bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fetal inheritance of GP*Mur causing severe HDFN in an unrecognized case of maternal alloimmunization
Authors: Mallari Rose A. , Chan Ada , Powers Richard J. , Pandipati Santosh , Bensing Kathleen M. , Biese Danielle , Denomme Gregory A. 
Published: February 2020

BACKGROUNDThe clinical and laboratory features of hemolytic disease of the newborn can be challenging to diagnose during pregnancy in the apparent absence of a blood group antibody. Low‐frequency antibodies go undetected due to the lack of appropriate antigen‐positive reagent red blood cells (RBCs).CASE REPORTA pregnant woman of Southeast Asian descent was referred to a maternal‐fetal medicine outpatient clinic due to a complicated obstetric history and a negative antibody screen. This initial visit at 29 weeks and 0 days’ gestational age (GA) was unremarkable. A hydropic infant, born at 29 weeks and 5 days’ GA, succumbed on the seventh day of life. Comprehensive laboratory testing was performed after birth. The hospital blood bank performed a maternal antibody identification. Direct antiglobulin test was performed on the cord blood. A reference laboratory confirmed an anti‐Mia, performed paternal Mia phenotyping, and identified a hybrid glycophorin B‐A‐B GP*Mur allele.DISCUSSIONMaternal alloimmunization to low‐frequency antigens remains a challenge. Southeast Asians make up a significant percentage in some US locations. Worldwide reports on the frequency of maternal alloimmunization of the MNS system can be used to guide the use of specific reagent RBCs for testing. Such strategies rely on the identification of blood donor units for reagent manufacture and use in perinatal antibody screens.CONCLUSIONThe incidence of Mia and related antibodies is significant among Southeast Asians. In North America, prenatal antibody screening cells are not routinely chosen to match this population. The clinical and societal implications are discussed.
Prospective evaluation of the influence of sampling method on bacterial culture results and antimicrobial selection in 52 dogs with infected wounds
Authors: Concannon Timothy M. , Kidd Linda , Osmond Christian , Dong Fanglong , Griffon Dominique 
Published: February 2020

AbstractObjectiveTo determine the influence of sampling methods on culture results and selection of antimicrobials for treating infected wounds in dogs.DesignProspective study from January to July 2016.SettingThree private multispecialty referral centers.AnimalsFifty‐two client‐owned dogs with infected wounds.InterventionsEach wound was sampled for culture by 3 methods: swabbing prior to preparation (dirty swabs), swabbing after debridement and sterile lavage (clean swabs), and biopsy. Bacterial species and phenotypes were compared. Three clinicians unaware of patient, wound, and sampling information selected antimicrobial drugs based on culture and sensitivity reports. Antimicrobials were divided into class I, II, or III based on established guidelines. The number, highest class of antimicrobial chosen, and inter‐investigator agreement were examined.Measurements and Main ResultsIdentical populations of bacteria were isolated for all 3 sampling techniques in only 31% of wounds. Significantly fewer bacterial species were isolated from biopsy samples (1.87 bacterial species per wound ± 1.14) than from clean swab samples (2.29 ± 1.18; P = 0.009) but not dirty swab samples (2.29 ± 1.29; P = 0.06). The recovery frequency for gram‐positive bacteria was lower for biopsy compared to either swabbing technique (P = 0.001 for both comparisons). No difference was observed between clean and dirty swabbing techniques for any parameter examined. Sampling technique did not affect the proportion of wounds with anaerobic, gram‐negative, or multi‐drug resistant bacteria. The number (P = 0.28) and highest class of antimicrobial (P = 0.9) selected per wound did not differ between the 3 sampling techniques (P = 0.28). Clinician agreement was 83–90% depending on sampling technique.ConclusionAlthough there were some differences in bacteria isolated from biopsy samples compared to swab samples from infected wounds, technique did not influence the number and highest class of antimicrobial selected by clinicians. Wound debridement prior to sampling by swabbing did not alter the number or type of bacteria isolated, nor the number or the highest class of antimicrobial selected by clinicians.
Evidence that distinct human primary motor cortex circuits control discrete and rhythmic movements
Authors: Wiegel Patrick , Kurz Alexander , Leukel Christian 
Published: February 2020

Key points
Discrete and rhythmic dynamics are inherent components of (human) movements.
We provide evidence that distinct human motor cortex circuits contribute to discrete and rhythmic movements. Excitability of supragranular layer circuits of the human motor cortex was higher during discrete movements than during rhythmic movements. Conversely, more complex corticospinal circuits showed higher excitability during rhythmic movements than during discrete movements. No task‐specific differences existed for corticospinal output neurons at infragranular layers.
The excitability differences were found to be time(phase)‐specific and could not be explained by the kinematic properties of the movements.
The same task‐specific differences were found between the last cycle of a rhythmic movement period and ongoing rhythmic movements.
AbstractHuman actions entail discrete and rhythmic movements (DM and RM, respectively). Recent insights from human and animal studies indicate different neural control mechanisms for DM and RM, emphasizing the intrinsic nature of the task. However, how distinct human motor cortex circuits contribute to these movements remains largely unknown. In the present study, we tested distinct primary motor cortex and corticospinal circuits and proposed that they show differential excitability between DM and RM. Human subjects performed either 1) DM or 2) RM using their right wrist. We applied an advanced electrophysiological approach involving transcranial magnetic stimulation and peripheral nerve stimulation to test the excitability of the neural circuits. Probing was performed at different movement phases: movement initiation (MI, 20 ms after EMG onset) and movement execution (ME, 200 ms after EMG onset) of the wrist flexion. At MI, excitability at supragranular layers was significantly higher in DM than in RM. Conversely, excitability of more complex corticospinal circuits was significantly lower in DM than RM at ME. No task‐specific differences were found for direct corticospinal output neurons at infragranular layers. The neural differences could not be explained by the kinematic properties of the movements and also existed between ongoing RM and the last cycle of RM. Our results therefore strengthen the hypothesis that different neural control mechanisms engage in DM and RM.
From Scan Strategy to Melt Pool Prediction: A Neighboring-Effect Modeling Method
Authors: Yang Zhuo , Lu Yan , Yeung Ho , Krishnamurty Sundar 
Published: February 2020

Abstract
The quality of additive manufacturing (AM) built parts is highly correlated to the melt pool characteristics. Hence, melt pool monitoring and control can potentially improve the AM part quality. This paper presents a neighboring-effect modeling method (NBEM) that uses a scan strategy to predict melt pool size. The prediction model can further assist in scan strategy optimization and real-time process control. The structure of the proposed model is formulated based on the physical principles of melt pool formation, while experimental data are used to identify the optimal coefficients. Compared to the traditional power-velocity prediction models, the NBEM model introduces the cumulative neighboring-effect factors as additional input variables. These factors represent the neighborhood impact of scan path on the focal point melt pool formation from time and distance perspective. Two experiments use different scan strategies to collect in situ measurements of the melt pool size for model construction and validation. By introducing the neighboring-effect factors, the global normalized root-mean-square Error (NRMSE) is improved from around 0.10 to 0.08. More importantly, the local NRMSE of irregular melt pool area prediction is improved to around 0.15 for more than 50% improvement. The case studies verify that the proposed method can predict the melt pool variations by seamlessly integrating scan strategy considerations.
Psychiatric adverse drug reactions in the paediatric population
Authors: Ekhart Corine , Vries Tjalling de , Hunsel Florence van 
Published: February 2020

ObjectiveDue to lack of information on drug use in children, many drugs are used off-label in paediatrics. Increased knowledge of adverse drug reactions (ADRs) would enable a better risk–benefit analysis. Our aim was to characterise drugs causing psychiatric ADRs in children by conducting a descriptive study based on pharmacovigilance reports.DesignReports submitted to the Netherlands Pharmacovigilance Centre Lareb from 2003 to 2016 were used to investigate drugs causing psychiatric ADRs in the Dutch paediatric population. These data were corrected for drug utilisation in order to correct the number of reports for the number of users of a drug.Main outcome measuresORs were calculated as a measure of disproportionality for drug–ADR associations for three different age groups. Significant drug–ADR associations were checked if it was labelled in the product information.ResultsLareb received 918 reports of psychiatric ADRs, which constitute 15% of the reports of ADRs in children. Drugs used for the treatment of ADHD (methylphenidate and atomoxetine) and drugs used for the treatment of asthma (montelukast and fluticasone) were the most frequently reported. However, psychiatric ADRs were also reported for less often prescribed medications such as oxybutynin and isotretinoin.ConclusionsReal-world data on psychiatric ADRs in the Dutch paediatric population show a consistent pattern with what is known from drug labels and the literature. Reports of psychiatric ADRs should be taken seriously because of the impact on medication adherence and the well-being of the child and its family.
Glycyrrhizic Acid Modulates Apoptosis through Extrinsic/Intrinsic Pathways and Inhibits Protein Kinase B- and Extracellular Signal-Regulated Kinase-Mediated Metastatic Potential in Hepatocellular CarcinomaIn VitroandIn Vivo
Authors: Tsai Jai-Jen , Pan Po-Jung , Hsu Fei-Ting , Chung Jing-Gung , Chiang I-Tsang 
Published: February 2020

A previous study presented that glycyrrhizic acid as the hepatoprotective agent inhibits total parenteral nutrition-associated acute liver injury in rats. However, the anticancer effect and mechanism of glycyrrhizic acid in human hepatocellular carcinoma (HCC) is ambiguous. The purpose of the present study was to investigate the effect of glycyrrhizic acid on apoptosis dysregulation and metastatic potential in HCC in vitro and in vivo. Both SK-Hep1 and Hep3B cells were treated with different concentrations of glycyrrhizic acid for 24 or 48[Formula: see text]h. SK-Hep1/luc2 tumor-bearing mice were treated with vehicle or glycyrrhizic acid (50[Formula: see text]mg/kg/day by intraperitoneal injection) for 7 days. Tumor cells growth, apoptotic, and metastatic signaling transduction were evaluated by using MTT assay, digital caliper, bioluminescence imaging (BLI), flow cytometry, western blotting assay, and immunohistochemistry (IHC) staining. The results demonstrated glycyrrhizic acid significantly inhibits tumor cell growth, cell invasion, and expression of AKT (Ser473), extracellular-signal-regulated kinase (ERK), epidermal growth factor receptor (EGFR) phosphorylation, anti-apoptotic and metastatic proteins in HCC in vitro and in vivo. Glycyrrhizic acid also significantly triggered apoptosis and extrinsic/intrinsic apoptotic signaling transduction. In addition, PD98059 (ERK inhibitor) and LY294002 (AKT inhibitor) obviously reduced cell invasion and expression of metastasis-associated proteins. Taken together, these results indicated that glycyrrhizic acid induces apoptosis through extrinsic/intrinsic apoptotic signaling pathways and diminishes EGFR/AKT/ERK-modulated metastatic potential in HCC in vitro and in vivo.
Blocking SHH/Patched Interaction Triggers Tumor Growth Inhibition through Patched-Induced Apoptosis
Authors: Bissey Pierre-Antoine , Mathot Pauline , Guix Catherine , Jasmin Mélissa , Goddard Isabelle , Costechareyre Clélia , Gadot Nicolas , Delcros Jean-Guy , Mali Sachitanand M. , Fasan Rudi , Arrigo André-Patrick , Dante Robert , Ichim Gabriel , Mehlen Patrick , Fombonne Joanna 
Published: February 2020

Abstract

The Sonic Hedgehog (SHH) pathway plays a key role in cancer. Alterations of SHH canonical signaling, causally linked to tumor progression, have become rational targets for cancer therapy. However, Smoothened (SMO) inhibitors have failed to show clinical benefit in patients with cancers displaying SHH autocrine/paracrine expression. We reported earlier that the SHH receptor Patched (PTCH) is a dependence receptor that triggers apoptosis in the absence of SHH through a pathway that differs from the canonical one, thus generating a state of dependence on SHH for survival. Here, we propose a dual function for SHH: its binding to PTCH not only activates the SHH canonical pathway but also blocks PTCH-induced apoptosis. Eighty percent, 64%, and 8% of human colon, pancreatic, and lung cancer cells, respectively, overexpressed SHH at transcriptional and protein levels. In addition, SHH-overexpressing cells expressed all the effectors of the PTCH-induced apoptotic pathway. Although the canonical pathway remained unchanged, autocrine SHH interference in colon, pancreatic, and lung cell lines triggered cell death through PTCH proapoptotic signaling. In vivo, SHH interference in colon cancer cell lines decreased primary tumor growth and metastasis. Therefore, the antitumor effect associated to SHH deprivation, usually thought to be a consequence of the inactivation of the canonical SHH pathway, is, at least in part, because of the engagement of PTCH proapoptotic activity. Together, these data strongly suggest that therapeutic strategies based on the disruption of SHH/PTCH interaction in SHH-overexpressing cancers should be explored.

Significance:
Sonic Hedgehog–overexpressing tumors express PTCH-induced cell death effectors, suggesting that this death signaling could be activated as an antitumor strategy.
Blockade of DC-SIGN+ Tumor-Associated Macrophages Reactivates Antitumor Immunity and Improves Immunotherapy in Muscle-Invasive Bladder Cancer
Authors: Hu Baoying , Wang Zewei , Zeng Han , Qi Yangyang , Chen Yifan , Wang Tao , Wang Jiajun , Chang Yuan , Bai Qi , Xia Yu , Wang Yiwei , Liu Li , Zhu Yu , Dai Bo , Guo Jianming , Xu Le , Zhang Weijuan , Xu Jiejie 
Published: February 2020

AbstractTumor-associated macrophages (TAM) play an indispensable role in the modulation of the cancer immune microenvironment. Despite the fact that TAMs may exert both antitumor and protumor activities, the molecular mechanisms involved remain poorly understood. Here, we characterized a subpopulation of TAMs expressing dendritic cell–specific C-type lectin (DC-SIGN) and investigated its relevance to the prognosis and immune microenvironment of muscle-invasive bladder cancer (MIBC). DC-SIGN+ TAMs were abundant in a significant proportion of human MIBC specimens. High levels of DC-SIGN+ TAMs were associated with dismal prognosis and unresponsiveness to adjuvant chemotherapy in MIBC. Notably, multiple anti-inflammatory cytokines were enriched in DC-SIGN+ TAMs. RNA-seq analysis revealed that multiple M2-like signaling pathways were significantly upregulated in DC-SIGN+ TAMs. High infiltration of DC-SIGN+ TAMs was associated with CD8+ T-cell tolerance in MIBC. Moreover, abrogating DC-SIGN function using a neutralizing antibody led to impaired expression of anti-inflammatory cytokines and augmented PD-1 inhibitor pembrolizumab-mediated cytotoxic effects of CD8+T cells toward MIBC cells. In summary, these results suggest that DC-SIGN+ TAM infiltration is closely linked to a protumor immune microenvironment and may serve as a promising therapeutic target in the immunotherapy of MIBC.Significance:DC-SIGN+ TAMs have an immunosuppressive and tumor-promoting function and may serve as a prognostic indicator and therapeutic target in MIBC.
Sudden Recanalization
Authors: García-Tornel Álvaro , Rubiera Marta , Requena Manuel , Muchada Marian , Pagola Jorge , Rodriguez-Luna David , Deck Matias , Juega Jesus , Rodríguez-Villatoro Noelia , Boned Sandra , Olivé-Gadea Marta , Tomasello Alejandro , Piñana Carlos , Hernández David , Molina Carlos A. , Ribo Marc 
Published: February 2020

Background and Purpose—
First pass (FP) recanalization has been shown to be a predictor of favorable outcome in endovascular treatment of stroke. The reasons why FP recanalization leads to better outcome as compared with multiple passes (MP) are unknown. We aim to investigate the recanalization pattern and its relationship with outcome.

Methods—
Six hundred nine consecutive patients underwent endovascular treatment. Recanalization was defined as modified Thrombolysis in Cerebral Infarction score 2B-3. Favorable outcome was defined as modified Rankin Scale score of 0 to 2 at 90 days. Sudden recanalization (SR) was considered when modified Thrombolysis in Cerebral Infarction score varied from 0-1 to 2B-3 in a single pass. Progressive recanalization (PR) was considered if modified Thrombolysis in Cerebral Infarction score 2A was achieved at an interim pass before achieving recanalization. Patients were also categorized as recanalizers at FP, MP, or nonrecanalizers.

Results—

Five hundred nine (83.9%) patients achieved recanalization. SR was achieved in 378 (62.1%) patients; 280 (46%) were FP-SR, and 98 (16.1%) were MP-SR. MP-PR was achieved in 131 (21.5%) patients. Rates of favorable outcome were similar between patients with FP-SR (57.5%) and MP-SR (57.1%; odds ratio [OR], 0.9 [CI, 0.53–1.54];
P
=0.7) but lower in MP-PR (29.8%; OR, 3.33 [CI, 1.71–5.63];
P
<0.01). Patients with MP-PR had better outcome than nonrecanalizer (17%; OR, 2.93 [CI, 1.42–6.15];
P
<0.01). In univariate analysis, both FP recanalization (OR, 1.91 [CI, 1.31–2.72];
P
<0.01) and SR (OR, 3.19 [CI, 2.12–4.95];
P
<0.01) were associated with favorable outcome. However multivariate analysis adjusting for FP recanalization showed that the only procedural predictor of favorable outcome was SR (OR, 3.12 [CI, 1.91–5.16];
P
<0.01). Higher number of passes were associated with worse outcome in patients with recanalization (OR, 0.75 [CI, 0.66–0.85];
P
<0.01) but not in those with SR (OR, 0.94 [CI, 0.59–1.61];
P
=0.937).

Conclusions—
SR strongly predicts favorable outcome in patients undergoing endovascular treatment, even after previous unsuccessful attempts. PR may reflect clot fragmentation and embolization due to more friable composition, leading to worse outcomes. Prospective studies with independent assessment of recanalization pattern should validate these results.
Impact of preventive screening and lifestyle interventions in women with a history of preeclampsia: A micro-simulation study
Authors: Lagerweij GR , Brouwers L , De Wit GA , Moons KGM , Benschop L , Maas AHEM , Franx A , Wermer MJH , Roeters van Lennep JE , van Rijn BB , Koffijberg H 
Published: February 2020

Background Preeclampsia is a female-specific risk factor for the development of future cardiovascular disease. Whether early preventive cardiovascular disease risk screenings combined with risk-based lifestyle interventions in women with previous preeclampsia are beneficial and cost-effective is unknown. Methods A micro-simulation model was developed to assess the life-long impact of preventive cardiovascular screening strategies initiated after women experienced preeclampsia during pregnancy. Screening was started at the age of 30 or 40 years and repeated every five years. Data (initial and follow-up) from women with a history of preeclampsia was used to calculate 10-year cardiovascular disease risk estimates according to Framingham Risk Score. An absolute risk threshold of 2% was evaluated for treatment selection, i.e. lifestyle interventions (e.g. increasing physical activity). Screening benefits were assessed in terms of costs and quality-adjusted-life-years, and incremental cost-effectiveness ratios compared with no screening. Results Expected health outcomes for no screening are 27.35 quality-adjusted-life-years and increase to 27.43 quality-adjusted-life-years (screening at 30 years with 2% threshold). The expected costs for no screening are €9426 and around €13,881 for screening at 30 years (for a 2% threshold). Preventive screening at 40 years with a 2% threshold has the most favourable incremental cost-effectiveness ratio, i.e. €34,996/quality-adjusted-life-year, compared with other screening scenarios and no screening. Conclusions Early cardiovascular disease risk screening followed by risk-based lifestyle interventions may lead to small long-term health benefits in women with a history of preeclampsia. However, the cost-effectiveness of a lifelong cardiovascular prevention programme starting early after preeclampsia with risk-based lifestyle advice alone is relatively unfavourable. A combination of risk-based lifestyle advice plus medical therapy may be more beneficial.