bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated DNA and RNA Sequencing Reveals Drivers of Endocrine Resistance in Estrogen Receptor–Positive Breast Cancer
Authors: Xia Youli , He Xiaping , Renshaw Lorna , Martinez-Perez Carlos , Kay Charlene , Gray Mark , Meehan James , Parker Joel S. , Perou Charles M. , Carey Lisa A. , Dixon J. Michael , Turnbull Arran 
Published: July 2022

Abstract

Purpose:
Endocrine therapy resistance (ETR) remains the greatest challenge in treating patients with hormone receptor–positive breast cancer. We set out to identify molecular mechanisms underlying ETR through in-depth genomic analysis of breast tumors.

Experimental Design:
We collected pre-treatment and sequential on-treatment tumor samples from 35 patients with estrogen receptor–positive breast cancer treated with neoadjuvant then adjuvant endocrine therapy; 3 had intrinsic resistance, 19 acquired resistance, and 13 remained sensitive. Response was determined by changes in tumor volume neoadjuvantly and by monitoring for adjuvant recurrence. Twelve patients received two or more lines of endocrine therapy, with subsequent treatment lines being initiated at the time of development of resistance to the previous endocrine therapy. DNA whole-exome sequencing and RNA sequencing were performed on all samples, totalling 169 unique specimens. DNA mutations, copy-number alterations, and gene expression data were analyzed through unsupervised and supervised analyses to identify molecular features related to ETR.

Results:
Mutations enriched in ETR included ESR1 and GATA3. The known ESR1 D538G variant conferring ETR was identified, as was a rarer E380Q variant that confers endocrine hypersensitivity. Resistant tumors which acquired resistance had distinct gene expression profiles compared with paired sensitive tumors, showing elevated pathways including ER, HER2, GATA3, AKT, RAS, and p63 signaling. Integrated analysis in individual patients highlighted the diversity of ETR mechanisms.

Conclusions:
The mechanisms underlying ETR are multiple and characterized by diverse changes in both somatic genetic and transcriptomic profiles; to overcome resistance will require an individualized approach utilizing genomic and genetic biomarkers and drugs tailored to each patient.
A Mesenchymal Tumor Cell State Confers Increased Dependency on the BCL-XL Antiapoptotic Protein in Kidney Cancer
Authors: Grubb Treg , Maganti Smruthi , Krill-Burger John Michael , Fraser Cameron , Stransky Laura , Radivoyevitch Tomas , Sarosiek Kristopher A. , Vazquez Francisca , Kaelin William G. , Chakraborty Abhishek A. 
Published: July 2022

Abstract

Purpose:
Advanced/metastatic forms of clear-cell renal cell carcinomas (ccRCC) have limited therapeutic options. Genome-wide genetic screens have identified cellular dependencies in many cancers. Using the Broad Institute/Novartis combined short hairpin RNA (shRNA) dataset, and cross-validation with the CRISPR/Cas9 DepMap (21Q3) dataset, we sought therapeutically actionable dependencies in kidney lineage cancers.

Experimental Design:
We identified preferential genetic dependencies in kidney cancer cells versus other lineages. BCL2L1, which encodes the BCL-XL antiapoptotic protein, scored as the top actionable dependency. We validated this finding using genetic and pharmacologic tools in a panel of ccRCC cell lines. Select BCL-XL–dependent (versus independent) cell lines were then transcriptionally profiled to identify biomarkers and mechanistic drivers of BCL-XL dependence. Cell-based studies (in vitro and in vivo) and clinical validations were used to address physiologic relevance.

Results:
Inactivation of BCL-XL, but not BCL-2, led to fitness defects in renal cancer cells, and sensitized them to chemotherapeutics. Transcriptomic profiling identified a “BCL-XL dependency” signature, including an elevated mesenchymal gene signature. A mesenchymal state was both necessary and sufficient to confer increased BCL-XL dependence. The “BCL-XL dependency” signature was observed in approximately 30% of human ccRCCs, which were also associated with worse clinical outcomes. Finally, an orally bioavailable BCL-XL inhibitor, A-1331852, showed antitumor efficacy in vivo.

Conclusions:
Our studies uncovered an unexpected link between cell state and BCL-XL dependence in ccRCC. Therapeutic agents that specifically target BCL-XL are available. Our work justifies testing the utility of BCL-XL blockade to target, likely, a clinically aggressive subset of human kidney cancers.
See related commentary by Wang et al., p. 4600
Study of ZnS:Mn2+,Te2+ phosphor for improving the hue rendering indicator of WLEDs
Authors: Liem Bui Van , Phuong Loan Nguyen Thi , Xuan Le Phan 
Published: July 2022

This research combines a phosphor-in-glass (PiG) YAG:Ce3+ with a red liquid-type quantum dot (LQD) to invent high-quality white light-emitting diodes (WLEDs). When the PiG LQD-built WLEDs reach 100 mA, they provide heated white illumination offering an outstanding color rendering index (CRI) (Ra=93.9, R9=97.7, and R13=98.1). The luminescent efficiency (LE) and correlating chromatic temperature, correspondingly, are 62 lm/W and 3764 K. In comparison to PiG integrated with solid-kind quantum dot, it has great LE, remarkable CRI, and lower top layer temperature because of self-aggregation and impediment in the outside flaws in semiconductor quantum dots (QDs) of the solid-condition, as well as effective thermal dissipation. The findings suggest that the produced WLEDs could be potential in high-quality lighting applications.
Heart disease classification using various heuristic algorithms
Authors: Ullah Arif , Khan Shakeel Ahmad , Alam Tanweer , Luma-Osmani Shkurte , Sadie Mahanz 
Published: July 2022

<span>In the health sector, the computer-aided diagnosis (CAD) system is a rapidly growing technology because medical diagnostic systems make a huge change as compared to the traditional system. Now a day huge availability of medical data and it needs a proper system to extract them into useful knowledge. Heart disease accounts to be the leading cause of death worldwide. Heuristic algorithms have been exposed to be operative in supporting making decisions and classification from the large quantity of data produced by the healthcare sector. Classification is a prevailing heuristic approach which is commonly used for classification purpose some heuristic algorithm predicts accurate result according to the marks whereas some others exhibit limited accuracy. This paper is used to categorize the attendance of heart disease with a compact number of aspects. Original, 13 attributes are involved in classifying heart disease. A reasonable analysis of these techniques was done to conclude how the cooperative techniques can be applied for improving prediction accuracy in heart disease. Four main classifiers used to construct heart disease prediction based on the experimental results demonstrate that support vector machine, artificial bee colony (ABC), Bat algorithm, and memory-based learner (MBL) provide efficient results. The accuracy differs between 13 features and 8 features in the training dataset is 1.9% and in the validation, dataset is 0.92% of vector machine which is the most accurate heuristic algorithm. </span>
A deep learning approach based defect visualization in pulsed thermography
Authors: Selvan Sethu Selvi , Delanthabettu Sharath , Murugesan Menaka , Balasubramaniam Venkatraman , Udupa Sathvik , Khandelwal Tanvi , Mulla Touqeer , Ittigi Varun 
Published: July 2022

<span lang="EN-US">Non-destructive evaluation (NDE) is very essential in measuring the properties of materials and in turn detect flaws and irregularities. Pulsed thermography (PT) is one of the advanced NDE technique which is used for detecting and characterizing subsurface defects. Recently many methods have been reported to enhance the signal and defect visibility in PT. In this paper, a novel unsupervised deep learning-based auto-encoder (AE) approach is proposed for enhancing the signal-to-noise ratio (SNR) and visualize the defects clearly. A detailed theoretical background of AE and its application to PT is discussed. The SNR and defect detectability results are compared with the existing approaches namely, higher order statistics (HOS), principal component thermography (PCT) and partial least square regression (PLSR) thermography. Experimental results show that AE approach provides better SNR at the cost of defect detectability.</span><br /><div id="ext-mouse-move" style="display: none;"> </div><div id="ext-mouse-down" style="display: none;"> </div><div id="ext-mouse-up" style="display: none;"> </div>
Testing content validity of teacher-made test: Profiling teacher perceptions and demographic variables
Authors: Musah Mohammed Borhandden , Tahir Lokman Mohd , Al-Hudawi Shafeeq Hussain , Issah Mohammad , Hussein Abdul Rawuf , Ibrahim Mikail 
Published: July 2022

<span lang="EN-US">The content validity of teacher-made tests (TMT) in Malaysian Chinese primary schools was explored in this research. The study used teacher-made tests to analyze the selected Chinese primary schools, which have yet to be thoroughly explored in the context of these school types. It also investigated how well teachers in the sampled schools understand the table of specifications (TOS). The study further examined the extent to which included demographic variables affect the validity of teacher-made tests. A total of 660 questionnaires were distributed randomly to teachers from 21 Chinese primary schools. There were 381 completed questionnaires (58% of total rate) received and analyzed. The findings demonstrated that most teachers have a basic understanding of the TOS and that teacher-made test levels are valid. K-group MANOVA analysis also revealed that work experience and age had a significant influence on teacher understanding. Work experience and age, on the other hand, had no effect on the teacher-made test. Furthermore, the findings demonstrated that both teacher understanding and teacher-made tests were unaffected by teacher gender. </span>
Students’ cognitive and metacognitive learning strategies towards hands-on science
Authors: Discipulo Leslie Gomez , Bautista Romiro Gordo 
Published: July 2022

<span>Cognitive and metacognitive learning strategies are geared towards giving autonomy to every learner in their studies. Students’ affordances on cognitive and metacognitive learning strategies in their studies are believed to predict their academic success and performances in their learning tasks. This study determined the cognitive and metacognitive learning strategies in science among the 278 education students in the three campuses of a state university in the Philippines as bases in crafting a developmental plan to bolster the science instruction in the university. Using the descriptive-inferential research and employing a questionnaire on the cognitive and metacognitive strategies of education students, the following are known: incomparable affordances of the students along planning and information management practices while comparable affordances were determined on the respondents’ cognitive learning strategies; and incomparable affordances along procedural knowledge while comparable affordances along declarative and conditional knowledge were determined on the respondents’ metacognitive learning strategies. Based on the results, a developmental plan was designed to bolster the science courses in the education programs of the university centering on the inclusion of research camp, research expo, shepherding on research through the niche program, immersion, and hands-on science. It was recommended that the proposed enhanced science program will be implemented in the university system as there is only one science course in their respective programs in the new curricular plot. </span>
Home fertilizer teaching module for Aborigine people
Authors: Mahanan Mangai Solomon , Ibrahim Nor Hasniza , Surif Johari , Ismail Norulhuda , Hanri Chuzairy , Arif Ahamad Muhammad Khairul , Serman Nur Sahrizan 
Published: July 2022

<span lang="EN-US">The Aborigines of Malaysia portray limited knowledge of domestic wastes conversion into homemade fertilizer for crops which is also needed to facilitate proper home hygiene. Therefore, this study developed a Home fertilizer teaching module that applies 5E model to educate the knowledge deficient Aborigine People. The study used a qualitative research approach through the collection of open-ended data and analyzed based on themes. The research procedure was divided into: i) Development of the Home fertilizer module; and ii) Validation of the Home fertilizer module. Validation of the module was done by eight experts in teaching science and mathematics who were selected based on the purposive sampling technique according to the study aim. An open-ended questionnaire that contains ten items about the suitability of the module to be implemented among the Aborigines community, the content of the module, and involvement of STEM learning was the instrument of the study. Results showed that the content of the module is easy to understand with a clear objective and also stimulates science, technology, engineering, and mathematics (STEM) learning. Also, the module was considered a sanitary STEM module that is suitable for educating the Aborigine people on domestic waste conversion into homemade fertilizer and maintaining a cleaner environment. </span>
Ablation of Refractory Ventricular Tachycardia Using Intramyocardial Needle Delivered Heated Saline-Enhanced Radiofrequency Energy: A First-in-Man Feasibility Trial
Authors: Packer Douglas L. , Wilber David J. , Kapa Suraj , Dyrda Katia , Nault Isabelle , Killu Ammar M. , Kanagasundram Arvindh , Richardson Travis , Stevenson William , Verma Atul , Curley Michael ,   for the SERF Investigators
Published: July 2022

Background:
Ablation of ventricular tachycardia (VT) is limited by the inability to create penetrating lesions to reach intramyocardial origins. Intramural needle ablation using in-catheter, heated saline-enhanced radio frequency (SERF) energy uses convective heating to increase heat transfer and produce deeper, controllable lesions at intramural targets. This first-in-human trial was designed to evaluate the safety and efficacy of SERF needle ablation in patients with refractory VT.

Methods:
Thirty-two subjects from 6 centers underwent needle electrode ablation. Each had recurrent drug-refractory monomorphic VT after implantable cardioverter defibrillator implantation and prior standard ablation. During the SERF study procedure, one or more VTs were induced and mapped. The SERF needle catheter was used to create intramural lesions at targeted VT site(s). Acute procedural success was defined as noninducibility of the clinical VT after the procedure. Patients underwent follow-up at 30 days, and 3 and 6 months, with implantable cardioverter defibrillator interrogation at follow-up to determine VT recurrence.

Results:
These refractory VT patients (91% male, 66±10 years, ejection fraction 35±11%; 56% ischemic, and 44% nonischemic) had a median of 45 device therapies (shock/antitachycardia pacing) for VT in the 3 to 6 months pre-SERF ablation. The study catheter was used to deliver an average of 10±5 lesions per case, with an average of 430±295 seconds of radiofrequency time, 122±65 minute of catheter use time, and a procedural duration of 4.3±1.3 hours. Acute procedural success was 97% for eliminating the clinical VT. At average follow-up of 5 months (n=32), device therapies were reduced by 89%. Complications included 2 periprocedural deaths: an embolic mesenteric infarct and cardiogenic shock, 2 mild strokes, and a pericardial effusion treated with pericardiocentesis (n=1).

Conclusions:
Intramural heated saline needle ablation showed complete acute and satisfactory mid-term control of difficult VTs failing 1 to 5 prior ablations and drug therapy. Further study is warranted to define safety and longer-term efficacy.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique Identifier: NCT03628534 and NCT02994446.
The Impact of Large-Scale Winds on Boundary Layer Structure, Thermally Driven Flows, and Exchange Processes over Mountainous Terrain
Authors: Weinkaemmerer Jan , Ďurán Ivan Bašták , Schmidli Jürg 
Published: July 2022

Abstract
The vertical heat and moisture exchange in the convective boundary layer over mountainous terrain is investigated using large-eddy simulation. Both turbulent and advective transport mechanisms are evaluated over the simple orography of a quasi-two-dimensional, periodic valley with prescribed surface fluxes. For the analysis, the flow is decomposed into a local turbulent part, a local mean circulation, and a large-scale part. It is found that thermal upslope winds are important for the moisture export from the valley to the mountain tops. Even a relatively shallow orography, possibly unresolved in existing numerical weather prediction models, modifies the domain-averaged moisture and temperature profiles. An analysis of the turbulent kinetic energy and turbulent heat and moisture flux budgets shows that the thermal circulation significantly contributes to the vertical transport. This transport depends on the horizontal heterogeneity of the transported variable. Therefore, the thermal circulation has a stronger impact on the moisture budget and a weaker impact on the temperature budget. If an upper-level wind is present, it interacts with the thermal circulation. This weakens the vertical transport of moisture and thus reduces its export out of the valley. The heat transport is less affected by the upper-level wind because of its weaker dependence on the thermal circulation. These findings were corroborated in a more realistic experiment simulating the full diurnal cycle using radiation forcing and an interactive land surface model.
Greenhouse Gas Emissions Drive Global Dryland Expansion but Not Spatial Patterns of Change in Aridification
Authors: Feng Shuyun , Gu Xihui , Luo Sijia , Liu Ruihan , Gulakhmadov Aminjon , Slater Louise J. , Li Jianfeng , Zhang Xiang , Kong Dongdong 
Published: July 2022

Abstract
Drylands play an essential role in Earth’s environment and human systems. Although dryland expansion has been widely investigated in previous studies, there is a lack of quantitative evidence supporting human-induced changes in dryland extent. Here, using multiple observational datasets and model simulations from phase 6 of the Coupled Model Intercomparison Project, we employ both correlation-based and optimal fingerprinting approaches to conduct quantitative detection and attribution of dryland expansion. Our results show that spatial changes in atmospheric aridity (i.e., the aridity index defined by the ratio of precipitation to potential evapotranspiration) between the recent period 1990–2014 and the past period 1950–74 are unlikely to have been caused by greenhouse gas (GHG) emissions. However, it is very likely (at least 95% confidence level) that dryland expansion at the global scale was driven principally by GHG emissions. Over the period 1950–2014, global drylands expanded by 3.67% according to observations, and the dryland expansion attributed to GHG emissions is estimated as ∼4.5%. Drylands are projected to continue expanding, and their populations to increase until global warming reaches ∼3.5°C above preindustrial temperature under the middle- and high-emission scenarios. If warming exceeds ∼3.5°C, a reduction in population density would drive a decrease in dryland population. Our results for the first time provide quantitative evidence for the dominant effects of GHG emissions on global dryland expansion, which is helpful for anthropogenic climate change adaptation in drylands.

Significance Statement
In the past decades, global drylands have been reported to show changes in space and time, based on atmospheric aridity (i.e., aridity index defined by the ratio of precipitation to potential evapotranspiration). Using two detection and attribution methods, the spatial change patterns of atmospheric aridity between 1990–2014 and 1950–74 are unlikely to be driven by greenhouse gas (GHG) emissions, whereas the temporal expansion of global drylands (i.e., 3.67% from 1950 to 2014) is principally attributed to GHG emissions (contribution: ∼122%). Quantitative evidence from the detection and attribution analysis supports the dominant role of greenhouse gas emissions in global dryland expansion, which will increase the population suffering from water shortages under future warming unless climate adaptation is adopted.
Are Screening Tools for Identifying Human Trafficking Victims in Health Care Settings Validated? A Scoping Review
Authors: Hainaut Mathilde , Thompson Katherine J. , Ha Caryn J. , Herzog Hayley L. , Roberts Timothy , Ades Veronica 
Published: July 2022

Objective: Although many screening tools, resources, and programs for identifying victims of human trafficking exist, consensus is lacking on which tools are most useful, which have been validated, and whether they are effective. The objectives of this study were to determine what tools exist to identify or screen for victims of human trafficking in health care settings and whether these tools have been validated. Method: We conducted a scoping review of the literature on human trafficking identification in health care settings following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) protocol for scoping reviews. We searched the MEDLINE, PsycInfo, Embase, and Scopus databases without language or date limitations. Two independent reviewers screened each citation. We included human research studies in English with populations of all ages, all genders, all geographic locations, and using quantitative and/or qualitative research methods. We excluded studies that were not conducted in a health care setting, review articles, and meta-analyses. We summarized additional screening tools available online and identified through hand-searching. Results: Database searches yielded 8730 studies, of which 4806 remained after removing duplicates. We excluded 4720 articles based on title/abstract review, we reviewed 85 full-text studies for eligibility, and we included 8 articles. Hand-searching revealed 9 additional screening tools not found in the literature. Through our search for validated screening tools, only 6 had been studied for validation in health care settings. Conclusions: Few studies have evaluated screening tools for identifying victims of human trafficking in health care settings. The absence of a gold standard for human trafficking screening and lack of consensus on the definition of human trafficking make screening tool validation difficult. Further research is required for the development of safe, effective approaches to patient screening.