bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting S100A9–ALDH1A1–Retinoic Acid Signaling to Suppress Brain Relapse inEGFR-Mutant Lung Cancer
Authors: Biswas Anup Kumar , Han Seoyoung , Tai Yifan , Ma Wanchao , Coker Courtney , Quinn S. Aidan , Shakri Ahmad Rushdi , Zhong Timothy James , Scholze Hanna , Lagos Galina G. , Mela Angeliki , Manova-Todorova Katia , de Stanchina Elisa , Ferrando Adolfo A. , Mendelsohn Cathy , Canoll Peter , Yu Helena A. , Paik Paul K. , Saqi Anjali , Shu Catherine A. , Kris Mark G. , Massague Joan , Acharyya Swarnali 
Published: January 2022

AbstractThe epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib has significantly prolonged progression-free survival (PFS) in patients with EGFR-mutant lung cancer, including those with brain metastases. However, despite striking initial responses, osimertinib-treated patients eventually develop lethal metastatic relapse, often to the brain. Although osimertinib-refractory brain relapse is a major clinical challenge, its underlying mechanisms remain poorly understood. Using metastatic models of EGFR-mutant lung cancer, we show that cancer cells expressing high intracellular S100A9 escape osimertinib and initiate brain relapses. Mechanistically, S100A9 upregulates ALDH1A1 expression and activates the retinoic acid (RA) signaling pathway in osimertinib-refractory cancer cells. We demonstrate that the genetic repression of S100A9, ALDH1A1, or RA receptors (RAR) in cancer cells, or treatment with a pan-RAR antagonist, dramatically reduces brain metastasis. Importantly, S100A9 expression in cancer cells correlates with poor PFS in osimertinib-treated patients. Our study, therefore, identifies a novel, therapeutically targetable S100A9–ALDH1A1–RA axis that drives brain relapse.Significance:Treatment with the EGFR TKI osimertinib prolongs the survival of patients with EGFR-mutant lung cancer; however, patients develop metastatic relapses, often to the brain. We identified a novel intracellular S100A9–ALDH1A1–RA signaling pathway that drives lethal brain relapse and can be targeted by pan-RAR antagonists to prevent cancer progression and prolong patient survival.This article is highlighted in the In This Issue feature, p. 873
Exploiting Natural Killer Cell Engagers to Control Pediatric B-cell Precursor Acute Lymphoblastic Leukemia
Authors: Colomar-Carando Natalia , Gauthier Laurent , Merli Pietro , Loiacono Fabrizio , Canevali Paolo , Falco Michela , Galaverna Federica , Rossi Benjamin , Bosco Frédéric , Caratini Mélody , Mingari Maria Cristina , Locatelli Franco , Vivier Eric , Meazza Raffaella , Pende Daniela 
Published: January 2022

Abstract

Natural killer (NK) cells represent a promising cell type in antitumor immunotherapy for efficacy and safety, particularly in the treatment of hematologic malignancies. NK cells have been shown to exert antileukemia activity in the context of haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Products have been developed to boost the activation of NK cells only when cross-linked by tumor cells, avoiding any off-target effect. Here, we tested the in vitro effect of different NK-cell engagers (NKCE), which trigger either NKp46 or NKp30 together with CD16A, and target either CD19 or CD20 to induce killing of pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Target cells were NALM-16 and MHH-CALL-4 cell lines and four primary leukemias, while effector cells were resting NK cells derived from healthy donors and pediatric patients with leukemia after αβT/B-depleted haplo-HSCT. The NK cell–resistant MHH-CALL-4 was efficiently killed using all NKCEs. Boosting of NK activity against MHH-CALL-4 was also evident by degranulation and IFNγ production. Because of the lack of CD20 and high expression of CD19 on primary BCP-ALL, we focused on NKCEs targeting CD19. NKp46- and NKp30-based NKCEs displayed similar potency at inducing NK-cell activity, even when challenged with primary BCP-ALL blasts. Their efficacy was shown also using NK cells derived from transplanted patients. NKCE-induced activation against BCP-ALL can override HLA-specific inhibitory interactions, although the strongest response was observed by the alloreactive NK-cell subset. These data support the therapeutic use of NKp46/CD16A/CD19-NKCE to fight refractory/relapsed leukemia in pretransplantation or posttransplantation settings.
Alegorias de uma guerra poética: figuras da autoridade na França do século XVII
Authors: Sá Luiz César de 
Published: January 2022

Na França do século XVII, consolida-se o entendimento de que as “querelas” são o mecanismo privilegiado de instituição da autoridade letrada. Escritos propondo disputas galantes, que enalteciam a violência verbal em contraposição aos horrores da guerra, disseminam-se até fundamentar um gênero discursivo específico. Este artigo se volta para a análise das relações entre autoridade e controvérsia assim fundamentadas a partir do estudo da Nouvelle Allégorique (1658), texto que alegoriza os conflitos letrados de seu tempo com o objetivo principal de arquivar o próprio ato de querelar.
Identifying scientific publications countrywide and measuring their open access: The case of the French Open Science Barometer (BSO)
Authors: Chaignon Lauranne , Egret Daniel 
Published: January 2022

Abstract
We use several sources to collect and evaluate academic scientific publication on a country-wide scale, and we apply it to the case of France for the years 2015–2020, while presenting a more detailed analysis focused on the reference year 2019. These sources are diverse: databases available by subscription (Scopus, Web of Science) or open to the scientific community (Microsoft Academic Graph), the national open archive HAL, and databases serving thematic communities (ADS and PubMed). We show the contribution of the different sources to the final corpus. These results are then compared to those obtained with another approach, that of the French Open Science Barometer for monitoring open access at the national level. We show that both approaches provide a convergent estimate of the open access rate. We also present and discuss the definitions of the concepts used, and list the main difficulties encountered in processing the data. The results of this study contribute to a better understanding of the respective contributions of the main databases and their complementarity in the broad framework of a countrywide corpus. They also shed light on the calculation of open access rates and thus contribute to a better understanding of current developments in the field of open science.
Climatic Effects of the Indian Ocean Tripole on the Western United States in Boreal Summer
Authors: Zhang Yazhou , Li Jianping , Hou Zhaolu , Zuo Bin , Xu Yidan , Tang Xinxin , Wang Hao 
Published: January 2022

Abstract
The Indian Ocean tripole (IOT) is an independent mode of ocean–atmosphere circulation centered on the tropical Indian Ocean. This study explores the physical mechanisms of the IOT affecting the western United States climate variation during the boreal summer. We find that the IOT is significantly correlated with both western United States summer surface temperature and precipitation anomalies. During positive IOT events, the westerly wind anomalies over the northern Indian Ocean are intensified by two cross-equator airflows over the tropical eastern Indian Ocean and the east coast of Africa. The resulting convergence of air over the northern Bay of Bengal–Indochina Peninsula–northern South China Sea (NBB–IP–NSCS) region (15°–25°N, 80°–125°E) exacerbates the surplus precipitation there. Serving as a heat source, these NBB–IP–NSCS precipitation anomalies can excite a circumglobal teleconnection (CGT)-like pattern that propagates eastward from west-central Asia toward North America along the Asia subtropical westerly jet, further influencing local circulation anomalies. Development of strong anticyclonic circulation over the western United States enhances descending motion and divergence there, resulting in negative precipitation anomalies. This circulation anomaly also induces the diabatic heating anomalies through allowing more solar radiation to reach the ground surface, further increasing the surface temperature anomalies. Meanwhile, the increased tropospheric temperature also raises local surface temperatures by modulating the adiabatic air expansion and compression. Ultimately, the CGT-like pattern associated with NBB–IP–NSCS precipitation anomalies sets up an atmospheric bridge by which the IOT can impact summer climate in the western United States.
Quantifying the Effect of Rainfall and Visibility Conditions on Road Traffic Travel Time Reliability
Authors: Mathew Sonu , Pulugurtha Srinivas S. 
Published: January 2022

Abstract
This research explores a data-driven methodological framework to quantify the effect of rainfall and visibility on travel time reliability (TTR) by considering selected road segments in North Carolina. The framework includes capturing, processing, and integrating weather-related information and travel time data for the selected road segments. Various TTR indices were computed for the selected road segments under different rainfall and visibility ranges by day of the week (DOW) and time of the day (TOD). The TTR indices were computed for one week before and after (same DOW and TOD) under the normal weather condition and compared with those obtained under different intensities of rainfall and visibility. The variability in travel time patterns due to other events is expected to be marginal when considering the same DOW and TOD for comparison purposes. The results indicate that poor visibility with different rainfall intensities has the maximum adverse effect on the TTR. The outcomes from the data-driven methodological framework help the transportation planners in developing weather-responsive traffic management strategies and assessing their effectiveness using TTR indices.

Significance Statement
Travel time reliability (TTR) generally refers to the level of consistency or dependability in transportation service. It is considered as a measure of road operational performance. Ensuring higher levels of reliability is critical for efficient transportation system management along with mobility and accessibility needs. However, factors such as weather condition have a negative effect on the TTR. A data-driven methodological framework is proposed by integrating weather information and travel time data to quantify the effect of common weather conditions like rainfall and visibility on the TTR. The results indicated that heavy rain and poor visibility have an adverse effect on the TTR. These results are useful for agencies to better manage the traffic under different weather conditions.
The Prognostic Value of C-Reactive Protein/Albumin Ratio in Acute Mesenteric Ischemia
Authors: Kaçer İlker , Çağlar Ahmet , Akıllı Nazire Belgin 
Published: January 2022

Background Diagnosis of acute mesenteric ischemia (AMI) in its early stages is important for reversing ischemic damage. The CRP to albumin (CRP/Alb) ratio has been defined as an inflammatory indicator and is associated with the severity of inflammation and mortality rates. However, the prognostic value of CRP/Alb has not been evaluated in patients with AMI. Here, we aimed to examine the prognostic significance of CRP/Alb and compare it with other inflammatory markers. Materials and Methods In this retrospective, case-control study, we included patients diagnosed with AMI at the emergency department between January 1, 2016, and December 31, 2020. In addition to demographic characteristics, lactate, D-dimer, white blood cell (WBC), CRP/Alb, and neutrophil/lymphocyte ratio (NLR) were recorded. Testing characteristics of CRP/Alb in predicting in-hospital mortality were studied. Results The mean age of 132 patients was 66.48 ± 15.95 years and 71 (53.8%) of them were male. The cut-off value obtained using the receiver operating characteristic (ROC) curve for in-hospital mortality was a CRP/Alb ratio of >1.32 (sensitivity, 93.65%; specificity, 69.57%; +LR, 3.08; −LR, .091; AUC, .782; 95% CI, .70-.85; P < .0001). The comparison of ROC curves between CRP/Alb and WBC, NLR, and lactate revealed a statistically significant difference ( P < .05), whereas there was not any statistically significant difference between the ROC curves of CRP/Alb and D-dimer ( P = .47). Conclusion C-reactive protein/albumin ratio is a powerful predictor of in-hospital mortality for AMI patients. It was superior to WBC, NLR, and lactate. It could be used to determine low-risk patients and help clinicians with treatment options.
The Impact of Hyperuricemia on Patients With Low Body Mass Index After Endovascular Treatments: Data From the I-PAD Registry
Authors: Nagae Ayumu , Ebisawa Soichiro , Saigusa Tatsuya , Nishikawa Ken , Fujimori Koki , Yui Hisanori , Maruyama Shusaku , Nakamura Chie , Kashiwagi Daisuke , Kobayashi Hideki , Sakai Takahiro , Senda Keisuke , Kato Tamon , Miura Takashi , Okada Ayako , Motoki Hirohiko , Kuwahara Koichiro 
Published: January 2022

We investigated the prognostic effects of hyperuricemia and high or low body mass index (BMI) in peripheral artery disease (PAD) after endovascular therapy (EVT). Between July 2015–2016, 357 consecutive patients with PAD who underwent EVT were enrolled. Patients were divided into 2 groups: BMI < 25 kg/m2 (low BMI) and ≥ 25 kg/m2 (high BMI); they were also divided into 2 more groups based on the presence/absence of hyperuricemia. The primary and secondary endpoints were major adverse cardiovascular and limb events (MACLE), and all-cause death at 3 years post-EVT. Patients with hyperuricemia had significantly lower freedom from MACLE than patients without hyperuricemia at 3 years (57.0 vs 71.9%, p = .0068). The overall survival of patients with hyperuricemia was significantly lower than that of patients without hyperuricemia (63.9 vs 81.7%, p = .0012). Patients with hyperuricemia who had low BMI experienced significantly lower freedom from MACLE than those without hyperuricemia who had low BMI (48.2 vs 69.9%, p = .002). The overall survival of patients with hyperuricemia who had low BMI was significantly lower than that of patients without hyperuricemia who had low BMI (55.2 vs 77.1%, p = .003). Patients with hyperuricemia had significantly more MACLE and a lower survival at 3 years than patients without hyperuricemia, even if they had a low BMI.
Efficacy of pulsed electromagnetic field on pain and physical function in patients with low back pain: A systematic review and meta-analysis
Authors: Sun Xin , Huang Liyi , Wang Lu , Fu Chenying , Zhang Qing , Cheng Hongxin , Pei Gaiqin , Wang Yang , He Chengqi , Wei Quan 
Published: January 2022

Objective To assess the effectiveness of pulsed electromagnetic field (PEMF) on pain and physical function in patients with low back pain. Data sources A search of PubMed, Embase, Cochrane Library, and Web of Science was conducted up to December 2021. Methods We included randomized controlled trials that investigated the effectiveness of PEMF in patients with low back pain. The primary outcome was pain intensity and the secondary outcome was physical function, both were evaluated by assessment scales. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated for the summary statistics analysis. The registration number of this systematic review in PROSPERO is CRD42020213829. Results Fourteen trials involving 618 participants were included. The PEMF treatment showed more significant pain alleviation than placebo or other therapy alone in patients with low back pain (SMD = −1.01, 95% CI −1.42 to −0.6, P < 0.001, I2 = 31%; SMD = −0.36, 95% CI −0.62 to −0.11, P = 0.005, I2 = 37%, respectively.) In addition, a significant difference in pain alleviation was observed in patients with chronic low back pain (SMD = −0.6, 95%CI − 0.94 to −0.25, p < 0.001, I2 = 67%), whereas no significant difference was observed in patients with acute low back pain (SMD = −0.46, 95%CI − 0.99 to 0.07, p = 0.09, I2 = 0%). PEMF did not improve physical function compared with the control treatment (SMD = −0.45, 95% CI − 0.98 to 0.07, p = 0.09, I2 = 86%). Conclusion PEMF is beneficial for alleviating pain in patients with chronic low back pain despite having no advantage in improving physical function.
Effects of the timing and intensity of treatment on septic shock patients treated with CytoSorb®: Clinical experience
Authors: Berlot Giorgio , Samola Valentina , Barbaresco Ilaria , Tomasini Ariella , di Maso Vittorio , Bianco Francesco , Gerini Ugo 
Published: January 2022

Introduction: A group of adult septic shock patients treated with hemoperfusion (HA) with the Cytosorb® associated with CVVHD were studied to determine (a) the effects of this technique on different clinical variables; and (b) the impact of the pre CytoSorb® interval and its intensity on the outcome. Methods: The catecholamine index (CI) and the pressure-catecholamine Index (PCAI) were used to assess the amount of catecholamine administered at baseline and during the procedure, respectively. The pre-treatment time was calculated since the onset of the septic-shock related hypotension and the initiation of the first session and the intensity was assessed considering either the total volume of blood processed and the duration of the HA. Results: Overall, 51 patients with septic shock (30 m, 21 f), age 68 years (IQR 59–76) were retrospectively enrolled in the study; 26 were discharged alive form the ICU (S) and 25 died in ICU (NS); in the S group either CI and PCAI decreased significantly but in NS the CI increased and the PCAI remained stable in NS. In S, the time elapsing from the onset of symptoms and the start of Cytosorb® was shorter than in NS; the duration of the treatment and the volume of blood processed were significantly higher in S than in NS. Conclusions: In this group of septic shock patients, the earlier initiation of Cytosorb®, its longer duration and the higher volume of blood processed were associated with a better survival.
Investigation of crack detection properties of elastomer-based nanocomposites under cyclic strain loading with graphene and carbon black interaction filler
Authors: Kasim Hasan , Boztoprak Yalçın , Yazici Murat 
Published: January 2022

In this study, the synergistic effect created by adding Graphene (GE) nanoplatelets and carbon black (CB) fillers to the rubber matrix was used to determine the high stretchable sensor properties. GE and CB-filled rubber nanocomposite (HcN) strain sensors have been shown to detect and trace crack initiation and crack propagation of different sizes under cyclic loading. Tests were performed with four different crack sizes (0, 2.5, 5, and 10 mm) at five different strain levels (0%, 5%, 10%, 15%, and 20%) to determine the strain sensing performance of the specimens. The electrical response of HcNs under loading was measured with the four-point probe technique and recorded with a high-performance data acquisition system. The progression of external cracks created by scalpel on HcNs was examined by measuring electrical resistance changes caused by cyclic strain loading between 0% and 20%. The electrical response of 4 phr and 8 phr filled HcNs behaved qualitatively similar to each other, while 1 phr filled HcNs showed a significantly different response in terms of quality and quantity. In 4 phr GE-filled specimens, the resistance increase was changed steadily depending on the crack length, and unstable conditions occurred at 5 and 10 mm crack lengths at 1 and 8 phr GE filler ratios. The flexible and stretchable elastomer-based conductive strain sensing sensors, developed with the synergistic interaction of well-dispersed carbon-based fillers in the matrix, can detect and record damaged conditions caused by cyclic loading in many application areas.
Medication adherence in systemic lupus erythematosus during Brazilian COVID-19 pandemic
Authors: Albuquerque Emmanuele S , Pinto Larissa dS , Neto Valfrido LdM , Fragoso Thiago S 
Published: January 2022

Background Patients with chronic diseases are potential candidates for inadequate follow-up of drug therapy, tending to incur damage to the intended results. This deserves greater attention in the pandemic period, as they are in the considered risk group. Methods We aim to assess Treatment Adherence Measure and analyze associations with characteristics related to the patient, treatment, disease, health professionals and service, and sociodemographic issues in patients with Systemic Lupus Erythematosus (SLE). W conducted a cross-sectional study with a sample of 116 participants, whose data were collected through individual interviews and review of medical records, during the first months of the COVID-19 pandemic in Brazil. Adherence was measured using the Treatment Adherence Measure, and associations were evidenced through described and inferential statistics. Results The percentage of adherent patients was 55.2%. An association was found between MTA (Medication Treatment Adherence) and physical exercise practice ( p = 0.032), and difficulties with treatment ( p = 0.002). Conclusion: Participants who did not practice physical exercise were 3.71 times more likely to not adhere to the treatment. Individuals who identified difficulties in the treatment were 3.43 times more likely to not adhere to the treatment; we believe that the pandemic may have influenced this result. More targeted studies are needed to measure the impact on MTA in these patients.
A Biomechanical Analysis of Peroneus Brevis Split Lesions, Repair, and Partial Resection
Authors: Trache Tudor , Camenzind Roland S. , Bachmann Elias , Viehöfer Arnd , Jud Lukas , Wirth Stephan , Imhoff Florian B. 
Published: January 2022

Background: Peroneus brevis tendon tears are associated with chronic ankle pain and instability following sprain injuries. The aim of this study is to elucidate the biomechanical changes induced by a peroneus brevis split and surgical treatment by tubularizing suture or partial resection. Methods: Nine human lower leg specimens were biomechanically tested. Preexisting tendon pathology was ruled out by magnetic resonance imaging and histology. Specimens were subjected to sequential testing of 4 conditions of the peroneus brevis tendon: (1) native, (2) longitudinal lesion, (3) tubularizing suture, and (4) 50% resection. The outcome parameters were the tendon stiffness (N/mm) and the length variation of the split portion at 5 N load. Results: The median specimen age at death was 55.8 years (range 50-64 years). The longitudinal tendon split led to an elongation by 1.21 ± 1.15 mm, which was significantly reduced by tubularizing suture to 0.24 ± 0.97 mm ( P = .021). Furthermore, 50% resection of the tendon elongated it by a mean 2.45 ± 1.9 mm ( P = .01) and significantly reduced its stiffness compared to the intact condition (4.7 ± 1.17 N/mm, P = .024) and sutured condition (4.76 ± 1.04 N/mm, P = .011). Conclusion: Longitudinal split and 50% resection of the peroneus brevis tendon led to elongation and loss of tendon stiffness. These properties were improved by tubularizing suture. The significance of these changes in the clinical setting needs further investigation. Clinical Relevance: Tubularizing suture of a peroneus brevis split can restore biomechanical properties to almost native condition, potentially aiding ankle stability in symptomatic cases. A split lesion and partial resection of the tendon showed reduced stiffness and increased elongation.