bluuebunny/crossref_metadata_2025 huggingface dataset:
Toll‐Like Receptor 8 Agonist GS‐9688 Induces Sustained Efficacy in the Woodchuck Model of Chronic Hepatitis B
Authors: Daffis Stephane , Balsitis Scott , Chamberlain Jason , Zheng Jim , Santos Rex , Rowe William , Ramakrishnan Dhivya , Pattabiraman Divya , Spurlock Sandra , Chu Ruth , Kang Don , Mish Michael , Ramirez Ricardo , Li Li , Li Bei , Ma Sarina , Hung Magdeleine , Voitenleitner Christian , Yon Changsuek , Suresh Manasa , Menne Stephan , Cote Paul , Delaney William E. , Mackman Richard , Fletcher Simon P.
Published: April 2020

Background and Aims

GS‐9688 (selgantolimod) is an oral selective small molecule agonist of toll‐like receptor 8 in clinical development for the treatment of chronic hepatitis B. In this study, we evaluated the antiviral efficacy of GS‐9688 in woodchucks chronically infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to hepatitis B virus.

Approach and Results

WHV‐infected woodchucks received eight weekly oral doses of vehicle, 1 mg/kg GS‐9688, or 3 mg/kg GS‐9688. Vehicle and 1 mg/kg GS‐9688 had no antiviral effect, whereas 3 mg/kg GS‐9688 induced a >5 log10 reduction in serum viral load and reduced WHV surface antigen (WHsAg) levels to below the limit of detection in half of the treated woodchucks. In these animals, the antiviral response was maintained until the end of the study (>5 months after the end of treatment). GS‐9688 treatment reduced intrahepatic WHV RNA and DNA levels by >95% in animals in which the antiviral response was sustained after treatment cessation, and these woodchucks also developed detectable anti‐WHsAg antibodies. The antiviral efficacy of weekly oral dosing with 3 mg/kg GS‐9688 was confirmed in a second woodchuck study. The antiviral response to GS‐9688 did not correlate with systemic GS‐9688 or cytokine levels but was associated with transient elevation of liver injury biomarkers and enhanced proliferative response of peripheral blood mononuclear cells to WHV peptides. Transcriptomic analysis of liver biopsies taken prior to treatment suggested that T follicular helper cells and various other immune cell subsets may play a role in the antiviral response to GS‐9688.

Conclusions

Finite, short‐duration treatment with a clinically relevant dose of GS‐9688 is well tolerated and can induce a sustained antiviral response in WHV‐infected woodchucks; the identification of a baseline intrahepatic transcriptional signature associated with response to GS‐9688 treatment provides insights into the immune mechanisms that mediate this antiviral effect.
Nonalcoholic Fatty Liver Disease and Alcoholic Liver Disease are Major Drivers of Liver Mortality in the United States
Authors: Paik James M. , Golabi Pegah , Biswas Rakesh , Alqahtani Saleh , Venkatesan Chapy , Younossi Zobair M.
Published: April 2020

In the United States, chronic viral hepatitis B and C (CHB and CHC), nonalcoholic fatty liver disease (NAFLD), and alcohol‐related liver disease (ALD) are the main causes of liver deaths attributable to hepatocellular carcinoma (HCC) and cirrhosis. Our aim was to assess the changes in the rates of mortality and years of potential life lost (YLL) for HCC and cirrhosis due to different liver diseases. We used multiple‐cause mortality data (2007‐2017) from the National Center for Health Statistics. Annual percentage change (APC) in age‐standardized death rate per 100,000 (ASDR) and age‐standardized years of life lost per 100,000 (ASYLLR) were calculated. In the United States in 2017, there were 2,797,265 deaths with 73,424 liver deaths, contributing to 1,467,742 of YLL. Of the liver deaths, HCC was noted in 12,169 (16.6%) and cirrhosis in 60,111 (82.0%). CHC was responsible for 50.4% of HCC deaths; NAFLD, 35.4%; HBV, 6.0%; ALD, 5.4%; and others, 2.8%. NAFLD was responsible for 48.9% of cirrhosis deaths; ALD, 34.7%; CHC, 12.3%; CHB, 0.9%; and others, 3.2%. Between 2007 and 2017, the increase in ASDR for HCC due to ALD and NAFLD accelerated after 2014 (APC, 11.38% and 6.55%, respectively) whereas CHC stabilized (APC, 0.63%; P = 0.272) after 2011. The increase in ASYLLR of HCC escalated after 2014 for ALD and NAFLD (APC, 12.12% and 6.15%, respectively) and leveled out for CHC after 2012 (APC, −1.05%; P = 0.056). Furthermore, the highest annual increase in ASDR and ASYLLR for cirrhosis was due to ALD (APC, 3.24% and 3.34%, respectively) followed by NAFLD (APC, 1.23% and 0.49%, respectively). Conclusion: Over the past decade, ASDR and ASYLLR due to ALD and NAFLD have been increasing in the United States. The rising burden of HCC and cirrhosis are primarily driven by NAFLD and ALD.
An overview of digital and online strategies to reduce gambling harm
Authors: Paterson Marisa , Whitty Megan , Boyer Charlotte
Published: April 2020

Issue addressed

Advancements in mobile‐ and web‐based technologies proliferate everyday opportunities to gamble. The increased availability, popularity and intensity of online gambling platforms and interactive gaming activities also changes the way we construct gambling harm reduction interventions. Information and communication technologies (ICT) provide potential opportunities to reduce harm from online gambling through harm minimisation initiatives and currently available services. The aim of this review was to firstly understand the scope of peer‐reviewed evidence on ICT‐based strategies to reduce online gambling harm, and secondly, what evidence exists specifically in relation to ICT‐based harm reduction initiatives for people who gamble online.

Methods

Scoping review methods and a five‐stage model of analysis were used to: identify the published literature on ICT‐based harm minimisation activities for online gambling; distil models appropriate to address gambling harm in this setting; and synthesise all available evidence, noting gaps and patterns.

Results

Sixteen gambling‐specific ICT‐based interventions were reviewed in depth. The majority of included studies focused on different components of computer‐assisted or online therapy programs for disordered gambling, specifically the development of individual skills in managing problematic gambling behaviour.

Conclusions

The review found that despite the widespread potential ICT represent for addressing gambling harm there has been only limited published research to date.

So what

There is a clear need for further investigation into uptake, usage, focus and effectiveness of all online gambling interventions on offer. The dearth of gambling‐specific empirical knowledge potentially indicates a serious resourcing and reporting issues in this area.
Comparison of no adjuvant treatment and radiotherapy in early‐stage cervical carcinoma with intermediate risk factors
Authors: Akilli Huseyin , Tohma Yusuf A. , Bulut Ayça N. , Karakas Latife Atasoy , Haberal Asuman N. , Kuscu Ulku E. , Ayhan Ali
Published: April 2020

Objective

To evaluate the results of receiving no adjuvant treatment (NAT) or radiotherapy after radical hysterectomy in patients with International Federation of Gynecology and Obstetrics 2018 Stage IB1–IB3 cervical cancer with intermediate risk factors.

Methods

A retrospective cohort study was conducted at Baskent University School of Medicine's Department of Gynecology and Obstetrics in Ankara, Turkey between January 1, 2008, and December 31, 2016. In total, 134 women with at least two intermediate risk factors (positive LVSI, deep stromal invasion, and tumor size ≥4 cm) were included in the study. Patients were divided into two groups: NAT and radiotherapy.

Results

There were 66 patients in the NAT group and 68 in the radiotherapy group. The median follow‐up time was 61.05 months. The 5‐year overall survival (OS) rates were similar in both groups (84.1% vs 82.9%, respectively; P=0.57), while the 5‐year disease‐free survival (DFS) rates were 80.2% and 78.2% in the NAT and radiotherapy groups, respectively (P=0.25). Most importantly, both groups had similar local recurrence rates: 8 (12.1%) in the NAT group and 9 (13.2%) in the radiotherapy group (P=0.82). Multivariant analyses showed that the only independent risk factor for recurrence was tumor size ≥4 cm with a hazard ratio of 2.4 (95% confidence interval 1.12–5.24; P=0.02).

Conclusion

Adjuvant treatment improved neither DFS nor local recurrence rates.
Retracted: Effect of adjunctive vaginal progesterone after McDonald cerclage on the rate of second‐trimester abortion in singleton pregnancy: a randomized controlled trial
Authors: Ali Mohammed K. , Ahmed Sameh E. , Sayed Gamal H. , Badran Esraa Y. , Abbas Ahmed M.
Published: April 2020

Objective

To evaluate the effect of adjunctive use of vaginal progesterone after McDonald cerclage on the rate of second‐trimester abortion in singleton pregnancy.

Methods

A randomized controlled trial at Woman's Health Hospital, Assiut University, Egypt, between April 2017 and March 2019 enrolled women eligible for McDonald cerclage. After cerclage, participants were randomly assigned to receive progesterone (400 mg pessary) once daily until 37 weeks or no progesterone. The primary outcome was rate of abortion before 28 weeks. Secondary outcomes included gestational age at delivery, preterm delivery, mean birthweight, Apgar score, and admission to the neonatal intensive care unit (NICU).

Results

The rate of spontaneous abortion was higher in the no‐progesterone group (P=0.016). Mean gestational age and mean birthweight was higher in the progesterone group (P<0.001 and P=0.002, respectively). The frequency of preterm neonates, neonates with Apgar score less than 7, and admission to NICU was higher in the progesterone group than in the no‐progesterone group (P=0.005, P=0.008, and P=0.044, respectively).

Conclusion

Adjunctive use of vaginal progesterone after McDonald cerclage was found to decrease the frequency of second‐trimester abortion and to improve perinatal outcomes in singleton pregnancy.

Clinicaltrials.gov: NCT02846909.
Concentrations of fatty acids among macrosomic neonates delivered by healthy women and women with type 1 diabetes mellitus
Authors: Ivanisevic Marina , Delmis Karlo , Herman Mislav , Horvaticek Marina , Berberovic Edina , Djelmis Josip
Published: April 2020

Objective

To evaluate the concentration and profile of fatty acids (FAs) among macrosomic neonates delivered by healthy pregnant women and pregnant women with type 1 diabetes mellitus (T1DM).

Methods

A prospective study of women who delivered macrosomic neonates at a University Hospital Center, Zagreb, Croatia, 2016–2018. Maternal, umbilical vein, and arterial blood samples were collected immediately on delivery. After lipid extraction, total FAs in maternal, umbilical vein, and arterial serum samples were assessed by gas chromatography. Data were compared between women with T1DM and healthy control women.

Results

In total, 50 women were enrolled: 22 with T1DM and 28 control women. Neonates in the T1DM group had a higher ponderal index as compared with the control group (P=0.006). Umbilical vein insulin, insulin resistance, and leptin concentration were higher in the T1DM group than in the control group (all P<0.001). Umbilical vein serum concentrations of total saturated, monounsaturated, n‐3 polyunsaturated, and n‐6 polyunsaturated FAs were higher in the T1DM group (P=0.004, P<0.001, P=0.015, and P=0.014, respectively).

Conclusion

Macrosomic neonates delivered by women with T1DM had a higher Ponderal index, and higher concentrations of insulin, leptin, and FAs in the umbilical vein and artery as compared with control group newborns.
Therapeutic role of granulocyte macrophage colony‐stimulating factor (GM‐CSF) in patients with persistent thin endometrium: A prospective and randomized study
Authors: Mao Xiaoyan , Zhang Jie , Cai Renfei , Tao Yu , Gao Hongyuan , Kuang Yanping , Zhang Shaozhen
Published: April 2020

Objective

To assess the effect of granulocyte macrophage colony‐stimulating factor (GM‐CSF) on unresponsive thin (<7 mm) endometrium in women undergoing frozen‐thawed embryo transfer.

Methods

A single‐center, randomized, prospective study enrolled 304 women with thin unresponsive endometrium from Shanghai Ninth People's Hospital between March 2017 and May 2018. Of them, 161 patients received an intrauterine infusion of GM‐CSF and 143 patients served as controls. After hysteroscopy, a gel with or without GM‐CSF was administered to fill the uterine cavity completely or up to 5 mL only. The primary outcome was confirmed pregnancy and secondary outcomes included endometrial thickness and implantation rate.

Results

Patients who were administered GM‐CSF had a significantly higher chemical pregnancy rate (35.3% vs 20.0%; P=0.009) and clinical pregnancy rate (28.6% vs 13.3%; P=0.005) compared with patients in the control group. Patients treated with GM‐CSF had significantly higher endometrial thickness compared with controls (7.83 ± 1.45 mm vs 7.37 ± 0.70 mm, P=0.003).

Conclusion

GM‐CSF therapy can effectively increase endometrial thickness and improve the clinical pregnancy rate in patients with persistent thin endometrium. The therapeutic role of GM‐CSF for infertile women under in vitro fertilization and embryo transfer (IVF‐ET) treatment can be further explored.

Chinese Clinical Trial Register

ChiCTR‐IPR‐17011242
Implantable self‐aligning fiber‐optic optomechanical devices for in vivo intraocular pressure‐sensing in artificial cornea
Authors: Hui Pui‐Chuen , Shtyrkova Katia , Zhou Chengxin , Chen Xiaoniao , Chodosh James , Dohlman Claes H. , Paschalis Eleftherios I.
Published: April 2020

Artificial cornea is an effective treatment of corneal blindness. Yet, intraocular pressure (IOP) measurements for glaucoma monitoring remain an urgent unmet need. Here, we present the integration of a fiber‐optic Fabry‐Perot pressure sensor with an FDA‐approved keratoprosthesis for real‐time IOP measurements using a novel strategy based on optical‐path self‐alignment with micromagnets. Additionally, an alternative noncontact sensor‐interrogation approach is demonstrated using a bench‐top optical coherence tomography system. We show stable pressure readings with low baseline drift (<2.8 mm Hg) for >4.5 years in vitro and efficacy in IOP interrogation in vivo using fiber‐optic self‐alignment, with good initial agreement with the actual IOP. Subsequently, IOP drift in vivo was due to retroprosthetic membrane (RPM) formation on the sensor secondary to surgical inflammation (more severe in the current pro‐fibrotic rabbit model). This study paves the way for clinical adaptation of optical pressure sensors with ocular implants, highlighting the importance of controlling RPM in clinical adaptation.
Real‐time video mosaicking to guide handheld in vivo microscopy
Authors: Yin Chengbo , Wei Linpeng , Kose Kivanc , Glaser Adam K. , Peterson Gary , Rajadhyaksha Milind , Liu Jonathan T. C.
Published: April 2020

Handheld and endoscopic optical‐sectioning microscopes are being developed for noninvasive screening and intraoperative consultation. Imaging a large extent of tissue is often desired, but miniature in vivo microscopes tend to suffer from limited fields of view. To extend the imaging field during clinical use, we have developed a real‐time video mosaicking method, which allows users to efficiently survey larger areas of tissue. Here, we modified a previous post‐processing mosaicking method so that real‐time mosaicking is possible at >30 frames/second when using a device that outputs images that are 400 × 400 pixels in size. Unlike other real‐time mosaicking methods, our strategy can accommodate image rotations and deformations that often occur during clinical use of a handheld microscope. We perform a feasibility study to demonstrate that the use of real‐time mosaicking is necessary to enable efficient sampling of a desired imaging field when using a handheld dual‐axis confocal microscope.
Helping a Few a Lot or Many a Little: Political Ideology and Charitable Giving
Authors: Farmer Adam , Kidwell Blair , Hardesty David M.
Published: April 2020

The authors examine political ideology as it influences how people distribute their donations across multiple charities. Findings from five studies indicate that liberals and conservatives donate similar overall amounts of money; however, liberals tend to give to a greater number of charities, people, and causes overall while giving less to each (breadth). Conservatives tend to donate to fewer charities, people, and causes overall while giving more to each (depth). Using the model of moral motives, conservatives’ endorsement of social order led to their focus on smaller groups and protecting members of these groups as they give with depth. In contrast, liberals’ endorsement of social justice led to their focus on eliminating broad inequality as they give with breadth. However, these ideological tendencies can be reversed as conservatives gave with breadth when protecting social order and liberals gave with depth when equality was restored.
Environmental enrichment and pain sensitivity; a study in maternally separated rats
Authors: Mohtashami Borzadaran Fatemeh , Joushi Sara , Taheri Zadeh Zahra , Sheibani Vahid , Esmaeilpour Khadijeh
Published: April 2020

Rodents are highly dependent on maternal care after birth. Maternal separation (MS) is an animal model for studying neglect and abuse. Depriving the pup of such care renders the animal with Hypothalamic–Pituitary–adrenal (HPA) dysfunction and these animals are more susceptible to anxiety and stress as well as poor cognition. These effects are due to abnormal brain development in these animals. We have tried to investigate how maternal separation can affect pain sensation and whether a non‐pharmacological intervention such as enriched environment (EE) can restore an abnormal pain sensation. Animals were put into four groups MS, control (CTRL) and MS + EE and CTRL + EE groups that underwent EE after weaning until adulthood. These groups were tested for pain sensitivity with hot plate and tail flick for sensory pain and formalin for affect pain. The results showed that MS rats are more sensitive to pain in the hot plate test and formalin test, however, no significant difference was seen between groups for tail flick test. When MS rats experience EE their pain sensitivity is restored at the behavioral level. Further research is required to see how EE restores pain sensation in MS rats.
A homozygous missense variant in the homeobox domain of the NKX6‐2 results in progressive spastic ataxia type 8 associated with lower limb weakness and neurological manifestations
Authors: Almatrafi Ahmad , Umair Muhammad , Eldardear Amr , Al‐Luqmani Majid , Hashmi Jamil A. , Albalawi Alia M. , Alfadhel Majid , Ramzan Khushnooda , Basit Sulman
Published: April 2020

Background

Progressive spastic ataxia is a heterogeneous disorder characterized by cerebellar ataxia and limb spasticity associated with other severe neurological complications. Spastic ataxia is classified into pure and complex types, inherited in both an autosomal recessive and autosomal dominant manner. It is caused by pathogenic variants in at least eight different genes, including NKX6‐2 (MIM 607063) located on chromosome 10q26.3. The present study aimed to identify the genetic variant(s) underlying progressive spastic ataxia and to establish the genotype–phenotype correlation.

Methods

We collected a large consanguineous family having four affected individuals segregating progressive spastic ataxia in an autosomal recessive manner. To investigate the molecular cause of the disease, genomic DNA of three affected individuals underwent whole exome sequencing.

Results

All of the affected individuals showed progressive clinical features such as spastic ataxia, lower limb weakness and other mild neurological abnormalities. Whole exome sequencing data were analyzed using different filters. Filtering of rare and shared homozygous variants revealed a novel homozygous missense variant (c.545C>T; p.Ala182Val) in a highly conserved homeobox domain of the NKX6‐2 protein.

Conclusions

The findings of the present study add a novel variant to the NKX6‐2 mutation spectrum and provide evidence that homozygous variants in the NKX6‐2 cause progressive spastic ataxia associated with other abnormalities.
Is the alpha‐galactosidase A variant p.Asp313Tyr (p.D313Y) pathogenic for Fabry disease? A systematic review
Authors: Effraimidis Grigoris , Rasmussen Åse K. , Bundgaard Henning , Sørensen Søren S. , Feldt‐Rasmussen Ulla
Published: April 2020

The identification of pathogenic GLA variants plays a central role in the establishment of a definite Fabry disease (FD) diagnosis. We aimed to review and interpret the published data on the p.Asp313Tyr (p.D313Y) variant pathogenicity and clinical relevance.

We performed a systematic review of peer‐reviewed publications and case‐reports on individuals and populations harbouring the p.Asp313Tyr variant.

Overall, 35 studies were included in this review. We collected data regarding the clinical manifestations, alpha‐galactosidase A enzyme activity, levels of the biomarkers globotriaosylceramide (Gb3) and sphingosine‐globotriaosylceramide (lyso‐Gb3) and histological findings of p.Asp313Tyr carriers. The prevalence of p.Asp313Tyr in populations at risk for FD (kidney, heart, neurologic disorders, or symptomatic populations) was calculated. We found high residual enzyme activity, low frequency of clinical features specific for FD, non‐elevated lysoGb3/Gb3 concentrations and lack of intracellular Gb3 accumulation in biopsies in the p.Asp313Tyr carriers. The prevalence of the variant in populations at risk for FD was comparable to the reported frequency in the general population. A possible higher frequency was only observed in neurologic disorders.

p.Asp313Tyr can be classified as neutral or variant of unknown significance. Further investigations will be helpful to clarify a possible association between the variant and manifestations in the brain vessels.
Academic Leadership in a Time of Crisis: The Coronavirus and COVID‐19
Authors: Fernandez Antonio Arturo , Shaw Graham Paul
Published: April 2020

The novel coronavirus and the disease it causes, COVID‐19 is one of the most unpredictable global public health crises in recent times. Academic leaders across the United States have responded by moving their educational and associated activities online; as a sense of immediacy swept the nation. The decision to pivot to remote learning was made swiftly, particularly by those institutions operating a shared leadership model, benefitting from a greater degree of agility, innovation, and collaboration. The current article highlights three of the leadership best practices for navigating unpredictable adaptive challenges such as that posed by the coronavirus pandemic. Firstly, by utilizing a type of servant leadership, that emphasizes empowerment, involvement, and collaboration, academic leaders with emotional intelligence and emotional stability should place the interests of others above their own. Secondly, academic leaders should distribute leadership responsibilities to a network of teams throughout the organization to improve the quality of the decisions made in crisis resolution and thirdly, leaders should communicate clearly and frequently to all stakeholders through a variety of communication channels. Looking forward, the rise of the flexible “allostatic leader” with the adaptive capacity to learn and evolve in crisis, to emerge better able to address future crises, is described.
The Lysosomal Diseases Testing Laboratory: A review of the past 47 years
Authors: Wenger David A. , Luzi Paola
Published: April 2020

Lysosomal disorders are diseases that involve mutations in genes responsible for the coding of lysosomal enzymes, transport proteins, activator proteins and protein processing enzymes. These defects lead to the storage of specific metabolites within lysosomes resulting in a great variety of clinical features depending on the tissues with the storage, the storage products and the extent of the storage. The methods for rapidly diagnosing patients started in the late 1960's when the enzyme defects were identified eliminating the need for tissue biopsies. The first requests for diagnostic help in this laboratory came in 1973. In that year, patients with Krabbe disease and Niemann‐Pick type A were diagnosed. Since that time samples from about 62 000 individuals have been received for diagnostic studies, and 4900 diagnoses have been made. The largest number of diagnosed individuals had metachromatic leukodystrophy and Krabbe disease because of our research interest in leukodystrophies. A number of new disorders were identified and the primary defects in other disorders were clarified. With new methods for diagnosis, including newborn screening, molecular analysis, microarrays, there is still a need for biochemical confirmation before treatment is considered. With new treatments, including gene therapy, stem cell transplantation, enzyme replacement used alone or in combination becoming more available, the need for rapid, accurate diagnosis is critical.
Thermal‐ and collision‐induced dissociation studies of functionalized imidazolium‐based ionic liquid cations
Authors: De Silva Maleesha , Brown Andrew C. , Patrick Amanda L.
Published: April 2020

Ionic liquids are now used in applications ranging from chemical synthesis to spacecraft propulsion. With this comes the need to characterize new syntheses, identify environmental contamination, and determine eventual fate in terrestrial and space environments. This work investigates the effects of source conditions, particularly capillary temperature, on the observed mass spectrum and determines the collision‐induced dissociation (CID) patterns of imidazolium‐based ionic liquid cations as a function of their substituent types. Experiments were carried out on a Thermo LTQ‐XL ion‐trap mass spectrometer and a Bruker microTOF‐Q II mass spectrometer. Dissociation of the imidazolium cations occurred predominantly via substituent losses, except in benzyl‐substituted systems, for which the neutral loss of the imidazole was exclusively observed. Several of these dissociation pathways were studied in greater depth using complementary quantum chemical calculations. The nature of the neutral losses from the substituents was found to be highly dependent upon the nature of the substituent, as would be expected, establishing bases for characterization.
Enhanced winter and summer trend difference of Madden–Julian Oscillation intensity since 1871
Authors: Wang Ziyue , Li Tim , Gao Jianyun , Peng Melinda
Published: April 2020

Long‐term winter and summer Madden–Julian Oscillation (MJO) trends in the past 138 years (1871–2008) were examined using National Oceanic and Atmospheric Administration (NOAA) 20th Century Reanalysis V2c dataset. It is found that MJO shows a distinctive different trend between boreal winter and summer. While the MJO intensity in both boreal winter and summer has a rising trend, the winter trend is much greater than the summer trend. As a result, the winter–summer difference shows a significant increasing trend. The distinctive winter and summer trends are attributed to the difference of atmospheric background circulation (such as vertical velocity) and static stability responses to the global warming between boreal winter and summer over equatorial eastern Indian Ocean. In boreal winter, both the surface moistening and strengthened inter‐tropical convergence zone convection contribute to an increase of MJO activity. This is in contrast to boreal summer when a greater static stability and anomalous subsidence tend to offset the moistening effect, leading to a relatively weaker increase of the MJO activity.
Guest editorial: Clarifications on the use of the new classification of periodontitis
Authors: Sanz Mariano , Papapanou Panos N. , Tonetti Maurizio S. , Greenwell Henry , Kornman Ken
Published: April 2020

This editorial provides clarifications on the application of the Stage and Grade classification of periodontitis. In particular it describes: (1) how to apply the extent criterion to the defined Stage of the disease; and (2) how to calculate tooth loss because of periodontitis in Stage III and IV cases presenting with evidently hopeless (irrational to treat) teeth with a clinical definition of such teeth.
A comparison of the nutritional value of Einkorn, Emmer, Khorasan and modern wheat: whole grains, processed in bread, and population‐level intake implications
Authors: Van Boxstael Frank , Aerts Hanna , Linssen Sarah , Latré Joos , Christiaens Anneline , Haesaert Geert , Dierickx Isabelle , Brusselle Joeri , De Keyzer Willem
Published: April 2020

BACKGROUND

Interest in alternatives to the traditional wheat Triticum aestivum among farmers, millers, bakers, and consumers is increasing. The Altergrain project aimed to compare the Belgian‐soil cultivated Einkorn (1K), Emmer (EMM), Khorasan (KH), and modern wheat (MW) with respect to nutritional values of kernels, breads made from these cereals, and population‐level nutrient intake implications.

RESULTS

Ancient wheats 1K, EMM, and KH contain lower total carbohydrate content than MW. Further, ancient wheats are higher in both protein and crude ash content. Vitamin E levels in breads prepared using 1K and EMM were higher than those in MW, but those prepared from KH had lower vitamin E levels than MW. Breads prepared using ancient wheats have higher total phenol content (TPC) than those from MW. Baking caused a decrease in vitamin E and TPC in bread prepared from ancient wheat, the exception being the one prepared using KH, which had a higher TPC than MW. When replacing bread made from MW with those made from ancient grains, no differences were observed with respect to conformance with the Belgian Recommend Daily Requirements.

CONCLUSION

Ancient wheats from Belgian soil are as nutritive as MWs even after being processed into bread. At the kernel level, nutritional differences are present, but only small differences are present in terms of nutritional intake when nutrition parameters are calculated for consumed bread. © 2020 Society of Chemical Industry
Fermentation with mono‐ and mixed cultures of Lactobacillus plantarum and L. casei enhances the phytochemical content and biological activities of cherry silverberry (Elaeagnus multiflora Thunb.) fruit
Authors: Lizardo Rona Camille M , Cho Hyun Dong , Won Yeong Seon , Seo Kwon Il
Published: April 2020

BACKGROUND

Lactic acid fermentation has been widely used to improve the nutritional and functional properties of food products. Cherry silverberry (Elaeagnus multiflora Thunb.) is considered as an invasive plant species with known medicinal and functional properties. In this study, improvement of the biological activity and health benefits of cherry silverberry fruit through lactic acid fermentation was investigated.

RESULTS

Extracts of cherry silverberry fruits fermented by pure cultures of Lactobacillus plantarum KCTC 33131 and L. casei KCTC 13086 exhibited favorable physicochemical properties and enhanced phytochemical content, antioxidant properties (DPPH radical scavenging activity, reducing power, superoxide dismutase‐like property and hydrogen peroxide scavenging activity) and α‐glucosidase and tyrosinase enzyme inhibitory activity as compared with unfermented fruits. Despite a decrease in the specific phenolic acid contents among the fermented samples, the cherry silverberry fruit fermented by mixed cultures of L. plantarum and L. casei contained superior total polyphenols (3.78 ± 0.22 mg GAE g−1) and total (0.66 ± 0.12 mg QE g−1) and individual flavonoid contents in comparison with fruits fermented by single cultures and unfermented ones. Multivariate analysis also showed strong association among total phytochemical contents and biological activities.

CONCLUSIONS

This work has elucidated the effect of fermentation with L. plantarum KCTC 33131 and L. casei KCTC 13086 on the improvement of the physicochemical properties and biological activity of cherry silverberry fruit. It also revealed the potential application of fermented cherry silverberry in the production of food materials beneficial for health. © 2020 Society of Chemical Industry
A long‐term follow‐up study of extracorporeal irradiated autografts in limb salvage surgery for malignant bone and soft tissue tumors: A minimum follow‐up of 10 years after surgery
Authors: Outani Hidetatsu , Takenaka Satoshi , Hamada Kenichiro , Imura Yoshinori , Kakunaga Shigeki , Tamiya Hironari , Wakamatsu Toru , Naka Norifumi , Ueda Takafumi , Araki Nobuhito
Published: April 2020

Background and Objectives

The aim of this study is to assess the survival, function, radiographic appearance, and modes of failure of extracorporeal irradiated (ECI) autografts in a long‐term setting.

Methods

We retrospectively reviewed 87 patients who were treated for bone and soft tissue tumors using ECI autografts between 1988 and 2009.

Results

The 56 patients had a minimum follow‐up of 10 years, and the median follow‐up period was 16.5 years. The reimplantation procedures included 24 osteoarticular grafts, 16 intercalary grafts, 10 autograft‐prosthetic composite grafts, and 6 hemicortical grafts. The 15‐year graft and event‐free survival rates were 76.8% and 47.9%, respectively. Infection and structural failure were the most common reasons for additional surgery. The time for additional surgery was significantly longer in patients with composite grafts (P < .01). The median Musculoskeletal Tumor Society score and the International Society of Limb Salvage score were 80% and 84%, respectively.

Conclusions

ECI autografts are a durable option for reconstruction after resection of musculoskeletal tumors and provide good function over more than 15 years. Most graft failures occurred within 5 years of the index surgery. However, composite grafts showed a tendency to fail more than 10 years after the surgery.
Photo‐stimulated “turn‐on/off” molecularly imprinted polymers based on magnetic mesoporous silicon surface for efficient detection of sulfamerazine
Authors: Xu Wanzhen , Gao Minmin , Yin Xifeng , Zhang Liming , Cao Yunfei , Zhang Yiyun , Huang Weihong
Published: April 2020

In this study, novel photo‐stimulated molecularly imprinted polymers based on magnetic mesoporous carrier surface were developed for selective identification and intelligent separation of sulfamerazine in complex samples. The photosensitive monomer of the molecularly imprinted polymers was azobenzene derivative 5‐[(4‐(methacryloyloxy)phenyl) diazenyl] isophthalic acid with stimulus reaction mechanisms, which has photoisomerization between trans and cis for N=N bonds. Further, the properties of the photo‐stimulated molecularly imprinted polymers were further evaluated through several sets of adsorption experiments. It illustrated that the maximum adsorption amount is 0.45 mmol/L. By ultraviolet spectrophotometry, the material reaches typical characteristic peaks of photo sensitivity, and the cycle time is 16 min. Three adsorption and desorption processes were repeated, the adsorption rate reached 34.4%. Overall, the photo‐stimulated molecularly imprinted polymers can enrich and separate determine sulfamerazine with high selectivity, which have good recovery for real samples.
EAT‐10 Scores and Fiberoptic Endoscopic Evaluation of Swallowing in Head and Neck Cancer Patients
Authors: Florie Michelle , Pilz Walmari , Kremer Bernd , Verhees Femke , Waltman Ghislaine , Winkens Bjorn , Winter Naomi , Baijens Laura
Published: April 2020

Objective

The purpose of this study was to determine the relationship between patient‐reported symptoms of oropharyngeal dysphagia (OD) using the Eating Assessment Tool (EAT)‐10 and the swallowing function using a standardized fiberoptic endoscopic evaluation of swallowing (FEES) protocol in head and neck cancer (HNC) patients with confirmed OD.

Methods

Fifty‐seven dysphagic HNC patients completed the EAT‐10 and a FEES. Two blinded clinicians scored the randomized FEES examinations. Exclusion criteria consisted of presenting with a concurrent neurological disease, scoring below 23 on a Mini‐Mental State Examination, being older than 85 years, having undergone a total laryngectomy, and being illiterate or blind. Descriptive statistics, linear regression, sensitivity, specificity, and predictive values were calculated.

Results

The majority of the dysphagic patients (N = 38; 66.7%) aspirated after swallowing thin liquid consistency. A large number of patients showed postswallow pharyngeal residue while swallowing thick liquid consistency. More specifically, 42 (73.0%) patients presented postswallow vallecular residue, and 39 (67.9%) patients presented postswallow pyriform sinus residue. All dysphagic patients had an EAT‐10 score ≥ 3. Linear regression analyses showed significant differences in mean EAT‐10 scores between the dichotomized categories (abnormal vs. normal) of postswallow vallecular (P = .037) and pyriform sinus residue (P = .013). No statistically significant difference in mean EAT‐10 scores between the dichotomized categories of penetration or aspiration was found (P = .966).

Conclusion

The EAT‐10 questionnaire seems to have an indicative value for the presence of postswallow pharyngeal residue in dysphagic HNC patients, and a value of 19 points turned out to be useful as a cutoff point for the presence of pharyngeal residue in this study population.

Level of Evidence: 2b
Evaluating Common Cavity Cochlear Deformities Using CT Images and 3D Reconstruction
Authors: Weiss Nora M. , Langner Soenke , Mlynski Robert , Roland Peter , Dhanasingh Anandhan
Published: April 2020

Objectives

The aim of this study is to compare the common cavity (CC) with the normal anatomy inner ear in order to evaluate whether the cavity is representing both the cochlear and the vestibular parts of the inner ear and to revisit CC deformity from a three‐dimensional (3D) perspective.

Methods

High‐resolution computed tomography image datasets of 17 temporal bones initially identified as CC were evaluated with 3D reconstruction and multiplanar image analysis using a free available software for 3D segmentation of the inner ear. All 3D images of CC were compared to a normal inner ear. Maximum and minimum diameter of the CC were correlated with the circumference of the CC in an axial plane.

Results

In 13 cases (76%), CC represented only the vestibular part of the inner ear and did not represent CC as defined here and by Sennaroglu, Kontorinis, and Khan. True CC was correctly diagnosed in only one case (6%). In three cases (18%), a rudimentary part of the cochlear portion could be identified. The axes' length of the elliptical cavity showed a strong positive linear relation to the circumference of the cavity (long axis: r = 0.94; P < .0001; short axis: r = 0.68; P = .0029).

Conclusion

This study supports the assumption that many reported CC cases only represent the vestibular part of the inner ear and are therefore cases of cochlear aplasia. 3D segmentation and systematic analysis of CT‐imaging add clinical value to the comprehension of the morphology of the anatomical structures of the inner ear.

Level of Evidence

2C Laryngoscope, 131:386–391, 2021
Urban and agricultural soils in Southern California are a reservoir of carbapenem‐resistant bacteria
Authors: Lopez Nicolas V. , Farsar Cameron J. , Harmon Dana E. , Ruiz Cristian
Published: April 2020

Carbapenems are last‐resort β‐lactam antibiotics used in healthcare facilities to treat multidrug‐resistant infections. Thus, most studies on identifying and characterizing carbapenem‐resistant bacteria (CRB) have focused on clinical settings. Relatively, little is still known about the distribution and characteristics of CRBs in the environment, and the role of soil as a potential reservoir of CRB in the United States remains unknown. Here, we have surveyed 11 soil samples from 9 different urban or agricultural locations in the Los Angeles–Southern California area to determine the prevalence and characteristics of CRB in these soils. All samples tested contained CRB with a frequency of <10 to 1.3 × 104 cfu per gram of soil, with most agricultural soil samples having a much higher relative frequency of CRB than urban soil samples. Identification and characterization of 40 CRB from these soil samples revealed that most of them were members of the genera Cupriavidus, Pseudomonas, and Stenotrophomonas. Other less prevalent genera identified among our isolated CRB, especially from agricultural soils, included the genera Enterococcus, Bradyrhizobium, Achromobacter, and Planomicrobium. Interestingly, all of these carbapenem‐resistant isolates were also intermediate or resistant to at least 1 noncarbapenem antibiotic. Further characterization of our isolated CRB revealed that 11 Stenotrophomonas, 3 Pseudomonas, 1 Enterococcus, and 1 Bradyrhizobium isolates were carbapenemase producers. Our findings show for the first time that both urban and agricultural soils in Southern California are an underappreciated reservoir of bacteria resistant to carbapenems and other antibiotics, including carbapenemase‐producing CRB.
A Novel DBS Paradigm for Axial Features in Parkinson's Disease: A Randomized Crossover Study
Authors: Karl Jessica A. , Ouyang Bichun , Goetz Steven , Metman Leo Verhagen
Published: April 2020

Background

High‐frequency (130–185 Hz) deep brain stimulation (DBS) of the subthalamic nucleus is more effective for appendicular than axial symptoms in Parkinson's disease (PD). Low‐frequency (60–80 Hz) stimulation (LFS) may reduce gait/balance impairment but typically results in worsening appendicular symptoms. We created a “dual‐frequency” programming paradigm (interleave‐interlink, IL‐IL) to address both axial and appendicular symptoms. In IL‐IL, 2 overlapping LFS programs are applied to the DBS lead, with the overlapping area focused on the optimal cathode. The nonoverlapping area (LFS) is thought to reduce gait/balance impairment, whereas the overlapping area (high‐frequency stimulation, HFS) aims to control appendicular symptoms.

Methods

We performed a randomized, double‐blind crossover trial comparing patients’ previously optimized IL‐IL and conventional HFS paradigms. Each arm was 2 weeks in duration. The primary outcome measure was the patient/caregiver Modified Clinical Global Impression Severity (CGI‐S). Secondary outcome measures included blinded motor evaluations, timed tests, patient/caregiver questionnaires, and Personal KinetiGraphs (PKG).

Results

Twenty‐five patients were enrolled, and 20 completed. The patient/caregiver CGI‐S for gait/balance (P = 0.01) and appendicular symptom control (P = 0.001), and the blinded rater MDS‐UPDRS‐III (−5.22, P = 0.02), CGI‐S gait/balance (P = 0.01), and CGI‐S speech (P = 0.02) were better while on IL‐IL. Scores on Parkinson's Disease Quality of Life (P = 0.002) and Freezing‐of‐Gait Questionnaires (P = 0.04) were better on IL‐IL. The Timed‐Up‐and‐Go was 9.8% faster (P = 0.01), with 11.8% reduction in steps (P = 0.001) on IL‐IL. There was no difference in PKG bradykinesia (P = 0.18) or tremor (P = 0.23) between paradigms.

Conclusions

Our results prompt consideration of this novel programming paradigm (IL‐IL) for PD patients with axial symptom impairment as a new treatment option for both axial and appendicular symptoms. © 2020 International Parkinson and Movement Disorder Society
Microvascular coupler device versus hand‐sewn venous anastomosis: A systematic review of the literature and data meta‐analysis
Authors: Maruccia Michele , Fatigato Giusy , Elia Rossella , Ragusa Luigi Amerigo , Vestita Michelangelo G. , Nacchiero Eleonora , Robusto Fabio , Nicoli Fabio , Pedro Ciudad  , Giudice Giuseppe
Published: April 2020

Background

Successful vascular anastomosis is essential for the survival of free tissue transfer. The aim of the study is to review the current literature and perform a meta‐analysis to assess the potential advantages of a mechanical anastomosis coupler device (MACD) over the hand‐sewn (HS) technique for venous anastomoses.

Methods

A systematic Medline search was performed to gather all reports of articles related to MACD from 1984 until now. The following data were extracted: first author and publication date, study design, number of patients and anastomosis, coupler size, site and type of reconstruction, venous anastomotic time, flap failure. A meta‐analysis was performed on articles that met the following inclusion criteria: studies comparing MACD and HS technique in venous anastomosis, reporting anastomotic time, and postoperative complications.

Results

Thirty‐three studies were included for the analysis. Twenty‐four were retrospective case series and nine were retrospective comparative studies. A total of 12,304 patients were enrolled with a mean age of 49.23 years (range 31–72). A total of 13,669 flaps were accomplished. The thrombosis rate recorded with MACD was 1.47%. The meta‐analysis revealed that MACD significantly decreased anastomotic time (standard difference in means = −0.395 ± 0.105; Z = −3.776; p < .001) and postoperative flap failure risk (odds ratio [OR] = 0.362, 95% confidence interval [CI] = 0.218–0.603, Z = −3.908, p < .001), but it did not decrease postoperative venous thrombosis risk (OR = 0.504, 95% CI = 0.255–1.129, Z = −1.666, p = .096).

Conclusions

MACDs are a safe and effective alternative to traditional anastomosis. The anastomotic coupler is easier, much faster, and requires less technical skills than a HS microvascular anastomosis.
The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction
Authors: Sergi Domenico , Boulestin Hakim , Campbell Fiona M. , Williams Lynda M.
Published: April 2020

Advanced glycation end products (AGEs) are a heterogeneous group of molecules produced, non‐enzymatically, from the interaction between reducing sugars and the free amino groups of proteins, nucleic acids, and lipids. AGEs are formed as a normal consequence of metabolism but can also be absorbed from the diet. They have been widely implicated in the complications of diabetes affecting cardiovascular health, the nervous system, eyes, and kidneys. Increased levels of AGEs are also detrimental to metabolic health and may contribute to the metabolic abnormalities induced by the Western diet, which is high in processed foods and represents a significant source of AGEs. While increased AGE levels are a consequence of diabetic hyperglycaemia, AGEs themselves activate signaling pathways, which compromise insulin signaling and pancreatic β‐cell function, thus, contributing to the development of type 2 diabetes mellitus (T2DM). Furthermore, AGEs may also contribute to the obesogenic effects of the Western diet by promoting hypothalamic inflammation and disrupting the central control of energy balance. Here, the role of dietary AGEs in metabolic dysfunction is reviewed with a focus on the mechanisms underpinning their detrimental role in insulin resistance, pancreatic β‐cell dysfunction, hypothalamic control of energy balance, and the pathogenesis of T2DM and obesity.
Design and fabrication of a high‐precision 360° laser receiver for leveling applications
Authors: Wang Xianfan , Yang Jianhua , Huang Tengchao
Published: April 2020

The laser technique based sensors and actuators can provide many superior properties as noncontact, high sensitivity, remote operation, and reliable performance in contrast to other mechanical and electrical techniques. In this paper, we design and fabricate a high‐precision 360° laser receiver for leveling, especially for agricultural and construction field. The laser receiver is primarily composed of photoelectrical conversion module, electrical signal processing module, and display panel module. Based on the centroid method, the detection error of the laser receiver with respect to laser source and silicon photocell array, is analyzed and simulated. The design and fabrication process are described in detail, including the overall structure and electrical circuits. Furthermore, this fabricated laser receiver is demonstrated to be high precision through several static and dynamic tests in the distance of 10 and 50 m. Besides, this fabricated laser possesses wireless transmission function, which provides much convenient for users in remote operation.