bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genomic diversification of grapevine clones
Authors: Vondras Amanda M. , Minio Andrea , Blanco-Ulate Barbara , Figueroa-Balderas Rosa , Penn Michael A. , Zhou Yongfeng , Seymour Danelle , Ye Zirou , Liang Dingren , Espinoza Lucero K. , Anderson Michael M. , Walker M. Andrew , Gaut Brandon , Cantu Dario 
Published: December 2019

Abstract
Background
Vegetatively propagated clones accumulate somatic mutations. The purpose of this study was to better appreciate clone diversity and involved defining the nature of somatic mutations throughout the genome. Fifteen Zinfandel winegrape clone genomes were sequenced and compared to one another using a highly contiguous genome reference produced from one of the clones, Zinfandel 03.

Results
Though most heterozygous variants were shared, somatic mutations accumulated in individual and subsets of clones. Overall, heterozygous mutations were most frequent in intergenic space and more frequent in introns than exons. A significantly larger percentage of CpG, CHG, and CHH sites in repetitive intergenic space experienced transition mutations than in genic and non-repetitive intergenic spaces, likely because of higher levels of methylation in the region and because methylated cytosines often spontaneously deaminate. Of the minority of mutations that occurred in exons, larger proportions of these were putatively deleterious when they occurred in relatively few clones.

Conclusions
These data support three major conclusions. First, repetitive intergenic space is a major driver of clone genome diversification. Second, clones accumulate putatively deleterious mutations. Third, the data suggest selection against deleterious variants in coding regions or some mechanism by which mutations are less frequent in coding than noncoding regions of the genome.
Transcriptome analysis reveals mechanism underlying the differential intestinal functionality of laying hens in the late phase and peak phase of production
Authors: Wang Wei-wei , Wang Jing , Zhang Hai-jun , Wu Shu-geng , Qi Guang-hai 
Published: December 2019

AbstractBackgroundThe compromised performance of laying hens in the late phase of production relative to the peak production was thought to be associated with the impairment of intestinal functionality, which plays essential roles in contributing to their overall health and production performance. In the present study, RNA sequencing was used to investigate differences in the expression profile of intestinal functionality-related genes and associated pathways between laying hens in the late phase and peak phase of production.ResultsA total of 104 upregulated genes with 190 downregulated genes were identified in the ileum (the distal small intestine) of laying hens in the late phase of production compared to those at peak production. These upregulated genes were found to be enriched in little KEGG pathway, however, the downregulated genes were enriched in the pathways of PPAR signaling pathway, oxidative phosphorylation and glutathione metabolism. Besides, these downregulated genes were mapped to several GO clusters in relation to lipid metabolism, electron transport of respiratory chain, and oxidation resistance. Similarly, there were lower activities of total superoxide dismutase, glutathione S-transferase and Na+/K+-ATPase, and reductions of total antioxidant capacity and ATP level, along with an elevation in malondialdehyde content in the ileum of laying hens in the late phase of production as compared with those at peak production.ConclusionsThe intestine of laying hens in the late phase of production were predominantly characterized by a disorder of lipid metabolism, concurrent with impairments of energy production and antioxidant property. This study uncovers the mechanism underlying differences between the intestinal functionality of laying hens in the late phase and peak phase of production, thereby providing potential targets for the genetic control or dietary modulation of intestinal hypofunction of laying hens in the late phase of production.
Transcriptome sequencing of Saccharina japonica sporophytes during whole developmental periods reveals regulatory networks underlying alginate and mannitol biosynthesis
Authors: Shao Zhanru , Zhang Pengyan , Lu Chang , Li Shaoxuan , Chen Zhihang , Wang Xiuliang , Duan Delin 
Published: December 2019

Abstract
Background
Alginate is an important cell wall component and mannitol is a soluble storage carbon substance in the brown seaweed Saccharina japonica. Their contents vary with kelp developmental periods and harvesting time. Alginate and mannitol regulatory networks and molecular mechanisms are largely unknown.

Results
With WGCNA and trend analysis of 20,940 known genes and 4264 new genes produced from transcriptome sequencing of 30 kelp samples from different stages and tissues, we deduced that ribosomal proteins, light harvesting complex proteins and “imm upregulated 3” gene family are closely associated with the meristematic growth and kelp maturity. Moreover, 134 and 6 genes directly involved in the alginate and mannitol metabolism were identified, respectively. Mannose-6-phosphate isomerase (MPI2), phosphomannomutase (PMM1), GDP-mannose 6-dehydrogenase (GMD3) and mannuronate C5-epimerase (MC5E70 and MC5E122) are closely related with the high content of alginate in the distal blade. Mannitol accumulation in the basal blade might be ascribed to high expression of mannitol-1-phosphate dehydrogenase (M1PDH1) and mannitol-1-phosphatase (M1Pase) (in biosynthesis direction) and low expression of mannitol-2-dehydrogenase (M2DH) and Fructokinase (FK) (in degradation direction). Oxidative phosphorylation and photosynthesis provide ATP and NADH for mannitol metabolism whereas glycosylated cycle and tricarboxylic acid (TCA) cycle produce GTP for alginate biosynthesis. RNA/protein synthesis and transportation might affect alginate complex polymerization and secretion processes. Cryptochrome (CRY-DASH), xanthophyll cycle, photosynthesis and carbon fixation influence the production of intermediate metabolite of fructose-6-phosphate, contributing to high content of mannitol in the basal blade.

Conclusions
The network of co-responsive DNA synthesis, repair and proteolysis are presumed to be involved in alginate polymerization and secretion, while upstream light-responsive reactions are important for mannitol accumulation in meristem of kelp. Our transcriptome analysis provides new insights into the transcriptional regulatory networks underlying the biosynthesis of alginate and mannitol during S. japonica developments.
Radical radiotherapy in patients with cervix uteri carcinoma: experience of Ondokuz Mayis University
Authors: Serarslan Alparslan , Gursel Bilge , Meydan Deniz , Ozbek Okumus Nilgun 
Published: December 2019

Abstract
Background
Radical radiotherapy is the standard treatment for patients with locally advanced cervix uteri carcinoma (FIGO stage IB2–IVA). Worldwide, incidence and mortality rates vary among regions because of differences in lifestyles and treatment standards. Herein, we evaluated the outcomes of radical radiotherapy in patients with locally advanced cervix uteri carcinoma from the middle Black Sea region of Turkey.

Methods
We retrospectively reviewed the records of 64 consecutive patients with locally advanced cervix uteri carcinoma who were treated from January 2013 to 2016 in our radiation oncology department. All patients staging and radiotherapy planning were performed with modern imaging techniques including magnetic resonance imaging and positron-emission-tomography/computed tomography before radical radiotherapy. Thereafter, all of them were treated with external beam radiotherapy and concurrent cis-platinum-based chemotherapy followed by three-dimensional intra-cavitary high-dose-rate brachytherapy.

Results
The median age at diagnosis was 54.5 years. The median follow-up period was 21 months. Acute grade 3 toxicity was detected in 3.1% of patients. Late toxicity was not detected in any patient. The 1- and 3-year progression-free survival rates were 83.6 and 67.5%, respectively. The 1- and 3-year overall survival rates were 95.7 and 76.9%, respectively. The most important prognostic factor was the FIGO stage. Distant metastasis was the most common cause of death in patients with locally advanced cervix uteri carcinoma despite radical radiotherapy.

Conclusions
In patients with locally-advanced cervix uteri carcinoma from the middle Black Sea region of our developing country, acceptable toxicity and survival rates are achieved similar to the recent literature from developed countries with using of modern staging, planning and radical radiotherapy techniques. However, recurrence was mostly in the form of distant metastases and further investigations on systemic therapies are required.
Pharmacotherapy of borderline personality disorder: what has changed over two decades? A retrospective evaluation of clinical practice
Authors: Timäus Charles , Meiser Miriam , Bandelow Borwin , Engel Kirsten R. , Paschke Anne M. , Wiltfang Jens , Wedekind Dirk 
Published: December 2019

Abstract
Background
The purpose of this study was to assess the pharmacological treatment strategies of inpatients with borderline personality disorder between 2008 and 2012. Additionally, we compared pharmacotherapy during this period to a previous one (1996 to 2004).

Methods
Charts of 87 patients with the main diagnosis of borderline personality disorder receiving inpatient treatment in the University Medical Center of Goettingen, Germany, between 2008 and 2012 were evaluated retrospectively. For each inpatient treatment, psychotropic drug therapy including admission and discharge medication was documented. We compared the prescription rates of the interval 2008–2012 with the interval 1996–2004.

Results
94% of all inpatients of the interval 2008–2012 were treated with at least one psychotropic drug at time of discharge. All classes of psychotropic drugs were applied. We found high prescription rates of naltrexone (35.6%), quetiapine (19.5%), mirtazapine (18.4%), sertraline (12.6%), and escitalopram (11.5%). Compared to 1996–2004, rates of low-potency antipsychotics, tri−/tetracyclic antidepressants and mood stabilizers significantly decreased while usage of naltrexone significantly increased.

Conclusions
In inpatient settings, pharmacotherapy is still highly prevalent in the management of BPD. Prescription strategies changed between 1996 and 2012. Quetiapine was preferred, older antidepressants and low-potency antipsychotics were avoided. Opioid antagonists are increasingly used and should be considered for further investigation.
The trend of full vaccination coverage in infants and inequalities by wealth quintile and maternal education: analysis from four recent demographic and health surveys in Nepal
Authors: Acharya Kiran , Paudel Yuba Raj , Dharel Dinesh 
Published: December 2019

AbstractBackgroundDespite policy intention to reach disadvantaged populations, inequalities in health care resource use and health outcomes persist in Nepal. The current study aimed to investigate the trend of full vaccination coverage among infants and its equity gaps between Nepal Demographic and Health Surveys (NDHS) 2001 and 2016.MethodsUsing data from NDHS conducted in 2001, 2006, 2011 and 2016, we investigated the trend of coverage of six antigens: Bacille Calmette Guerin (BCG), Diptheria, Pertussis, Tetanus (DPT), Polio, and Measles during their infancy among children aged 12–23 months. We presented trends and correlates of full vaccination coverage by different socio-demographic factors. We measured inequalities in full vaccination coverage by wealth quintile and maternal education using absolute measure (slope index of inequality) and relative measures (Relative index of inequality, concentration index) of inequalities.ResultsFull vaccination coverage among infants steadily increased from 65.6% in 2001 to 87.0% in 2011; however, it decreased to 77.8% in 2016. Province 2 had a significantly lower full vaccination coverage compared to Province1.Although decreasing over time, there were significant inequalities by household wealth quintiles and maternal educational status. The slope index of inequality (SII) for wealth quintiles decreased from − 32.3 [− 45.5,-19.1] in 2001 to an SII of-8.4 [− 18.6,-1.7] in 2016. Similarly, the SII for education decreased from − 61.8 [− 73.5,-50.1] in 2001 to an SII of − 30.5 [− 40.7,-20.2] in 2016. Similarly, the relative index of inequality (RII) also showed an improvement over time, indicating the narrowing equity gap. Additionally, concentration index on full vaccination coverage by wealth quintiles dropped from 0.21 (0.12–0.28) in 2001 to 0.054 (− 0.01–0.12) in 2016. Absolute and relative inequalities were persistently larger by maternal educational status compared to household wealth quintiles throughout the study period.ConclusionFull vaccination coverage in Nepal increased from 2001 until 2011 but saw a significant decrement away from the national target after 2011. However, the equity gap by household wealth quintile and maternal education status has narrowed over time. National Immunization programs need to give higher emphasis to infants born to mothers with less education, those born in the poorer wealth quintile households, and those living in Province 2.
Migration analysis of a metaphyseal-anchored short femoral stem in cementless THA and factors affecting the stem subsidence
Authors: Schaer Michael O. , Finsterwald Michael , Holweg Iris , Dimitriou Dimitris , Antoniadis Alexander , Helmy Naeder 
Published: December 2019

AbstractBackgroundEarly femoral stem subsidence following a cementless THA is correlated with aseptic loosening of the femoral component. The short femoral stems allow bone sparing and implantation through a minimally invasive approach; however, due to their metaphyseal anchoring, they might demonstrate different subsidence pattern than the conventional stems.MethodsIn this prospective single-center study, a total of 68 consecutive patients with an average age of 63 years, and a minimum follow-up of 5 years following a cementless THA with a metaphyseal-anchored short femoral stem were included. The femoral stem subsidence was evaluated using “Ein Bild Roentgen Analyse” (EBRA).ResultsAverage stem migration was 0.96 +/− 0.76 mm at 3 months, 1.71 +/− 1.26 mm at 24 months, and 2.04+/− 1.42 mm at last follow-up 60 months postoperative. The only factor that affected migration was a stem size of 6 or more (r2 = 5.74;p = 0.039). Subdivision analysis revealed, that only in females migration appeared to be affected by stem size irrespective of weight but not in men (female stem size of 6 or more vs. less (Difference = − 1.48 mm, R2 = 37.5;p = 0.001). Migration did not have an impact on clinical outcome measures.ConclusionsThe examined metaphyseal-anchored short femoral stem showed the highest subsidence within the first 3 months postoperative, the implant began to stabilize at about 24 months but continued to slowly migrate with average total subsidence of 2.04 mm at 5 years following the THA. The amount of stem subsidence was not associated with worse clinical outcomes such as HHS, patient satisfaction, or pain.
Is diverting loop ileostomy necessary for completion proctectomy with ileal pouch-anal anastomosis? A multicenter randomized trial of the GETAID Chirurgie group (IDEAL trial): rationale and design (NCT03872271)
Authors:   GETAID Chirurgie group, Beyer-Berjot Laura , Baumstarck Karine , Loubière Sandrine , Vicaut Eric , Berdah Stéphane V. , Benoist Stéphane , Lefèvre Jérémie H. 
Published: December 2019

Abstract
Background
There is no quality evidence of the benefit of defunctioning ileostomy (DI) in ileal pouch-anal anastomoses (IPAAs) performed for inflammatory bowel disease (IBD), but most surgical teams currently resort to DI. In the case of a staged procedure with subtotal colectomy first, completion proctectomy with IPAA is performed for healthy patients, namely, after nutritional support, inflammation reduction and immunosuppressive agent weaning. Therefore, the aim of this trial is to assess the need for systematic DI after completion proctectomy and IPAA for IBD.

Methods/design
This is a multicenter randomized open trial comparing completion proctectomy and IPAA without (experimental) or with (control) DI in patients presenting with ulcerative colitis or indeterminate colitis. Crohn’s disease patients will not be included. The design is a superiority trial. The main objective is to compare the 6-month global postoperative morbidity, encompassing both surgical and medical complications, between the two groups. The morbidity of DI closure will be included, as appropriate. The sample size calculation is based on the hypothesis that the overall 6-month morbidity rate is 30% in the case of no stoma creation (i.e., experimental group) vs. 55% otherwise (control group). With the alpha risk and power are fixed to 0.05 and 0.80, respectively, and considering a dropout rate of 10%, the objective is set to 194 patients. The secondary objectives are to compare both strategies in terms of morbi-mortality at 6 months and functional results as well as quality of life at 12 months, namely, the 6-month major morbidity and unplanned reoperation rates, 6-month anastomotic leakage rate, 6-month mortality, length of hospital stay, 6-month unplanned readmission rate, quality of life assessed 3 and 12 months from continuity restoration (i.e., either IPAA or stoma closure), functional results assessed 3 and 12 months from continuity restoration, 12-month pouch results, 12-month cost-utility analysis, and 12-month global morbidity.

Discussion
The IDEAL trial is a nationwide multicenter study that will help choose the optimal strategy between DI and no ileostomy in completion proctectomy with IPAA for IBD.

Trial registration
ClinicalTrial.gov: NCT03872271, date of registration March 13th, 2019.
Self-care habits among people who inject drugs with skin and soft tissue infections: a qualitative analysis
Authors: Gilbert Andrew R. , Hellman Julia L. , Wilkes Michael S. , Rees Vaughan W. , Summers Phillip J. 
Published: December 2019

Abstract
Background
Injection drug use is on the rise in the USA, and skin and soft tissue infections (SSTI) are a common complication, resulting in significant morbidity and mortality. Due to structural barriers to care-seeking, many people who inject drugs avoid formal care and resort to self-care techniques, but little is known about the nature of these techniques, or more generally about the accuracy or breadth of this population’s knowledge of SSTIs.

Methods
Semi-structured qualitative interviews were conducted with 12 people who inject heroin in two metropolitan areas: Sacramento and Boston, USA.

Results
These interviews reveal a robust and accurate knowledge base regarding skin infections, including the progression from simple cellulitis to an abscess, and acknowledgment of the possibility of serious infections. Nonetheless, there remains a reticence to seek care secondary to past traumatic experiences. A step-wise approach to self-care of SSTI infections was identified, which included themes of whole-body health, topical applications, use of non-prescribed antibiotics, and incision and drainage by non-medical providers.

Conclusions
The reported SSTI self-care strategies demonstrate resilience and ingenuity, but also raise serious concerns about inappropriate antibiotic consumption and complications of invasive surgical procedures performed without proper training, technique, or materials. Harm reduction agencies and health care providers should work to obviate the need for these potentially dangerous practices by improving healthcare access for this population. In the absence of robust solutions to meet the needs of this population, education materials should be developed to optimize the efficacy and minimize the harms of these practices, while empowering and supporting the autonomy of people who use drugs and providing clear guidance on when self-care should be abandoned in favor of formal medical care.
FKB327, an adalimumab biosimilar, versus the reference product: results of a randomized, Phase III, double-blind study, and its open-label extension
Authors: Genovese Mark C. , Glover Josephine , Greenwald Maria , Porawska Wieslawa , El Khouri Elias Chalouhi , Dokoupilova Eva , Vargas Juan Ignacio , Stanislavchuk Mykola , Kellner Herbert , Baranova Elena , Matsunaga Nobuhito , Alten Rieke 
Published: December 2019

Abstract
Objective
To compare the efficacy, serum drug concentrations, immunogenicity, and safety of FKB327 with the adalimumab reference product (RP) in combination with methotrexate in patients with moderate-to-severe, active rheumatoid arthritis (RA).

Methods
Patients were randomized 1:1 in a double-blind study (NCT02260791), received 40 mg of FKB327 or RP by subcutaneous injection every other week for 24 weeks (Period I), then re-randomized 2:1, remaining on the same study drug or switching to the other up to week 54 in an open-label extension (Period II, NCT02405780). Efficacy was evaluated using American College of Rheumatology (ACR20) response rate difference at week 24 with equivalence margins of ± 13% and − 12% to + 15% using 95% and 90% confidence intervals (CIs), respectively. Efficacy, serum drug concentrations, immunogenicity, and safety were compared at week 54.

Results
A total of 730 patients were randomized in Period I (n = 367 FKB327, n = 363 RP), and 645 transitioned to Period II (n = 216 FKB327–FKB327, n = 108 FKB327–RP, n = 108 RP–FKB327, n = 213 RP–RP). At week 24, ACR20 response rates were 74.1% with FKB327 versus 75.7% with RP. 95% and 90% CI of the response rate difference were − 7.9 to 4.7% and − 7.3 to 3.6%, respectively, meeting predefined equivalence margins. The ACR20 response rate remained over 70% of patients to week 54 with all treatment sequences. In Period I, mean trough serum drug concentrations were slightly higher for patients receiving FKB327 than those receiving RP. Mean concentrations were stable over time and reflected steady state in Period II. The proportions of patients with samples positive for neutralizing antidrug antibodies (ADAs) were comparable (57.7% with FKB327 vs. 55.5% with RP) at week 24, and no consistent difference in ADA were seen between continuous and switched treatments in Period II. Efficacy was slightly reduced in the small proportion of patients with high ADA titers in all treatment groups. No clinically significant differences were observed in the incidence of commonly reported treatment-emergent adverse events between the treatments across Periods I and II.

Conclusion
FKB327 was equivalent to RP in clinical efficacy and demonstrated comparable safety and immunogenicity in patients with moderate-to-severe RA. No effect of switching between FKB327 and RP was observed.

Trial registration
ClinicalTrials.gov, NCT02260791, Registered 29 July 2014.
ClinicalTrials.gov, NCT02405780, Registered 17 July 2015.