bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bleeding and Thrombosis With Pediatric Extracorporeal Life Support: A Roadmap for Management, Research, and the Future From the Pediatric Cardiac Intensive Care Society: Part 2*
Authors: Penk Jamie S. , Reddy Sushma , Polito Angelo , Cisco Michael J. , Allan Catherine K. , Bembea Melania , Giglia Therese M. , Cheng Henry H. , Thiagarajan Ravi R. , Dalton Heidi J. 
Published: September 2019

Objectives:
To make recommendations on improving understanding of bleeding and thrombosis with pediatric extracorporeal life support including future research directions.

Data Sources:
Evaluation of literature and consensus conferences of pediatric critical care and extracorporeal life support experts.

Study Selection:
A team of 10 experts with pediatric cardiac and extracorporeal membrane oxygenation experience and expertise met through the Pediatric Cardiac Intensive Care Society to review current knowledge and make recommendations for future research to establish “best practice” for anticoagulation management related to extracorporeal life support.

Data Extraction/Data Synthesis:
This white paper focuses on clinical understanding and limitations of current strategies to monitor anticoagulation. For each test of anticoagulation, limitations of current knowledge are addressed and future research directions suggested.

Conclusions:
No consensus on best practice for anticoagulation monitoring exists. Structured scientific evaluation to answer questions regarding anticoagulation monitoring and bleeding and thrombotic events should occur in multicenter studies using standardized approaches and well-defined endpoints. Outcomes related to need for component change, blood product administration, healthcare outcome, and economic assessment should be incorporated into studies. All centers should report data on patient receiving extracorporeal life support to a registry.
Relationship Between Shear Wave Elastography Findings and Histologic Prognostic Factors of Invasive Breast Cancer
Authors: Gemici Aysegul Akdogan , Ozal Safiye Tokgoz , Hocaoglu Elif , Inci Ercan 
Published: September 2019

ObjectiveShear wave elastography (SWE) is an adjunct to grayscale ultrasound examinations for evaluating breast masses. This study aimed to determine the SWE features that correlated with prognostic parameters for breast cancer.MethodsBetween January 2018 and May 2018, 80 patients who were confirmed to have invasive cancers by core-needle biopsy and who were scheduled for surgery were imaged using B-mode ultrasound and SWE. Measurements were taken from a region of interest positioned over the stiffest part of the peripheral zone and mass. Three measurements were taken, and the average of the mean stiffness value was used for analysis.ResultsThe mean tumor size, elasticity value of tumors, and elasticity of the peripheral zone were 2.9 ± 1.48 cm (range, 0.6–8 cm), 154.8 ± 8.55 kPa (range, 116.25–179 kPa), and 171.34 ± 5.22 kPa (range, 150.95–182.43 kPa), respectively. The types of breast cancer included were invasive ductal carcinoma (n = 71 [88.75%]; 69 invasive ductal carcinoma not otherwise specified, 1 solid papillary carcinoma, and 1 invasive micropapillary carcinoma), invasive lobular carcinoma (n = 2 [2.5%]), mixed invasive ductal and lobular carcinoma (n = 4 [5%]), mucinous carcinoma (n = 2 [2.5%]), and metaplastic cancer (n = 1 [1.25%]). A strong correlation was found between mean elasticity values and tumor grade (P= 0.018) and between mean elasticity values and lymphovascular invasion (LVI) positivity (P= 0.008). There were no significant differences between SWE values and tumor diameter or between histological tumor characteristics and SWE.ConclusionsWe found that some clinicohistopathologic features of poor prognosis had higher elasticity values than those of favorable prognosis.
Coagulation System Disorders and Thrombosis Prophylaxis During Laparoscopic Fundoplications
Authors: Zostautiene Indre , Skrodeniene Erika , Vitkauskiene Astra , Zviniene Kristina , Mickevicius Antanas , Gerbutavicius Rolandas , Gerbutaviciene Rima , Kiudelis Mindaugas 
Published: September 2019

Background:
The aim of this study was to assess and recommend the optimal deep vein thrombosis (DVT) prophylaxis regimen during and after laparoscopic fundoplication according to the blood coagulation disorders and the rate of DVT in 2 patient groups, receiving different DVT prophylaxis regimens.

Materials and Methods:
This was a prospective randomized, single-center clinical study. The study population, 121 patients, were divided into 2 groups: group I received low–molecular-weight heparin 12 hours before the operation; group II received low–molecular-weight heparin only 1 hour before the laparoscopic fundoplication. Both groups received intermittent pneumatic compression during the entire procedure. Bilateral Doppler ultrasound to exclude DVT was performed before the surgery. Venous phase computed tomographic images were acquired from the ankle to the iliac tubercles on the third postoperative day to determine the presence and location of DVT. Hypercoagulation state was assessed by measuring the prothrombin fragment F1+2 (F1+2), the thrombin-antithrombin complex (TAT), and tissue factor microparticles activity (MP-TF) in plasma. The hypocoagulation effect was evaluated by measuring plasma free tissue factor pathway inhibitor (fTFPI).

Results:
F1+2, TAT, and MP-TF indexes increased significantly, whereas fTFPI levels decreased significantly during and after laparoscopic fundoplication, when molecular-weight heparin was administered 12 hours before the operation. Computed tomography venography revealed peroneal vein thrombosis in 2 group I patients on the third postoperative day. Total postsurgical DVT frequency was 1.65%: 3.6% in group I, with no DVT in group II.

Conclusion:
Molecular-weight heparin and intraoperative intermittent pneumatic compression controls the hypercoagulation effect more efficiently when it is administered 1 hour before surgery: it causes significant reduction of F1+2, TAT, and MP-TF indexes and significant increases of fTFPI levels during and after laparoscopic fundoplication.
Impact of Menopausal Status on Uropathogen Prevalence and Antimicrobial Resistance Profiles
Authors: Venuti Kristen , Cabrera Camila , Burkett Linda S. , Bradley Megan S. 
Published: September 2019

Objectives
The unique factors associated with urinary tract infections (UTIs) in postmenopausal (PMP) women have been significantly less investigated as compared with premenopausal (PreMP) women. Our objective was to compare the prevalence of uropathogens and antibiotic resistance patterns between PreMP and PMP women with UTIs.

Methods
This was a cross-sectional analysis of PreMP and PMP women treated for a UTI in a urogynecologic practice between November 2016 and November 2017. Diagnostic criteria for UTI included lower urinary tract symptoms and a positive urine culture. Our primary outcome was proportion of non–Escherichia coli UTIs between groups.

Results
We had 370 women with mean (SD) age of 66.7 (12.8) years and body mass index of 29.1 (7.1) kg/m2. Most women were PMP (88.6%). Postmenopausal status did not increase the proportion of non–E. coli UTI (42.7% PMP vs 33.3% PreMP, P = 0.25) or decrease the proportion of pansensitive UTI (36.0% PMP vs 42.9% PreMP, P = 0.38).
In multivariable analysis, women with a history of rUTI were at higher odds of having a non–E. coli UTI (adjusted odds ratio, 1.93; 95% confidence interval, 1.21–3.08; P = 0.01) and at lower odds of pansensitive urine culture (adjusted odds ratio, 0.37; 95% confidence interval, 0.22–0.63; P < 0.01) as compared with those without rUTI, when controlling for confounders. Postmenopausal women with a history of rUTI had the highest proportion of non–E. coli UTIs (51.1%, P < 0.01) and lowest proportion of pansensitive uropathogens (29.1%, P < 0.01) as compared with other PMP women and PreMP without a history of rUTI.

Conclusions
In a urogynecologic population, a history of rUTI, more than menopausal status, significantly impacted the prevalence of specific uropathogens and resistant organisms.
Impact of Donor Hepatitis C Virus on Kidney Transplant Outcomes for Hepatitis C-positive Recipients in the Direct-acting Antiviral Era: Time to Revise the Kidney Donor Risk Index?
Authors: Cannon Robert M. , Locke Jayme E. , Orandi Babak J. , Anderson Douglas J. , Davis Eric G. , Mackelaite Lina , Dave Hitarth , Eng Mary , Jones Christopher M. 
Published: September 2019

Background.
Kidneys from donors with hepatitis C virus (HCV) infection are traditionally considered to be at risk for poorer survival outcomes, as reflected in the kidney donor profile index (KDPI). Modern direct-acting antivirals may modify this risk.

Methods.
Using United Network for Organ Sharing data, HCV-infected adult first-time kidney transplant recipients from 2014 to 2017 were examined. Graft and patient survival were compared in a propensity-matched cohort of recipients of HCV antibody (Ab)(+) kidneys versus Ab(-) kidneys. Subsequent analysis was performed in a propensity-matched cohort of recipients of HCV-viremic (RNA positive) versus HCV-naïve kidneys.

Results.
There were 379 recipients each in the matched cohort of recipients of HCV Ab(+) versus HCV Ab(-) kidneys. Despite a higher KDPI (58.2% for HCV Ab[+] versus 38.8% for HCV Ab[-]), 1-year patient and graft survival were similar in the HCV(+) and HCV(-) groups (95.4% and 94.9% versus 97.9% and 96.0%, P = 0.543 and P = 0.834, respectively). There were 200 recipients each in the cohort of recipients of HCV-viremic versus HCV-naïve kidneys, with the KDPI again higher in the HCV-viremic group (56.8% versus 35.2%). Baseline hazard ratios (HRs) for graft failure (HR, 4.69; P = 0.009) and death (HR, 7.60; P = 0.003) were significantly elevated in the viremic group, but crossed 1 at 21 and 24 months, respectively.

Conclusions.
In the modern direct-acting antiviral era, calculated likely KDPI overestimates risk kidneys from HCV (+) donors. Donor viremia conveys an early risk which appears to subside over time. These results suggest that it may be time to revise the kidney donor risk index.
Clinical Relevance of Arteriolar C4d Staining in Patients With Chronic-active Antibody-mediated Rejection: A Pilot Study
Authors: Snijders Malou L.H. , Sablik Kasia A. , van den Bosch Thierry P.P. , Hesselink Dennis A. , Betjes Michiel G.H. , Batal Ibrahim , Clahsen-van Groningen Marian C. 
Published: September 2019

Background.
C4d staining in peritubular capillaries is a well-established feature of antibody-mediated rejection (AMR). The relevance of C4d staining outside peritubular capillaries is not well understood. We investigated the significance of arteriolar C4d staining in chronic-active AMR (c-aAMR).

Methods.
All for-cause renal allograft biopsies performed in 2007–2014 at the Erasmus MC and meeting the criteria for suspicious/diagnostic c-aAMR using the Banff Classification 2015 were included. For comparison, renal allograft biopsies from a matched control group and native renal biopsies were analyzed. Arteriolar C4d staining was semiquantitatively scored as negative (0), small deposits in 1 arteriole (1+), small/large deposits in >1 arterioles (2+), or at least extensive deposits in most arterioles (3+).

Results.
Thirty-four of 40 (85%) patients with c-aAMR showed arteriolar C4d staining. A significant difference in arteriolar C4d score was observed between cases and matched controls (P = 0.01) and a trend toward significance difference between cases and native renal biopsies (P = 0.05). In the cases, arteriolar C4d staining was significantly associated with severity of arteriolar hyalinosis (P = 0.004) and ≥2 arteriolar C4d staining was independently associated with better graft outcome in a multivariate Cox regression analysis (hazard ratio, 0.260; 95% CI, 0.104-0.650; P = 0.004).

Conclusions.
This pilot study shows that arteriolar C4d staining is more common in biopsies with c-aAMR compared with those without and that it is associated with arteriolar hyalinosis and ≥2 arteriolar C4d staining is associated with superior graft outcome. However, larger studies are needed to examine these findings in more detail to asses if arteriolar C4d staining is truly related to antibody-mediated injury.
Relationship Between mTOR Signaling Activation and Postoperative Neurocognitive Disorder in Aged Rats
Authors: Wang Bin , Dong Rui , Lin Xu , Sun Xiaopeng , Chen Huailong , Zhou Jiahui , Li Xiaoxiao , Wang Mingshan , Bi Yanlin 
Published: September 2019

Background:
Although incidence rates of postoperative neurocognitive disorder (PND) in aged individuals following noncardiac major surgery are rising as individuals are living longer, the mechanism of PND remains poorly understood. We wondered if mammalian target of rapamycin (mTOR) signaling might be associated with PND since mTOR controls some essential intracellular events.

Objective:
To investigate whether surgery activates the mTOR signaling pathway in aged rats, leading to PND, and whether the mTOR inhibitor, rapamycin, can be used to alleviate PND.

Methods:
We randomly assigned aged rats to four groups: normal control (C), isoflurane (I), surgery (S), and rapamycin (R). Then, we anesthetized Groups I, S, and R, following which, Groups S and R underwent a splenectomy. After surgery, Group R was administered rapamycin. We used the Morris water maze to test the rats’ spatial learning and memory after surgery.

Results:
In Group S, escape latency (ie, the time to find the platform) was markedly higher, and the ratio of swimming time in the target quadrant was lower, compared to the other groups. In Group R, escape latency was markedly lower as compared with Group S, and the ratio of swimming time in the target quadrant was higher.

Conclusions:
Our results indicate that an altered mTOR signaling pathway after a splenectomy causes PND in aged rats, which can be alleviated by rapamycin.
Alcohol use and cognitive functioning in young adults: improving causal inference
Authors: Mahedy Liam , Suddell Steph , Skirrow Caroline , Fernandes Gwen S. , Field Matt , Heron Jon , Hickman Matthew , Wootton Robyn , Munafò Marcus R. 
Published: September 2019

AbstractBackground and AimsThere have been few longitudinal studies of association between alcohol use and cognitive functioning in young people. We aimed to examine whether alcohol use is a causal risk factor for deficient cognitive functioning in young adults.DesignLinear regression was used to examine the relationship between longitudinal latent class patterns of binge drinking and subsequent cognitive functioning. Two-sample Mendelian randomisation (MR) tested evidence for the causal relationship between alcohol use and cognitive functioning.SettingSouth West England.ParticipantsThe observational study included 3,155 adolescents and their parents (fully adjusted models) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Genetic instruments for alcohol use were based on almost 1,000,000 individuals from the GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN). Genome-wide association studies for cognitive outcomes were based on 2,500 individuals from ALSPAC.MeasurementsBinge drinking was assessed at approximately 16, 17, 18, 21, and 23 years. Cognitive functioning comprised working memory, response inhibition, and emotion recognition assessed at 24 years of age. Ninety-nine independent genome-wide significant SNPs associated with ‘number of drinks per week’ were used as the genetic instrument for alcohol consumption. Potential confounders were included in the observational analyses.FindingsFour binge drinking classes were identified: ‘low-risk’ (41%), ‘early-onset monthly’ (19%), ‘adult frequent’ (23%), and ‘early-onset frequent’ (17%). The association between early-onset frequent binge drinking and cognitive functioning: working memory (b=0.09, 95%CI=-0.10 to 0.28), response inhibition (b=0.70, 95%CI=-10.55 to 11.95), and emotion recognition (b=0.01, 95%CI=-0.01 to 0.02) in comparison to low-risk drinkers were inconclusive as to whether a difference was present. Two-sample MR analyses similarly provided little evidence that alcohol use is associated with deficits in working memory using the inverse variance weight (b=0.29, 95%CI=-0.42 to 0.99), response inhibition (b=-0.32, 95%CI=-1.04 to 0.39), and emotion recognition (b=0.03, 95%CI=-0.55 to 0.61).ConclusionsBinge drinking in adolescence and early adulthood may not be causally related to deficiencies in working memory, response inhibition, or emotion recognition in youths.
Inferring the role of the microbiome on survival in patients treated with immune checkpoint inhibitors: causal modeling, timing, and classes of concomitant medications
Authors: Spakowicz Daniel , Hoyd Rebecca , Muniak Mitchell , Husain Marium , Bassett James S. , Wang Lei , Tinoco Gabriel , Patel Sandip H. , Burkart Jarred , Miah Abdul , Li Mingjia , Johns Andrew , Grogan Madison , Carbone David P. , Verschraegen Claire F. , Kendra Kari L. , Otterson Gregory A. , Li Lang , Presley Carolyn J. , Owen Dwight H. 
Published: September 2019

ABSTRACTThe microbiome has been shown to affect the response to Immune Checkpoint Inhibitors (ICIs) in a small number of cancers. Here, we sought to more broadly survey cancers to identify those in which the microbiome will play a role using retrospective analyses. We created a causal model for the relationship between medications, the microbiome and ICI response and used it to guide the abstraction of electronic health records of 690 patients who received ICI therapy for advanced cancer. Medications associated with changes to the microbiome including antibiotics, corticosteroids, proton pump inhibitors, histamine receptor blockers, non-steroid anti-inflammatories and statins were abstracted. We tested the effect of medication timing on overall survival (OS) and evaluated the robustness of medication effects in each cancer. Finally, we compared the size of the effect observed for antibiotics classes to taxa correlated with ICI response and a literature review of culture-based antibiotic susceptibilities. Of the medications assessed, only antibiotics and corticosteroids significantly associated with lower OS. The hazard ratios (HRs) for antibiotics and corticosteroids were highest near the start of ICI treatment but remained significant when given prior to ICI. Antibiotics and corticosteroids remained significantly associated with OS even when controlling for multiple factors such as Eastern Cooperative Oncology Group performance status, Charlson Comorbidity Index score, and stage. When grouping antibiotics by class, β-lactams showed the strongest association with OS across all tested cancers. The timing and strength of these effects after controlling for confounding factors are consistent with role for the microbiome in response to ICIs.
Multifocal breast cancers are more prevalent inBRCA2versusBRCA1mutation carriers
Authors: McCrorie Alan D , Ashfield Susannah , Begley Aislinn , Mcilmunn Colin , Morrison Patrick J. , Boyd Clinton , Eccles Bryony , Greville-Heygate Stephanie , Copson Ellen R , Cutress Ramsey I. , Eccles Diana M , Savage Kienan I. , McIntosh Stuart A 
Published: September 2019

AbstractMultifocal/multicentric breast cancer is generally considered to be where two or more breast tumours are present within the same breast, and is seen in ∼10% of breast cancer cases. This study investigates the prevalence of multifocality/multicentricity in a cohort ofBRCA1/2mutation carriers with breast cancer from Northern Ireland via cross-sectional analysis. Data from 211 women withBRCA1/2mutations (BRCA1- 91), (BRCA2- 120), with breast cancer were collected including age, tumour focality, size, type, grade, and receptor profile. The prevalence of multifocality/multicentricity within this group was 25%, but within subgroups, prevalence amongstBRCA2carriers was more than double that ofBRCA1carriers (p=0.001). Women affected by multifocal/multicentric tumours had proportionately higher oestrogen receptor positivity (p=0.001) and lower triple negativity (p=0.004). These observations are likely to be driven by the higher BRCA2 mutation prevalence observed within this cohort. Odds of aBRCA2carrier developing multifocal/multicentric cancer were almost four-fold higher than aBRCA1carrier (OR: 3.71, CI: 1.77-7.78, p=0.001). These findings were subsequently validated in a second, large independent cohort of patients withBRCA-associated breast cancers from a UK-wide multicentre study. This confirmed a significantly higher prevalence of multifocal/multicentric tumours amongstBRCA2mutation carriers compared withBRCA1mutation carriers. This has important implications for clinicians involved in the treatment of BRCA2-associated breast cancer, both in the diagnostic process, in ensuring that tumour focality is adequately assessed to facilitate treatment decision-making, and for breast surgeons, particularly if breast conserving surgery is being considered as a treatment option for these patients.
Village-scale persistence and elimination of gambiense human African trypanosomiasis
Authors: Davis Christopher N. , Rock Kat S. , Miaka Erick Mwamba , Keeling Matt J. 
Published: September 2019

AbstractGambiense human African trypanosomiasis (gHAT) is one of several neglected tropical diseases that is targeted for elimination by the World Health Organization. Recent years have seen a substantial decline in the number of globally reported cases, largely driven by an intensive process of screening and treatment. However, this infection is highly focal, continuing to persist at low prevalence even in small populations. Regional elimination, and ultimately global eradication, rests on understanding the dynamics and persistence of this infection at the local population scale. Here we develop a stochastic model of gHAT dynamics, which is underpinned by screening and reporting data from one of the highest gHAT incidence regions, Kwilu Province, in the Democratic Republic of Congo. We use this model to explore the persistence of gHAT in villages of different population sizes and subject to different patterns of screening. Our models demonstrate that infection is expected to persist for long periods even in relatively small isolated populations. We further use the model to assess the risk of recrudescence following local elimination and consider how failing to detect cases during active screening events informs the probability of elimination. These quantitative results provide insights for public health policy in the region, particularly highlighting the difficulties in achieving and measuring the 2030 elimination goal.Author summaryGambiense human African trypanosomiasis (gHAT) is a vector-borne infectious disease that causes sleeping sickness across many African countries. Reported gHAT cases show a continued decline, but it is unclear if this is sufficient to reach the WHO goal of stopping transmission by 2030. We develop a stochastic model necessary to address the critical question of persistence of gHAT infection at the local-scale. In contrast to other commonly studied infections, we predict long-term persistence of gHAT in small populations (< 1, 000 people) despite very low prevalence. Our local-scale predictions (together with previous larger-scale studies) suggest that, to achieve regional elimination, controls need to be widespread and intensified in the worst affected regions, while the movement of infected people could rapidly lead to re-emergence.