bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromatographic fingerprints analysis and determination of seven components in Danmu preparations by HPLC–DAD/QTOF-MS
Authors: Li Nanxin , Zhang Jinju , Zhang Ying , Ma Zhiguo , Liao Jinhong , Cao Hui , Wu Menghua 
Published: February 2020

Abstract
Background
Danmu preparations (Danmu Capsule and Danmu Syrup), which are made from Nauclea officinalis stem extracts, have good clinical efficacy in acute tonsillitis, acute pharyngitis and upper respiratory tract infection. However, there is currently no reliable and systematic method to control the quality of these two Danmu preparations.

Methods
Using high-performance liquid chromatography (HPLC) coupled with diode array detection (DAD), the fingerprints of the Danmu preparations were established at 250 nm to comprehensively investigate the stability of preparation process. The chemical constituents in the Danmu preparations were separated and identified by HPLC coupled with quadrupole-time-of-flight high-definition mass spectrometry (HPLC–Q-TOF-MS). And seven major components were simultaneously determined at dual wavelengths (250 nm, 326 nm).

Results
The results of HPLC fingerprint similarity evaluation showed that the similarity values of 25 batches of Danmu preparations were more than 0.993. Twenty-three compounds, including 10 alkaloids, 6 phenolic acids, 2 iridoids, and 5 unknown compounds, were identified or tentatively characterized according to the retention times and MS/MS fragment patterns of compounds. The developed assay method of seven components was validated with acceptable linearity, precision, repeatability, stability and recovery. The contents of strictosamide belonging to alkaloids as the most abundant constituent in Danmu Capsule and Danmu Syrup were 43,681.20–99,652.49 μg/g and 1567.83–2427.25 μg/mL respectively. The contents of protocatechuic acid which were the highest in measured phenolic acids were 2633.01–7739.78 μg/g in Danmu Capsule and 192.05–448.71 μg/mL in Danmu Syrup, respectively. As an iridoid, the contents of sweroside in Danmu Capsule and Danmu Syrup were 1573.82–2789.81 μg/g and 70.32–182.81 μg/mL, respectively.

Conclusion
The established qualitative analysis method of fingerprint can be used to attain standardization, uniformity and stability of the preparation process. Meanwhile, the quantitative analysis in this study can be used as an accurate assay method for preparations.
The use of sodium DL-3-Hydroxybutyrate in severe acute neuro-metabolic compromise in patients with inherited ketone body synthetic disorders
Authors: Bhattacharya Kaustuv , Matar Walid , Tolun Adviye Ayper , Devanapalli Beena , Thompson Sue , Dalkeith Troy , Lichkus Kate , Tchan Michel 
Published: February 2020

AbstractBackgroundKetone bodies form a vital energy source for end organs in a variety of physiological circumstances. At different times, the heart, brain and skeletal muscle in particular can use ketones as a primary substrate. Failure to generate ketones in such circumstances leads to compromised energy delivery, critical end-organ dysfunction and potentially death. There are a range of inborn errors of metabolism (IEM) affecting ketone body production that can present in this way, including disorders of carnitine transport into the mitochondrion, mitochondrial fatty acid oxidation deficiencies (MFAOD) and ketone body synthesis. In situations of acute energy deficit, management of IEM typically entails circumventing the enzyme deficiency with replenishment of energy requirements. Due to profound multi-organ failure it is often difficult to provide optimal enteral therapy in such situations and rescue with sodium DL-3-hydroxybutyrate (S DL-3-OHB) has been attempted in these conditions as documented in this paper.ResultsWe present 3 cases of metabolic decompensation, one with carnitine-acyl-carnitine translocase deficiency (CACTD) another with 3-hydroxyl, 3-methyl, glutaryl CoA lyase deficiency (HMGCLD) and a third with carnitine palmitoyl transferase II deficiency (CPT2D). All of these disorders are frequently associated with death in circumstance where catastrophic acute metabolic deterioration occurs. Intensive therapy with adjunctive S DL-3OHB led to rapid and sustained recovery in all. Alternative therapies are scarce in these situations.ConclusionS DL-3-OHB has been utilised in multiple acyl co A dehydrogenase deficiency (MADD) in cases with acute neurological and cardiac compromise with long-term data awaiting publication. The use of S DL-3-OHB is novel in non-MADD fat oxidation disorders and contribute to the argument for more widespread use.
Circulating cell-free mitochondrial DNA levels in Parkinson’s disease are influenced by treatment
Authors: Lowes Hannah , Pyle Angela , Santibanez-Koref Mauro , Hudson Gavin 
Published: February 2020

AbstractSeveral studies have linked circulating cell-free mitochondrial DNA (ccf-mtDNA) to human disease. In particular, reduced ccf-mtDNA levels in the cerebrospinal fluid (CSF) of both Alzheimer’s and Parkinson’s disease (PD) patients have raised the hypothesis that ccf-mtDNA could be used as a biomarker for neurodegenerative disease onset and progression. However, how a reduction of CSF ccf-mtDNA levels relates to neurodegeneration remains unclear. Many factors are likely to influence ccf-mtDNA levels, such as concomitant therapeutic treatment and comorbidities. In this study we aimed to investigate these factors, quantifying CSF ccf-mtDNA from the Parkinson’s Progression Markers Initiative in 372 PD patients and 159 matched controls at two time points. We found that ccf-mtDNA levels appear significantly reduced in PD cases when compared to matched controls and are associated with cognitive impairment. However, our data indicate that this reduction in ccf-mtDNA is also associated with the commencement, type and duration of treatment. Additionally, we found that ccf-mtDNA levels are associated with comorbidities such as depression and insomnia, however this was only significant if measured in the absence of treatment. We conclude that in PD, similar to reports in HIV and sepsis, comorbidities and treatment can both influence ccf-mtDNA homeostasis, raising the possibility that ccf-mtDNA may be useful as a biomarker for treatment response or the development of secondary phenotypes. Given that, clinically, PD manifests often decades after neurodegeneration begins, predicting who will develop disease is important. Also, identifying patients who will respond to existing treatments or develop secondary phenotypes will have increased clinical importance as PD incidence rises.
Injury-related deaths before and during the Islamic State insurgency – Baghdad, Iraq, 2010–2015
Authors: Goers Matthew , Leidman Eva , Sultan Abdul-Salam Saleh , Hassan Ahmed , Bilukha Oleg 
Published: February 2020

Abstract
Background
Following a period of low intensity conflict during 2009–2012, the emergence of the Islamic State of Iraq and Levant (or Islamic State) in 2013 was associated with a resurgence of violence in Baghdad, Iraq’s capital and largest city. We evaluated trends in injury-related deaths in Baghdad before and during the Islamic State insurgency.

Methods
Iraqi National Injury Mortality Surveillance System prospectively collects information on fatal injuries from governorate coroner offices using standardized reporting forms. Trained coroner clerks collect information on victim demographics, intention of injury and mechanism of injury during medical examinations using reports from police and families. We analyzed data on all deaths reported by the Baghdad Forensic Institute from January 1, 2010 to December 31, 2015.

Results
There were 17,555 injury-related deaths with documented intent and mechanism (range 2385–3347 per year): 6241 from gunfire (36%), 1381 explosions (8%), 1348 non-gunfire assaults (8%), 3435 traffic accidents (20%), and 5150 other unintentional injuries (29%). Rates of gunfire (23.45 per 100,000) and explosion (5.90 per 100,000) deaths were significantly higher in 2014 than in all other years during the review period (p < 0.001 and p = 0.03, respectively). During the same period from 2010 to 2015, traffic accident deaths declined significantly from 13.29 to 6.35 (p = 0.002), with declines observed primarily among pedestrians. Trends in the rate of non-gunfire-assault and unintentional deaths, comparing 2010 and 2015, were not significant (p = 0.12 and p = 0.63, respectively). Unintentional deaths were mostly attributed to burns (46%) and electricity-related injuries (31%). The proportion of both females and children was highest in unintentional injury deaths.

Conclusions
During the study period, deaths from both gunfire and explosions in Baghdad peaked in 2014, corresponding with emergence of the Islamic State. Trends suggest a potential impact of insurgency-related activity on other injuries as evidenced by a decrease in the death rate from traffic accidents. The decreased traffic-related death rate could be from decreased vehicle and pedestrian activity during times of violence. Monitoring trends in injury mortality during conflict allows Iraq to identify priority injury causes to inform public health interventions.
Upregulation of Beta4 subunit of BKCa channels in the anterior cingulate cortex contributes to mechanical allodynia associated anxiety-like behaviors
Authors: Zhao Huan , Xue Qian , Li Cong , Wang Qingchuan , Han Shichao , Zhou Yongsheng , Yang Tao , Xie Yingli , Fu Hao , Lu Changbo , Meng Fancheng , Zhang Ming , Zhang Yan , Wu Xianglong , Wu Shengxi , Zhuo Min , Xu Hui 
Published: February 2020

AbstractThe anterior cingulate cortex (ACC) serves as a critical hub for the anxiety and pain perception. The large-conductance Ca2+-activated potassium channels, or BKCachannels, are ubiquitously expressed throughout the central nervous system including the cingulate cortex. However, what changes of cortical BKCachannels undergo in the ACC remains unknown in pain-related anxiety. In the present study, a significant upregulation of synaptic and non-synaptic BKCachannel accessory β4 subunits in the ACC was accompanied with pain-associated anxiety-like behaviors in the chronic compression of multiple dorsal root ganglia (mCCD) of the rat. NS1619, an opener of BKCachannels, significantly rescued the alteration of fAHP and AP duration of ACC pyramidal neurons in mCCD rats. The mRNA expression of BKCaβ4 subunits was extremely upregulated in the ACC after mCCD with the increased amount of both synaptic and non-synaptic BKCaβ4 subunit protein. Meanwhile, NS1619 reversed the enhanced AMPA receptor-mediated spontaneous excitatory postsynaptic current (sEPSC) frequency and the attenuated PPR of ACC neurons in mCCD rats. Local activation of BKCachannels in the ACC reversed mechanical allodynia and anxiety-like behaviors. These results suggest that the upregulation of postsynaptic and presynaptic BKCaβ4 subunit may contribute to neuronal hyperexcitability and the enhanced synaptic transmission in the ACC in neuropathic pain state, and then may result in anxiety-like behavior induced by neuropathic pain.
PoDFEd: Podiatrists and Diabetes Footcare Education Survey ‐ How do Australian podiatrists provide diabetes education?
Authors: Yuncken Julia , Haines Terrance , Stolwyk Renerus J. , Williams Cylie M. 
Published: February 2020

AbstractBackgroundPodiatrists provide care and education to people with diabetes. This often includes the use of education relating to complications of the disease and how to prevent them. It is currently unknown how Australian podiatrists provide this education. This study aimed to describe the foot related diabetes education being delivered to people with diabetes within the Australian podiatry setting.MethodsThis cross‐sectional cohort study contacted Australian podiatrists to complete an online survey regarding their provision of diabetes education. The Qualtrics online survey application was advertised to Australian podiatrists via social media, at state conferences and through the Australian Podiatry Association and other similar association group emails. A multivariate stepwise progression was utilised to collate and decipher data. A chi‐squared test was used to determine significant links between podiatrist's method of education, demographic variables and topics of education.ResultsFindings linked the use of visual, written, generic handout and individualised handouts to various components of education and demographic information of Australian podiatrists. Verbal education had no significant links to demographic and topics of education relating to diabetes.ConclusionsThis paper discovered a range of topics covered and methods used by Australian podiatrists during consultations with patients with diabetes.
Protein velocity and acceleration from single-cell multiomics experiments
Authors: Gorin Gennady , Svensson Valentine , Pachter Lior 
Published: February 2020

AbstractThe simultaneous quantification of protein and RNA makes possible the inference of past, present, and future cell states from single experimental snapshots. To enable such temporal analysis from multimodal single-cell experiments, we introduce an extension of the RNA velocity method that leverages estimates of unprocessed transcript and protein abundances to extrapolate cell states. We apply the model to six datasets and demonstrate consistency among cell landscapes and phase portraits. The analysis software is available as the protaccel Python package.
Driving Pressure During General Anesthesia for Open Abdominal Surgery (DESIGNATION): study protocol of a randomized clinical trial
Authors:   The DESIGNATION–investigators
Published: February 2020

AbstractBackgroundIntraoperative driving pressure (ΔP) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (VT) is kept constant, ΔP may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. ΔP may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery.MethodsThe “Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial” (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged ≥ 18 years and with a body mass index ≤ 40 kg/m2, scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) (“individualized high PEEP”) or one in which PEEP of 5 cm H2O without RM is used (“low PEEP”). In the “individualized high PEEP” group, PEEP is set at the level at which ΔP is lowest. In both groups of the trial, VTis kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events.DiscussionDESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery.Trial registrationClinicaltrials.gov,NCT03884543. Registered on 21 March 2019.
Correction to: The Invested in Diabetes Study Protocol: a cluster randomized pragmatic trial comparing standardized and patient-driven diabetes shared medical appointments
Authors: Kwan Bethany M. , Dickinson L. Miriam , Glasgow Russell E. , Sajatovic Martha , Gritz Mark , Holtrop Jodi Summers , Nease Don E. , Ritchie Natalie , Nederveld Andrea , Gurfinkel Dennis , Waxmonsky Jeanette A. 
Published: February 2020

After publication of our article [1] the authors have notified us that the title for Figure 1 was incorrectly captioned.
Evaluating the re-identification risk of a clinical study report anonymized under EMA Policy 0070 and Health Canada Regulations
Authors: Branson Janice , Good Nathan , Chen Jung-Wei , Monge Will , Probst Christian , El Emam Khaled 
Published: February 2020

Abstract
Background
Regulatory agencies, such as the European Medicines Agency and Health Canada, are requiring the public sharing of clinical trial reports that are used to make drug approval decisions. Both agencies have provided guidance for the quantitative anonymization of these clinical reports before they are shared. There is limited empirical information on the effectiveness of this approach in protecting patient privacy for clinical trial data.

Methods
In this paper we empirically test the hypothesis that when these guidelines are implemented in practice, they provide adequate privacy protection to patients. An anonymized clinical study report for a trial on a non-steroidal anti-inflammatory drug that is sold as a prescription eye drop was subjected to re-identification. The target was 500 patients in the USA. Only suspected matches to real identities were reported.

Results
Six suspected matches with low confidence scores were identified. Each suspected match took 24.2 h of effort. Social media and death records provided the most useful information for getting the suspected matches.

Conclusions
These results suggest that the anonymization guidance from these agencies can provide adequate privacy protection for patients, and the modes of attack can inform further refinements of the methodologies they recommend in their guidance for manufacturers.
Rapid host expansion of an introduced parasite, the spiny rat louse Polyplax spinulosa (Psocodea: Phthiraptera: Polyplacidae), among endemic rodents in Australia
Authors: Wang Wei , Durden Lance A. , Shao Renfu 
Published: February 2020

AbstractBackgroundHistorical European exploration and colonization resulted in the introduction of four species of rodents to the Australian continent from Eurasia: the brown rat,Rattus norvegicus, the black rat,R. rattus, the Pacific rat,R. exulans, and the house mouse,Mus musculus. The spread of these rodents created opportunities for their co-introduced sucking lice to parasitize and adapt to endemic rodents in Australia.MethodsWe collected sucking lice from rodent specimens in seven museums across Australia. We identified the spiny rat louse,Polyplax spinulosa, based on morphology. We sequenced the mitochondrialcox1 andrrnLgenes ofP. spinulosaspecimens and constructed a phylogenetic tree withrrnLsequences.ResultsWe examined 989 rodent specimens of 54 species and collected 2111 adult sucking lice and 1064 nymphal sucking lice. We found thatP. spinulosahad nearly doubled its host range by parasitizing at least six endemic rodent species in Australia. The other two introduced lice,P. serrataandHoplopleura pacifica, however, have apparently failed to expand to any endemic rodents in Australia. Our analysis of mitochondrialrrnLgene sequences dividedP. spinulosainto two genotypes (EuropeanvsSoutheast Asian), which differ by 7.5%; both genotypes were introduced into Australia and then expanded their host ranges to include endemic rodents.ConclusionsThe earliest record of a European ship landing in Australia was in 1606, followed by British settlement in 1788. The expansion ofP. spinulosato at least six endemic rodent species in Australia has therefore occurred in the time frame of 200 to 400 years, which is extremely rapid relative to its host expansion to eight native rat species in Eurasia in ~ 16 million years since it diverged fromP. serrata. The host expansion ofP. spinulosais remarkable for a blood-sucking louse and is in stark contrast to the absence of host expansion byP. serrataandH. pacifica. Comparison among these three introduced sucking lice indicated that both louse-specific factors and host-specific factors can contribute to the success or failure of host expansion.
Genetic differentiation and population structure of Anopheles funestus from Uganda and the southern African countries of Malawi, Mozambique, Zambia and Zimbabwe
Authors: Kaddumukasa Martha A. , Wright Jane , Muleba Mbanga , Stevenson Jenny C. , Norris Douglas E. , Coetzee Maureen 
Published: February 2020

AbstractBackgroundAnopheles funestus(s.s.) is a primary vector of the malaria parasitePlasmodium falciparumin Africa, a human pathogen that causes almost half a million deaths each year. The population structure ofAn. funestuswas examined in samples from Uganda and the southern African countries of Malawi, Mozambique, Zambia and Zimbabwe.MethodsTwelve microsatellites were used to estimate the genetic diversity and differentiation ofAn. funestusfrom 13 representative locations across five countries. These were comprised of four sites from Uganda, three from Malawi and two each from Mozambique, Zambia and Zimbabwe.ResultsAll loci were highly polymorphic across the populations with high allelic richness and heterozygosity. A high genetic diversity was observed with 2–19 alleles per locus and an average number of seven alleles. Overall, expected heterozygosity (He) ranged from 0.65 to 0.79. When samples were pooled three of the 12 microsatellite loci showed Hardy–Weinberg equilibrium. Unsupervised Bayesian clustering analysis of microsatellite data revealed two clusters withAn. funestussamples from Mozambique, Uganda and Zambia falling into one group and Malawi and Zimbabwe into another. The overall genetic differentiation between the populations was moderate (FST = 0.116). Pairwise differentiation between the pairs was low but significant. A weak but significant correlation was established between genetic and geographical distance for most populations.ConclusionsHigh genetic diversity revealed by the loci with low to moderate differentiation, identified two clusters among theAn. funestuspopulations. Further research on the population dynamics ofAn. funestusin east and southern Africa is essential to understand the implications of this structuring and what effect it may have on the efficient implementation of mosquito vector control strategies.