bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic engineering with ATP-citrate lyase and nitrogen source supplementation improves itaconic acid production in Aspergillus niger
Authors: Hossain Abeer H. , van Gerven Roy , Overkamp Karin M. , Lübeck Peter S. , Taşpınar Hatice , Türker Mustafa , Punt Peter J. 
Published: October 2019

Abstract

Background
Bio-based production of organic acids promises to be an attractive alternative for the chemicals industry to substitute petrochemicals as building-block chemicals. In recent years, itaconic acid (IA, methylenesuccinic acid) has been established as a sustainable building-block chemical for the manufacture of various products such as synthetic resins, coatings, and biofuels. The natural IA producer Aspergillus terreus is currently used for industrial IA production; however, the filamentous fungus Aspergillus niger has been suggested to be a more suitable host for this purpose. In our previous report, we communicated the overexpression of a putative cytosolic citrate synthase citB in an A. niger strain carrying the full IA biosynthesis gene cluster from A. terreus, which resulted in the highest final titer reported for A. niger (26.2 g/L IA). In this research, we have attempted to improve this pathway by increasing the cytosolic acetyl-CoA pool. Additionally, we have also performed fermentation optimization by varying the nitrogen source and concentration.

Results
To increase the cytosolic acetyl-CoA pool, we have overexpressed genes acl1 and acl2 that together encode for ATP-citrate lyase (ACL). Metabolic engineering of ACL resulted in improved IA production through an apparent increase in glycolytic flux. Strains that overexpress acl12 show an increased yield, titer and productivity in comparison with parental strain CitB#99. Furthermore, IA fermentation conditions were improved by nitrogen supplementation, which resulted in alkalization of the medium and thereby reducing IA-induced weak-acid stress. In turn, the alkalizing effect of nitrogen supplementation enabled an elongated idiophase and allowed final titers up to 42.7 g/L to be reached at a productivity of 0.18 g/L/h and yield of 0.26 g/g in 10-L bioreactors.

Conclusion
Ultimately, this study shows that metabolic engineering of ACL in our rewired IA biosynthesis pathway leads to improved IA production in A. niger due to an increase in glycolytic flux. Furthermore, IA fermentation conditions were improved by nitrogen supplementation that alleviates IA induced weak-acid stress and extends the idiophase.
CSACI position statement: Newer generation H1-antihistamines are safer than first-generation H1-antihistamines and should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria
Authors: Fein Michael N. , Fischer David A. , O’Keefe Andrew W. , Sussman Gord L. 
Published: October 2019

Abstract
Oral H1-antihistamines (AHs) are the most commonly used therapy to treat allergic rhinitis and chronic urticaria. Older, first-generation AHs (e.g. diphenhydramine, hydroxyzine) have significant and common side effects including sedation, impairment with decreased cognitive function, poor sleep quality, dry mouth, dizziness, and orthostatic hypotension. These drugs have also been found to result in death from accidents, intentional or unintentional overdoses, and sudden cardiac death. The unfavourable risk–benefit profile of first-generation AHs led to the development of newer, less-sedating second- and third-generation AHs, which first became available in Canada in the 1980s. High-quality trials have proven that newer generation AHs are superior in safety compared to older first-generation AHs. On average, they have improved potency and efficacy. Second- and third-generation AHs are the recommended first-line treatment for mild allergic rhinitis and acute and chronic urticaria. Despite this evidence, older first-generation AHs continue to be over-utilized because of their over-the-counter (OTC) status and long history of use. The Canadian Society of Allergy Clinical Immunology (CSACI) recommends that newer generation AHs should be preferred over first-generation AHs for the treatment of allergic rhino-conjunctivitis and urticaria. To promote this recommendation, education of health professionals and the public is necessary. Further, given the dangers of older first-generation AHs, we believe they should be used only as a last resort with eventual consideration given to having them only available behind the counter in pharmacies.
Lactoferrin translocates to the nucleus of bovine rectal epithelial cells in the presence of Escherichia coli O157:H7
Authors: Rybarczyk Joanna , Khalenkow Dmitry , Kieckens Evelien , Skirtach Andre G. , Cox Eric , Vanrompay Daisy 
Published: October 2019

Abstract
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a foodborne pathogen which causes illness in humans. Ruminants are the main reservoirs and EHEC predominantly colonizes the epithelium of the recto-anal junction of cattle. Immunosuppression by EHEC promotes re-infection of cattle. However, bovine lactoferrin (bLF) apparently can overrule the immunosuppression by inducing EHEC-specific IgA responses at the mucosal site. The IgA responses are significantly correlated with reduced EHEC shedding and the absence of colonization at the rectal mucosa following re-infection. Therefore, to examine the interaction between bLF and bovine rectal epithelial cells, we first developed a method to establish a primary cell culture of epithelial cells of the rectum of cattle. Furthermore, we used LC–MS/MS to demonstrate the presence of secreted lactoferrin in bovine milk and the absence of a “delta” isoform which is known to translocate to the nucleus of cells. Nevertheless, lactoferrin derived from bovine milk was internalized by rectal epithelial cells and translocated to the nuclei. Moreover, nuclear translocation of bLF was significantly enhanced when the epithelial cells were inoculated with EHEC, as demonstrated by confocal fluorescence microscopy and confirmed by Raman microscopy and 3D imaging.
Precise large deviations for the aggregate claims in a dependent compound renewal risk model
Authors: Wang Kaiyong , Chen Lamei 
Published: October 2019

AbstractWe consider a dependent compound renewal risk model, where the interarrival times of accidents and the claim numbers follow a dependence structure characterized by a conditional tail probability and the claim sizes have a pairwise negatively quadrant dependence structure or a related dependence structure with the upper tail asymptotical dependence structure. When the distributions of the claim sizes belong to the dominated variation distribution class, we give the asymptotic lower and upper bounds for the precise large deviations of the aggregate claims.
Counting the non-existing: causes of death of undocumented migrants in Brussels-Capital Region (Belgium), 2005–2010
Authors: Lafaut Dirk , Vandenheede Hadewijch , Surkyn Johan , Coene Gily 
Published: October 2019

Abstract

Background
So far knowledge about undocumented migrant health status is poor. The objective of this study is to compare patterns in causes of death between undocumented migrants and legal residents, of both migrant and non-migrant origin.

Method
Using cause-of-death data, we compared undocumented migrants with Belgian residents and documented migrants through logistic regression analyses..

Results
This study shows that male undocumented migrants have a significantly higher risk of death from cardiovascular diseases compared to male Belgian residents (OR: 1.37) and documented migrants (OR: 2.17). Male undocumented migrants also have an increased risk of dying from external causes of death compared to documented migrants (OR: 1.93). Furthermore, we found a lower risk of suicidal death in undocumented migrants compared to Belgian residents (OR men: 0.29, OR women: 0.15).

Conclusions
We found important differences in underlying causes of death between undocumented migrants and residents in Belgium. These findings urge us to claim improved healthcare provision for undocumented migrants in Belgium.

Trial registration
Medical ethics committee UZ Jette, Brussels, Belgium – Registration date: 18/05/2016 – Registration number: B.U.N. 143201628279.
Perceptions of extended-release naltrexone, methadone, and buprenorphine treatments following release from jail
Authors: Velasquez Melissa , Flannery Mara , Badolato Ryan , Vittitow Alexandria , McDonald Ryan D. , Tofighi Babak , Garment Ann R. , Giftos Jonathan , Lee Joshua D. 
Published: October 2019

Abstract
Background
Few studies have documented patient attitudes and experiences with extended-release naltrexone (XR-NTX) opioid relapse prevention in criminal justice settings. This study assessed barriers and facilitators of jail-to-community reentry among adults with opioid use disorder (OUD) treated with XR-NTX, buprenorphine, methadone, and no medications.

Methods
This qualitative study conducted individual interviews with a purposeful and convenience sample of adults with OUD who were recently released from NYC jails. XR-NTX, no medication, and methadone participants were concurrently enrolled in a large randomized controlled trial evaluating XR-NTX vs. a no medication Enhanced Treatment As Usual (ETAU) condition, or enrolled in a non-randomized quasi-experimental methadone maintenance cohort. Buprenorphine participants were referred from NYC jails to a public hospital office-based buprenorphine program and not enrolled in the parent trial. Interviews were audio recorded, transcribed, independently coded by two researchers, and analyzed per a grounded theory approach adapted to the Social Cognitive Theory framework. The research team reviewed transcripts and coding to reach consensus on emergent themes.

Results
N = 33 adults with OUD (28 male, 5 female) completed a single individual interview. Purposeful sampling recruited persons leaving jail on XR-NTX (n = 11), no active medication treatment (n = 9), methadone (n = 9), and buprenorphine (n = 4). Emergent themes were: (1) general satisfaction with XR-NTX’s long-acting antagonist effects and control of cravings; (2) “testing” XR-NTX’s blockade with heroin upon reentry was common; (3) early discontinuation of XR-NTX treatment was most common among persons with high self-efficacy and/or heavy exposure to drug use environments and peers; (4) similar satisfaction regarding effects of methadone and buprenorphine maintenance among retained-in-treatment individuals, alongside general dissatisfaction with daily observed dosing requirements and misinformation and stigmas regarding methadone adverse effects; (5) unstable housing, economic insecurity, and exposure to actively using peers were attributed to early termination of treatment and relapse; (6) individual motivation and willpower as central to long-term opioid abstinence and reentry success.

Conclusions
In the context of more familiar agonist maintenance treatments, XR-NTX relapse prevention during jail-to-community reentry was viewed as a helpful and unique intervention though with important limitations. Commonly described barriers to treatment retention and heroin abstinence included homelessness, economic insecurity, and drug-using peers.
Trial registration ClinicalTrials.gov, NCT01999946 (XOR), Registered 03 December 2013, https://clinicaltrials.gov/ct2/show/NCT01999946.
The impact of the Green Revolution on indigenous crops of India
Authors: Eliazer Nelson Ann Raeboline Lincy , Ravichandran Kavitha , Antony Usha 
Published: October 2019

AbstractThe Green Revolution in India was initiated in the 1960s by introducing high-yielding varieties of rice and wheat to increase food production in order to alleviate hunger and poverty. Post-Green Revolution, the production of wheat and rice doubled due to initiatives of the government, but the production of other food crops such as indigenous rice varieties and millets declined. This led to the loss of distinct indigenous crops from cultivation and also caused extinction. This review deals with the impacts the Green Revolution had on the production of indigenous crops, its effects on society, environment, nutrition intake, and per capita availability of foods, and also the methods that can be implemented to revive the indigenous crops back into cultivation and carry the knowledge to the future generation forward.
Do we really need a surgery for hip fractures in elderly patients? Mortality rate and influencing factors
Authors: Hwang Kyu-Tae , Moon Jun-Ki , Kim Young-Ho 
Published: October 2019

AbstractBackgroundHip fractures are associated with notable mortality rates in elderly patients. The purpose of the study was to evaluate the mortality rate and influencing factors associated with mortality in the elderly patients with hip fractures.MethodsBetween October 2000 and December 2009, 807 elderly patients with hip fractures were enrolled in this study. There were 197 men and 610 women. The mean age at injuries were 78 years (range, 65–99 years). The fractures consisted of 390 femoral neck fractures and 417 intertrochanteric fractures. The mortality rate was evaluated between patients who underwent surgical and nonsurgical treatments. The influencing factors associated with mortality rate were evaluated statistically.ResultsOverall, 691 (85.6%) patients treated surgically and 116 (14.4%) patients treated nonsurgically were included. The overall mortality rates one and two years after injuries were 16.6 and 39.4%, respectively. In surgical treatment group, the mortality rate one and two years after injuries were 12.0 and 35.7%, respectively. In nonsurgical treatment group, the mortality rates were 44.0 and 61.2%, respectively (p < 0.05). No significant difference was noted between the types of fractures and the time from injury to surgery. Regardless of surgical methods, a significantly higher mortality rate was observed in patients with heart disease, chronic renal disease, dementia, and cancer, or in patients with 3 or more comorbidities.ConclusionsIn elderly patients with hip fractures, surgical treatments can decrease the mortality rate as compared with nonsurgical treatments. In addition, patients who had three or more comorbidities (heart disease, chronic renal failure, dementia, and history of cancer) are associated with a higher risk of mortality.Trial registrationRetrospectively registered.
Just say N2O – nitrous oxide misuse: essential information for psychiatrists
Authors: Sheldon Rollo J. G. , Reid Michael , Schon Frederick , Poole Norman A. 
Published: October 2019

SUMMARYNitrous oxide (N2O) misuse is widespread in the UK. Although it is well-known that it can cause devastating myeloneuropathy, psychiatric presentations are poorly described. There is little understanding of who it affects, how it presents, its mechanism of action and principles of treatment. We begin this article with a case study. We then review the literature to help psychiatrists understand this area and deal with this increasing problem, and make diagnosis and treatment recommendations. We describe a diagnostic pentad of weakness, numbness, paraesthesia, psychosis and cognitive impairment to alert clinicians to the need to urgently treat these patients. Nitrous oxide misuse is a pending neuropsychiatric emergency requiring urgent treatment with vitamin B12 to prevent potentially irreversible neurological and psychiatric symptoms.
Effectiveness of cognitive–behavioural therapy for depression in advanced cancer: CanTalk randomised controlled trial
Authors: Serfaty Marc , King Michael , Nazareth Irwin , Moorey Stirling , Aspden Trefor , Mannix Kathryn , Davis Sarah , Wood John , Jones Louise 
Published: October 2019

BackgroundDepression is one of the most common mental disorders in people with advanced cancer. Although cognitive–behavioural therapy (CBT) has been shown to be effective for depression in people with cancer, it is unclear whether this is the case for people with advanced cancer and depression.AimsWe sought to determine whether CBT is more clinically effective than treatment as usual (TAU) for treating depression in people with advanced cancer (trial registration number ISRCTN07622709).MethodA multi-centre, parallel-group single-blind randomised controlled trial comparing TAU with CBT (plus TAU). Participants (n = 230) with advanced cancer and depression were randomly allocated to (a) up to 12 sessions of individual CBT or (b) TAU. The primary outcome measure was the Beck Depression Inventory-II (BDI-II). Secondary outcome measures included the Patient Health Questionnaire-9, the Eastern Cooperative Oncology Group Performance Status, and Satisfaction with Care.ResultsMultilevel modelling, including complier-average intention-to-treat analysis, found no benefit of CBT. CBT delivery was proficient, but there was no treatment effect (−0.84, 95% CI −2.76 to 1.08) or effects for secondary measures. Exploratory subgroup analysis suggested an effect of CBT on the BDI-II in those widowed, divorced or separated (−7.21, 95% CI −11.15 to −3.28).ConclusionsUK National Institute for Health and Care Excellence (NICE) guidelines recommend CBT for treating depression. Delivery of CBT through the Improving Access to Psychological Therapies (IAPT) programme has been advocated for long-term conditions such as cancer. Although it is feasible to deliver CBT through IAPT proficiently to people with advanced cancer, this is not clinically effective. CBT for people widowed, divorced or separated needs further exploration. Alternate models of CBT delivery may yield different results.
Variation Between and Within Hospitals in Single Injection Caudal Local Anesthetic Dose: A Report From the Pediatric Regional Anesthesia Network
Authors: Taenzer Andreas H. , Hoyt Matthew , Krane Elliot J. , Walker Benjamin J. , Flack Sean , Bosenberg Adrian , Sethna Navil F. , Franklin Andrew D. , Polaner David M. ,   for the PRAN investigators
Published: October 2019

BACKGROUND:
Given that variation exists in health care utilization, expenditure, and medical practice, there is a paucity of data on variation within the practice of anesthesia. The Pediatric Regional Anesthesia Network (PRAN) data lend itself to explore whether different medical practice patterns exist and if there are nerve blocks with more local anesthetic dosing variation than others. The primary aim of this study was to quantify variation in single injection caudal block dosing, and the secondary aim was to explore possible causes for variation (eg, number of blocks performed versus geographic location).

METHODS:
We queried the PRAN database for single injection caudal blocks in children <1 year of age. Data were analyzed for local anesthetic dose, variation within and across institutions, and possible causes.

RESULTS:
Mean dose of bupivacaine equivalents per kilogram (BE·kg−1) among sites ranged from 1.39 to 2.22 with an interdecile range (IDR) containing the mid 80% of all doses ranging from 0.21 to 1.48. Mean dose (BE·kg−1) was associated with site, age, weight, and local anesthetic used (all P < .0001). Cohen’s F effect size estimate was 10 times higher for site (0.65) than for age (0.05) or weight (0.02). Variation (IDR) was not related to number of blocks done at each site (P = .23). Mean volume per kilogram was 0.9± ± 0.2 (mean ± ±standard deviation) and was more strongly associated with site (Cohen’s F 0.3) than age (0.04) or weight (0.07).

CONCLUSIONS:
Wide variation in caudal local anesthetic dosing and administered volume exists. This variation is independent of the number of cases performed at each center but rather is determined by study site (ie, variation between centers) with considerable additional variation within study centers, suggesting additional variability dependent on individual practitioners. While there are legitimate reasons to vary dosing, the current approach is inconsistent and not supported by strong evidence over giving a standardized dose.
Cellular senescence in development, regeneration and disease
Authors: Rhinn Muriel , Ritschka Birgit , Keyes William M. 
Published: October 2019

ABSTRACT
Cellular senescence is a state comprising an essentially irreversible proliferative arrest combined with phenotypic changes and pronounced secretory activity. Although senescence has long been linked with aging, recent studies have uncovered functional roles for senescence in embryonic development, regeneration and reprogramming, and have helped to advance our understanding of this process as a highly coordinated and programmed cellular state. In this Primer article, we summarize some of the key findings in the field and attempt to explain them in a simple model that reconciles the normal and pathological roles for senescence. We discuss how a primary role of cellular senescence is to contribute to normal development, cell plasticity and tissue repair, as a dynamic and tightly regulated cellular program. However, when this process is perturbed, the beneficial effects turn detrimental and can contribute to disease and aging.
Development of human limb muscles based on whole-mount immunostaining and the links between ontogeny and evolution
Authors: Diogo Rui , Siomava Natalia , Gitton Yorick 
Published: October 2019

ABSTRACT
We provide the first detailed ontogenetic analysis of human limb muscles using whole-mount immunostaining. We compare our observations with the few earlier studies that have focused on the development of these muscles, and with data available on limb evolution, variations and pathologies. Our study confirms the transient presence of several atavistic muscles – present in our ancestors but normally absent from the adult human – during normal embryonic human development, and reveals the existence of others not previously described in human embryos. These atavistic muscles are found both as rare variations in the adult population and as anomalies in human congenital malformations, reinforcing the idea that such variations/anomalies can be related to delayed or arrested development. We further show that there is a striking difference in the developmental order of muscle appearance in the upper versus lower limbs, reinforcing the idea that the similarity between various distal upper versus lower limb muscles of tetrapod adults may be derived.
The use of genetically humanized animal models for personalized medicine approaches
Authors: Aartsma-Rus Annemieke , van Putten Maaike 
Published: October 2019

ABSTRACT
For many genetic diseases, researchers are developing personalized medicine approaches. These sometimes employ custom genetic interventions such as antisense-mediated exon skipping or genome editing, aiming to restore protein function in a mutation-specific manner. Animal models can facilitate the development of personalized medicine approaches; however, given that they target human mutations and therefore human genetic sequences, scientists rely on the availability of humanized animal models. Here, we outline the usefulness, caveats and potential of such models, using the example of the hDMDdel52/mdx model, a humanized model recently generated for Duchenne muscular dystrophy (DMD).