bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of a pathogenic variant in GBA for Parkinson’s disease with mild cognitive impairment patients
Authors: Jiang Zhiqiang , Huang Yilin , Zhang Piao , Han Chongyin , Lu Yueer , Mo Zongchao , Zhang Zhanyu , Li Xin , Zhao Sisi , Cai Fuqiang , Huang Lizhen , Chen Chunbo , Shi Zhihong , Zhang Yuhu , Ling Fei
Published: July 2020

Parkinson’s disease (PD) is the second most common neurodegenerative disease, and mild cognitive impairment (MCI) is a well-established risk factor for the development of dementia in PD. A growing body of evidence suggests that low expression of glucocerebrosidase (GBA) promotes the transmission of α-synuclein (α-Syn) interpolymers and the progression of PD. However, how GBA mutations affect the pathogenesis of PD via abnormal aggregation of α-Syn is unclear, and no clinically valid PD-MCI genetic markers have been identified. Here, we first located a GBA eQTL, rs12411216, by analysing DHS, eQTL SNP, and transcription factor binding site data using the UCSC database. Subsequently, we found that rs12411216 was significantly associated with PD-MCI (P < 0.05) in 306 PD patients by genotyping. In exploring the relationship between rs12411216 and GBA expression, the SNP was found to be associated with GBA expression in 50 PD patients through qPCR verification. In a further CRISPR/Cas9-mediated genome editing module, the SNP was identified to cause a decrease in GBA expression, weaken enzymatic activity and enhance the abnormal aggregation of α-Syn in SH-SY5Y cells. Additionally, using an electrophoretic mobility shift assay, we confirmed that the binding efficiency of transcription factor E2F4 was affected by the rs12411216 SNP. In conclusion, our results showed that rs12411216 regulated GBA expression, supporting its potential role as a PD-MCI genetic biomarker and highlighting novel mechanisms underlying Parkinson’s disease.
Development and evaluation of a dual density insole for people standing for long periods of time at work
Authors: Anderson Jennifer , Williams Anita E. , Nester Chris
Published: July 2020

Background

Appropriate footwear is important for those who stand for prolonged periods of time at work, enabling them to remain comfortable, healthy and safe. Preferences for different footwear cushioning or hardness are often person specific and one shoe or insole will not be the choice for all. The aim of this study was to develop a range of insole options to maintain comfort during long periods of standing at work and test insole material preferences in the workplace.

Methods

The study consisted of two parts. Part one evaluated 9 insoles of the same geometry that varied in hardness under 2 different plantar regions (n = 34). Insole preference, plantar pressure and selected anthropometric foot measures were taken. Three insole designs based on the most preferred options were identified from this part.

In part two, these three insoles were evaluated with 22 workers immediately after trying them on (1 min) and after a working day. Foot anthropometric measures and subjective questions concerning material hardness preferences and self‐reported foot characteristics were used to investigate whether either had a relationship with insole preference.

Results

Part one found insole preference predominantly varied according to material hardness under the medial arch rather than the heel/forefoot. Softer material under the heel and forefoot was associated with a reduction in peak pressures in these regions (p < 0.05). The most preferred insole had lower pressures under the hallux and first metatarsal phalangeal joint, and greater pressures and contact area under the medial midfoot (p < 0.05) compared to the least preferred insole. Height and foot anthropometrics were related to insole preference.

In part two, under real world conditions, insole preference changed for 65% of participants between the immediate assessment (1 min) and after a whole workday, with dorsum height related to the latter (p < 0.05). Subjective questions for self‐assessed arch height and footwear feel identified 66.7% of the insole preferences after 1 day at work, compared to 36% using immediate assessment of insole preference.

Conclusion

Preference for material hardness varies underneath the medial arch of the foot and is time dependent. Simple foot measures and questions about comfort can guide selection of preferred insoles.
Identification, collection, and reporting of harms among non-industry-sponsored randomized clinical trials of pharmacologic interventions in the critically ill population: a systematic review
Authors: Moskowitz Ari , Andersen Lars W. , Holmberg Mathias J. , Grossestreuer Anne V. , Berg Katherine M. , Granfeldt Asger
Published: July 2020

Background

Prescribing pharmacologic therapies for critically ill patients requires a careful balancing of risks and benefits. Defining, monitoring, and reporting harms that occur in clinical trials conducted in critically ill populations, however, is challenging given that the natural history of most critical illnesses includes progressive multiple organ failure and death. In this study, we assessed harms reporting in clinical trials performed in critically ill populations.

Methods

Randomized, non-industry-sponsored, human clinical trials of pharmacologic interventions in adult critically ill populations published between 2015 and 2018 in high-impact journals were included in this systematic review. Harms data, adherence to Consolidated Standards of Reporting Trials (CONSORT) harms reporting guidelines, and restrictions on harms reporting were recorded.

Results

A total of 707 abstracts were screened with 40 trials ultimately being included in the analysis. Included trials represent 28,636 randomized patients with a median of 292 (IQR 100–546) patients per trial. The most common disease states were general critical care (33%) and sepsis (28%). Of 18 included CONSORT items, the median number met was 12 (IQR 9, 14). The most commonly missed items were adverse event (AE) severity grading definitions and AE attribution (relationship of AE to study drug), which were only reported in 35 and 38% of manuscripts, respectively. Half of the manuscripts (48%) provided definitions for recorded AEs. There were 5 studies investigating the effects of corticosteroids in sepsis, with the number of AEs reported per analyzed patient ranging from 0.01 to 1.89. AE definitions in studies of similar/equivalent interventions often varied substantially. Study protocols were available for 30/40 (75%) of studies, with 13 (43%) of those not providing any guidance regarding AE attribution.

Conclusions

Randomized trials of pharmacologic interventions conducted in critically ill populations and published in high impact journals often fail to adequately describe AE definitions, severity, attribution, and collection procedures. Among trials of similar interventions in comparable populations, variation in AE collection and reporting procedures is substantial. These factors may limit a clinician’s ability to accurately balance the potential benefits and harms of an intervention.
Superior breast cancer metastasis risk stratification using an epithelial-mesenchymal-amoeboid transition gene signature
Authors: Emad Amin , Ray Tania , Jensen Tor W. , Parat Meera , Natrajan Rachael , Sinha Saurabh , Ray Partha S.
Published: July 2020

Background

Cancer cells are known to display varying degrees of metastatic propensity, but the molecular basis underlying such heterogeneity remains unclear. Our aims in this study were to (i) elucidate prognostic subtypes in primary tumors based on an epithelial-to-mesenchymal-to-amoeboid transition (EMAT) continuum that captures the heterogeneity of metastatic propensity and (ii) to more comprehensively define biologically informed subtypes predictive of breast cancer metastasis and survival in lymph node-negative (LNN) patients.

Methods

We constructed a novel metastasis biology-based gene signature (EMAT) derived exclusively from cancer cells induced to undergo either epithelial-to-mesenchymal transition (EMT) or mesenchymal-to-amoeboid transition (MAT) to gauge their metastatic potential. Genome-wide gene expression data obtained from 913 primary tumors of lymph node-negative breast cancer (LNNBC) patients were analyzed. EMAT gene signature-based prognostic stratification of patients was performed to identify biologically relevant subtypes associated with distinct metastatic propensity.

Results

Delineated EMAT subtypes display a biologic range from less stem-like to more stem-like cell states and from less invasive to more invasive modes of cancer progression. Consideration of EMAT subtypes in combination with standard clinical parameters significantly improved survival prediction. EMAT subtypes outperformed prognosis accuracy of receptor or PAM50-based BC intrinsic subtypes even after adjusting for treatment variables in 3 independent, LNNBC cohorts including a treatment-naïve patient cohort.

Conclusions

EMAT classification is a biologically informed method that provides prognostic information beyond that which can be provided by traditional cancer staging or PAM50 molecular subtype status and may improve metastasis risk assessment in early stage, LNNBC patients, who may otherwise be perceived to be at low metastasis risk.
Evolution of pogo, a separate superfamily of IS630-Tc1-mariner transposons, revealing recurrent domestication events in vertebrates
Authors: Gao Bo , Wang Yali , Diaby Mohamed , Zong Wencheng , Shen Dan , Wang Saisai , Chen Cai , Wang Xiaoyan , Song Chengyi
Published: July 2020

Abstracts

Background

Tc1/mariner and Zator, as two superfamilies of IS630-Tc1-mariner (ITm) group, have been well-defined. However, the molecular evolution and domestication of pogo transposons, once designated as an important family of the Tc1/mariner superfamily, are still poorly understood.

Results

Here, phylogenetic analysis show that pogo transposases, together with Tc1/mariner, DD34E/Gambol, and Zator transposases form four distinct monophyletic clades with high bootstrap supports (> = 74%), suggesting that they are separate superfamilies of ITm group. The pogo superfamily represents high diversity with six distinct families (Passer, Tigger, pogoR, Lemi, Mover, and Fot/Fot-like) and wide distribution with an expansion spanning across all the kingdoms of eukaryotes. It shows widespread occurrences in animals and fungi, but restricted taxonomic distribution in land plants. It has invaded almost all lineages of animals—even mammals—and has been domesticated repeatedly in vertebrates, with 12 genes, including centromere-associated protein B (CENPB), CENPB DNA-binding domain containing 1 (CENPBD1), Jrk helix–turn–helix protein (JRK), JRK like (JRKL), pogo transposable element derived with KRAB domain (POGK), and with ZNF domain (POGZ), and Tigger transposable element-derived 2 to 7 (TIGD2–7), deduced as originating from this superfamily. Two of them (JRKL and TIGD2) seem to have been co-domesticated, and the others represent independent domestication events. Four genes (TIGD3, TIGD4, TIGD5, and POGZ) tend to represent ancient domestications in vertebrates, while the others only emerge in mammals and seem to be domesticated recently. Significant structural variations including target site duplication (TSD) types and the DDE triad signatures (DD29–56D) were observed for pogo transposons. Most domesticated genes are derived from the complete transposase genes; but CENPB, POGK, and POGZ are chimeric genes fused with additional functional domains.

Conclusions

This is the first report to systematically reveal the evolutionary profiles of the pogo transposons, suggesting that pogo and Tc1/Mariner are two separate superfamilies of ITm group, and demonstrating the repeated domestications of pogo in vertebrates. These data indicate that pogo transposons have played important roles in shaping the genome and gene evolution of fungi and animals. This study expands our understanding of the diversity of pogo transposons and updates the classification of ITm group.
Quantitative EEG as a biomarker in mild cognitive impairment with Lewy bodies
Authors: Schumacher Julia , Taylor John-Paul , Hamilton Calum A. , Firbank Michael , Cromarty Ruth A. , Donaghy Paul C. , Roberts Gemma , Allan Louise , Lloyd Jim , Durcan Rory , Barnett Nicola , O’Brien John T. , Thomas Alan J.
Published: July 2020

Objectives

To investigate using quantitative EEG the (1) differences between patients with mild cognitive impairment with Lewy bodies (MCI-LB) and MCI with Alzheimer’s disease (MCI-AD) and (2) its utility as a potential biomarker for early differential diagnosis.

Methods

We analyzed eyes-closed, resting-state, high-density EEG data from highly phenotyped participants (39 MCI-LB, 36 MCI-AD, and 31 healthy controls). EEG measures included spectral power in different frequency bands (delta, theta, pre-alpha, alpha, and beta), theta/alpha ratio, dominant frequency, and dominant frequency variability. Receiver operating characteristic (ROC) analyses were performed to assess diagnostic accuracy.

Results

There was a shift in power from beta and alpha frequency bands towards slower frequencies in the pre-alpha and theta range in MCI-LB compared to healthy controls. Additionally, the dominant frequency was slower in MCI-LB compared to controls. We found significantly increased pre-alpha power, decreased beta power, and slower dominant frequency in MCI-LB compared to MCI-AD. EEG abnormalities were more apparent in MCI-LB cases with more diagnostic features. There were no significant differences between MCI-AD and controls. In the ROC analysis to distinguish MCI-LB from MCI-AD, beta power and dominant frequency showed the highest area under the curve values of 0.71 and 0.70, respectively. While specificity was high for some measures (up to 0.97 for alpha power and 0.94 for theta/alpha ratio), sensitivity was generally much lower.

Conclusions

Early EEG slowing is a specific feature of MCI-LB compared to MCI-AD. However, there is an overlap between the two MCI groups which makes it difficult to distinguish between them based on EEG alone.
Neoplastic pathology at the crossroads between neck imaging and cardiothoracic imaging
Authors: Melendez Patricia E. , Nguyen Trinh T. , Bhatt Alok A. , Kaproth-Joslin Katherine
Published: July 2020

The thoracic inlet is located at the crossroads between imaging of the neck and the chest. Its location is an important anatomic landmark, serving as the central conducting pathway for many vital structures extending from the neck into the chest and vice versa. Many critical body systems, including the respiratory, lymphatic, neurologic, enteric, musculoskeletal, endocrine, and vascular systems, are located within this region. Neoplasms, both benign and malignant, can arise in any of the body systems located in this area. Due to the small size of this anatomic location, pathology is easily overlooked and imagers should be aware of the imaging appearance of these neoplasms, as well as which imaging modality is the most appropriate for neoplasm evaluation. This article will present an image rich, system-based discussion of the neoplastic pathology that can occur in this region. The anatomy of the thoracic inlet and the non-neoplastic pathology of the thoracic inlet have been covered in our companion article.
Exosomes derived from human umbilical cord MSCs rejuvenate aged MSCs and enhance their functions for myocardial repair
Authors: Zhang Ning , Zhu Jinyun , Ma Qunchao , Zhao Yun , Wang Yingchao , Hu Xinyang , Chen Jinghai , Zhu Wei , Han Zhongchao , Yu Hong
Published: July 2020

Background

Age and other cardiovascular risk factors have been reported to impair the activities of mesenchymal stem cells (MSCs), which will affect the efficacy of stem cell transplantation. The objective of the study is to investigate whether exosomes derived from human umbilical cord MSCs (UMSCs) could enhance the activities of bone marrow MSCs from old person (OMSCs), and improve their capacity for cardiac repair.

Methods

Exosomes extracted from conditioned medium of UMSCs were used to treat OMSCs to generate OMSCsExo. The key molecule in the exosomes that have potential to rejuvenate aged MSCs were screened, and the role of OMSC was tested in the mouse model of mycardial infarction (MI).

Results

We found the activity of senescence-associated β-galactosidase and the expression of aging-related factors such as p53, p21, and p16 were significantly higher in OMSCs than those in UMSCs. After treatment with UMSC exosomes, these senescence phenotypes of OMSCs were remarkably reduced. The proliferation, migration, differentiation, and anti-apoptotic and paracrine effect were increased in OMSCsExo. In vivo study, mice with cardiac infarction had significantly better cardiac function, less fibrosis, and more angiogenesis after they were injected with OMSCsExo as compared with those with OMSC. There was more miR-136 expression in UMSCs and OMSCsExo than in OMSCs. Upregulation of miR-136 by transfection of miR-136 mimic into OMSCs significantly attenuated the apoptosis and senescence of OMSCs. Apoptotic peptidase activating factor (Apaf1) was found to be the downstream gene that is negatively regulated by miR-136 via directly targeting at its 3′UTR.

Conclusion

Our data suggest that exosomes from young MSCs can improve activities of aged MSCs and enhance their function for myocardial repair by transferring exosomal miR-136 and downregulating Apaf1.
Current progress in stem cell therapy for type 1 diabetes mellitus
Authors: Chen Shuai , Du Kechen , Zou Chunlin
Published: July 2020

Type 1 diabetes mellitus (T1DM) is the most common chronic autoimmune disease in young patients and is characterized by the loss of pancreatic β cells; as a result, the body becomes insulin deficient and hyperglycemic. Administration or injection of exogenous insulin cannot mimic the endogenous insulin secreted by a healthy pancreas. Pancreas and islet transplantation have emerged as promising treatments for reconstructing the normal regulation of blood glucose in T1DM patients. However, a critical shortage of pancreases and islets derived from human organ donors, complications associated with transplantations, high cost, and limited procedural availability remain bottlenecks in the widespread application of these strategies. Attempts have been directed to accommodate the increasing population of patients with T1DM. Stem cell therapy holds great potential for curing patients with T1DM. With the advent of research on stem cell therapy for various diseases, breakthroughs in stem cell-based therapy for T1DM have been reported. However, many unsolved issues need to be addressed before stem cell therapy will be clinically feasible for diabetic patients. In this review, we discuss the current research advances in strategies to obtain insulin-producing cells (IPCs) from different precursor cells and in stem cell-based therapies for diabetes.
The impact of high intensity care around birth on long-term neurodevelopmental outcomes
Authors: Bolbocean Corneliu , Shevell Michael
Published: July 2020

Background

An equitable and affordable healthcare system requires a constant search for the optimal way to deliver increasingly expensive neonatal care. Therefore, evaluating the impact of hospital intensity around birth on long-term health outcomes is necessary if we are to assess the value of high intensity neonatal care against its costs.

Methods

This study exploits uneven geographical distribution of high intensity birth hospitals across Canada to generate comparisons across similar Cerebral Palsy (CP) related births treated at hospitals with different intensities. We employ a rich dataset from the Canadian Multi-Regional CP Registry (CCPR) and instrumental variables related to the mother’s location of residence around birth.

Results

We find that differences in hospitals’ intensities are not associated with differences in clinically relevant, long-term CP health outcomes.

Conclusions

Our results suggest that existing matching mechanism of births to hospitals within large metropolitan areas could be improved by early detection of high risk births and subsequent referral of these births to high intensity birthing centers. Substantial hospitalization costs might be averted to Canadian healthcare system ($16 million with a 95% CI of $6,131,184 - $24,103,478) if CP related births were assigned to low intensity hospitals and subsequently transferred if necessary to high intensity hospitals.
Avian Metapneumovirus subtype B around Europe: a phylodynamic reconstruction
Authors: Franzo Giovanni , Legnardi Matteo , Mescolini Giulia , Tucciarone Claudia Maria , Lupini Caterina , Quaglia Giulia , Catelli Elena , Cecchinato Mattia
Published: July 2020

Avian Metapneumovirus (aMPV) has been recognized as a respiratory pathogen of turkey and chickens for a long time. Recently, a crescent awareness of aMPV, especially subtype B, clinical and economic impact has risen among European researchers and veterinarians. Nevertheless, the knowledge of its epidemiology and evolution is still limited. In the present study, the broadest available collection of partial G gene sequences obtained from European aMPV-B strains was analyzed using different phylodynamic and biostatistical approaches to reconstruct the viral spreading over time and the role of different hosts on its evolution. After aMPV-B introduction, approximatively in 1985 in France, the infection spread was relatively quick, involving the Western and Mediterranean Europe until the end of the 1990s, and then spreading westwards at the beginning of the new millennium, in parallel with an increase of viral population size. In the following period, a wider mixing among aMPV-B strains detected in eastern and western countries could be observed. Most of the within-country genetic heterogeneity was ascribable to single or few introduction events, followed by local circulation. This, combined with the high evolutionary rate herein demonstrated, led to the establishment of genetically and phenotypically different clusters among countries, which could affect the efficacy of natural or vaccine-induced immunity and should be accounted for when planning control measure implementation. On the contrary, while a significant strain exchange was proven among turkey, guinea fowl and chicken, no evidence of differential selective pressures or specific amino-acid mutations was observed, suggesting that no host adaptation is occurring.
Recombinant tandem epitope vaccination provides cross protection against Actinobacillus pleuropneumoniae challenge in mice
Authors: Xiao Jiameng , Liu Jianfang , Bao Chuntong , Zhu Rining , Gu Jingmin , Sun Changjiang , Feng Xin , Du Chongtao , Han Wenyu , Li Yang , Lei Liancheng
Published: July 2020

Actinobacillus pleuropneumoniae (A. pleuropneumoniae/APP) is the pathogen that causes porcine contagious pleuropneumonia. Actinobacillus pleuropneumoniae is divided into 18 serovars, and the cross protection efficacy of epitopes is debatable, which has resulted in the slow development of a vaccine. Consequently, epitope-based vaccines conferring Actinobacillus pleuropneumoniae cross protection have rarely been reported. In this study, B cell epitopes in the head domain of trimeric autotransporter adhesin were predicted, and 6 epitopes were selected. Then, the predicted epitopes (Ba1, Bb5, C1, PH1 and PH2) were connected by linkers to construct a recombinant tandem antigen (rta) gene. The RTA protein encoded by the recombinant rta gene was expressed, and finally the ICR mice were immunized with the RTA protein with or without inactivated Actinobacillus pleuropneumoniae (serovars 1 and 5b) and challenged with Actinobacillus pleuropneumoniae to evaluate the protective effect of the epitope-based vaccine and combined vaccine. The mice in the RTA-immunized group and RTA plus inactivated Actinobacillus pleuropneumoniae vaccine group had a significant improvement in clinical symptoms and a higher level of antibody in the serum than those in the control group. The RTA immune group had a 40% survival rate after Actinobacillus pleuropneumoniae infection, whereas the combination of RTA and inactivated Actinobacillus pleuropneumoniae produced very strong cross immune protection in mice, at least 50% (RTA IB1 + C5) and at most 100% (RTA IB5 + C1), whereas no cross immunoprotection was found in the solo Actinobacillus pleuropneumoniae immune group. Overall, the combination of the RTA protein and inactivated bacteria significantly enhanced the cross protection effects. This implies that RTA protein in combination with a suitable inactivated Actinobacillus pleuropneumoniae strain could be a candidate vaccine for porcine contagious pleuropneumonia.
Ulam–Hyers–Rassias stability for nonlinear Ψ-Hilfer stochastic fractional differential equation with uncertainty
Authors: Chaharpashlou Reza , Saadati Reza , Atangana Abdon
Published: July 2020

We consider a nonlinear Cauchy problem involving the Ψ-Hilfer stochastic fractional derivative with uncertainty, and we give a stability result. Using fixed point theory, we are able to provide a fuzzy Ulam–Hyers–Rassias stability for the considered nonlinear stochastic fractional differential equations.
Existence results of nonlocal Robin boundary value problems for fractional $(p,q)$-integrodifference equations
Authors: Soontharanon Jarunee , Sitthiwirattham Thanin
Published: July 2020

The existence results of a fractional$(p,q)$(p,q)-integrodifference equation with nonlocal Robin boundary condition are investigated by using Banach’s and Schauder’s fixed point theorems. Moreover, we study some properties of$(p,q)$(p,q)-integral that will be used as a tool for our calculations.
A new approach for urinary vanillylmandelic acid determination using eVol microextraction by packed sorbent coupled to liquid chromatography-tandem mass spectrometry
Authors: Xiong Xin , Zhang Yuanyuan
Published: July 2020

Vanillylmandelic acid (VMA) is one of the most important catecholamine metabolites, and it is usually used to aid in diagnosis of pheochromocytoma and paraganglioma. A new digital control microextraction by packed sorbent (MEPS) procedure coupled to liquid chromatography-mass spectrometry (LC-MS/MS) method has been developed to determine VMA in human urine. We evaluated important parameters influencing MEPS efficiency, including stationary phase, extracting cycles, and sample dilution. In optimized MEPS conditions, Only 10 μL of sample volume and 3 min preparation time for one sample were needed. Chromatographic separation was achieved with a hydrophilic interaction liquid chromatography (HILIC) column using gradient elution. VMA was detected using multiple reaction monitoring (MRM) with an electrospray source operating in negative ion mode. The method was validated for linearity, limit of quantification, accuracy, imprecision, matrix effect, and interference. Linearity was 0.5–100 μg/mL for VMA. Intra-assay, inter-assay, and total imprecision were less than 9.6%. Interferences precluding quantitation of VMA in dilute-and-shoot approach were reduced significantly using a MEPS approach. Method comparison of LC-MS/MS and homogeneous enzyme immunoassay was performed, and the reference interval was established. The developed MEPS-LC-MS/MS method certainly contributes to method robustness and makes it suitable for measurement of urinary VMA in routine clinical biochemistry laboratories.
Geological structures controlled the rupture process of the 2011 M9.0 Tohoku-Oki earthquake in the Northeast Japan Arc
Authors: Baba Kei , Yoshida Takeyoshi
Published: July 2020

By interpreting the 2D/3D seismic survey data acquired in the surrounding ocean areas of the Northeast (NE) Japan Arc, we clarified the detailed geological structure and demonstrated that the basic structure in the hanging-wall plate of the subduction system consists of many structural blocks (segments) separated by NW–SE trending large transcurrent faults (strike-slip faults). This structural configuration showed a close relationship with the distribution of foreshocks, mainshock, and aftershocks, coseismic slip models of the 2011 M9.0 Tohoku-Oki megathrust earthquake, coseismic slip area of M-7 class earthquakes, quasi-static slip rates, back slip rate, and seismic tomography images. In addition, the coseismic slip models revealed that the trenchward forearc of the structural blocks between the Offshore Hidaka tectonic line and the Honjo-Sendai tectonic line fitted well with the coseismic slip area of the 2011 Tohoku-Oki earthquake. These findings suggest that the structural blocks bounded by these two tectonic lines slipped rapidly trenchward when the mainshock occurred. The M7 earthquakes were also concentrated along these two tectonic lines, thereby suggesting a close relationship between seismic activity and the inherited geological structure of the overriding plate in the NE Japan forearc.
Evaluation of the effect of high dose intravenous vitamin C on delayed allograft function in deceased donor kidney transplantation: a preliminary report
Authors: Borran Mina , Dashti-Khavidaki Simin , Alamdari Azam , Naderi Neda , Minoo Farzanehsadat
Published: July 2020

Background

Delayed graft function (DGF) can affect short- and long-term allograft outcomes in kidney transplant recipients. One of the pathophysiological pathways in the occurrence of DGF is ischemia-reperfusion injury (IRI). High dose intravenous vitamin C has proven efficacy in decreasing IRI consequences. Accordingly, we designed this study to assess the effect of high dose intravenous vitamin C on the incidence and duration of DGF.

Methods

This is a pilot, single-center, double-blinded, randomized, placebo-controlled trial. In the treatment group, kidney transplant recipients received vitamin C infusion at the dose of 70 mg/kg diluted in 0.45% saline, and in another study arm, only the diluent solution was administered. Data regarding allograft function and other clinical information was recorded.

Results

This preliminary study on 19 patients (9 cases in the vitamin C and 10 cases in the placebo group) showed that after administration of single, high dose vitamin C the incidence of DGF was not significantly different between the groups, but the duration of DGF was substantially shorter in the vitamin C group than the placebo group (7.33 ± 5.68 versus 19.66 ± 0.57 days; P = 0.02). Acute rejection episodes were more seen in the vitamin C group than in the placebo group. Although this data was not statistically significant (P = 0.37), it led to the termination of the study.

Conclusion

A high dose of intravenous vitamin C before allograft implantation was effective in decreasing DGF duration but not DGF incidence.

Trial registration

The trial was registered in the Iranian registry of clinical trials encoded IRCT20100111003043N13 on June 24, 2019.
Smaller cross-sectional areas of the hamstring tendon measured from preoperative ultrasonography are likely to need additional gracilis harvesting for double-bundle anterior cruciate ligament reconstructions
Authors: Goto Kazumi , Hara Masahiko , Yamazaki Yoshiyuki , Urata Taihei , Shimizu Yuki , Shimizu Naofumi
Published: July 2020

Background/Purpose

Hamstring tendon autografts are commonly used for double-bundle anterior cruciate ligament reconstruction (DB-ACLR). If the volume of the semitendinosus (ST) tendon is insufficient, the gracilis (G) tendon is also harvested. Additional harvesting of the G autograft can affect patients’ short-term postoperative outcome, such as muscle recovery; thus, preoperative information about whether an additional G autograft is needed would be useful. The purpose of this study was to investigate whether preoperative measurement of the ST tendon using ultrasonography could inform the intraoperative decision to harvest the G tendon.

Methods

We enrolled 20 patients (13 men and seven women) who underwent DB-ACLR between October 2017 and March 2019. The mean patient age was 28.5 years. The ipsilateral ST tendon was measured using ultrasonography before surgery. Measurements included the diameter and breadth of the short-axis image. The cross-sectional area (CSA) was calculated from these measurements. During surgery, when two grafts with diameters of ≥ 5.0 mm could not be made, the G tendon was also harvested. Patients were categorized into two groups: the ST group where only the ST tendon was harvested, and the semitendinosus gracilis tendon (STG) group where the ST and G tendons were both harvested. The CSA value was compared between the two groups, and the cutoff value was calculated.

Results

In the ST group (n = 8), the mean diameter and breadth of the semitendinosus tendon were 4.21 and 2.34 mm, respectively. In the STG group (n = 12), the mean diameter and breadth of the ST tendon were 3.39 and 1.78 mm, respectively. The CSAs calculated for the ST group and the STG group were 7.74 mm2 and 4.79 mm2, respectively. A cutoff value of 7.0 mm2 was found to correspond to a specificity and sensitivity to harvest the G tendon of 87.5% and 75.0%, respectively.

Conclusions

The preoperative CSA of the ST tendon determined using ultrasonography can, therefore, be informative for deciding whether to harvest the G tendon for DB-ACLR. The results of this study provide valuable information for graft selection in anterior cruciate ligament reconstruction.

Level of Evidence

IV (Retrospective case series design).
Quantitative scintigraphy in discriminating sacroiliac joint physiological and pathological uptake
Authors: Abdelhai Shaimaa F. , Abdelhamed Heba M. , El-Shafey Abeer M. , Almolla Rania M.
Published: July 2020

Background

Bone scintigraphy is a highly sensitive diagnostic nuclear medicine imaging technique that uses a radiotracer to evaluate the distribution of active bone formation in the skeleton related to malignant and benign diseases, as well as physiological processes. Subjective increase of the radioactivity at the sacroiliac joint in cancer patients could indicate physiological, metastatic, or inflammatory (sacroiliitis) cause. In this single-center study, we aimed to settle the normal sacroiliac index (SII) in males and females and if it differs from side to other, as a more accurate quantitative method than qualitative one, and assess its validity in discriminating the cause in pathological increase.

Results

Sacroiliac index can differentiate physiological uptake at the SIJ from pathological uptake with a highly significant value (P < 0.001). Using SII at a cutoff value 1.17 had 100% sensitivity and specificity in differentiating between the two conditions. The normal SII in our institute ranged from 0.9 to 1.14 with no significant difference between right and left SIJs. The mean SII was 1.33 ± 0.11 in patients with ankylosing spondylitis (AS) and 1.38 ± 0.1 in metastatic cases with no significant difference in SII between the two diseased groups (P = 0.49).

Conclusion

Bone scintigraphy is widely used in our institute and qualitative assessment of SIJ uptake is sometimes confusing. In this study, we assessed the normal SII range in physiological uptake and assessed a cutoff value (which is lower than other races) above which any increase in SIJ uptake is considered pathological. We could not confirm a cutoff value to discriminate between AS and metastatic affection of SIJ.
Meta-Analysis of Prevalence of Triple-Negative Breast Cancer and Its Clinical Features at Incidence in Indian Patients With Breast Cancer
Authors: Kulkarni Apurv , Kelkar Devaki A. , Parikh Nidhi , Shashidhara Lingadahalli S. , Koppiker Chaitanyanand B. , Kulkarni Madhura
Published: July 2020

PURPOSE

Breast cancer is the most common cancer in women in India, with higher incidence rates of aggressive subtypes, such as triple-negative breast cancer (TNBC).

METHODS

A systematic review was performed to compute pooled prevalence rates of TNBC among patients with breast cancer, and clinical features at presentation were systematically compared with non-TNBC in an Indian cohort of 20,000 patients.

RESULTS

Combined prevalence of TNBC among patients with breast cancer was found to be on the higher side (27%; 95% CI, 24% to 31%). We found that the estrogen receptor (ER) expression cutoff used to determine ER positivity had an influence on the pooled prevalence and ranged from 30% (ER/progesterone receptor [PR] cut ff at 1%) to 24% (ER/PR cutoff at 10%). Odds for TNBC to present in the younger age-group were significantly higher (pooled odds ratio [OR], 1.35; 95% CI, 1.08 to 1.69), with a significantly younger mean age of incidence (weighted mean difference, −2.75; 95% CI, −3.59 to −1.92). TNBC showed a significantly higher odds of presenting with high grade (pooled OR, 2.57; 95% CI, 2.12 to 3.12) and lymph node positivity (pooled OR, 1.39; 95% CI, 1.21 to 1.60) than non-TNBC.

CONCLUSION

Systematic review and meta-analysis of 34 studies revealed a high degree of heterogeneity in prevalence of TNBC within Indian patients with breast cancer, yet pooled prevalence of TNBC is high in India. High proportions of patients with TNBC present with aggressive features, such as high grade and lymph node positivity, compared with patients without TNBC. We emphasize the need for standardized methods for accurate diagnosis in countries like India.
Evaluation of Omics-Based Strategies for the Management of Advanced Lung Cancer
Authors: Salgia Ravi , Mambetsariev Isa , Pharaon Rebecca , Fricke Jeremy , Baroz Angel Ray , Hozo Iztok , Chen Chen , Koczywas Marianna , Massarelli Erminia , Reckamp Karen , Djulbegovic Benjamin
Published: July 2020

PURPOSE:

Omic-informed therapy is being used more frequently for patients with non–small-cell lung cancer (NSCLC) being treated on the basis of evidence-based decision-making. However, there is a lack of a standardized framework to evaluate those decisions and understand the association between omics-based management strategies and survival among patients. Therefore, we compared outcomes between patients with lung adenocarcinoma who received omics-driven targeted therapy versus patients who received standard therapeutic options.

PATIENTS AND METHODS:

This was a retrospective study of patients with advanced NSCLC adenocarcinoma (N = 798) at City of Hope who received genomic sequencing at the behest of their treating oncologists. A thoracic oncology registry was used as a clinicogenomic database to track patient outcomes.

RESULTS:

Of 798 individuals with advanced NSCLC (median age, 65 years [range, 22-99 years]; 60% white; 50% with a history of smoking), 662 patients (83%) had molecular testing and 439 (55%) received targeted therapy on the basis of the omic-data. A fast-and-frugal decision tree (FFT) model was developed to evaluate the impact of omics-based strategy on decision-making, progression-free survival (PFS), and overall survival (OS). We calculated that the overall positive predictive value of the entire FFT strategy for predicting decisions regarding the use of tyrosine kinase inhibitor–based targeted therapy was 88% and the negative predictive value was 96%. In an adjusted Cox regression analysis, there was a significant correlation with survival benefit with the FFT omics-driven therapeutic strategy for both PFS (hazard ratio [HR], 0.56; 95% CI, 0.42 to 0.74; P < .001) and OS (HR, 0.51; 95% CI, 0.36 to 0.71; P < .001) as compared with standard therapeutic options.

CONCLUSION:

Among patients with advanced NSCLC who received care in the academic oncology setting, omics-driven therapy decisions directly informed treatment in patients and was correlated with better OS and PFS.
Decline in Muscle Strength and Performance Predicts Fracture Risk in Elderly Women and Men
Authors: Alajlouni Dima , Bliuc Dana , Tran Thach , Eisman John A , Nguyen Tuan V , Center Jacqueline R
Published: July 2020

Context

Muscle strength and performance are associated with fractures. However, the contribution of their rate of decline is unclear.

Objective

To assess the independent contribution of the rate of decline in muscle strength and performance to fracture risk.

Design, Setting, and Participants

Community-dwelling women (n = 811) and men (n = 440) aged 60 years or older from the prospective Dubbo Osteoporosis Epidemiology Study followed from 2000 to 2018 for incident fracture. Clinical data, appendicular lean mass/height2 (ht)2, bone mineral density, quadricep strength/ht (QS), timed get-up-and-go (TGUG), 5 times repeated sit-to-stand (5xSTS), and gait speed (GS) measured biennially. Rates of decline in muscle parameters were calculated using ordinary least squares regression and fracture risk was assessed using Cox’s models.

Main Outcome

Incident low-trauma fracture ascertained by x-ray report.

Results

Apart from lean mass in women, all muscle parameters declined over time. Greater rates of decline in physical performance were associated with increased fracture risk in women (Hazard ratios [HRs] ranging from 2.1 (95% CI: 1.5–2.9) for GS to 2.7 (95% CI: 1.9–3.6) for 5xSTS, while in men only the decline in GS was associated with fracture risk (HR: 3.4 [95% CI: 1.8–6.3]). Baseline performance and strength were also associated with increased fracture risk in men (HRs ranging from 1.8 (95% CI: 1.1–3.0) for QS to 2.5 (95% CI: 1.5–4.1) for TGUG, but not in women.

Conclusion

Rate of decline in physical performance in both genders, and baseline strength and performance in men, contributed independently to fracture risk. Sit-to-stand and GS were the tests most consistently associated with fractures. Further studies are required to determine whether muscle strength and/or performance improve the predictive accuracy of fracture prediction models.
Introduction
Authors: Ali Ashna , Foster Christopher Ian , Nair Supriya M.
Published: July 2020

The first of its kind, this special focus section examines a relatively understudied concept and brings together new literary works and scholarship across continents and languages. Contemporary authors and activists like Fatou Diome, Shailja Patel, Abdourahman Waberi, and Igiaba Scego contribute to a new literary, cultural, and political genre called migritude. Migritude initially indicated a group of younger African authors in Paris but has since expanded to include Europe beyond France, such as Britain and Italy, as well as South Asian and Caribbean diasporas. This body of work reveals intersections between complex histories of colonialism, immigration, globalization, and racism against migrants and highlights differences in region, class, gender, and sexuality that constrain the movement of many people. In an era characterized by openly belligerent nationalism and anti-immigrant and anti-LGBTQ rhetoric, this special focus section aims to unpack migritude cultural production in an international context to study and combat these violent trends.
The Transits and Transactions of Migritude in Bay Mademba’s Il mio viaggio della speranza (My Voyage of Hope)
Authors: Paynter Eleanor
Published: July 2020

Migritude literature, or the literature of postcolonial migration, is often autobiographical and thus productively read through the lens of life writing. How authors position the immigrant self as subject sheds light on narrative possibilities and their potential impact on readers in contexts where racist, anti-immigrant discourses dominate. This article explores the scope and stakes of migritude life writing through the example of Il mio viaggio della speranza (My Voyage of Hope), a 2011 memoir by Bay Mademba, who recounts his journey from Senegal to Italy and bears witness to the discrimination he faces there. Mademba’s testimony responds to duress, which Ann Stoler defines as the “colonial entailments” that shape contemporary spaces, institutions, and relations. Produced by a small Tuscan press, the memoir circulates via immigrant street vendors. Through the convergence of narrative and material transactions, the book prompts reader-consumers to recognize their complicity in the duress that shapes their interactions.
Migritude’s Progress
Authors: Haskell Rosemary
Published: July 2020

Novelist Fatou Diome, Senegalese migrant to France, in 2019 reached the twenty-fifth year in her adopted country. Silver-anniversary motives encouraged the author to chart the quarter century of progress of this “megaphone of migritude,” as Lila Azam Zanganeh notably called her. Moving from the rich exegeses of the liminal, haunted, frequently abjected, migritude conditions of her fictional—and often autobiographical—heroines, Diome has now arrived inside the Hexagon, where her words harmonize with a sizable chorus of interior-left establishment voices. However, she has not abandoned her powerful interest in the complexities of migritude’s pains and difficult opportunities. On the contrary, in Marianne porte plainte! Identité nationale: Des passerelles, pas des barrières! (Marianne Complains! National Identity: Gangways, Not Barriers!) (2017), Diome takes up the many threads of the migritude tapestry so fully depicted in her novels and reweaves them into a portrait of an ideal new multicultural French identity.
Activist by Default
Authors: Ali Ashna
Published: July 2020

This interview with Igiaba Scego, renowned Italian author and journalist of Somali descent, explores the relationship between letteratura della migrazione, the italophone migrant literary movement of the 1990s and early 2000s, and migritude, a burgeoning global literary genre and field of scholarship that addresses contemporary discourses of migration and their colonial histories. Scego discusses her resistance to the category of “migrant writer” and the challenge of retelling stories of postcolonial African diaspora to Italy in the context of Italian colonialism in the Horn of Africa. She discusses what it means to claim the city of Rome as one’s own as a black Italian, and places stories of flight and belonging in a global and historical context. This interview was conducted over WhatsApp, transcribed, and translated into English in February 2019.
Cinema against Communication
Authors: Berger Kenneth
Published: July 2020

This essay reassesses the concept of spectacle and argues for aesthetic refusal as a key strategy for contesting spectacle’s expanding hold on everyday existence. Against the view that spectacle renders the individual passive, the essay asserts instead that spectacle develops as a central postwar mechanism for intensifying the subject’s productivity and managing the growing anxiety that pervades post-Fordist social life. Highlighting the “refusal of work” that grounds 1960s Italian workerist movements, the essay proposes a corresponding refusal of communication, a form of aesthetic refusal that, as with political refusal, operates not through simple negation, but through creating openings or ruptures that allow new possibilities to emerge. Such aesthetic refusal, which finds its most radical postwar expression in the antispectacular films of Guy Debord, thus arises as a means to reorient perception, to break with existing modes of seeing so that different forms of existence might be envisioned and initiated.