bluuebunny/crossref_metadata_2025 huggingface dataset:
A Phase 2, Double‐Blind, Placebo‐Controlled Trial to Investigate Potential Drug‐Drug Interactions Between Cannabidiol and Clobazam
Authors: VanLandingham Kevan E. , Crockett Julie , Taylor Lesley , Morrison Gilmour
Published: July 2020

We investigated the effects of cannabidiol (CBD; 21‐day maintenance dose) on the pharmacokinetics (PK) of clobazam (CLB) and monitored the safety of CBD (or placebo) plus CLB in 20 patients with uncontrolled epilepsy on stable doses of CLB. Blood samples collected until 24 hours postdose were evaluated by liquid chromatography tandem mass spectrometry. PK parameters of CLB and major metabolite N‐desmethylclobazam (N‐CLB), valproic acid, stiripentol, levetiracetam, topiramate, plant‐derived highly purified CBD (Epidiolex in the United States; 100 mg/mL oral solution) and its major metabolites were derived using noncompartmental analysis. There was no evidence of a drug‐drug interaction (DDI) between CBD and CLB: geometric mean ratio (GMR) of day 33:day 1 CLB was 1.0 (90%CI, 0.8‐1.2) for Cmax and 1.1 (90%CI, 0.9‐1.2) for AUCtau. There was a significant DDI between CBD and N‐CLB: the GMR of day 33:day 1 N‐CLB was 2.2 (90%CI, 1.4‐3.5) for Cmax and 2.6 (90%CI, 2.0‐3.6) for AUCtau. Placebo had no effect on CLB or N‐CLB; CBD had no effect on levetiracetam. Data were insufficient regarding DDIs with other antiepileptic drugs. The safety profile of CBD (20 mg/kg/day) with CLB was acceptable; all but 1 adverse events (AEs) were mild or moderate. One serious AE (seizure cluster) led to CBD discontinuation. One patient withdrew after intolerable AEs. Although there was no evidence of a CBD and CLB DDI, there was a significant DDI between CBD and N‐CLB. The safety profile of GW Pharmaceuticals’ CBD formulation with CLB was consistent with other GW‐sponsored trials.
How engineering students use domain knowledge when problem‐solving using different visual representations
Authors: Johnson‐Glauch Nicole , Choi Dong San , Herman Geoffrey
Published: July 2020

Background

Engineering students commonly learn domain knowledge by engaging with visual representations of it. However, at times they have trouble accessing information from these representations due to the way information is encoded in features of the representation.

Purpose

To describe how students engage with representation features, we explored two research questions: (a) what is the interplay between how concepts are encoded within representations, students' use of those concepts, and how students translate between representations during their problem‐solving and (b) how is the interplay described in Research Question 1 similar and different across students in statics versus those in digital logic?

Design/Method

We synthesized findings from two of our prior research studies using the constant comparative method. We described the effect of representations on students' ability to access and use domain knowledge during problem‐solving within and across engineering disciplines.

Results

We identified three themes that describe how visual representations affect students’ reasoning. First, students conflated concepts that were represented using similar features. Second, students consistently failed to use concepts that were not represented with visually salient features. Third, statics students coordinated multiple representations when translating between representations during problem‐solving more often than the digital logic students.

Conclusions

These themes provide possible domain‐general pathways for redesigning the notation and representations that we use to teach engineering concepts and suggest future avenues of research to further explore the generality of these findings.
Opportunities and challenges in the management of celiac disease in Asia
Authors: Agarwal Ashish , Chauhan Ashish , Ahuja Vineet , Makharia Govind K
Published: July 2020

Although once considered uncommon, there is increasing recognition of celiac disease (CeD) in Asia. It is now clear that CeD is a disorder as frequent in certain Asian countries as that in western countries, although it often remains undiagnosed. With increasing awareness and diagnosis, the absolute numbers of celiac patients are expected to increase markedly in Asia. Asia, with 60% of the population of the world, is probably the major “reservoir” of undiagnosed CeD in the world. As Asia has a huge landscape along with highly heterogenous genetic, social, cultural, and nutritional practices, similar heterogeneity is seen in the epidemiology, diagnostic, and therapeutic facilities for CeD in Asia. In this article, we have reviewed the changes in the epidemiology, diagnostics, and management of CeD in Asia and summarized the challenges and opportunities for its emergence in Asia.
Does adjuvant treatment improve prognosis after curative resection of ampulla of Vater carcinoma? A multicenter retrospective study
Authors: Kim Hyung Sun , Jang Jin‐Young , Yoon Yoo‐Seok , Park Sang‐Jae , Kwon Wooil , Kim Sun‐Whe , Han Ho Seong , Han Sung‐Sik , Park Joon Seong , Yoon Dong Sup
Published: July 2020

Background/Purpose

Ampulla of Vater (AoV) carcinoma is a rare tumor that accounts for approximately 0.2% of gastrointestinal malignancies. There are no clinical guidelines concerning the treatment of AoV carcinoma. This study aimed to investigate the effectiveness of adjuvant treatment in AoV carcinoma following curative resection and define the “high‐risk” group.

Methods

Clinical data of patients who underwent curative resection for AoV carcinoma in four hospitals, namely Yonsei Gangnam Severance Hospital, Seoul National University Hospital, Seoul National University Bundang Hospital, and National Cancer Center (n = 651; 2002–2015), were reviewed. Overall survival (OS) and recurrence‐free survival (RFS) rates were compared using Kaplan–Meier estimates.

Results

Data of 651 patients who had undergone curative resection were retrospectively reviewed. Age, T stage, N stage, and differentiation type remained strong and independent risk factors for RFS and OS. In early‐stage AoV carcinoma (T1N0, T2N0), the non‐adjuvant group had better prognosis based on the RFS and OS than the adjuvant group (P < .001, P = .007). In advanced T stage (T3N0, T4N0), the adjuvant group had better prognosis than the non‐adjuvant group, but the difference was not statistically significant (P > .05). In node‐positive patients (any T, N1/2), adjuvant treatment did not affect RFS and OS (P > .05).

Conclusions

Adjuvant treatment after curative resection of AoV carcinoma is not associated with improved survival. The high‐risk group (node‐positive or advanced T stage (T3, T4)) treated with adjuvant treatment was not statistically associated with improved survival; however, our study showed that the adjuvant treatment for the high‐risk group might help achieve better patient outcome.
Structural elucidation of V‐type nerve agents by liquid chromatography/electrospray ionization mass spectrometry
Authors: Shamai Yamin Tamar , Prihed Hagit , Madmon Moran , Blanca Merav , Weissberg Avi
Published: July 2020

V‐nerve agents present information‐poor spectra, both in GC‐EI‐MS and LC‐ESI‐MS/MS, with dominant fragments/product ions corresponding to the amine‐containing residue. Hence, derivatives/isomers with the same amine residue exhibit similar mass spectral patterns, leading to ambiguity in the phosphonate structure. We present a simple approach for their structural elucidation based on two complementary experiments: ESI‐MS/MS of the original compound, which provides information about the amine moiety, and ESI‐MS/MS of the phosphonic acid hydrolysis products generated by N‐iodosuccinimide, which provides ions' characteristic of the phosphonate structure. This approach enables the structural elucidation of the original V‐agents with a higher degree of certainty.
Genetic variants in IL4RA, IL6, and IL12B genes and susceptibility to hepatitis B and C virus infections among Iraqi patients
Authors: Al‐Saffar Osama B. , Ad'hiah Ali H.
Published: July 2020

Hepatitis B and C viruses (HBV and HCV) are common causative pathogens of viral hepatitis. Progression of both infections is determined by virus‐ and host‐related factors. Cytokines are important host genetic factors that may have a predisposing role in HBV and HCV infections. This case‐control study evaluated the genetic association of IL4RA+1902 (rs1801275), IL6−174 (rs1800795), IL6−597 (rs1800797), and IL12B−1188 (rs3212227) variants with chronic HBV and HCV infections among Iraqi patients. A total of 220 viral hepatitis patients were enrolled in the study (113 HBV and 107 HCV), together with 141 healthy subjects. Sequence‐specific primer polymerase chain reaction assay was the genotyping method. Results revealed that under a dominant genetic model, IL6−174 variant was significantly associated with HBV infection, whereas no association with the HCV risk was reported. However, the risk for both infections was markedly associated with IL6−597 variant under recessive, dominant, and codominant genetic models. Estimation of IL6−174‐IL6−597 haplotypes depicted that G‐A haplotype was significantly associated with an increased risk to develop HBV infection, whereas a significantly decreased risk was associated with G‐G and C‐G haplotypes. For HCV, G‐G and C‐A haplotypes were significantly associated with risk of HCV infection. IL4RA+1902 and IL12B−1188 variants showed no association with HBV or HCV risk. Analysis of variance revealed no significant association between genotypes of the four determined single‐nucleotide polymorphisms and HBV or HCV viral load. In conclusion, the study supports the concept that IL6−597 variant is associated with susceptibility to HBV and HCV infections among Iraqis. The risk of HBV infection is further associated with IL6−174 variant.
Prognostic impact of tumor location in resected gallbladder cancer: A national cohort analysis
Authors: Lafaro Kelly , Blakely Andrew M. , Melstrom Laleh G. , Warner Susanne G. , Lee Byrne , Singh Gagandeep , Fong Yuman , Raoof Mustafa
Published: July 2020

Background and Objectives

Tumor location (peritoneal vs hepatic) has been incorporated in the 8th edition of the American Joint Committee on Cancer Staging system for gallbladder cancer. However, larger studies are needed to confirm the prognostic impact of tumor location.

Methods

Patients with pathologically‐confirmed gallbladder cancer with information on primary tumor location were included from the National Cancer Database (2009‐2012). We compared patients with hepatic‐side tumors to those on the peritoneal side. Survival data were plotted using the Kaplan‐Meier method. Prognostic factors were modeled with a multivariate Cox Proportional Hazards Model. Primary outcome was overall survival (OS).

Results

A total of 1251 patients were included. In comparison to patients with peritoneal‐sided tumors, patients with hepatic‐sided tumors were more likely to: be of higher pT stage (pT3: 49% vs 24%; P < .001); node positive (31% vs 24%; P = .016); undergo liver resection (53% vs 25%; P < .001); or have positive margins (29% vs 16%; P < .001). However, on multivariate analysis, there was no difference in OS between the groups (HR, 0.97; 95% CI, 0.79‐1.18; P = .753). Liver resection was associated with improved survival regardless of tumor location in pT2 tumors (peritoneal: HR, 0.57; P = .034; hepatic: HR, 0.67; P < .001).

Conclusions

This study failed to demonstrate the independent prognostic value of primary tumor location in patients with gallbladder cancer.
A Longitudinal Analysis of Outcomes in Tracheostomy Placement Among Preterm Infants
Authors: Wood William , Wang Cynthia S. , Mitchell Ron B. , Shah Gopi B. , Johnson Romaine F.
Published: July 2020

Objectives

To study a case series of preterm and extremely preterm infants, comparing their decannulation and survival rates after tracheostomy.

Methods

We performed a single‐institution longitudinal study of preterm infants with a tracheostomy. Infants were categorized as premature (born > 28 weeks and < 37 weeks) and extremely premature (born ≤ 28 weeks). Decannulation and survival rates were determined using the Kaplan–Meier method. Neurocognitive quality of life (QOL) was reported as normal, mild/moderately, and severely impaired. Statistical significance was set at P < .05.

Results

This study included 240 patients. Of those, 111 were premature and 129 were extremely preterm. The median age (interquartile range) at tracheostomy was 4.8 months (0.4). Premature infants were more likely than extremely preterm to have airway obstruction (54% vs. 32%, P < .001); whereas extremely preterm infants were more likely to have bronchopulmonary dysplasia (68% vs. 15%, P < .001) and to be ventilation‐dependent (68% vs. 54%, P < .001). The 5‐year decannulation rate for premature infants was 46% and for extremely preterm was 64%. The 5‐year survival rate post‐tracheostomy for preterm was 79% and for extremely preterm was 73%. The log‐rank test of equality showed that decannulation and survival were similar (P > .05) for both groups, even after controlling for potentially confounding factors like race, age, gender, birth weight, and age at tracheostomy. For neurocognitive QOL, 47% of patients survived with severely impaired QOL after tracheostomy. Preterm had 56% with severely impaired QOL and extremely preterm had 40% with severely impaired QOL (P = .03).

Conclusion

This study demonstrated that the time to decannulation and the likelihood of survival did not vary among premature and extremely premature infants even when controlling for other confounding variables.

Level of Evidence

3b Laryngoscope, 131:417–422, 2021
Antibiotic eluting sinus stents
Authors: Thompson Harrison M. , Lim Dong‐Jin , Banks Catherine , Grayson Jessica W. , Ayinala Samrath , Cho Do‐Yeon , Woodworth Bradford A.
Published: July 2020

Objectives

Chronic rhinosinusitis (CRS) is a multifactorial disease affecting up to 16% of the United States population and disproportionately affecting the cystic fibrosis (CF) patient population. Despite treating the underlying infection, the use of systemic antibiotics has shown little efficacy in alleviation of symptom burden. This review seeks to discuss recent research on novel antibiotic eluting stent therapy in vitro and within animal models as well as the factors that contribute to its efficacy.

Data Sources

PubMed literature review.

Review Methods

A review of all published literature related to antibiotic eluting sinus stents was conducted to integrate and summarize this innovative approach to chronic sinus infections.

Results

Placement of the ciprofloxacin sinus stent (CSS) and ciprofloxacin‐ivacaftor sinus stent (CISS) exhibited improvement in endoscopic and radiographic findings in rabbit CRS models. While the CSS showed an overall trend toward improvement in microscopic findings and a reduction in biofilm mass, there remained a significant quantity of planktonic bacteria due to antibiotic depletion from an initial burst release in the first 48 hours of stent placement. The CISS and ciprofloxacin‐azithromycin sinus stents (CASSs) exhibited controlled antibiotic release over the study period leading to greatly reduced planktonic bacterial load and biofilm mass. In vitro studies indicate that CASS may be just as efficacious at reducing biofilm mass.

Conclusion

Antibiotic eluting sinus stents show significant promise as a novel therapeutic strategy for CRS. The CISS may have particular promise for the CF patient population by addressing both the infectious and genetic components of disease. Animal studies demonstrate significant promise for translation into human studies. Human clinical trials are warranted to determine the efficacy of antibiotic sinus stents in human patients.

Level of Evidence

NA
Introducing the Self‐Cleaning FiLtrAtion for Water quaLity SenSors (SC‐FLAWLeSS) system
Authors: Khandelwal Aashish , González‐Pinzón Ricardo , Regier Peter , Nichols Justin , Van Horn David J.
Published: July 2020

Sensor‐based, semicontinuous observations of water quality parameters have become critical to understanding how changes in land use, management, and rainfall‐runoff processes impact water quality at diurnal to multidecadal scales. While some commercially available water quality sensors function adequately under a range of turbidity conditions, other instruments, including those used to measure nutrient concentrations, cease to function in high turbidity waters (> 100 nephelometric turbidity units [NTU]) commonly found in large rivers, arid‐land rivers, and coastal areas. This is particularly true during storm events, when increases in turbidity are often concurrent with increases in nutrient transport. Here, we present the development and validation of a system that can affordably provide Self‐Cleaning FiLtrAtion for Water quaLity SenSors (SC‐FLAWLeSS), and enables long‐term, semicontinuous data collection in highly turbid waters. The SC‐FLAWLeSS system features a three‐step filtration process where: (1) a coarse screen at the inlet removes particles with diameter > 397 μm, (2) a settling tank precipitates and then removes particles with diameters between 10 and 397 μm, and (3) a self‐cleaning, low‐cost, hollow fiber membrane technology removes particles ≥ 0.2 μm. We tested the SC‐FLAWLeSS system by measuring nitrate sensor data loss during controlled, serial sediment additions in the laboratory and validated it by monitoring soluble phosphate concentrations in the arid Rio Grande river (New Mexico, U.S.A.), at hourly sampling resolution. Our data demonstrate that the system can resolve turbidity‐related interference issues faced by in situ optical and wet chemistry sensors, even at turbidity levels > 10,000 NTU.
Cultivable microbiota associated with Aurelia aurita and Mnemiopsis leidyi
Authors: Weiland‐Bräuer Nancy , Prasse Daniela , Brauer Annika , Jaspers Cornelia , Reusch Thorsten B. H. , Schmitz Ruth A.
Published: July 2020

The associated microbiota of marine invertebrates plays an important role to the host in relation to fitness, health, and homeostasis. Cooperative and competitive interactions between bacteria, due to release of, for example, antibacterial substances and quorum sensing (QS)/quorum quenching (QQ) molecules, ultimately affect the establishment and dynamics of the associated microbial community. Aiming to address interspecies competition of cultivable microbes associated with emerging model species of the basal animal phyla Cnidaria (Aurelia aurita) and Ctenophora (Mnemiopsis leidyi), we performed a classical isolation approach. Overall, 84 bacteria were isolated from A. aurita medusae and polyps, 64 bacteria from M. leidyi, and 83 bacteria from ambient seawater, followed by taxonomically classification by 16S rRNA gene analysis. The results show that A. aurita and M. leidyi harbor a cultivable core microbiome consisting of typical marine ubiquitous bacteria also found in the ambient seawater. However, several bacteria were restricted to one host suggesting host‐specific microbial community patterns. Interbacterial interactions were assessed by (a) a growth inhibition assay and (b) QS interference screening assay. Out of 231 isolates, 4 bacterial isolates inhibited growth of 17 isolates on agar plates. Moreover, 121 of the 231 isolates showed QS‐interfering activities. They interfered with the acyl‐homoserine lactone (AHL)‐based communication, of which 21 showed simultaneous interference with autoinducer 2. Overall, this study provides insights into the cultivable part of the microbiota associated with two environmentally important marine non‐model organisms and into interbacterial interactions, which are most likely considerably involved in shaping a healthy and resilient microbiota.
High Glucosylceramides and Low Anandamide Contribute to Sensory Loss and Pain in Parkinson's Disease
Authors: Klatt‐Schreiner Katharina , Valek Lucie , Kang Jun‐Suk , Khlebtovsky Alexander , Trautmann Sandra , Hahnefeld Lisa , Schreiber Yannick , Gurke Robert , Thomas Dominique , Wilken‐Schmitz Annett , Wicker Sabine , Auburger Georg , Geisslinger Gerd , Lötsch Jörn , Pfeilschifter Waltraud , Djaldetti Ruth , Tegeder Irmgard
Published: July 2020

Background

Parkinson's disease (PD) causes chronic pain in two‐thirds of patients, in part originating from sensory neuropathies. The aim of the present study was to describe the phenotype of PD‐associated sensory neuropathy and to evaluate its associations with lipid allostasis, the latter motivated by recent genetic studies associating mutations of glucocerebrosidase with PD onset and severity. Glucocerebrosidase catalyzes the metabolism of glucosylceramides.

Methods

We used quantitative sensory tests, pain ratings, and questionnaires and analyzed plasma levels of multiple bioactive lipid species using targeted lipidomic analyses. The study comprised 2 sets of patients and healthy controls: the first 128 Israeli PD patients and 224 young German healthy controls for exploration, the second 50/50 German PD patients and matched healthy controls for deeper analyses.

Results

The data showed a 70% prevalence of PD pain and sensory neuropathies with a predominant phenotype of thermal sensory loss plus mechanical hypersensitivity. Multivariate analyses of lipids revealed major differences between PD patients and healthy controls, mainly originating from glucosylceramides and endocannabinoids. Glucosylceramides were increased, whereas anandamide and lysophosphatidic acid 20:4 were reduced, stronger in patients with ongoing pain and with a linear relationship with pain intensity and sensory losses, particularly for glucosylceramide 18:1 and glucosylceramide 24:1.

Conclusions

Our data suggest that PD‐associated sensory neuropathies and PD pain are in part caused by accumulations of glucosylceramides, raising the intriguing possibility of reducing PD pain and sensory loss by glucocerebrosidase substituting or refolding approaches. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Two novel mutations in the MCM8 gene shared by two Chinese siblings with primary ovarian insufficiency and short stature
Authors: Wang Fei , Guo Sheng , Li Pin
Published: July 2020

Background

Minichromosome maintenance complex component 8 (MCM8) is responsible for homologous recombination and DNA double‐strand breaks (DSBs) repair and is the cause of primary ovarian insufficiency (POI), which is seldom diagnosed in adolescents and children.

Methods

Whole‐exome sequencing was performed in a 13‐year‐old girl, and Sanger sequencing was used to identify potentially pathogenic variants in her sister (aged 6 years and 7 months) and parents. To identify potential pathogenic mutations, DSBs were induced by mitomycin C (MMC), and the DNA repair capacity was evaluated by the histone H2AX phosphorylation level.

Results

Two novel mutations of MCM8, i.e., c.724T>C (p.C242R) and c.1334C>A (p.S445*), were identified in a 13‐year‐old girl with POI who exhibited disappeared bilateral ovaries and short stature (height standard difference score [HtSDS] = −3.05), and her sister (aged 6 years and 7 months) with progressive POI whose ovary size decreased from normal to unclear and height growth gradually slowed. In the functional experiments, compared with the wild‐type, HeLa cells overexpressing mutant p.C242R and p.S445* showed a higher sensitivity to MMC. Furthermore, the mutant p.S445* has a more deleterious effect on DNA damage repair.

Conclusion

Our results reveal that affected children with the novel pathogenetic mutations p.C242R and p.S445* in the MCM8 gene are characterized by POI, short stature, cancer susceptibility, and genomic instability.
Lymphedema microsurgery improved outcomes of pediatric primary extremity lymphedema
Authors: Cheng Ming‐Huei , Liu Tiffany Ting‐Fong
Published: July 2020

Background

Primary lymphedema is an anomaly of the regional lymphatic system with long symptom duration or severe lymphatic obstruction. Few microsurgical treatments for primary lymphedema have been reported. This aim of this study was to investigate the outcomes of microsurgical treatments in pediatric primary lymphedema patients.

Methods

Between 2013 and 2017, pediatric primary lymphedema patients who underwent either lymphovenous anastomosis (LVA) or vascularized lymph node transfer (VLNT) were retrospectively reviewed. Cheng's Lymphedema Grading, Taiwan Lymphoscintigraphy Staging and indocyanine green lymphography were used to select the procedures. No compression garments were used postoperatively. Outcome measurements included circumferential difference, episodes of cellulitis, and Lymphedema‐specific Quality of life questionnaire (LYMQoL).

Results

Nine patients with mean age of 9.2 years (range, 2–19 years) with 11 lower and two upper lymphedematous limbs underwent 11 VLNT and two LVA. All VLNT flaps survived. At a mean 38.4‐months (range, 16–63 months) of follow‐up, the mean circumferential difference in nine unilateral lymphedematous limbs was improved by 6.7 ± 9.9% (p= .066). Two patients with bilateral lower limb lymphedema had mean limb circumference improvements of 1.3 and 6.5 cm, respectively. In nine limbs with cellulitis preoperatively, episodes of cellulitis decreased by 2.67 times/year (p= .007). At a mean 22.3‐months of follow‐up (range, 13–24 months), the LYMQoL overall score in 6 patients older than 7 years was improved by 3.2 ± 1.1 points (p= .007).

Conclusions

Lymphedema microsurgery significantly improved the episodes of cellulitis and quality of life without utilizing compression garments in pediatric primary lymphedema patients.
Analytical solutions for the consolidation of unsaturated foundation with prefabricated vertical drain
Authors: Huang Yuanchun , Li Tianyi , Fu Xianlei , Chen Zheng
Published: July 2020

Based on the consolidation theory raised by Fredlund, the solutions for the equal‐strain consolidation of unsaturated foundation with the prefabricated vertical drain considering smear effect and drain resistance are analytically formulated in this paper. Firstly, governing equations for excess pore pressures (i.e., excess pore‐air and pore‐water pressures) under the equal‐strain hypothesis are derived with the introduction of radial boundary conditions. Afterwards, the obtained coupled equations are solved by applying general integration, decoupling process, and Fourier sine series expansion. The smear coefficients and factors of drain resistance corresponding to air and water phases are both captured explicitly in the final solutions. Furthermore, the degenerated solutions are employed to verify the reliability of the current solutions. Finally, a parametric study is conducted to study the consolidation characteristics of the proposed foundation model against modeling sizes (S and N), smear coefficients (αa and αw), and drain resistance factors (Ga and Gw).
Risk factors for infection in home health care: Analysis of national Outcome and Assessment Information Set data
Authors: Shang Jingjing , Wang Jinjiao , Adams Victoria , Ma Chenjuan
Published: July 2020

Patients in home health care (HHC), a rapidly growing healthcare sector, are at high risk for infections. This study aimed to identify risk factors for infections among HHC patients using the Outcome and Assessment Information Set (OASIS) data. We used a 5% random sample of the 2013 national OASIS data. Infections were identified if records indicated that patients were hospitalized or received emergency care for one of three types of infections (respiratory, wound site, and urinary tract infection). Multivariate logistic regression models were used to identify risk factors for each individual infection type. The final analysis included 128,163 patients from 8,255 HHC agencies nationwide. Approximately 3.2% of the patients developed infections during their HHC stay that led to hospitalization or emergency care treatment. We found that associations between demographics and infection risk are specific to the type of infection. In general, a history of multiple hospitalizations in past 6 months, comorbidity, having a severe condition at HHC admission, and impaired physical functioning increased HHC patients' risk of infections. We also identified that HHC patients with caregivers who needed training in providing medical procedure or treatment are at higher risk for wound‐site infections. Our findings suggest that patients with underlying medical conditions and limited physical function status are more likely to develop infection. The caregiver's lack of training in providing needed care at home also places HHC patients at high risk for infection. Education for patients and caregivers should be tailored based on their health literacy level to ensure complete understanding.
Molecular and functional characterization of urine‐derived podocytes from patients with Alport syndrome
Authors: Iampietro Corinne , Bellucci Linda , Arcolino Fanny O , Arigoni Maddalena , Alessandri Luca , Gomez Yonathan , Papadimitriou Elli , Calogero Raffaele A , Cocchi Enrico , Van Den Heuvel Lambertus , Levtchenko Elena , Bussolati Benedetta
Published: July 2020

Alport syndrome (AS) is a genetic disorder involving mutations in the genes encoding collagen IV α3, α4 or α5 chains, resulting in the impairment of glomerular basement membrane. Podocytes are responsible for production and correct assembly of collagen IV isoforms; however, data on the phenotypic characteristics of human AS podocytes and their functional alterations are currently limited. The evident loss of viable podocytes into the urine of patients with active glomerular disease enables their isolation in a non‐invasive way. Here we isolated, immortalized, and subcloned podocytes from the urine of three different AS patients for molecular and functional characterization. AS podocytes expressed a typical podocyte signature and showed a collagen IV profile reflecting each patient's mutation. Furthermore, RNA‐sequencing analysis revealed 348 genes differentially expressed in AS podocytes compared with control podocytes. Gene Ontology analysis underlined the enrichment in genes involved in cell motility, adhesion, survival, and angiogenesis. In parallel, AS podocytes displayed reduced motility. Finally, a functional permeability assay, using a podocyte–glomerular endothelial cell co‐culture system, was established and AS podocyte co‐cultures showed a significantly higher permeability of albumin compared to control podocyte co‐cultures, in both static and dynamic conditions under continuous perfusion. In conclusion, our data provide a molecular characterization of immortalized AS podocytes, highlighting alterations in several biological processes related to extracellular matrix remodelling. Moreover, we have established an in vitro model to reproduce the altered podocyte permeability observed in patients with AS. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland..
Spontaneously occurring melanoma in animals and their relevance to human melanoma
Authors: van der Weyden Louise , Brenn Thomas , Patton E Elizabeth , Wood Geoffrey A , Adams David J
Published: July 2020

In contrast to other cancer types, melanoma incidence has been increasing over the last 50 years, and while it still represents less than 5% of all cutaneous malignancies, melanoma accounts for the majority of skin cancer deaths, due to its propensity to metastasise. Whilst melanoma most commonly affects the skin, it can also arise in mucosal surfaces, the eye, and the brain. For new therapies to be developed, a better understanding of the genetic landscape, signalling pathways, and tumour–microenvironmental interactions is needed. This is where animal models are of critical importance. The mouse is the foremost used model of human melanoma. Arguably this is due to its plethora of benefits as a laboratory animal; however, it is important to note that unlike humans, melanocytes are not present at the dermal–epidermal junction in mice and mice do not develop melanoma without genetic manipulation. In contrast, there are numerous reports of animals that spontaneously develop melanoma, ranging from sharks and parrots to hippos and monkeys. In addition, several domesticated and laboratory‐bred animals spontaneously develop melanoma or UV‐induced melanoma, specifically, fish, opossums, pigs, horses, cats, and dogs. In this review, we look at spontaneously occurring animal ‘models’ of melanoma and discuss their relevance to the different types of melanoma found in humans. © 2020 The Authors. TheJournal of Pathologypublished by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland..
Esophageal atresia in twins compared to singletons: In utero manifestation and characteristics
Authors: Weissbach Tal , Kassif Eran , Kushnir Anya , Shust‐Barequet Shir , Leibovitch Leah , Eliasi Elior , Elkan‐Miller Tal , Zajicek Michal , Yinon Yoav , Weisz Boaz
Published: July 2020

Objective

Esophageal atresia with/without tracheo‐esophageal fistula (EA/TEF) is more common among twins. The detection of polyhydramnios might be altered in twins, leading to EA/TEF underdiagnosis, prenatally. The aim of the study was to compare the prenatal manifestation of EA/TEF between twins and singletons.

Methods

A 12‐year study of EA/TEF cases was performed at a tertiary center. Cases exhibiting (a) small/absent stomach or (b) polyhydramnios were considered “suspected”; cases with (c) esophageal pouch were considered “detected.” We compared the rate and timing of appearance of these signs between the groups.

Results

There were 76 cases of EA/TEF, of which 17 were a co‐twin. All twin pairs were EA/TEF discordant. The prevalence of EA/TEF at our center was 1:750 for twins (1:319 monochorionic and 1:1133 dichorionic) and 1:2399 for singletons. The rate of small/absent stomach, polyhydramnios and pouch in twins vs singletons was 23.5%, 47.1%, 29.4% and 39.7%, 72.4%,34.5%, respectively (P = .2, P = .09 and P = .7). Esophageal pouch was detected earlier in twins (P = .03). Twins were scanned more frequently (×1.8 times, P = .01).

Conclusion

EA/TEF is more prevalent in twins. Despite lower rate of polyhydramnios, twins were similarly detected prenatally as singletons, and this was accomplished earlier in pregnancy; perhaps reflecting more frequent scans.
Multiscale analysis of nanoparticles size effects on thermal, elastic, and viscoelastic properties of nano‐reinforced polymers
Authors: Blivi Adoté S. , Bedoui Fahmi , Weigand Steven , Kondo Djimédo
Published: July 2020

Dependency of microstructural organization, thermal, and mechanical properties of reinforced polymers on the size of the fillers was investigated on model nano‐reinforced polymers. Binary systems made of poly(methyl methacrylate) and silica spheres were prepared. While volume fraction was kept constant, silica sphere diameters were varied from 500 nm down to 15 nm. X‐ray scattering techniques along with static and dynamic mechanical analysis were conducted on the different prepared binary systems. From our experimental results, it appears that decreasing particle size lead to reduced interchain distances which could be interpreted as matrix densification. In addition, intrachain distance reflecting distance between two carbonyl groups within the same chain was also affected by particle size. Decrease of such distance was interpreted as local segmental rotation induced by size reduction. From mechanical aspects, reducing the size enhanced elastic properties, as evidenced by the increase in the elastic modulus. Dynamic analysis also confirmed such trend where the storage modulus increases for sample with smaller silica particle. Chain mobility quantified through the composite glass transition and the damping factor revealed size‐induced mobility restriction through the observed increase of the glass transition. Particle size, when less than 60 nm, appeared as an important parameter contribution to material properties enhancement through multiscale microstructural characterization and mechanical analysis.
The Difference in Medial Meniscal Extrusion between Non‐Weight‐Bearing and Weight‐Bearing Positions in People with and without Medial Compartment Knee Osteoarthritis
Authors: Reisner Jacob H. , Franco John M. , Hollman John H. , Johnson Adam C. , Sellon Jacob L. , Finnoff Jonathan T.
Published: July 2020

Background

Medial meniscal extrusion (MME) has been correlated with medial meniscal injury and progression of medial knee osteoarthritis (OA).

Objective

To examine the difference in MME between non‐weight‐bearing (supine) and weight‐bearing (standing) positions in patients with and without medial knee OA. Determine the correlation between body mass index (BMI), Kellgren‐Lawrence (KL) grade, Knee Osteoarthritis Outcome Score (KOOS), and MME.

Design

Prospective.

Setting

Tertiary institution PM&R Department.

Participants

Forty five participants (29 female, 16 male), 24 with healthy knees and 21 with OA.

Methods or Interventions

A single physician sonographer measured supine and standing MME with ultrasound (US) on each participant. The physician was blinded to all measurements. BMI was recorded on all participants. KL grades and KOOS questionnaires were obtained for the OA group.

Main Outcome Measures

MME in supine and standing positions, change in MME from supine to standing, BMI, KL grade, and KOOS subscale scores.

Results

MME increased .52 mm from supine to standing (P < .001). MME was greater in the OA group in both the supine (P = .002) and standing (P < .001) positions. Increasing BMI was moderately correlated with increasing MME (supine P = .001, standing <.001). Increasing age was correlated with increasing MME (supine P = .012, standing P = .002). Increasing KL grade (from 1 to 4) was correlated with increasing MME (supine P = .015, standing = .006). There was a small‐to‐moderate correlation between KOOS activities of daily living (ADL) subscale score and change in MME from supine to standing (P = .035). The change in MME from supine to standing positions had a small‐to‐moderate correlation (P = .035) with KOOS ADL subscale score alone but did not correlate with any of the other KOOS subscale scores or KOOS total scores. Receiver operating characteristic curve analysis suggested a standing MME value of 4.2 mm provides a positive likelihood ratio of 6.02 for knee OA.

Conclusions

MME is greater in those with OA and with weight‐bearing. MME correlates with BMI, age, KL grade, and the KOOS ADL subscale score. Finally, standing MME of 4.2 mm yielded a higher positive likelihood ratio to differentiate between healthy knees and those with medial compartment OA than the previously reported value of 3.0 mm.
Characterization of flupyradifurone resistance in the whitefly Bemisia tabaci Mediterranean (Q biotype)
Authors: Wang Ran , Wang Jinda , Zhang Jiasong , Che Wunan , Feng Honglin , Luo Chen
Published: July 2020

BACKGROUND

Bemisia tabaci is one of most notorious pests on various crops worldwide and many populations show high resistance to different types of insecticides. Flupyradifurone is a novel insecticide against sucking pests. B. tabaci resistance to flupyradifurone has been detected in the field, however the mechanism of flupyradifurone resistance has rarely been studied.

RESULTS

The flupyradifurone‐resistant strain (FLU‐SEL) was selected from the susceptible strain of B. tabaci (MED‐S) using flupyradifurone for 24 generations. The FLU‐SEL strain exhibited 105.56‐fold resistance to flupyradifurone, and moderate cross‐resistance to imidacloprid, but no cross‐resistance to other tested neonicotinoids. Synergism tests and metabolic enzyme assays suggested that FLU‐SEL resistance can be attributed to enhanced detoxification mediated by glutathione S‐transferase (GST) and P450 monooxygenase (P450). Compared with MED‐S strain, CYP6CX4 and GSTs2 were significantly overexpressed in FLU‐SEL, and silencing CYP6CX4 or GSTs2 increased the mortality of whiteflies to flupyradifurone challenge in FLU‐SEL. In addition, silencing CYP6CX4 also increased the mortality of whiteflies exposed to imidacloprid.

CONCLUSION

Overexpression of CYP6CX4 and GSTs2 was associated with flupyradifurone resistance, as confirmed by RNA interference. Our findings suggested that metabolic resistance to flupyradifurone might be mediated by P450s and GSTs. © 2020 Society of Chemical Industry
Nicarbazin has no effect on reducing feral pigeon populations in Barcelona
Authors: Senar Juan Carlos , Navalpotro Helena , Pascual Jordi , Montalvo Tomás
Published: July 2020

BACKGROUND

Nicarbazin is an anti‐coccidial product sometimes used as a contraceptive to reduce the size of feral pigeon populations. However, its effectiveness in reducing pigeon population size in cities has caused some controversy. Here, we evaluate its effectiveness in the city of Barcelona.

RESULTS

In 2017, the Barcelona City Council set 23 feeding stations with nicarbazin and ten with placebo (untreated corn). Censuses were undertaken before and after one year of treatment, within a 200‐m radius around each feeder. We also censused 28 circles of 200 m radius distributed randomly 200 m from the feeders and 28 circles > 500 m from the feeders, which acted as controls. Population size across the whole city was also evaluated pre‐ and post treatment. We found that feral pigeon density did not change after one year of treatment, either in the circles around feeding stations with nicarbazin or in the areas around control stations at 200 and > 500 m from the feeders. Population size in placebo circles rose after a year by 10%. A pigeon census for the whole of Barcelona showed a 10% increase.

CONCLUSION

Overall, our results indicate that the nicarbazin treatment had no effect on feral pigeon population size, and we advise against its use as a pigeon control method, at least in large cities.
Protective efficacy of phenoxyacetyl oxazolidine derivatives as safeners against nicosulfuron toxicity in maize
Authors: Zhang Yuan‐Yuan , Gao Shuang , Hoang Minh‐Tu , Wang Zi‐Wei , Ma Xin , Zhai Yue , Li Na , Zhao Li‐Xia , Fu Ying , Ye Fei
Published: July 2020

BACKGROUND

Herbicide safeners mitigate crop damage without reducing herbicide efficacy. Here, the protective effects of phenoxyacetyl oxazolidine derivatives as potential safeners were evaluated with a view toward reducing injury caused by sulfonylurea herbicide nicosulfuron to sensitive maize varieties.

RESULTS

Growth indices demonstrated that the bioactivity of compound 9 (N‐phenoxyacety‐2‐methyl‐2,4‐diethyl‐1,3‐oxazolidine) was superior to that of R‐28725 and all other compounds tested. Compound 9 induced endogenous glutathione and upregulated glutathione‐S‐transferase (GST) in maize. Thus, it could enhance maize tolerance to nicosulfuron. Compared with the untreated water control group, the maximum reaction rate of GST was increased by 37.62%, while the maximum velocity of GST was decreased by 61.93% after treatment with compound 9. Acetolactate synthase relative activity was significantly enhanced in the case of treatment with compound 9, indicating the excellent protective effects of compound 9 against nicosulfuron in maize.

CONCLUSIONS

The present work demonstrates that phenoxyacetyl oxazolidine derivatives are potentially efficacious as herbicide safeners and merit further investigation.
Cold hardiness of the South American tomato pinworm Tuta absoluta (Lepidoptera: Gelechiidae): both larvae and adults are chill‐susceptible
Authors: Tarusikirwa Vimbai L , Mutamiswa Reyard , Chidawanyika Frank , Nyamukondiwa Casper
Published: July 2020

BACKGROUND

For many insects, including invasive species, overwintering survival is achieved behaviourally (e.g. through migration) or physiologically by entering diapause, a state of arrested physiological development that may be accompanied with depressed supercooling points (SCPs). Diapause allows in situ adaptation to adverse environmental conditions, providing sufficient parent propagules for insect pest proliferation when optimal conditions resurface. This phenomenon has however not been observed in the invasive South American tomato pinworm Tuta absoluta in its Mediterranean invaded areas. Moreover, no studies have looked at its overwintering survival in sub‐Saharan Africa. Here, we thus investigated the cold hardiness of Tuta absoluta larvae and adults to better explain its local overwintering adaptation strategy.

RESULTS

Larval lower lethal temperatures ranged from −1 to −17 °C for 0.5 to 4 h durations. Adults showed lower temperature activity limits than larvae albeit freeze strategy experiments showed neither survived internal freezing. Fasting and dehydration pre‐treatment generally depressed SCPs, although asymmetrically, conferring more negative SCPs for larvae. Ramping rates, synonymic to diurnal temperature changes also significantly affected SCPs while, inoculative freezing significantly compromised freezing temperatures in both larvae and adults.

CONCLUSION

Our results suggest that (i) Tuta absoluta larvae and adults are chill‐susceptible and may successfully overwinter, (ii) larvae appear more cold hardy than adults and (iii) ecological factors e.g. inoculative freezing, cooling rates, feeding‐ and hydration‐status may affect cold hardiness. These results are important in determining species range limits, population phenology, modelling pest risk status and allows temporal life‐stage specific targeting of management strategies.
Sound Speed in Glassy AsxSe1−x (x = 0.4, 0.5, and 0.6) by Inelastic X‐Ray Scattering
Authors: Inui Masanori , Matsuda Kazuhiro , Hosokawa Shinya , Nakajima Yoichi , Tsutsui Satoshi , Ishikawa Daisuke , Baron Alfred Q. R.
Published: July 2020

Inelastic X‐ray scattering (IXS) measurements are carried out for glassy , , and to investigate atomic dynamics in the glasses. Momentum transfer (Q) dependence of the acoustic excitation energy in each glass follows the ultrasonic sound speed. No positive dispersion is observed in these glasses although liquid near the melting point shows it. The stoichiometric glass shows a maximum sound speed and the speed decreases with increasing As concentration. The results seem to be correlated with a prediction by rigidity theory that glassy is most stable.
Moist shallow‐water response to tropical forcing: Initial‐value problems
Authors: Suhas D.L. , Sukhatme Jai
Published: July 2020

The response of a spherical moist shallow‐water system to tropical imbalances in the presence of inhomogeneous saturation fields is examined. While the initial moist response is similar to the dry reference run, albeit with a reduced equivalent depth, the long‐time solution depends quite strikingly on the nature of the saturation field. For a saturation field that depends only on latitude, specifically one with a peak at the Equator and which falls off meridionally in both hemispheres, height imbalances adjust to large‐scale, low‐frequency westward‐propagating modes. When the background saturation environment is also allowed to vary with longitude, in addition to a westward quadrupole, there is a distinct eastward‐propagating response at long times. The nature of this eastward‐propagating mode is well described by moist potential vorticity conservation and it consists of wave packets that arc out to the midlatitudes and return to the Tropics, and are predominantly rotational in character. In all the moist cases, initially formed Kelvin waves decay, and this appears to be tied to the mostly off‐equatorial organization of moisture anomalies by rotational modes. Many of these basic features carry over to the response in the presence of realistic saturation fields derived from reanalysis‐based precipitable water. Considering an imbalance in the equatorial Indian Ocean in the boreal summer, the long‐time eastward response is restricted to the Northern Hemisphere and takes the form of a wave train that passes over the Indian landmass into the Subtropics, reaching across the Pacific to North America. In the boreal winter, the eastward mode consists of a subtropically confined rotational quadrupole along with the midlatitudinal disturbances. Thus, in addition to circumnavigating westward Rossby waves, slow eastward‐propagating modes appear to be a robust feature of the shallow‐water system with interactive moisture in the presence of saturation fields that vary with latitude and longitude.