bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exome sequencing study revealed novel susceptibility loci in subarachnoid hemorrhage (SAH)
Authors: Hao Xiwa , Pang Jiangxia , Li Ruiming , Lv Lin , Liu Guorong , Li Yuechun , Cheng Guojuan , Zhang Jingfen 
Published: May 2020

Abstract
Aim
To expand our current understanding of the genetic basis of subarachnoid hemorrhage (SAH), and reveal the susceptibility genes in SAH risk.

Methods
We conducted whole-exome sequencing (WES) in a cohort of 196 individuals, including 94 SAH patients and 94 controls, as well as 8 samples that belong to two pedigrees. Systematically examination for rare variations (through direct genotyping) and common variations (through genotyping and imputation) for SAHs were performed in this study.

Results
A total of 16,029 single-nucleotide polymorphisms (SNPs) and 108,999 short indels were detected in all samples, and among them, 30 SNPs distributed on 17 genes presented a strong association signal with SAH. Two novel pathogenic gene variants were identified as associated risk loci, including mutation in TPO and PALD1. The statistical analysis for rare, damaging variations in SAHs identified several susceptibility genes which were involved in degradation of the extracellular matrix and transcription factor signal pathways. And 25 putative pathogenic genes for SAH were also identified basic on functional interaction network analysis with the published SAH-associated genes. Additionally, pedigree analysis revealed autosomal dominant inheritance of pathogenic genes.

Conclusion
Systematical analysis revealed a key role for rare variations in SAH risk and discovered SNPs in new complex loci. Our study expanded the list of candidate genes associated with SAH risk, and will facilitate the investigation of disease-related mechanisms and potential clinical therapies.
Decision support tool and suggestions for the development of guidelines for the helicopter transport of patients with COVID-19
Authors: Bredmose Per P. , Diczbalis Monica , Butterfield Emma , Habig Karel , Pearce Andrew , Osbakk Svein Are , Voipio Ville , Rudolph Marcus , Maddock Alistair , O’Neill John 
Published: May 2020

AbstractThe novel coronavirus SARS-CoV2 emerged in December 2019 and is now pandemic. Initial analysis suggests that 5% of infected patients will require critical care, and that respiratory failure requiring intubation is associated with high mortality.Sick patients are geographically dispersed: most patients will remain in situ until they are in need of critical care. Additionally, there are likely to be patients who require retrieval for other reasons but who are co-incidentally infected with SARS-CoV-2 or shedding virus.The COVID-19 pandemic therefore poses a challenge to critical care retrieval systems, which often depend on small teams of specialists who live and work together closely. The infection or quarantining of a small absolute number of these staff could catastrophically compromise service delivery.Avoiding occupational exposure to COVID-19, and thereby ensuring service continuity, is the primary objective of aeromedical retrieval services during the pandemic. In this discussion paper we collaborated with helicopter emergency medical services(HEMS) worldwide to identify risks in retrieving COVID-19 patients, and develop strategies to mitigate these.Simulation involving the whole aeromedical retrieval team ensures that safety concerns can be addressed during the development of a standard operating procedure. Some services tested personal protective equipment and protocols in the aeromedical environment with simulation. We also incorporated experiences, standard operating procedures and approaches across several HEMS services internationally.As a result of this collaboration, we outline an approach to the safe aeromedical retrieval of a COVID-19 patient, and describe how this framework can be used to develop a local standard operating procedure.
Hypertrophied reversed palmaris longus muscle (pseudotumor) of the forearm causing median nerve compression: a case report
Authors: Hashem Majdi , Alatassi Raheef , Narinder Kaushal , Emran Fawaz 
Published: May 2020

Abstract
Background
The palmaris longus muscle is considered one of the most anatomically variable muscles in the human body. Localized swelling of the forearm due to hypertrophy of the palmaris longus muscle is rare.

Case presentation
Here, we report a rare case of a 24-year-old Arab man who presented with a painful mass on his forearm with symptoms of median nerve compression. A full radiological assessment was performed, and he was treated conservatively.

Conclusion
This case confirmed that a hypertrophied palmaris longus muscle can be the cause of swelling on the forearm and should always be considered in the differential diagnosis. With this report, we aimed to increase awareness regarding the unusual variations of palmaris longus muscle and the importance of using radiological investigations to establish a diagnosis.
Integration of new moving object segmentation and classification techniques using optimal salp swarm-based feature fusion with linear multi k-SVM classifier
Authors: G. Jemilda , S. Baulkani 
Published: May 2020

AbstractThe feature extraction technique is applied on least enclosing rectangle (LER) of the segmented object to increase the processing speed. The main intuition of this salp swarm algorithm relays on reducing the computational load of the proposed classifier by removing the repetitive and unrelated features from the feature vector. Also, increased training samples of similarly shaped classes when applied on the classifier can generate the misclassification results. Thus, a new layered kernel-based support vector machine (k-SVM) classifier is developed by means of integrating the k-neural network classifier and layered SVM classifier. Because of the high dimensional features, a difficulty occurs in the application of a single classifier. In order to ease the computational load, this multi classifier is integrated with a shadow elimination technique to classify the object categories of intelligent transportations system such as motorcycles, bicycles, cars, and pedestrians.
European ceramic technology in the Far East: enamels and pigments in Japanese art from the 16th to the 20th century and their reverse influence on China
Authors: Montanari Riccardo , Murakami Nobuyuki , Colomban Philippe , Alberghina Maria Francesca , Pelosi Claudia , Schiavone Salvatore 
Published: May 2020

Abstract
The production of Japanese enamels for porcelain decoration was thought to have originated from the direct and exclusive influence of Chinese potters who moved to Japan during the chaotic Ming to Qing dynastic change in 1644. Recent systematic studies have identified, for the first time, the crucial influence of Jesuit missionaries on pigment and enamel production in Japan from the late 16th-century. In particular, such first encounter laid the foundation for the continued influence exerted by European technology on Japanese art throughout the centuries. The present study has further identified European enamels used for the decoration of polychrome wares fired in Arita, the porcelain production center of Japan. This continued exchange not only marked the Edo period, but also extended into the twentieth century. For the first time, the lack of written records regarding the use of western pigments for enamel production caused by the persecutions of European and Japanese Christians has been overcome in the work herein presented. The nature of the imported materials has been firmly identified and characterized. The analytical results (EDXRF and Raman) have finally revealed how western technology and materials not only kept influencing Japanese art during the isolation (sakoku) period, but also accompanied the strong westernization process that marked Japanese history from the late nineteenth century. Moreover, the significant reverse influence of Japanese-made enamels on Chinese polychrome porcelain production in the late Qing and twentieth century has been fully identified for the first time. Furthermore, results show that the shift of the Pb mode of lead antimonate (Naples Yellow) is affected by the firing temperature for enamel decoration, and that this characteristic, along with the chemical composition, enables the identification of the origin and manufacture period of the yellow enamel.
Soft optical metamaterials
Authors: Chen Yixin , Ai Bin , Wong Zi Jing 
Published: May 2020

AbstractOptical metamaterials consist of artificially engineered structures exhibiting unprecedented optical properties beyond natural materials. Optical metamaterials offer many novel functionalities, such as super-resolution imaging, negative refraction and invisibility cloaking. However, most optical metamaterials are comprised of rigid materials that lack tunability and flexibility, which hinder their practical applications. This limitation can be overcome by integrating soft matters within the metamaterials or designing responsive metamaterial structures. In addition, soft metamaterials can be reconfigured via optical, electrical, thermal and mechanical stimuli, thus enabling new optical properties and functionalities. This paper reviews different types of soft and reconfigurable optical metamaterials and their fabrication methods, highlighting their exotic properties. Future directions to employ soft optical metamaterials in next-generation metamaterial devices are identified.
Transverse colon perforation in the mediastinum after esophagectomy: a case report
Authors: Konno-Kumagai Takuro , Sakurai Tadashi , Taniyama Yusuke , Sato Chiaki , Takaya Kai , Ito Ken , Kamei Takashi 
Published: May 2020

Abstract
Background
While anastomotic leakage, recurrent laryngeal nerve paralysis, and pneumonia are well-known complications of esophagectomy, the incidence of hiatal hernia after esophagectomy for carcinoma has been reported to only be between 0.6 and 10%. We report a very rare case of hiatal hernia with transverse colon rupture in the mediastinum after esophagectomy in a 65-year-old woman.

Case presentation
The patient underwent definitive chemoradiotherapy for clinical stage IIA esophageal squamous cell carcinoma and salvage esophagectomy with gastric tube reconstruction through a posterior mediastinum route for residual carcinoma. Three years after the initial surgery, two metastatic nodules in the lateral and posterior segments of the liver were detected on follow-up CT and were treated with oral anticancer drugs. After 6 months, the patient was readmitted for anorexia. Upon admission, computed tomography revealed an ileus caused by a hiatal hernia. Emergent operative repair was performed; an incarcerated herniation of the transverse colon was perforated in the mediastinum, and partial transverse colon resection and colostomy were performed. Intensive care was required to control septic shock after surgery, and the patient was discharged on the 53rd postoperative day.

Conclusions
Cases of hiatal hernia with digestive tract prolapsing into the mediastinum after esophagectomy with reconstruction through posterior mediastinum are rare but potentially life-threatening complications.
Computational modeling and ligand-based design of some novel hypothetical compound as prominent inhibitors against Mycobacterium tuberculosis
Authors: Adeniji Shola Elijah , Adalumo Olajumoke Bosede 
Published: May 2020

Abstract
Background
Time consumed and expenses in discovering and synthesizing new hypothetical drugs with improved biological activity have been a major challenge toward the treatment of multi-drug-resistant strain Mycobacterium tuberculosis (TB). To solve the above problem, quantitative structure activity relationship (QSAR) is a recent approach developed to discover novel agents with better biological activity against M. tuberculosis.

Results
A validated QSAR model was developed in this study to predict the biological activities of some anti-tubercular compounds and to design new hypothetical drugs is influenced with the molecular descriptors, AATS7s, VR1_Dzi, VR1_Dzs, SpMin7_Bhe, and TDB8e, which has been validated through internal and external validation test. Prior to high anti-tubercular activity of the lead compound, compound 17 served as a template structure to design compounds with improved activity. Among the compounds designed, compounds 17i, 17j, and 17n were observed with improved anti-tubercular activities which ranges from 8.8981 to 9.0377 pBA.

Conclusion
The outcome of this research is recommended for pharmaceutical and medicinal chemists to synthesis and carry out an in vivo and in vitro screening for the proposed designed compounds in order to substantiate the computational findings.
KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer.
Authors: Cortes Javier , Cescon David W. , Rugo Hope S. , Nowecki Zbigniew , Im Seock-Ah , Yusof Mastura Md , Gallardo Carlos , Lipatov Oleg , Barrios Carlos Henrique , Holgado Esther , Iwata Hiroji , Masuda Norikazu , Torregroza Otero Marco , Gokmen Erhan , Loi Sherene , Guo Zifang , Zhao Jing , Aktan Gursel , Karantza Vassiliki , Schmid Peter 
Published: May 2020

1000 Background: Pembrolizumab (pembro) monotherapy showed promising antitumor activity and manageable safety in patients (pts) with metastatic TNBC in KEYNOTE-012, -086 and -119. KEYNOTE-355 (ClinicalTrials.gov, NCT02819518) compared pembro + chemotherapy (chemo) vs placebo (pbo) + chemo for previously untreated locally recurrent inoperable or metastatic TNBC. Methods: Pts with ≥6 mo DFI were randomized 2:1 to pembro + chemo (nab-paclitaxel; paclitaxel; or gemcitabine/carboplatin) or pbo + chemo for up to 35 administrations of pembro/pbo or until progression/intolerable toxicity. Pts were stratified by chemo type (taxane vs gemcitabine/carboplatin), PD-L1 status (CPS ≥1 vs <1), and prior (neo)adjuvant treatment with same-class chemo (yes vs no). Dual primary endpoints are PFS (RECIST v1.1, blinded independent central review) and OS by tumor PD-L1 expression (CPS ≥10 and ≥1) and in all pts. PFS was estimated using the Kaplan-Meier method. Stratified log-rank tests were used to assess treatment group differences. HR and 95% CIs were based on a stratified Cox regression model. AEs were monitored throughout the study and graded per NCI CTCAE v4.0. Results: As of Dec 11 2019, median follow-up was 17.5 mo for pembro + chemo (n=566) and 15.5 mo for chemo (n=281). Pembro + chemo significantly improved PFS vs chemo alone in pts with CPS ≥10 tumors (Table), meeting one of the protocol-defined primary objectives. Although the boundary for a statistically significant benefit of pembro + chemo in pts with CPS ≥1 tumors was not met and formal testing in ITT was not performed, the pembro treatment effect increased with PD-L1 enrichment (Table). OS follow-up is ongoing. Grade 3-5 treatment-related AE rates were 68.1% with pembro + chemo (2 deaths) vs 66.9% with chemo (0 deaths); rates of grade 3-4 immune-mediated AEs and infusion reactions were 5.5% vs 0%. Clinical trial information: NCT02819518 . Conclusion: Pembro combined with several chemo partners showed a statistically significant and clinically meaningful improvement in PFS vs chemo alone in pts with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1 (CPS ≥10). Pembro + chemo was generally well tolerated, with no new safety concerns. [Table: see text]
Long-term follow up of lifileucel (LN-144) cryopreserved autologous tumor infiltrating lymphocyte therapy in patients with advanced melanoma progressed on multiple prior therapies.
Authors: Sarnaik Amod , Khushalani Nikhil I. , Chesney Jason Alan , Lewis Karl D. , Medina Theresa Michelle , Kluger Harriet M. , Thomas Sajeve Samuel , Domingo Musibay Evidio , Pavlick Anna C. , Whitman Eric D. , Martin-Algarra Salvador , Corrie Philippa Gail , Lutzky Jose , Hamid Omid , Wu Renee , Shi Wen , Fardis Maria , Weber Jeffrey S. , Larkin James M. G. , Kirkwood John M. 
Published: May 2020

10006 Background: Treatment options are limited for patients with advanced melanoma who have progressed on checkpoint inhibitors and targeted therapies. Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) leverages and enhances the body’s natural defense against cancer and has shown durable responses in heavily pretreated melanoma patients. Methods: C-144-01 is a global Phase 2 open-label, multicenter study of efficacy & safety of lifileucel in patients with unresectable metastatic melanoma who have progressed on checkpoint inhibitors and BRAF/MEK inhibitors, if BRAFv600 mutant. We report on Cohort 2 (N = 66) patients who have received TIL. Tumors were resected at local institutions, processed in central GMP facilities for TIL production, manufactured, cryopreserved & shipped back to sites in a 22-day process. Therapy consisted of one week of lymphodepletion, a single lifileucel infusion, and up to 6 IL-2 doses. ORR was based on RECIST v1.1 by investigator assessment. Data cutoff was Feb 2, 2020. Results: Baseline characteristics: 3.3 mean prior therapies (anti-PD1 100%; anti-CTLA-4 80%; BRAF/MEK inhibitor 23%), high baseline tumor burden (106 mm mean target lesion sum of diameters), 44% liver/brain lesions, 40.9% LDH > ULN. ORR by investigator was 36.4% (2 CR, 22 PR) and DCR was 80.3%. Mean time to response was 1.9 months (range: 1.3-5.6). After a median study follow-up of 17.0 months, median DOR (mDOR) was still not reached. Six responders have progressed, 2 have died and 2 started other anti-cancer therapy without progression. The adverse event profile was consistent with the underlying advanced disease and the lymphodepletion and IL-2 regimens. Additional follow-up data will be available for presentation. Conclusions: Lifileucel treatment results in a 36.4% ORR and mDOR was not reached at 17.0 months of median study follow up in a heavily pretreated metastatic melanoma patients with high baseline disease burden who progressed on multiple prior therapies, including anti-PD1 and BRAF/MEK inhibitors, if BRAFv600 mutant. Clinical trial information: NCT02360579.
Integrative tumor and immune cell multi-omic analyses to predict melanoma response to immune checkpoint blockade.
Authors: Anagnostou Valsamo , Bruhm Daniel C. , Niknafs Noushin , White James R , Sidhom John-William , Stein Julie E. , Tsai Hua-Ling , Wang Hao , Belcaid Zineb , Murray Joseph Christopher , Ross-Macdonald Petra B. , Wind-Rotolo Megan , Baras Alexander S , Taube Janis M. , Scharpf Robert B. , Grasso Catherine , Ribas Antoni , Pardoll Drew M. , Topalian Suzanne Louise , Velculescu Victor E. 
Published: May 2020

10009 Background: The complex crosstalk between tumor and immune cells during immune checkpoint blockade mandates the development of integrated models to interpret the antitumor immune response and predict clinical outcome. Methods: We performed comprehensive genomic, transcriptomic and T cell repertoire analyses on tumor biopsies from 64 patients with advanced melanoma receiving nivolumab +/- ipilimumab on CheckMate-038 (NCT01621490). Tumor biopsies were obtained at baseline and 2-4 weeks on therapy. Machine learning and Cox proportional hazards regression analyses were employed to integrate multi-omics features in predictive models of response, defined by RECISTv1.1 as complete and partial response, and survival (PFS and OS). Results: Responding patients had a higher tumor mutation burden (TMB) than non-responders. Expressed TMB more accurately predicted overall survival than genomic TMB (log rank p = 0.028 vs 0.078). High tumor aneuploidy was associated with worse prognosis especially for the patients in the nivolumab + ipilimumab group (log rank p = 0.01). TCR sequencing of paired tumors before and on-treatment revealed that responders had a significantly higher number of unique TCR clones at baseline and more clonotypic shifts on-treatment (p = 0.0018). Gene rearrangement analyses using transcriptome data identified a higher number of rearrangements involving immunoglobulin (Ig) genes in baseline tumors from responders. Deconvolution of transcriptomic data confirmed an enrichment in tumor associated B cells in baseline tumors of responders, suggesting that pre-existing B cell infiltration is a predictor of clinical outcome. Random forests were utilized to integrate Ig rearrangements, expressed TMB and tumor aneuploidy, into a predictive model of response that was superior to TMB (AUC = 0.89 and 0.65 respectively). Multivariate Cox proportional hazards analysis incorporating the same features was utilized to generate a risk score for each patient; those with high risk scores had a significantly shorter PFS compared to low risk patients (median PFS 1.45 months vs 29.01 months, log rank p = 3.4e-06, HR = 9.18, 95% CI: 3.14-26.85). Conclusions: Our findings highlight the multi-faceted interactions between the tumor and the immune system and the importance of pre-existing T and B cell immunity in driving clinical response and PFS after immune checkpoint blockade, laying the groundwork for integration of genomic and immune features into predictive models that may ultimately optimize therapeutic decisions.
Update on overall survival in COLUMBUS: A randomized phase III trial of encorafenib (ENCO) plus binimetinib (BINI) versus vemurafenib (VEM) or ENCO in patients with BRAF V600-mutant melanoma.
Authors: Gogas Helen , Ascierto Paolo Antonio , Flaherty Keith , Arance Ana , Mandalà Mario , Liszkay Gabriella , Garbe Claus , Schadendorf Dirk , Krajsova Ivana , Gutzmer Ralf , de Groot Jan Willem , Dutriaux Caroline , Loquai Carmen , Gollerkeri Ashwin , Pickard Michael D , Robert Caroline , Dummer Reinhard 
Published: May 2020

10012 Background: Treatment of patients with BRAF V600–mutant melanoma includes BRAF/MEK-inhibitor combinations based on demonstrated benefits on progression-free survival (PFS) and overall survival (OS). To better understand the proportion of patients who derive long-lived benefit and their characteristics, we performed an updated analysis of OS and other endpoints from the COLUMBUS trial. Methods: In Part 1 of COLUMBUS, 577 patients with advanced/metastatic BRAF V600‒mutant melanoma, untreated or progressed after first-line immunotherapy, were randomized 1:1:1 to ENCO 450 mg QD + BINI 45 mg BID (COMBO450) vs VEM 960 mg BID (VEM) or ENCO 300 mg QD (ENCO300). An updated analysis including PFS, OS, objective response rate (ORR), and safety was conducted after an additional 24 months’ follow-up from the initial analysis. The study is ongoing. Results: At data cutoff (November 2019, as-is data), events had occurred in 65%, 59%, and 75% of patients in the COMBO450, ENCO300, and VEM treatment arms, respectively. Across arms, median follow-up for OS was 60.6 months (mo), with median OS of 33.6 mo (95% CI, 24.4–39.2) for COMBO450, 23.5 mo (95% CI, 19.6–33.6) for ENCO300, and 16.9 mo (95% CI, 14.0–24.5) for VEM. Compared to VEM, COMBO450 decreased the risk of death by 38% (HR, 0.62 [95% CI, 0.49–0.79]). Updated median PFS was COMBO450, 14.9 mo (95% CI, 11.0–20.2), ENCO300, 9.6 mo (95% CI, 7.4–14.8), and VEM, 7.3 mo (95% CI, 5.6–7.9). PFS was longer for COMBO450 vs VEM (HR, 0.52 [95% CI, 0.40–0.67]). A landmark analysis showed a higher rate of OS for COMBO450 at each year analyzed, with OS rates at 4 years of 39%, 37%, and 26% COMBO450, ENCO300, and VEM, respectively. Updated safety analysis confirmed the beneficial long-term tolerability of COMBO450. Conclusions: In the COLUMBUS trial, results for updated PFS and OS with COMBO450 continue to demonstrate long-term benefits in patients with BRAF V600‒mutated melanoma. Clinical trial information: NCT01909453.