bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reference Genome of the Northwestern Pond Turtle,Actinemys marmorata
Authors: Todd Brian D , Jenkinson Thomas S , Escalona Merly , Beraut Eric , Nguyen Oanh , Sahasrabudhe Ruta , Scott Peter A , Toffelmier Erin , Wang Ian J , Shaffer H Bradley 
Published: April 2022

AbstractThe northwestern pond turtle, Actinemys marmorata, and its recently recognized sister species, the southwestern pond turtle, A. pallida, are the sole aquatic testudines occurring over most of western North America and the only living representatives of the genus Actinemys. Although it historically ranged from Washington state through central California, USA, populations of the northwestern pond turtle have been in decline for decades and the species is afforded state-level protection across its range; it is currently being considered for protection under the US Endangered Species Act. Here, we report a new, chromosome-level assembly of A. marmorata as part of the California Conservation Genomics Project (CCGP). Consistent with the reference genome strategy of the CCGP, we used Pacific Biosciences HiFi long reads and Hi-C chromatin-proximity sequencing technology to produce a de novo assembled genome. The assembly comprises 198 scaffolds spanning 2,319,339,408 base pairs, has a contig N50 of 75 Mb, a scaffold N50 of 146Mb, and BUSCO complete score of 96.7%, making it the most complete testudine assembly of the 24 species from 13 families that are currently available. In combination with the A. pallida reference genome that is currently under construction through the CCGP, the A. marmorata genome will be a powerful tool for documenting landscape genomic diversity, the basis of adaptations to salt tolerance and thermal capacity, and hybridization dynamics between these recently diverged species.
The European Court of Human Rights—Can there be too much Success? A Comment
Authors: Schmahl Stefanie 
Published: April 2022

AbstractLike almost no other international human rights protection system, the system of the European Convention on Human Rights is institutionally consolidated. The present contribution briefly traces the genesis and development of the European Court of Human Rights and then turns to the examination of three challenges the Court is currently faced with. In the section on the lack of implementation of judgments, the approach of the German Federal Constitutional Court to the Strasbourg case law, which contrasts principled openness towards European human rights law with emphasizing constitutional identity, is analysed. Moreover, the contribution examines how this approach has been taken up by actors in the United Kingdom and Russia. The problem of the insufficient qualification of some candidates proposed by States is addressed in the section on the election of judges. A solution might be to formally integrate the members of the Advisory Panel into the official hearing of the candidates. The section on dynamic interpretation looks at the nexus between the Court’s interpretation of the Convention and the States’ acceptance of its jurisprudence. By transferring the interpretation of the Convention to an independent international authority, States relinquish part of their power. They will only accept this transfer of power permanently if the judicial interpretation by the Strasbourg Court remains consistent, comprehensible and plausible. The Court should therefore not act as a human rights’ ‘trendsetter’ or a ‘judicial activist’. Overall, three principles are decisive for an effective international human rights protection that meets with both the general and long-term acceptance on the part of the Contracting States and the undeniable needs of individuals to have their human rights and fundamental freedoms protected against unlawful State interference. These principles are the judicial self-restraint of the Court, the subsidiarity principle and a margin of appreciation left to the Contracting States.
Management of elderly patients with malignant lymphoma
Authors: Miyazaki Kana 
Published: April 2022

Abstract
More than half of patients with malignant lymphoma are 65 years old or older. The outcome for older patients is poorer than that for younger patients. A poor prognosis is associated with heterogeneity and consists of physical function, performance status, poor nutritional status and various comorbidities. Therefore, attention should be given to serious treatment-related toxicities. Diffuse large B-cell lymphoma is the most frequently diagnosed type of malignant lymphoma. Most patients with diffuse large B-cell lymphoma can be potentially cured with the current standard chemotherapeutic regimen of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. However, a reduced-dose regimen of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or alternative treatment options might be suitable for older patients who are frail or unfit and have cardiac comorbidities. A comprehensive geriatric assessment is a potential tool for determining an appropriate therapeutic approach for each older patient. Follicular lymphoma is the second most common type of non-Hodgkin lymphoma, and the disease course is usually characterized by an indolent clinical course. Advanced follicular lymphoma with a high tumor burden has historically been treated with chemoimmunotherapy, but the treatment goal for older patients is relief of symptoms. Incorporating novel targeted agents such as brentuximab vedotin into therapies for older Hodgkin lymphoma patients might be a promising alternative to the anthracycline-containing regimen.
Interim results from a postmarketing surveillance study of patients with FLT3-mutated relapsed/refractory AML treated with the FLT3 inhibitor gilteritinib in Japan
Authors: Sugamori Haruko , Lee Takumi , Mitomi Takeshi , Yamagishi Chika 
Published: April 2022

Abstract

Objective
Gilteritinib received approval for the treatment of FLT3-mutated relapsed or refractory acute myeloid leukemia in Japan in 2018. In accordance with regulatory requirements, we conducted a multicenter, observational surveillance of gilteritinib use in Japan.

Methods
Patients were followed for 6 months from gilteritinib treatment initiation. The primary endpoint of the surveillance was incidence of adverse drug reactions related to each element of the safety specification defined in the Japanese Risk Management Plan. This interim analysis presents data collected from 3 December 2018 to 20 September 2020.

Results
Among 204 patients with case report forms, 107 consented to data publication. Of these 107 patients, 59.8% (n = 64) were male and 58.9% (n = 63) were aged ≥65 years; most received a 120-mg/day initial (80.4%; 86/107) and maximum (74.8%; 80/107) daily dose. The discontinuation rate was 61.7% (66/107); the most common reasons for discontinuation were disease progression (18.7%), transplantation (16.8%) and adverse events (15.0%). The adverse drug reaction rate was 77.6%. The incidences of adverse drug reactions (grade ≥ 3) related to each element of the safety specification were myelosuppression, 44.9% (38.3%); liver function disorder, 24.3% (6.5%); infections, 24.3% (21.5%); prolonged QT interval, 10.3% (2.8%); hemorrhage, 9.3% (6.5%); renal dysfunction, 6.5% (0); hypersensitivity, 5.6% (1.9%); interstitial lung disease, 4.7% (3.7%); cardiac failure/pericarditis/pericardial effusion, 1.9% (0.9%); pancreatitis, 0.9% (0); posterior reversible encephalopathy syndrome, 0.9% (0.9%). The composite complete remission rate was 62.7%; the 6-month overall survival rate was 77.7%.

Conclusion
Gilteritinib treatment for 6 months in Japan was associated with acceptable efficacy and no new safety concerns were observed.
Impact of chronological age on efficacy and safety of fluoropyrimidine plus bevacizumab in older non-frail patients with metastatic colorectal cancer: a combined analysis of individual data from two phase II studies of patients aged &gt;75 years
Authors: Moriwaki Toshikazu , Nishina Tomohiro , Sakai Yoshinori , Yamamoto Yoshiyuki , Shimada Mitsuo , Ishida Hiroyasu , Amagai Kenji , Sato Mikio , Endo Shinji , Negoro Yuji , Kuramochi Hidekazu , Denda Tadamichi , Hatachi Yukimasa , Ikezawa Kazuto , Nakajima Go , Bando Yoshiaki , Tsuji Akihito , Yamamoto Yuji , Morimoto Masamitsu , Kobayashi Kazuma , Hyodo Ichinosuke 
Published: April 2022

Abstract

Objective
Many clinical trials for older patients with metastatic colorectal cancer have been conducted, and fluoropyrimidine and bevacizumab are standard treatments. However, the relationship between age and the efficacy and safety of this treatment is unclear in older metastatic colorectal cancer patients.

Methods
Individual data from two phase II studies on older (≥75 years), non-frail patients with metastatic colorectal cancer treated with uracil-tegafur/leucovorin or S-1 combined with bevacizumab were collected. Patient characteristics were evaluated with multiple regression analyses for survival outcomes, using the Cox proportional hazard model and linear regression analyses for the worst grade of adverse events.

Results
We enrolled 102 patients with a median age of 80 years (range, 75–88 years). Of the 70 patients who died, seven (10%) died of causes unrelated to disease or treatment. The study treatment was discontinued due to adverse events in 19 patients (18.6%), with 63% aged ≥85 years. The adverse event that most commonly resulted in treatment discontinuation was grade 2 fatigue (21%). Chronological age was not associated with progression-free survival (Hazard ratio, 1.03; P = 0.40) or overall survival (Hazard ratio, 1.02; P = 0.65). Age was weakly associated with non-hematologic adverse events (regression coefficient [R], 0.27; P = 0.007), especially fatigue (R, 0.23; P = 0.02) and nausea (R, 0.19; P = 0.06), but not with hematologic (R, 0.05; P = 0.43) or bevacizumab-related (R, −0.06; P = 0.56) adverse events.

Conclusions
The efficacy of fluoropyrimidine plus bevacizumab was age-independent in patients with metastatic colorectal cancer aged ≥75 years, and attention should be paid to non-hematologic adverse events as age increases.
Tumor metabolic alterations after neoadjuvant chemoradiotherapy predict postoperative recurrence in patients with pancreatic cancer
Authors: Wada Yukiko , Okano Keiichi , Sato Kiyotoshi , Sugimoto Masahiro , Shimomura Ayaka , Nagao Mina , Matsukawa Hiroyuki , Ando Yasuhisa , Suto Hironobu , Oshima Minoru , Kondo Akihiro , Asano Eisuke , Kishino Takayoshi , Kumamoto Kensuke , Kobara Hideki , Kamada Hideki , Masaki Tsutomu , Soga Tomoyoshi , Suzuki Yasuyuki 
Published: April 2022

Abstract

Objective
We investigated the metabolic changes in pancreatic ductal adenocarcinoma to identify the mechanisms of treatment response of neoadjuvant chemoradiation therapy.

Methods
Frozen tumor and non-neoplastic pancreas tissues were prospectively obtained from 88 patients with pancreatic ductal adenocarcinoma who underwent curative-intent surgery. Sixty-two patients received neoadjuvant chemoradiation therapy and 26 patients did not receive neoadjuvant therapy (control group). Comprehensive analysis of metabolites in tumor and non-neoplastic pancreatic tissue was performed by capillary electrophoresis-mass spectrometry.

Results
Capillary electrophoresis-mass spectrometry detected 90 metabolites for analysis among more than 500 ionic metabolites quantified. There were significant differences in 27 tumor metabolites between the neoadjuvant chemoradiation therapy and control groups. There were significant differences in eight metabolites [1-MethylnNicotinamide, Carnitine, Glucose, Glutathione (red), N-acetylglucosamine 6-phosphate, N-acetylglucosamine 1-phosphate, UMP, Phosphocholine] between good responder and poor responder for neoadjuvant chemoradiation therapy. Among these metabolites, phosphocholine, Carnitine and Glutathione were associated with recurrence-free survival only in the neoadjuvant chemoradiation therapy group. Microarray confirmed marked gene suppression of choline transporters [CTL1-4 (SLC44A1-44A4)] in pancreatic ductal adenocarcinoma tissue of neoadjuvant chemoradiation therapy group.

Conclusion
The present study identifies several important metabolic consequences and potential neoadjuvant chemoradiation therapy targets in pancreatic ductal adenocarcinoma. Choline metabolism is one of the key pathways involved in recurrence of the patients with pancreatic ductal adenocarcinoma who received neoadjuvant chemoradiation therapy.
Association Between Medicaid Expansion Under the Affordable Care Act and Survival Among Newly Diagnosed Cancer Patients
Authors: Han Xuesong , Zhao Jingxuan , Yabroff K Robin , Johnson Christopher J , Jemal Ahmedin 
Published: April 2022

Abstract

Background
Medicaid expansion under the Affordable Care Act (ACA) is associated with increased insurance coverage among patients with cancer. Whether these gains translate to improved survival is largely unknown. This study examines changes in 2-year survival among patients newly diagnosed with cancer following the ACA Medicaid expansion.

Methods
Patients aged 18-62 years from 42 states’ population-based cancer registries diagnosed pre (2010-2012) and post (2014-2016) ACA Medicaid expansion were followed through September 30, 2013, and December 31, 2017, respectively. Difference-in-differences (DD) analysis of 2-year overall survival was stratified by sex, race and ethnicity, census tract–level poverty, and rurality.

Results
A total of 2 555 302 patients diagnosed with cancer were included from Medicaid expansion (n = 1 523 585) and nonexpansion (n = 1 031 717) states. The 2-year overall survival increased from 80.58% pre-ACA to 82.23% post-ACA in expansion states and from 78.71% to 80.04% in nonexpansion states, resulting in a net increase of 0.44 percentage points (ppt) (95% confidence interval [CI] = 0.24ppt to 0.64ppt) in expansion states after adjusting for sociodemographic factors. By cancer site, the net increase was greater for colorectal cancer (DD = 0.90ppt, 95% CI = 0.19ppt to 1.60ppt), lung cancer (DD = 1.29ppt, 95% CI = 0.50ppt to 2.08ppt), non-Hodgkin lymphoma (DD = 1.07ppt, 95% CI = 0.14ppt to 1.99ppt), pancreatic cancer (DD = 1.80ppt, 95% CI = 0.40ppt to 3.21ppt), and liver cancer (DD = 2.57ppt, 95% CI = 1.00ppt to 4.15ppt). The improvement in 2-year overall survival was larger among non-Hispanic Black patients (DD = 0.72ppt, 95% CI = 0.12ppt to 1.31ppt) and patients residing in rural areas (DD = 1.48ppt, 95% CI= -0.26ppt to 3.23ppt), leading to narrowing survival disparities by race and rurality.

Conclusions
Medicaid expansion was associated with greater increase in 2-year overall survival, and the increase was prominent among non-Hispanic Blacks and in rural areas, highlighting the role of Medicaid expansion in reducing health disparities. Future studies should monitor changes in longer-term health outcomes following the ACA.
Helicobacter pylori Modulated Host Immunity in Gastric Cancer Patients With S-1 Adjuvant Chemotherapy
Authors: Koizumi Yuka , Ahmad Sheny , Ikeda Miyuki , Yashima-Abo Akiko , Espina Ginny , Sugimoto Ryo , Sugai Tamotsu , Iwaya Takeshi , Tamura Gen , Koeda Keisuke , Liotta Lance A , Takahashi Fumiaki , Nishizuka Satoshi S ,   the Northern Japan Gastric Cancer Study Consortium
Published: April 2022

Abstract

Background
Paradoxically, Helicobacter pylori–positive (HP+) advanced gastric cancer patients have a better prognosis than those who are HP–negative (HP-). Immunologic and statistical analyses can be used to verify whether systemic mechanisms modulated by HP are involved in this more favorable outcome.

Methods
A total of 658 advanced gastric cancer patients who underwent gastrectomy were enrolled. HP infection, mismatch repair, programmed death–ligand 1 (PD-L1) and CD4/CD8 proteins, and microsatellite instability were analyzed. Overall survival (OS) and relapse-free survival (RFS) rates were analyzed after stratifying clinicopathological factors. Cox proportional hazards regression analysis was performed to identify independent prognostic factors.

Results
Among 491 patients that were analyzed, 175 (36%) and 316 (64%) patients were HP+ and HP−, respectively. Analysis of RFS indicated an interaction of HP status among the subgroups for S-1 dose (Pinteraction = .049) and PD-L1 (P = .02). HP+ patients in the PD-L1- group had statistically higher 5-year OS and RFS than HP- patients (81% vs 68%; P = .0011; hazard ratio [HR] = 0.48, 95% confidence interval [CI] = 0.303 to 0.751, and 76% vs 63%; P = .001; HR = 0.508, 95% CI = 0.335 to 0.771, respectively). The 5-year OS and RFS was also statistically higher for HP+ compared with HP- patients in the "PD-L1- and S-1–r educed" group (86% vs 46%; P = .001; HR = 0.205, 95% CI = 0.07 to 0.602, and 83% vs 34%; P = .001; HR = 0.190, 95% CI = 0.072 to 0.498, respectively). Thus, HP status was identified as one of the most potentially important independent factors to predict prolonged survival.

Conclusion
This retrospective study suggests that an HP-modulated host immune system may contribute to prolonged survival in the absence of immune escape mechanisms of gastric cancer.
Rhizosphere and root fungal community of the invasive plant Galinsoga quadriradiata changes along its elevational expansion route
Authors: Liu Rui-Ling , Zhang Wen-Gang , Lee Benjamin R , Liu Gang , Song Xing-Jiang , Chen Xiao-Yan , Zou Jia-Bin , Huang Fang-Fang , Zhu Zhi-Hong 
Published: April 2022

Abstract
Fungal communities related to invasive plants may change with an elevational gradient, which may affect the performance and invasiveness of invasive plants. Our recent study revealed that root arbuscular mycorrhizal fungi colonization rate of invasive plant Galinsoga quadriradiata decreased with elevation. However, it is unclear whether it is caused by the changes in the fungal community along elevation. To address this issue, we used high-throughput sequencing techniques, functional groupings and linear statistics to examine how fungal communities in the rhizosphere and roots of G. quadriradiata are changed across the elevation in Qinling and Bashan Mountains, China. Our results revealed that species diversity and composition of the rhizosphere and root fungal communities changed along the elevation. The Shannon–Wiener diversity index in the rhizosphere and roots increased and decreased with elevation, respectively. In contrast, the relative abundance of pathotroph in the rhizosphere decreased while it increased in the roots with elevation. These suggest that, when the invasive plant colonizes into high altitudes, it may not suffer from limited rhizosphere fungal symbionts, but rather the ability of the plant to create and maintain these associations decreases. The invader tends to accumulate more pathogenic fungi in the roots, while the dependence on symbiotic fungi is reduced during expansion into higher elevations. These results highlight that the interactions between invasive plants and fungal community substantially change along elevation, and that belowground interactions may be key in our understanding of how invasive plants derive success in stressful, high-elevation environments.
Assessing Aspects of Social Relationships in Youth Across Middle Childhood and Adolescence: The NIH Toolbox Pediatric Social Relationship Scales
Authors: Dietz Laura J , Cyranowski Jill M , Fladeboe Kaitlyn M , Kelly Morgen A R , Pilkonis Paul A , Butt Zeeshan , Salsman John M , Cella David 
Published: April 2022

Abstract

Objective
Social relationships are a critical context for children’s socioemotional development and their quality is closely linked with concurrent and future physical and emotional wellbeing. However, brief self-report measures of social relationship quality that translate across middle childhood, adolescence, and adulthood are lacking, limiting the ability to assess the impact of social relationships on health outcomes over time. To address this gap, this article describes the development and testing of the National Institutes of Health (NIH) Toolbox Pediatric Social Relationship Scales, which were developed in parallel with the previously-reported Adult Social Relationship Scales.

Methods
Item sets were selected from the NIH Toolbox adult self-report item banks in the domains of social support, companionship, and social distress, and adapted for use in preadolescent (ages 8–11 years) and adolescent (ages 12–18 years) cohorts. Items were tested across a U.S. community sample of 1,038 youth ages 8–18 years. Classical test and item response theory approaches were used to identify items for inclusion in brief unidimensional scales. Concurrent validity was assessed by comparing resultant scales to established pediatric social relationship instruments.

Results
Internal reliability and concurrent validity were established for five unique scales, with 5–7 items each: Emotional Support, Friendship, Loneliness, Perceived Rejection, and Perceived Hostility.

Conclusions
These brief scales represent developmentally appropriate and valid instruments for assessing the quality of youth social relationships across childhood and adolescence. In conjunction with previously published adult scales, they provide an opportunity for prospective assessment of social relationships across the developmental spectrum.
Berberine suppresses the migration and invasion of colon cancer cells by inhibition of lipogenesis through modulation of promyelocytic leukemia zinc finger-mediated sterol-regulatory element binding proteins cleavage-activating protein ubiquitination
Authors: Liu Yunxin , Fang Xianjun , Li Yao , Bing Liu , Li Yang , Fang Jing , Xian Xirui , Zhang Wen , Li Jun , Zhao Zheng , Zhu Yubing 
Published: April 2022

Abstract

Objectives
This study was aimed to explore whether and how berberine suppresses colon cancer cell metastasis via lipid modulation.

Methods
Lipid accumulation was measured by an oil red O staining kit. The expression of proteins and message RNA was detected by Western blot and quantitative real-time PCR. The interaction of sterol-regulatory element-binding proteins cleavage-activating protein (SCAP) with promyelocytic leukaemia zinc finger (PLZF) was confirmed by co-immunoprecipitation assay. Expressions of fatty acid synthase (FASN) and PLZF were knocked down by specific small interfering RNA.

Key findings
Berberine inhibited the migration and invasion of HCT-8, HCT-116 and HT-29 cells. Moreover, it was observed that berberine decreased lipid droplet accumulation. FASN knockdown abolished the inhibitory effects of berberine on cell migration and invasion. Further investigation revealed that berberine induced the ubiquitination degradation of SCAP. And PLZF interacted with SCAP and promoted its ubiquitination, which was inhibited by berberine treatment. Silence of PLZF impaired the effects of berberine on SCAP ubiquitination and lipogenesis.

Conclusions
Berberine suppressed lipogenesis via promotion of PLZF-mediated SCAP ubiquitination, thereby inhibiting colon cancer cell metastasis.