bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myeloproliferative disorders and their effects on bone homeostasis: the role of megakaryocytes
Authors: Karagianni Aikaterini , Ravid Katya 
Published: August 2021

AbstractMyeloproliferative neoplasms (MPNs) are a heterogeneous group of chronic hematological diseases that arise from the clonal expansion of abnormal hematopoietic stem cells, of which polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) have been extensively reviewed in the context of control of clonal expansion, fibrosis, and other phenotypes. Herein, we review current knowledge on the influence of different forms of MPN on bone health. In studies, murine models and human data have implicated various degrees of effect of different forms of MPN on bone density and on osteoblast proliferation and differentiation. Most results have shown that bone volume is generally increased in patients with PMF, whereas it is slightly decreased or not altered in patients with ET or PV, although possible differences between male and female phenotypes were not fully explored in most MPN forms. Osteosclerosis in patients with PMF is a serious complication that can lead to bone marrow failure, and the loss of bone reported in some patients with ET or PV can lead to osteoporotic fractures. Some MPN forms are associated with an increased number of megakaryocytes (MKs), and several of the MK-associated factors in MPN are known to affect bone development. We review known mechanisms involved in these processes, with a focus on the role of MKs and secreted factors. Understanding MPN-associated changes in bone health could improve early intervention and treatment of this side effect of the pathology.
Phase 1 study of oral azacitidine (CC-486) plus R-CHOP in previously untreated intermediate- to high-risk DLBCL
Authors: Martin Peter , Bartlett Nancy L. , Chavez Julio C. , Reagan John L. , Smith Sonali M. , LaCasce Ann S. , Jones Jeffrey , Drew James , Wu Chengqing , Mulvey Erin , Revuelta Maria V. , Cerchietti Leandro , Leonard John P. 
Published: August 2021

Abstract
Resistance to standard immunochemotherapy remains an unmet challenge in diffuse large B-cell lymphoma (DLBCL), and aberrant DNA methylation may contribute to chemoresistance. Promising early-phase results were reported with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) plus subcutaneous azacitidine, a hypomethylating agent. In this phase 1 study, we evaluated CC-486 (oral azacitidine) plus 6 cycles of R-CHOP in patients with previously untreated intermediate- to high-risk DLBCL or grade 3B/transformed follicular lymphoma. CC-486 doses of 100, 150, 200, or 300 mg given 7 days before cycle 1 and on days 8-21 of cycles 1-5 were evaluated; additional patients were enrolled in the expansion phase to examine preliminary efficacy. The primary objectives were to determine the safety and the maximum tolerated dose (MTD) of CC-486 in combination with R-CHOP. The most common grade 3/4 toxicities were hematologic, including neutropenia (62.7%) and febrile neutropenia (25.4%); grade 3/4 nonhematologic toxicities were uncommon (&lt;7%). The MTD was not established; 2 patients had dose-limiting toxicities (1 with grade 4 febrile neutropenia; 1 with grade 4 prolonged neutropenia). The recommended phase 2 dose was established as 300 mg. The overall response rate was 94.9%, with 52 patients (88.1%) achieving complete responses. With a median follow-up of 28.9 months, estimated 1- and 2-year progression-free survival rates were 84.1% and 78.6%, respectively. Overall, epigenetic priming with CC-486 before R-CHOP can be delivered with acceptable safety to patients with previously untreated intermediate- to high-risk DLBCL or grade 3B/transformed follicular lymphoma. ClinicalTrials.gov: NCT02343536.
Correlation between estimated plasma remnant-like particle cholesterol and vegetable fat intake in Uku town, Japan
Authors: Adachi Hisashi , Kakuma Tatsuyuki , Enomoto Mika , Fukami Ako , Nakamura Sachiko , Nohara Yume , Morikawa Nagisa , Sakaue Akiko , Yamamoto Maki , Fukumoto Yoshihiro 
Published: August 2021

Abstract
Background
Remnant-like particle cholesterol (RLP-C) is highly atherogenic, which is associated with atherosclerosis. However, RLP-C has not been routinely measured in the clinical practice. We estimated RLP-C levels using conventional lipid profiles and examined the association between estimated RLP-C and related factors including nutrient intake.

Methods
This study was performed in Uku town, Nagasaki prefecture, Japan in 2019. A total of 225 subjects were enrolled and directly measured RLP-C levels. Estimated RLP-C levels were defined as the following formula [total cholesterol − (LDL-cholesterol) − (HDL-cholesterol)]. Multivariate analyses were used to assess the relationship between estimated RLP-C and atherogenic factors. We calculated cut-off values on dichotomized RLP-C (< 7.5 mg/dL vs. ≥ 7.5 mg/dL) by receiver operating characteristic (ROC) curve.

Results
The mean values of directly measured RLP-C levels and estimated RLP-C were 4.0 mg/dL and 16.4 mg/dL, respectively. In the multiple stepwise linear regression analysis, directly measured and estimated RLP-C levels were independently and commonly associated with apolipoprotein E, triglycerides, and vegetable fat intake (inversely). Using ROC curves, we found the cut-off value of estimated RLP-C was 22.0 mg/dL.

Conclusion
We demonstrated that the estimated RLP-C levels using conventional lipid profiles may substitute for directly measured RLP-C and these levels were independently and inversely associated with vegetable fat intake in the community-dwelling Japanese population.
Effect of calcium content of diet on crystal formation in urine of patients with calcium oxalate stones: a randomized crossover clinical trial
Authors: Gopala Sathish Kumar , Joe Jim 
Published: August 2021

Abstract
Background
Patients with idiopathic calcium oxalate stones are advised to consume a low-oxalate diet to prevent recurrence. In this study, on patients with calcium oxalate stones we have attempted to determine the effect of calcium content of diet on the formation of calcium oxalate crystals in urine by in vitro supersaturation study of fresh postprandial urine samples and observing the morphology of the crystals formed using polarized optical microscopy.

Methods
The trial was conducted as a prospective interventional randomised crossover clinical trial in a repeated measures design. Sixty patients with calcium oxalate stones and no metabolic abnormalities in urine treated by lithotripsy at a tertiary care centre during the period May 2016 to May 2019 were recruited. Following a 14 h overnight fasting, urine samples were collected after providing the patient with either a low- or high-calcium meal for breakfast followed four hours later, by high-oxalate meal for lunch. Urine was tested for multiple parameters including urine pH, specific gravity, calcium/creatinine ratio and supersaturation of urine with sodium oxalate followed by optical density measurement by spectrophotometry and microscopic analysis of crystals formed.

Results
Optical density values and calcium/creatinine ratio of urine samples obtained after high-calcium meal are significantly higher than in corresponding sample obtained after low-calcium meal (p < 0.001). These findings were reflected in the morphology of formed crystals in their size, shape and number. When urinary calcium levels were low, no crystals were formed during supersaturation study of postprandial urine samples following a high-oxalate diet.

Conclusions
High calcium content in diet significantly contributes to kidney stone formation. There is a lower risk of kidney stone formation with a low-calcium meal even on consumption of a high-oxalate diet.
TMC4 is a novel chloride channel involved in high-concentration salt taste sensation
Authors: Kasahara Yoichi , Narukawa Masataka , Ishimaru Yoshiro , Kanda Shinji , Umatani Chie , Takayama Yasunori , Tominaga Makoto , Oka Yoshitaka , Kondo Kaori , Kondo Takashi , Takeuchi Ayako , Misaka Takumi , Abe Keiko , Asakura Tomiko 
Published: August 2021

Abstract“Salty taste” sensation is evoked when sodium and chloride ions are present together in the oral cavity. The presence of an epithelial cation channel that receives Na+ has previously been reported. However, no molecular entity involving Cl− receptors has been elucidated. We report the strong expression of transmembrane channel-like 4 (TMC4) in the circumvallate and foliate papillae projected to the glossopharyngeal nerve, mediating a high-concentration of NaCl. Electrophysiological analysis using HEK293T cells revealed that TMC4 was a voltage-dependent Cl− channel and the consequent currents were completely inhibited by NPPB, an anion channel blocker. TMC4 allowed permeation of organic anions including gluconate, but their current amplitudes at positive potentials were less than that of Cl−. Tmc4-deficient mice showed significantly weaker glossopharyngeal nerve response to high-concentration of NaCl than the wild-type littermates. These results indicated that TMC4 is a novel chloride channel that responds to high-concentration of NaCl.
Staying in touch: how highly specialised moth pollinators track host plant phenology in unpredictable climates
Authors: Finch Jonathan T. D. , Power Sally A. , Welbergen Justin A. , Cook James M. 
Published: August 2021

Abstract
Background
For specialised pollinators, the synchrony of plant and pollinator life history is critical to the persistence of pollinator populations. This is even more critical in nursery pollination, where pollinators are obligately dependant on female host plant flowers for oviposition sites. Epicephala moths (Gracillariidae) form highly specialised nursery pollination mutualisms with Phyllanthaceae plants. Several hundred Phyllanthaceae are estimated to be exclusively pollinated by highly specific Epicephala moths, making these mutualisms an outstanding example of plant–insect coevolution. However, there have been no studies of how Epicephala moths synchronise their activity with host plant flowering or persist through periods when flowers are absent. Such knowledge is critical to understanding the ecology and evolutionary stability of these mutualisms. We surveyed multiple populations of both Breynia oblongifolia (Phyllanthaceae) and it’s Epicephala pollinators for over two years to determine their phenology and modelled the environmental factors that underpin their interactions.

Results
The abundance of flowers and fruits was highly variable and strongly linked to local rainfall and photoperiod. Unlike male flowers and fruits, female flowers were present throughout the entire year, including winter. Fruit abundance was a significant predictor of adult Epicephala activity, suggesting that eggs or early instar larvae diapause within dormant female flowers and emerge as fruits mature. Searches of overwintering female flowers confirmed that many contained pollen and diapausing pollinators. We also observed diapause in Epicephala prior to pupation, finding that 12% (9/78) of larvae emerging from fruits in the autumn entered an extended diapause for 38–48 weeks. The remaining autumn emerging larvae pupated directly without diapause, suggesting a possible bet-hedging strategy.

Conclusions
Epicephala appear to use diapause at multiple stages in their lifecycle to survive variable host plant phenology. Furthermore, moth abundance was predicted by the same environmental variables as male flowers, suggesting that moths track flowering through temperature. These adaptations may thereby mitigate against unpredictability in the timing of fruiting and flowering because of variable rainfall. It remains to be seen how widespread egg diapause and pre-pupal diapause may be within Epicephala moths, and, furthermore, to what degree these traits may have facilitated the evolution of these highly diverse mutualisms.
Mother-to-infant transmission of the carcinogenic colibactin-producing bacteria
Authors: Tsunematsu Yuta , Hosomi Koji , Kunisawa Jun , Sato Michio , Shibuya Noriko , Saito Emiko , Murakami Haruka , Yoshikawa Yuko , Iwashita Yuji , Miyoshi Noriyuki , Mutoh Michihiro , Ishikawa Hideki , Sugimura Haruhiko , Miyachi Motohiko , Wakabayashi Keiji , Watanabe Kenji 
Published: August 2021

Abstract
Background
The Escherichia coli strain that is known to produce the genotoxic secondary metabolite colibactin is linked to colorectal oncogenesis. Therefore, understanding the properties of such colibactin-positive E. coli and the molecular mechanism of oncogenesis by colibactin may provide us with opportunities for early diagnosis or prevention of colorectal oncogenesis. While there have been major advances in the characterization of colibactin-positive E. coli and the toxin it produces, the infection route of the clb + strain remains poorly characterized.

Results
We examined infants and their treatments during and post-birth periods to examine potential transmission of colibactin-positive E. coli to infants. Here, analysis of fecal samples of infants over the first month of birth for the presence of a colibactin biosynthetic gene revealed that the bacterium may be transmitted from mother to infant through intimate contacts, such as natural childbirth and breastfeeding, but not through food intake.

Conclusions
Our finding suggests that transmission of colibactin-positive E. coli appears to be occurring at the very early stage of life of the newborn and hints at the possibility of developing early preventive measures against colorectal cancer.
Inhibition of Streptococcus mutans biofilms with bacterial-derived outer membrane vesicles
Authors: Wang Yihui , Hoffmann Joseph P. , Baker Sarah M. , Bentrup Kerstin Höner zu , Wimley William C. , Fuselier Joseph A. , Bitoun Jacob P. , Morici Lisa A. 
Published: August 2021

Abstract
Background
Biofilms are microbial communities surrounded by a self-produced extracellular matrix which protects them from environmental stress. Bacteria within biofilms are 10- to 1000-fold more resistant to antibiotics, making it challenging but imperative to develop new therapeutics that can disperse biofilms and eradicate infection. Gram-negative bacteria produce outer membrane vesicles (OMV) that play critical roles in communication, genetic exchange, cargo delivery, and pathogenesis. We have previously shown that OMVs derived from Burkholderia thailandensis inhibit the growth of drug-sensitive and drug-resistant bacteria and fungi.

Results
Here, we examine the antibiofilm activity of Burkholderia thailandensis OMVs against the oral biofilm-forming pathogen Streptococcus mutans. We demonstrate that OMV treatment reduces biofilm biomass, biofilm integrity, and bacterial cell viability. Both heat-labile and heat-stable components, including 4-hydroxy-3-methyl-2-(2-non-enyl)-quinoline and long-chain rhamnolipid, contribute to the antibiofilm activity of OMVs. When OMVs are co-administered with gentamicin, the efficacy of the antibiotic against S. mutans biofilms is enhanced.

Conclusion
These studies indicate that bacterial-derived OMVs are highly effective biological nanoparticles that can inhibit and potentially eradicate biofilms.
Multifoci and multiserotypes circulation of dengue virus in Senegal between 2017 and 2018
Authors: Dieng Idrissa , Ndione Marie Henriette Dior , Fall Cheikh , Diagne Moussa Moïse , Diop Mamadou , Gaye Aboubacry , Barry Mamadou Aliou , Diop Boly , Ndiaye Mamadou , Bousso Abdoulaye , Fall Gamou , Loucoubar Cheikh , Faye Oumar , Sall Amadou Alpha , Faye Ousmane 
Published: August 2021

Abstract
Background
Dengue fever is a mosquito born disease associated with self-limited to life threatening illness. First detected in Senegal in the nineteenth century, and despite its growing incidence this last decade, significant knowledge gaps exist in our knowledge of genetic diversity of circulating strains. This study highlights the circulating serotypes and genotypes between January 2017 and December 2018 and their spatial and temporal distribution throughout all regions of Senegal.

Methods
We used 56 dengue virus (DENV) strains for the analysis collected from 11 sampling areas: 39 from all regions of Senegal, and 17 isolates from Thiès, a particular area of the country. Two real time RT-qPCR systems were used to confirm dengue infection and corresponding serotypes. For molecular characterization, CprM gene was sequenced and submitted to phylogenetic analysis for serotypes and genotypes assignment.

Results
Three dengue virus serotypes (DENV-1–3) were detected by all used methods. DENV-3 was detected in 50% (28/56) of the isolates, followed by DENV-1 and DENV-2, each representing 25% (14/56) of the isolates. DENV-3 belongs to genotype III, DENV-1 to genotype V and DENV-2 to Cosmopolitan genotype. Serotype 3 was detected in 7 sampling locations and a co-circulation of different serotypes was observed in Thiès, Fatick and Richard-toll.

Conclusions
These results emphasize the need of continuous DENV surveillance in Senegal to detect DENV cases, to define circulating serotypes/genotypes and to prevent the spread and the occurrence of severe cases.
Longitudinal observational study of boxing therapy in Parkinson’s disease, including adverse impacts of the COVID-19 lockdown
Authors: Horbinski Craig , Zumpf Katelyn B. , McCortney Kathleen , Eoannou Dean 
Published: August 2021

Abstract
Background
Parkinson’s Disease (PD) is a highly prevalent neurodegenerative disease whose incidence is increasing with an aging population. One of the most serious manifestations of PD is gait instability, leading to falls and subsequent complications that can be debilitating, even fatal. Boxing therapy (BT) uses gait and balance exercises to improve ambulation in people with PD, though its efficacy has not yet been fully proven.

Methods
In the current longitudinal observational study, 98 participants with idiopathic PD underwent twice-weekly BT sessions. Primary outcome was self-reported falls per month; secondary outcomes were quantitative and semi-quantitative gait and balance performance evaluations. Statistical methods included segmented generalized estimating equation with an independent correlation structure, binomial distribution, and log link.

Results
The average number of self-reported falls per month per participant decreased by 87%, from 0.86 ± 3.58 prior to BT, to 0.11 ± 0.26 during BT. During the lockdown imposed by COVID-19, this increased to 0.26 ± 0.48 falls per month. Females and those > 65 years old reported the greatest increase in falls during the lockdown period. Post-lockdown resumption of BT resulted in another decline in falls, to 0.14 ± 0.33. Quantitative performance metrics, including standing from a seated position and standing on one leg, largely mirrored the pattern of falls pre-and post-lockdown.

Conclusions
BT may be an effective option for many PD patients.
Effect of an individualised nutritional intervention on gestational diabetes mellitus prevention in a high-risk population screened by a prediction model: study protocol for a multicentre randomised controlled trial
Authors: Zhang Chenjie , Wang Lulu , Sun Wenguang , Chen Lei , Zhang Chen , Li Hong , Yu Jiale , Fan Jianxia , Ruan Huijuan , Zheng Tao , Wu Dongling , Li Shaojing , Lu Huan , Wang Man , Mol Ben W. , Huang Hefeng , Wu Yanting 
Published: August 2021

Abstract
Background
The ability of a preventive nutritional intervention to reduce the morbidity of gestational diabetes mellitus (GDM) remains controversial. We aim to assess whether GDM can be prevented by an individualised nutritional intervention in pregnant women who are at high risk for the disease based on a prediction model.

Methods/design
A multicentre randomised controlled trial was designed to assess the efficacy of an individualised nutritional intervention for the prevention of GDM in a high-risk population screened by a novel prediction model in the first trimester. Pregnant women evaluated to be at high risk for GDM by the prediction model at less than 14 gestational weeks will be included. Women with pre-existing chronic diseases, including pregestational diabetes, or who are currently prescribed medicines that affect glucose values will be excluded. Allocation to intervention/control at a ratio of 1:1 will be conducted by a computerized randomisation system. The intervention group will complete 3-day food records and receive 3 individualised nutritional consultations with professional dieticians before the oral glucose tolerance test. The primary intention of the intervention is to promote a long-term healthy dietary pattern and prevent excessive gestational weight gain throughout pregnancy. The control group will complete 3-day food records at designated gestational weeks and receive standard antenatal care according to local health care provisions. The primary outcome is the incidence of GDM according to the criteria of the International Association of Diabetes and Pregnancy Study Group (IADPSG). A sample of 464 participants will provide 80% power to detect a 30% reduction in GDM incidence (α = 0.05 two tailed, 10% dropout). A total of 500 participants will be recruited.

Discussion
To date, this is the first randomised controlled trial aimed to evaluate the protective effect of an individualised nutritional intervention against GDM based on a logistic regression prediction model. Eligibility is not limited to obese women or singleton pregnancies, as in previous studies. This pragmatic trial is expected to provide valuable information on early screening and effective GDM prevention methods.

Trial registration number
ChiCTR, ChiCTR1900026963. Registered 27 October 2019.