bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival of bovine digital dermatitis treponemes on hoof knife blades and the effects of various disinfectants
Authors: Gillespie Amy , Carter Stuart D , Blowey Roger W , Evans Nicholas 
Published: November 2019

BackgroundBovine digital dermatitis (BDD) is a painful infectious foot disease of cattle, and much evidence implicates a pathogenic role for treponemes. This study measured the survival of BDD treponemes on hoof knife blades and tested the efficacy of relevant disinfectants under laboratory conditions.MethodsTwo strains of BDD treponemes were applied to hoof knife blades under aerobic conditions. Swabs were taken at different time points (10 minutes, one hour, two hours, four hours and 18 hours) and again after 20‐second disinfection time with one of five disinfectants. Swabs were used directly for nested PCR to detect treponemes or inoculated for anaerobic growth, and subsequently examined using phase contrast microscopy and PCR.ResultsBDD treponeme DNA was detectable by nested PCR at all survival time points, and these organisms were culturable from hoof knives for two hours after exposure under aerobic conditions in the laboratory. Three of the five disinfectants—1 per cent volume per volume (v/v) FAM30®, 2 per cent weight per volume (w/v) Virkon® or 2 per cent (v/v) sodium hypochlorite—were effective at preventing visible growth of treponemes following 20‐seconds contact, and 1 per cent (v/v) FAM30® also prevented detection of treponemes by PCR.ConclusionTreponeme viability of two hours under aerobic conditions suggests BDD treponemes could be transmitted between cows on hoof knives. It is therefore important to apply a disinfection protocol during foot‐trimming; the authors have identified three common disinfectants that may be suitable.
The effects of split application of enhanced efficiency fertilizers on non-winter nitrous oxide emissions from winter wheat
Authors: Owens Jen , An Haibo , Beres Brian , Mohr Ramona , Hao Xiying 
Published: November 2019

This study tested if non-winter cumulative nitrous oxide (N2O) emissions, emission factors, and yield-scaled N2O emissions were affected by split application of enhanced efficiency nitrogen fertilizers in a rain-fed winter wheat crop. Based on initial soil tests, fertilizers were applied at 84 kg N ha−1in year 1 and 72 kg N ha−1in year 2. Two trials were completed each year. Trial 1 applied (1) urea, (2) urea with nitrification inhibitor, (3) nitrification and urease inhibitors, and (4) polymer-coated urea as (1) 100% side-banded at planting, 30% side-banded at planting and (2) 70% surface-applied in late fall, or (3) 70% surface-applied in spring at Feekes growth stage 4 (GS4). Trial 2 applied (1) urea–ammonium nitrate (UAN), (2) UAN treated with nitrification inhibitor, (3) urease inhibitor, (4) a combination of both, (5) granular urea, and (6) polymer-coated urea, all applied 50% side-banded at planting and 50% surface-applied at GS4. Cumulative N2O emissions from fertilized soils ranged from 0.101 to 0.433 kg N ha−1. The emission factors for trial 1 were greater in year 1 than year 2 (P ≤ 0.05). There were no treatment differences in cumulative N2O emissions in trial 2. However, cumulative N2O emissions, emission factors, and yield-scaled N2O emissions from trial 1 were higher when fertilizer was split-applied in late fall compared with at GS4 (all P ≤ 0.05). This study demonstrates that under best management practices, it is better to apply the required rate in the form of conventional fertilizer at planting rather than split application.
Hyperbaric Normoxia Improved Glucose Metabolism and Decreased Inflammation in Obese Diabetic Rat
Authors: Fujita Naoto , Goto Natsuki , Nakamura Tomoya , Nino Wataru , Ono Taketoshi , Nishijo Hisao , Urakawa Susumu 
Published: November 2019

Hyperbaric treatment improves hyperglycemia and hyperinsulinemia in type 2 diabetes associated with obesity. However, its mode of action is unknown. The purpose of the present study was to investigate the influences of regular hyperbaric treatment with normal air at 1.3 atmospheres absolute (ATA) on glucose tolerance in type 2 diabetes with obesity. The focus was directed on inflammatory cytokines in the adipose tissue and skeletal muscle. Otsuka Long-Evans Tokushima Fatty (OLETF) rats were used as models of type 2 diabetes with obesity and Long-Evans Tokushima Otsuka (LETO) rats served as healthy controls. The rats were randomly assigned to untreated or hyperbaric treatment groups exposed to 1.3 ATA for 8 h d-1 and 5 d wk-1 for 16 wks. Glucose levels were significantly higher in the diabetic than in the healthy control rats. Nevertheless, glucose levels at 30 and 60 min after glucose administration were significantly lower in the diabetic rats treated with 1.3 ATA than in the untreated diabetic rats. Insulin levels at fasting and 120 min after glucose administration were significantly lower in the diabetic rats treated with 1.3 ATA than in the untreated diabetic rats. Hyperbaric treatment also increased interleukin-10 (IL-10) expression in the skeletal muscle and decreased tumor necrosis factor α (TNFα) expression in adipose tissue. These results suggested that TNFα downregulation and IL-10 upregulation in diabetic rats subjected to hyperbaric treatment participate in the crosstalk between the adipose and skeletal muscle tissues and improve glucose intolerance.
Identification of Hypermutation and Defective Mismatch Repair in ctDNA from Metastatic Prostate Cancer
Authors: Ritch Elie , Fu Simon Y.F. , Herberts Cameron , Wang Gang , Warner Evan W. , Schönlau Elena , Taavitsainen Sinja , Murtha Andrew J. , Vandekerkhove Gillian , Beja Kevin , Loktionova Yulia , Khalaf Daniel , Fazli Ladan , Kushnir Igal , Ferrario Cristiano , Hotte Sebastien , Annala Matti , Chi Kim N. , Wyatt Alexander W. 
Published: November 2019

AbstractPurpose:DNA mismatch repair defects (MMRd) and tumor hypermutation are rare and under-characterized in metastatic prostate cancer (mPC). Furthermore, because hypermutated MMRd prostate cancers can respond to immune checkpoint inhibitors, there is an urgent need for practical detection tools.Experimental Design:We analyzed plasma cell-free DNA-targeted sequencing data from 433 patients with mPC with circulating tumor DNA (ctDNA) purity ≥2%. Samples with somatic hypermutation were subjected to 185 × whole-exome sequencing and capture of mismatch repair gene introns. Archival tissue was analyzed with targeted sequencing and IHC.Results:Sixteen patients (3.7%) had somatic hypermutation with MMRd etiology, evidenced by deleterious alterations in MSH2, MSH6, or MLH1, microsatellite instability, and characteristic trinucleotide signatures. ctDNA was concordant with mismatch repair protein IHC and DNA sequencing of tumor tissue. Tumor suppressors such as PTEN, RB1, and TP53 were inactivated by mutation rather than copy-number loss. Hotspot mutations in oncogenes such as AKT1, PIK3CA, and CTNNB1 were common, and the androgen receptor (AR)-ligand binding domain was mutated in 9 of 16 patients. We observed high intrapatient clonal diversity, evidenced by subclonal driver mutations and shifts in mutation allele frequency over time. Patients with hypermutation and MMRd etiology in ctDNA had a poor response to AR inhibition and inferior survival compared with a control cohort.Conclusions:Hypermutated MMRd mPC is associated with oncogene activation and subclonal diversity, which may contribute to a clinically aggressive disposition in selected patients. In patients with detectable ctDNA, cell-free DNA sequencing is a practical tool to prioritize this subtype for immunotherapy.See related commentary by Schweizer and Yu, p. 981
Ceramide Analogue SACLAC Modulates Sphingolipid Levels and MCL-1 Splicing to Induce Apoptosis in Acute Myeloid Leukemia
Authors: Pearson Jennifer M. , Tan Su-Fern , Sharma Arati , Annageldiyev Charyguly , Fox Todd E. , Abad Jose Luis , Fabrias Gemma , Desai Dhimant , Amin Shantu , Wang Hong-Gang , Cabot Myles C. , Claxton David F. , Kester Mark , Feith David J. , Loughran Thomas P. 
Published: November 2019

Abstract

Acute myeloid leukemia (AML) is a disease characterized by uncontrolled proliferation of immature myeloid cells in the blood and bone marrow. The 5-year survival rate is approximately 25%, and recent therapeutic developments have yielded little survival benefit. Therefore, there is an urgent need to identify novel therapeutic targets. We previously demonstrated that acid ceramidase (ASAH1, referred to as AC) is upregulated in AML and high AC activity correlates with poor patient survival. Here, we characterized a novel AC inhibitor, SACLAC, that significantly reduced the viability of AML cells with an EC50 of approximately 3 μmol/L across 30 human AML cell lines. Treatment of AML cell lines with SACLAC effectively blocked AC activity and induced a decrease in sphingosine 1-phosphate and a 2.5-fold increase in total ceramide levels. Mechanistically, we showed that SACLAC treatment led to reduced levels of splicing factor SF3B1 and alternative MCL-1 mRNA splicing in multiple human AML cell lines. This increased proapoptotic MCL-1S levels and contributed to SACLAC-induced apoptosis in AML cells. The apoptotic effects of SACLAC were attenuated by SF3B1 or MCL-1 overexpression and by selective knockdown of MCL-1S. Furthermore, AC knockdown and exogenous C16-ceramide supplementation induced similar changes in SF3B1 level and MCL-1S/L ratio. Finally, we demonstrated that SACLAC treatment leads to a 37% to 75% reduction in leukemic burden in two human AML xenograft mouse models.

Implications:
These data further emphasize AC as a therapeutic target in AML and define SACLAC as a potent inhibitor to be further optimized for future clinical development.
Determining Diasporic Chinese Identities from a Legal Perspective in China
Authors: Liu (刘国福) Guofu , Zhu (朱倩) Qian 
Published: November 2019

Abstract
The Chinese diaspora broadly includes the groups of huaren (华人, ethnic Chinese of different nationalities), huaqiao (华侨, overseas Chinese who are Chinese citizens overseas), guiqiao (归侨, returned overseas Chinese), and qiaojuan (侨眷, relatives in China of overseas Chinese). In the Chinese legal system, the determining of Chinese diasporic status is an important issue in the Chinese diaspora law, as it pertains to the protection of diaspora rights and interests by governmental authorities. The diaspora law in China identifies Chinese diasporic status and grants rights and duties according to nationality and residential qualifications but does not consider the actual contact between the Chinese diaspora and China. This has caused substantive legal procedural issues regarding the confirmation of the legal identity of Chinese diaspora and the issuing of relevant certifications both in China and abroad. These legal issues have presented significant challenges for the Chinese government in its efforts to engage with and manage the Chinese diaspora and it has created a bureaucratic barrier to the protection of their rights and interests. This paper aims to explore the current issues in determining the legal status of the Chinese diaspora, to critically review relevant laws, policies, and empirical research, and to suggest possible solutions for improving diaspora law in the legal system.
Epidemiology of Pediatric Tracheostomy and Risk Factors for Poor Outcomes: An 11‐Year Single‐Center Experience
Authors: Chia Aletheia Z. H. , Ng Zhi Min , Pang Yu Xian , Ang Annette H. C. , Chow Cristelle C. T. , Teoh Oon Hoe , Lee Jan Hau 
Published: November 2019

ObjectiveChildren with long‐term tracheostomies are at higher risk of complications. This study aims to describe the epidemiology, outcomes, and factors associated with successful decannulation in children undergoing tracheostomy.Study DesignCase series with chart review.SettingTertiary hospital.Subjects and MethodsA retrospective analysis was conducted on pediatric tracheostomies performed from 2006 to 2016. Demographics, preexisting comorbidities, indications for tracheostomy, and pretracheostomy ventilatory requirements were collected. A multivariate regression model with covariates of age, failure to thrive (FTT), and comorbidities was used to identify factors associated with successful decannulation. Secondary outcomes were ventilation and oxygen requirements at hospital discharge, hospital and intensive care unit length of stay, and complications.ResultsIn total, 105 patients received a tracheostomy at a median age of 8.0 months (interquartile range, 2.0‐45.0). The most common indication was anatomic airway obstruction (55 of 105, 52.5%). Forty‐four (41.9%) patients had preexisting FTT. In‐hospital mortality was 14 of 105 (13.3%). None were directly related to tracheostomy. At discharge, 40 of 91 (44.0%) and 12 of 91 (13.2%) required home mechanical ventilation and supplemental oxygen, respectively. Forty‐one (39%) patients underwent successful decannulation at a median 408 days (interquartile range, 170‐1153) posttracheostomy. On adjusted analysis, unsuccessful decannulation was more common in patients with FTT and neurologic comorbidities. Postoperative complications were more common in younger patients and those with a longer time to decannulation.ConclusionNeurologic comorbidities and FTT were risk factors for unsuccessful decannulation after pediatric tracheostomy. Nutritional interventions may have a role in improving long‐term outcomes following pediatric tracheostomies and should be investigated in future studies.
Pathway-specific modulatory effects of neuromuscular electrical stimulation during pedaling in chronic stroke survivors
Authors: Bao Shi-Chun , Leung Wing-Cheong , K. Cheung Vincent C. , Zhou Ping , Tong Kai-Yu 
Published: November 2019

Abstract
Background
Neuromuscular electrical stimulation (NMES) is extensively used in stroke motor rehabilitation. How it promotes motor recovery remains only partially understood. NMES could change muscular properties, produce altered sensory inputs, and modulate fluctuations of cortical activities; but the potential contribution from cortico-muscular couplings during NMES synchronized with dynamic movement has rarely been discussed.

Method
We investigated cortico-muscular interactions during passive, active, and NMES rhythmic pedaling in healthy subjects and chronic stroke survivors. EEG (128 channels), EMG (4 unilateral lower limb muscles) and movement parameters were measured during 3 sessions of constant-speed pedaling. Sensory-level NMES (20 mA) was applied to the muscles, and cyclic stimulation patterns were synchronized with the EMG during pedaling cycles. Adaptive mixture independent component analysis was utilized to determine the movement-related electro-cortical sources and the source dipole clusters. A directed cortico-muscular coupling analysis was conducted between representative source clusters and the EMGs using generalized partial directed coherence (GPDC). The bidirectional GPDC was compared across muscles and pedaling sessions for post-stroke and healthy subjects.

Results
Directed cortico-muscular coupling of NMES cycling was more similar to that of active pedaling than to that of passive pedaling for the tested muscles. For healthy subjects, sensory-level NMES could modulate GPDC of both ascending and descending pathways. Whereas for stroke survivors, NMES could modulate GPDC of only the ascending pathways.

Conclusions
By clarifying how NMES influences neuromuscular control during pedaling in healthy and post-stroke subjects, our results indicate the potential limitation of sensory-level NMES in promoting sensorimotor recovery in chronic stroke survivors.
Jumping translocations of chromosome 1q occurring by a multi-stage process in an acute myeloid leukemia progressed from myelodysplastic syndrome with a TET2 mutation
Authors: Lee Ina , Gudipati Mary A. , Waters Elizabeth , Duong Vu H. , Baer Maria R. , Zou Ying 
Published: November 2019

Abstract
Background
Jumping translocations (JTs) are rare chromosome rearrangements characterized by re-localization of one donor chromosome to multiple recipient chromosomes. Here, we describe an acute myeloid leukemia (AML) that progressed from myelodysplastic syndrome (MDS) in association with acquisition of 1q JTs. The sequence of molecular and cytogenetic changes in our patient may provide a mechanistic model for the generation of JTs in leukemia.

Case presentation
A 68-year-old man presented with pancytopenia. Bone marrow aspirate and biopsy showed a hypercellular marrow with multilineage dysplasia, consistent with MDS, with no increase in blasts. Karyotype and MDS fluorescence in situ hybridization (FISH) panel were normal. Repeat bone marrow aspirate and biopsy after 8 cycles of azacitidine, with persistent pancytopenia, showed no changes in morphology, and karyotype was again normal. Myeloid mutation panel showed mutations in RUNX1, SRSF2, ASXL1, and TET2. Three years after diagnosis, he developed AML with myelodysplasia-related changes. Karyotype was abnormal, with unbalanced 1q JTs to the short arms of acrocentric chromosomes 14 and 21, leading to gain of 1q.

Conclusions

Our patient had MDS with pathogenic mutations of the RUNX1, SRSF2, ASXL1, and TET2 genes and developed 1q JTs at the time of progression from MDS to AML. Our data suggest that the formation of 1q JTs involves multiple stages and may provide a mechanistic model for the generation of JTs in leukemia.
Colonisation with pathogenic drug-resistant bacteria and Clostridioides difficile among residents of residential care facilities in Cape Town, South Africa: a cross-sectional prevalence study
Authors: September Jason , Geffen Leon , Manning Kathryn , Naicker Preneshni , Faro Cheryl , Mendelson Marc , Wasserman Sean 
Published: November 2019

Abstract
Background
Residential care facilities (RCFs) act as reservoirs for multidrug-resistant organisms (MDRO). There are scarce data on colonisation with MDROs in Africa. We aimed to determine the prevalence of MDROs and C. difficile and risk factors for carriage amongst residents of RCFs in Cape Town, South Africa.

Methods
We performed a cross-sectional surveillance study at three RCFs. Chromogenic agar was used to screen skin swabs for methicillin-resistant S. aureus (MRSA) and stool samples for extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E). Antigen testing and PCR was used to detect Clostridiodes difficile. Risk factors for colonisation were determined with logistic regression.

Results
One hundred fifty-four residents were enrolled, providing 119 stool samples and 152 sets of skin swabs. Twenty-seven (22.7%) stool samples were positive for ESBL-E, and 13 (8.6%) residents had at least one skin swab positive for MRSA. Two (1.6%) stool samples tested positive for C. difficile. Poor functional status (OR 1.3 (95% CI, 1.0–1.6)) and incontinence (OR 2.9 (95% CI, 1.2–6.9)) were significant predictors for ESBL-E colonisation. MRSA colonization appeared higher in frail care areas (8/58 v 5/94, p = 0.07).

Conclusions
There was a relatively high prevalence of colonisation with MDROs, particularly ESBL-E, but low C. difficile carriage, with implications for antibiotic prescribing and infection control practice.
Citrus limetta peels: a promising substrate for the production of multienzyme preparation from a yeast consortium
Authors: Shariq Maria , Sohail Muhammad 
Published: November 2019

AbstractCitrus limettapeels (CLP), a waste material generated by juice industries, has scarcely been reported for the production of yeast enzymes. The study was conducted to obtain a multienzyme preparation from a yeast consortium under solid-state fermentation of CLP. The substrate, CLP, was pretreated using either acid or alkali, and factors affecting production of multienzyme were studied by generating two separate Plackett–Burman designs. Since, alkali-pretreated CLP yielded higher titers; therefore, significant factors affecting multienzyme preparation using this substrate were optimized by employing Box–Behnken design. The analysis revealed that under optimized conditions, i.e., cultivation of yeast strains for 72 h to alkali-pretreated CLP moistened with mineral salt medium having pH 5 yielded more than 10 IU mL−1of cellulase, xylanase, and amylase. The multienzyme was studied for its application to saccharify fruit and non-fruit wastes and for orange juice clarification. The data showed that the enzyme preparation could release 3.03 mg L−1 h−1of reducing sugars from various crude substrates and was able to reduce turbidity of orange juice by 11% with substantial decrease in viscosity and acidity. Hence, CLP appeared as a promising substrate to produce multienzyme preparation from yeast consortium.
Planning and practice of clinical research: Basic principles and errors as exemplified by Russian diabetology (A lecture)
Authors: Starostina Ye. G. , Antsiferov M. B. 
Published: November 2019

In one of the previous publications, the main indicators of the quality of diabetes care in our country have already been analyzed. One of the main (if not the main) reasons for its unsatisfactory quality, in our opinion, is inconsistency of theory and practice with the modern world scientific and clinical level of diabetology. A number of provisions of domestic diabetology are still based on the approaches of the 50-70s. For some recommendations, it is generally impossible to find scientific justifications in either foreign or domestic literature. They are transmitted orally from endocrinologists of the older generation to the young, like legends, without being scientifically proven. The only justification for them is the statement this is our school or this is how practice shows.
Any approaches are really tested by practice. That is why unsatisfactory indicators of compensation and acute complications and disability for diabetes mellitus indicate significant shortcomings in domestic diabetology. When an endocrinologist says that he repeatedly had to note, for example, the appearance of acetonuria in patients with insulin-dependent diabetes mellitus after a fatty meal, or the ophthalmologist discovers a positive dynamics of the state of the retina while taking angioprotectors, these facts in themselves, observations, even numerous ones, do not prove the existence of a causal relationship between the two phenomena. Even the ancients said: "After this - does not mean therefore." Due to the selectivity of attention and memory, the opposite cases, which are no less (in our example, the absence of acetonuria after a fatty meal or the preservation of hemorrhages, despite the many months of taking angioprotectors), prefer to not notice.
That is why it seems appropriate to discuss strictly defined principles and rules of evidence-based scientific and clinical research existing in the world practice. The main objective of this article is to help scientists avoid methodological errors in research, learn how to plan them correctly, and practical doctors to critically and thoughtfully understand the publications of medical journals. Programs of medical faculties of many countries include special courses on the formation of a critical type of medical thinking and the ability to reasoned analysis (the course medical logic, decision analysis, critical analysis of the postulates of medicine, etc.), which also address research planning problems. For clarity, this publication will focus on clinical trials conducted with the participation of patients and with the goal, as a rule, of studying the effectiveness of a treatment method or an individual drug, the characteristics of the course of the disease under certain conditions, etc.