bluuebunny/crossref_metadata_2025 huggingface dataset:
Do my feelings fit the diagnosis? Avoiding misdiagnoses in psychosomatic consultation services
Authors: Seidl Elias , Seidl Otmar
Published: January 2021

Objective

Misdiagnoses are a major concern with far‐reaching consequences, which have rarely been studied systematically. Therefore, the present study evaluated factors causing misdiagnoses identified by psychosomatic consultation services.

Methods

Over a period of 5 years, all patients referred to the psychosomatic consultation services of a large university hospital were analyzed consecutively for misdiagnoses. We analyzed the reasons for suspecting a misdiagnosis through systematic introspection during peer supervision and evaluated the causes during semistructured interviews with the referring physician.

Results

In 165 psychosomatic consultations, 24 disorders were misdiagnosed (15%). The reasons for questioning the initial diagnoses were the consulting physician's feelings and thoughts resulting from the patients’ inappropriate behavior during the consultation and unusual clinical features. In eight cases, the misdiagnosis resulted from availability bias, and in three cases each it resulted from confirmation bias, search satisfaction bias, and framing effect and attribution bias. However, lack of medical knowledge played only a minor role.

Conclusion

This study highlights the nonrational elements of the diagnostic process. In the context of psychosomatic consultation services, introspection and intuitive thought processes are helpful in identifying misdiagnoses. Self‐satisfaction (availability bias) and overconfidence (confirmation bias) are most likely to result in misdiagnoses.
Mutations in SARS‐CoV‐2 nsp7 and nsp8 proteins and their predicted impact on replication/transcription complex structure
Authors: Reshamwala Shamlan M. S. , Likhite Vishakha , Degani Mariam S. , Deb Shalini S. , Noronha Santosh B.
Published: January 2021

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) RNA‐dependent RNA polymerase (RdRp) has been identified to be a mutation hot spot, with the P323L mutation being commonly observed in viral genomes isolated from North America. RdRp forms a complex with nonstructural proteins nsp7 and nsp8 to form the minimal replication/transcription machinery required for genome replication. As mutations in RdRp may affect formation of the RdRp–nsp7–nsp8 supercomplex, we analyzed viral genomes to identify mutations in nsp7 and nsp8 protein sequences. Based on in silico analysis of predicted structures of the supercomplex comprising of native and mutated proteins, we demonstrate that specific mutations in nsp7 and nsp8 proteins may have a role in stabilization of the replication/transcription complex.
A snapshot of the prescribing patterns and off‐label use of gabapentinoid agents in tertiary care: a retrospective, cross‐sectional, descriptive study
Authors: Prior Felicity H.
Published: January 2021

Background

Prescribing of gabapentinoids has increased worldwide and off‐label use is well‐described. Patients may be at risk of harm from inappropriate use. Prescribing patterns in tertiary care have not been described in the Australian setting.

Aim

The aim of this study was to assess the prescribing patterns of gabapentinoids across a Local Health District in New South Wales, Australia.

Method

Clinical and prescribing records over a 48‐h period were reviewed. Patient demographics, renal function and concurrent opioid use were recorded. Dosing details and the indications for treatment were analysed.

Results

Almost 40% of patients were prescribed concomitant opioid therapy, half of which were in the postoperative setting, an indication for which there is little evidence. Appropriate dose reductions were made in the majority of patients with renal impairment. Methods used for ceasing therapy were not in accordance with best practice. Indications for use were difficult to ascertain from medical records. However, only approximately half of usage of both agents appeared to be for approved indications.

Conclusion

Prescribing of gabapentinoids could be improved. Although dosages are largely in accordance with recommended dosages for renal impairment, there is significant concern with concurrent use of opioids and use for non‐approved indications, many of which lack clinical evidence. Further investigation into prescribing habits in the postoperative setting is warranted. There is a potential role for increased education and intervention to optimise use.
MARSFT: Efficient fitting of CARS spectra using a library‐based genetic algorithm
Authors: Greifenstein M. , Dreizler A.
Published: January 2021

A loss‐less compressed library scheme is presented in this publication that allows for computationally efficient fitting of coherent anti‐Stokes Raman spectra with no restriction to the number of degrees of freedom for the spectral fit. The compression is achieved by convolving the squared modulus and the real part of the complex susceptibility with a Gaussian kernel narrower than the experimental apparatus function. This effectively reduces library size while allowing to convolve to the final experimental linewidth during the fit. For the optimization procedure, a gradient‐free mixed‐integer genetic algorithm was implemented due to its ability to extract library spectra without interpolation. We demonstrate the ability of the code by comparing it to CARSFT in terms of dependency on starting solution, computational cost and accuracy using simulated spectra with varying noise contribution.
Fabrication of fish gelatin / sodium alginate double network gels for encapsulation of probiotics
Authors: Liu Jialin , Liu Fenghua , Ren Teng , Wang Jiong , Yang Mengxuan , Yao Yao , Chen Hao
Published: January 2021

BACKGROUND

To improve the environmental resistance of probiotics, and particularly their survival in the gastrointestinal environment, a fish gelatin (FG) / sodium alginate (SA) double network gelation (FSDN) was developed to encapsulate them. Thermal treatment and calcium ion inducement were adopted to fabricate fish gelatin and sodium alginate gels. It was feasible to scale up this process. The effects of FG concentration (0–60 g/L) on FSDN properties, including morphology, water‐holding capacity, and encapsulation efficiency were evaluated.

RESULTS

The results indicated that the addition of FG could improve the transparency, rehydration, and water‐holding capacity of FSDN. Scanning electronic microscope (SEM) images revealed that FSDN had a denser and more complete structure than SA. Encapsulation efficiency improved from 15.85% to 91.91% as the FG concentration ranged from 0 to 50 g/L. Bifidobacterium longum embedded by FSDN showed better thermal stability than when it was free. Compared with bare probiotics (1.7%), the encapsulated ones exhibited higher viability (above 15%) in simulated gastric fluid.

CONCLUSION

In conclusion, interpenetrating FSDN is an effective barrier constituent and could achieve the targeted delivery of probiotics. It is a potential new delivery carrier for the oral administration of probiotics. © 2021 Society of Chemical Industry
The prognostic value of tumor deposits and the impact on the TNM classification system in esophageal cancer patients
Authors: Zhang Guochao , Zhang Chaoqi , Wang Lide , Xue Liyan , Jia Jia , Zuo Zhichao , Sun Nan , Gao Shugeng , Xue Qi , He Jie
Published: January 2021

Objective

To explore the prognostic significance of tumor deposits (TDs), isolated tumor foci lacking residual lymph nodes, in esophageal cancer (EC).

Methods

A retrospective review of patients with EC undergoing esophagectomy between 2005 and 2017 was conducted. The prognostic value of TD was evaluated using a Cox regression model. Patients from different sources and periods were split into discovery and validation sets. A propensity score matching model was used in the validation set to reduce the confounding bias. The impact of TD on the TNM classification system was evaluated.

Results

The discovery and validation sets included 179 and 2875 patients, respectively. Propensity‐matched patients with and without TDs were constructed in the validation set with 132 patients in each group. Overall survival (p < .001 and p = .004, respectively) and disease‐free survival (p < .001 and p = .019, respectively) were both decreased in TD positive patients in the discovery set and propensity‐matched groups of validation set. Classifying patients with TDs into pN3 stage improved the discriminative power of the current TNM staging system.

Conclusions

TD is an independent prognostic factor for EC. The inclusion of TD in the TNM staging system may upstage appropriate patients to help guide therapy, and future studies are warranted.
Screening and isolation of potential lipoxidase and superoxide dismutase inhibitors from Scutellaria baicalensis Georgi using high‐speed countercurrent chromatography target‐guided by ultrafiltration‐liquid chromatography‐mass spectrometry
Authors: Xia Jianli , Liu Chunming , Niu Huazhou , Hou Wanchao , Li Sainan
Published: January 2021

We present a simple and efficient method based on ultrafiltration high‐performance liquid chromatography coupled with a photodiode array detector and electrospray ionization mass spectrometry for the rapid screening and identification of ligands obtainable from the extract of Scutellaria baicalensis. Five major compounds (chrysin‐6‐C‐arabinosyl‐8‐C‐glucoside, chrysin‐6‐C‐glucosyl‐8‐C‐arabinoside, baicalin, oroxylin A‐7‐O‐glucuronide, and wogonoside) were identified as potentially effective inhibitors of lipoxidase and superoxide dismutase. Subsequently, specific binding ligands were separated by high‐speed countercurrent chromatography, using ethyl acetate/ethyl alcohol/water acetate (0.1%) (1.0:0.1:1.0, v/v/v) as the solvent system. To the best of our knowledge, this is the first report of S. baicalensis extracts containing potent lipoxidase and superoxide dismutase inhibitors. Our results demonstrate that the systematic isolation of bioactive components from the n‐butyl alcohol layer of S. baicalensis guided by ultrafiltration high‐performance liquid chromatography coupled with photodiode array detection and electrospray ionization mass spectrometry represents a feasible and efficient technique that could also be employed for the identification and isolation of other enzyme inhibitors.
Fetal Outcomes Associated with the Sequence of Doppler Deterioration in Severely Growth‐Restricted Fetuses
Authors: Kanagawa Takeshi , Ishii Keisuke , Yamamoto Ryo , Sasahara Jun , Mitsuda Nobuaki
Published: January 2021

Objectives

Various patterns of Doppler deterioration exist in fetal growth restriction (FGR). However, the factors that differentiate these patterns are still unknown. The purpose of this study was to clarify the perinatal outcomes and factors to determine the pattern of Doppler deterioration in severe FGR.

Materials and Methods

We conducted a retrospective cohort study of preterm severe FGR with Doppler abnormality, wherein the clinical features, including maternal characteristics, medical history, and sonographic findings, were compared between the patterns of Doppler deterioration. We used the multivariable logistic regression analyses to identify the factors associated with the pattern of Doppler deterioration.

Results

Of 322 eligible fetuses, 143 had Doppler abnormalities. Fetuses with Doppler deterioration from ductus venosus uniquely featured fetal and placental‐umbilical abnormalities detected after birth. Gestational age (GA) at diagnosis of FGR and at the first diagnosis of Doppler abnormality in fetuses with Doppler deterioration from middle cerebral artery (MCA) were later than those from umbilical artery. In addition, the factor associated with Doppler deterioration from MCA was 31‐week GA at the first diagnosis of Doppler abnormality (adjusted odds ratio [aOR]: 26.7; 95% CI: 8.35–103), not GA at diagnosis of FGR (aOR: 1.82; 95% CI: 0.50–5.96).

Conclusions

Characteristics of each Doppler deterioration pattern might reflect FGR etiology. Undetectable anomalies and umbilical‐placental abnormalities were found in fetuses with Doppler deterioration from the ductus venosus. Doppler deterioration from the MCA was observed after 31 weeks of gestation not only in the late‐onset FGR but also in the early‐onset FGR with normal umbilical artery Doppler findings.
Kinetic analysis of the degradation of HDPE+PP polymer mixtures
Authors: Briceno Jhon , Lemos Maria Amélia , Lemos Francisco
Published: January 2021

An in depth understanding of the kinetics of the decomposition of plastic mixtures is necessary to enhance chemical recycling approaches, in particular by pyrolysis. The fact that plastic waste is usually composed of mixtures of plastics constitutes a hindrance for secondary recycling but may not be a particular difficulty for tertiary recycling. In this study, an analysis of the thermal degradation of mixtures of high‐density polyethylene (HDPE) and polypropylene (PP), in different proportions, was carried‐out under pyrolysis conditions using thermogravimetric analysis (TGA) under nonisothermal conditions, at different heating rates. Both isoconversional and model‐fitting approaches were used to estimate kinetic parameters from the experimental information. It was found that both the degradation of HDPE and PP, as well as their mixtures, can be described by a single‐step degradation process but that the degradation process is influenced by the proportion between the two plastics. The HDPE/PP mixtures in which PP has a higher ratio than HDPE cause the degradation onset temperature for the mixture to be lower than either pure PP or pure HDPE. Also, it was found that the apparent activation energy estimated was lower for these mixtures in comparison with the pure polymers. This implies that there are extensive interactions between the plastics during the degradation procedure and, from an operational point of view, it may be actually easier to degrade plastic mixtures than the corresponding pure streams, a conclusion that is important in the context of tertiary recycling of plastic mixtures. Furthermore, it was observed that a compensation effect exists that encompasses all the kinetic data for the mixtures, regardless of the composition, indicating that, although significant changes occur in relation to the activation energy, the underlying degradation mechanism remains the same.
Prognostic Value of Third Cervical Vertebra Skeletal Muscle Index in Oral Cavity Cancer: A Retrospective Study
Authors: Chang Sheng‐Wei , Hsu Cheng‐Ming , Tsai Yuan‐Hsiung , Chang Geng‐He , Tsai Ming‐Shao , Huang Ethan I. , Tsai Yao‐Te
Published: January 2021

Objectives/Hypothesis

To assess the prognostic utility of third cervical vertebra skeletal muscle index (C3 SMI) measured from preoperative head and neck computed tomography (CT) in patients with oral cavity squamous cell carcinoma (OSCC).

Study Design

Retrospective study.

Methods

We retrospectively reviewed the medical records of 125 patients who underwent primary curative surgery for OSCC between 2009 and 2017. Their preoperative C3 SMI was calculated by adjusting the C3 cross‐sectional area delineated on head and neck CT by body height squared. A Cox proportional hazard model was employed to identify prognostic factors, and a novel nomogram based on C3 SMI was built for individualized survival prediction.

Results

In Kaplan–Meier analysis, high C3 SMI was significantly associated with higher 5‐year disease‐free survival (DFS) and overall survival (OS) than low C3 SMI. In multivariate analysis, low C3 SMI was an independent risk factor for poor DFS and OS (hazard ratio [HR]: 2.197; 95% confidence interval [CI], 1.170–4.512, P = .032 and HR: 2.143; 95% CI, 1.232–3.728, P = .007, respectively). The concordance‐index (C‐index) of the nomogram based on C3 SMI was 0.814 for OS, higher than that of the nomogram based on tumor–node–metastasis staging alone (C‐index = 0.731).

Conclusions

C3 SMI might serve as a novel prognosticator in OSCC patients undergoing curative surgery, and the nomogram based on C3 SMI might provide good prognostic discrimination ability for individualized survival prediction.

Level of Evidence

IV Laryngoscope, 131:E2257–E2265, 2021
The divergent impact of phenology change on the productivity of alpine grassland due to different timing of drought on the Tibetan Plateau
Authors: Hu Guozheng , Gao Qingzhu , Ganjurjav Hasbagan , Wang Zixin , Luo Wenrong , Wu Hongbao , Li Yu , Yan Yulong , Gornish Elise S. , Schwartz Mark W. , Wan Yunfan , Li Yue
Published: January 2021

Droughts are predicted to become more frequent and persist for longer periods in the future, especially in alpine regions due to climate change. However, the association mechanism between plant productivity response to drought timing and phenology in the alpine grassland of the Tibetan Plateau is unclear. We conducted manipulative drought experiments on early growing season drought (ED) and middle growing season drought (MD) to determine the impacts of drought timing on the alpine grassland. The results showed ED significantly delayed the green‐up of the community vegetation (8.20%, p < .05). However, MD advanced the withered date of the community vegetation (−2.98%, p < .05). ED and MD depressed the growing season duration, cover, height, and the aboveground biomass of the community vegetation. However, the structural equation model revealed that the effect of phenology changes on the aboveground net primary production shifts was divergent among graminoid, weeds, and community. Our results shed light on the drought tolerance mechanisms of diverse vegetation groups at different drought timings. Thus, the drought timing should not be neglected in climate change studies, especially in research related to climate extremes.
Prolonged inpatient stay after upfront total laryngectomy is associated with overall survival
Authors: Jacobs Daniel , Kafle Samipya , Earles Joseph , Rahmati Rahmatullah , Mehra Saral , Judson Benjamin L.
Published: January 2021

Objectives

To investigate factors and complications associated with prolonged inpatient length of stay (LOS) in patients who receive total laryngectomy (TL), and to analyze its effect on short‐term and long‐term overall survival (OS).

Methods

The National Cancer Database (NCDB) was queried from 2004 to 2016 for patients with laryngeal cancer, who received TL within 60 days of diagnosis, and who had an inpatient LOS ≥1 night. Multivariable binary logistic regression and survival analyses on propensity score matched cohorts with Kaplan‐Meier analysis and extended Cox regression were utilized.

Results

Eight thousand two hundred and ninety‐eight patients from the NCDB were included. Median inpatient LOS was 8 days after TL (IQR: 7, 12). Prolonged LOS was defined as above the 75th percentile or 13 days or greater. On multivariable analysis, increasing patient age (OR 1.14 per 10 years, P = .003), female sex (OR 1.35, P < .001), and Charlson‐Deyo comorbidity score of ≥2 compared to a score of 0 (OR 1.43, P < .001) were associated with prolonged LOS. Patients treated at high surgical case volume centers had a decreased likelihood for prolonged LOS (OR 0.67, P < .001). Ninety‐day mortality increased over time in patients who stayed ≥13 days. Prolonged LOS was independently associated with worse OS on multivariable analysis (HR 1.40, 95% CI: 1.22, 1.61) in a matched cohort.

Conclusions

Prolonged LOS after TL serves as a strong indicator for postoperative long‐term mortality and may help identify patients who warrant closer surveillance.

Level of Evidence

3.
Ultra‐Bright and Stable Pure Blue Light‐Emitting Diode from O, N Co‐Doped Carbon Dots
Authors: Wang Xiao , Ma Yurong , Wu Qingyao , Wang Zhenzhen , Tao Yichen , Zhao Yajie , Wang Bo , Cao Jingjing , Wang Hui , Gu Xiaoqing , Huang Hui , Li Si , Wang Xiaoyong , Hu Fengrui , Shao Mingwang , Liao Liangsheng , Sham Tsun‐Kong , Liu Yang , Kang Zhenhui
Published: January 2021

The pure blue light‐emitting diodes (LEDs) play a key role in the application of solid display and illumination. Most of pure blue LEDs reported so far, are based on semiconductor quantum dots and metal complex, involving heavy metal elements. Here, the fabrication of O, N co‐doped carbon dots (CDs) by a hydrothermal method from perylene‐3,4,9,10‐tetracarboxylic dianhydride and 2,3‐diaminophenazine is shown. These CDs show strong photoluminescence (PL) emission peaked at 447 nm (in ethanol) with absolute PL quantum yields of 88.9%. They are then doped into poly(vinyl carbazole) to form the active emission layer in the pure blue CDs LEDs. The electroluminescence emission of these CDs LEDs is centered at 452 nm with Commission Internationale d'Eclairage (CIE) coordinates of (0.14, 0.10). Moreover, the pure blue CDs LEDs show a high external quantum efficiency of 2.114%, high brightness of 648 cd m–2, long half‐lifetime (T50) of 200 h, and a favorable current efficiency of 2.2 cd A−1. This work opens a new way to develop cost‐effective, environmental‐friendly, and high‐efficient metal‐free pure blue LEDs.
A fixed point theory over stratified truth
Authors: Cantini Andrea
Published: January 2021

We present a theory of stratified truth with a μ‐operator, where terms representing fixed points of stratified monotone operations are available. We prove that is relatively intepretable into Quine's (or subsystems thereof). The motivation is to investigate a strong theory of truth, which is consistent by means ofstratification, i.e., by adopting an implicit type theoretic discipline, and yet is compatible with self‐reference (to a certain extent). The present version of is an enhancement of the theory presented in [2].
Agreement reducibility
Authors: Epstein Rachel , Lange Karen
Published: January 2021

We introduce agreement reducibility and highlight its major features. Given subsets A and B of , we write if there is a total computable function satisfying for all , .

We shall discuss the central role plays in this reducibility and its connection to strong‐hyper‐hyper‐immunity. We shall also compare agreement reducibility to other well‐known reducibilities, in particular s1‐ and s‐reducibility. We came upon this reducibility while studying the computable reducibility of a class of equivalence relations on based on set‐agreement. We end by describing the origin of agreement reducibility and presenting some results in that context.
General approach to Köthe echelon algebras
Authors: Ciaś Tomasz , Piszczek Krzysztof
Published: January 2021

We provide a study of Köthe sequence algebras. These are Fréchet sequence algebras which can be viewed as abstract analogoues of algebras of smooth or holomorphic functions. Of particular treatment are the following properties: unitality,m‐convexity,Q‐property and variants of amenability. These properties are then checked against the topological ‐(Ω) type conditions of Vogt–Zaharjuta. Description of characters and closed ideals in Köthe echelon algebras is provided. We show that these algebras are functionally continuous and we characterize completely which of them factor. Moreover, we prove that closed subalgebras of Montelm‐convex Köthe echelon algebras are Köthe echelon algebras as well and we give a version of Stone–Weiestrass theorem for these algebras. We also emphasize connections with the algebra of smooth operators.
Regorafenib inhibits migration, invasion, and vasculogenic mimicry of hepatocellular carcinoma via targeting ID1‐mediated EMT
Authors: Zhang Nan , Zhang Shaoqin , Wu Wenda , Lu Wenxian , Jiang Mingting , Zheng Ning , Huang Jing , Wang Long , Liu Hekun , Zheng Min , Wang Jichuang
Published: January 2021

Regorafenib is approved for patients with unresectable hepatocellular carcinoma (HCC) following sorafenib. However, the effect of regorafenib on HCC metastasis and its mechanism are poorly understood. Here, our data showed that regorafenib significantly restrained the migration, invasion and vasculogenic mimicry (VM) of HCC cells, and downregulated the expression of epithelial‐to‐mesenchymal transition (EMT)/VM‐related molecules. Using RNA‐seq and cellular thermal shift assays, we found that inhibitor of differentiation 1 (ID1) was a key target of regorafenib. In HCC tissues, the protein expression of ID1 was positively correlated with EMT and VM formation (CD34−/PAS+). Functionally, ID1 knockdown inhibited HCC cell migration, invasion, metastasis, and VM formation in vitro and in vivo, with upregulation of E‐cadherin and downregulation of Snail and VE‐cadherin. Moreover, Snail overexpression promoted the migration, invasion, and VM formation of ID1 knockdown cells. Snail knockdown reduced the migration, invasion, and VM formation of ID1 overexpression cells. Finally, regorafenib suppressed VM formation and decreased the expression of ID1, VE‐cadherin and Snail in HCC PDX model. In conclusion, we manifested that regorafenib distinctly inhibited EMT in HCC cells via targeting ID1, leading to the suppression of cell migration, invasion and VM formation. These findings suggest that regorafenib may be developed as a suitable therapeutic agent for HCC metastasis.
Germline MC1R variants and frequency of somatic BRAF, NRAS, and TERT mutations in melanoma: Literature review and meta‐analysis
Authors: Zanna Ines , Caini Saverio , Raimondi Sara , Saieva Calogero , Masala Giovanna , Massi Daniela , Cocorocchio Emilia , Queirolo Paola , Stanganelli Ignazio , Gandini Sara
Published: January 2021

Germline variants of the melanocortin‐1‐receptor (MC1R) gene are the most common genetic trait predisposing to cutaneous melanoma (CM). Here, we performed a literature review and meta‐analysis of the association between MC1R gene variants and the frequency of somatic mutations of the BRAF, NRAS, and TERT genes in CM patients. We included studies published until January 2020 in MEDLINE, EMBASE, Ovid Medline, and two grey literature databases. Random effect models were used to pool study‐specific estimates into summary odds ratio (SOR) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity and assess the robustness of pooled estimates. Twelve studies published between 2006 and 2018 (encompassing 3566 CM, mostly on nonacral sites) were included. MC1R gene variants were not significantly associated with the frequency of somatic mutations of the BRAF and NRAS genes. Only three studies focused on somatic mutations of the TERT gene promoter, all of which reported moderate‐to‐strong positive associations with MC1R germline variants. MC1R gene variants appear to make only moderate changes, if any, to the risk of BRAF‐ or NRAS‐mutant CM. The association with TERT promoter mutations is suggestive, yet it warrants confirmation as it is based on a still limited number of studies
The effects of uncertainties over R&D policy or market demand on R&D levels
Authors: Mai Chao‐Cheng , Lin Shih‐Chuan
Published: January 2021

This paper investigates how product market uncertainty and government research and development (R&D) subsidy uncertainty affect R&D levels in a duopoly with R&D rivalry and technological spillovers from an advanced large firm. Within this framework, one small firm and one large firm compete on R&D and output. We find that if firms' R&D efforts are strategic complements, then the firms' R&D outputs would decrease due to increased uncertainty over R&D policy but would increase due to increased uncertainty over market demand. Thus, we conclude that different types of uncertainties exert different impacts on R&D investment decisions.
Brain Motor Network Changes in Parkinson's Disease: Evidence from Meta‐Analytic Modeling
Authors: Herz Damian M. , Meder David , Camilleri Julia A. , Eickhoff Simon B. , Siebner Hartwig R.
Published: January 2021

Background

Motor‐related brain activity in Parkinson's disease has been investigated in a multitude of functional neuroimaging studies, which often yielded apparently conflicting results. Our previous meta‐analysis did not resolve inconsistencies regarding cortical activation differences in Parkinson's disease, which might be related to the limited number of studies that could be included. Therefore, we conducted a revised meta‐analysis including a larger number of studies. The objectives of this study were to elucidate brain areas that consistently show abnormal motor‐related activation in Parkinson's disease and to reveal their functional connectivity profiles using meta‐analytic approaches.

Methods

We applied a quantitative meta‐analysis of functional neuroimaging studies testing limb movements in Parkinson's disease comprising data from 39 studies, of which 15 studies (285 of 571 individual patients) were published after the previous meta‐analysis. We also conducted meta‐analytic connectivity modeling to elucidate the connectivity profiles of areas showing abnormal activation.

Results

We found consistent motor‐related underactivation of bilateral posterior putamen and cerebellum in Parkinson's disease. Primary motor cortex and the supplementary motor area also showed deficient activation, whereas cortical regions localized directly anterior to these areas expressed overactivation. Connectivity modeling revealed that areas showing decreased activation shared a common pathway through the posterior putamen, whereas areas showing increased activation were connected to the anterior putamen.

Conclusions

Despite conflicting results in individual neuroimaging studies, this revised meta‐analytic approach identified consistent patterns of abnormal motor‐related activation in Parkinson's disease. The distinct patterns of decreased and increased activity might be determined by their connectivity with different subregions of the putamen. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Efficient transfer of DNP‐enhanced 1H magnetization to half‐integer quadrupolar nuclei in solids at moderate spinning rate
Authors: Nagashima Hiroki , Trébosc Julien , Kon Yoshihiro , Lafon Olivier , Amoureux Jean‐Paul
Published: January 2021

We show herein how the proton magnetization enhanced by dynamic nuclear polarization (DNP) can be efficiently transferred at moderate magic‐angle spinning (MAS) frequencies to half‐integer quadrupolar nuclei, S ≥ 3/2, using the Dipolar‐mediated Refocused Insensitive Nuclei Enhanced by Polarization Transfer (D‐RINEPT) technique, in which a symmetry‐based
recoupling scheme built from adiabatic inversion 1H pulses reintroduces the 1H–S dipolar couplings, while suppressing the 1H–1H ones. The use of adiabatic pulses also improves the robustness to offsets and radiofrequency (rf)‐field inhomogeneity. Furthermore, the efficiency of the polarization transfer is further improved by using 1H composite pulses and continuous‐wave irradiations between the recoupling blocks, as well as by manipulating the S satellite transitions during the first recoupling block. Furthermore, in the case of large 1H–S dipolar couplings, the D‐RINEPT variant with two pulses on the quadrupolar channel results in an improved transfer efficiency. We compare here the performances of this new adiabatic scheme with those of its parent version with single π pulses, as well as with those of PRESTO and CPMAS transfers. This comparison is performed using simulations as well as DNP‐enhanced 27Al, 95Mo, and 17O NMR experiments on isotopically unmodified γ‐alumina, hydrated titania‐supported MoO3, Mg(OH)2, and l‐histidine·HCl·H2O. The introduced RINEPT method outperforms the existing methods, both in terms of efficiency and robustness to rf‐field inhomogeneity and offset.
Student and instructor perceptions of engagement after the rapid online transition of teaching due to COVID‐19
Authors: Walker Kristen A. , Koralesky Katherine E.
Published: January 2021

Engagement involves students’ investment in learning activities, as well as interrelated affective (emotive responses), behavioral (active responses), and cognitive (mental effort) components. This study assessed undergraduate student and instructor perceptions of the interrelated components of engagement during and after the rapid online transition of teaching in March 2020 due to the COVID‐19 pandemic. Fifteen courses—including laboratory, discussion‐based, large lecture, tutorial, and problem‐based learning—within a multi‐disciplinary faculty at a large research‐intensive Canadian university were surveyed to: (a) assess student and instructor perceptions of students’ levels of engagement during and after the rapid transition to online teaching due to the COVID‐19 pandemic; (b) describe which aspects of engagement were enhanced or diminished due to the rapid online transition; and (c) identify which learning activities students would find most engaging in an online setting so as to assist in developing student‐centered online pedagogical techniques. Student engagement was lower after the rapid online transition. Students who engaged by connecting with peers and instructors through in‐class discussion (affective engagement) had diminished engagement, whereas students who engaged by listening to lectures, reading course materials, and reviewing slides (cognitive engagement) had enhanced engagement. Overall, students found synchronous activities more engaging. Students experienced positive and negative outcomes related to classroom engagement when transitioning rapidly to online learning during a global pandemic.
COVID‐19 field instruction: Bringing the forests of British Columbia to students 8,000 km away
Authors: Culbert Patrick D.
Published: January 2021

Field instruction is a crucial component of natural sciences education. The COVID‐19 pandemic has shifted many university courses to an online format, significantly impacting field instruction. FRST 350, Foundational Field School, is an 8‐day University of British Columbia Forestry field course taught to incoming transfer students from partner universities in China. In August 2020, I taught this course online to students studying remotely. In re‐developing the course, I spent 9 days in the field filming high definition (HD) video, 360° video, and 360° photography to best recreate the course in a short time‐frame. A 360° video records omnidirectionally, allowing viewers to “look around” in all directions, resulting in a highly immersive experience. Students expressed favorable opinions of the course, especially traditional HD and 360° video. Students generally preferred HD videos over 360°, though this was due mostly to the high bandwidth needed for 360° video and the fact that core course content was primarily conveyed as HD videos (in recognition of bandwidth challenges), with supplementary 360° videos. Students favorably noted the interactivity and immersive feel of 360° videos and photographs. This technology is financially and logistically feasible for use in a natural sciences course. Instructors engaged in online field instruction should weigh the strengths and weaknesses of various technologies, including 360° video, when determining how to best meet their learning objectives.
Decatic B‐spline collocation scheme for approximate solution of Burgers' equation
Authors: Jena Saumya R. , Gebremedhin Guesh S.
Published: January 2021

A decatic B‐spline collocation technique is employed to compute the numerical result of a nonlinear Burgers' equation. The nonlinear term of Burgers' equation is locally linearized using Taylor series technique. The present method is effective for the approximate solution of Burgers' with a very small value of kinematic viscosity “a.” Some illustrated numerical experiments are taken into consideration to focus on the importance of the current work and some comparative studies are reported with others as well as with the exact solutions. The linear stability of the method is analyzed with Von Neumann technique. Application of higher‐order derivatives rather than lower‐order derivatives of the decatic B‐splines on the boundary conditions is the keynote to obtain a better approximate solution of the present method.
Blood is thicker than baptismal water: A late medieval perinatal burial in a small household chest
Authors: Cootes Kevin , Thomas Matthew , Jordan David , Axworthy Janet , Carlin Rea
Published: January 2021

The interment of stillborn infants in later medieval burial grounds stands at odds with Catholic Church Law, which forbade the inclusion of unbaptised children within consecrated ground. When perinatal remains occur within graveyards, their interpretation can be problematic. Did they live to be baptised, or do such examples represent clandestine burials? Historical documents indicate that some parents disobeyed the Church and secretly buried their offspring within consecrated ground. Proving such actions in the archaeological record, however, is another matter. This paper therefore investigates the discovery of a perinatal burial (Sk953) within a rural graveyard at Poulton in Cheshire, England, placed in a small household box. A multifaceted approach was used to interpret the varying strands of evidence. These comprised church law, the birth, container, orientation of the corpse, local topography, date of burial, and status of the graveyard when the infant was interred. The authors interpret the evidence as characteristic of a clandestine burial, and a rare expression of grief and love visible in the archaeological record.
Induced hepatic stellate cell integrin, α8β1, enhances cellular contractility and TGFβ activity in liver fibrosis
Authors: Nishimichi Norihisa , Tsujino Kazuyuki , Kanno Keishi , Sentani Kazuhiro , Kobayashi Tsuyoshi , Chayama Kazuaki , Sheppard Dean , Yokosaki Yasuyuki
Published: January 2021

No effective therapy exists for fatal fibrosis. New therapeutic targets are needed for hepatic fibrosis because the incidence keeps increasing. The activation and differentiation of fibroblasts into myofibroblasts that causes excessive matrix deposition is central to fibrosis. Here, we investigated whether (and which) integrin receptors for matrix proteins activate hepatic stellate cells (HSCs). First, integrin α‐subunits were investigated systematically for their expression over the course of HSC activation and their distribution on fibroblasts and other systemic primary cells. The most upregulated in plate culture‐activated HSCs and specifically expressed across fibroblast linages was the α8 subunit. An anti‐α8 neutralizing mAb was evaluated in three different murine fibrosis models: for cytotoxic (CCl4 treatment), non‐alcoholic steatohepatitis‐associated and cholestatic fibrosis. In all models, pathology and fibrosis markers (hydroxyproline and α‐smooth muscle actin) were improved following the mAb injection. We also CCl4‐treated mice with inducible Itga8−/−; these mice were protected from increased hydroxyproline levels. Furthermore, ITGA8 was upregulated in specimens from 90 patients with liver fibrosis, indicating the relevance of our findings to liver fibrosis in people. Mechanistically, inhibition or ligand engagement of HSC α8 suppressed and enhanced myofibroblast differentiation, respectively, and HSC/fibroblast α8 activated latent TGFβ. Finally, integrin α8β1 potentially fulfils the growing need for anti‐fibrotic drugs and is an integrin not to be ignored. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Discrepancies between F‐18‐FDG PET/CT findings and conventional imaging in Langerhans cell histiocytosis
Authors: Ferrell Justin , Sharp Susan , Kumar Ashish , Jordan Michael , Picarsic Jennifer , Nelson Adam
Published: January 2021

Background

Accurate risk stratification of Langerhans cell histiocytosis (LCH) is essential as management can range from conservative in single system, low risk for central nervous system (CNS) involvement lesions to intensive chemotherapy for multisystem or high‐risk disease. Additionally, being able to differentiate metabolically active from inactive lesions is essential for both prognostic reasons and to avoid potentially unnecessary treatment.

Methods

A retrospective review was performed on all patients with histopathology‐confirmed LCH at Cincinnati Children's Hospital Medical Center (CCHMC) between 2009 and 2019.

Results

One hundred seven positron emission tomography (PET)/computerized tomography (CT) images were included in the review. A discrepancy between PET/CT and conventional imaging occurred on 53 occasions. On 13 occasions, increased uptake was observed on PET in an area with no identifiable lesion on conventional imaging. On 40 occasions, lesions were found on conventional imaging where no increased uptake was observed on PET. On eight skeletal surveys, three other radiographs, four diagnostic CTs, five localization CTs, and one bone scan, no lesion was identified in an area with increased fluorodeoxyglucose (FDG) uptake. This occurred exclusively in bone. On nine skeletal surveys, one other radiograph, four diagnostic CTs, six localization CTs, 19 magnetic resonance imaging (MRI) scans, and one bone scan, a lesion was identified in a location without increased FDG uptake. This occurred in bone, CNS, and lungs.

Conclusion

F‐18‐FDG PET/CT is vital in the evaluation of LCH lesions given its ability to detect LCH lesions not detectable on conventional imaging modalities, as well as its ability to distinguish metabolically active from inactive disease. MRI and diagnostic CT are still useful adjunctive tests for identification of CNS and lung lesions.
The positive outcome of educating HIV‐infected children about beauty in an African village
Authors: Papi Massimo , Fiscarelli Ersilia
Published: January 2021

We report the interesting experience of the African Village of Hope (Dodoma, Tanzania) where HIV‐positive orphan children have been hosted, cured, and educated in the last 15 years. The particular attention to beauty in the education of the children amazed us when we were in the village working as doctors. The project and the effort to create such a model of social and medical assistance were born from the idea of the founders, Sister Maria Rosaria Gargiulo and Don Vincenzo Boselli. In light of this experience and of the healthy result obtained in the village, we believe that education in the perception of beauty is a formative aspect for all children, but may also be a powerful adjuvant therapy in severely immunocompromised young patients.
Omphalocele—What should we tell the prospective parents?
Authors: Adams April D. , Stover Samantha , Rac Martha W.
Published: January 2021

An omphalocele is a congenital defect in the abdominal wall characterized by absent abdominal muscles, fascia, and skin. The characteristic ultrasound appearance includes a midline defect with herniation of abdominal contents into the base of the umbilical cord. Other anatomic abnormalities are seen in approximately 50% of cases, most notably cardiac defects (19%–32%). Approximately, 50% of cases are associated with genetic and multiple malformation syndromes including trisomy 13/18, pentalogy of Cantrell and Beckwith–Wiedemann syndrome. Therefore, a thorough evaluation is recommended, including detailed anatomic survey, fetal echocardiogram, genetic counseling, and prenatal diagnostic testing. Overall prognosis depends on the size of the omphalocele, genetic studies, and associated anomalies. Early prenatal diagnosis remains important in order to provide parental counseling and assist in pregnancy management. Delivery should occur at a tertiary care center. Timing and mode of delivery should be based on standard obstetric indications with cesarean delivery reserved for large omphalocele (>5 cm) or those that involve the fetal liver. Neonatal management involves either primary or staged reduction, both of which can be associated with a prolonged neonatal hospitalization.
Outcomes in patients with lung cancer treated with crizotinib and erlotinib in routine clinical practice: A post‐authorization safety cohort study conducted in Europe and in the United States
Authors: Ehrenstein Vera , Huang Kui , Kahlert Johnny , Bahmanyar Shahram , Karlsson Pär , Löfling Lukas , Nunes Anthony P. , Enger Cheryl , Bezemer Irene D. , Kuiper Josephina G. , Hoti Fabian , Juuti Rosa , Korhonen Pasi , Mo Jingping , Schachterle Stephen E. , Wilner Keith D. , Rørth Mikael , Sørensen Henrik T.
Published: January 2021

Purpose

We examined safety outcomes of interest (SOI) and overall survival (OS) among lung cancer patients initiating crizotinib and erlotinib in routine clinical practice.

Methods

This descriptive cohort study used routinely collected health data in Denmark, Finland, Sweden, the Netherlands, and the United States (US) during 2011–2017, following crizotinib commercial availability in each country. Among crizotinib or erlotinib initiators, we reported baseline characteristics and incidence rates and cumulative incidences of the SOI – hepatotoxicity, pneumonitis/interstitial lung disease, QT interval prolongation‐related events, bradycardia, vision disorders, renal cysts, edema, leukopenia, neuropathy, photosensitivity, malignant melanoma, gastrointestinal perforation, cardiac failure and OS. Results from the European Union (EU) countries were combined using meta‐analysis; results from the US were reported separately.

Results

There were 456 patients in the crizotinib cohort and 2957 patients in the erlotinib cohort. Rates of the SOI per 1000 person‐years in the crizotinib cohort ranged from 0 to 65 in the EU and from 0 to 374 in the US. Rates of the SOI per 1000 person‐years in the erlotinib cohort ranged from 0 to 91 in the EU and from 3 to 394 in the US. In the crizotinib cohort, 2‐year OS was ~50% in both EU and US. In the erlotinib cohort, 2‐year OS was 21% in the EU and 35% in the US.

Conclusions

This study describes clinical outcomes among lung cancer patients initiating crizotinib or erlotinib in routine clinical practice. Differences between SOI rates in EU and US may be partially attributable to differences in the underlying databases.
Bacteriophage therapy for infections in CF
Authors: Chan Benjamin K. , Stanley Gail , Modak Mrinalini , Koff Jon L. , Turner Paul E.
Published: January 2021

Pseudomonas aeruginosa and Staphylococcus aureus are bacterial pathogens frequently associated with pulmonary complications and disease progression in cystic fibrosis (CF). However, these bacteria increasingly show resistance to antibiotics, necessitating novel management strategies. One possibility is bacteriophage (phages; bacteria‐specific viruses) therapy, where lytic phages are administered to kill target bacterial pathogens. Recent publications of case reports of phage therapy to treat antibiotic‐resistant lung infections in CF have garnered significant attention. These cases exemplify the renewed interest in phage therapy, an older concept that is being newly updated to include rigorous collection and analysis of patient data to assess clinical benefit, which will inform the development of clinical trials. As outcomes of these trials become public, the results will valuable gauge the potential usefulness of phage therapy to address the rise in antibiotic‐resistant bacterial infections. In addition, we highlight the further need for basic research to accurately predict the different responses of target bacterial pathogens when phages are administered alone, sequentially, or as mixtures (cocktails), and whether within‐cocktail interactions among phages hold consequences for the efficacy of phage therapy in patient treatment.