bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of reductions in amyloid levels on cognitive change in randomized trials: instrumental variable meta-analysis
Authors: Ackley Sarah F , Zimmerman Scott C , Brenowitz Willa D , Tchetgen Tchetgen Eric J , Gold Audra L , Manly Jennifer J , Mayeda Elizabeth Rose , Filshtein Teresa J , Power Melinda C , Elahi Fanny M , Brickman Adam M , Glymour M Maria 
Published: February 2021

Abstract

Objective
To evaluate trials of drugs that target amyloid to determine whether reductions in amyloid levels are likely to improve cognition.

Design
Instrumental variable meta-analysis.

Setting
14 randomized controlled trials of drugs for the prevention or treatment of Alzheimer’s disease that targeted an amyloid mechanism, identified from ClinicalTrials.gov.

Population
Adults enrolled in randomized controlled trials of amyloid targeting drugs. Inclusion criteria for trials vary, but typically include adults aged 50 years or older with a diagnosis of mild cognitive impairment or Alzheimer’s disease, and amyloid positivity at baseline.

Main outcome measures
Analyses included trials for which information could be obtained on both change in brain amyloid levels measured with amyloid positron emission tomography and change in at least one cognitive test score reported for each randomization arm.

Results
Pooled results from the 14 randomized controlled trials were more precise than estimates from any single trial. The pooled estimate for the effect of reducing amyloid levels by 0.1 standardized uptake value ratio units was an improvement in the mini-mental state examination score of 0.03 (95% confidence interval −0.06 to 0.1) points. This study provides a web application that allows for the re-estimation of the results when new data become available and illustrates the magnitude of the new evidence that would be necessary to achieve a pooled estimate supporting the benefit of reducing amyloid levels.

Conclusions
Pooled evidence from available trials reporting both reduction in amyloid levels and change in cognition suggests that amyloid reduction strategies do not substantially improve cognition.
Geographical and temporal variation in reduction of malaria infection among children under 5 years of age throughout Nigeria
Authors: Oyibo Wellington , Ntadom Godwin , Uhomoibhi Perpetua , Oresanya Olusola , Ogbulafor Nnenna , Ajumobi Olufemi , Okoh Festus , Maxwell Kolawole , Ezeiru Sonachi , Nwokolo Ernest , Amajoh Chioma , Ezeigwe Nnenna , Audu Mohammed , Conway David 
Published: February 2021

IntroductionGlobal progress in reducing malaria has stalled since 2015. Analysis of the situation is particularly needed in Nigeria, the country with by far the largest share of the burden, where approximately a quarter of all cases in the world are estimated to occur.MethodsWe analysed data from three nationwide surveys (Malaria Indicator Surveys in 2010 and 2015 and a National Demographic and Health Survey in 2018), with malaria parasite prevalence in children under 5 years of age determined by sampling from all 36 states of Nigeria, and blood slide microscopy performed in the same accredited laboratory for all samples. Changes over time were evaluated by calculating prevalence ratio (PR) values with 95% CIs for each state, together with Mantel-Haenszel-adjusted PRs (PRadj) for each of the six major geopolitical zones of the country.ResultsBetween 2010 and 2018, there were significant reductions in parasite prevalence in 25 states, but not in the remaining 11 states. Prevalence decreased most in southern zones of the country (South West PRadj=0.53; South East PRadj=0.59; South South PRadj=0.51) and the North Central zone (PRadj=0.36). Changes in the north were less marked, but were significant and indicated overall reductions by more than 20% (North-West PRadj=0.74; North East PRadj=0.70). Changes in the south occurred mostly between 2010 and 2015, whereas those in the north were more gradual and most continued after 2015. Recent changes were not correlated with survey-reported variation in use of preventive measures.ConclusionReductions in malaria infection in children under 5 have occurred in most individual states in Nigeria since 2010, but substantial geographical variation in the timing and extent indicate challenges to be overcome to enable global malaria reduction.
Hepatobiliary phenotypes of adults with alpha-1 antitrypsin deficiency
Authors: Fromme Malin , Schneider Carolin V , Pereira Vitor , Hamesch Karim , Pons Monica , Reichert Matthias C , Benini Federica , Ellis Paul , H Thorhauge Katrine , Mandorfer Mattias , Burbaum Barbara , Woditsch Vivien , Chorostowska-Wynimko Joanna , Verbeek Jef , Nevens Frederik , Genesca Joan , Miravitlles Marc , Nuñez Alexa , Schaefer Benedikt , Zoller Heinz , Janciauskiene Sabina , Abreu Nélia , Jasmins Luís , Gaspar Rui , Liberal Rodrigo , Macedo Guilherme , Mahadeva Ravi , Gomes Catarina , Schneider Kai Markus , Trauner Michael , Krag Aleksander , Gooptu Bibek , Thorburn Douglas , Marshall Aileen , Hurst John R , Lomas David A , Lammert Frank , Gaisa Nadine T , Clark Virginia , Griffiths William , Trautwein Christian , Turner Alice M , McElvaney Noel G , Strnad Pavel 
Published: February 2021

ObjectiveAlpha-1 antitrypsin deficiency (AATD) is a common, potentially lethal inborn disorder caused by mutations in alpha-1 antitrypsin (AAT). Homozygosity for the ‘Pi*Z’ variant of AAT (Pi*ZZ genotype) causes lung and liver disease, whereas heterozygous ‘Pi*Z’ carriage (Pi*MZ genotype) predisposes to gallstones and liver fibrosis. The clinical significance of the more common ‘Pi*S’ variant remains largely undefined and no robust data exist on the prevalence of liver tumours in AATD.DesignBaseline phenotypes of AATD individuals and non-carriers were analysed in 482 380 participants in the UK Biobank. 1104 participants of a multinational cohort (586 Pi*ZZ, 239 Pi*SZ, 279 non-carriers) underwent a comprehensive clinical assessment. Associations were adjusted for age, sex, body mass index, diabetes and alcohol consumption.ResultsAmong UK Biobank participants, Pi*ZZ individuals displayed the highest liver enzyme values, the highest occurrence of liver fibrosis/cirrhosis (adjusted OR (aOR)=21.7 (8.8–53.7)) and primary liver cancer (aOR=44.5 (10.8–183.6)). Subjects with Pi*MZ genotype had slightly elevated liver enzymes and moderately increased odds for liver fibrosis/cirrhosis (aOR=1.7 (1.2–2.2)) and cholelithiasis (aOR=1.3 (1.2–1.4)). Individuals with homozygous Pi*S mutation (Pi*SS genotype) harboured minimally elevated alanine aminotransferase values, but no other hepatobiliary abnormalities. Pi*SZ participants displayed higher liver enzymes, more frequent liver fibrosis/cirrhosis (aOR=3.1 (1.1–8.2)) and primary liver cancer (aOR=6.6 (1.6–26.9)). The higher fibrosis burden was confirmed in a multinational cohort. Male sex, age ≥50 years, obesity and the presence of diabetes were associated with significant liver fibrosis.ConclusionOur study defines the hepatobiliary phenotype of individuals with the most relevant AATD genotypes including their predisposition to liver tumours, thereby allowing evidence-based advice and individualised hepatological surveillance.
Increased risk of infective endocarditis after traumatic skin wound
Authors: Ohbe Hiroyuki , Iwagami Masao , Sasabuchi Yusuke , Yasunaga Hideo 
Published: February 2021

ObjectiveCurrent data suggest that a history of traumatic open skin wounds may be a risk factor for infectious endocarditis, with limited evidence. We tested the hypothesis that traumatic skin wound is a risk factor for infectious endocarditis.MethodsUsing the Japan Medical Data Center (JMDC) database (4 650 927 people aged 20–64 years, 2012–2018) and the Kumamoto database (493 414 people aged ≥65 years, 2012–2017), we conducted nested case–control and self-controlled case series (SCCS) analyses.ResultsIn the JMDC database, 544 cases hospitalised for infective endocarditis (IE) were matched with 2091 controls; 2.8% of cases and 0.5% of controls were exposed to traumatic skin wounds in the previous 1–4 weeks, with an adjusted OR of 4.31 (95% CI 1.74 to 10.7). In the Kumamoto database, 4.0% (27/670) of cases and 1.1% (29/2581) of controls were exposed to traumatic skin wounds in the previous 1–4 weeks, with an adjusted OR of 4.15 (95% CI 2.04 to 8.46). In the SCCS, the incidence rate ratios for IE were 2.61 (95% CI 1.67 to 4.09), 1.73 (95% CI 1.01 to 2.94), 1.19 (95% CI 0.63 to 2.27) and 1.52 (95% CI 0.82 to 2.74) for the Kumamoto database and 3.78 (95% CI 2.07 to 6.92), 1.58 (95% CI 0.64 to 3.89), 1.60 (95% CI 0.65 to 3.94) and 1.29 (95% CI 0.47 to 3.53) for the JMDC database at 1–4, 5–8, 9–12 and 13–16 weeks after traumatic skin wound, respectively, compared with the baseline period.ConclusionsThis study suggests that traumatic skin wound is a risk factor for IE 1–4 weeks after the wound.
Integrative transcriptome analysis of malignant pleural mesothelioma reveals a clinically relevant immune-based classification
Authors: Alay Ania , Cordero David , Hijazo-Pechero Sara , Aliagas Elisabet , Lopez-Doriga Adriana , Marín Raúl , Palmero Ramón , Llatjós Roger , Escobar Ignacio , Ramos Ricard , Padrones Susana , Moreno Víctor , Nadal Ernest , Solé Xavier 
Published: February 2021

BackgroundMalignant pleural mesothelioma (MPM) is a rare and aggressive neoplasia affecting the lung mesothelium. Immune checkpoint inhibitors (ICI) in MPM have not been extremely successful, likely due to poor identification of suitable candidate patients for the therapy. We aimed to identify cellular immune fractions associated with clinical outcome and classify patients with MPM based on their immune contexture. For each defined group, we sought for molecular specificities that could help further define our MPM classification at the genomic and transcriptomic level, as well as identify differential therapeutic strategies based on transcriptional signatures predictive of drug response.MethodsThe abundance of 20 immune cell fractions in 516 MPM samples from 7 gene expression datasets was inferred using gene set variation analysis. Identification of clinically relevant fractions was performed with Cox proportional-hazards models adjusted for age, stage, sex, and tumor histology. Immune-based groups were defined based on the identified fractions.ResultsT-helper 2 (TH2) and cytotoxic T (TC) cells were found to be consistently associated with overall survival. Three immune clusters (IG) were subsequently defined based on TH2 and TC immune infiltration levels: IG1 (54.5%) was characterized by high TH2 and low TC levels, IG2 (37%) had either low or high levels of both fractions, and IG3 (8.5%) was defined by low TH2 and high TC levels. IG1 and IG3 groups were associated with worse and better overall survival, respectively. While no differential genomic alterations were identified among immune groups, at the transcriptional level, IG1 samples showed upregulation of proliferation signatures, while IG3 samples presented upregulation of immune and inflammation-related pathways. Finally, the integration of gene expression with functional signatures of drug response showed that IG3 patients might be more likely to respond to ICI.ConclusionsThis study identifies a novel immune-based signature with potential clinical relevance based on TH2 and TC levels, unveiling a fraction of patients with MPM with better prognosis and who might benefit from immune-based therapies. Molecular specificities of the different groups might be used to tailor specific potential therapies in the future.
Rapid exponential increase in neurosurgery departmental scholarly output following an intensive research initiative
Authors: Karimov Zafar , Kazim Syed Faraz , Schmidt Meic , Gandhi Chirag , Vanderhooft Jordan , Cole Chad , Stein Alan , Al-Mufti Fawaz , Bowers Christian 
Published: February 2021

AbstractThere has been extensive research into methods of increasing academic departmental scholarly activity (DSA) through targeted interventions. Residency programmes are responsible for ensuring sufficient scholarly opportunities for residents. We sought to discover the outcomes of an intensive research initiative (IRI) on DSA in our department in a short-time interval. IRI was implemented, consisting of multiple interventions, to rapidly produce an increase in DSA through resident/medical student faculty engagement. We compare pre-IRI (8 years) and post-IRI (2 years) research products (RP), defined as the sum of oral presentations and publications, to evaluate the IRI. The study was performed in 2020. The IRI resulted in an exponential increase in DSA with an annual RP increase of 350% from 2017 (3 RP) to 2018 (14 RP), with another 92% from 2018 (14 RP) to 2019 (27 RP). RP/year exponentially increased from 2.1/year to 10.5/year for residents and 0.5/year to 10/year for medical students, resulting in a 400% and 1900% increase in RP/year, respectively. The common methods in literature to increase DSA included instituting protected research time (23.8%) and research curriculum (21.5%). We share our department's increase in DSA over a short 2-year period after implementing our IRI. Our goal in reporting our experience is to provide an example for departments that need to rapidly increase their DSA. By reporting the shortest time interval to achieve exponential DSA growth, we hope this example can support programmes in petitioning hospitals and medical colleges for academic support resources.
Maternal asthma is associated with reduced lung function in male infants in a combined analysis of the BLT and BILD cohorts
Authors: de Gouveia Belinelo Patricia , Collison Adam M , Murphy Vanessa E , Robinson Paul D , Jesson Kathryn , Hardaker Kate , de Queiroz Andrade Ediane , Oldmeadow Christopher , Martins Costa Gomes Gabriela , Sly Peter D , Usemann Jakob , Appenzeller Rhea , Gorlanova Olga , Fuchs Oliver , Latzin Philipp , Gibson Peter G , Frey Urs , Mattes Joerg 
Published: February 2021

RationaleAsthma in pregnancy is associated with respiratory diseases in the offspring.ObjectiveTo investigate if maternal asthma is associated with lung function in early life.MethodsData on lung function measured at 5–6 weeks of age were combined from two large birth cohorts: the Bern Infant Lung Development (BILD) and the Australian Breathing for Life Trial (BLT) birth cohorts conducted at three study sites (Bern, Switzerland; Newcastle and Sydney, Australia). The main outcome variable was time to reach peak tidal expiratory flow as a percentage of total expiratory time(tPTEF:tE%). Bayesian linear hierarchical regression analyses controlling for study site as random effect were performed to estimate the effect of maternal asthma on the main outcome, adjusting for sex, birth order, breast feeding, weight gain and gestational age. In separate adjusted Bayesian models an interaction between maternal asthma and sex was investigated by including an interaction term.Measurements and main resultsAll 406 BLT infants were born to mothers with asthma in pregnancy, while 193 of the 213 (91%) BILD infants were born to mothers without asthma. A significant interaction between maternal asthma and male sex was negatively associated with tPTEF:tE% (intercept 37.5; estimate: –3.5; 95% credible interval –6.8 to –0.1). Comparing the model posterior probabilities provided decisive evidence in favour of an interaction between maternal asthma and male sex (Bayes factor 33.5).ConclusionsMaternal asthma is associated with lower lung function in male babies, which may have lifelong implications on their lung function trajectories and future risk of wheezing and asthma.
Development and validation of a prediction model for 30-day mortality in hospitalised patients with COVID-19: the COVID-19 SEIMC score
Authors: Berenguer Juan , Borobia Alberto M , Ryan Pablo , Rodríguez-Baño Jesús , Bellón Jose M , Jarrín Inmaculada , Carratalà Jordi , Pachón Jerónimo , Carcas Antonio J , Yllescas María , Arribas José R 
Published: February 2021

Objective
To develop and validate a prediction model of mortality in patients with COVID-19 attending hospital emergency rooms.

Design
Multivariable prognostic prediction model.

Setting
127 Spanish hospitals.

Participants
Derivation (DC) and external validation (VC) cohorts were obtained from multicentre and single-centre databases, including 4035 and 2126 patients with confirmed COVID-19, respectively.

Interventions
Prognostic variables were identified using multivariable logistic regression.

Main outcome measures
30-day mortality.

Results
Patients’ characteristics in the DC and VC were median age 70 and 61 years, male sex 61.0% and 47.9%, median time from onset of symptoms to admission 5 and 8 days, and 30-day mortality 26.6% and 15.5%, respectively. Age, low age-adjusted saturation of oxygen, neutrophil-to-lymphocyte ratio, estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, dyspnoea and sex were the strongest predictors of mortality. Calibration and discrimination were satisfactory with an area under the receiver operating characteristic curve with a 95% CI for prediction of 30-day mortality of 0.822 (0.806–0.837) in the DC and 0.845 (0.819–0.870) in the VC. A simplified score system ranging from 0 to 30 to predict 30-day mortality was also developed. The risk was considered to be low with 0–2 points (0%–2.1%), moderate with 3–5 (4.7%–6.3%), high with 6–8 (10.6%–19.5%) and very high with 9–30 (27.7%–100%).

Conclusions
A simple prediction score, based on readily available clinical and laboratory data, provides a useful tool to predict 30-day mortality probability with a high degree of accuracy among hospitalised patients with COVID-19.
E-cigarette-inclusive smoke-free policies, excise taxes, tobacco 21 and changes in youth e-cigarette use: 2017–2019
Authors: Choi Kelvin , Omole Toluwa , Wills Thomas , Merianos Ashley L 
Published: February 2021

BackgroundWe examined whether the implementation of electronic cigarette (e-cigarette) policies at the state level (e-cigarette-inclusive smoke-free (ESF) policies, excise taxes on e-cigarettes and raising tobacco legal purchasing age to 21 years (T21)) affected recent upward trends in youth e-cigarette use.MethodsData were from participants from 34 US states who completed the Youth Risk Behavior Survey (YRBS) state surveys in 2017 and 2019 (n=278 271). States were classified as having or not having ESF policies, any e-cigarette excise tax and T21 policies by 1 January 2019. Participants reported ever, past 30-day and frequent (≥20 days) e-cigarette use; past 30-day combustible cigarette smoking; and age, sex and race/ethnicity. Weighted multivariable logistic regression models assessed whether changes in e-cigarette use over time differed by policy status, adjusting for participants’ demographics and combustible cigarette smoking.ResultsPrevalence of ever and past 30-day youth e-cigarette use in states with ESF policies decreased during 2017–2019, while the prevalence of these measures in states without ESF policies increased. States with T21 policies showed non-significant changes in prevalence of ever and past 30-day youth e-cigarette use, whereas states without T21 policies showed significant increases in ever and past 30-day youth e-cigarette use. States with ESF and T21 policies showed slower increases in youth frequent e-cigarette use. E-cigarette excise taxes were not associated with decreasing prevalence of youth e-cigarette use.ConclusionsState-level ESF and T21 policies could be effective for limiting growth of youth e-cigarette use despite an overall national increase. Higher e-cigarette excise tax rates may be needed to effectively reduce youth e-cigarette use.
Mass spectrum and strong decays of tetraquark $${\bar{c}}{\bar{s}} qq$$ states
Authors: Wang Guang-Juan , Meng Lu , Xiao Li-Ye , Oka Makoto , Zhu Shi-Lin 
Published: February 2021

AbstractWe systematically study the mass spectrum and strong decays of the S-wave $${\bar{c}}{\bar{s}} q q$$

c

¯

s

¯

q
q

states in the compact tetraquark scenario with the quark model. The key ingredients of the model are the Coulomb, the linear confinement, and the hyperfine interactions. The hyperfine potential leads to the mixing between different color configurations, and to the large mass splitting between the two ground states with $$I(J^P)=0(0^+)$$

I

(

J
P

)

=
0

(

0
+

)

and $$I(J^P)=1(0^+)$$

I

(

J
P

)

=
1

(

0
+

)

. We calculate their strong decay amplitudes into the $${\bar{D}}^{(*)}K^{(*)}$$

D

¯

(

∗
)

K

(

∗
)

channels with the wave functions from the mass spectrum calculation and the quark-interchange method. We examine the interpretation of the recently observed $$X_0(2900)$$

X
0

(
2900
)

as a tetraquark state. The mass and decay width of the $$I(J^P)=1(0^+)$$

I

(

J
P

)

=
1

(

0
+

)

state are $$M=2941$$

M
=
2941

MeV and $$\Gamma _X=26.6$$

Γ
X

=
26.6

MeV, respectively, which indicates that it might be a good candidate for $$X_0(2900)$$

X
0

(
2900
)

. Meanwhile, we also obtain an isospin partner state $$I(J^P)=0(0^+)$$

I

(

J
P

)

=
0

(

0
+

)

with $$M=2649$$

M
=
2649

MeV and $$\Gamma _{X\rightarrow {\bar{D}} K}=48.1$$

Γ

X
→

D

¯

K

=
48.1

MeV, respectively. Future experimental search for X(2649) will be very helpful.
Pan-cancer Transcriptomic Predictors of Perineural Invasion Improve Occult Histopathologic Detection
Authors: Guo Jimmy A. , Hoffman Hannah I. , Shroff Stuti G. , Chen Peter , Hwang Peter G. , Kim Daniel Y. , Kim Daniel W. , Cheng Stephanie W. , Zhao Daniel , Mahal Brandon A. , Alshalalfa Mohammed , Niemierko Andrzej , Wo Jennifer Y. , Loeffler Jay S. , Fernandez-del Castillo Carlos , Jacks Tyler , Aguirre Andrew J. , Hong Theodore S. , Mino-Kenudson Mari , Hwang William L. 
Published: February 2021

Abstract

Purpose:
Perineural invasion (PNI) is associated with aggressive tumor behavior, recurrence, and metastasis, and can influence the administration of adjuvant treatment. However, standard histopathologic examination has limited sensitivity in detecting PNI and does not provide insights into its mechanistic underpinnings.

Experimental Design:
A multivariate Cox regression was performed to validate associations between PNI and survival in 2,029 patients across 12 cancer types. Differential expression and gene set enrichment analysis were used to learn PNI-associated programs. Machine learning models were applied to build a PNI gene expression classifier. A blinded re-review of hematoxylin and eosin (H&E) slides by a board-certified pathologist helped determine whether the classifier could improve occult histopathologic detection of PNI.

Results:
PNI associated with both poor overall survival [HR, 1.73; 95% confidence interval (CI), 1.27–2.36; P &lt; 0.001] and disease-free survival (HR, 1.79; 95% CI, 1.38–2.32; P &lt; 0.001). Neural-like, prosurvival, and invasive programs were enriched in PNI-positive tumors (Padj &lt; 0.001). Although PNI-associated features likely reflect in part the increased presence of nerves, many differentially expressed genes mapped specifically to malignant cells from single-cell atlases. A PNI gene expression classifier was derived using random forest and evaluated as a tool for occult histopathologic detection. On a blinded H&E re-review of sections initially described as PNI negative, more specimens were reannotated as PNI positive in the high classifier score cohort compared with the low-scoring cohort (P = 0.03, Fisher exact test).

Conclusions:
This study provides salient biological insights regarding PNI and demonstrates a role for gene expression classifiers to augment detection of histopathologic features.