bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID‐19 spreading across world correlates with C677T allele of the methylenetetrahydrofolate reductase (MTHFR) gene prevalence
Authors: Ponti Giovanni , Pastorino Lorenza , Manfredini Marco , Ozben Tomris , Oliva Gabriella , Kaleci Shaniko , Iannella Raffaele , Tomasi Aldo
Published: June 2021

Background

Homocysteine assessment has been proposed as a potential predictive biomarker for the severity of COVID‐19 infection. The purpose of this review was to analyze the correlation between the prevalence of MTHFR C677 T gene polymorphism and COVID‐19 incidence and mortality worldwide.

Methods

Data regarding MTHFR C677 T gene mutation were obtained from the interrogation of the Genome Aggregation Database (genomAD), which is publicly available from the web“https://gnomad.broadinstitute.org.” COVID‐19 cases, including prevalence and mortality, were obtained from“https://www.worldometers.info/coronavirus” 27 August 2020.

Results

There is a clear trend toward the worldwide prevalence of MTHFR 677 T and COVID‐19 incidence and mortality. The prevalence of MTHFR 677 T allele in the Latino population, and the incidence and mortality for COVID‐19 was higher for this ethnic group than that reported for most other populations globally. Statistical analysis showed a relatively strong correlation between C677 T and death from coronavirus.

Conclusions

Genetic polymorphism of MTHFR C677 T may modulate the incidence and severity of COVID‐19 pandemic infection.
Evaluating the feasibility of a consumer‐grade wearable EEG headband to aid assessment of state and trait mindfulness
Authors: Hunkin Hugh , King Daniel L. , Zajac Ian T.
Published: June 2021

Objectives

Measures from wearable devices could be a valuable supplement to mindfulness assessment and intervention. This observational study evaluated measures from a consumer‐grade EEG headband (Muse, InteraXon, Inc.) as novel correlates of state mindfulness during focused attention meditation.

Methods

Adult participants (N = 68, M
age = 22.66, SD
age = 7.35) completed a task‐based measure of state mindfulness and thought probe measures of subjective mind wandering while meditating with the EEG headband. A subset completed 14 days of home practice (n = 29).

Results

Device measures were sensitive to attention lapses within‐participants in the state mindfulness task (d = 0.56) and had large between‐participants associations for the same task (r = −0.50). Mean device metrics from home practice together explained approximately 30% of variance in self‐reported trait mindfulness, attentional control, nonattachment, and decentering.

Conclusion

EEG biomarkers show potential as correlates of mindfulness with distinct benefits over existing assessment methods.
Novel TREM2 splicing isoform that lacks the V-set immunoglobulin domain is abundant in the human brain
Authors: Kiianitsa Kostantin , Kurtz Irina , Beeman Neal , Matsushita Mark , Chien Wei-Ming , Raskind Wendy H , Korvatska Olena
Published: June 2021

Triggering receptor expressed on myeloid cells 2 (TREM2) is an immunoglobulin-like receptor expressed by certain myeloid cells, such as macrophages, dendritic cells, osteoclasts, and microglia. In the brain, TREM2 plays an important role in the immune function of microglia, and its dysfunction is linked to various neurodegenerative conditions in humans. Ablation of TREM2 or its adaptor protein TYROBP causes polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (also known as Nasu-Hakola disorder) with early onset of dementia, whereas some missense variants in TREM2 are associated with an increased risk of late-onset Alzheimer's disease. The human TREM2 gene is subject to alternative splicing, and its major, full-length canonic transcript encompasses 5 exons. Herein, we report a novel alternatively spliced TREM2 isoform without exon 2 (Δe2), which constitutes a sizable fraction of TREM2 transcripts and has highly variable inter-individual expression in the human brain (average frequency 10%; range 3.7–35%). The protein encoded by Δe2 lacks a V-set immunoglobulin domain from its extracellular part but retains its transmembrane and cytoplasmic domains. We demonstrated Δe2 protein expression in TREM2-positive THP-1 cells, in which the expression of full-length transcript was precluded by CRISPR/Cas9 disruption of the exon 2 coding frame. Similar to the full-length TREM2, Δe2 is sorted to the plasma membrane and is subject to receptor shedding. In “add-back” experiments, Δe2 TREM2 had diminished capacity to restore phagocytosis of amyloid beta peptide and promote IFN-I response as compared to full-length TREM2. Our findings suggest that changes in the balance of two mutually exclusive TREM2 isoforms may modify the dosage of full-length transcript potentially weakening some TREM2 receptor functions in the human brain.
ELISPOT assay of interferon‐γ secretion for evaluating human cytomegalovirus reactivation risk in allo‐HSCT recipients
Authors: Liang Hanying , Xia Jintao , Zhang Runan , Yang Bing , Wu Jian , Gui Genyong , Huang Yaping , Chen Xiaoming , Yang Rong , Wang Huiqi , Gong Shengnan , Fan Jun
Published: June 2021

Human cytomegalovirus (HCMV) is a common cause of significant morbidity and mortality in transplant recipients after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We evaluated interferon‐γ (IFN‐γ) secretion by HCMV NLV‐specific CD8+ T cells in HCMV‐reactivated allo‐HSCT recipients using an enzyme‐linked immunospot (ELISPOT) assay at 3 months post‐transplantation. Blood samples from 47 recipients were tested for HCMV DNAemia, HCMV pp65 antigenemia, and anti‐HCMV immunoglobulins (IgG/IgM) over 3 months post‐transplantation. Of the 47 transplant recipients, 26 were HLA‐A*02 positive and 21 were HLA‐A*02 negative. The results were essentially consistent between the 47 transplant recipients and the HLA‐A*02‐positive recipients. HCMV DNAemia was not linearly correlated with IFN‐γ spot‐forming cells (SFCs) counts; IFN‐γ SFCs counts did not differ significantly between the HCMV DNAemia‐positive and ‐negative groups, whereas the HCMV‐DNA virus loads were inversely correlated with the IFN‐γ SFCs counts. HCMV pp65 antigenemia was not linearly correlated with IFN‐γ SFCs counts; IFN‐γ SFCs counts in the HCMV pp65 antigenemia‐positive and ‐negative groups were similar. More IFN‐γ SFCs counts were detected in transplant recipients with high anti‐HCMV‐IgG antibody titers than in those with low anti‐HCMV‐IgG titers pre‐transplantation in the 47 recipients. Anti‐HCMV‐IgG antibody titers were positively linearly correlated with IFN‐γ SFCs counts in HLA‐A*02‐positive recipients. The HCMV infection indicators used to monitor HCMV reactivation had different values in transplant recipients. The use of the IFN‐γ SFCs counts measured by ELISPOT to evaluate the risk of HCMV reactivation needs further study.
Clinical study evaluating the efficacy of ivermectin in COVID‐19 treatment: A randomized controlled study
Authors: Abd‐Elsalam Sherief , Noor Rasha A. , Badawi Rehab , Khalaf Mai , Esmail Eslam S. , Soliman Shaimaa , Abd El Ghafar Mohamed S. , Elbahnasawy Mohamed , Moustafa Ehab F. , Hassany Sahar M. , Medhat Mohammed A. , Ramadan Haidi Karam‐Allah , Eldeen Maii A. S. , Alboraie Mohamed , Cordie Ahmed , Esmat Gamal
Published: June 2021

Researchers around the world are working at record speed to find the best ways to treat and prevent coronavirus disease 2019 (COVID‐19). This study aimed to evaluate the efficacy of ivermectin for the treatment of hospitalized mild to moderate COVID‐19 infected patients. This was a randomized open‐label controlled study that included 164 patients with COVID‐19. Patients were randomized into two groups where Group 1 (Ivermectin group) included patients who received ivermectin 12 mg once daily for 3 days with standard care and Group 2 (control group) included patients who received standard protocol of treatment alone for 14 days. The main outcomes were mortality, the length of hospital stay, and the need for mechanical ventilation. All patients were followed up for 1 month. Overall, 82 individuals were randomized to receive ivermectin plus standard of care and 82 to receive standard of care alone. Patients in the ivermectin group had a shorter length of hospital stay (8.82 ± 4.94 days) than the control group (10.97 ± 5.28 days), but this was not statistically significant (p = 0.085). Three patients (3.7%) in each group required mechanical ventilation (p = 1.00). The death rate was three patients in the ivermectin group (3.7%) versus four patients (4.9%) in the control group without any significant difference between the two groups (p = 1.00). Although there was no statistically significant difference in any endpoints by ivermectin doses (12 mg/day for 3 days); there was an observed trend to reducing hospital stay in the ivermectin‐treated group.
The Indirect Effects of Self‐Esteem and Future Work Self on Career Adaptability Factors: A Study of Chinese Undergraduate Students
Authors: Joanne Chan Sow Hup , Chan Kuan‐Thye
Published: June 2021

This study examined the indirect effects of global self‐esteem (GSE) on the linkage between proactive personality (PP), appearance‐contingent self‐worth (ACSW), and career adaptability (CA) among 372 Chinese undergraduate students. The indirect effect of future work self (FWS) on the linkage between GSE and CA and between PP and CA was also examined. Results demonstrated that GSE mediated the PP‐CA relationship; however, GSE was not a mediator in the ACSW‐CA relationship. FWS mediated both the GSE‐CA and PP‐CA relationships. Gender differences in the strength of the relationships were also observed. The findings expand existing empirical work by demonstrating the important indirect effects of GSE and FWS in relation to CA. Career counselors and educators may encourage students to be more proactive and boost their GSE to accomplish their career goals.
The consequences of self‐reporting biases: Evidence from the crash preventability program
Authors: Scott Alex , Balthrop Andrew T.
Published: June 2021

Relying on firms to self‐report information is an information‐gathering mechanism that often results in biased measures due to the incentives of the reporting firms. What is less commonly understood is that using self‐reported information for decision‐making results in endogenous selection bias, which creates spurious associations between the measure being reported and factors that influence reporting. Thus, conditioning on self‐reported information can lead to inaccurate evaluations of firms and bias predictions of future performance, even when the self‐reported measure is not intentionally misrepresented. We examine endogenous selection bias in self‐reporting regimes using directed acyclic graphs (DAGs). We illustrate the problem using data from a policy change by the U.S. Department of Transportation that allowed firms to report not‐at‐fault for accidents. We find that large for‐hire firms are much more likely to report not‐at‐fault for accidents—over 40 times more likely than independent drivers—even after controlling for time, location, and weather. When comparing independent drivers with large firms, the reporting disparities make large firms appear 25% safer when using at‐fault accidents versus all accidents while providing no improvement in predicting future accidents. This study highlights the consequences of poorly designed information‐gathering mechanisms and the usefulness of DAGs for understanding causality in supply chain research.
Periodontitis in patients with systemic lupus erythematosus: A nationwide study of 1,990 patients
Authors: Bolstad Anne Isine , Sehjpal Pria , Lie Stein Atle , Fevang Bjørg‐Tilde Svanes
Published: June 2021

Background

The aim of this study was to examine the association between systemic lupus erythematosus (SLE) and periodontitis in Norway during a 10‐year period from 2008 through 2017.

Methods

In this population‐based study, 1,990 patients were included in the SLE‐cohort based on diagnostic codes registered in the Norwegian Patient Registry. The control group (n = 170,332) comprised patients registered with diagnostic codes for non‐osteoporotic fractures or hip or knee replacement because of osteoarthritis. The outcome was periodontitis, defined by procedure codes registered in the Control and Payment of Health Refunds database. Logistic regression analyses were performed to estimate odds ratio for periodontitis in patients versus controls adjusted for potential covariates.

Results

Periodontitis was significantly more common in SLE patients compared to controls (OR 1.78, 95% CI 1.47‐2.14) and the difference was highest in SLE‐patients 20 to 30 years of age (OR 3.24, 95% CI 1.23 – 8.52). The periodontitis rate in SLE patients was in the same range as for patients with diabetes mellitus type 2.

Conclusions

Patients with SLE had an almost doubled risk of periodontitis compared with the control population, and the difference was most accentuated in the young patients. These findings warrant an increased focus on dental health in SLE‐patients.
Comparison between robotic natural orifice specimen extraction surgery and traditional laparoscopic low anterior resection for middle and low rectal cancer: A propensity score matching analysis
Authors: Feng Qingyang , Ng Simon S. M. , Zhang Zhiyuan , Lin Songbin , Niu Zhengchuan , Wei Ye , He Guodong , Chang Wenju , Zhu Dexiang , Xu Jianmin
Published: June 2021

Background and Objectives

This study aimed to find the advantages of robotic natural orifice specimen extraction surgery (NOSES) for middle and low rectal cancer, compared with traditional laparoscopic low anterior resection (LAR).

Methods

Patients receiving robotic NOSES or traditional laparoscopic LAR were retrospectively enrolled from 2013‐10 to 2019‐06, with middle and low rectal cancer, maximum diameter ≤ 5 cm, pT1–3 or ypT1–3 stage, no distant metastases. The baseline of the two groups was balanced using the propensity score matching method. Surgical quality, postoperative recovery, and long‐term oncological outcomes were compared.

Results

Totally 137 eligible patients with robotic NOSES and 137 matched patients with traditional laparoscopic LAR were enrolled. Robotic NOSES had a significantly lower open conversion rate (0 vs. 4.4%, p = .030), less intraoperative hemorrhage (50 ml vs. 80 ml, p < .001) and longer distance from distal resection margin of low rectal cancer (1.5 cm vs. 1.0 cm, p = .030). Robotic NOSES significantly reduced the 30‐day postoperative complication rate of Clavien‐Dindo grade II or higher (17.5% vs. 31.4%, p = .008), promoted gastrointestinal and urinary function recovery, reduced postoperative pain and hospital stay (6.0 vs. 7.0 d, p = .022). The two groups were similar in long‐term survival.

Conclusions

Compared with traditional laparoscopic LAR, robotic NOSES had significant advantages in improving surgical quality and promoting postoperative recovery.
Is there a difference in utilization of a perioperative treatment approach for gastric cancer between safety net hospitals and tertiary referral centers?
Authors: Turgeon Michael K. , Lee Rachel M. , Keilson Jessica M. , Ju Michelle R. , Porembka Matthew R. , Alterio Rodrigo E. , Kronenfeld Joshua , Datta Jashodeep , Goel Neha , Wang Annie , Lee Ann Y. , Fernandez Manuel , Richter Harry , Maker Ajay V. , Maithel Shishir K. , Russell Maria C.
Published: June 2021

Background and Objectives

Perioperative therapy is a favored treatment strategy for gastric cancer. We sought to assess utilization of this approach at safety net hospitals (SNH) and tertiary referral centers (TRC).

Materials and Methods

Patients in the US Safety Net Collaborative (2012–2014) with resectable gastric cancer across five SNH and their sister TRC were included. Primary outcomes were receipt of neoadjuvant chemotherapy (NAC) and perioperative therapy.

Results

Of 284 patients, 36% and 64% received care at SNH and TRC. The distribution of Stage II/III resectable disease was similar across facilities. Receipt of NAC at SNH and TRC was similar (56% vs. 46%, p = 0.27). Compared with overall clinical stage, 38% and 36% were pathologically downstaged at SNH and TRC, respectively. Among patients who received NAC, those who also received adjuvant chemotherapy at SNH and TRC were similar (66% vs. 60%, p = 0.50). Asian race and higher clinical stage were associated with receipt of perioperative therapy (both p < 0.05) while treatment facility type was not.

Conclusions

There was no difference in utilization of a perioperative treatment strategy between facility types for patients with gastric cancer. Pathologic downstaging from NAC was similar across treatment facilities, suggesting similar quality and duration of therapy. Treatment at an SNH is not a barrier to receiving standard‐of‐care perioperative therapy for gastric cancer.
Comparison between short and long‐term outcomes after minimally invasive versus open primary liver resections for hepatocellular carcinoma: A 1:1 matched analysis
Authors: Goh Brian K. P. , Syn Nicholas , Koh Ye‐Xin , Teo Jin‐Yao , Cheow Peng‐Chung , Jeyaraj Prema R. , Chow Pierce K. H. , Ooi London L. P. J. , Chung Alexander Y. F. , Chan Chung‐Yip
Published: June 2021

Background

This study aims to compare the short‐ and long‐term outcomes of patients undergoing minimally invasive liver resection (MILR) versus open liver resection (OLR) for nonrecurrent hepatocellular carcinoma (HCC).

Methods

Review of 204 MILR and 755 OLR without previous LR performed between 2005 and 2018. 1:1 coarsened exact matching (CEM) and 1:1 propensity‐score matching (PSM) were performed.

Results

Overall, 190 MILR were well‐matched with 190 OLR by PSM and 86 MILR with 86 OLR by CEM according to patient baseline characteristics. After PSM and CEM, MILR was associated with a significantly longer operation time [230 min (interquartile range [IQR], 145–330) vs. 160 min (IQR, 125–210), p < .001] [215 min (IQR, 135–295) vs. 153.5 min (120–180), p < .001], shorter postoperative stay [4 days (IQR, 3–6) vs. 6 days (IQR, 5–8), p = .001)] [4 days (IQR, 3–5) vs. 6 days (IQR, 5–7), p = .004] and lower postoperative morbidity [40 (21%) vs. 67 (35.5%), p = .003] [16 (18.6%) vs. 27 (31.4%), p = .036] compared to OLR. MILR was also associated with a significantly longer median time to recurrence (70 vs. 40.3 months, p = .014) compared to OLR after PSM but not CEM. There was no significant difference in terms of overall survival and recurrence‐free survival.

Conclusion

MILR is associated with superior short‐term postoperative outcomes and with at least equivalent long‐term oncological outcomes compared to OLR for HCC.
Enantioseparation of phenethylamines by using high‐performance liquid chromatography column permanently coated with methylated β‐cyclodextrin
Authors: Terashima Hiroyuki , Yamamoto Atsushi , Aizawa Sen‐ichi , Taga Atsushi , Mikami Ikko , Ishihara Yoshimi , Kodama Shuji
Published: June 2021

Cyclodextrins and their derivatives have been used for chiral high‐performance liquid chromatography selectors, while they are costly to use as mobile phase additives in high‐performance liquid chromatography. Here, we report application of phenyl column coated permanently with methylated β‐cyclodextrin for chiral high‐performance liquid chromatography. A 0.1% (v/v) phosphoric acid solution containing 1 M NaCl and 0.5% (w/v) methylated β‐cyclodextrin was subjected to a phenyl column at a flow rate of 0.5 mL/min at 30°C for 2 h. Using the precoating phenyl column, all the enantiomers of the four phenethylamines (norepinephrine, epinephrine, octopamine, and synephrine) were successfully separated simultaneously by high‐performance liquid chromatography with a mobile phase without methylated β‐cyclodextrin at a flow rate of 0.2 mL/min at 30°C. The enantioseparation ability was retained for successive analyses during 1 week. It is suggested that inclusion complex of methylated β‐cyclodextrin with a phenyl group on the surface of the stationary phase could be formed and that the inclusion complex could form the ternary complex with the injected analytes. The longer retention time of (S)‐enantiomers of analytes than corresponding (R)‐enantiomers for high‐performance liquid chromatography could be explained from the higher stability of the methylated β‐cyclodextrin complexes with (S)‐enantiomers, which were confirmed by capillary electrophoresis and 1H NMR spectroscopy experiments.
Locoregional Recurrence in p16‐Positive Oropharyngeal Squamous Cell Carcinoma After TORS
Authors: Carey Ryan M. , Brody Robert M. , Shimunov David , Shinn Justin R. , Mady Leila J. , Rajasekaran Karthik , Cannady Steven B. , Lin Alexander , Lukens John N. , Bauml Joshua M. , Cohen Roger B. , Basu Devraj , O'Malley Bert W. , Weinstein Gregory S. , Newman Jason G.
Published: June 2021

Objective

To analyze the patterns, risk factors, and salvage outcomes for locoregional recurrences (LRR) after treatment with transoral robotic surgery (TORS) for HPV‐associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC).

Study Design

Retrospective analysis of HPV+ OPSCC patients completing primary TORS, neck dissection, and NCCN‐guideline‐compliant adjuvant therapy at a single institution from 2007 to 2017.

Methods

Features associated with LRR, detailed patterns of LRR, and outcomes of salvage therapy were analyzed. Disease‐free survival (DFS) and overall survival (OS) were calculated for subgroups of patients receiving distinct adjuvant treatments.

Results

Of 541 patients who completed guideline‐indicated therapy, the estimated 5‐year LRR rate was 4.5%. There were no identifiable clinical or pathologic features associated with LRR. Compared to patients not receiving adjuvant therapy, those who received indicated adjuvant radiation alone had a lower risk of LRR (HR 0.28, 95% CI [0.09–0.83], P = .023), but there was no difference in DFS (P = .21) and OS (P = .86) between adjuvant therapy groups. The 5‐year OS for patients who developed LRR was 67.1% vs. 93.9% for those without LRR (P < .001). Patients who initially received adjuvant chemoradiation and those suffering local, in‐field, and/or retropharyngeal node recurrences had decreased disease control after salvage therapy.

Conclusion

LRR rates are low for HPV+ OPSCCs completing TORS and guideline‐compliant adjuvant therapy. Patients without indication for adjuvant therapy more often suffer LRR, but these recurrences are generally controllable by salvage therapy. Improved understanding of the patterns of recurrence most amenable to salvage therapy may guide treatment decisions, counseling, and adjuvant therapy de‐escalation trials.

Level of Evidence

3 Laryngoscope, 131:E2865–E2873, 2021
A science of collaborative learning health systems
Authors: Seid Michael , Hartley David M. , Margolis Peter A.
Published: June 2021

Introduction

Improving the U.S. healthcare system and health outcomes is one of the most pressing public health challenges of our time. Previously described Collaborative Learning Health Systems (CLHSs) are a promising approach to outcomes improvement. In order to fully realize this promise, a deeper understanding of this phenomenon is necessary.

Methods

We drew on our experience over the past decade with CLHSs as well as qualitative literature review to answer three questions: What kind of phenomena are CLHSs? and what is an appropriate scientific approach? How might we frame CLHSs conceptually? What are potential mechanisms of action?

Results

CLHSs are complex adaptive systems in which all stakeholders are able to collaborate, at scale, to create and share resources to satisfy a variety of needs. This is accomplished by providing infrastructure and services that enable stakeholders to act on their inherent motivations. This framing has implications for both research and practice.

Conclusion

Articulating this framework and potential mechanisms of action should facilitate research to test and refine hypotheses as well as guide practice to develop and optimize this promising approach to improving healthcare systems.
α‐Synuclein Deposition in Sympathetic Nerve Fibers in Genetic Forms of Parkinson's Disease
Authors: Isonaka Risa , Goldstein David S. , Zhu William , Yoon Esther , Ehrlich Debra , Schindler Alice B. , Kokkinis Angela D. , Sabir Marya S. , Scholz Sonja W. , Bandres‐Ciga Sara , Blauwendraat Cornelis , Gonzalez‐Alegre Pedro , Lopez Grisel , Sidransky Ellen , Narendra Derek P.
Published: June 2021

Background

Cytoplasmic inclusions of α‐synuclein (α‐syn) in brainstem neurons are characteristic of idiopathic Parkinson's disease (PD). PD also entails α‐syn buildup in sympathetic nerves. Among genetic forms of PD, the relative extents of sympathetic intraneuronal accumulation of α‐syn have not been reported.

Objective

This cross‐sectional observational study compared magnitudes of intraneuronal deposition of α‐syn in common and rare genetic forms of PD.

Methods

α‐Syn deposition was quantified by the α‐syn‐tyrosine hydroxylase colocalization index in C2 cervical skin biopsies from 65 subjects. These included 30 subjects with pathogenic mutations in SNCA (n = 3), PRKN [biallelic (n = 7) and monoallelic (n = 3)], LRRK2 (n = 7), GBA (n = 7), or PARK7/DJ1 [biallelic (n = 1) and monoallelic (n = 2)]. Twenty‐five of the mutation carriers had PD and five did not. Data were also analyzed from 19 patients with idiopathic PD and 16 control participants.

Results

α‐Syn deposition varied as a function of genotype (F = 16.7, P < 0.0001). It was above the control range in 100% of subjects with SNCA mutations, 100% with LRRK2 mutations, 95% with idiopathic PD, 83% with GBA mutations, and 0% with biallelic PRKN mutations. α‐Syn deposition in the biallelic PRKN group was significantly higher than in the control group. In addition, patients with biallelic PRKN mutations had higher α‐syn deposition than their unaffected siblings.

Conclusions

Individuals with SNCA, DJ‐1, LRRK2, or GBA mutations have substantial intraneuronal α‐syn deposition in sympathetic noradrenergic nerves in skin biopsies, whereas those with biallelic PRKN mutations do not. Biallelic PRKN patients may have mildly increased α‐syn deposition compared with control subjects. © 2021 International Parkinson and Movement Disorder Society
Interleaved water and fat MR thermometry for monitoring high intensity focused ultrasound ablation of bone lesions
Authors: Lena Beatrice , Bartels Lambertus W. , Ferrer Cyril J. , Moonen Chrit T. W. , Viergever Max A. , Bos Clemens
Published: June 2021

Purpose

To demonstrate that interleaved MR thermometry can monitor temperature in water and fat with adequate temporal resolution. This is relevant for high intensity focused uUltrasounds (HIFU) treatment of bone lesions, which are often found near aqueous tissues, as muscle, or embedded in adipose tissues, as subcutaneous fat and bone marrow.

Methods

Proton resonance frequency shift (PRFS)‐based thermometry scans and T1‐based 2D variable flip angle (2D‐VFA) thermometry scans were acquired alternatingly over time. Temperature in water was monitored using PRFS thermometry, and in fat by 2D‐VFA thermometry with slice profile effect correction. The feasibility of interleaved water/fat temperature monitoring was studied ex vivo in porcine bone during MR‐HIFU sonication. Precision and stability of measurements in vivo were evaluated in a healthy volunteer under non‐heating conditions.

Results

The method allowed observing temperature change over time in muscle and fat, including bone marrow, during MR‐HIFU sonication, with a temporal resolution of 6.1 s. In vivo, the apparent temperature change was stable on the time scale of the experiment: In 7 min the systematic drift was <0.042°C/min in muscle (PRFS after drift correction) and <0.096°C/min in bone marrow (2D‐VFA). The SD of the temperature change averaged over time was 0.98°C (PRFS) and 2.7°C (2D‐VFA).

Conclusions

Interleaved MR thermometry allows temperature measurements in water and fat with a temporal resolution high enough for monitoring HIFU ablation. Specifically, combined fat and water thermometry provides uninterrupted information on temperature changes in tissue close to the bone cortex.
Tocilizumab is safe and tolerable and reduces C‐reactive protein concentrations in the plasma and cerebrospinal fluid of ALS patients
Authors: Milligan Carol , Atassi Nazem , Babu Suma , Barohn Richard J. , Caress James B. , Cudkowicz Merit E. , Evora Armineuza , Hawkins Gregory A. , Wosiski‐Kuhn Marlena , Macklin Eric A. , Shefner Jeremy M. , Simmons Zachary , Bowser Robert P. , Ladha Shafeeq S.
Published: June 2021

Introduction/Aims

We tested safety, tolerability, and target engagement of tocilizumab in amyotrophic lateral sclerosis (ALS) patients.

Methods

Twenty‐two participants, whose peripheral blood mononuclear cell (PBMC) gene expression profile reflected high messenger ribonucleic acid (mRNA) expression of inflammatory markers, were randomized 2:1 to three tocilizumab or placebo treatments (weeks 0, 4, and 8; 8 mg/kg intravenous). Participants were followed every 4 wk in a double‐blind fashion for 16 wk and assessed for safety, tolerability, plasma inflammatory markers, and clinical measures. Cerebrospinal fluid (CSF) was collected at baseline and after the third treatment. Participants were genotyped for Asp358Ala polymorphism of the interleukin 6 receptor (IL‐6R) gene.

Results

Baseline characteristics, safety, and tolerability were similar between treatment groups. One serious adverse event was reported in the placebo group; no deaths occurred. Mean plasma C‐reactive protein (CRP) level decreased by 88% in the tocilizumab group and increased by 4% in the placebo group (−3.0‐fold relative change, P < .001). CSF CRP reduction (−1.8‐fold relative change, P = .01) was associated with IL‐6R C allele count. No differences in PBMC gene expression or clinical measures were observed between groups.

Discussion

Tocilizumab treatment was safe and well tolerated. PBMC gene expression profile was inadequate as a predictive or pharmacodynamic biomarker. Treatment reduced CRP levels in plasma and CSF, with CSF effects potentially dependent on IL‐6R Asp358Ala genotype. IL‐6 trans‐signaling may mediate a distinct central nervous system response in individuals inheriting the IL‐6R C allele. These results warrant further study in ALS patients where IL‐6R genotype and CRP levels may be useful enrichment biomarkers.
Photophysics of the electronic states S0 and S1 for the coplanar molecular structures of the α,ω‐diphenylpolyenes DPH and DPO
Authors: Catalán Javier
Published: June 2021

Spectroscopy of the monoclinic and orthorhombic crystalline forms of all‐trans‐diphenylhexatriene (DPH) and all‐trans‐diphenyloctatetraene (DPO) show absorption and emission bands that do not generate the widely known Stokes shift of the polyene compounds, discovered by Hausser et al. in 1953 and repeatedly studied over the last 60 years. It can be concluded from our study that the crystallization system, whether in a monoclinic or orthorhombic system, does not significantly influence the photophysics of DPH and DPO in the crystal phase.
Tachyonic de Sitter Solutions of 10d Type II Supergravities
Authors: Andriot David
Published: June 2021

Cosmological models of the early or late universe exhibit (quasi) de Sitter space‐times with different stability properties. Considering models derived from string theory, the swampland program does not provide for now a definite characterisation of this stability. In this work we focus on de Sitter solutions of 10d type II supergravities, candidates for classical de Sitter string backgrounds: surprisingly, all known examples are unstable with . We aim at proving the existence of such a systematic tachyon, and getting formally a bound on the value of . To that end, we develop three methods, giving us various sufficient conditions for having a tachyon upon assumptions, in analogy with de Sitter no‐go theorems. Our analysis eventually indicates the existence of variety of different tachyons, and related bounds on . We use this knowledge to find 10 new de Sitter solutions of type IIB supergravity, that have tachyons of a different kind, higher values and new 6d geometries. One solution even appears to be stable, with however non‐compact extra dimensions.
AC/DC Magnetic Field Sensing Utilizing Mechanically Mediated Product Effect of Ampere Force Caused by Eddy Currents and Piezoelectricity in a Magnetoelectric Disk
Authors: Qi Bing , Zhang Yudong , Yao Taiping , Shang Haikun
Published: June 2021

The last two decades have witnessed an ever‐increasing research effort devoted to the development and application of magnetoelectric (ME) sensing composites. Herein, the ME effect in a metallic/polymeric composite fabricated by adhering silver electrodes to two surfaces of one poly(vinylidine fluoride) (PVDF) disk is explored. To obtain obvious ME response, the resonance frequency of the experimental setup is measured. Furthermore, it is proved that the ME coupling in the composite (silver/PVDF/silver) originates from the product effect of the piezoelectric effect and ampere force produced by eddy currents under DC bias magnetic fields. By observing measurement results, the ME voltage is approximately considered to be proportional to both AC and DC magnetic fields. Consequently, the average ME voltage coefficient is obtained as 384.73 mV cm−1 Oe at a DC magnetic field value of 1000 Oe. Considering the magnetic fields and eddy current, a theoretical model of ME coupling is developed by combining the ampere force expression and piezoelectric equations, which matches well with measurement results. Without the need of magnetic phase and an external power supply, the proposed disk with excellent linear responses and a considerable ME voltage coefficient has the potential for application in real‐time monitoring sensors.
Benchmarking Electrolyte‐Gated Monolayer MoS2 Field‐Effect Transistors in Aqueous Environments
Authors: Rühl Steffen , Heyl Max , Gärisch Fabian , Blumstengel Sylke , Ligorio Giovanni , List-Kratochvil Emil J. W.
Published: June 2021

Most electrical sensor and biosensor elements require reliable transducing elements to convert small potential changes into easy to read out current signals. Offering inherent signal magnification and being operable in many relevant environments field‐effect transistors (FETs) are the element of choice in many cases. In particular, using electrolyte gating, numerous sensors and biosensors have been realized in aqueous environments. Over the past years, electrolyte‐gated FETs have been fabricated using a variety of semiconducting materials, including graphene, ZnO, as well as conjugated molecules and polymers. Above all, using conducting polymers top‐performing devices have been achieved. Herein, an approach to use a transition metal dichalcogenide (TMDC)‐based monolayer device as a transducing element is presented. Using MoS2 monolayers, it is shown that such electrolyte‐gated devices may be regarded as very promising transducing elements for sensor and biosensor applications, enabled by their high sensitivity for environmental changes and the possibility of using the naturally occurring sulfur vacancies as grafting points of biorecognition layers. Furthermore, the behavior of such a device under prolonged operation in a dilute biologically relevant electrolyte such as phosphate buffered saline solution (PBS) is reported.
Decomposition‐based over‐parameterization forgetting factor stochastic gradient algorithm for Hammerstein‐Wiener nonlinear systems with non‐uniform sampling
Authors: Liu Qilin , Xiao Yongsong , Ding Feng , Hayat Tasawar
Published: June 2021

This article investigates the parameter estimation problems of Hammerstein‐Wiener nonlinear systems with non‐uniform sampling. The over‐parameterization identification model for the Hammerstein‐Wiener nonlinear systems is established from the non‐uniformly sampled input‐output data. By applying the gradient search principle, we derive an over‐parameterization forgetting factor stochastic gradient algorithm for identifying the nonlinear systems. In order to improve the parameter estimation accuracy, a decomposition‐based over‐parameterization forgetting factor stochastic gradient algorithm is presented by using the decomposition technique. The key is to transform the original system into two subsystems and to estimate the parameters of each subsystem, respectively. The simulation results indicate that the proposed algorithms are effective.
A system approach to enable digital beamforming with direct radiating arrays: The joint use of precoding and sparse arrays
Authors: Vidal Florian , Legay Hervé , Goussetis George , Segneri Andrea
Published: June 2021

Digital beamforming with an active array antenna has become, these past years, the holy grail for flexible satellite payloads. This architecture enables a power, frequency and beam steering flexibility that meets the requirements of a wide range of user terminal distributions. Matching these distributions may be challenging, especially if user terminals are co‐located. In this case, narrower beams are needed to utilise high‐frequency reuse factors while avoiding inter‐beam interference. Small beamwidths, however, require large antenna diameters, which implies for conventional antenna arrays many radiating elements and subsequently an increased complexity. A way to reduce the number of radiating elements is to resort to sparse arrays with an irregular layout of radiating elements. A disadvantage of this type of antenna is their high side lobe levels when scanning the beams. A robust on‐board precoding strategy based on the knowledge of the users' positions and the antenna gain over the coverage is proposed to mitigate the interference arising from high side lobe levels. A circular direct radiating array and a sparse direct radiating array based on a sunflower design are compared with respect to the capacities they can achieve, and the complexity of the processor required to perform full digital beamforming.
Quantitative Ultrafast Electron‐Temperature Dynamics in Photo‐Excited Au Nanoparticles
Authors: Sygletou Maria , Benedetti Stefania , Ferrera Marzia , Pierantozzi Gian Marco , Cucini Riccardo , Della Valle Giuseppe , Carrara Pietro , De Vita Alessandro , di Bona Alessandro , Torelli Piero , Catone Daniele , Panaccione Giancarlo , Canepa Maurizio , Bisio Francesco
Published: June 2021

The femtosecond evolution of the electronic temperature of laser‐excited gold nanoparticles is measured, by means of ultrafast time‐resolved photoemission spectroscopy induced by extreme‐ultraviolet radiation pulses. The temperature of the electron gas is deduced by recording and fitting high‐resolution photo emission spectra around the Fermi edge of gold nanoparticles providing a direct, unambiguous picture of the ultrafast electron‐gas dynamics. These results will be instrumental to the refinement of existing models of femtosecond processes in laterally‐confined and bulk condensed‐matter systems, and for understanding more deeply the role of hot electrons in technological applications.
Incorporation of Cyano‐Substituted Aromatic Blocks into Naphthalene Diimide‐Based Copolymers: Toward Unipolar n‐Channel Field‐Effect Transistors
Authors: Wei Congyuan , Xu Pan , Zhang Weifeng , Zhou Yankai , Wei Xuyang , Zheng Yuanhui , Wang Liping , Yu Gui
Published: June 2021

The unipolar n‐type polymeric semiconductors are crucial for the development of complementary inverters and complementary logic circuits. To achieve this target, the polymer skeleton should be electron‐deficient, which guarantees the energy‐level alignment between the lowest unoccupied molecular orbital energy level of polymeric materials and the work function of electrode, further permitting effective electron injection. Different from the introduction of the sp2‐hybridized nitrogen atoms and fluorine atoms, cyano‐substituted aromatic blocks are synthesized and further copolymerized with naphthalene diimide (NDI) unit, affording a series of copolymers of PNDI‐BTCN, PNDI‐TVTCN, and PNDI‐SVSCN. The photophysical, electrochemical, and thermal properties of all the copolymers are systematically investigated, and their semiconducting performance is studied by fabricating field‐effect transistors and tested under atmosphere. All the polymers exhibit unipolar n‐type semiconducting performance because of the synergetic effect of strong electron‐withdrawing NDI units and cyano‐substituted aromatic blocks. The highest mobility of 0.20 cm2 V−1 s−1 is obtained. Moreover, theoretical simulation and thin‐film characterization are conducted to reveal the difference in semiconducting performance among the three polymeric materials.
Bifacial Color‐Tunable Transparent Photovoltaics for Application as Building‐Integrated Photovoltaics
Authors: Kim Sangho , Yi Junsin , Kim Joondong
Published: June 2021

Transparent photovoltaics (TPVs) have attracted enormous attention due to their potential to be applied as building‐integrated photovoltaics (BIPV). Transparent and semitransparent photovoltaics have achieved a high level of efficiency, but there are still a number of issues that limit their application, such as their device size, lack of stability, and transmittance in the visible wavelength region. The excellent color implementation of a bifacial color‐tunable (BCT) TPV by tuning the indium tin oxide (ITO) thickness is demonstrated. The BCT TPV has a bifacial factor of 97.2% while maintaining an average visible transmittance (AVT) of 41.6%. The use of a 16 cm2 large‐scale TPV device using a dry plasma fabrication process is also demonstrated. This dry process enables large‐scale device production and ensures long‐term device stability. The efficiency improvement with various background colors (blue 14%, red 25%, and white 35%) without any additional installation on the device is also confirmed. The BCT TPV is a promising candidate for BIPV applications due to its wide range of color tunability and excellent double‐sided photovoltaic operation, even under an indoor artificial light.
Interfacial Interactions between Co‐Based Cocatalysts and Semiconducting Light Absorbers for Solar‐Light‐Driven Redox Reactions
Authors: Guo Qing , Feng Xiyuan , Zhang Z. Conrad , Huang Limin
Published: June 2021

Solar‐light‐driven redox reactions, such as water splitting for hydrogen and oxygen evolution, and CO2 reduction, have recently shown great promise toward solar‐to‐fuel conversion. Herein, the recent achievements in establishing interfacial interactions between cocatalysts and semiconducting light absorbers to improve the efficiency of these reactions are focused on. Four kinds of interactions are summarized to clarify the accelerated photogenerated charge carrier kinetics, thereby resulting in enhanced activity of these redox reactions. Especially, the coordination interaction formed by chemical linkage seems to be more preferred because of a well‐provided tunnel for charge transfer. The extended applications of these interfacial interactions to other challenging reactions, such as N2 fixation and organic synthesis, are also predicted.
Bioinspired Electrolysis for Green Molecular Transformations of Organic Halides Catalyzed by B12 Complex
Authors: Shimakoshi Hisashi , Hisaeda Yoshio
Published: June 2021

Naturally‐occurring B12‐dependent enzymes catalyze various molecular transformations that are of particular interest from the viewpoint of biological chemistry as well as synthetic organic chemistry. Inspired by the unique property of the B12‐dependent enzymes, various catalytic reactions have been developed using its model complex. Among the B12 model complexes, heptamethyl cobyrinate, synthesized from natural vitamin B12, is highly soluble in various organic solvents and a redox active cobalt complex with an excellent catalysis in electroorganic synthesis. The electrochemical dechlorination of pollutant organic chlorides, such as DDT, was effectively catalyzed by the B12 complex. Modification of the electrode surface by the sol‐gel method to immobilize the B12 complex was also developed. The B12 modified electrodes were effective for the dehalogenation of organic halides with high turnover numbers based on the immobilized B12 complex. Electrolysis of an organic halide catalyzed by the B12 complex provided dechlorinated products under anaerobic conditions, while the electrolysis under aerobic conditions afforded oxygen incorporated products, such as an ester and amide along with dechlorination. Benzotrichloride was transformed into ethylbenzoate or N,N‐diethylbenzamide in the presence of ethanol or diethylamine, respectively. This amide formation was further expanded to a unique paired electrolysis. Electrochemical reductions of an alkene and alkyne were also catalyzed by the B12 complex. A cobalt‐hydrogen complex should be formed as a bioinspired intermediate. Using the B12 complex, light‐assisted electrosynthesis was also developed to save the applied energy.
Inhibition of Tau aggregation with BSc3094 reduces Tau and decreases cognitive deficits in rTg4510 mice
Authors: Anglada‐Huguet Marta , Rodrigues Sara , Hochgräfe Katja , Mandelkow Eckhard , Mandelkow Eva‐Maria
Published: June 2021

Background

One of the major hallmarks of Alzheimer's disease (AD)is the aberrant modification and aggregation of the microtubule‐associated protein Tau . The extent of Tau pathology correlates with cognitive decline, strongly implicating Tau in the pathogenesis of the disease. Because the inhibition of Tau aggregation may be a promising therapeutic target, we tested the efficacy of BSc3094, an inhibitor of Tau aggregation, in reducing Tau pathology and ameliorating the disease symptoms in transgenic mice.

Methods

Mice expressing human Tau with the P301L mutation (line rTg4510) were infused with BSc3094 into the lateral ventricle using Alzet osmotic pumps connected to a cannula that was placed on the skull of the mice, thus bypassing the blood‐brain barrier (BBB) . The drug treatment lasted for 2 months, and the effect of BSc3094 on cognition and on reversing hallmarks of Tau pathology was assessed.

Results

BSc3094 significantly reduced the levels of Tau phosphorylation and sarkosyl‐insoluble Tau. In addition, the drug improved cognition in different behavioral tasks and reduced anxiety‐like behavior in the transgenic mice used in the study.

Conclusions

Our in vivo investigations demonstrated that BSc3094 is capable of partially reducing the pathological hallmarks typically observed in Tau transgenic mice, highlighting BSc3094 as a promising compound for a future therapeutic approach for AD.