bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase I Study of Alpelisib in Combination with Trastuzumab and LJM716 in Patients with PIK3CA-Mutated HER2-Positive Metastatic Breast Cancer
Authors: Jhaveri Komal , Drago Joshua Z. , Shah Payal Deepak , Wang Rui , Pareja Fresia , Ratzon Fanni , Iasonos Alexia , Patil Sujata , Rosen Neal , Fornier Monica N. , Sklarin Nancy T. , Chandarlapaty Sarat , Modi Shanu 
Published: May 2021

Abstract

Purpose:
Activating mutations in PIK3CA promote resistance to HER2-targeted therapy in breast cancer; however, inhibition of PI3K alone leads to escape via feedback upregulation of HER3. Combined inhibition of HER2, HER3, and PI3K overcomes this mechanism preclinically.

Patients and Methods:
This phase I study investigated the MTD of alpelisib given in combination with trastuzumab and LJM716 (a HER3-targeted antibody) in patients with PIK3CA-mutant HER2-positive (HER2+) metastatic breast cancer (MBC) using the continual reassessment method. Secondary analyses included efficacy and exploratory correlative studies.

Results:
Ten patients were treated initially with daily alpelisib (arm A). Grade ≥3 adverse events seen in ≥2 patients included diarrhea (n = 6), hypokalemia (n = 3), abnormal liver enzymes (n = 3), hyperglycemia (n = 2), mucositis (n = 2), and elevated lipase (n = 2). The MTD of alpelisib in arm A was 250 mg daily. This prompted the opening of arm B in which 11 patients received intermittently dosed alpelisib. Grade ≥3 adverse events seen in ≥2 patients included diarrhea (n = 5), hypokalemia (n = 3), and hypomagnesemia (n = 2). The MTD of alpelisib in arm B was 350 mg given 4 days on, 3 days off. Among 17 patients assessed, 1 had a partial response, 14 had stable disease, and 2 had disease progression at best response. Five patients had stable disease for &gt;30 weeks. mRNA profiling of pre- and on-treatment tissue demonstrated PIK3CA target engagement by alpelisib via induction of downstream signaling and feedback pathways.

Conclusions:
Combination treatment with alpelisib, trastuzumab, and LJM716 was limited by gastrointestinal toxicity. Further efforts are warranted to target the PI3K pathway in HER2+ MBC.
Comprehensive Molecular and Clinicopathologic Analysis of 200 Pulmonary Invasive Mucinous Adenocarcinomas Identifies Distinct Characteristics of Molecular Subtypes
Authors: Chang Jason C. , Offin Michael , Falcon Christina , Brown David , Houck-Loomis Brian R. , Meng Fanli , Rudneva Vasilisa A. , Won Helen H. , Amir Sharon , Montecalvo Joseph , Desmeules Patrice , Kadota Kyuichi , Adusumilli Prasad S. , Rusch Valerie W. , Teed Sarah , Sabari Joshua K. , Benayed Ryma , Nafa Khedoudja , Borsu Laetitia , Li Bob T. , Schram Alison M. , Arcila Maria E. , Travis William D. , Ladanyi Marc , Drilon Alexander , Rekhtman Natasha 
Published: May 2021

AbstractPurpose:Invasive mucinous adenocarcinoma (IMA) is a unique subtype of lung adenocarcinoma, characterized genomically by frequent KRAS mutations or specific gene fusions, most commonly involving NRG1. Comprehensive analysis of a large series of IMAs using broad DNA- and RNA-sequencing methods is still lacking, and it remains unclear whether molecular subtypes of IMA differ clinicopathologically.Experimental Design:A total of 200 IMAs were analyzed by 410-gene DNA next-generation sequencing (MSK-IMPACT; n = 136) or hotspot 8-oncogene genotyping (n = 64). Driver-negative cases were further analyzed by 62-gene RNA sequencing (MSK-Fusion) and those lacking fusions were further tested by whole-exome sequencing and whole-transcriptome sequencing (WTS).Results:Combined MSK-IMPACT and MSK-Fusion testing identified mutually exclusive driver alterations in 96% of IMAs, including KRAS mutations (76%), NRG1 fusions (7%), ERBB2 alterations (6%), and other less common events. In addition, WTS identified a novel NRG2 fusion (F11R–NRG2). Overall, targetable gene fusions were identified in 51% of KRAS wild-type IMAs, leading to durable responses to targeted therapy in some patients. Compared with KRAS-mutant IMAs, NRG1-rearranged tumors exhibited several more aggressive characteristics, including worse recurrence-free survival (P &lt; 0.0001).Conclusions:This is the largest molecular study of IMAs to date, where we demonstrate the presence of a major oncogenic driver in nearly all cases. This study is the first to document more aggressive characteristics of NRG1-rearranged IMAs, ERBB2 as the third most common alteration, and a novel NRG2 fusion in these tumors. Comprehensive molecular testing of KRAS wild-type IMAs that includes fusion testing is essential, given the high prevalence of alterations with established and investigational targeted therapies in this subset.
Protección de la infancia y saberes expertos: un archivo interamericano como campo etnográfico
Authors: Rojas-Novoa Soledad 
Published: May 2021

(analítico)El objetivo de este artículo es conocer y comprender los procesos de construcción del campo especializado de saberes e intervención que constituyó la protección de la infancia en América a lo largo del siglo XX. El análisis se basa en un trabajo etnográfico en el archivo del Instituto Interamericano del Niño, la Niña y Adolescentes, concretamente en una sistematización documental a partir de la cual es posible explorar diversas versiones del modelo preventivo que se expandió en la región, y sobre el cual se erigieron las «voces autorizadas» para definir a determinadas infancias como modélicas. La hipótesis de trabajo es que los idearios de progreso y desarrollo que gravitaron sobre los proyectos de sociedad en ese periodo tuvieron un impacto específico en la construcción y legitimación de tales definiciones.
Palabras clave: Infancia, experto, etnografía, archivos, organismo internacional, América.
Tramas en la construcción de la intersectorialidad para atender la primera infancia
Authors: Ceballos Higuita Lorena , Otálvaro-Castro Gabriel Jaime 
Published: May 2021

(analítico)Este artículo presenta los resultados de la investigación cualitativa realizada desde una perspectiva interpretativa-histórica, para comprender la construcción de relaciones intersectoriales en el programa de atención a la primera infancia de Medellín entre el 2004 y el 2014. Se recurrió al análisis documental y a la observación participante en espacios de gestión de políticas públicas y se implementaron entrevistas semiestructuradas a funcionarios gubernamentales y no gubernamentales. La información se analizó desde tres dimensiones interdependientes: ideológica, política y administrativa. Según los resultados, las acciones intersectoriales se ven favorecidas por la adopción del enfoque de derechos, la implementación de instrumentos de política pública y la búsqueda del posicionamiento de los servicios en la comunidad; sin embargo, estos aspectos están atravesados por tensiones derivadas del intento de articular diferentes miradas, relaciones de poder y acciones administrativas.
Palabras clave: Primera infancia, política social, gestión, políticas, administración local, política gubernamental, intersectorialidad.
Acute Exposure to Diesel Exhaust Increases Muscle Sympathetic Nerve Activity in Humans
Authors: Rankin Gregory D. , Kabéle Mikael , Brown Rachael , Macefield Vaughan G. , Sandström Thomas , Bosson Jenny A. 
Published: May 2021

Background
Diesel exhaust (DE) emissions are a major contributor to ambient air pollution and are strongly associated with cardiovascular morbidity and mortality. Exposure to traffic‐related particulate matter is linked with acute adverse cardiovascular events; however, the mechanisms are not fully understood. We examined the role of the autonomic nervous system during exposure to DE that has previously only been indirectly investigated.

Methods and Results

Using microneurography, we measured muscle sympathetic nerve activity (MSNA) directly in the peroneal nerve of 16 healthy individuals. MSNA, heart rate, and respiration were recorded while subjects rested breathing filtered air, filtered air with an exposure mask, and standardized diluted DE (300 µg/m
3
) through the exposure mask. Heart rate variability was assessed from an ECG. DE inhalation rapidly causes an increase in number of MSNA bursts as well as the size of bursts within 10 minutes, peaking by 30 minutes (
P
<0.001), compared with baseline filtered air with an exposure mask. No significant changes occurred in heart rate variability indices during DE exposure; however, MSNA frequency correlated negatively with total power (
r
2
=0.294,
P
=0.03) and low frequency (
r
2
=0.258,
P
=0.045). Heart rate correlated positively with MSNA frequency (
r
2
=0.268,
P
=0.04) and the change in percentage of larger bursts (burst amplitude, height >50% of the maximum burst) from filtered air with an exposure mask (
r
2
=0.368,
P
=0.013).

Conclusions
Our study provides direct evidence for the rapid modulation of the autonomic nervous system after exposure to DE, with an increase in MSNA. The quick increase in sympathetic outflow may explain the strong epidemiological data associating traffic‐related particulate matter to acute adverse cardiovascular events such as myocardial infarction.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02892279.
Short‐Term Effects of Particle Size and Constituents on Blood Pressure in Healthy Young Adults in Guangzhou, China
Authors: Guo Peng‐Yue , He Zhi‐Zhou , Jalaludin Bin , Knibbs Luke D. , Leskinen Ari , Roponen Marjut , Komppula Mika , Jalava Pasi , Hu Li‐Wen , Chen Gongbo , Zeng Xiao‐Wen , Yang Bo‐Yi , Dong Guang‐Hui 
Published: May 2021

Background
Although several studies have focused on the associations between particle size and constituents and blood pressure, results have been inconsistent.

Methods and Results

We conducted a panel study, between December 2017 and January 2018, in 88 healthy university students in Guangzhou, China. Weekly systolic blood pressure and diastolic blood pressure were measured for each participant for 5 consecutive weeks, resulting in a total of 440 visits. Mass concentrations of particles with an aerodynamic diameter of ≤2.5 µm (PM
2.5
), ≤1.0 µm (PM
1.0
), ≤0.5 µm (PM
0.5
), ≤0.2 µm (PM
0.2
), and number concentrations of airborne particulates of diameter ≤0.1 μm were measured. Linear mixed‐effect models were used to estimate the associations between blood pressure and particles and PM
2.5
constituents 0 to 48 hours before blood pressure measurement. PM of all the fractions in the 0.2‐ to 2.5‐μm range were positively associated with systolic blood pressure in the first 24 hours, with the percent changes of effect estimates ranging from 3.5% to 8.8% for an interquartile range increment of PM. PM
0.2
was also positively associated with diastolic blood pressure, with an increase of 5.9% (95% CI, 1.0%–11.0%) for an interquartile range increment (5.8 μg/m
3
) at lag 0 to 24 hours. For PM
2.5
constituents, we found positive associations between chloride and diastolic blood pressure (1.7% [95% CI, 0.1%–3.3%]), and negative associations between vanadium and diastolic blood pressure (−1.6% [95% CI, −3.0% to −0.1%]).

Conclusions
Both particle size and constituent exposure are significantly associated with blood pressure in the first 24 hours following exposure in healthy Chinese adults.
Europe’s Seminal Proto-Fascist? Historically Approaching Ziya Gökalp, Mentor of Turkish Nationalism
Authors: Kieser Hans-Lukas 
Published: May 2021

Abstract
This essay considers Ziya Gökalp, the received “spiritual father of Turkish nationalism”, as an early mastermind of fascism in Greater Europe. During the 1910s, Gökalp acted as a prophet of expansive war and as a mentor of demographic engineering in the Ottoman capital, Istanbul, which was a laboratory for new political styles in a crisis-ridden empire. Gökalp’s thinking longed for a supreme leader in an army-like, disciplined and hierarchised society, while it rejected a social contract-based nation and state. An influential inspiration for and beyond the new élites in the capital, Gökalp combined the call for radical modernisation according to “European civilisation” with an assertive essentialism based on völkisch (cultural-racial-ethnic Turkish) and religious (political Islamic) references. He was the chief ideologist of the Young Turk party-state (1913–18) – side by side with Talaat Pasha, its main executive leader – and “the father of my thoughts” for Kemal Atatürk.
Increased impact of the Tibetan Plateau Spring Snow Cover to the Meiyu Rainfall over the Yangtze River Valley after 1990s
Authors: Zhang Chao , Jia XiaoJing , Wen Zhiping 
Published: May 2021

AbstractThis study investigated the increased impact of the spring (March-April-May) snow cover extent (SCE) over the western Tibetan Plateau (TP) (SSTP) to the Meiyu rainfall (June-July, JJ) over the Yangtze River valley (YRV) (MRYRV) after 1990s. The correlation between the MRYRV and SSTP is significantly increased from 1970-1992 (P1) to 1993-2015 (P2). In P1, the MRYRV-related SSTP anomalies locate southwest TP which cause a perturbation near the SWJ core and favor an eastward propagation in the form of a wave train. The wave train results in a southward shift of the SWJ over the ocean south of Japan in JJ and exerts a limited effect on the MRYRV. Differently, in P2, the MRYRV-related anomalous SSTP causes an anomalous cooling temperature and upper-level cyclonic system centered over the northwestern TP. The cyclonic system develops and extends eastward to the downstream region with time and reaches coastal East Asia in JJ. The anomalous westerly winds along its south flank cause an enhanced subtropical westerly jet (SWJ) which is accompanied by an anomalous lower-level air convergence and ascent motion near the YRV region, favoring enhanced MRYRV. In addition, the forecast experiments performed with empirical regression models illustrate that the prediction skill of the MRYRV variation is clearly increased in P2 with the additional forecast factor of the SSTP.
Assimilation Impact of Early FORMOSAT-7/COSMIC-2 GNSS Radio Occultation Data with Taiwan’s CWB Global Forecast System
Authors: Lien Guo-Yuan , Lin Chung-Han , Huang Zih-Mao , Teng Wen-Hsin , Chen Jen-Her , Lin Ching-Chieh , Ho Hsu-Hui , Huang Jyun-Ying , Hong Jing-Shan , Cheng Chia-Ping , Huang Ching-Yuang 
Published: May 2021

AbstractThe FORMOSAT-7/COSMIC-2 Global Navigation Satellite System (GNSS) Radio Occultation (RO) satellite constellation was launched on June 2019 as a successor of the FORMOSAT-3/COSMIC mission. The Central Weather Bureau (CWB) of Taiwan has received FORMOSAT-7/COSMIC-2 GNSS RO data in real time from Taiwan Analysis Center for COSMIC. With the global numerical prediction system at CWB, a parallel semi-operational experiment assimilating the FORMOSAT-7/COSMIC-2 bending angle data with all other operational observation data has been conducted to evaluate the impact of the FORMOSAT-7/COSMIC-2 data. The first seven-month results show that the quality of the early FORMOSAT-7/COSMIC-2 data has been satisfactory for assimilation. Consistent and significant positive impacts on global forecast skills have been observed since the start of the parallel experiment, with the most significant impact found in the tropical region, reflecting the low-inclination orbital design of the satellites. The impact of the FORMOSAT-7/COSMIC-2 RO data is also estimated using the Ensemble Forecast Sensitivity to Observation Impact (EFSOI) method, showing an average positive impact per observation similar to other existing GNSS RO datasets, while the total impact is impressive by virtue of its large amount. Sensitivity experiments suggest that the quality control processes built in the Gridpoint Statistical Interpolation (GSI) system for RO data work well to achieve a positive impact by the low-level FORMOSAT-7/COSMIC-2 RO data, while more effort on observation error tuning should be focused to obtain an optimal assimilation performance. This study demonstrates the usefulness of the FORMOSAT-7/COSMIC-2 RO data in global numerical weather prediction during the calibration/validation period and leads to the operational use of the data at CWB.
The paradox of citizen grievances in China: an institutional logics perspective
Authors: Kong Fanyi , Su Xuhong 
Published: May 2021

Grievance petitioning is a prevailing venue for voicing citizens’ discontent and seeking redress in China. Extant literature documents the simultaneous growth of citizen petitions and local containment, without addressing the dynamics of such a paradox. Inspired by the institutional logics perspective, this study surveyed over 300 onsite petitioners and explored how multiple institutional logics are at work and together produce the paradox. Citizens embrace the grassroots logic, flooding petitions into the grievance system. Local governments follow the state logic, engaging in comprehensive containment. Grievance agencies cope strategically with the rise of citizen petitions and bureaucratic influences, demonstrating the ombudsman logic. Despite local containment and often less than satisfactory resolutions, citizens still hold favorable attitudes toward the grievance system, as well as the top bureaucracy, thus sowing the seeds for more petitions. The paradox manifests the coexistence and interactions of multiple institutional logics, raising challenges for governance and accountability. Points for practitioners The simultaneous growth of citizens’ grievances and local containment presents a paradox. Citizens follow the grassroots logic, filing more petitions. Local governments adhere to the state logic, prescribing containment efforts. In face of competing demands, grievance agencies embrace the ombudsman logic. The coexistence of and interactions among different logics help to explain the recurrent patterns for all parties. Future reforms need to be designed with a sophisticated understanding of interactive institutional logics.
Thrombectomy of symptomatic isolated occlusions of posterior cerebral arteries in segment P1 and P2 in acute stroke treatment
Authors: Altenbernd Jens , Forsting Michael , Weber Werner , Fischer Sebastian 
Published: May 2021

Background Interventional stroke treatments for occlusions of the posterior circulation are established procedures. However, there are limited data on the treatment of isolated symptomatic P1 and P2 occlusions, which we have examined in this study. Purpose To investigate the mechanical thrombectomy of distal posterior occlusions Material and Methods Retrospectively, data from patients with isolated P1 and P2 occlusions treated with MT were evaluated. Successful reperfusions have been defined as modified thrombolysis in cerebral infarct (mTICI) Grade 2b–3. A good clinical outcome was defined as a 90-day modified Rankin score 0–2. Results All 79 treated patients were primarily aspirated. Stent retrievers were used secondarily in nine patients. Successful reperfusion was achieved in 95% of patients. Of the patients, 57% had a favorable clinical outcome after 90 days. Conclusion Mechanical thrombectomy with first line aspiration of symptomatic P1 and P2 occlusions is a safe and effective procedure.
Association between interleukin gene polymorphisms and susceptibility to gastric cancer in the Qinghai population
Authors: Song Xiaoyan , Wang Dongmei , Ben Baji , Xiao Chenghua , Bai Liyan , Xiao Han , Zhang Wenyan , Li Wanchao , Jia Jingying , Qi Yujuan 
Published: May 2021

Objective To investigate the associations between interleukin (IL) gene polymorphisms and susceptibility to gastric cancer in the Qinghai population, China. Methods Patients with gastric cancer and cancer-free controls were enrolled into the study from Qinghai Provincial People’s Hospital between September 2016 and September 2018. Single nucleotide polymorphisms (SNPs) were genotyped with the Sequenom MassARRAY® SNP genotype system. The Hardy–Weinberg equilibrium in allele and genotype frequencies, and general characteristics between patients with gastric cancer and cancer-free controls, were evaluated using χ2-test. Potential associations between interleukin gene variants and the risk of gastric cancer were analysed by logistic regression. Results Among eight candidate SNPs, the allele and genotype frequency distribution of IL-1B rs1143634 polymorphism was significantly different between patients with gastric cancer ( n = 190) and cancer-free controls ( n = 186). The IL-1B rs1143634 GA genotype and IL-1B rs1143634 GA + AA genotype were associated with a reduced risk of gastric cancer, however, the remaining SNPs were not statistically associated with gastric cancer risk in the Qinghai population. Conclusion The IL-1B rs1143634 polymorphism might be associated with a decreased risk of gastric cancer, and may be a protective factor against gastric cancer.
Cognitive orientation to daily occupation group in the adult day rehabilitation setting: A feasibility study
Authors: Zera Sarah M , Preissner Kathy , Fischer Heidi , Stoffel Ashley 
Published: May 2021

Introduction The Cognitive Orientation to daily Occupational Performance (CO-OP) ApproachTM is a leading approach in occupational therapy. Implementing the CO-OP ApproachTM in a group format in day rehabilitation has not yet been explored. Method In day rehabilitation, a barrier to implementing the CO-OP ApproachTM is the group model. To address these challenges, this feasibility study involved the development, implementation, and evaluation of a CO-OP group for adults. Four patients participated in six group sessions. Pre- and post-measures included the Canadian Occupational Performance Measure (COPM) and the Assessment of Motor and Process Skills (AMPS). Subjective data were collected to reflect the participant’s experiences during the group. Results 80% of participants recruited completed the group. All participants demonstrated improvement in goals addressed within the group and goals not addressed within the group on the COPM. AMPS findings were inconclusive. Subjective findings indicated participants appreciated the group learning environment, valued the CO-OP process, were motivated to participate, and would have liked more groups. Conclusion To our knowledge, this is the first adult CO-OP group in a clinical setting. Results support the feasibility of a CO-OP group in day rehabilitation and the need for further examination of the effectiveness of this intervention.