bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-1 Blockade Reinvigorates Bone Marrow CD8+ T Cells from Patients with Multiple Myeloma in the Presence of TGFβ Inhibitors
Authors: Kwon Minsuk , Kim Chang Gon , Lee Hoyoung , Cho Hyunsoo , Kim Youngun , Lee Eung Chang , Choi Seong Jin , Park Junsik , Seo In-Ho , Bogen Bjarne , Song Ik-Chan , Jo Deog-Yeon , Kim Jin Seok , Park Su-Hyung , Choi Inhak , Choi Yoon Seok , Shin Eui-Cheol 
Published: January 2020

Abstract

Purpose:
Immune-checkpoint inhibitors have shown therapeutic efficacy in various malignant diseases. However, anti-programmed death (PD)-1 therapy has not shown clinical efficacy in multiple myeloma.

Experimental Design:
Bone marrow (BM) mononuclear cells were obtained from 77 newly diagnosed multiple myeloma patients. We examined the expression of immune-checkpoint receptors in BM CD8+ T cells and their functional restoration by ex vivo treatment with anti–PD-1 and TGFβ inhibitors.

Results:
We confirmed the upregulation of PD-1 and PD-L1 expression in CD8+ T cells and myeloma cells, respectively, from the BM of multiple myeloma patients. PD-1–expressing CD8+ T cells from the BM of multiple myeloma patients coexpressed other checkpoint inhibitory receptors and exhibited a terminally differentiated phenotype. These results were also observed in BM CD8+ T cells specific to myeloma antigens NY-ESO-1 and HM1.24. BM CD8+ T cells from multiple myeloma patients exhibited reduced proliferation and cytokine production upon T-cell receptor stimulation. However, anti–PD-1 did not increase the proliferation of BM CD8+ T cells from multiple myeloma patients, indicating that T-cell exhaustion in multiple myeloma is hardly reversed by PD-1 blockade alone. Intriguingly, anti–PD-1 significantly increased the proliferation of BM CD8+ T cells from multiple myeloma patients in the presence of inhibitors of TGFβ, which was overexpressed by myeloma cells.

Conclusions:
Our findings indicate that combined blockade of PD-1 and TGFβ may be useful for the treatment of multiple myeloma.
A Phase II Study of Cabozantinib and Androgen Ablation in Patients with Hormone-Naïve Metastatic Prostate Cancer
Authors: Corn Paul G. , Zhang Miao , Nogueras-Gonzalez Graciela M. , Xiao Lianchun , Zurita Amado J. , Subudhi Sumit K. , Tu Shi-Ming , Aparicio Ana M. , Coarfa Cristian , Rajapakshe Kimal , Huang Shixia , Navone Nora M. , Lin Sue-Hwa , Wang Guocan , Ramachandran Sumankalai , Titus Mark A. , Panaretakis Theocharis , Gallick Gary E. , Efstathiou Eleni , Troncoso Patricia , Logothetis Christopher 
Published: January 2020

Abstract

Purpose:
Cabozantinib, an oral inhibitor of c-MET/VEGFR2 signaling, improved progression-free survival (mPFS) but not overall survival (OS) in metastatic castrate-resistant prostate cancer. We evaluated cabozantinib plus androgen deprivation therapy (ADT) in hormone-naïve metastatic prostate cancer (HNMPCa).

Patients and Methods:
Patients received ADT plus cabozantinib starting at 60 mg daily. The primary endpoint was castrate-resistant PFS by radiographic criteria, clinical progression, or receipt of additional therapy. Secondary endpoints included OS, safety, radiographic responses, and biomarker modulation.

Results:
Sixty-two patients received treatment. With a median follow-up of 31.2 months, the mPFS was 16.1 months (95% CI, 14.6–22.7 months), and mOS was not reached. Reductions in PSA ≥ 90%, bone-specific alkaline phosphatase ≥ 50%, and urine N-telopeptides ≥ 50% occurred in 83%, 87%, and 86% of evaluable patients, respectively. Responses in bone scan and measurable disease were observed in 81% of and 90% of evaluable patients, respectively. Most common grade 3 adverse events were hypertension (19%), diarrhea (6%), and thromboembolic events (6%), and dose reductions occurred in 85% of patients. Analysis of baseline cytokine and angiogenic factors (CAFs) revealed that higher plasma concentrations of Lumican, CXCL5, CD25, and CD30 were associated with shorter PFS as was high tumor expression of pFGFR1.

Conclusions:
Cabozantinib plus ADT has promising clinical activity in HNMPCa. CAF profiles and tissue markers suggest candidate prognostic and predictive markers of cabozantinib benefit and provide insights for rational therapy combinations.
Matrix-Targeting Immunotherapy Controls Tumor Growth and Spread by Switching Macrophage Phenotype
Authors: Deligne Claire , Murdamoothoo Devadarssen , Gammage Anís N. , Gschwandtner Martha , Erne William , Loustau Thomas , Marzeda Anna M. , Carapito Raphael , Paul Nicodème , Velazquez-Quesada Inés , Mazzier Imogen , Sun Zhen , Orend Gertraud , Midwood Kim S. 
Published: January 2020

Abstract
The interplay between cancer cells and immune cells is a key determinant of tumor survival. Here, we uncovered how tumors exploit the immunomodulatory properties of the extracellular matrix to create a microenvironment that enables their escape from immune surveillance. Using orthotopic grafting of mammary tumor cells in immunocompetent mice and autochthonous models of breast cancer, we discovered how tenascin-C, a matrix molecule absent from most healthy adult tissues but expressed at high levels and associated with poor patient prognosis in many solid cancers, controls the immune status of the tumor microenvironment. We found that, although host-derived tenascin-C promoted immunity via recruitment of proinflammatory, antitumoral macrophages, tumor-derived tenascin-C subverted host defense by polarizing tumor-associated macrophages toward a pathogenic, immune-suppressive phenotype. Therapeutic monoclonal antibodies that blocked tenascin-C activation of Toll-like receptor 4 reversed this phenotypic switch in vitro and reduced tumor growth and lung metastasis in vivo, providing enhanced benefit in combination with anti–PD-L1 over either treatment alone. Combined tenascin-C:macrophage gene-expression signatures delineated a significant survival benefit in people with breast cancer. These data revealed a new approach to targeting tumor-specific macrophage polarization that may be effective in controlling the growth and spread of breast tumors.
Mechanism of Recurrence of Atrial Tachycardia
Authors: Takigawa Masateru , Derval Nicolas , Martin Claire A. , Vlachos Konstantinos , Denis Arnaud , Nakatani Yosuke , Kitamura Takeshi , Cheniti Ghassen , Bourier Felix , Lam Anna , Martin Ruairidh , Frontera Antonio , Thompson Nathaniel , Massoullié Grégoire , Wolf Michael , Escande William , André Clémentine , Zeng Li-jun , Roux Jean-Rodolphe , Duchateau Josselin , Pambrun Thomas , Sacher Frederic , Cochet Hubert , Hocini Mélèze , Haïssaguerre Michel , Jaïs Pierre 
Published: January 2020

Background:
Atrial fibrillation ablation–related atrial tachycardia (AT) is complex and may demonstrate several forms: anatomic macroreentrant AT (AMAT), non-AMAT, and focal AT. We aimed to elucidate the recurrence rate and mechanisms of atrial fibrillation ablation–related AT recurrence.

Methods:
Among 147 patients with ATs treated with the Rhythmia system, 68 (46.3%) had recurrence at mean 4.2 (2.9–11.6) months, and 44 patients received a redo procedure. AT circuits in the first procedure were compared with those in the redo procedure.

Results:

Although mappable ATs were not observed in 7 patients, 68 ATs were observed in 37 patients during the first procedure: perimitral flutter (PMF) in 26 patients, roof-dependent macroreentrant AT (RMAT) in 18, peritricuspid flutter in 10, non-AMAT in 14, and focal AT in 3. During the redo AT ablation procedure, 54 ATs were observed in 41/44 patients: PMF in 24, RMAT in 14, peritricuspid flutter in 1, non-AMAT in 14, and focal AT in 1. Recurrence of PMF and RMAT was observed in 15 of 26 (57.7%) and 8 of 18 (44.4%) patients, respectively, while peritricuspid flutter did not recur. Neither the same focal AT nor the same non-AMAT were observed except in 1 case with septal scar–related biatrial AT. Epicardial structure–related ATs were involved in 18 of 24 (75.0%) patients in PMF, 4 of 14 (28.6%) in RMAT, and 4 of 14 (28.6%) in non-AMAT. Of 21 patients with a circuit including epicardial structures, 6 patients treated with ethanol infusion in the vein of Marshall did not show any AT recurrence, although 8 of 15 (53.3%) treated with radiofrequency showed AT recurrence (
P
=0.04).

Conclusions:
Although high-resolution mapping may lead to correct diagnosis and appropriate ablation in the first procedure, the recurrence rate is still high. The main mechanism of atrial fibrillation ablation–related AT is the recurrence of PMF and RMAT or non-AMAT different from the first procedure. Epicardial structures (eg, coronary sinus/vein of Marshall system) are often involved, and ethanol infusion in the vein of Marshall may be an additional treatment.
Impact of Bariatric Surgery on Atrial Fibrillation Type
Authors: Donnellan Eoin , Wazni Oussama M. , Elshazly Mohamed , Kanj Mohamed , Hussein Ayman A. , Baranowski Bryan , Kochar Arshneel , Trulock Kevin , Aminian Ali , Schauer Philip , Jaber Wael , Saliba Walid I. 
Published: January 2020

Background:
Obesity is an independent risk factor for atrial fibrillation (AF) and is associated with a higher AF burden. Recently, weight loss has been found to be associated with a significant reversal in AF type. Bariatric surgery (BS) is associated with reductions in inflammation, left atrial and ventricular remodeling, sleep apnea, blood pressure, and improved glycemic control, all of which may reduce AF burden. In this study, we sought to determine the impact of BS on AF type.

Methods:

We studied AF type before and after BS in 220 morbidly obese patients (body mass index, ≥40 kg/m
2
). All patients underwent extended outpatient cardiac rhythm monitoring within 12 months of BS and at least 1 year after BS.

Results:

There was a significant reduction in body mass index following BS from 49.7±9 to 37.2±9 kg/m
2
. Weight loss was the greatest in the gastric bypass group with a mean percentage weight loss of 25% compared with 19% in patients who underwent sleeve gastrectomy and 16% following gastric banding (
P
<0.0001). Significant reductions in CRP (C-reactive protein), NT-proBNP (N-terminal pro-B-type natriuretic peptide), HbA1C (glycated hemoglobin), and systolic blood pressure were observed in all 3 groups. Reversal of AF type occurred in 71% of patients following gastric bypass, 56% of patients who underwent sleeve gastrectomy, and 50% of patients following gastric banding (
P
=0.004). On Cox proportional hazards analyses, percentage weight loss was significantly associated with AF reversal (
P
=0.0002).

Conclusions:
BS is associated with significant reductions in weight, inflammatory markers, blood pressure, and AF type, and the beneficial effects appear to be the greatest in those undergoing gastric bypass surgery. This study further exemplifies the importance of weight loss and risk factor modification in AF management.
Economic assessment of nematode biological control agents in a potato production model
Authors: Dyrdahl-Young Ruhiyyih , Cole Emilie , Tornel Marisol Quintanilla , Weldon Richard , DiGennaro Peter 
Published: January 2020

Summary
Nematode parasitism is a yield limiting factor in many cropping systems, including potato production, which can translate into substantial economic losses. These impacted financial returns are simply calculated by subtracting the cost of production from total revenue (yield times the price per yield of potatoes). The production costs can include, but are not limited to, chemical and biological control agents. To assess economic returns associated with different nematode management strategies, we evaluated complete cost estimations for a representative commercial potato farm in central Michigan, USA. Economic returns were calculated using stochastic parameters for two biological control agents (MeloCon and Majestene), six chemical controls (Mocap, Movento, Nimitz, Velum and Vydate), and two soil amendments (poultry and dairy manure). Evaluated costs included stochastic estimations for price per unit weight of potatoes, fuel, labour and production land rent. Yield data from three field trials were used to create empirical distributions. Using yield data and stochastic cost estimations, we generated 500 simulations of net returns per treatment. The top three average returns were obtained from the use of Mocap, Nimitz and poultry manure. Velum, Movento, dairy manure and Vydate also gave returns significantly higher than no treatment at all; however, the biological nematicide, Majestene, showed negative returns. This simple financial model is a crucial layer of analysis on the performance of nematicides that can be adapted to advise growers through Agricultural Extension activities and needs to include the evaluation of biological control agents.
The Fading of Yearnings for Liberation and Passage When the Bet on Love Is Lost
Authors: El-Fakki El-Bashir Abdalla 
Published: January 2020

Abstract
This paper presents a study of the memoirs and letters of Princess Sālima bt. Saʿīd (d. 1922), whose father, Saʿīd b. Sulṭān (d. 1856), was the ruler of Oman and Zanzibar from 1832 to 1856. One hundred and fifty years ago, the princess entered into a relationship with a young German man, Rudolph Ruete. After the princess fell pregnant, putting her in conflict with the stipulations of her Islamic religion, she decided to elope with her lover and to bet on him. The paper argues that the princess was a revolutionary woman in opposition to traditional Zanzibari culture, and that her story highlights clearly the issue of women and the crisis of freedom in Arab and Islamic culture during that time.
The Impact of the 20–50-Day Atmospheric Intraseasonal Oscillation on the Gross Primary Productivity between the Yangtze and Yellow Rivers
Authors: Li Jianying , Kim Jin-Soo , Kug Jong-Seong 
Published: January 2020

AbstractGiven their high carbon uptake, the terrestrial ecosystems in the East Asia summer monsoon (EASM) region play an irreplaceable role in the global carbon cycle. Because the rich vegetation growth over East Asia benefits mainly from the sufficient water supply brought by the EASM, which is characterized by a strong intraseasonal oscillation (ISO), the intraseasonal spatiotemporal variations and underlying drivers of photosynthesis activity over East Asia have been comprehensively investigated using the daily gross primary productivity (GPP) and meteorological data. Strong intraseasonal fluctuations of GPP have been identified over the area between the Yangtze and Yellow Rivers (YYR) with a magnitude of 0.4 gC m−2 day−1. The mean power spectrum suggests that 20–50-day variation is the major component of the intraseasonal GPP anomalies over the YYR during the summers of 1980–2013. The 20–50-day ISO of YYR GPP anomalies is modulated by the local 20–50-day precipitation variation via soil moisture, with precipitation (soil moisture) leading GPP by 10 (7) days. The 20–50-day YYR precipitation anomalies are in turn controlled by tropical ISO signals, particularly the convective activity over the western North Pacific. This leading relationship between the 20–50-day atmospheric ISO and GPP suggests a potential for extended-range predictability of vegetation growth.
Trends in Landfalling Tropical Cyclone–Induced Precipitation over China
Authors: Liu Lu , Wang Yuqing 
Published: January 2020

AbstractIn this study, trends in landfalling tropical cyclone (TC)-induced precipitation over China during 1980–2017 and the involved possible mechanisms are analyzed. Consistent with previous studies, it is found that the total annual TC precipitation shows a distinct spatial distribution with a significant increasing trend in southeastern China but a decreasing trend in southern China. This characteristic is found to be related to the increase in both the annual TC precipitation frequency and the precipitation intensity per TC over southeastern China but to the decrease in the annual TC precipitation frequency over southern China. A noticeable northward shift of total landfalling TC-induced annual precipitation has been identified. It is shown that the precipitation induced by strong TCs (STCs) significantly increased in southern China, whereas that induced by weak TCs (WTCs) increased in southeastern China, with the latter dominating the northward shift of total landfalling TC-induced precipitation over mainland China. The increasing trend of STC-induced precipitation in southern China is found to be closely related to sufficient water vapor supply and the increase in average duration and intensity of STCs after landfall. The increasing trend of WTC-induced precipitation in southeastern China is related to the northward shift of the average landfalling position of WTCs and changes in the environmental conditions that are more favorable for TC maintenance and precipitation.
On PSI Interactions in Internal Gravity Wave Fields and the Decay of Baroclinic Tides
Authors: Olbers Dirk , Pollmann Friederike , Eden Carsten 
Published: January 2020

AbstractBarotropic tidal oscillations over seafloor topography generate baroclinic tides that may be damped in turn via nonlinear triad interactions with internal gravity waves, fueling the ambient wave field. We derive the kinetic equations for this tidal damping and the energy transfer to the ambient wave field and compute damping times and energy transfer rates for the M2 tide and a Garrett–Munk-like ambient wave field. We show that parametric subharmonic instability (PSI) interactions are important, where the tide interacts resonantly with two background waves, each of half the tidal frequency. PSI is restricted to the latitude belt 28.8°N/S and yields under typical conditions damping times of about 20 days for tides with low vertical wavenumber. Damping times decrease with equivalent mode number j roughly as 1/j2. Outside the critical latitudes PSI is not possible, and damping times are from one to two orders of magnitude larger. The energy transfer to the ambient wave field is concentrated at half the tidal frequency ω at all latitudes within the critical latitude belt. Outside, the transfer is much smaller and peaks at ω + f and N. An estimation of the tidal spectral transfer on the global scale is hampered by insufficient knowledge of the baroclinic energy distribution over the vertical modes. Using results from a numerical circulation model with tidal forcing, we find an energy transfer from the tide to the ambient wave field of typically 0.3 TW, about half of what is currently proposed for the conversion of barotropic to baroclinic energy.
Intravenous leiomyomatosis: Case series and review of the literature
Authors: Liu Na , Long Yan , Liu Yun 
Published: January 2020

Background We retrospectively reviewed the data of three patients with intravenous leiomyomatosis (IVL), one of whom had intracardiac leiomyomatosis, and analyzed their clinical symptoms, preoperative assessment findings, operative approaches, and recurrence. Case presentation: The present study describes three cases of IVL extending into the inferior vena cava, even as far as the right atrium and ventricle, and discusses the imaging findings and differential diagnosis of this tumor entity. The three patients, two of whom were diagnosed during the first operation and one of whom had a giant pelvic mass, were surgically treated with complete tumor resection, hysterectomy, and bilateral salpingo-oophorectomy. The pathological examination findings were suggestive of IVL. The duration of time from the first myomectomy or hysterectomy to IVL occurrence ranged from 2 to 18 months. No signs of recurrence were observed during follow-up. Computed tomography and magnetic resonance imaging played a vital role in the diagnostic process and presurgical assessment. Conclusion In clinical practice, IVL should be considered before surgery for a broad ligament myoma or giant pelvic mass. Surgery should always aim for complete tumor excision and include hysterectomy and bilateral salpingo-oophorectomy. Vascular reconstruction computed tomography is a good choice for diagnosis and follow-up.
Daily physical activity is associated with increased sonographically measured bone status during lactation
Authors: Ebina Aoi , Sawa Ryuichi , Kondo Yuki , Murata Shunsuke , Saito Takashi , Isa Tsunenori , Tsuboi Yamato , Torizawa Kohtaroh , Matsuda Naoka , Ono Rei 
Published: January 2020

Objectives: The purpose of this cross-sectional study was to investigate the association between daily physical activity and sonographically measured bone status among women during the lactation period. Methods: Final participants were 152 women 4 months after childbirth. Bone status of the participants was measured using quantitative ultrasonometry of the calcaneus (speed of sound). Daily physical activity was assessed using the Japanese version of International Physical Activity Questionnaire short version. After getting the International Physical Activity Questionnaire results, we classified participants into three categories (low/moderate/high) according to a protocol. Participants categorized into the low group according to the International Physical Activity Questionnaire were considered to be in the low physical activity group and those categorized into the moderate and high groups were considered to be in the moderate to vigorous physical activity group. Results: Speed of sound was significantly higher in the moderate to vigorous physical activity group (moderate to vigorous physical activity versus low physical activity, 1533 m/s versus 1523 m/s, p = 0.03). Daily physical activity was significantly associated with speed of sound, even after adjustment for confounding factors and prognosticators ( β = 0.195, p = 0.02). Conclusion: Sonographically measured bone status was significantly higher in women who were physically active than in those who were physically inactive, suggesting that daily physical activity might help to maintain good bone status.
Discriminant and convergent validity of the GSRS‐IBS symptom severity measure for irritable bowel syndrome: A population study
Authors: Ljótsson Brjánn , Jones Michael , Talley Nicholas J , Kjellström Lars , Agréus Lars , Andreasson Anna 
Published: January 2020

BackgroundThe Gastrointestinal Symptom Rating Scale–Irritable Bowel Syndrome (GSRS‐IBS) is a 13‐item measure of IBS symptom severity. The scale has been used in several studies, but its psychometric properties have been insufficiently investigated and population‐based data are not available.ObjectiveThe objective of this article is to establish the factor structure and discriminant and convergent validity of the GSRS‐IBS.MethodsThe study was based on a Swedish population sample (the Popcol study), of which 1158 randomly selected participants provided data on the GSRS‐IBS. We used confirmatory factor analysis (CFA) and compared total and subscales scores in different groups, including IBS diagnostic status, treatment‐seeking behavior, and predominant bowel habits. The GSRS‐IBS scores were also correlated with quality of life indexes.ResultsThe sample included 164 participants with a confirmed Rome III IBS diagnosis and 994 participants without the disease. The CFA confirmed the subscales with one exception, in which the incomplete bowel‐emptying item belonged to the constipation subscale rather than the diarrhea subscale. The GSRS‐IBS total score and subscales were associated with diagnostic status, treatment‐seeking behavior, and quality of life dimensions. The relevant subscales scores also differed between the diarrhea‐ and constipation‐predominant subtypes of IBS.ConclusionThe GSRS‐IBS total score and subscales have high discriminant and convergent validity. The CFA confirmed the overall validity of the subscales but suggest that a sense of incomplete emptying belongs to the constipation rather than the diarrhea symptom cluster. We conclude that the GSRS‐IBS is an excellent measure of IBS symptom severity in the general population.