bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sulfonated non‐saccharide molecules and human factor XIa: Enzyme inhibition and computational studies
Authors: Al‐Horani Rami A. , Parsaeian Elnaz , Mohammad Mariam , Mottamal Madhusoodanan 
Published: April 2022

AbstractHuman factor XIa (FXIa) is a serine protease in the intrinsic coagulation pathway. FXIa has been actively targeted to develop new anticoagulants that are associated with a reduced risk of bleeding. Thousands of FXIa inhibitors have been reported, yet none has reached the clinic thus far. We describe here a novel class of sulfonated molecules that allosterically inhibit FXIa with moderate potency. A library of 18 sulfonated molecules was evaluated for the inhibition of FXIa using a chromogenic substrate hydrolysis assay. Only six molecules inhibited FXIa with IC50 values of 4.6–29.5 μM. Michaelis–Menten kinetics indicated that sulfonated molecules are allosteric inhibitors of FXIa. Inhibition of FXIa by these molecules was reversed by protamine. The molecules also showed moderate anticoagulant effects in human plasma with preference to prolong activated partial thromboplastin time. Their binding to an allosteric site in the catalytic domain of FXIa was modeled to illustrate potential binding mode and potential important Arg/Lys residues. Particularly, inhibitor 16 (IC50 = 4.6 µM) demonstrated good selectivity over a panel of serine proteases including those in the coagulation process. Inhibitor 16 did not significantly compromise the viability of three cell lines. Overall, the reported sulfonated molecules serve as a new platform to design selective, potent, and allosteric inhibitors of FXIa for therapeutic applications.
Inequalities in the distribution of COVID‐19‐related financial difficulties for Australian families with young children
Authors: O'Connor Meredith , Greenwood Christopher J. , Letcher Primrose , Giallo Rebecca , Priest Naomi , Goldfeld Sharon , Hope Steven , Edwards Ben , Olsson Craig A. 
Published: April 2022

AbstractBackgroundWe examine (1) the frequency of financial difficulties in Australian families with young children (0–8 years) in the early and later phases of the pandemic; (2) the extent to which parents' pre‐pandemic socio‐economic disadvantage (SED) predicted financial difficulties; and (3) whether grandparent intergenerational SED further amplified this risk.MethodData: Australian Temperament Project (ATP; established 1983, N = 2443) and ATP Generation 3 study (ATPG3; established 2012; N = 702), of which 74% (N = 553) completed a COVID‐specific module in the early (May–September 2020) and/or later (October–December 2021) phases of the pandemic. Outcomes: Parent‐reported loss of employment/reduced income, difficulty paying for essentials, and financial strain. Exposures: Pre‐pandemic parent and grandparent education and occupation. Analysis: Logistic regressions, estimated via generalized estimating equations, were used to examine associations between the pre‐pandemic SED of parents and grandparents and their interaction with financial difficulties, adjusting for potential confounders.ResultsAt both pandemic time points, a third of parents reported adverse financial impacts (early: 34%, 95% confidence interval [CI] = 30–38; later: 32%, 95% CI = 28–36). Each standard deviation increase in the parents' pre‐pandemic SED was associated with a 36% increase in the odds of reporting multiple financial difficulties (odds ratio [OR] = 1.36, 95% CI = 1.04–1.78). There was little evidence of an interaction between the SED of parents and grandparents.ConclusionsFinancial impacts related to the COVID‐19 pandemic were common and, irrespective of grandparent SED, disproportionately borne by parents with higher pre‐pandemic SED. Given the well‐established relationship between disadvantage and child health and development, sustained and well‐targeted government supports will be critical to minimizing adverse impacts in years to come.
Does reproductive stage impact cardiovascular disease risk factors? Results from a population‐based cohort in Lausanne (CoLaus study)
Authors: Raguindin Peter Francis , Cardona Isabel , Muka Taulant , Lambrinoudaki Irene , Gebhard Catherine , Franco Oscar H. , Marques‐Vidal Pedro , Glisic Marija 
Published: April 2022

AbstractContextMenopause has been associated with adverse cardiovascular disease (CVD) risk profile, yet it is unclear whether the changes in CVD risk factors differ by reproductive stage independently of underlying ageing trajectories.DesignThe CoLaus study is a prospective population‐based cohort study in Lausanne, Switzerland.PatientsWe used data from women at baseline and follow‐up (mean: 5.6 ± 0.5 years) from 2003 to 2012 who did not use hormone therapy. We classified women into (i) premenopausal, (ii) menopausal transition, (iii) early (≤5 years) and (iv) late (>5 years) postmenopausal by comparing their menstruation status at baseline and follow‐up.MeasurementsWe measured fasting lipids, glucose and cardiovascular inflammatory markers. We used repeated measures (linear mixed models) for longitudinal analysis, using premenopausal women as a reference category. We adjusted analyses for age, medications and lifestyle factors.ResultsWe used the data from 1710 women aged 35–75 years. Longitudinal analysis showed that the changes in CVD risk factors were not different in the other three menopausal categories compared to premenopausal women. When age was used as a predictor variable and adjusted for menopause status, most CVD risk factors increased, while interleukin‐6 and interleukin‐1β decreased with advancing age.ConclusionThe current study suggests that women have a worsening cardiovascular risk profile as they age, and although menopausal women may have higher levels of cardiovascular risk factors compared to premenopausal women at any given time, the 5‐year changes in cardiovascular risk factors may not depend on the reproductive stage.
Robotic beyond total mesorectal excision surgery for primary and recurrent pelvic malignancy: Feasibility and short‐term outcomes
Authors: Larach José Tomás , Flynn Julie , Fernando Diharah , Mohan Helen , Rajkomar Amrish , Waters Peadar S. , Kong Joseph , McCormick Jacob J. , Heriot Alexander G. , Warrier Satish K. 
Published: April 2022

AbstractAimTo explore the feasibility and safety of robotic beyond total mesorectal excision (TME) surgery for primary and recurrent pelvic malignancy.MethodsPatients undergoing robotic beyond TME resections for primary or recurrent pelvic malignancy between July 2015 and July 2021 in a public quaternary and a private tertiary centre were included. Demographic and clinical data were recorded and outcomes analysed.ResultsTwenty‐four patients (50% males) were included, with a median age of 58 (45–70.8) years, and a BMI of 26 (24.3–28.1) kg/m2. Indication for surgery was rectal adenocarcinoma in nineteen, leiomyosarcoma in two, anal squamous cell carcinoma in one and combined rectal and prostatic adenocarcinoma in two patients. All patients required resection of at least one adjacent pelvic organ including genitourinary structures (n = 23), internal iliac vessels (n = 3) and/or bone (n = 2). Eleven patients had a restorative procedure. Of the 13 nonrestorative cases, nine needed perineal reconstruction with a flap. There was one conversion due to bleeding. The mean operating time was 370 (285–424) min, and the median blood loss was 400 (200–2,000) ml. The median length of stay was 16 (9.3–23.8) days. Fourteen patients (58.3%) had postoperative complications; eight of them (33.3%) were Clavien‐Dindo III or more complication. Twenty‐three (95.8%) patients had an R0 resection. During a median follow‐up of 10 (7–23.5) months, five patients (20.8%) had systemic recurrences. No local recurrences were identified during the study period.ConclusionImplementation of robotic beyond TME surgery for primary and recurrent pelvic malignancy is feasible within a highly specialised setting.
Cross‐Situational Word Learning With Multimodal Neural Networks
Authors: Vong Wai Keen , Lake Brenden M. 
Published: April 2022

AbstractIn order to learn the mappings from words to referents, children must integrate co‐occurrence information across individually ambiguous pairs of scenes and utterances, a challenge known as cross‐situational word learning. In machine learning, recent multimodal neural networks have been shown to learn meaningful visual‐linguistic mappings from cross‐situational data, as needed to solve problems such as image captioning and visual question answering. These networks are potentially appealing as cognitive models because they can learn from raw visual and linguistic stimuli, something previous cognitive models have not addressed. In this paper, we examine whether recent machine learning approaches can help explain various behavioral phenomena from the psychological literature on cross‐situational word learning. We consider two variants of a multimodal neural network architecture and look at seven different phenomena associated with cross‐situational word learning and word learning more generally. Our results show that these networks can learn word‐referent mappings from a single epoch of training, mimicking the amount of training commonly found in cross‐situational word learning experiments. Additionally, these networks capture some, but not all of the phenomena we studied, with all of the failures related to reasoning via mutual exclusivity. These results provide insight into the kinds of phenomena that arise naturally from relatively generic neural network learning algorithms, and which word learning phenomena require additional inductive biases.
Malware classification using a byte‐granularity feature based on structural entropy
Authors: Paik Joon‐Young , Jin Rize , Cho Eun‐Sun 
Published: April 2022

AbstractRapidly evolving malware has become a major cybersecurity threat. Several feature‐engineering techniques have been proposed to defend against malware attacks. An entropy is a typical indicator used in identifying malware. Structural entropy is a sequence of entropy values where an entropy of a segment is calculated by the equation of the entropy itself. However, entropy‐based features are likely to be abstract and miss important information. This article proposes a feature engineering technique that involves the concept of structural entropy. This technique allows every segment to be represented as 256 entropy values for every byte value, but not as an entropy value. Our research, fine‐granularity structural entropy (FiG_SE), incorporates global patterns across all segments, local patterns across adjacent segments, and internal patterns within the segments. To extract higher‐level characteristics from our entropy feature, we use a convolutional neural network (CNN) architecture because it is effective for extracting local and global patterns, and especially for shift‐invariant patterns. Our malware classification based on CNN with the proposed feature outperforms the previous classification methods that use byte streams, entropy streams, and structural‐entropy‐based streams as inputs. Moreover, our research combined with CNN is highly resilient to obfuscation techniques and is also well suited to malware detection.
Early and ongoing stable glycaemic control is associated with a reduction in major adverse cardiovascular events in people with type 2 diabetes: A primary care cohort study
Authors: Whyte Martin B. , Joy Mark , Hinton William , McGovern Andrew , Hoang Uy , van Vlymen Jeremy , Ferreira Filipa , Mount Julie , Munro Neil , de Lusignan Simon 
Published: April 2022

AbstractAimTo determine whether achieving early glycaemic control, and any subsequent glycaemic variability, was associated with any change in the risk of major adverse cardiovascular events (MACE).Materials and MethodsA retrospective cohort analysis from the Oxford‐Royal College of General Practitioners Research and Surveillance Centre database—a large, English primary care network—was conducted. We followed newly diagnosed patients with type 2 diabetes, on or after 1 January 2005, aged 25 years or older at diagnosis, with HbA1c measurements at both diagnosis and after 1 year, plus five or more measurements of HbA1c thereafter. Three glycaemic bands were created: groups A (HbA1c < 58 mmol/mol [<7.5%]), B (HbA1c ≥ 58 to 75 mmol/mol [7.5%‐9.0%]) and C (HbA1c ≥ 75 mmol/mol [≥9.0%]). Movement between bands was determined from diagnosis to 1 year. Additionally, for data after the first 12 months, a glycaemic variability score was calculated from the number of successive HbA1c readings differing by 0.5% or higher (≥5.5 mmol/mol). Risk of MACE from 1 year postdiagnosis was assessed using time‐varying Cox proportional hazards models, which included the first‐year transition and the glycaemic variability score.ResultsFrom 26 180 patients, there were 2300 MACE. Compared with group A‐>A transition over 1 year, those with C‐>A transition had a reduced risk of MACE (HR 0.75; 95% CI 0.60‐0.94; P = .014), whereas group C‐>C had HR 1.21 (0.81‐1.81; P = .34). Compared with the lowest glycaemic variability score, the greatest variability increased the risk of MACE (HR 1.51; 1.11‐2.06; P = .0096).ConclusionEarly control of HbA1c improved cardiovascular outcomes in type 2 diabetes, although subsequent glycaemic variability had a negative effect on an individual's risk.
Effect of glucagon‐like peptide‐1 receptor agonists on cardiovascular events in overweight or obese adults without diabetes: A meta‐analysis of placebo‐controlled randomized trials
Authors: Leite Ana Rita , Angélico‐Gonçalves António , Vasques‐Nóvoa Francisco , Borges‐Canha Marta , Leite‐Moreira Adelino , Neves João Sérgio , Ferreira João Pedro 
Published: April 2022

AbstractOur aim was to study the effect of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) on the risk of any cardiovascular event in adults with overweight or obesity and without diabetes. We conducted a random‐effects meta‐analysis of placebo‐controlled randomized controlled trials. Nine trials were eligible and, in total, 11 430 patients were included, of which 7702 (67%) were submitted to treatment with GLP‐1 RA. During follow‐up, 673 participants receiving GLP‐1 RA treatment (8.7%) and 416 participants receiving placebo (11.2%) had a cardiovascular event. Treatment with GLP‐1 RA versus placebo resulted in a reduction in the risk of any cardiovascular event (RR = 0.81, CI 0.70‐0.92; p = .001). In overweight or obese adults without diabetes, treatment with GLP‐1 RA reduced the risk of cardiovascular events. Our findings support the use of GLP‐1 RA for reducing the cardiovascular risk of these patients.
Chronic eosinophilic granulomatous tenosynovitis in a Quarter Horse mare
Authors: Williams Zoë J. , McIlmurray John , Nickels Frank 
Published: April 2022

SummaryA 5‐year‐old Quarter Horse mare was presented to the Michigan State University Equine Surgery Service for evaluation of a right hind metatarsophalangeal joint injury. On presentation, the horse was a grade 4/5 lame. Radiographs and ultrasonography showed peritendinous ossification/mineralisation of soft tissue structures and digital flexor tenosynovitis with profound intracapsular mineralisation. A digital flexor tendon sheath tenoscopy was performed with a plantar annular ligament desmotomy and a manica flexoria ligament tenotomy. During surgery, a significant amount of tan granular material was found within the digital tendon sheath. Approximately 80% of this material was removed, and a sample was sent for histopathology. The horse was diagnosed with eosinophilic granulomatous tenosynovitis. Long‐term follow‐up revealed improvement with four treatments of intralesional triamcinolone given 2–4 weeks apart. The horse became serviceably sound (grade 1/5) and was beginning light work under the saddle approximately 5 months post‐tenoscopy.
Effects of aging state on fatigue properties of 6A01 aluminum alloy
Authors: Gong Baishan , Zhang Zhenjun , Duan Qiqiang , Qu Zhan , Hou Jiapeng , Zhang Zhefeng 
Published: April 2022

AbstractThe high‐cycle fatigue (HCF) experiments were carried out for different aging states to study the effects of the aging state and yield strength on the fatigue properties of a 6A01 Al alloy. The results show that the 6A01 Al alloy with the highest yield strength at a peak‐aging (PA) state can exhibit the highest fatigue strength in comparison with the overaged (OA) state and the underaged (UA) state. The main reason is that the increased strength of the 6A01 Al alloy at the PA state can improve the plastic deformation resistance and inhibit the fatigue crack initiation. Additionally, the UA has a similar yield strength but a higher fatigue strength compared with the OA, which shows that the aging state also has a significant influence on the fatigue properties. Finally, combined with the previous studies on the 2XXX and 7XXX Al alloys, the effects of the aging state and yield strength on the fatigue properties of Al alloys are summarized.
Identifying main uncertainties in estimating past and present radiative forcing of peatlands
Authors: Mathijssen Paul J. H. , Tuovinen Juha‐Pekka , Lohila Annalea , Väliranta Minna , Tuittila Eeva‐Stiina 
Published: April 2022

AbstractReconstructions of past climate impact, that is, radiative forcing (RF), of peatland carbon (C) dynamics show that immediately after peatland initiation the climate warming effect of CH4 emissions exceeds the cooling effect of CO2 uptake, but thereafter the net effect of most peatlands will move toward cooling, when RF switches from positive to negative. Reconstructing peatland C dynamics necessarily involves uncertainties related to basic assumptions on past CO2 flux, CH4 emission and peatland expansion. We investigated the effect of these uncertainties on the RF of three peatlands, using either apparent C accumulation rates, net C balance (NCB) or NCB plus C loss during fires as basis for CO2 uptake estimate; applying a plausible range for CH4 emission; and assuming linearly interpolated expansion between basal dates or comparatively early or late expansion. When we factored that some C would only be stored temporarily (NCB and NCB+fire), the estimated past cooling effect of CO2 uptake increased, but the present‐day RF was affected little. Altering the assumptions behind the reconstructed CO2 flux or expansion patterns caused the RF to peak earlier and advanced the switch from positive to negative RF by several thousand years. Compared with NCB, including fires had only small additional effect on RF lasting less than 1000 year. The largest uncertainty in reconstructing peatland RF was associated with CH4 emissions. As shown by the consistently positive RF modelled for one site, and in some cases for the other two, peatlands with high CH4 emissions and low C accumulation rates may have remained climate warming agents since their initiation. Although uncertainties in present‐day RF were mainly due to the assumed CH4 emission rates, the uncertainty in lateral expansion still had a significant effect on the present‐day RF, highlighting the importance to consider uncertainties in the past peatland C balance in RF reconstructions.
Sarcopenia is as common in older patients with dementia with Lewy bodies as it is in those with Alzheimer's disease
Authors: Dost Fatma Sena , Ates Bulut Esra , Dokuzlar Ozge , Kaya Derya , Mutlay Feyza , Yesil Gurel Besra Hazal , Isik Ahmet Turan 
Published: April 2022

AimAlzheimer's disease (AD) and dementia with Lewy body (DLB) constitute the most common types of dementia, and are two common geriatric syndromes; however, sarcopenia has not been elaborately evaluated in DLB so far. Therefore, this study aimed to investigate the relationship between sarcopenia and DLB in older adults.MethodsIn this retrospective and cross‐sectional study, 662 participants, who were followed in a memory clinic at the Geriatrics department of a university hospital, were included. Comprehensive Geriatric Assessment, including the activities of daily living, malnutrition and malnutrition risk, frailty, cognition, and sarcopenia were assessed. Sarcopenia was defined according to the revised European Working Group on Sarcopenia in Older People‐2 criteria.ResultsA total of 662 participants (461 healthy controls, 133 with AD and 68 with DLB) with a mean age of 73.60 ± 7.50 years were included. The prevalence of probable sarcopenia and sarcopenia was 53.4% and 19.5%, respectively, in patients with AD, whereas it was 55.9% and 19.1%, respectively, in patients with DLB. After adjustment analyses, probable sarcopenia, sarcopenia and low muscle mass were related to AD (P < 0.001, P = 0.001, P < 0.001, respectively). Probable sarcopenia and slow gait speed were associated with DLB (P < 0.01, P < 0.001, respectively).ConclusionsSarcopenia is common in patients with DLB and in those with AD, and seems to be closely related to low muscle strength and slow gait speed in DLB patients. Considering sarcopenia‐related negative health outcomes in older adults, the evaluation of sarcopenia, therefore, should also be among the follow‐up and treatment goals of DLB patients. Geriatr Gerontol Int 2022; 22: 418–424.
The future of artificial intelligence in digital pathology – results of a survey across stakeholder groups
Authors: Heinz Céline N , Echle Amelie , Foersch Sebastian , Bychkov Andrey , Kather Jakob Nikolas 
Published: April 2022

AimsArtificial intelligence (AI) provides a powerful tool to extract information from digitised histopathology whole slide images. During the last 5 years, academic and commercial actors have developed new technical solutions for a diverse set of tasks, including tissue segmentation, cell detection, mutation prediction, prognostication and prediction of treatment response. In the light of limited overall resources, it is presently unclear for researchers, practitioners and policymakers which of these topics are stable enough for clinical use in the near future and which topics are still experimental, but worth investing time and effort into.Methods and resultsTo identify potentially promising applications of AI in pathology, we performed an anonymous online survey of 75 computational pathology domain experts from academia and industry. Participants enrolled in 2021 were queried about their subjective opinion on promising and appealing subfields of computational pathology with a focus upon solid tumours. The results of this survey indicate that the prediction of treatment response directly from routine pathology slides is regarded as the most promising future application. This item was ranked highest in the overall analysis and in subgroups by age and professional background. Furthermore, prediction of genetic alterations, gene expression and survival directly from routine pathology images scored consistently high throughout subgroups.ConclusionsTogether, these data demonstrate a possible direction for the development of computational pathology systems in clinical, academic and industrial research in the near future.