bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Effect of Intrauterine 3-Dimensional Ultrasound on the Function of the Intrauterine Cavity of Puerpera With Intrauterine Adhesions and Safety of Pregnancy
Authors: Li Qin 
Published: April 2022

Abstract
This study aimed to analyze the diagnostic value of intrauterine 3-dimensional ultrasound and the functional characteristics of the intrauterine cavity for puerpera with intrauterine adhesions, and to explore the safety of pregnancy after treatment. A total of 102 puerperas with intrauterine adhesions were randomly selected, and intrauterine 3-dimensional ultrasound and 2-dimensional ultrasound were performed, respectively. Patients were followed up for 3 years to observe the pregnancy outcome and safety. The overall accuracy of diagnosing intrauterine adhesions through intrauterine 3-dimensional ultrasound was significantly higher than that through 2-dimensional ultrasound, and the accuracy of detecting mild intrauterine adhesions was significantly higher than that through 2-dimensional ultrasound, with statistically significant difference (P < 0.05). There was no significant difference in the accuracy between intrauterine 3-dimensional and 2-dimensional ultrasound in detecting moderate and severe intrauterine adhesions (P > 0.05). The difference in missed diagnosis and misdiagnosis rates between the 2 methods was statistically significant (P < 0.05). All patients received hysteroscopic surgery, and 78 cases (76.47%) were naturally fertilized during postoperative follow-up, including 24 cases of mature delivery, 45 cases of cesarean delivery, and 9 cases of spontaneous abortion. The intrauterine 3-dimensional ultrasound examination of the intrauterine cavity will provide intuitive and comprehensive diagnostic information for a parturient with intrauterine adhesion. Its detection accuracy is higher, and the clinical application is noninvasive and safe, which has certain guiding significance for treatment.
Early expression of IL-10, IL-12, ARG1, and NOS2 genes in peripheral blood mononuclear cells synergistically correlate with patient outcome after burn injury
Authors: Mahung Cressida , Stepp Wesley H. , Long Clayton , Malfitano Madison , Saklayici Irmak , Wallet Shannon M. , Zhou Laura Y. , Zhou Haibo , Cairns Bruce A. , Maile Robert 
Published: April 2022

BACKGROUND
No methods exist to rapidly and accurately quantify the immune insult created by burn injuries. The development of a rapid, noninvasive clinical biomarker assay that evaluates a burn patient's underlying immune dysfunction and predicts clinical outcomes could transform burn care. We aimed to determine a set of peripheral biomarkers that correlates with clinical outcomes of burn patients.

METHODS
This prospective observational study enrolled two patient cohorts within a single burn center into an institutionally approved institutional review board study. Blood draws were performed <48 hours after injury. Initial unbiased immune gene expression analysis compared 23 burn patients and 6 healthy controls using multiplex immune gene expression analysis of RNA from peripheral blood mononuclear cells. We then performed confirmatory outcomes analysis in 109 burn patients and 19 healthy controls using a targeted rapid quantitative polymerase chain reaction. Findings were validated and modeled associations with clinical outcomes using a regression model.

RESULTS
A total of 149 genes with a significant difference in expression from burn patients compared with controls were identified. Pathway analysis identified pathways related to interleukin (IL)-10 and inducible nitric oxide synthase signaling to have significant z scores. quantitative polymerase chain reaction analysis of IL-10, IL-12, arginase 1 (ARG1), and inducible nitric oxide synthase demonstrated that burn injury was associated with increased expression of ARG1 and IL-10, and decreased expression of nitric oxide synthase 2 (NOS2) and IL-12. Burn severity, acute lung injury, development of infection, failure of skin autograft, and mortality significantly correlated with expression of one or more of these genes. Ratios of IL-10/IL-12, ARG1/NOS2, and (ARG1–IL-10)/(NOS2–IL-12) transcript levels further improved the correlation with outcomes. Using a multivariate regression model, adjusting for patient confounders demonstrated that (ARG1–IL-10)/(NOS2–IL-12) significantly correlated with burn severity and development of acute lung injury.

CONCLUSION
We present a means to predict patient outcomes early after burn injury using peripheral blood, allowing early identification of underlying immune dysfunction.

LEVEL OF EVIDENCE
Prognostic/Epidemiological; Level II.
Epidemiology and outcomes of multiple organ dysfunction syndrome following pediatric trauma
Authors: Killien Elizabeth Y. , Zahlan Jana M. , Lad Hetal , Watson R. Scott , Vavilala Monica S. , Huijsmans Roel L.N. , Rivara Frederick P. 
Published: March 2022

BACKGROUND
Existing studies have found a low prevalence of multiple organ dysfunction syndrome (MODS) in pediatric trauma patients, typically applying adult criteria to single-center pediatric cohorts. We used pediatric criteria to determine the prevalence, risk factors, and outcomes of MODS among critically injured children in a national pediatric intensive care unit (PICU) database.

METHODS
We conducted a retrospective cohort study of PICU patients 1 month to 17 years with traumatic injury in the Virtual Pediatric Systems, LLC database from 2009 to 2017. We used International Pediatric Sepsis Consensus Conference criteria to identify MODS on Day 1 of PICU admission and estimated the risk of mortality and poor functional outcome (Pediatric Overall/Cerebral Performance Category ≥3 with ≥1 point worsening from baseline) for MODS and for each type of organ dysfunction using generalized linear Poisson regression adjusted for age, comorbidities, injury type and mechanism, and postoperative status.

RESULTS
Multiple organ dysfunction syndrome was present on PICU Day 1 in 23.1% of 37,177 trauma patients (n = 8,592), with highest risk among patients with injuries associated with drowning, asphyxiation, and abuse. Pediatric intensive care unit mortality was 20.1% among patients with MODS versus 0.5% among patients without MODS (adjusted relative risk, 32.3; 95% confidence interval, 24.1–43.4). Mortality ranged from 1.5% for one dysfunctional organ system to 69.1% for four or more organ systems and was highest among patients with hematologic dysfunction (43.3%) or renal dysfunction (29.6%). Death or poor functional outcome occurred in 46.7% of MODS patients versus 8.3% of patients without MODS (adjusted relative risk, 4.3; 95% confidence interval 3.4–5.3).

CONCLUSION
Multiple organ dysfunction syndrome occurs more frequently following pediatric trauma than previously reported and is associated with high risk of morbidity and mortality. Based on existing literature using identical methodology, both the prevalence and mortality associated with MODS are higher among trauma patients than the general PICU population. Consideration of early organ dysfunction in addition to injury severity may aid prognostication following pediatric trauma.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level III.
Perspectives on competencies for care in austere settings
Authors: Kauvar David S. , Yelon Jay A. , Wilson Alison , Gaines Barbara A. , Martin Matthew J. , Cannon Jeremy W. 
Published: March 2022

ABSTRACT
Austerity in surgical care may manifest by limited equipment/supplies, deficient infrastructure (power, water), rationing/triage requirements, or the unavailability of specialty surgical or medical expertise. Some settings in which surgeons may experience austerity include the following: military deployed operations (domestic and foreign), humanitarian surgical missions, care in rural or remote settings, mass-casualty events, natural disasters, and/or care in low- and some middle-income countries. Expanded competencies beyond those required in routine surgical practice can optimize the quality of surgical care in such settings. The purpose of this expert panel review is to introduce those competencies.
A cystic fibrosis lung disease modifier locus harbors tandem repeats associated with gene expression
Authors: Roshandel Delnaz , Mastromatteo Scott , Wang Cheng , Gong Jiafen , Thiruvahindrapuram Bhooma , Sung Wilson W.L. , Wang Zhuozhi , Hamdan Omar , Whitney Joe , Panjwani Naim , Lin Fan , Keenan Katherine , Chen Angela , Esmaeili Mohsen , Halevy Anat , Avolio Julie , Ratjen Felix , Celedón Juan C. , Forno Erick , Chen Wei , Kim Soyeon , Sun Lei , Rommens Johanna M. , Strug Lisa J. 
Published: April 2022

AbstractVariable number of tandem repeats (VNTRs) are major source of genetic variation in human. However due to their repetitive nature and large size, it is challenging to genotype them by short-read sequencing. Therefore, there is limited understanding of how they contribute to complex traits such as cystic fibrosis (CF) lung function. Genome-wide association study (GWAS) of CF lung disease identified two independent signals near SLC9A3 displaying a high density of VNTRs and CpG islands. Here, we used long-read (PacBio) phased sequence (N=58) to identify the boundaries and lengths of 49 common (frequency >2%) VNTRs in the region. Subsequently, associations of the VNTRs with gene expression were investigated in CF nasal epithelia using RNA sequencing (N=46). Two VNTRs tagged by the two GWAS signals and overlapping CpG islands were independently associated with SLC9A3 expression in CF nasal epithelia. The two VNTRs together explained 24% of SLC9A3 gene expression variation. One of them was also associated with TPPP expression. We then showed that the VNTR lengths can be estimated with good accuracy in short-read sequence in a subset of individuals with data on both long (PacBio) and short-read (10X Genomics) technologies (N=52). VNTR lengths were then estimated in the Genotype-Tissue Expression project (GTEx) and their association with gene expression was investigated. Both VNTRs were associated with SLC9A3 expression in multiple non-CF GTEx tissues including lung. The results confirm that VNTRs can explain substantial variation in gene expression and be responsible for GWAS signals, and highlight the critical role of long-read sequencing.
External Validation of the Predicting Asthma Risk in Children (PARC) tool in a clinical cohort
Authors: Berger Daria Olena , Pedersen Eva S L , Mallet Maria Christina , de Jong Carmen C M , Usemann Jakob , Regamey Nicolas , Spycher Ben D , Ardura-Garcia Cristina , Kuehni Claudia E 
Published: March 2022

AbstractRationaleThe Predicting Asthma Risk in Children (PARC) tool uses questionnaire-based respiratory symptoms collected from preschool children to predict their risk of asthma 5 years later. The tool was originally developed and externally validated in population-based settings and has not yet been validated in a clinical setting.ObjectiveTo externally validate the PARC tool in children seen in paediatric pulmonology clinics.MethodsThe Swiss Paediatric Airway Cohort (SPAC) is a prospective study of children seen in respiratory outpatient clinics across Switzerland. This analysis included children seen at ages 1-6 years for cough or wheeze at baseline and who completed the follow-up questionnaire 2 years later. The outcome was defined as current wheeze plus use of asthma medication. In sensitivity analyses, we explored effects of varied inclusion criteria and outcomes. We assessed performance by describing sensitivity, specificity, negative and positive predictive value (NPV, PPV), area under the curve (AUC), scaled Brier’s score and Nagelkerke’s R2 scores and compared performance in SPAC to that achieved in the original population, the Leicester Respiratory Cohort (LRC).ResultsAmong the 346 children included, 125 (36%) reported the outcome after 2 years. At a PARC score cut-off of 4, sensitivity was higher (95% vs 79%) but specificity lower (14% vs 57%) in SPAC compared to LRC. NPV was comparable (0.84 vs. 0.87) as was PPV (0.37 vs.0.42). Discrimination was lower in SPAC (AUC of 0.71 vs 0.78), as were Nagelkerke’s R2 (0.18 vs 0.28) and scaled Brier’s scores (0.13 vs 0.22). When the outcome was changed to moderately severe asthma (>4 attacks plus use of asthma medication), there were improvements in AUC (0.74), sensitivity (0.97), specificity (0.22) and NPV (0.99), but some deterioration in PPV (0.13), R2 (0.15) and scaled Brier score (0.09).ConclusionWhile the PARC tool performs well in a population-based setting and has some clinical utility, in particular for ruling out the development of asthma, this study highlights the need for new prognostic prediction tools to be developed specifically for the clinical setting.FundingSNSF:320030_182628, SLA2019-03_641670
Ivacaftor, not ivacaftor/lumacaftor, is associated with lower pulmonary inflammation in preschool cystic fibrosis
Authors: Shanthikumar Shivanthan , Ranganathan Sarath , Neeland Melanie R. 
Published: March 2022

ABSTRACTAirway inflammation is a key driver of cystic fibrosis (CF) lung disease. The advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators has the potential to transform the care of CF, however the direct effect of these therapies on lung inflammation is unknown. Here, we profile airway inflammation in bronchoalveolar lavage (BAL) of preschool aged children with CF on CFTR modulator therapy (ivacaftor or ivacaftor/lumacaftor), untreated children with CF, and age-matched healthy controls. We show that children treated with ivacaftor have lower pulmonary concentrations of inflammatory mediators CCL3, CXCL9, CCL2, IL-8, IL-1β, and IL-6 relative to untreated children with CF. Conversely, there was no significant effect of lumacaftor/ivacaftor treatment on airway inflammation. This is the first work to illustrate a difference in early life airway inflammation with CFTR treatment, highlights the effectiveness of ivacaftor in early life, and suggests that BAL inflammatory profile may represent a biomarker of therapeutic response to treatment.
Reduction in risk of death among patients admitted with COVID-19 between first and second epidemic waves in New York City
Authors: Bowen Anthony , Zucker Jason , Shen Yanhan , Huang Simian , Yan Qiheng , Annavajhala Medini K. , Uhlemann Anne-Catrin , Kuhn Louise , Sobieszczyk Magdalena , Castor Delivette 
Published: March 2022

AbstractMany regions have experienced successive epidemic waves of COVID-19 since the emergence of SARS-CoV-2 with heterogeneous differences in mortality. Elucidating factors differentially associated with mortality between epidemic waves may inform clinical and public health strategies. We examined clinical and demographic data among patients admitted with COVID-19 during the first (March-June 2020) and second (December 2020-March 2021) epidemic waves at an academic medical center in New York City. Hospitalized patients (N=4631) had lower mortality during the second wave (14%) than the first (23%). Patients in the second wave had a lower 30-day mortality (Hazard Ratio (HR) 0.52, 95% CI 0.44, 0.61) than those in the first wave. The mortality decrease persisted after adjusting for confounders except for the volume of COVID-19 admissions (HR 0.88, 95% CI 0.70, 1.11), a measure of health system strain. Several demographic and clinical patient factors were associated with an increased risk of mortality independent of wave.Article summaryUsing clinical and demographic data from COVID-19 hospitalizations at a tertiary New York City medical center, we show that a reduction in mortality during the second epidemic wave was associated with decreased strain on healthcare resources.
The impact of reactive case detection on malaria transmission in Zanzibar in the presence of human mobility
Authors: Das Aatreyee M. , Hetzel Manuel W. , Yukich Joshua O. , Stuck Logan , Fakih Bakar S. , Al-mafazy Abdul-wahid H. , Ali Abdullah , Chitnis Nakul 
Published: March 2022

AbstractMalaria persists at low levels on Zanzibar despite the use of vector control and case management. We use a metapopulation model to investigate the role of human mobility in malaria persistence on Zanzibar, and the impact of reactive case detection. The model was parameterized using survey data on malaria prevalence, reactive case detection, and travel history. We find that in the absence of imported cases from mainland Tanzania, malaria would likely cease to persist on Zanzibar. We also investigate potential intervention scenarios that may lead to elimination, especially through changes to reactive case detection. While we find that some additional cases are removed by reactive case detection, a large proportion of cases are missed due to many infections having a low parasite density that go undetected by rapid diagnostic tests, a low rate of those infected with malaria seeking treatment, and a low rate of follow up at the household level of malaria cases detected at health facilities. While improvements in reactive case detection would lead to a reduction in malaria prevalence, none of the intervention scenarios tested here were sufficient to reach elimination. Imported cases need to be treated to have a substantial impact on prevalence.
Telomere length and its associations with mental disorders, age and genetic risk for mental disorders
Authors: Mutz Julian , Lewis Cathryn M 
Published: March 2022

AbstractBackgroundMental disorders are associated with substantially increased morbidity and reduced life expectancy. Accelerated biological ageing might contribute to excess mortality of individuals with mental disorders. The aim of this study was to characterise telomere length, a biological hallmark of ageing, in individuals with mental disorders, and to examine associations between telomere length, age and genetic risk for mental disorders.MethodsThe UK Biobank is a multicentre, community-based observational study that recruited >500,000 middle-aged and older adults across England, Scotland and Wales. Average leukocyte telomere length (T/S ratio) was measured using quantitative polymerase chain reaction. Polygenic risk scores (PRS) were calculated for individuals of European ancestry. We estimated differences in T/S ratio and age-related changes in T/S ratio between individuals with anxiety disorder, depression or bipolar disorder and people without mental disorders. We also estimated associations between T/S ratio and PRS for these three disorders.ResultsThe analyses included up to 308,725 participants. Individuals with depression had shorter telomeres than people without mental disorders (adjustedβ= -0.011, 95% CI -0.019 to -0.004,pBonf.= 0.027). There was only limited evidence of case-control differences in telomere length for anxiety disorders or bipolar disorders. Age-related changes in telomere length did not differ between individuals with and without mental disorders. PRS for depression were associated with shorter telomeres (β= -0.006, 95% CI -0.010 to -0.003,pBonf.= 0.001). There was no evidence that PRS for anxiety disorder or bipolar disorder were associated with telomere length.ConclusionAlthough telomere length is a biological hallmark of ageing, we observed limited evidence that leukocyte telomere length is a clinically useful marker to quantify accelerated biological ageing in middle-aged and older adults with a lifetime history of anxiety disorder, depression or bipolar disorder.
Endemicity is not a victory: the unmitigated downside risks of widespread SARS-CoV-2 transmission
Authors: Stoddard Madison , Novokhodko Alexander , Sarkar Sharanya , Van Egeren Debra , White Laura F. , Hochberg Natasha S. , Rogers Michael , Zetter Bruce , Joseph-McCarthy Diane , Chakravarty Arijit 
Published: March 2022

AbstractWe have entered a new phase of the ongoing COVID-19 pandemic, as the strategy of relying solely on the current SARS-CoV-2 vaccines to bring the pandemic to an end has become infeasible. In response, public-health authorities in many countries have advocated for a strategy of using the vaccines to limit morbidity and mortality while permitting unchecked SARS-CoV-2 spread (“learning to live with the disease”). The feasibility of this strategy is critically dependent on the infection fatality rate (IFR) of COVID-19. An expectation exists, both in the lay public and in the scientific community, that future waves of the virus will exhibit decreased IFR, either due to viral attenuation or the progressive buildup of immunity. In this work, we examine the basis for that expectation, assessing the impact of virulence on transmission. Our findings suggest that large increases in virulence for SARS-CoV-2 would result in minimal loss of transmission, implying that the IFR may be free to increase or decrease under neutral evolutionary drift. We further examine the effect of changes in the IFR on the steady-state death toll under conditions of endemic COVID-19. Our modeling suggests that endemic SARS-CoV-2 implies vast transmission resulting in yearly US COVID-19 death tolls numbering in the hundreds of thousands under many plausible scenarios, with even modest increases in the IFR leading to an unsustainable mortality burden. Our findings thus highlight the critical importance of enacting a concerted strategy (involving for example global access to vaccines, therapeutics, prophylactics and nonpharmaceutical interventions) to suppress SARS-CoV-2 transmission, thereby reducing the risk of catastrophic outcomes. Our findings also highlight the importance of continued investment in novel biomedical interventions to prevent viral transmission.
A Distinct Chromatin State Drives Therapeutic Resistance in Invasive Lobular Breast Cancer
Authors: Nardone Agostina , Qiu Xintao , Feiglin Ariel , Fu Xiaoyong , Spisak Sandor , Feit Avery , Feit Gabriela Cohen , Xie Yingtian , Font-Tello Alba , Guarducci Cristina , Hermida-Prado Francisco , Syamala Sudeepa , Lim Klothilda , Pun Matthew , Cornwell MacIntosh , Liu Weihan , Ors Aysegul , Mohammed Hisham , Brock Jane , Freedman Matthew L. , Schiff Rachel , Winer Eric P. , Long Henry , Filho Otto Metzger , Jeselsohn Rinath 
Published: March 2022

AbstractMost invasive lobular breast cancers (ILC) are of the luminal A subtype and strongly hormone receptor positive. Yet, they are relatively resistant to tamoxifen and are associated with inferior long-term outcomes compared to invasive ductal cancers (IDC). In this study, we sought to gain mechanistic insights into these clinical findings that are not explained by the genetic landscape of ILC and to identify strategies to improve patient outcomes. Through a comprehensive analysis of the epigenome of ILC in pre-clinical models and clinical samples we found that compared to IDC, ILC has a distinct chromatin state that is linked to gained recruitment of FOXA1, a lineage-defining pioneer transcription factor. This results in an ILC-unique FOXA1-estrogen receptor (ER) axis that promotes the transcription of genes associated with tumor progression and poor outcomes. The ILC-unique FOXA1-ER axis leads to retained ER chromatin binding after tamoxifen treatment thereby facilitating tamoxifen resistance while remaining strongly dependent on ER signaling. Mechanistically, gained FOXA1 binding was associated with the auto-induction of FOXA1 in ILC through an ILC-unique FOXA1 binding site. Targeted silencing of this regulatory site resulted in the disruption of the feed-forward loop and growth inhibition in ILC.In summary, we show that ILC is characterized by a unique cell state and FOXA1-ER axis that dictate tumor progression and offer a novel mechanism of tamoxifen resistance. These results underscore the importance of conducting clinical trials dedicated to patients with ILC to optimize endocrine treatments in this breast cancer subtype.