bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toe flexor strength is associated with mobility in older adults with pronated and supinated feet but not with neutral feet
Authors: Kusagawa Yuki , Kurihara Toshiyuki , Imai Aiko , Maeo Sumiaki , Sugiyama Takashi , Kanehisa Hiroaki , Isaka Tadao 
Published: September 2020

AbstractBackgroundOlder adults are known to have more pronated foot posture and decreased toe flexor strength (TFS), as well as decreased mobility in daily life compared to young adults. Although foot posture is reported to be an influential factor for walking biomechanics in young adults, there is less information on this subject in older adults. Age‐related reduction in TFS is shown to be associated with impairments of functional performance, but it is poorly understood whether foot posture influences the relationships between TFS and functional performances. Therefore, the present study aimed to elucidate this concern by examining older women.MethodsSeventy community‐dwelling older women (76.8 ± 4.4 years) voluntarily participated in this study. Foot posture was evaluated by the 6‐item foot posture index (FPI). Based on the FPI score, participants were allocated to pronated, neutral, or supinated group (n = 33, 26, and 11, respectively). TFS was assessed using a toe grip dynamometer in a seated position. Scores of 30‐s chair stand, timed up‐and‐go, 5‐m comfortable‐speed walking, and static balance tests were determined to evaluate functional performances. Pearson's correlation coefficients were computed to examine the relationships between TFS and functional performances in each group.ResultsTFS positively correlated with comfortable walking speed in the pronated (r = 0.37, p = 0.03) and supinated (r = 0.76, p < 0.001) groups, but not in the neutral group (r = 0.17, p = 0.42). For the two significant relationships, an analysis of covariance showed that there was no significant difference between the pronated and supinated groups in the slopes of the regression lines, suggesting a similar relative contribution of TFS to comfortable walking speed between the two groups. In addition, TFS tended to negatively correlate with timed up‐and‐go time in the pronated (r = − 0.32, p = 0.07) and supinated (r = − 0.56, p = 0.08) groups, and positively correlate with 30‐s chair stand score in the pronated group (r = 0.31, p = 0.08).ConclusionsThe present study indicates that TFS would be associated with mobility, walking performance in particular, in older women with pronated and supinated feet but not with neutral feet.
Impact of the COVID-19 epidemic at a high-volume facility in gynecological oncology in Tokyo, Japan: a single-center experience
Authors: Nogami Yuya , Kobayashi Yusuke , Tsuji Kosuke , Yokota Megumi , Nishio Hiroshi , Nakamura Masaru , Yamagami Wataru , Morisada Tohru , Tominaga Eiichiro , Banno Kouji , Aoki Daisuke 
Published: September 2020

Abstract
Background
The number of cases of novel coronavirus disease 2019 (COVID-19) in Japan have risen since the first case was reported on January 24, 2020, and 6225 infections have been reported as of June 30, 2020. On April 8, 2020, our hospital began screening patients via pre-admission reverse transcriptase-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and chest computed tomography (CT). Although no patients exhibited apparent pneumonia, treatment delay or changes in treatment plans were required for a few patients based on the results of screening tests. During an emerging infectious disease pandemic, the likelihood of being infected, as well as the disease itself, affects clinical decision making in several ways. We summarized and presented our experience.

Case presentation
After the introduction of pre-admission screening, RT-PCR and CT were performed in 200 and 76 patients, respectively, as of June 30, 2020. The treatment of five patients, including two patients with cervical cancer, two patients with ovarian tumors, and one patient with ovarian cancer, was affected by the results. Two asymptomatic RT-PCR-positive patients did not develop COVID-19, but their treatment was delayed until the confirmation of negative results. The other three patients were RT-PCR-negative, but abnormal CT findings suggested the possibility of COVID-19, which delayed treatment. The patients receiving first-line preoperative chemotherapy for ovarian cancer had clinically evident exacerbations because of the treatment delay.

Conclusion
During the epidemic phase of an emerging infectious disease, we found that COVID-19 has several other effects besides its incidence. The postponing treatment was the most common, therefore, treatment of ovarian tumors and ovarian cancer was considered to be the most likely to be affected among gynecological diseases. Protocols that allow for easy over-diagnosis can be disadvantageous, mainly because of treatment delays, and therefore, the protocols must be developed in light of the local infection situation.
A phase 1b study evaluating the effect of elacestrant treatment on estrogen receptor availability and estradiol binding to the estrogen receptor in metastatic breast cancer lesions using 18F-FES PET/CT imaging
Authors: Jager Agnes , de Vries Elisabeth G. E. , der Houven van Oordt C. Willemien Menke-van , Neven Patrick , Venema Clasina M. , Glaudemans Andor W. J. M. , Wang Yamei , Bagley Rebecca G. , Conlan Maureen G. , Aftimos Philippe 
Published: September 2020

Abstract
Background
Elacestrant is an oral selective estrogen receptor (ER) degrader. This phase 1b open-label, non-randomized study (RAD1901-106) was initiated to determine the effect of elacestrant on the availability of ER in lesions from postmenopausal women with ER+ advanced breast cancer (ABC) using 16α-18F-fluoro-17β-estradiol positron emission tomography with low-dose computed tomography (FES-PET/CT).

Methods
Eligible patients were postmenopausal women with ER+, HER2− ABC; tumor progression after ≥ 6 months of 1–3 lines of endocrine treatment for ABC; and measurable or evaluable disease. Two 8-patient cohorts were enrolled: one treated with 400 mg elacestrant once daily (QD) and one treated with 200 mg elacestrant QD with dose escalation to 400 mg QD after 14 days. Elacestrant was dosed continuously until progressive disease, toxicity, or withdrawal. FES-PET/CT was performed pre-dose at baseline and 4 h post-dose on day 14. The primary endpoint was the percentage difference in FES uptake in tumor lesions (maximum 20) after 14 days of treatment compared to baseline. Overall response was investigator-assessed by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1.

Results
Patients (n = 16; median age, 53.5 years) had ABC with a median 2.5 prior lines of endocrine therapy. Median reduction in tumor FES uptake from baseline to day 14 was 89.1% (Q1, Q3: 75.1%, 94.1%) and was similar in both cohorts (89.1% [Q1, Q3: 67.4%, 94.2%], 200/400 mg and 88.7% [Q1, Q3: 79.5%, 94.1%], 400 mg). Residual ER availability (> 25% persistence in FES uptake) on day 14 was observed in 3 patients receiving 200/400 mg (3/78, 37.5%) and 1 patient receiving 400 mg (1/8, 12.5%). The overall response rate (ORR) was 11.1% (1 partial response), and clinical benefit rate (CBR) was 30.8%. Median percentage change in FES uptake did not correlate with ORR or CBR. Adverse events occurring in > 20% of the patients were nausea (68.8%), fatigue (50.0%), dyspepsia (43.8%), vomiting (37.5%), and decreased appetite, dysphagia, and hot flush (31.3% each). Most events were grade 2 in severity.

Conclusion
Elacestrant 200 mg and 400 mg QD greatly reduced ER availability measured by FES-PET/CT. In a heavily pretreated population, elacestrant was associated with antitumor activity.

Trial registration
ClinicalTrials.gov, NCT02650817. Registered on 08 January 2016
Dual-energy CT in gout patients: Do all colour-coded lesions actually represent monosodium urate crystals?
Authors: Christiansen Sara Nysom , Müller Felix Christoph , Østergaard Mikkel , Slot Ole , Møller Jakob M. , Børgesen Henrik F. , Gosvig Kasper Kjærulf , Terslev Lene 
Published: September 2020

Abstract
Background
Dual-energy CT (DECT) can acknowledge differences in tissue compositions and can colour-code tissues with specific features including monosodium urate (MSU) crystals. However, when evaluating gout patients, DECT frequently colour-codes material not truly representing MSU crystals and this might lead to misinterpretations. The characteristics of and variations in properties of colour-coded DECT lesions in gout patients have not yet been systematically investigated.
The objective of this study was to evaluate the properties and locations of colour-coded DECT lesions in gout patients.

Methods
DECT of the hands, knees and feet were performed in patients with suspected gout using factory default gout settings, and colour-coded DECT lesions were registered. For each lesion, properties [mean density (mean of Hounsfield Units (HU) at 80 kV and Sn150kV), mean DECT ratio and size] and location were determined. Subgroup analysis was performed post hoc evaluating differences in locations of lesions when divided into definite MSU depositions and possibly other lesions.

Results
In total, 4033 lesions were registered in 27 patients (23 gout patients, 3918 lesions; 4 non-gout patients, 115 lesions). In gout patients, lesions had a median density of 160.6 HU and median size of 6 voxels, and DECT ratios showed an approximated normal distribution (mean 1.06, SD 0.10), but with a right heavy tail consistent with the presence of smaller amounts of high effective atomic number lesions (e.g. calcium-containing lesions).
The most common locations of lesions were 1st metatarsophalangeal (MTP1), knee and midtarsal joints along with quadriceps and patella tendons. Subgroup analyses showed that definite MSU depositions (large volume, low DECT ratio, high density) had a similar distribution pattern, whereas possible calcium-containing material (high DECT ratio) and non-gout MSU-imitating lesions (properties as definite MSU depositions in non-gout patients) were primarily found in some larger joints (knee, midtarsal and talocrural) and tendons (Achilles and quadriceps). MTP1 joints and patella tendons showed only definite MSU depositions.

Conclusion
Colour-coded DECT lesions in gout patients showed heterogeneity in properties and distribution. MTP1 joints and patella tendons exclusively showed definite MSU depositions. Hence, a sole focus on these regions in the evaluation of gout patients may improve the specificity of DECT scans.
Effects of disease activity on lipoprotein levels in patients with early arthritis: can oxidized LDL cholesterol explain the lipid paradox theory?
Authors: Fernández-Ortiz Ana M. , Ortiz Ana M. , Pérez Silvia , Toledano Esther , Abásolo Lydia , González-Gay Miguel A. , Castañeda Santos , González-Álvaro Isidoro 
Published: September 2020

Abstract
Background
An increased risk of cardiovascular (CV) complications has been described in patients with rheumatoid arthritis (RA). It is the result of the combined effect of classic CV risk factors and others that are specific to the disease.

Methods
We assessed data from 448 early arthritis (EA) patients: 79% women, age (median [p25-p75]) at onset: 55 [44–67] years and disease duration at study entry 5 [3–8] months; and 72% fulfilled the 1987 RA criteria at 2 years of follow-up. Rheumatoid factor was positive in 54% of patients and anti-citrullinated peptide antibodies in 50%. The follow-up of patients ranged from 2 to 5 years with more than 1400 visits with lipoprotein measurements available (mean 2.5 visits/patient). Demographic- and disease-related variables were systematically recorded. Total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) levels were obtained from routine laboratory tests. Oxidized-LDL (oxLDL-C) levels were assessed using a commercial ELISA kit. We fitted population-averaged models nested by patient and visit to determine the effect of independent variables on serum levels of TC, its fractions, and oxLDL-C.

Results
After adjustment for several confounders, high-disease activity was significantly associated with decreased TC, HDL-C, and LDL-C levels and increased oxLDL-C levels. Standardized coefficients showed that the effect of disease activity was greater on oxLDL-C and HDL-C. Interestingly, we observed that those patients with lower levels of LDL-C showed higher oxLDL-C/LDL-C ratios.

Conclusions
High-disease activity in EA patients results in changes in the HDL-C and oxLDL-C levels, which in turn may contribute to the increased risk of CV disease observed in these patients.
Reduced mitochondrial D-loop methylation levels in sporadic amyotrophic lateral sclerosis
Authors: Stoccoro Andrea , Smith Adam R. , Mosca Lorena , Marocchi Alessandro , Gerardi Francesca , Lunetta Christian , Cereda Cristina , Gagliardi Stella , Lunnon Katie , Migliore Lucia , Coppedè Fabio 
Published: September 2020

Abstract
Background
Mitochondrial dysregulation and aberrant epigenetic mechanisms have been frequently reported in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), and several researchers suggested that epigenetic dysregulation in mitochondrial DNA (mtDNA) could contribute to the neurodegenerative process. We recently screened families with mutations in the major ALS causative genes, namely C9orf72, SOD1, FUS, and TARDBP, observing reduced methylation levels of the mtDNA regulatory region (D-loop) only in peripheral lymphocytes of SOD1 carriers. However, until now no studies investigated the potential role of mtDNA methylation impairment in the sporadic form of ALS, which accounts for the majority of disease cases. The aim of the current study was to investigate the D-loop methylation levels and the mtDNA copy number in sporadic ALS patients and compare them to those observed in healthy controls and in familial ALS patients. Pyrosequencing analysis of D-loop methylation levels and quantitative analysis of mtDNA copy number were performed in peripheral white blood cells from 36 sporadic ALS patients, 51 age- and sex-matched controls, and 27 familial ALS patients with germinal mutations in SOD1 or C9orf72 that represent the major familial ALS forms.

Results
In the total sample, D-loop methylation levels were significantly lower in ALS patients compared to controls, and a significant inverse correlation between D-loop methylation levels and the mtDNA copy number was observed. Stratification of ALS patients into different subtypes revealed that both SOD1-mutant and sporadic ALS patients showed lower D-loop methylation levels compared to controls, while C9orf72-ALS patients showed similar D-loop methylation levels than controls. In healthy controls, but not in ALS patients, D-loop methylation levels decreased with increasing age at sampling and were higher in males compared to females.

Conclusions
Present data reveal altered D-loop methylation levels in sporadic ALS and confirm previous evidence of an inverse correlation between D-loop methylation levels and the mtDNA copy number, as well as differences among the major familial ALS subtypes. Overall, present results suggest that D-loop methylation and mitochondrial replication are strictly related to each other and could represent compensatory mechanisms to counteract mitochondrial impairment in sporadic and SOD1-related ALS forms.
Attractor-state itinerancy in neural circuits with synaptic depression
Authors: Chen Bolun , Miller Paul 
Published: September 2020

AbstractNeural populations with strong excitatory recurrent connections can support bistable states in their mean firing rates. Multiple fixed points in a network of such bistable units can be used to model memory retrieval and pattern separation. The stability of fixed points may change on a slower timescale than that of the dynamics due to short-term synaptic depression, leading to transitions between quasi-stable point attractor states in a sequence that depends on the history of stimuli. To better understand these behaviors, we study a minimal model, which characterizes multiple fixed points and transitions between them in response to stimuli with diverse time- and amplitude-dependencies. The interplay between the fast dynamics of firing rate and synaptic responses and the slower timescale of synaptic depression makes the neural activity sensitive to the amplitude and duration of square-pulse stimuli in a nontrivial, history-dependent manner. Weak cross-couplings further deform the basins of attraction for different fixed points into intricate shapes. We find that while short-term synaptic depression can reduce the total number of stable fixed points in a network, it tends to strongly increase the number of fixed points visited upon repetitions of fixed stimuli. Our analysis provides a natural explanation for the system’s rich responses to stimuli of different durations and amplitudes while demonstrating the encoding capability of bistable neural populations for dynamical features of incoming stimuli.
Disruption in iron homeostasis and impaired activity of iron-sulfur cluster containing proteins in the yeast model of Shwachman-Diamond syndrome
Authors: Jain Ayushi , Nilatawong Phubed , Mamak Narinrat , Jensen Laran T. , Jensen Amornrat Naranuntarat 
Published: September 2020

Abstract
Background
Shwachman-Diamond syndrome (SDS) is a congenital disease that affects the bone marrow, skeletal system, and pancreas. The majority of patients with SDS have mutations in the SBDS gene, involved in ribosome biogenesis as well as other processes. A Saccharomyces cerevisiae model of SDS, lacking Sdo1p the yeast orthologue of SBDS, was utilized to better understand the molecular pathogenesis in the development of this disease.

Results
Deletion of SDO1 resulted in a three-fold over-accumulation of intracellular iron. Phenotypes associated with impaired iron-sulfur (ISC) assembly, up-regulation of the high affinity iron uptake pathway, and reduced activities of ISC containing enzymes aconitase and succinate dehydrogenase, were observed in sdo1∆ yeast. In cells lacking Sdo1p, elevated levels of reactive oxygen species (ROS) and protein oxidation were reduced with iron chelation, using a cell impermeable iron chelator. In addition, the low activity of manganese superoxide dismutase (Sod2p) seen in sdo1∆ cells was improved with iron chelation, consistent with the presence of reactive iron from the ISC assembly pathway. In yeast lacking Sdo1p, the mitochondrial voltage-dependent anion channel (VDAC) Por1p is over-expressed and its deletion limits iron accumulation and increases activity of aconitase and succinate dehydrogenase.

Conclusions
We propose that oxidative stress from POR1 over-expression, resulting in impaired activity of ISC containing proteins and disruptions in iron homeostasis, may play a role in disease pathogenesis in SDS patients.
Identification of multidimensional Boolean patterns in microbial communities
Authors: Golovko George , Kamil Khanipov , Albayrak Levent , Nia Anna M. , Duarte Renato Salomon Arroyo , Chumakov Sergei , Fofanov Yuriy 
Published: September 2020

Abstract
Background
Identification of complex multidimensional interaction patterns within microbial communities is the key to understand, modulate, and design beneficial microbiomes. Every community has members that fulfill an essential function affecting multiple other community members through secondary metabolism. Since microbial community members are often simultaneously involved in multiple relations, not all interaction patterns for such microorganisms are expected to exhibit a visually uninterrupted pattern. As a result, such relations cannot be detected using traditional correlation, mutual information, principal coordinate analysis, or covariation-based network inference approaches.

Results
We present a novel pattern-specific method to quantify the strength and estimate the statistical significance of two-dimensional co-presence, co-exclusion, and one-way relation patterns between abundance profiles of two organisms as well as extend this approach to allow search and visualize three-, four-, and higher dimensional patterns. The proposed approach has been tested using 2380 microbiome samples from the Human Microbiome Project resulting in body site-specific networks of statistically significant 2D patterns as well as revealed the presence of 3D patterns in the Human Microbiome Project data.

Conclusions
The presented study suggested that search for Boolean patterns in the microbial abundance data needs to be pattern specific. The reported presence of multidimensional patterns (which cannot be reduced to a combination of two-dimensional patterns) suggests that multidimensional (multi-organism) relations may play important roles in the organization of microbial communities, and their detection (and appropriate visualization) may lead to a deeper understanding of the organization and dynamics of microbial communities.
Analysis of ACE2 genetic variants in 131 Italian SARS-CoV-2-positive patients
Authors: Novelli Antonio , Biancolella Michela , Borgiani Paola , Cocciadiferro Dario , Colona Vito Luigi , D’Apice Maria Rosaria , Rogliani Paola , Zaffina Salvatore , Leonardis Francesca , Campana Andrea , Raponi Massimiliano , Andreoni Massimo , Grelli Sandro , Novelli Giuseppe 
Published: September 2020

Abstract
Background
Coronaviruses (CoV) are a large family of viruses that are common in humans and many animal species. Animal coronaviruses rarely infect humans with the exceptions of the Middle East respiratory syndrome (MERS-CoV), the severe acute respiratory syndrome corona virus (SARS-CoV), and now SARS-CoV-2, which is the cause of the ongoing pandemic of coronavirus disease 2019 (COVID-19). Several studies suggested that genetic variants in the ACE2 gene may influence the host susceptibility or resistance to SARS-CoV-2 infection according to the functional role of ACE2 in human pathophysiology. However, many of these studies have been conducted in silico based on epidemiological and population data. We therefore investigated the occurrence of ACE2 variants in a cohort of 131 Italian unrelated individuals clinically diagnosed with COVID-19 and in an Italian control population, to evaluate a possible allelic association with COVID-19, by direct DNA analysis.

Methods
As a pilot study, we analyzed, by whole-exome sequencing, genetic variants of ACE2 gene in 131 DNA samples of COVID-19 patients hospitalized at Tor Vergata University Hospital and at Bambino Gesù Children’s Hospital, Rome. We used a large control group consisting of 1000 individuals (500 males and 500 females).

Results
We identified three different germline variants: one intronic c.439+4G>A and two missense c.1888G>C p.(Asp630His) and c.2158A>G p.(Asn720Asp) in a total of 131 patients with a similar frequency in male and female. Thus far, only the c.1888G>C p.(Asp630His) variant shows a statistically different frequency compared to the ethnically matched populations. Therefore, further studies are needed in larger cohorts, since it was found only in one heterozygous COVID-19 patient.

Conclusions
Our results suggest that there is no strong evidence, in our cohort, of consistent association of ACE2 variants with COVID-19 severity. We might speculate that rare susceptibility/resistant alleles could be located in the non-coding regions of the ACE2 gene, known to play a role in regulation of the gene activity.