bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel immune‐modulating drugs for advanced head and neck cancer
Authors: Chen Tien‐Hua , Chang Peter M. ‐H. , Yang Muh‐Hwa 
Published: October 2019

AbstractBackgroundRecently, two anti‐PD‐1 immune checkpoint inhibitors, pembrolizumab and nivolumab, have been approved by the US Food and Drug Administration for patients who fail on platinum‐based chemotherapy. However, overall response and progression‐free survival are still limited, and multiple novel agents are under development to fulfill this unmet clinical need.MethodsPublications between 1992 and 2019 regarding the immunological/biological mechanisms and early phase clinical trial outcomes of immunomodulatory agents for head and neck cancer were described in this review article.ResultsEleven immunomodulatory agents for advanced head and neck, including small molecules, antibodies, and therapeutic vaccines were described. Treatment responses were noted in nearly all 11 agents, as monotherapy or combination therapy.ConclusionsPotentials of the novel immunomodulatory agents to improve treatment efficacy of head and neck cancer and to maintain tolerable safety profile have been disclosed.
Effects of infant negative affect and contextual factors on infant regulatory capacity: The moderating role of infant sex
Authors: Petrenko Anton , Kanya Meghan J. , Rosinski Leanna , McKay Erin R. , Bridgett David J. 
Published: October 2019

AbstractInfants' abilities to orient and regulate are directly linked to self‐regulatory capacity in childhood, which is subsequently associated with indicators of health and well‐being. However, relatively little is known regarding factors affecting early orienting and regulation. The current study evaluated the effects of infant negative affect and household chaos when children were 4 months old and parenting at 6 months of age on subsequent regulatory capacity at 8 months of age in a sample of 179 mother‐infant dyads. The potential moderating role of infant sex was examined in consideration of the viability–vulnerability tradeoff theory, which posits that females may be more susceptible to the impact of stressful environments in early development. Analyses indicated that early household chaos was related to subsequently lower orienting/regulatory abilities at 8 months of age. Additionally, there were significant sex‐by‐negative affectivity and sex‐by‐household chaos interactions, such that boys' regulatory capacity was negatively impacted by early negative affectivity and girls' was adversely affected by household chaos. Findings indicate some support for the viability–vulnerability tradeoff theory.Highlights

The current study evaluated whether early negative affect and contextual factors impacted infant orienting/regulation at 8 months of age, and whether they influenced boys and girls differently.
Results indicate that chaotic household environments negatively impact infants' ability to orient/regulate, and that male and female infants are differently affected by early negative affectivity and household chaos.
This study suggests that parents should aim to decrease levels of home chaos to promote optimal regulatory development, and finds some support for the viability‐vulnerability tradeoff theory.
An updated single center experience with plerixafor and granulocyte colony‐stimulating factor for stem cell mobilization in light chain amyloidosis
Authors: Badar Talha , Dhakal Binod , Szabo Aniko , Padmanabhan Anand , Johnson Bryon D. , Heidtke Sarah , Esselmann Jean , Chhabra Saurabh , Hamadani Mehdi , Hari Parameswaran , D'Souza Anita 
Published: October 2019

AbstractThe use of granulocyte‐colony stimulating factor (G‐CSF) with or without chemotherapy to mobilize hematopoietic progenitor cells (HPCs) can result in significant morbidity in light chain (AL) amyloidosis patients. Plerixafor, a strong inducer and mobilizer of HPCs, can be used as an adjunct to G‐CSF to improve mobilization efficiency. We describe the outcomes for combined G‐CSF/plerixafor mobilized patients with AL amyloidosis. We reviewed data of 53 consecutive AL amyloidosis patients who underwent combined G‐CSF/plerixafor HPC mobilization between May 2011 and October 2017 at our institution. We evaluated patients for HPC collection efficiency, perimobilization toxicity and postautologous hematopoietic cell transplantation (autoHCT) outcomes. Median CD34+ cell collection was 12.4 × 106 cells/kg (range 2.5 × 106 to 34.1 × 106 cells/kg) and 45 (85%) patients had collections of ≥5.0 × 106 CD34+ cells/kg. There were no mobilization failures or perimobilization mortality. During mobilization, 37 (70%) patients had weight gain (median 1.3 kg, range 0.1‐4) but none >10% body weight, 5 (10%) patients had diarrhea, and one patient each had hypotension and cardiac arrhythmia. Among the 31 patients analyzed for CD34 collection efficiency (CE), the median CD34 CE was 47% (range 36‐62). At 5 years follow‐up 82% and 84% of patients were progression‐free and alive, respectively. Our results suggest that G‐CSF/plerixafor mobilization is safe, well tolerated, and effective in AL amyloidosis.
A proof‐of‐concept study on the effects of low total cfDNA content and solutions to increase the NIPT trisomy 21 detection rate
Authors: Du Yang , Chen Ailing , Yang Rui , Zhou Tao , Zhou Qin , Yang Lan , Wang Juan , Hong Yan , Chen Chen , Wan Qian , Yang Lin , Chen Ying 
Published: October 2019

AbstractBackgroundNon‐invasive prenatal testing (NIPT) is routinely used in clinical practice for fetal trisomy screening, but low total cfDNA content and low fetal fraction (LFF) are two factors that affect the detection rate. Samples with low total cfDNA or LFF usually end up with “no‐call” results, followed by the blood redraw and re‐testing, which is inconvenient for pregnant women and clinicians.MethodsWe created mock trisomy 21 (T21) samples to investigate the effects of low total cfDNA with low LFF and possible solutions to increase their detection rate.ResultsSamples with low total cfDNA resulted in the decreased unique reads number and increased duplication rate. Abnormal correlations between library concentration and raw reads number and the coverage fluctuation value, ZsdNorm, were also discovered, suggesting that low total cfDNA could lead to the overestimation of the library concentration. Additionally, a non‐reference‐based derivative value method (DV method) was evaluated and the data demonstrated that the detection sensitivity of trisomy 21 was increased from 33.33% (6/18) to 94.44% (17/18) in samples with 5% fetal fraction comparing with the z‐score approach, whereas for LFF (3.5%) group, the performance was raised from 0% to 35.29% (6/17).ConclusionLow total cfDNA has significant impacts on NIPT performance by altering sequencing quality. The non‐reference‐based DV method could increase the T21 detection rate in samples with limited cfDNA content and 5% fetal fraction, but it was not as effective for those with LFF.
Attachment and social support in romantic dyads: A systematic review
Authors: McLeod Saul , Berry Katherine , Hodgson Catherine , Wearden Alison 
Published: October 2019

AbstractObjectiveTaking a dyadic perspective, this systematic review examined the relationship between attachment constructs and differences in support behavior in romantic couples.MethodFour databases were searched including PsychINFO, Embase, OVOID MEDLINE, and AMED. Out of 2,401 unique references, 43 met the study inclusion criteria.ResultsThe review findings offer validation for an attachment‐based model of support processes in couples. Maladaptive support behaviors were more likely to occur when one or both members of a romantic dyad had an insecure attachment. Individuals with an avoidant or anxious attachment were more likely to provide poor quality support, and when receiving support, to interpret it in a negative manner.ConclusionWe recommend therapeutic interventions to help individuals with insecure attachments to follow more adaptive ways of support seeking, so social relationships are more able to offer a buffering effect against the development of mental health problems.
Long noncoding RNA MIAT2 alleviates lipopolysaccharide‐induced inflammatory damage in WI‐38 cells by sponging microRNA‐15
Authors: Zhang Hong , Zhao Jing , Shao Peng 
Published: October 2019

AbstractNeonatal pneumonia is a high neonatal mortality disease. We studied the function and mechanism of long noncoding RNA myocardial infarction‐associated transcript 2 (lncRNA MIAT2) on lipopolysaccharide (LPS)‐induced inflammation in WI‐38 cells. Cell Counting Kit‐8 and apoptosis assay were respectively used to detect the functions of LPS, MIAT2, and microRNA‐15 (miR‐15) on viability and apoptosis. MIAT2 and miR‐15 expressions were changed by cell transfection. Moreover, reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR), western blot, and enzyme‐linked immunosorbent assay were used to detect the expressions of interleukin (IL)‐6 and monocyte chemoattractant protein‐1 (MCP‐1). The levels of Bax, cleaved‐caspase‐3, and cell pathways‐related proteins were tested by western blot. Besides, the levels of miR‐15 and MIAT2 were tested by RT‐qPCR. We found that LPS declined cell viability and heightened apoptosis and levels of Bax, cleaved‐caspase‐3, IL‐6, and MCP‐1. MIAT2 was negatively regulated by LPS and it alleviated LPS‐induced damage. Furthermore, MIAT2 reversely regulated miR‐15 and miR‐15 mimic could reverse the effects of MIAT2. Finally, MIAT2 restrained the p38MAPK and NF‐κB pathways by downregulating miR‐15. In conclusion, MIAT2 alleviated LPS‐induced inflammation damage in WI‐38 cells by sponging miR‐15 via p38MAPK and NF‐κB pathways.
β-Catenin stabilization in NOD dendritic cells increases IL-12 production and subsequent induction of IFN-γ-producing T cells
Authors: Zirnheld Arin L , Villard Marine , Harrison Alisha M , Kosiewicz Michele M , Alard Pascale 
Published: October 2019

Abstract
Dendritic cells (DC) from diabetes-prone NOD mice and patients with type 1 diabetes (T1D) produce excess IL-12 that drives development of β-cell-destroying IFN-γ-producing T cells. The molecular mechanisms that control IL-12 production in T1D are unclear. In this study, we report that β-catenin, a multifunctional protein involved in inflammation, is dramatically increased in DC from NOD mice. We further investigated the mechanisms leading to accumulation of β-catenin in NOD DC and its role in the inflammatory pathogenic responses associated with T1D. Hyperphosphorylation of β-catenin at a stabilizing residue, serine 552, mediated by activation of Akt, appears to lead to β-catenin accumulation in NOD DC. Elevated β-catenin in DC correlated with IL-12 production and induction of IFN-γ-producing CD4 cells. On the one hand, knockdown/inhibition of β-catenin significantly reduced NOD DC production of IL-12 and their ability to induce IFN-γ-producing CD4 cells. On the other hand, overexpression of β-catenin in control DC resulted in increased IL-12 production and induction of IFN-γ-production in T cells. Additionally, we found that β-catenin inhibitors decreased NF-κB activation in NOD DC and IFN-γ production by NOD T cells in vivo. These data strongly suggest that accumulation of β-catenin in DC from NOD mice drives IL-12 production, and consequently, development of pathogenic IFN-γ-producing T cells. Targeting the defect responsible for β-catenin accumulation and subsequent overproduction of pro-inflammatory cytokines by NOD DC could be an effective therapeutic strategy for the prevention and/or treatment of T1D.
A mutation in mannose‐phosphate‐dolichol utilization defect 1 reveals clinical symptoms of congenital disorders of glycosylation type I and dystroglycanopathy
Authors: van Tol Walinka , Ashikov Angel , Korsch Eckhard , Abu Bakar Nurulamin , Willemsen Michèl A. , Thiel Christian , Lefeber Dirk J. 
Published: October 2019

AbstractCongenital disorders of glycosylation type I (CDG‐I) are inborn errors of metabolism, generally characterized by multisystem clinical manifestations, including developmental delay, hepatopathy, hypotonia, and skin, skeletal, and neurological abnormalities. Among others, dolichol‐phosphate‐mannose (DPM) is the mannose donor for N‐glycosylation as well as O‐mannosylation. DOLK‐CDG, DPM1‐CDG, DPM2‐CDG, and DPM3‐CDG are defects in the DPM synthesis showing both CDG‐I abnormalities and reduced O‐mannosylation of alpha‐dystroglycan (αDG), which leads to muscular dystrophy‐dystroglycanopathy. Mannose‐phosphate‐dolichol utilization defect 1 (MPDU1) plays a role in the utilization of DPM. Here, we report two MPDU1‐CDG patients without skin involvement, but with massive dilatation of the biliary duct system and dystroglycanopathy characteristics including hypotonia, elevated creatine kinase, dilated cardiomyopathy, buphthalmos, and congenital glaucoma. Biochemical analyses revealed elevated disialotransferrin in serum, and analyses in fibroblasts showed shortened lipid linked oligosaccharides and DPM, and reduced O‐mannosylation of αDG. Thus, MPDU1‐CDG can be added to the list of disorders with overlapping biochemical and clinical abnormalities of CDG‐I and dystroglycanopathy.SynopsisMannose‐phosphate‐dolichol utilization defect 1 patients can have overlapping biochemical and clinical abnormalities of congenital disorders of glycosylation type I and dystroglycanopathy.
Prediction of biochemical recurrence in prostate cancer patients who underwent prostatectomy using routine clinical prostate multiparametric MRI and decipher genomic score
Authors: Jambor Ivan , Falagario Ugo , Ratnani Parita , Perez Ileana Montoya , Demir Kadir , Merisaari Harri , Sobotka Stanislaw , Haines George K. , Martini Alberto , Beksac Alp Tuna , Lewis Sara , Pahikkala Tapio , Wiklund Peter , Nair Sujit , Tewari Ash 
Published: October 2019

BackgroundBiochemical recurrence (BCR) affects a significant proportion of patients who undergo robotic‐assisted laparoscopic prostatectomy (RALP).PurposeTo evaluate the performance of a routine clinical prostate multiparametric magnetic resonance imaging (mpMRI) and Decipher genomic classifier score for prediction of biochemical recurrence in patients who underwent RALP.Study TypeRetrospective cohort study.SubjectsNinety‐one patients who underwent RALP performed by a single surgeon, had mpMRI before RALP, Decipher taken from RALP samples, and prostate specific antigen (PSA) follow‐up for >3 years or BCR within 3 years, defined as PSA >0.2 mg/ml.Field Strength/SequencempMRI was performed at 27 different institutions using 1.5T (n = 10) or 3T scanners and included T2w, diffusion‐weighted imaging (DWI), or dynamic contrast‐enhanced (DCE) MRI.AssessmentAll mpMRI studies were reported by one reader using Prostate Imaging Reporting and Data System v. 2.1 (PI‐RADsv2.1) without knowledge of other findings. Eighteen (20%) randomly selected cases were re‐reported by reader B to evaluate interreader variability.Statistical TestsUnivariate and multivariate analysis using greedy feature selection and tournament leave‐pair‐out cross‐validation (TLPOCV) were used to evaluate the performance of various variables for prediction of BCR, which included clinical (three), systematic biopsy (three), surgical (six: RALP Gleason Grade Group [GGG], extracapsular extension, seminal vesicle invasion, intraoperative surgical margins [PSM], final PSM, pTNM), Decipher (two: Decipher score, Decipher risk category), and mpMRI (eight: prostate volume, PSA density, PI‐RADv2.1 score, MRI largest lesion size, summed MRI lesions' volume and relative volume [MRI‐lesion‐percentage], mpMRI ECE, mpMRI seminal vesicle invasion [SVI]) variables. The evaluation metric was the area under the curve (AUC).ResultsForty‐eight (53%) patients developed BCR. The best‐performing individual features with TLPOCV AUC of 0.73 (95% confidence interval [CI] 0.64–0.82) were RALP GGG, MRI‐lesion‐percentage followed by biopsy GGG (0.72, 0.62–0.82), and Decipher score (0.71, 0.60–0.82). The best performance was achieved by feature selection of Decipher+Surgery and MRI + Surgery variables with TLPOCV AUC of 0.82 and 0.81, respectivelyData ConclusionRelative lesion volume measured on a routine clinical mpMRI failed to outperform Decipher score in BCR prediction.Level of Evidence: 3Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2020;51:1075–1085.
Characterizing rainfall in the south‐western Cape, South Africa: 1841–2016
Authors: Ndebele Nothabo E. , Grab Stefan , Turasie Alemtsehai 
Published: October 2019

AbstractThe rainfall series from the South African Astronomical Observatory in Cape Town, South Africa, is one of the longest known single site instrumental records in the southern hemisphere, spanning over 176 years. Rainfall data are analysed to determine trends and periodicity in the series for annual, seasonal and monthly time scales. Using the Mann Kendall test and Sen's slope, significant negative rainfall trends are recorded for the months of March and October, and for the spring season (from September to November). Using the Mann Kendall and its modified versions to account for serial correlation, as well as a multi‐temporal trend analysis, we demonstrate a positive rainfall trend during the first 60 years (i.e., 1841–1900), which thereafter changes to a long‐term (1900–2016) negative trend, but incorporating a shorter 40 years significant positive trend between 1930 and 1970. We identify cyclic patterns with recorded periods of 9–12 years, 16–30 years and 30–42 years for rainfall, the Southern annular mode (SAM) and Southern oscillation index (SOI). In addition to the notable 9–12 years rainfall cycle that is evidently associated with sunspot cycles, 20–30 years and longer 32–40 years rainfall, solar, SAM and SOI cycles are also identified.
Impact of amplified evaporation due to lake expansion on the water budget across the inner Tibetan Plateau
Authors: Song Chunqiao , Sheng Yongwei , Zhan Shengan , Wang Jida , Ke Linghong , Liu Kai 
Published: October 2019

AbstractOver the past decades, changing climate has exerted pronounced influences on the cryo‐hydrological environment on the Tibetan Plateau. One major manifestation is the widespread lake expansions over Tibetan endorheic basins. The enlarged lake water surface areas are expected to significantly alter land‐atmosphere water fluxes, which in return may pose feedbacks to the climate system and hydrological processes. The goal of this study is to investigate the potential influences of the recent lake expansions on amplifying the evaporation flux over the basins of inner Tibetan Plateau (ITP). We detected that the ITP lakes have experienced a net inundation increase of 4,542.3 km2 during 2000–2015, about 95.6% of which was contributed by lakes larger than 1 km2. We further estimated the land and water evaporations based on multi‐source, available actual evapotranspiration (ETa) and potential evapotranspiration data sets, and in situ evaporation records. The differences between land ETa and lake water evaporation were employed to represent the evaporation alternation over newly inundated basin (named “land‐to‐lake” hereafter) areas. The land ETa was estimated based on the average of three commonly used gridded data sets while the over‐lake evaporation was calculated by the empirical correction of potential evaporation estimates by spatial interpolation of pan evaporation. A conservative estimate using the pan coefficient of 0.6 indicates that the newly inundated lake area may have led to a potential evaporation increase of 3.08 ± 1.08 Gt/year on the ITP. The increased evaporation flux is close to half of the recent annual growth rate of lake water storage in the ITP. Despite unneglectable uncertainties, our estimates initiate an important assessment of how the recent lake expansion across the ITP has influenced the local land‐atmosphere interactions and the water cycle. Accounting this evaporation amplification is crucial to reduce the uncertainty in estimating basin‐scale water budgets and projecting the regional water balance.
Integrated large‐scale circulation impact on rainy season precipitation in the source region of the Yangtze River
Authors: Du Yiheng , Berndtsson Ronny , An Dong , Zhang Linus , Yuan Feifei , Hao Zhenchun 
Published: October 2019

AbstractMonthly precipitation data at regular grids of 0.5° × 0.5° derived from observations during June–August 1961–2016 were used to reveal characteristics of large‐scale circulations associated with rainy season precipitation over the source region of the Yangtze River (SRYR). The integrated impact of major influencing circulation patterns was examined by principal component analysis and composites. Results showed that the first rainy season precipitation mode associates with the Southern Oscillation Index (SOI) and the Pacific Decadal Oscillation (PDO), explaining 64% of spatial and temporal rainy season precipitation variance in the region. Composites of precipitation pattern under different phases of SOI and PDO revealed that the effect of PDO on precipitation varies with the SOI phase. When in phase with the SOI, PDO‐induced precipitation anomalies are magnified. When out‐of‐phase, anomalies weaken or even disappear. Composites of moisture flux patterns show that large‐scale atmospheric circulation affects the strength of westerlies that transport moisture to the study area and formation of convergence. In coming decades, the PDO is likely to continue in a negative phase with La Niña (positive SOI) events, implying more precipitation during the rainy season. Consequently, this knowledge can be used to improve decision making regarding water supply and flood risk management in the SRYR.
Observed and projected intra‐seasonal variability of Australian monsoon rainfall
Authors: Moise Aurel , Smith Ian , Brown Josephine R. , Colman Robert , Narsey Sugata 
Published: October 2019

AbstractIndices derived from daily rainfall time series are used to measure “burst” features of the northern Australia monsoon, corresponding to one or more days of heavy rainfall. These indices include number of burst days, numbers and durations of burst events, and average intensity. The results using observational data show how these features can vary from one year to the next, and how they can vary from the station scale (Darwin) to the regional scale (northern Australia). The results from Coupled Model Intercomparison Project Phase 5 (CMIP5) climate model simulations under both historical and future greenhouse gas conditions have also been analysed and indicate how well models can capture these features and how they might change by the end of the 21st century under a high emissions scenario. While most models provide a reasonable simulation of present‐day burst features, there is little consensus for a significant change to seasonal rainfall totals when looking at the full CMIP5 ensemble. A subset of models with detectable skills with respect to the Madden‐Julian Oscillation shows evidence for an increase in the seasonal total rainfall amount and most other monsoon metrics, except a slight decrease in the number of burst events. This is consistent with a basic thermodynamic response to warming and consistent with findings elsewhere. However, the Australian monsoon is strongly influenced by the large‐scale circulation and there remains some doubt about whether we can confidently diagnose all the changes to monsoon bursts that could occur given the limited ability of many of the current generation of models to simulate tropical cyclones, the Madden‐Julian Oscillation and other relevant features.