bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory Conditions Promote Resistance to Immune Checkpoint Inhibitors in High Microsatellite Instability Colorectal Cancer
Authors: Sui Qiaoqi , Zhang Xi , Tang Jinghua , Han Kai , Jiang Wu , Leen Liao , Kong Lingheng , Li Yuan , Hou Zhenlin , Zhou Chi , Zhang Chenzhi , Zhang Linjie , Xiao Binyi , Mei Wei-Jian , Xu Yanbo , Zheng Jian , Pan Zhi-Zhong , Ding Pei-Rong 
Published: September 2021

Abstract
Inflammatory conditions are common complications in colorectal cancer (CRC) and play significant roles in tumor progression and immunosuppression. However, the influence of inflammatory conditions on the tumor response to immune checkpoint inhibitors (ICIs) remains unclear. We included a high microsatellite instability (MSI-H) CRC patient whose primary tumor progressed and liver metastasis regressed after Pembrolizumab treatment. An organoid-T cell coculture model demonstrated an inhibited local immune response instead of systemic immunosuppression. Single-cell RNA sequencing suggested that neutrophils suppress the immune microenvironment, mostly through CTLA-4-associated pathways. A cohort of 73 patients with MSI-H CRC who received ICIs were enrolled, among whom inflammatory conditions were correlated with a poor tumor response. We demonstrated that inflammatory conditions in MSI-H CRCs correlate with resistance to ICIs through neutrophil-associated immunosuppression. Additional CTLA-4 blockade may improve the sensitivity to PD-1 blockade. Clinically, inflammatory conditions could predict a poor response to ICIs in MSI-H CRCs.
Intrinsic First and Higher-Order Topological Superconductivity in a Doped Topological Insulator
Authors: Scammell Harley , Ingham Julian , Geier Max , Li Tommy 
Published: September 2021

Abstract
We explore higher-order topological superconductivity in an artificial Dirac material with intrinsic spin-orbit coupling. A mechanism for superconductivity due to repulsive interactions – pseudospin pairing – has recently been shown to result in higher-order topology in Dirac systems past a minimum chemical potential [1]. Here we apply this theory through microscopic modelling of a superlattice potential imposed on an inversion symmetric hole-doped semiconductor heterostructure, and extend previous work to include the effects of spin-orbit coupling. We find spin-orbit coupling enhances interaction effects, providing an experimental handle to increase the efficiency of the superconducting mechanism. We find that the phase diagram, as a function of chemical potential and interaction strength, contains three superconducting states – a first-order topological p + ip state, a second-order topological spatially modulated p + iτp state, and a second-order topological extended s-wave state, sτ. We calculate the symmetry-based indicators for the p + iτp and sτ states, which prove these states possess second-order topology. Exact diagonalisation results are presented which illustrate the interplay between the boundary physics and spin orbit interaction. We argue that this class of systems offer an experimental platform to engineer and explore first and higher-order topological superconducting states.
Indonesian Genomic Landscape of Pathogenic Mutation of APC, KRAS, TP53, PIK3CA, and MLH1 in Colorectal Cancer
Authors: Marbun Vania Myralda Giamour , Lalisang Toar Jean Maurice , Erlina Linda 
Published: September 2021

Abstract
Background : Knowing colorectal cancer’s heterogeneity and dynamic features, recognizing its biological behaviour requires detailed identification of mutated genes involved. Colorectal cancer (CRC) requires several mutated genes to occur and those are dissimilar in each person hence essential to be discovered in specific population. Until recently, there is no known study describing genomic landscape of CRC in Indonesian population. This study aims to describe profile of pathogenic mutation of APC, TP53, PIK3CA, KRAS, and MLH1 in CRC patients treated at 3 different hospitals in Jakarta. Methods : This is a descriptive study conducted on CRC patients who underwent neoadjuvant, surgical, and adjuvant therapy at RSCM, RSKJ, and MRCCC in 2017-2018. DNA analysis was performed using next-generation sequencing and aligned against GRCh38. Pathogenic variant was identified using ACMG classification and FATHMM score. Data related to behaviour and survival were collected from medical records. Results : There were total 22 subjects in which APC, TP53, and PIKCA were mutated. KRAS mutation occurred in 64%, while MLH1 in 45%. Five types of mutation were identified, including nonsense, missense, frameshift, splice-site, and silent mutation. There are 4 groups of co-occurring mutations, which are APC, TP53, PIK3CA (triple mutation/TM) alone; TM+KRAS; TM+MLH1; and TM+KRAS+MLH1, presenting different nature and survival. Conclusion : Indonesia having various ethnicities with diverse diet and lifestyle has distinct profile of pathogenic mutation presenting mostly with locally-advanced stage with various outcome and survival rate.
The Pregnancy Experiences and Antenatal Care Services of Chinese Migrants in Switzerland: A Qualitative Study
Authors: CAI Ding cui , Villanueva Paulina , Stuijfzand Susannah , Lu Hong , Zimmermann Basile , Horsch Antje 
Published: September 2021

Abstract
Background: Differences in reproductive health outcomes according to the mother's origins have been reported in Switzerland, for example, women from European countries and non-European countries. The Swiss Federal Office of Public Health has therefore called for specific Swiss-wide studies on migrant populations. This study explores the pregnancy and antenatal care experiences of Chinese migrants in Switzerland, intending to clarify their maternity care needs.Methods: In-depth interviews of 14 Chinese mothers and 13 family members were conducted in Chinese or English and audio recorded. All audio-recordingswere transcribed verbatim. All Chinese transcripts were translated into English.Thematic analysis was performed with the assistance of the qualitative dataanalysis software, MAXQDA Analytics Pro 2020.Results: Five themes were extracted from the transcripts: (1) Motivations andconcerns about having children, (2) The merits of the Swiss maternity caresystem, (3) The inconvenience and barriers of accessing Swiss maternity careservices, (4) Strategies to deal with the inconveniences of the Swiss maternitycare system, and (5) The need for culturally sensitive care.Conclusions: The results of our study provide new knowledge and understandingof pregnancy experiences and antenatal care services of Chinese mothers andtheir families in Switzerland. Their unique positive experiences included: familyplanning, the continuity of maternity services, humane care with the privacyrespected, personalized sensitive care needs, preferences for female obstetriciansand obstetricians of Asian origin. Several barriers were highlighted, suchasinformation seeking difficulties, communication difficulties, and a rigidappointment system. Reducing barriers enabling access to maternity care serviceswithin the Swiss healthcare system is necessary to provide equal qualitymaternitycare for individuals, irrespective of their origins.
The New Putative Type III Effector SkP48 in Bradyrhizobium sp. DOA9 is Involved in Legume Nodulation
Authors: Piromyou Pongdet , Songwattana Pongpan , Boonchuen Pakpoom , Nguyen Hien P. , Manassila Monchai , Tantanuch Waraporn , Maikhunthod Bussayarat , Teamtisong Kamonluck , Tittabut Panlada , Boonkerd Nantakorn , Giraud Eric , Teaumroong Neung 
Published: September 2021

Abstract
Bradyrhizobium sp. DOA9 can nodulate a wide spectrum of legumes; however, unlike other bradyrhizobia, DOA9 carries a symbiotic plasmid harboring type III secretion system (T3SS) and several effector (T3E) genes, one of which encodes a new putative type III effector—SkP48. Here, we demonstrated the pivotal roles of SkP48 from Bradyrhizobium sp. DOA9 in inhibiting nodulation of various Vigna species and Crotalaria juncea and suppressing nodulation efficiency of Arachis hypogea. By contrast, the nodulation efficiency of a SkP48 mutant did not differ significantly with the DOA9 wild-type strain on Macroptilium atropurpureum and Stylosanthes hamata. An evolutionary analysis revealed that the SkP48 effector which contains a shikimate kinase and a SUMO protease (C48 cysteine peptidase) domain is distinct from the others effectors previously identified in others bradyrhizobia and pathogenic bacteria. Our findings suggest that the new putative T3E SkP48 is a key factor suppressing nodulation and nodule organogenesis in several legumes by activation of effector-triggered immunity through salicylic acid biosynthesis induction, which is deleterious to rhizobial infection. In addition, nodulation may be modulated by the function of defensins involved in jasmonic acid signalling in V. radiata SUT1.
Differential Diagnosis of Lipoma and Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma by Cytological Analysis
Authors: Sugiyama Kana , Washimi Kota , Sato Shinya , Hiruma Toru , Sakai Mai , Okubo Yoichiro , Miyagi Yohei , Yokose Tomoyuki 
Published: September 2021

Abstract
Background: Adipocytic tumors are the most common soft tissue tumors, with lipomas and atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDL) comprising the majority of cases. Preoperative differential diagnosis of lipoma or ALT/WDL can provide important information for decisions regarding treatment. We evaluated the cytological findings of 20 cases of lipoma and ALT/WDL.Methods: Fluorescence in situ hybridization (FISH) was performed on formalin-fixed paraffin-embedded specimens (FFPE) to examine mouse double minute 2 homolog (MDM2) amplification in all cases. Tissue samples were collected from the center of the surgical materials, stained with Papanicolaou, and evaluated for 12 cytological parameters by six cytotechnologists.Results: The findings regarding large atypical cells, multinucleated cells, and nuclear pleomorphism were highly concordant among the cytotechnologists and were associated with MDM2 amplification. Large atypical cells, considered a highly specific feature of ALT/WDL, were not observed in the lipoma cases. However, the sensitivity of the large atypical cell findings was not high (67%), and therefore, comprehensive evaluation of multinucleated cells and pleomorphism is crucial for predicting the diagnosis of ALT/WDL. FISH of MDM2 on Papanicolaou-stained specimens was performed in four cases. In two cases, the results were similar to those of MDM2 FISH performed on FFPE sections and were reproducible, whereas in two other cases, the signal could not be evaluated because of the strong background coloration. Conclusions: Cytology specimens may be useful for preoperative diagnosis of adipocytic tumors, particularly if the FISH conditions for Papanicolaou-stained specimens and the detection accuracy of MDM2 amplification can be improved.
Immunophenotypic Landscape and Prognosis-Related mRNA Signature in Diffuse Large B Cell Lymphoma
Authors: Jiang Yanan , Sun Huimeng , Xu Hong , Wu Wenqi , Lv Yangyang , Wang Jinhuan , Liu Su , Zhai Yixin , Tian LinYan , Wang Yafei , Zhao Zhigang 
Published: September 2021

Abstract
Diffuse large B cell lymphoma (DLBCL) exhibits a tightly complexity immune landscape. In this study, we intended to identify different immune phenotype and to examine the immune related mRNA signature for clinical characteristic, therapeutic responsiveness as well as risk stratification and survival prediction in DLBCL. We separated 738 DLCBL patients into two robust subtypes with distinct immune features based on 28 immune cell types. GO analysis uncovered the concordant classification of two robust significant subtypes of DLBCL. Immunity-L group, associated with poorer outcomes, was characterized by significantly lower immune cell infiltration. Immunity-H group, associated with better outcomes, was characterized by significantly higher immune cell infiltration. Further, a prognostic gene signature related immune infiltration was established by a least absolute shrinkage and selection operator (LASSO)-Cox regression model. The comprehensive results showed that the high-risk group was correlated with lower immune infiltration, more aggressive phenotypes, lower overall survival and more sensitive to lenalidomide. In contrast, a low-risk group score was associated with higher immune infiltration, less aggressive phenotypes, better overall survival and more likely to benefit from PD-1/PD-L1 inhibitors. Finally, a nomogram comprised of the immune risk score and IPI score was verified to more accurately predict the overall survival of DLBCL than traditional clinical prediction models. Altogether, our data demonstrate the heterogeneity of immune patterns within DLBCL and deepen our molecular understanding of this tumor entity.
An Analysis of the Selection Criteria for Postgraduate Physician Assistant Residency and Fellowship Programs in the United States
Authors: Kidd Vasco Deon , Vanderlinden Sarah , Spisak Jennifer M 
Published: September 2021

Abstract
BackgroundThis study aims to investigate the admission criteria used by PA postgraduate education programs in selecting licensed PA applicants for postgraduate training in the United States. To our knowledge, there have been no previously published reports on selection criteria and/or other factors influencing postgraduate PA admission decisions. This study both draws on and builds upon previous research conducted by Vasco Deon Kidd et. al in exploring the characteristics of PA postgraduate education programs in the United States.Method A non-experimental, descriptive research study was designed to obtain information from members of the Association of Postgraduate Physician Assistant Programs (APPAP). ResultsTwenty-three out of 73 postgraduate programs (35.1%) responded to the survey; the low response rate in our survey may have been attributed to the resurgence of COVID-19 fueled by the delta variant. Nevertheless, the study reported that applicant PAs and NPs are largely selected on the basis of several factors. The most heavily weighted factor is the interview itself; other selection criteria perceived to be extremely/very important included board certification/eligibility, letters of recommendation, advanced degree, and personal essay. Survey data suggest that publications, undergraduate transcripts, and class rankings are not considered to be of high importance in applicant selection. The total cost of training a PA resident or fellow in postgraduate programs is currently $93,000 whereas the average cost of training a categorical physician resident is estimated at $150,000 per year when considering both salary and benefits. The number of PA applicants applying to each postgraduate training program averages around 26 and total number of enrollees is 3.6 per program.ConclusionsThis is the first study to examine criteria and others factors used by postgraduate PA programs in selecting candidates for admission. Results can be used by postgraduate programs for quality improvement initiatives related to including additional or modifying current selection criteria to improve the quality of trainee selection. Further research is needed to examine correlations between applicant attributes, selection criteria, and trainee success in completing postgraduate training.
Pre-Trained Transformer-Based Language Models for Sundanese
Authors: Wongso Wilson , Lucky Henry , Suhartono Derwin 
Published: September 2021

Abstract
The Sundanese language has over 32 million speakers worldwide, but the language has reaped little to no benefits from the recent advances in natural language understanding. Like other low-resource languages, the only alternative is to fine-tune existing multilingual models. In this paper, we pre-trained three monolingual Transformer-based language models on Sundanese data. When evaluated on a downstream text classification task, we found that most of our monolingual models outperformed larger multilingual models despite the smaller overall pre-training data. In the subsequent analyses, our models benefited strongly from the Sundanese pre-training corpus size and do not exhibit socially biased behavior. We released our models for other researchers and practitioners to use.
Does Safety Netting for Lung Cancer Symptoms Help Patients to Reconsult Appropriately? A Qualitative Study
Authors: Black Georgia , Os Sandra van , Renzi Christina , Walter Fiona , Hamilton Willie , Whitaker Katriina L 
Published: September 2021

Abstract
Background

Safety netting in primary care is considered an important intervention for managing diagnostic uncertainty. This is the first study to examine how patients understand and interpret safety netting advice around low-risk potential lung cancer symptoms, and how this affects reconsultation behaviours.
Methods

Qualitative dyadic interview study in UK primary care. Pre-covid-19, five patients were interviewed face-to-face twice (shortly after a primary care consultation for potential lung cancer symptom(s) and 2–5 months later). The general practitioner (GP) they last saw was interviewed face-to-face once. During the covid-19 pandemic, an additional 15 patients were interviewed once via telephone. Audio-recorded interviews were transcribed verbatim and analysed using a mix of inductive and deductive thematic analysis.
Results

The findings from our thematic analysis suggest that patients prefer active safety, as part of thorough and logical diagnostic uncertainty management. Passive safety netting may be perceived as dismissive and cause delayed reconsultation. GP safety netting strategies are not always understood, potentially causing patient worry and dissatisfaction. Telephone consultations and the diagnostic overshadowing of COVID-19 on respiratory symptoms impacted GPs’ safety netting strategies and patients’ appetite for active follow up measures.
Conclusions

Safety netting guidelines do not yet offer solutions that have been proven to promote symptom vigilance and timely reconsultation for low-risk lung cancer symptoms. Patients prefer active safety netting coupled with thorough consultation techniques and a comprehensible diagnostic strategy, and may respond adversely to passive safety netting advice.
Methotrexate-Loaded Nanoparticles Ameliorate Autoimmune Arthritis by Regulating the Balance of Interleukin-17-Producing T Cells and Regulatory T and B Cells
Authors: Park Jin-Sil , Lee Donghyun , Yang SeungCheon , Na Hyun Sik , Cho Keun-Hyung , Choi JeongWon , Koo Heebeom , Cho Mi-La , Park Sung-Hwan 
Published: September 2021

Abstract
Background: Rheumatoid arthritis (RA) is a progressive systemic autoimmune disease that is characterized by infiltration of inflammatory cells into the hyperplastic synovial tissue, resulting in subsequent destruction of adjacent articular cartilage and bone. Methotrexate (MTX), the first conventional disease-modifying antirheumatic drug (DMARD), could alleviate articular damage in RA and is implicated in humoral and cellular immune responses. However, MTX has several side effects, so efficient delivery of low-dose MTX is important. Methods: To investigate the efficacy of MTX-loaded nanoparticles (MTX-NPs) against RA, free MTX or MTX-NPs were administered as subcutaneous route to mice with collagen-induced arthritis (CIA) at 3 weeks after CII immunization. The levels of inflammatory factors in tissues were determined by immunohistochemistry, confocal microscopy, real-time PCR, and flow cytometry. Results: MTX-NPs ameliorated arthritic severity and joint destruction in collagen-induced arthritis (CIA) mice compared to free MTX-treated CIA mice. The levels of inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α, and vascular endothelial growth factor, were reduced in MTX-NPs-treated mice. Numbers of phosphorylated STAT3-positive CD4+ cells and CD4+IL-17+ cells were reduced whereas the number of CD4+CD25+Foxp3+ cells increased in spleens from MTX- NPs-treated CIA mice compared to MTX-treated CIA mice. The frequency of CD19+CD25+Foxp3+ regulatory B cells increased in ex vivo splenocytes from MTX-loaded NPs-treated CIA mice compared to MTX-treated CIA mice. Conclusion: The results suggest that MTX-loaded NPs have therapeutic potential for RA.
The Effect of Counseling With Cognitive Behavior Approach on Self-esteem and Body Image in Lactating Mothers: Randomized Clinical Trial
Authors: Zamiri-Miandoab Nasrin , Mirghafourvand Mojgan , Nemati Fatemeh , kamalifard mahin 
Published: September 2021

Abstract
BackgroundSelf-esteem and body image are the factors that change during different periods of a women’s life. Some of the women experience low self-esteem and negative body image in pregnancy and postpartum. These two factors along with other factors can reduce the rate of exclusive breastfeeding among women. Cognitive-behavior therapy is one of the psychological approaches that is effective on the betterment of many of the psychological and personality disorders such as body image disorders as well as improvement of self-esteem. The aim of this randomized control trial is to recognize the effects of cognitive-behavior counseling during pregnancy period on self-esteem, body image (primary outcome) and exclusive breastfeeding (secondary outcome).Methodsin this randomized controlled trial, 70 eligible pregnant women referring to health centers of Tabriz- Iran were assigned to two groups of 35 as intervention and control groups using randomized blocking method. For intervention group, 8 sessions of cognitive-behavior therapy based on Cash and Strachan’s body image protocol and Michael Freeʼs for self-esteem were performed.Rosenberg self-esteem scale and multidimensional body self-relation questionnaire (MBSRQ) were completed before intervention, immediately after intervention and 4 weeks after delivery. Likewise, exclusive breastfeeding questionnaire was completed 4 weeks after childbirth. Independent t-test, chi square and repeated measures ANOVA tests were used to analyze the data.ResultsAccording to repeated measures ANOVA test and with controlling baseline score, the mean scores on self-esteem (adjusted mean difference (AMD): 7.18; 95%CI: 4.43 to 9.94; p<0.001) and body image (AMD: 49.74; 95%CI: 70.91 to 28.54; p<0.001) in the intervention group were significantly higher than the control group. 63.6 % of intervention group mothers and 30.3% of control group mothers had exclusive breastfeeding which for the intervention group was significantly higher than the control group based on chi square test (p=0.007). Conclusionscognitive-behavior approach was effective on the improvement of self-esteem and body image and through which might lead to the increase of exclusive breastfeeding among women. Trial register number: Iranian registry clinical trials (IRCT20110524006582N33). Date of registration: 2020-8-19. URL: https://en.irct.ir/trial/43395.