bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rates and intensity of freeze–thaw cycles affect nitrous oxide and carbon dioxide emissions from agricultural soils
Authors: Pelster David E. , Chantigny Martin H. , Rochette Philippe , Bertrand Normand , Angers Denis A. , Zebarth Bernie J. , Goyer Claudia 
Published: September 2019

In cool temperate regions, large emissions of nitrous oxide (N2O), an important greenhouse and ozone-depleting gas, have been observed during freeze–thaw (FT) cycles. However, it is unclear how freezing and thawing rates, freezing intensity, and freezing duration influence N2O emissions. We used a laboratory incubation to measure N2O emissions from two soils (sandy loam, silty clay) undergoing a single FT cycle of various freezing and thawing rates [rapid (0.5 °C h−1) vs. slow (0.017 °C h−1)], freezing intensity (−1 vs. −3 °C), and freezing duration (24 vs. 48 freezing degree-days). In general, soil carbon dioxide fluxes during freezing were highest when soils were frozen slowly at −1 °C, whereas fluxes after thawing were highest from the soils frozen and thawed rapidly at −3 °C. Soil N2O emissions during both the freezing and thawing periods were greatest in the soils exposed to rapid freezing to −3 °C, intermediate under rapid freezing to −1 °C and slow freezing to −3 °C, and smallest under slow freezing to −1 °C and the control treatment (constant +1 °C). The similar N2O emissions between the unfrozen control and the slowly frozen −1 °C treatment was unexpected as previous field studies with similar freezing rates and temperatures still experienced high N2O emissions during thaw. This suggests that the physical disruptions caused by freezing and thawing of the surface soil are not the primary driver of FT-induced N2O emissions under field conditions.
Electron affinity and ionization potential of 2D octagon-structure nitrogen under strain
Authors: He Chunshan , Wang Weiliang 
Published: September 2019

We studied the electron affinity (EA) and ionization potential (IP) of 2D octagon-structure nitrogen with density functional theory (DFT). The monolayer, bilayer, trilayer and tetralayer configurations of this material are investigated. We discussed the effect of strain and the effect on number of layers. The variation of EA and IP is found to be larger than 0.6 eV under strain less than 10%. The IPs decrease with number of layers while EAs are almost independent on number of layers. The difference of IP is larger than 0.4 eV between monolayer and tetralayer structures.
MiR-21 in Substance P-induced exosomes promotes cell proliferation and migration in human colonic epithelial cells
Authors: Bakirtzi Kyriaki , Man Law Ivy Ka , Fang Kai , Iliopoulos Dimitrios , Pothoulakis Charalabos 
Published: September 2019

Exosomes are cellular vesicles involved in intercellular communication via their specialized molecular cargo, such as miRNAs. Substance P (SP), a neuropeptide/hormone, and its high-affinity receptor, NK-1R, are highly expressed during colonic inflammation. Our previous studies show that SP/NK-1R signaling stimulates differential miRNA expression and promotes colonic epithelial cell proliferation. In this study, we examined whether SP/NK-1R signaling regulates exosome biogenesis and exosome-miRNA cargo sorting. Moreover, we examined the role of SP/NK-1R signaling in exosome-regulated cell proliferation and migration. Exosomes produced by human colonic NCM460 epithelial cells overexpressing NK-1R (NCM460-NK1R) were isolated from culture media. Exosome abundance and uptake were assessed by Western blot analysis (abundance) and Exo-Green fluorescence microscopy (abundance and uptake). Cargo-miRNA levels were assessed by RT-PCR. Cell proliferation and migration were assessed using xCELLigence technology. Colonic epithelial exosomes were isolated from mice pretreated with SP for 3 days. Cell proliferation in vivo was assessed by Ki-67 staining. SP/NK-1R signaling in human colonic epithelial cells (in vitro) and mouse colons (in vivo) increased 1) exosome production, 2) the level of fluorescence in NCM460s treated with Exo-Green-labeled exosomes, and 3) the level of miR-21 in exosome cargo. Moreover, our results showed that SP/NK-1R-induced cell proliferation and migration are at least in part dependent on intercellular communication via exosomal miR-21 in vitro and in vivo. Our results demonstrate that SP/NK-1R signaling regulates exosome biogenesis and induces its miR-21 cargo sorting. Moreover, exosomal miR-21 promotes proliferation and migration of target cells. NEW & NOTEWORTHY Substance P signaling regulates exosome production in human colonic epithelial cells and colonic crypts in wild-type mice. MiR-21 is selectively sorted into exosomes induced by Substance P stimulation and promotes cell proliferation and migration in human colonocytes and mouse colonic crypts.
Metformin alters the duodenal microbiome and decreases the incidence of pancreatic ductal adenocarcinoma promoted by diet-induced obesity
Authors: Dong Tien S. , Chang Hui-Hua , Hauer Meg , Lagishetty Venu , Katzka William , Rozengurt Enrique , Jacobs Jonathan P. , Eibl Guido 
Published: September 2019

Pancreatic ductal adenocarcinoma (PDAC)’s growing incidence has been linked to the rise in obesity and type 2 diabetes mellitus. In previous work, we have shown that metformin can prevent the increased incidence of PDAC in a KrasG12D mouse model subjected to a diet high in fat and calories (HFCD). One potential way that metformin can affect the host is through alterations in the gut microbiome. Therefore, we investigated microbial associations with PDAC development and metformin use in the same mouse model. Lox-Stop-Lox Kras G12D/+ (LSL-Kras G12D/+); p48-Cre (KC) mice were given control diet, HFCD, or HFCD with 5 mg/mL metformin in drinking water for 3 mo. At the end of the 3 mo, 16S rRNA sequencing was performed to characterize microbiome composition of duodenal mucosal, duodenal luminal, and cecal luminal samples. KC mice on an HFCD demonstrated depletion of intact acini and formation of advanced pancreatic intraepithelial neoplasia. This effect was completely abrogated by metformin treatment. HFCD was associated with significant changes in microbial composition and diversity in the duodenal mucosa and lumen, much of which was prevented by metformin. In particular, Clostridium sensu stricto was negatively correlated with percent intact acini and seemed to be inhibited by the addition of metformin while on an HFCD. Administration of metformin eliminated PDAC formation in KC mice. This change was associated with significant microbial changes in both the mucosal and luminal microbiome of the duodenum. This suggests that the microbiome may be a potential mediator of the chemopreventive effects of metformin. NEW & NOTEWORTHY Pancreatic ductal adenocarcinoma (PDAC)’s growing incidence has been linked to the rise in obesity and type 2 diabetes mellitus. Administration of metformin eliminated PDAC formation in KC mice with diet-induced obesity. This change was associated with significant microbial changes in both the mucosal and luminal microbiome of the duodenum. This suggests that the microbiome may be a potential mediator of the chemopreventive effects of metformin.
Enteric neuron density correlates with clinical features of severe gut dysmotility
Authors: Boschetti Elisa , Malagelada Carolina , Accarino Anna , Malagelada Juan R. , Cogliandro Rosanna F. , Gori Alessandra , Bonora Elena , Giancola Fiorella , Bianco Francesca , Tugnoli Vitaliano , Clavenzani Paolo , Azpiroz Fernando , Stanghellini Vincenzo , Sternini Catia , De Giorgio Roberto 
Published: September 2019

Gastrointestinal (GI) symptoms can originate from severe dysmotility due to enteric neuropathies. Current methods used to demonstrate enteric neuropathies are based mainly on classic qualitative histopathological/immunohistochemical evaluation. This study was designed to identify an objective morphometric method for paraffin-embedded tissue samples to quantify the interganglionic distance between neighboring myenteric ganglia immunoreactive for neuron-specific enolase, as well as the number of myenteric and submucosal neuronal cell bodies/ganglion in jejunal specimens of patients with severe GI dysmotility. Jejunal full-thickness biopsies were collected from 32 patients (22 females; 16–77 yr) with well-characterized severe dysmotility and 8 controls (4 females; 47–73 yr). A symptom questionnaire was filled before surgery. Mann-Whitney U test, Kruskal-Wallis coupled with Dunn’s posttest and nonparametric linear regression tests were used for analyzing morphometric data and clinical correlations, respectively. Compared with controls, patients with severe dysmotility exhibited a significant increase in myenteric interganglionic distance ( P = 0.0005) along with a decrease in the number of myenteric ( P < 0.00001) and submucosal ( P < 0.0004) neurons. A 50% reduction in the number of submucosal and myenteric neurons correlated with an increased interganglionic distance and severity of dysmotility. Our study proposes a relatively simple tool that can be applied for quantitative evaluation of paraffin sections from patients with severe dysmotility. The finding of an increased interganglionic distance may aid diagnosis and limit the direct quantitative analysis of neurons per ganglion in patients with an interganglionic distance within the control range. NEW & NOTEWORTHY Enteric neuropathies are challenging conditions characterized by a severe impairment of gut physiology, including motility. An accurate, unambiguous assessment of enteric neurons provided by quantitative analysis of routine paraffin sections may help to define neuropathy-related gut dysmotility. We showed that patients with severe gut dysmotility exhibited an increased interganglionic distance associated with a decreased number of myenteric and submucosal neurons, which correlated with symptoms and clinical manifestations of deranged intestinal motility.
Early suppression of peripheral mononuclear blood cells in sepsis in response to stimulation with cytomegalovirus, OKT3, and pokeweed mitogen
Authors: Malewicz N. M. , Walstein K. , Heine T. , Engler A. , Bick A. , Cox L. , Dötsch A. , Westendorf A. M. , Horn P. A. , Lindemann M. , Peters J. , Schäfer S. T. 
Published: September 2019

Critically ill patients are at risk for sepsis, and immunosuppressive mechanisms may prevail. Whether functional tests are helpful to detect immune alterations is largely unknown. Therefore, we tested the hypotheses that reactivity of peripheral blood mononuclear cells (PBMCs) to secrete interferon-γ (IFNγ) following stimulation in vitro is decreased in patients with early sepsis compared with postoperative patients. IFNγ secretion [enzyme-linked immunospot (ELISpot)] in response to stimulation with cytomegalovirus (CMV), pokeweed mitogen (PWM), muromonab-anti-CD3 (OKT3), and human leukocyte antigen (HLA)-DRA-mRNA expression and serum cytokine concentrations were repeatedly [ days 1, 3, 5, and 7 after intensive care unit (ICU) admission] determined in patients with sepsis ( n = 7) and patients undergoing major abdominal surgery (radical prostatectomy, cystectomy, n = 10). In a second cohort, HLA-DRA expression was assessed in 80 patients with sepsis, 30 postoperative patients, and 44 healthy volunteers (German clinical trials database no. 00007694). In patients with sepsis, IFNγ secretion (ELISpot) was decreased compared with controls after stimulation with CMV ( P = 0.01), OKT3 ( P = 0.02), and PWM ( P = 0.02 on day 5), whereas unstimulated IFNγ secretion did not differ. HLA-DRA expression was also significantly decreased in patients with sepsis at all time points ( P = 0.004) compared with postoperative surgical patients, a finding confirmed in the larger cohort. Reactivity of PBMCs to stimulation with CMV, PWM, and OKT3 as well as HLA-DRA expression was already decreased upon ICU admission in patients with sepsis when compared with postoperative controls, suggesting early depression of acquired immunity. ELISpot assays may help to clinically characterize the time course of immunocompetence in patients with sepsis. NEW & NOTEWORTHY We observed suppression of reactivity to stimulation with cytomegalovirus, muromonab-anti-CD3, and pokeweed mitogen in mononuclear blood cells of patients with early sepsis when compared with postoperative controls. Thus, there is early depression of acquired immunity in sepsis. Enzyme-linked immunospot assays may help to characterize immunocompetence in patients with sepsis.
Torque gains and neural adaptations following low-intensity motor nerve electrical stimulation training
Authors: Vitry Florian , Martin Alain , Papaiordanidou Maria 
Published: September 2019

The purpose of the study was to assess neural adaptations of the plantar-flexors induced by an electrical stimulation training applied over the motor nerve at low intensity using two different stimulation frequencies. Thirty subjects were randomly assigned into 3 groups: 20 Hz, 100 Hz, and control group. The training consisted of 15 sessions of 25 stimulation trains applied over the tibial nerve and delivered at an intensity evoking 10% maximal voluntary isometric contraction (MVIC). Before and after training, MVIC was assessed and neural adaptations were evaluated by the voluntary activation level (VAL) and the V-wave (normalized by the superimposed muscle compound action potential, V/MSUP). H-reflex and motor-evoked potential (MEP) recorded during MVIC were studied to assess spinal and corticospinal excitabilities [i.e., maximal H-reflex during maximal voluntary isometric contraction (HSUP)/MSUPand maximal motor-evoked potential during maximal voluntary isometric contraction (MEPSUP)/MSUP]. MVIC significantly increased after training only for the two training groups ( P = 0.017). This increase was accompanied by a significant increase of VAL only for these groups ( P = 0.014), whereas statistical analysis revealed a time effect for V/MSUP( P = 0.022). HSUP/MSUPand MEPSUP/MSUPwere significantly increased at post conditions only for the 100 Hz group ( P = 0.021 and P = 0.029). Results show that low-intensity electrical stimulation training applied over the motor nerve can induce torque gains, accompanied by neural adaptations. Stimulation frequency differentially affected spinal and corticospinal excitabilities, indicating that neural adaptations could have a supraspinal origin for the 20-Hz protocol, whereas spinal and supraspinal mechanisms were implicated in the torque increases after the 100-Hz training.NEW & NOTEWORTHY This study brings new insights into the neurophysiological mechanisms responsible for torque gains after electrical stimulation training using wide pulse duration and low stimulation intensity applied over the motor nerve. Stimulation frequency had a distinct impact on spinal and/or supraspinal origins of the observed neural adaptations. The use of the aforementioned stimulation parameters in rehabilitation settings can be proved beneficial in terms of strength gains while avoiding any serious discomfort because of stimulation.
Breast Cancer in San Francisco: Disentangling Disparities at the Neighborhood Level
Authors: Guan Alice , Lichtensztajn Daphne , Oh Debora , Jain Jennifer , Tao Li , Hiatt Robert A. , Gomez Scarlett Lin , Fejerman Laura 
Published: September 2019

Abstract

Background:
This study uses a novel geographic approach to summarize the distribution of breast cancer in San Francisco and aims to identify the neighborhoods and racial/ethnic groups that are disproportionately affected by this disease.

Methods:
Nine geographic groupings were newly defined on the basis of racial/ethnic composition and neighborhood socioeconomic status. Distribution of breast cancer cases from the Greater Bay Area Cancer Registry in these zones were examined. Multivariable logistic regression models were used to determine neighborhood associations with stage IIB+ breast cancer at diagnosis. Cox proportional hazards regression was used to estimate the hazard ratios for all-cause and breast cancer–specific mortality.

Results:
A total of 5,595 invasive primary breast cancers were diagnosed between January 1, 2006 and December 31, 2015. We found neighborhood and racial/ethnic differences in stage of diagnosis, molecular subtype, survival, and mortality. Patients in the Southeast (Bayview/Hunter's Point) and Northeast (Downtown, Civic Center, Chinatown, Nob Hill, Western Addition) areas were more likely to have stage IIB+ breast cancer at diagnosis, and those in the East (North Beach, Financial District, South of Market, Mission Bay, Potrero Hill) and Southeast were more likely to be diagnosed with triple-negative breast cancers (TNBC). Compared with other racial/ethnic groups, Blacks/African Americans (B/AA) experienced the greatest disparities in breast cancer–related outcomes across geographic areas.

Conclusions:
San Francisco neighborhoods with lower socioeconomic status and larger minority populations experience worse breast cancer outcomes.

Impact:
Our findings, which reveal breast cancer disparities at sub-county geographic levels, have implications for population-level health interventions.
FDA Approval Summary: Tagraxofusp-erzs For Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm
Authors: Jen Emily Y. , Gao Xin , Li Liang , Zhuang Luning , Simpson Natalie E. , Aryal Baikuntha , Wang Rong , Przepiorka Donna , Shen Yuan Li , Leong Ruby , Liu Chao , Sheth Christopher M. , Bowen Steven , Goldberg Kirsten B. , Farrell Ann T. , Blumenthal Gideon M. , Pazdur Richard 
Published: September 2019

Abstract
Tagraxofusp-erzs (Elzonris, Stemline) is a cytotoxin that targets CD123-expressing cells. On December 21, 2018, FDA approved tagraxofusp-erzs for the treatment of blastic plasmacytoid dendritic cell neoplasms (BPDCN) in adult and pediatric patients 2 years and older. Approval was based on the response rate in a single-arm trial, Study STML-401-0114; the pivotal cohort included 13 patients with treatment-naïve BPDCN who received tagraxofusp-erzs monotherapy. The complete response or clinical complete response (CR/CRc) rate in the pivotal cohort was 54% (95% CI: 25%–81%), and the median duration of CR/CRc was not reached with a median follow-up of 11.5 months (range: 0.2–12.7). In a separate exploratory cohort, a CR/CRc was achieved by 2 (13%) patients with R/R BPDCN. Safety was assessed in 94 patients with myeloid neoplasms treated with tagraxofusp-erzs at the approved dose and schedule. The major toxicity was capillary leak syndrome (CLS), which occurred in 55% of patients and was fatal in 2%. Hepatotoxicity and hypersensitivity reactions were reported in 88% and 46% of patients, respectively. Other common (≥30%) adverse reactions were nausea, fatigue, peripheral edema, pyrexia, and weight increase. A high proportion of patients (85%) developed neutralizing antidrug antibodies. Tagraxofusp-erzs is the first FDA-approved treatment for BPDCN.
Feasibility and Safety of Intraoperative Optical Coherence Tomography-Guided Short-Term Posturing Prescription after Macular Hole Surgery
Authors: Lorusso Massimo , Micelli Ferrari Luisa , Cicinelli Maria Vittoria , Nikolopoulou Eleni , Zito Roberta , Bandello Francesco , Querques Giuseppe , Micelli Ferrari Tommaso 
Published: September 2019

<b><i>Purpose:</i></b> To assess closure rate and visual outcome of a court of patients with macular hole (MH) who underwent surgical repair with intraoperative optical coherence tomography (iOCT)-confirmed MH closure and short-term postoperative face-down posturing (FDP). Secondary aim was to assess the correlation between iOCT and postoperative OCT at day 1. <b><i>Methods:</i></b> Retrospective clinical study conducted in the Miulli Hospital Acquaviva delle Fonti (Italy), enrolling patients with idiopathic MH who underwent 25-G pars plana vitrectomy plus internal limiting membrane peeling. During surgery, closure of MH was confirmed by iOCT and short-term FDP (12–24 h, until day-1 visit) was prescribed. All patients had measurement of best-corrected visual acuity (BCVA) and spectral domain-OCT before the surgery and during follow-up (at 1 day, 1 month, 3 months). <b><i>Results:</i></b> Twenty-nine eyes of 29 patients (14 males, 62.1%) were enrolled in the study. MH mean size was 451.7 ± 139.7 µm and baseline BCVA was 0.77 ± 0.26 logarithm of the minimum angle of resolution (LogMAR). MH was confirmed to be closed in 100% of patients intraoperatively (iOCT) and at OCT during early follow-up (1–3 days). Mean time of FDP was 18 ± 2.6 h. At 3 months, MH closure rate was 93%; 2 eyes ­underwent secondary MH repair surgery. Final BCVA was 0.39 ± 0.22 LogMAR (<i>p</i> &#x3c; 0.0001). <b><i>Conclusion:</i></b> iOCT-based confirmation of MH closure could be a safe and useful tool for prescribing short-term FDP after surgery, with high closure rate and no additional complication. The execution of an OCT in the immediate postoperative days could be potentially unnecessary.
Social Status May Interfere in the Prognosis of Frontal Fibrosing Alopecia in Female Patients: An Observational Study
Authors: Papanikou Sofia , Xydeas-Kikemenis Anastasia , Nicolaidou Electra , Chatziioannou Argiro , Rigopoulos Dimitrios , Stratigos Alexandros , Chasapi Vasiliki 
Published: September 2019

<b><i>Introduction:</i></b> Frontal fibrosing alopecia (FFA) is a cicatricial alopecia whose incidence has greatly increased worldwide over the last years. The main purpose of the study was to investigate the possible association of the social status of FFA patients with the prognosis of the disease. <b><i>Methods:</i></b> A total of 100 female patients with FFA, monitored at Andreas Sygros Hospital, Athens, Greece, during the last 3 years, were recruited in this observational study. The age of the women ranged from 29 to 92 years with a mean age of 61.2 years (SD = 10.3); 97% of them were Greek, with skin type II and III. <b><i>Results:</i></b> In total, 46% of the patients were intermediate graduates, and 42% had received tertiary education; 82% were married and 21% had 1 child. The duration of the disease ranged from 0.5 to 20 years with a mean duration of 5.2 years. In 53% of the women, the frontal hairline recession was &#x3c;1 cm, in 26% it was 1–2 cm, and in 15% it was 3–4.99 cm. Overall, 55.6% of patients were professionals, 26% were technicians and associate professionals, 23% were office workers, 9% were service and sales workers, and 13% were at elementary occupations. The severity of the disease was higher in lower-educated patients, who belong to the category of unskilled or with elementary occupation. <b><i>Conclusions:</i></b> Women with high educational level and social status are more likely to be diagnosed earlier, resulting in sufficient therapeutic response.
SUMOylation in Neurodegenerative Diseases
Authors: Princz Andrea , Tavernarakis Nektarios 
Published: September 2019

Posttranslational modifications are ubiquitous regulators of cellular processes. The regulatory role of SUMOylation, the attachment of a small ubiquitin-related modifier to a target protein, has been implicated in fundamental processes like cell division, DNA damage repair, mitochondrial homeostasis, and stress responses. Recently, it is gaining more attention in drug discovery as well. As life expectancy keeps rising, more individuals are at risk for developing age-associated diseases. This not only makes a person’s life uncomfortable, but it also places an economic burden on society. Therefore, finding treatments for age-related diseases is an important issue. Understanding the basic mechanisms in the cell under normal and disease conditions is fundamental for drug discovery. There is an increasing number of reports showing that the ageing process could be influenced by SUMOylation. Similarly, SUMOylation is essential for proper neuronal function. In this review we summarize the latest results regarding the connection between SUMOylation and neurodegenerative diseases. We highlight the significance of specific SUMO target proteins and the importance of SUMO isoform specificity.