bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attitudes to functional neurology and some other ‘prescriptive’ chiropractic techniques and their associations with chiropractic conservatism: a cross-sectional survey of chiropractic students
Authors: Demortier Marine , Goncalves Guillaume , Leboeuf-Yde Charlotte , Le Scanff Christine , Wedderkopp Niels 
Published: May 2020

Abstract
Background
Chiropractic technique systems (‘prescriptive’ techniques) might be interpreted as helpful guidelines. However, ‘prescriptive’ techniques, such as Functional Neurology (FN), Sacro-Occipital Technique, and Applied Kinesiology are more concerned with the ‘technical’ diagnosis than the condition and its symptoms and, thus, seem to provide easy solutions.

Design and objectives
In a voluntary anonymous questionnaire survey carried out late 2017, we explored interest in ‘prescriptive’ techniques, particularly FN, among French chiropractic students in grades 3–6, and the possible link with chiropractic conservatism. We investigated their: i) attitudes to the use of ‘prescriptive’ techniques, ii) awareness of FN, and iii) attitudes to FN. Further, if their attitudes to some conservative chiropractic concepts influenced their clinical approach on iv) some ‘prescriptive’ chiropractic techniques and v) attitudes to FN.

Method
Data reported in tables illustrated the prevalence of the use of ‘prescriptive’ techniques, awareness of FN, and positive attitude to FN (i.e. interest in and acceptance of). Students were given a FN score based on five questions on their interest in and acceptance of FN (0 to 5), dichotomized into two groups: ‘not positive attitude’ (0 to 1) and ‘positive attitude’ (2 to 5). Chiropractic conservatism was graded from 1 to 4. Associations were tested between conservatism groups and i) interest in ‘prescriptive’ techniques and ii) FN attitudes groups.

Results
The response rate was 67% (N = 359), of which 90% were positive toward ‘prescriptive’ techniques. Only 10% had never heard about FN and in the 6th year all had heard about it. Only a minority, unrelated to the year of study, approved of the two examples given of FN concepts. Nevertheless, a majority were positive towards FN, more so in the higher grades. Students with the most conservative beliefs were 17 times more likely to want to use ‘prescriptive’ techniques and 11 times more likely to have a higher FN score.

Conclusion
Although not taught in the curriculum, these students were attracted to ‘prescriptive’ techniques including FN, particularly in the higher grades. Curiously, despite this interest they do not generally agree with some key concepts within FN.
Integrating clinical and research training in child psychiatry: fifteen-year outcomes of a federally supported program
Authors: Calhoun Amanda , Bloch Michael H. , Stubbe Dorothy , Leckman James F. , Martin Andrés 
Published: May 2020

Abstract
Background
The Albert J. Solnit Integrated Training Program (AJSP) is an educational initiative designed to prepare physician-scientists for independent careers in the investigation and treatment of childhood psychiatric disorders.

Methods
We compared fifteen cohorts (each representing a consecutive year of matriculation) of AJSP trainees and graduates (n = 30) to peers who were comparably ranked in our original match lists but ultimately pursued residency programs elsewhere (n = 60). Outcomes of interest between the two groups included professional affiliation, as measured by: (1) membership in the American Academy of Child and Adolescent Psychiatry (AACAP); and (2) certification by the American Board of Psychiatry and Neurology (ABPN), as well as three domains of research productivity: (1) Competitive awards received from AACAP; (2) Publication-related metrics derived from the National Library of Medicine (NLM); and (3) Federal grant funding from the National Institutes of Health (NIH).

Results
AJSP participants were more commonly affiliated with AACAP and board certified in CAP. AJSP graduates and trainees outperformed their control group peers in several research outcomes: (1) Receipt of AACAP awards and number of awards per recipient were higher, and time to first award shorter in the AJSP than in the control group; (2) AJSP participants had more publications in PubMed, more first-authored publications, a higher h-index, and a shorter time to first publication than participants in the control group; and (3) NIH K- or R-series funding success rate was higher among AJSP participants (p < 0.05 for all comparisons).

Conclusions
A program designed to support the development of clinician-scientists specifically dedicated to childhood mental health needs has been successful in fostering scientific creativity, productivity and independence. The expansion and replication of similar training initiatives will be an in important step forward to address the high level of morbidity and mortality associated with child and adolescent psychiatric disorders.
Report of trisomy 2q34-qter and monosomy 4q35.2-qter in a child with mild dysmorphic syndrome and karyotype 46,XY,der(4)t(2;4)(q34;q35.2)pat
Authors: Meza-Espinoza Juan Pablo , Sáinz González Enrique , León-León Christian J. N. , Arámbula-Meraz Eliakym , Contreras-Gutiérrez José Alfredo , García-Magallanes Noemí , Madueña-Molina Jesús , Luque-Ortega Fred , Cervín-Serrano Salvador , Picos-Cárdenas Verónica Judith 
Published: May 2020

Abstract
Background
Concomitant trisomy 2q3 and monosomy 4q3 have been rarely reported. Pure trisomy 2q3 has been associated with microcephaly, hypertelorism, low-set ears, micrognathia, visceral abnormalities, and growth retardation. Monosomy 4q3 includes a wide variety of dysmorphic features such an abnormal skull shape, hypertelorism, Pierre Robin sequence, short nose with abnormal bridge, fifth finger clinodactyly, congenital heart, and genitourinary defects, in addition to intellectual disability, developmental delay, and hypotonia, but more distal deletions involving 4q34-qter may result in milder phenotypes. Here, we present a child with a mild dysmorphic syndrome, resulted of a duplication 2q34-qter and a deletion 4q35.2-qter inherited of his father.

Case presentation
We report a child, who at birth presented hypotonia, dysmorphism, and bilateral cryptorchidism. At 2 years and 9 month of age he showed brachycephaly, narrow forehead, bilateral frontoparietal hypertrichosis, down slanting palpebral fissures, sparse eyebrows, sparse short eyelashes, hypertelorism, depressed nasal root, broad nasal bridge, bulbous nasal tip, prominent colummela, broad nasal ala, smooth filtrum, high arched palate, thin upper lips, and ears rotated backwards. He also showed telethelia, hypertrichosis from dorsal to the sacral region, hands with clinodactyly and hypoplasia of the terminal phalanx of the fifth finger, and broad thumbs, broad first toes, and right cryptorchidism. A chromosomal study revealed a karyotype 46,XY,der(4)t(2;4)(q34;q35.2), while an array comparative genomic hybridization showed a 31.12 Mb duplication of the chromosome 2q34-q37.3 and a 1.49 Mb deletion in the chromosome 4q35.2.

Conclusions
To our knowledge, only four families with translocation t(2;4) have been reported, two of them involving t(2q;4q), but the breakpoints involved in our patient have not been previously observed. The genomic imbalance in this patient was a duplication of 318 genes of the region 2q34-q37.3 and a deletion of 7 genes of 4q35.2. We discuss difficulty to assign specific congenital abnormalities to these duplicated/deleted regions and include some cases with terminal deletions of 4q with normal or just mildly detectable phenotypic effects.
PD1/PD-L1 targeting in advanced soft-tissue sarcomas: a pooled analysis of phase II trials
Authors: Italiano Antoine , Bellera Carine , D’Angelo Sandra 
Published: May 2020

AbstractImmune checkpoint inhibitors, especially the programmed cell death receptor-1/ligand 1 (PD-1/L1) inhibitors, displayed promising efficacy in several solid tumor types and hematological malignancies. Data related to their activity in soft-tissue sarcomas (STS) are scarce.We performed a pooled analysis of clinical trials investigating a PD1 or PD-L1 antagonist in patients with advanced STS. Three hundred eighty-four patients were included in the pooled analysis; of those, 153 (39.8%) received a PD1/PD-L1 antagonist as a single agent. In patients treated with anti-PD1/PDL1 as a single agent, the overall response rate (ORR) and non-progression rate (NPR) were 15.1% and 58.5% respectively. In patients treated with a combination regimen, the ORR and NPR were 13.4% and 55.8% respectively. Analysis by histological subtype revealed that patients with alveolar soft part sarcoma and undifferentiated pleomorphic sarcoma exhibited the highest response rates and leiomyosarcoma the lowest. PD-L1 expression rate was low and inconsistently associated with objective response.PD-1/PD-L1 antagonists have limited activity in unselected STS. Future studies should implement histology and immune-based stratification of STS in their design as well as sequential blood and tissue sampling to better understand the mechanisms of resistance and response given sarcomas inherent heterogeneity.
Emerging role of RNA methyltransferase METTL3 in gastrointestinal cancer
Authors: Wang Qiang , Geng Wei , Guo Huimin , Wang Zhangding , Xu Kaiyue , Chen Chen , Wang Shouyu 
Published: May 2020

AbstractGastrointestinal cancer, the most common solid tumor, has a poor prognosis. With the development of high-throughput sequencing and detection technology, recent studies have suggested that many chemical modifications of human RNA are involved in the development of human diseases, including cancer. m6A, the most abundant modification, was revealed to participate in a series of aspects of cancer progression. Recent evidence has shown that methyltransferase-like 3 (METTL3), the first identified and a critical methyltransferase, catalyzes m6A methylation on mRNA or non-coding RNA in mammals, affecting RNA metabolism. Abnormal m6A levels caused by METTL3 have been reported to be involved in different aspects of cancer development, including proliferation, apoptosis, and metastasis. In this review, we will shed light on recent findings regarding the biological function of METTL3 in gastrointestinal cancer and discuss future research directions and potential clinical applications of METTL3 for gastrointestinal cancer.
ABCA8 is regulated by miR-374b-5p and inhibits proliferation and metastasis of hepatocellular carcinoma through the ERK/ZEB1 pathway
Authors: Cui Yifeng , Liang Shuhang , Zhang Shugeng , Zhang Congyi , Zhao Yunzheng , Wu Dehai , Wang Jiabei , Song Ruipeng , Wang Jizhou , Yin Dalong , Liu Yao , Pan Shangha , Liu Xirui , Wang Yan , Han Jihua , Meng Fanzheng , Zhang Bo , Guo Hongrui , Lu Zhaoyang , Liu Lianxin 
Published: May 2020

Abstract
Background
ATP binding cassette subfamily A member 8 (ABCA8) belongs to the ATP binding cassette (ABC) transporter superfamily. ABCA8 is a transmembrane transporter responsible for the transport of organics, such as cholesterol, and drug efflux. Some members of the ABC subfamily, such as ABCA1, may inhibit cancer development. However, the mechanism of ABCA8 in the process of cancer activation is still ambiguous.

Methods
The expression of ABCA8 in human hepatocellular carcinoma (HCC) tissues and cell lines was examined using qPCR, immunoblotting, and immunohistochemical staining. The effects of ABCA8 on the proliferation and metastasis of HCC were examined using in vitro and in vivo functional tests. A luciferase reporter assay was performed to explore the binding between microRNA-374b-5p (miR-374b-5p) and the ABCA8 3′-untranslated region (UTR).

Results
ABCA8 was frequently down-regulated in HCC and this down-regulation was negatively correlated with prognosis. The overexpression of ABCA8 inhibited growth and metastasis in HCC, whereas the knockdown of ABCA8 exerted the antithetical effects both in vivo and in vitro. ABCA8 was down-regulated by miR-374b-5p; this down-regulation can induce epithelial transformation to mesenchyme via the ERK/ZEB1 signaling pathway and promote HCC progression.

Conclusion
We exposed the prognostic value of ABCA8 in HCC, and illuminated a novel pathway in ABCA8-regulated inhibition of HCC tumorigenesis and metastasis. These findings may lead to a new targeted therapy for HCC through the regulation of ABCA8, and miR-374b-5p.
Humanization of care in pediatric wards: differences between perceptions of users and staff according to department type
Authors: Mandato C. , Siano M. A. , De Anseris A. G. E. , Tripodi M. , Massa G. , De Rosa R. , Buffoli M. , Lamanna A. , Siani P. , Vajro P. 
Published: May 2020

Abstract
Background
As the quality and quantity of patient-centered care may be perceived differently by recipients and independent observers, assessment of humanization of pediatric care remains an elusive issue. Herein we aim to analyze differences between the degrees of verified existing vs. perceived humanization issues of a pediatric ward. Furthermore, we examine whether there is concurrence between the degrees of humanization perceived by users (parents/visitors) vs. staff members.

Methods
The study was conducted in the pediatric wards of seven medical centers of the Campania region (Italy) categorized as general (n = 4), children’s (n = 1), and university (n = 2) hospitals. The degree of existing humanization was assessed by a multidisciplinary focus group for each hospital through a pediatric care-oriented checklist specifically developed to individuate the most critical areas (i.e., those with scores < 2.5). The degree of perceived humanization was assessed through four indicators: well-being, social aspects, safety and security, and health promotion.

Results
The focus groups showed that critical areas common to all centers were mainly concerned with welfare, mediation, translation, and interpretation services. Specific critical issues were care and organizational processes oriented to the respect and specificity of the person and care of the relationship with the patient. Perceived humanization questionnaires revealed a lack of recreational facilities and mediation and translation services.
As for specific features investigated by both tools, it was found that mediation and interpretation services were lacking in all facilities while patient perceptions and observer ratings for space, comfort, and orientation concurred only in the general hospital evaluations.

Conclusions
Future humanization interventions to ensure child- and family-friendly hospital care call for careful preliminary assessments, tailored to each pediatric ward category, which should consider possible differences between perceived and verified characteristics.
The Italian paediatric society raccomandations on children and adolescents extra-domestic activities during the SARS COV-2 emergency phase 2
Authors: Villani Alberto , Bozzola Elena , Siani Paolo , Corsello Giovanni 
Published: May 2020

Abstract
Background
Due to novel coronavirus infection emergency, restricting measures have been imposed in Italy. As well as adults, also children are limited in their daily routine.

Main text
As the lockdown period is expected to end on 3rd May 2020, we discuss the opportunity for children to practice safely recreational or physical activity outdoor.

Conclusion
The Italian Paediatric Society recommends specific recreational and physical activities according to the age of the children and respecting social distancing.
Antitumor activity of Z-endoxifen in aromatase inhibitor-sensitive and aromatase inhibitor-resistant estrogen receptor-positive breast cancer
Authors: Jayaraman Swaathi , Hou Xiaonan , Kuffel Mary J. , Suman Vera J. , Hoskin Tanya L. , Reinicke Kathryn E. , Monroe David G. , Kalari Krishna R. , Tang Xiaojia , Zeldenrust Megan A. , Cheng Jingfei , Bruinsma Elizabeth S. , Buhrow Sarah A. , McGovern Renee M. , Safgren Stephanie L. , Walden Chad A. , Carter Jodi M. , Reid Joel M. , Ingle James N. , Ames Matthew M. , Hawse John R. , Goetz Matthew P. 
Published: May 2020

Abstract
Background
The tamoxifen metabolite, Z-endoxifen, demonstrated promising antitumor activity in endocrine-resistant estrogen receptor-positive (ER+) breast cancer. We compared the antitumor activity of Z-endoxifen with tamoxifen and letrozole in the letrozole-sensitive MCF7 aromatase expressing model (MCF7AC1), as well as with tamoxifen, fulvestrant, exemestane, and exemestane plus everolimus in a letrozole-resistant MCF7 model (MCF7LR).

Methods
MCF7AC1 tumor-bearing mice were randomized to control (no drug), letrozole (10 μg/day), tamoxifen (500 μg/day), or Z-endoxifen (25 and 75 mg/kg). Treatment in the letrozole arm was continued until resistance developed. MCF7LR tumor-bearing mice were then randomized to Z-endoxifen (50 mg/kg) or tamoxifen for 4 weeks and tumors harvested for microarray and immunohistochemistry analysis. The antitumor activity of Z-endoxifen in the MCF7LR tumors was further compared in a second in vivo study with exemestane, exemestane plus everolimus, and fulvestrant.

Results
In the MCF7AC1 tumors, both Z-endoxifen doses were significantly superior to control and tamoxifen in reducing tumor volumes at 4 weeks. Additionally, the 75 mg/kg Z-endoxifen dose was additionally superior to letrozole. Prolonged letrozole exposure resulted in resistance at 25 weeks. In MCF7LR tumor-bearing mice, Z-endoxifen significantly reduced tumor volumes compared to tamoxifen, letrozole, and exemestane, with no significant differences compared to exemestane plus everolimus and fulvestrant. Additionally, compared to tamoxifen, Z-endoxifen markedly inhibited ERα target genes, Ki67 and Akt expression in vivo.

Conclusion
In endocrine-sensitive and letrozole-resistant breast tumors, Z-endoxifen results in robust antitumor and antiestrogenic activity compared to tamoxifen and aromatase inhibitor monotherapy. These data support the ongoing development of Z-endoxifen.
MHC-I genotype and tumor mutational burden predict response to immunotherapy
Authors: Goodman Aaron M. , Castro Andrea , Pyke Rachel Marty , Okamura Ryosuke , Kato Shumei , Riviere Paul , Frampton Garrett , Sokol Ethan , Zhang Xinlian , Ball Edward D. , Carter Hannah , Kurzrock Razelle 
Published: May 2020

Abstract
Background
Immune checkpoint blockade (ICB) with antibodies inhibiting cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein-1 (PD-1) (or its ligand (PD-L1)) can stimulate immune responses against cancer and have revolutionized the treatment of tumors. The influence of host germline genetics and its interaction with tumor neoantigens remains poorly defined. We sought to determine the interaction between tumor mutational burden (TMB) and the ability of a patient’s major histocompatibility complex class I (MHC-I) to efficiently present mutated driver neoantigens in predicting response ICB.

Methods
Comprehensive genomic profiling was performed on 83 patients with diverse cancers treated with ICB to determine TMB and human leukocyte antigen-I (HLA-I) genotype. The ability of a patient’s MHC-I to efficiently present mutated driver neoantigens (defined by the Patient Harmonic-mean Best Rank (PHBR) score (with lower PHBR indicating more efficient presentation)) was calculated for each patient.

Results
The median progression-free survival (PFS) for PHBR score < 0.5 vs. ≥ 0.5 was 5.1 vs. 4.4 months (P = 0.04). Using a TMB cutoff of 10 mutations/mb, the stable disease > 6 months/partial response/complete response rate, median PFS, and median overall survival (OS) of TMB high/PHBR high vs. TMB high/PHBR low were 43% vs. 78% (P = 0.049), 5.8 vs. 26.8 months (P = 0.03), and 17.2 months vs. not reached (P = 0.23), respectively. These findings were confirmed in an independent validation cohort of 32 patients.

Conclusions
Poor presentation of driver mutation neoantigens by MHC-I may explain why some tumors (even with a high TMB) do not respond to ICB.
Modeling neuronal consequences of autism-associated gene regulatory variants with human induced pluripotent stem cells
Authors: Ross P. Joel , Mok Rebecca S. F. , Smith Brandon S. , Rodrigues Deivid C. , Mufteev Marat , Scherer Stephen W. , Ellis James 
Published: May 2020

AbstractGenetic factors contribute to the development of autism spectrum disorder (ASD), and although non-protein-coding regions of the genome are being increasingly implicated in ASD, the functional consequences of these variants remain largely uncharacterized. Induced pluripotent stem cells (iPSCs) enable the production of personalized neurons that are genetically matched to people with ASD and can therefore be used to directly test the effects of genomic variation on neuronal gene expression, synapse function, and connectivity. The combined use of human pluripotent stem cells with genome editing to introduce or correct specific variants has proved to be a powerful approach for exploring the functional consequences of ASD-associated variants in protein-coding genes and, more recently, long non-coding RNAs (lncRNAs). Here, we review recent studies that implicate lncRNAs, other non-coding mutations, and regulatory variants in ASD susceptibility. We also discuss experimental design considerations for using iPSCs and genome editing to study the role of the non-protein-coding genome in ASD.
A novel role of vitronectin in promoting survival of mesenchymal stem cells under serum deprivation stress
Authors: Goyal Umesh , Ta Malancha 
Published: May 2020

AbstractBackgroundDue to their immunomodulatory and trophic support functions, mesenchymal stem cells (MSCs) are promising in the field of cell-based regenerative medicine. However, MSC survival post-transplantation is challenged by various microenvironment stress factors. Here, we investigated the role of vitronectin (VTN) in the survival strategy of MSCs under serum deprivation stress condition.MethodsProliferation kinetics and cell adhesion of MSCs under serum deprivation were determined from population doublings and cell-matrix de-adhesion studies, respectively. mRNA and protein expression levels of VTN were confirmed by qRT-PCR and Western blotting, respectively. Immunofluorescence technique revealed distribution of VTN under serum deprivation stress. siRNA and inhibitor-based studies were performed to confirm the role and regulation of VTN. Apoptosis and cell cycle status of MSCs were assessed using flow cytometric analysis.ResultsSubjecting MSCs to serum deprivation led to significant increase in cell spread area and cell-matrix adhesion. An upregulation of VTN expression was noted with an arrest in G0/G1 phase of cell cycle and no appreciable apoptotic change. Pro-survival PI3kinase pathway inhibition led to further increase in VTN expression with no apoptotic change. siRNA-mediated inhibition of VTN resulted in reversal in G0/G1 cell cycle arrest and a marked increase in apoptosis, suggesting a role of VTN in preventing serum deprivation-induced apoptotic cell death. In addition, p65 knockdown resulted in downregulation of VTN establishing an association between NF-κβ pathway and VTN.ConclusionsVTN was identified as a survival factor in providing protection from serum deprivation-induced apoptosis in MSCs.