) and ICU admission (P = 0.007; OR, 7.93; 95% CI, 1.75‐35.69) in LT recipients.

Conclusions

Liver injury is associated with higher mortality and ICU admission in LT recipients with COVID‐19. Hence, monitoring liver enzymes closely can help in early identification of patients at risk for adverse outcomes. Reduction of immunosuppression during COVID‐19 did not increase risk for mortality or graft failure.
Safety and bleeding patterns of the levonorgestrel 52‐mg intrauterine system among women with thrombosis or coagulopathy
Authors: Brull Eliza P. , Fernandes Arlete , Monteiro Ilza , Bahamondes Luis , Juliato Cassia R. T.
Published: September 2020

Objective

To assess the safety of the levonorgestrel 52‐mg intrauterine system (LNG‐IUS) in women with a history of thrombosis or coagulopathy and to evaluate bleeding patterns.

Methods

A retrospective chart review was conducted of 117 women attending a clinic between 2007 and 2019. Their sociodemographic characteristics, hematologic status, reasons for using LNG‐IUS, duration of use, use of oral anticoagulants, complications, and bleeding patterns were analyzed.

Results

Ninety‐nine women had a history of thrombosis (71.7% in use of oral anticoagulants) and 18 had coagulopathies. No bleeding or any other complications occurred during placement of the LNG‐IUS. Around two‐thirds of the women reported amenorrhea or oligomenorrhea at 12, 24, and 54 months of follow‐up, with no difference between the groups using the IUS for contraception or to treat heavy menstrual bleeding (HMB) (P=0.07), those with a history of thrombosis or coagulopathy (P=0.53), and users or non‐users of oral anticoagulants (P=0.59).

Conclusion

The LNG‐IUS is safe for women with hematologic disorders. It was associated with amenorrhea or oligomenorrhea in a large proportion of users up to 54 months of follow‐up regardless of use of oral anticoagulants, reason for use of LNG‐IUS (contraception or HMB), or history of coagulopathy or thrombosis.
Recovery after enhanced versus conventional care laparoscopic hysterectomy performed in the afternoon: A randomized controlled trial
Authors: Kilpiö Olga , Härkki Päivi S. M. , Mentula Maarit J. , Väänänen Antti , Pakarinen Päivi I.
Published: September 2020

Objective

To compare enhanced recovery after surgery (ERAS) and conventional care (CC) protocols on outcomes of laparoscopic hysterectomy (LH) performed in the afternoon.

Methods

A single‐center randomized controlled trial was conducted on 120 women undergoing LH who were randomly divided into the intervention group (IG; n=60) and control group (CG; n=60). Women in the IG were treated according to the ERAS protocol and those in the CG according to the CC protocol. The primary outcome was the length of hospitalization. Secondary outcomes were postoperative opioid use, postoperative pain and emesis, complications, operative bleeding, and time.

Results

More women discharged during 24 hours in the IG than in the CG (88% vs 55%, P<0.001). The time to actual discharge (19 vs 22 hours, P<0.001) and ready‐to‐discharge time (15 vs 21 hours, P<0.001) were shorter and the use of oxycodone was lower (0 mg [0–0 vs 2.5 mg [0–10], P<0.001) in the IG than in the CG, respectively. Otherwise, no other significant differences between the groups were observed. The follow‐up time was one month.

Conclusion

The ERAS protocol reduces hospital stay and decreases the use of opioids with no impairment in surgical outcome of LH.

ClinicalTrials.gov: NCT03828981.
Endothelial Function and Oxidant Stress
Authors: Harrison David G.
Published: September 2020

Both endothelial cells and vascular smooth muscle cells are capable of producing reactive oxygen species from a variety of enzymatic sources. In disease states such as atherosclerosis and hypertension, vascular production of these reactive oxygen metabolites can increase substantially. Increases in the production of superoxide anion can lead to decreases in ambient levels of nitric oxide via a facile radical/radical reaction that occurs more rapidly than the reaction of superoxide anion with superoxide dismutase. This phenomenon alters endothelial regulation of vasomotion in a variety of disease conditions. Recent evidence suggests that the major source of vascular superoxide ion and hydrogen peroxide is a membrane‐bound, reduced nicotinamide‐adenine dinucleotide (NADH)‐dependent oxidase. The activity of this enzyme system is regulated by angiotensin II and is elevated following prolonged exposure to nitroglycerin. Alterations of vascular oxidant state caused by angiotensin II may contribute substantially to vascular pathology and may also provide a link between hypertension and atherosclerosis.
Low‐intensity pulsed ultrasound promotes the formation of periodontal ligament stem cell sheets and ectopic periodontal tissue regeneration
Authors: Li Han , Zhou Jie , Zhu Mengyuan , Ying Siqi , Li Lingjie , Chen Duanjing , Li Jie , Song Jinlin
Published: September 2020

Human periodontal ligament stem cells (hPDLSCs) sheets play an important role in periodontal tissue engineering. Low‐intensity pulsed ultrasound (LIPUS) has been reported as an effective stimulus to regulate cell biological behavior. The present study aims to explore the potential of LIPUS to promote the formation and function of hPDLSC sheets (hPDLSCSs). Hematoxylin–eosin (H&E) staining, western blot, real‐time PCR, alkaline phosphatase (ALP), and alizarin red staining were used to evaluate the formation and osteogenic effect of LIPUS on hPDLSCSs in vitro. Hydroxyapatite with or without hPDLSCSs was transplanted in the subcutaneous pockets on the back of nude mice and histological analysis was performed. H&E staining showed increased synthesis of extracellular matrix (ECM) and real‐time PCR detected a significant increase in ECM‐related genes after LIPUS treatment. In addition, LIPUS could promote the expression of osteogenic differentiation‐related genes and proteins. ALP and alizarin red staining also found LIPUS enhanced the osteogenesis of hPDLSCSs. After transplantation in vivo, more dense collagen fibers similar to periodontal ligament were regenerated. Collectively, these results indicate that LIPUS not only promotes the formation and osteogenic differentiation of hPDLSCSs but also is a potential treatment strategy for periodontal tissue engineering.
Poor Bone Quality is Associated With Greater Arterial Stiffness: Insights From the UK Biobank
Authors: Raisi-Estabragh Zahra , Biasiolli Luca , Cooper Jackie , Aung Nay , Fung Kenneth , Paiva José M , Sanghvi Mihir M , Thomson Ross J , Curtis Elizabeth , Paccou Julien , Rayner Jennifer J , Werys Konrad , Puchta Henrike , Thomas Katharine E , Lee Aaron M , Piechnik Stefan K , Neubauer Stefan , Munroe Patricia B , Cooper Cyrus , Petersen Steffen E , Harvey Nicholas C
Published: September 2020

Osteoporosis and ischemic heart disease (IHD) represent important public health problems. Existing research suggests an association between the two conditions beyond that attributable to shared risk factors, with a potentially causal relationship. In this study, we tested the association of bone speed of sound (SOS) from quantitative heel ultrasound with (i) measures of arterial compliance from cardiovascular magnetic resonance (aortic distensibility [AD]); (ii) finger photoplethysmography (arterial stiffness index [ASI]); and (iii) incident myocardial infarction and IHD mortality in the UK Biobank cohort. We considered the potential mediating effect of a range of blood biomarkers and cardiometabolic morbidities and evaluated differential relationships by sex, menopause status, smoking, diabetes, and obesity. Furthermore, we considered whether associations with arterial compliance explained association of SOS with ischemic cardiovascular outcomes. Higher SOS was associated with lower arterial compliance by both ASI and AD for both men and women. The relationship was most consistent with ASI, likely relating to larger sample size available for this variable (n = 159,542 versus n = 18,229). There was no clear evidence of differential relationship by menopause, smoking, diabetes, or body mass index (BMI). Blood biomarkers appeared important in mediating the association for both men and women, but with different directions of effect and did not fully explain the observed effects. In fully adjusted models, higher SOS was associated with significantly lower IHD mortality in men, but less robustly in women. The association of SOS with ASI did not explain this observation. In conclusion, our findings support a positive association between bone and vascular health with consistent patterns of association in men and women. The underlying mechanisms are complex and appear to vary by sex. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Angiotensin‐(1‐7) prevents T3‐induced cardiomyocyte hypertrophy by upregulating FOXO3/SOD1/catalase and downregulating NF‐ĸB
Authors: Senger Nathalia , C. Parletta Aline , Marques Bruno V. D. , Akamine Eliana H. , Diniz Gabriela P. , Campagnole‐Santos Maria J. , Santos Robson A. S. , Barreto‐Chaves Maria Luiza M.
Published: September 2020

Clinical studies have shown a correlation between thyroid disorders and cardiac diseases. High levels of triiodothyronine (T3) induce cardiac hypertrophy, a risk factor for cardiac complications and heart failure. Previous results have demonstrated that angiotensin‐(1‐7) is able to block T3‐induced cardiac hypertrophy; however, the molecular mechanisms involved in this event have not been fully elucidated. Here, we evidenced the contribution of FOXO3 signaling to angiotensin‐(1‐7) effects. Angiotensin‐(1‐7) treatment increased nuclear FOXO3 levels and reduced p‐FOXO3 levels (inactive form) in isolated cardiomyocytes. Knockdown of FOXO3 by RNA silencing abrogated the antihypertrophic effect of angiotensin‐(1‐7). Increased expression of antioxidant enzymes superoxide dismutase 1 (SOD1 and catalase) and lower levels of reactive oxygen species and nuclear factor‐κB (NF‐κB) were observed after angiotensin‐(1‐7) treatment in vitro. Consistent with these results, transgenic rats overexpressing angiotensin‐(1‐7) displayed increased nuclear FOXO3 and SOD1 levels and reduced NF‐κB levels in the heart. These results provide a new molecular mechanism responsible for the antihypertrophic effect of angiotensin‐(1‐7), which may contribute to future therapeutic targets.
Lead exposure results in defective behavior as well as alteration of gut microbiota composition in flies and their offsprings
Authors: Sun Yu , Tang Yi , Xu Xinwen , Hu Kehan , Zhang Zixiao , Zhang Yue , Yi Zhongyuan , Zhu Qihui , Xu Rui , Zhang Yumin , Liu Zhi , Liu Xingyin
Published: September 2020

Background

Lead (Pb) has become one of the most dangerous metals to human health, especially to the nervous system as its persistent accumulation and high toxicity. However, how the gut microbiota influence the Pb‐related neurotoxicity remains unclear. The aim of our study was to explore the link among Pb exposure, behavior changes, and gut microbiota.

Methods

Using Drosophila melanogaster as model, climbing assay, social avoidance, social space, and short‐term memory analysis were preformed to study the behavioral changes in flies exposed to Pb and their offspring. 16S rRNA sequencing was used to explore the changes in the gut microbiota of the flies with/without Pb‐exposure.

Results

The crawling ability, memory, and social interactions of Pb‐exposed parent flies decreased significantly. For the offspring, behaviors were more significantly affected in male offspring whose male parent was exposed to Pb. The alpha diversity and the beta diversity of gut microbiota were significantly different between the Pb‐exposed flies and the controls, as well as between the male offspring and the controls. Two genera, Lactobacillus and Bifidobacterium were found significantly decreased in the Pb‐exposed flies when compared to the controls and significantly correlated with the learning and memory. Four genera, Bilophila, Coprococcus, Desulfovibrio, and Ruminococcus were found depleted in the female offspring of the Pb‐exposed flies.

Conclusions

Lead exposure resulted in defective behavior and alteration of gut microbiota composition in flies and their offspring, alteration in gut microbiota might be the link between behavioral changes induced by Pb‐exposure.
Synthesis and anticancer evaluation of some new pyrazolo[3,4‐d][1,2,3]triazin‐4‐ones, pyrazolo[1,5‐a]pyrimidines, and imidazo[1,2‐b]pyrazoles clubbed with carbazole
Authors: Bondock Samir , Alqahtani Salwa , Fouda Ahmed M.
Published: September 2020

Carbazole represents as a promising template for cancer treatment as it exists in the skeleton of numerous man‐made and natural anticancer agents. In this regard, new sets of novel functionalized pyrazolo[3,4‐d][1,2,3]triazin‐4‐ones 6a‐e and 10a‐e, pyrazolo[1,5‐a]pyrimidines 16a,b and imidazo[1,2‐b]pyrazoles 20a,b and 23a‐c having carbazole moiety were efficiently synthesized, characterized, and mechanistically discussed. They were also evaluated against three human cancer cell lines (HCT‐116, HepG‐2, and MCF‐7) and one standard human cell line (REP1) for their in vitro anticancer activity. The results declared that seven compounds 10d, 10e, 12b, 12d, 12e, 16a, and 23a had potent anticancer activity, having IC50 values in the range 2.97 to 10.31 μM. The most effective compounds 10d and 10e inhibited the growth of all screened cancer cell lines and did not reveal human toxicity.
Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises and no primary energetic defect
Authors: Bérat Claire‐Marine , Montealegre Sebastian , Wiedemann Arnaud , Nuzum Malou Le Corronc , Blondel Amélie , Debruge Hugo , Cano Aline , Chabrol Brigitte , Hoebeke Célia , Polak Michel , Stoupa Athanasia , Feillet François , Torre Stéphanie , Boddaert Nathalie , Bruel Henri , Barth Magalie , Damaj Lena , Abi‐Wardé Marie‐Thérèse , Afenjar Alexandra , Benoist Jean‐François , Madrange Marine , Caccavelli Laure , Renard Perrine , Hubas Arnaud , Nusbaum Patrick , Pontoizeau Clément , Gobin Stéphanie , van Endert Peter , Ottolenghi Chris , Maltret Alice , de Lonlay Pascale
Published: September 2020

TANGO2 disease is a severe inherited disorder associating multiple symptoms such as metabolic crises, encephalopathy, cardiac arrhythmias, and hypothyroidism. The mechanism of action of TANGO2 is currently unknown. Here, we describe a cohort of 20 French patients bearing mutations in the TANGO2 gene. We found that the main clinical presentation was the association of neurodevelopmental delay (n = 17), acute metabolic crises (n = 17) and hypothyroidism (n = 12), with a large intrafamilial clinical variability. Metabolic crises included rhabdomyolysis (15/17), neurological symptoms (14/17), and cardiac features (12/17; long QT (n = 10), Brugada pattern (n = 2), cardiac arrhythmia (n = 6)) that required intensive care. We show previously uncharacterized triggers of metabolic crises in TANGO2 patients, such as some anesthetics and possibly l‐carnitine. Unexpectedly, plasma acylcarnitines, plasma FGF‐21, muscle histology, and mitochondrial spectrometry were mostly normal. Moreover, in patients' primary myoblasts, palmitate and glutamine oxidation rates, and the mitochondrial network were also normal. Finally, we found variable mitochondrial respiration and defective clearance of oxidized DNA upon cycles of starvation and refeeding. We conclude that TANGO2 disease is a life‐threatening disease that needs specific cardiac management and anesthesia protocol. Mechanistically, TANGO2 disease is unlikely to originate from a primary mitochondrial defect. Rather, we suggest that mitochondrial defects are secondary to strong extrinsic triggers in TANGO2 deficient patients.
Use of point‐of‐care molecular tests reduces hospitalization and oseltamivir administration in children presenting with influenza‐like illness
Authors: Dimopoulou Dimitra , Vourli Sophia , Douros Konstantinos , Pournaras Spyridon , Papaevangelou Vassiliki
Published: September 2020

Influenza is associated with increased morbidity, healthcare costs, hospitalization rates, and mortality in children. Rapid immunochromatography assay (ICA), a test with low sensitivity, is often used as point‐of‐care (POC) test. Recently, the rapid syndromic molecular test FilmArray has become available. This observational study aims to evaluate whether the use of FilmArray would decrease the use of antivirals and hospitalization rates among children presenting to the emergency room (ER) with influenza‐like illness (ILI) symptoms. Nasopharyngeal swabs were prospectively collected from children, aged 0–16 years, presenting with ILI at the ER of a tertiary hospital during the peak endemic period. Patients were allocated to be tested by either FilmArray or ICA. The use of antivirals and hospitalization rates were noted. Logistic regression models were used to investigate the impact of testing methods on decision‐making. Overall, 80 children were included (mean age: 5 years). Admissions were more likely to occur if an ICA test was performed (OR, 3.16; 95% CI, 1.01–9.82; p = .046). Oseltamivir administration was more likely among children who had undergone the ICA test (OR, 4.67; 95% CI, 1.06–20.43; p = .041). The implementation of rapid molecular test had no impact on complementary diagnostic testing or antibacterial prescription. The use of FilmArray significantly reduced both hospitalization and oseltamivir administration in children. Further knowledge on the use of POC tests is required to improve current management of children presenting with ILI and decrease associated healthcare costs.
One‐step quantitative RT‐PCR assay with armored RNA controls for detection of SARS‐CoV‐2
Authors: Goncharova Ekaterina A. , Dedkov Vladimir G. , Dolgova Anna S. , Kassirov Ilia S. , Safonova Marina V. , Voytsekhovskaya Yana , Totolian Areg A.
Published: September 2020

Coronavirus disease 2019 (COVID‐19) has become pandemic since March 11, 2020. Thus, development and integration in clinics of fast and sensitive diagnostic tools are essential. The aim of the study is a development and evaluation of a one‐step quantitative reverse transcription‐polymerase chain reaction (RT‐qPCR) assay (COVID‐19 Amp) for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) detection with an armored positive control and internal controls constructed from synthetic MS2‐phage‐based RNA particles. The COVID‐19 Amp assay limit of detection was 103 copies/ml, the analytical specificity was 100%. A total of 109 biological samples were examined using COVID‐19 Amp and World Health Organization (WHO)‐based assay. Discordance in nine samples was observed (negative by the WHO‐based assay) and discordant samples were retested as positive according to the results obtained from the Vector‐PCRrv‐2019‐nCoV‐RG assay. The developed COVID‐19 Amp assay has high sensitivity and specificity, includes virus particles‐based controls, provides the direct definition of the SARS‐CoV‐2 RdRp gene partial sequence, and is suitable for any hospital and laboratory equipped for RT‐qPCR.
Tailoring the radiotherapy approach in patients with anal squamous cell carcinoma based on inguinal sentinel lymph node biopsy
Authors: De Nardi Paola , Mistrangelo Massimiliano , Burtulo Giovanni , Passoni Paolo , Slim Najla , Ronzoni Monica , Canevari Carla , Parolini Danilo , Massimino Luca , Franco Pierfrancesco , Cassoni Paola , Lesca Adriana , Testa Valentina , Rosati Riccardo
Published: September 2020

Background and Objectives

The aim of our study was to analyze the results of selective inguinal node irradiation in patients with anal cancer, based on the biopsy of the inguinal sentinel lymph node (SLN), in terms of local control and prognosis.

Methods

Records of patients with anal squamous cell carcinoma from January 2001 to December 2016 were retrospectively reviewed. Tc99 lymphoscintigraphy was performed in all the clinically inguinal negative patients, followed by radio‐guided surgical removal of the inguinal SLN. All patients were treated with combined radiochemotherapy. In patients with negative sentinel nodes, the inguinal area was excluded in the radiotherapy field.

Results

A total of 123 patients, 76 females (61.8%), mean age 60.1 ± 12.19 years old, underwent intraoperative lymph node retrieval. The histological analysis showed metastasis in the SLN in 28 patients (22.8%). The mean follow‐up was 43.44 ± 31.86 months. No inguinal recurrence was observed in patients with negative inguinal sentinel node(s). A statistically significant difference was observed for overall and disease‐free survivals in a patient with positive and negative inguinal sentinel nodes.

Conclusions

In patients with anal canal cancer, the exclusion of the inguinal regions from the radiotherapy field, in patients with negative SLN, does not compromise locoregional control nor prognosis.
Applicability of capillary electrophoresis‐frontal analysis for displacement studies: Effect of several drugs on l‐tryptophan and lidocaine binding to human serum albumin
Authors: Nevídalová Hana , Michalcová Lenka , Glatz Zdeněk
Published: September 2020

The effective concentration of a drug in the blood, i.e. the concentration of a free drug in the blood, is influenced by the strength of drug binding onto plasma proteins. Besides its efficacy, these interactions subsequently influence the liberation, absorption, distribution, metabolism, excretion, and toxicological properties of the drug. It is important to not only determine the binding strength and stoichiometry, but also the binding site of a drug on the plasma protein molecule, because the co‐administration of drugs with the same binding site can affect the above‐mentioned concentration and as a result the pharmacological behavior of the drugs and lead to side effects caused by the change in free drug concentration, its toxicity. In this study, the binding characteristics of six drugs with human serum albumin, the most abundant protein in human plasma, were determined by capillary electrophoresis‐frontal analysis, and the obtained values of binding parameters were compared with the literature data. The effect of several drugs and site markers on the binding of l‐tryptophan and lidocaine to human serum albumin was investigated in subsequent displacement studies which thus demonstrated the usability of capillary electrophoresis as an automated high‐throughput screening method for drug‐protein binding studies.
Weather Influences Multiple Components of Greater Prairie‐Chicken Reproduction
Authors: Londe David W. , Elmore R. Dwayne , Davis Craig A. , Fuhlendorf Samuel D. , Hovick Torre J. , Luttbeg Barney , Rutledge Jimmy
Published: September 2020

The influence of weather on wildlife populations has been documented for many species; however, much of the current literature has focused on the effects of weather within a season and consists of short‐term studies. The use of long‐term datasets that cover a variety of environmental conditions will be essential for assessing possible carry‐over effects of weather experienced in one season on behavior and fitness in subsequent seasons. In this study, we evaluated the effects of weather variables measured over multiple temporal scales on the reproductive performance and behavior of greater prairie‐chickens (Tympanuchus cupido) in Osage County, Oklahoma, USA, from 2011–2019. Considering weather over a range of temporal extents allowed us to determine the relative importance of short‐term weather events, such as daily temperature and precipitation, versus more chronic shifts in weather such as persistent drought on the reproductive performance of greater prairie‐chickens. We used an information‐theoretic model building approach to develop models describing the effects of daily weather variables and drought conditions on daily nest survival, nest incubation start dates, and clutch size. Daily nest survival was primarily influenced by conditions experienced during incubation with daily nest success declining in years with wetter than average springs and during extreme precipitation events. Daily nest survival also declined under higher maximum daily temperatures, especially in years with below‐average rainfall. Greater prairie‐chickens began nesting earlier and had smaller clutch sizes for initial nests and renests in years with warmer temperatures prior to the nesting season. Additionally, incubation of nests started later in drought years, indicating carry‐over effects in greater prairie‐chicken reproductive behaviors. Our work shows that if the weather in the Great Plains becomes more variable, with increasing frequency of drought and extreme precipitation events, wildlife species that inhabit these grassland landscapes will likely experience changes in reproduction, potentially influencing future populations. © 2020 The Wildlife Society.
The association of weather, temperature, and holidays on pediatric maxillofacial trauma
Authors: Rabbani Cyrus C. , Kao Richard , Shin Timothy J. , Burgeson Jack E. , Ting Jonathan Y. , Sim Michael W. , Shipchandler Taha Z.
Published: September 2020

Objective

To evaluate the association of weather, seasons, months and holidays on the frequency and pattern of pediatric facial fractures.

Methods

Retrospective review of pediatric patients treated for facial fractures at two Level I trauma centers in a midsize Midwestern US city over a 5‐year period. Patients were included only if presentation was within 3 hours of inciting trauma, transfers from other facilities were excluded. Demographic characteristics, fracture patterns, operative interventions, weather data, and local public school schedules were acquired and associations were analyzed with unpaired t tests, χ2, multivariate and binomial regression model analyses.

Results

Two hundred and sixty patients were included. The average age (SD) was 11.8 (5.0) years, with 173 males and 87 females. The highest distribution of presentations occurred in the summer season (35.0%), on weekends and holidays (58.1%), and when the weather was described as clear (48.5%). The most common mechanisms of injury were motor vehicle collisions (25.8%), followed by sports—(21.5%) and assault—(16.5%) related injuries. Mechanisms were significantly associated with certain fracture patterns. Older age was associated with fewer orbital fractures (P < .01). Seventy‐five patients (28.8%) required operative intervention. Age was found to impact the likelihood of operative intervention (Exp(β) = 1.081, P = .03) while weather, temperature, and mechanism did not.

Conclusion

Pediatric facial fractures are linked to warmer weather with clear skies and warmer season. Age predicts some fracture patterns and need for operative intervention. These results can be used to inform public health interventions, policymaking, and trauma staffing.

Level of Evidence: Level 2b (retrospective cohort).
Highly enriched N‐containing organic molecules of Synechococcus lysates and their rapid transformation by heterotrophic bacteria
Authors: Zheng Qiang , Lin Wenxin , Wang Yu , Li Yunyun , He Chen , Shen Yuan , Guo Weidong , Shi Quan , Jiao Nianzhi
Published: September 2020

Phytoplankton are major contributors of labile dissolved organic matter to marine euphotic zone ecosystems. Viral‐mediated phytoplankton lysis releases a considerable amount of bioavailable cellular contents and facilitates localized heterotrophic bacterial growth. The rapid turnover times of this labile organic matter renders it difficult to trace their transformation within natural environments. In the present study, we used a model phototroph‐heterotroph coculture system to investigate the organic molecular variation during cyanophage‐induced Synechococcus lysis and post‐lysis periods using fluorescence spectroscopy and ultrahigh resolution mass spectrometry analyses. Approximately 80% of the Synechococcus lysates were respired to carbon dioxide within 2 days coupled to rapid regeneration of inorganic nutrients. Five fluorescent dissolved organic matter components were detected in the incubations including four humic‐like and one protein‐like components, and their abundances varied markedly with the succession of the viral lysis process. Viral lysis promoted the transformation of Synechococcus biomass to dissolved organic matter, and heterotrophic bacterial metabolism facilitated the transformation of organic molecules from relatively high (avg. ~ 430 Da) to low (avg. ~ 360 Da) molecular weight, corresponding to variation in their bioavailability. The Synechococcus‐derived organic matter was highly enriched in N‐containing organic molecules. Identified metabolites within the cultures primarily comprised amino acids or oligopeptides and other low‐molecular‐weight organic acids, carbohydrates, nucleotides, lipids, biogenic amines, and porphyrins. Among these, oligopeptides, nucleotides, and lipid compounds significantly increased with viral lysis. These results provide insight into biogeochemical cycling mediated by viral shunts in oceans, thus deepening our understanding of microbial food webs at the molecular level.
A method to measure marine particle aggregate disruption in situ
Authors: Ackleson Steven G. , Rau Matthew J.
Published: September 2020

Particle aggregation within aquatic environments is a primary factor controlling the vertical flux of suspended matter. The aggregation process is controlled by the rate of particle interaction, enhanced by turbulent motions and differential settling, and the probability that particles making contact will stick together. The larger the particle aggregate, the faster it will sink. We describe a new and novel method to measure the state of particle aggregation in situ as a function of turbulent energy using an inexpensive attachment, the in situ dis‐aggregation system (iDAS), to a commercially available particle size instrument, a Sequoia Scientific LISST‐100X. A small chamber is attached to the instrument tand sample is drawn into the chamber using an inexpensive, variable speed thruster designed for remotely operated underwater vehicles. Ambient water drawn into the sample chamber passes through a flexible tube of defined diameter and length. The flow velocity through the tube and tube dimensions are used to estimate the turbulent energy that particles experience. As turbulence increases, particle aggregations disrupt, shifting the size distribution towards smaller particles. The method was tested under controlled laboratory conditions using standard test clay material and within several coastal environments along the East Coast of the United States. In all instances, particle aggregations are shown to disrupt as turbulence increases, causing the particle size distribution to shift toward smaller fractured aggregates and component particles. The iDAS can be used to directly measure the aggregation state of suspended material and potentially to estimate the bonding strength between aggregated particles of different type.
Fractional‐Pixel CO2 Laser Treatment in Patients With Urodynamic Stress Urinary Incontinence: 1‐Year Follow‐Up
Authors: Alcalay Menachem , Ben Ami Moshe , Greenshpun Anatoly , Hagay Zion , Schiff Eyal
Published: September 2020

Background and Objectives

Vaginal pixelated low power and long pulses (LPLP) CO2 laser has been suggested as an optional treatment for stress urinary incontinence (SUI) with many studies reporting short‐term improvements. The objective of this study was to assess the 1‐year subjective and objective efficacy of vaginal CO2 laser in women with urodynamic SUI.

Study Design/Materials and Methods

This was a prospective multicenter study. Patients with confirmed urodynamic SUI graded as mild or moderate were included. We used three sessions of fractional pixelated CO2 laser for vaginal application and followed up the patients at 6 and 12 months. We used the following measures at follow‐up: 1‐hour pad test (ICS protocol), questionnaires including Pelvic Floor Distress Inventory 20 (PFDI‐20), Pelvic Floor Impact Questionnaire (PFIQ), Patient Global Impression of Improvement (PGI‐I), and a 3‐day urinary diary. The urodynamic assessment was repeated at 6 months.

Results

Fifty‐two patients with SUI had three laser treatments, of whom 48 completed a 6‐month follow‐up and 42 patients completed 12‐month follow‐up. No serious adverse events were recorded during the study period. A significant reduction on the 1‐hour pad test was found from baseline (6.3 ± 1.6 g) to the 12‐month follow‐up (3.7 ± 1.4 g, P < 0.05) was found. PGI‐I showed 75.0%, 61.9%, and 64.3% improvements at 3, 6, and 12 months, respectively. PFDI improved significantly and consistently from baseline until 12 months (37.2 ± 3.89 to 16.1 ± 3.7, P < 0.05). Similarly, PFIQ showed significant improvements from the first treatment up to 12 months. Urodynamic assessment at 6 months showed that 41.4% of patients had no stress incontinence.

Conclusion

The vaginal CO2 laser was found to be effective for mild‐to‐moderate SUI over a follow‐up period of 1 year, according to a variety of objective and subjective parameters. The wide range of parameters enables optimal patient consultation and subsequent treatment. Lasers Surg. Med. © 2020 Wiley Periodicals LLC
Direct Polymerization Approach to Synthesize Acid‐Degradable Block Copolymers Bearing Imine Pendants for Tunable pH‐Sensitivity and Enhanced Release
Authors: Hu Xiaolei , Oh Jung Kwon
Published: September 2020

The development of effective approaches to synthesize smart amphiphilic block copolymers (ABPs) exhibiting acid‐responsive degradation through the cleavage of acid‐labile imine bonds is extensively explored for controlled release of encapsulated biomolecules, particularly in drug delivery. Here, a new approach based on direct polymerization utilizing a controlled radical polymerization technique to synthesize acid‐degradable ABPs bearing pendant imine linkages in hydrophobic block is reported. The approach centers on the synthesis of a novel methacrylate bearing benzoic imine group that can be polymerized to form the hydrophobic imine pendant block. The formed ABPs respond to mild acidic pHs equivalent to tumoral and endosomal/lysosomal acidic environments. This causes the dissociation of self‐assembled nanoassemblies through change in their hydrophilic/hydrophobic balance upon the cleavage of pendant imine linkages to the corresponding aldehyde and primary amine, thus leading to the enhanced release of encapsulated drugs. The proof‐of‐concept results suggest that this robust approach is versatile to further design advanced nanoassemblies responding to dual/multiple stimuli, thus being more effective to intracellular drug delivery.
Orthostatic Hypotension: A Prodromal Marker of Parkinson's Disease?
Authors: Dommershuijsen Lisanne J. , Heshmatollah Alis , Mattace Raso Francesco U.S. , Koudstaal Peter J. , Ikram M. Arfan , Ikram M. Kamran
Published: September 2020

Background

Orthostatic hypotension is common in patients with Parkinson's disease (PD). However, it remains unknown whether orthostatic hypotension is a marker of prodromal PD or more advanced disease. The objectives of this study were to assess whether orthostatic hypotension is a prodromal marker of PD in the general population.

Methods

This study was embedded in the Rotterdam Study, a large prospective population‐based cohort in the Netherlands. We measured orthostatic hypotension in 6910 participants. First, we determined the relation between prevalent PD and orthostatic hypotension using logistic regression. Second, we followed PD‐free participants for the occurrence of PD until 2016 and studied the association between orthostatic hypotension and the risk of PD using Cox proportional hazards models. All models were adjusted for age and sex.

Results

At baseline, the mean age ± standard deviation of the study population was 69.0 ± 8.8 years, and 59.1% were women. Orthostatic hypotension was present in 1245 participants (19.8%), and 62 participants (1.0%) had PD at the time of orthostatic hypotension measurement. Participants with PD were significantly more likely to have orthostatic hypotension (odds ratio, 1.88; 95% confidence interval, 1.09–3.24). During a median (interquartile range) follow‐up of 16.1 years (8.5–22.7 years), 122 participants were diagnosed with incident PD. Orthostatic hypotension at baseline was not associated with an increased risk of PD (hazard ratio, 0.97; 95% confidence interval, 0.59–1.58).

Conclusions

Our study suggests that orthostatic hypotension is common in patients with PD, but that orthostatic hypotension is not associated with an increased risk of PD and thus is not a prodromal marker of PD in the general population. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
The genetic basis for the inverse relationship between rheumatoid arthritis and schizophrenia
Authors: Zamanpoor Mansour , Ghaedi Hamid , Omrani Mir Davood
Published: September 2020

Introduction

Rheumatoid arthritis is a common autoimmune disease and schizophrenia is a relatively common and debilitating neurological disorder. There are several common features between rheumatoid arthritis and schizophrenia. The inverse relationship between rheumatoid arthritis and schizophrenia has been replicated in several studies. Despite evidence for an inverse epidemiological relationship and negative correlations for risk between rheumatoid arthritis and schizophrenia, there are no biological data that directly support this inverse relationship.

Materials and Methods’

We meta‐analyzed the genome‐wide association studies to investigate the shared association loci between rheumatoid arthritis and schizophrenia at the genome‐wide scale. Rheumatoid arthritis‐ and schizophrenia‐associated loci in most recent genome‐wide association studies of rheumatoid arthritis and schizophrenia were tested. Genetic risk score analysis was also conducted to investigate the collective contribution of schizophrenia risk loci to rheumatoid arthritis risk.

Results

Rheumatoid arthritis and schizophrenia meta‐genome‐wide association study showed a significant peak at the major histocompatibility complex locus on chromosome 6 in both rheumatoid arthritis‐schizophrenia meta‐genome‐wide association study and inverted meta‐genome‐wide association study datasets. Testing rheumatoid arthritis‐ and schizophrenia‐associated loci outside the human leukocyte antigen region showed no association with both rheumatoid arthritis and schizophrenia at a genome‐wide level of significance. Weighted genetic risk scores showed no evidence for a statistically significant association between rheumatoid arthritis and schizophrenia.

Conclusion

The finding of our study is consistent with the role of the major histocompatibility complex locus in the genetic correlation between rheumatoid arthritis and schizophrenia, and suggests that either schizophrenia has an autoimmune basis and/or rheumatoid arthritis has an active neurological component.
REDBot: Natural language process methods for clinical copy number variation reporting in prenatal and products of conception diagnosis
Authors: Liu Mengmeng , Zhong Yunshan , Liu Hongqian , Liang Desheng , Liu Erhong , Zhang Yu , Tian Feng , Liang Qiaowei , Cram David S. , Wang Hua , Wu Lingqian , Yu Fuli
Published: September 2020

Background

Current copy number variation (CNV) identification methods have rapidly become mature. However, the postdetection processes such as variant interpretation or reporting are inefficient. To overcome this situation, we developed REDBot as an automated software package for accurate and direct generation of clinical diagnostic reports for prenatal and products of conception (POC) samples.

Methods

We applied natural language process (NLP) methods for analyzing 30,235 in‐house historical clinical reports through active learning, and then, developed clinical knowledge bases, evidence‐based interpretation methods and reporting criteria to support the whole postdetection pipeline.

Results

Of the 30,235 reports, we obtained 37,175 CNV‐paragraph pairs. For these pairs, the active learning approaches achieved a 0.9466 average F1‐score in sentence classification. The overall accuracy for variant classification was 95.7%, 95.2%, and 100.0% in retrospective, prospective, and clinical utility experiments, respectively.

Conclusion

By integrating NLP methods in CNVs postdetection pipeline, REDBot is a robust and rapid tool with clinical utility for prenatal and POC diagnosis.
Targeted muscle reinnervation at the time of amputation in the management of complex regional pain syndrome of the lower extremity
Authors: Stoehr Jenna R. , Sood Rachita , Jordan Sumanas W. , Dumanian Gregory A.
Published: September 2020

Background

Complex regional pain syndrome (CRPS) is a chronic, posttraumatic condition defined by severe pain and sensorimotor dysfunction. In cases of severe CRPS, patients request amputation, which may cause phantom limb pain (PLP) and residual limb pain (RLP). Targeted muscle reinnervation (TMR) reduces the risk of PLP and RLP. This report describes the use of TMR at the time of amputation in a series of patients with CRPS.

Patients and methods

Four patients (ages 38–71 years) underwent TMR at the time of amputation for CRPS between April 2018 and January 2019. Three patients had a history of trauma and surgery to the affected limb. All patients attempted pharmacologic and interventional treatments for 1–7 years before requesting amputation. Three patients underwent below‐knee amputations (BKA) and one had an above‐knee amputation (AKA). Target muscles included the soleus, gastrocnemius, and flexor hallucis longus (BKA), and semitendinosus, biceps femoris, and vastus medialis (AKA). Postoperative phantom and residual limb pain symptoms were collected via a telephone survey adapted from the Patient‐Reported Outcomes Measurement Information System (PROMIS).

Results

There were no complications related to the TMR procedure. Average follow‐up time was 12.75 months. Patients reported varied outcomes: two had RLP and PLP, one had RLP only, and one had PLP only. All patients reported successful prosthetic use.

Conclusion

TMR may be performed at the time of amputation for CRPS. Further study is necessary to determine the effect of TMR on pain, pain medication use, prosthesis use, and other domains of function.
Distance‐based invariants of zigzag polyhex nanotube
Authors: Ahmad Haseeb , Hussain Muhammad , Nazeer Waqas , Chu Yu‐Ming
Published: September 2020

Hosoya polynomial is a vertex‐distance based polynomial highly consigned with Wiener and hyper‐Wiener index. Nanotubes are the nano scale material which can be used to explain novel attributes like highlights contrasted and expanded quality conductivity of material. In this paper, we presented the Hosoya polynomial and Harary polynomial for zigzag polyhex nanotube TUHC6. Moreover, some distance‐dependent indices, for example, generalized Harary index, modified Wiener index, and modified hyper‐Wiener index, are also computed for zigzag polyhex nanotubes TUHC6.
Food Structure Modulates the Bioavailability of Triglycerides and Vitamin D, and Partly That of Lutein: A Randomized Trial with a Crossover Design in Adults
Authors: Gleize Béatrice , Hiolle Manon , Meunier Nathalie , Pereira Bruno , Richard Ruddy , Savary‐Auzeloux Isabelle , Buffière Caroline , Peyron Marie‐Agnès , Halimi Charlotte , Caris‐Veyrat Catherine , Nau Françoise , Reboul Emmanuelle
Published: September 2020

Scope

The specific effect of the food matrix structure on fat‐soluble micronutrient bioavailability is only partly understood. Evaluating fat‐soluble micronutrient bioavailability after consumption of foods displaying similar composition but different structure is aimed at.

Methods and results

Twelve healthy subjects are enrolled in a randomized, open label, crossover postprandial trial. Four different model foods are tested: custard, pudding, sponge cake, and biscuit. Vitamin D3, lutein, and triglyceride chylomicron responses, evaluated as postprandial areas under the curve, are then assayed. Custard triglyceride response is higher than pudding and biscuit responses (up to +122.7%, p < 0.0001). Sponge cake vitamin D3 response is higher than biscuit response (+26.6%, p = 0.047). No difference between the model foods are observed regarding lutein responses. Triglyceride responses peak at 3 h for all conditions, while vitamin D3 and lutein peaks are delayed by 1 h with the biscuit matrix compared to other model foods.

Conclusion

Food structure can significantly impact on triglyceride and vitamin D3 bioavailability in terms of absorbed amounts and/or maximum absorption time. The data highlight positive correlations between triglyceride, vitamin D, and lutein nutrient responses. These results are of particular interest to develop functional foods for population subgroups such as the elderly.