bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single-centre observational study comparing the impact of different cytomegalovirus prophylaxis strategies on cytomegalovirus infections in kidney transplant recipients
Authors: Tan Mabel Si Hua , Chung Shimin Jasmine , Ho Quan Yao , Thangaraju Sobhana , Kee Terence Yi Shern 
Published: September 2020

Background/objective: Prevention of cytomegalovirus (CMV) infection is an important component of post kidney transplant care. We aimed to evaluate the impact of two different CMV prophylaxis protocols on the epidemiology and outcomes of CMV infections at our centre. Methods: This is a single-centre retrospective before/after observational study. Kidney transplant recipients who received Protocol 1, a valacyclovir- or valganciclovir-based regimen prescribed for one to three months based on the CMV risk status between 2004 and 2008, were compared to those who received Protocol 2, a valganciclovir-based regimen prescribed for three months and six months for those at moderate and high risk, respectively, between 2010 and 2014. The impact of different prophylaxis regimens on the incidence of CMV infections, disease, recurrent infections and onset of CMV infection at 24 months were reviewed. Results: There were 192 patients included; 106 patients received Protocol 1, 86 received Protocol 2. At 24 months, the incidence of CMV infection was 53.8% and 55.8% in Protocols 1 and 2, respectively ( p=0.884). The incidence rates of CMV disease and recurrent CMV infections were higher in Protocol 1, but this was not statistically significant. The median time to first CMV infection was significantly shorter in patients who received Protocol 1: 132 days (interquartile range (IQR) 125–139 days) versus 185 days (IQR 178–192 days), p=0.001. Both prophylaxis protocols were well tolerated. Conclusion: The incidence of CMV infection was similar in both protocols. Where valganciclovir is not available, valacyclovir may be considered over no prophylaxis. Post-prophylaxis CMV infections are not uncommon, and vigilance for it should be advocated.
Interdisciplinary Surgical Management of Simultaneous Bone Metastases in Uterine Cervix Carcinoma: Total Replacement of Temporomandibular Joint and Stabilization of the Cervical Spine
Authors: Eckardt André M. , Reichstein Klaus , Heine M. 
Published: September 2020

Metastasis to the mandibular condyle and cervical spine in oncologic patients is rare, and clinicians should therefore be alert if patients present with such suspicious lesions for further clinical and pathological examinations. A 58-year old female patient with uterine cervical cancer initially presented with mild left condylar dysfunction. CT-imaging revealed a progressive osteolytic lesion of the left condyle and at the same time CT-scans revealed an osteolytic lesion of the cervical spine. Further metastatic bone lesions were ruled out. An incisional biopsy of the left condyle revealed metachronous metastasis from the uterine cervical carcinoma. Based on clinical and radiological examinations the patient underwent surgery with total alloplastic replacement of the temporomandibular joint (TMJ) and in a second surgical approach stabilization of the cervical spine. Suspicious symptoms with TMJ dysfunction in conjunction with osteolytic lesions of the maxillofacial skeleton in oncologic patients should be addressed quickly to prevent further diagnostic delay. Surgical resection of metastatic lesions should be considered as a palliative treatment option in selected patients.
Thrombospondin-1 promotes hemostasis through modulation of cAMP signaling in blood platelets
Authors: Aburima Ahmed , Berger Martin , Spurgeon Benjamin E. J. , Webb Bethany A. , Wraith Katie S. , Febbraio Maria , Poole Alastair W. , Naseem Khalid M. 
Published: September 2020

Abstract
Thrombospondin-1 (TSP-1) is released by platelets upon activation and can increase platelet activation, but its role in hemostasis in vivo is unclear. We show that TSP-1 is a critical mediator of hemostasis that promotes platelet activation by modulating inhibitory cyclic adenosine monophosphate (cAMP) signaling. Genetic deletion of TSP-1 did not affect platelet activation in vitro, but in vivo models of hemostasis and thrombosis showed that TSP-1–deficient mice had prolonged bleeding, defective thrombosis, and increased sensitivity to the prostacyclin mimetic iloprost. Adoptive transfer of wild-type (WT) but not TSP-1−/− platelets ameliorated the thrombotic phenotype, suggesting a key role for platelet-derived TSP-1. In functional assays, TSP-1–deficient platelets showed an increased sensitivity to cAMP signaling, inhibition of platelet aggregation, and arrest under flow by prostacyclin (PGI2). Plasma swap experiments showed that plasma TSP-1 did not correct PGI2 hypersensitivity in TSP-1−/− platelets. By contrast, incubation of TSP-1−/− platelets with releasates from WT platelets or purified TSP-1, but not releasates from TSP-1−/− platelets, reduced the inhibitory effects of PGI2. Activation of WT platelets resulted in diminished cAMP accumulation and downstream signaling, which was associated with increased activity of the cAMP hydrolyzing enzyme phosphodiesterase 3A (PDE3A). PDE3A activity and cAMP accumulation were unaffected in platelets from TSP-1−/− mice. Platelets deficient in CD36, a TSP-1 receptor, showed increased sensitivity to PGI2/cAMP signaling and diminished PDE3A activity, which was unaffected by platelet-derived or purified TSP-1. This scenario suggests that the release of TSP-1 regulates hemostasis in vivo through modulation of platelet cAMP signaling at sites of vascular injury.
mbend: an R package for bending non-positive-definite symmetric matrices to positive-definite
Authors: Nilforooshan Mohammad Ali 
Published: September 2020

Abstract
Background
R package mbend was developed for bending symmetric non-positive-definite matrices to positive-definite (PD). Bending is a procedure of transforming non-PD matrices to PD. The covariance matrices used in multi-trait best linear unbiased prediction (BLUP) should be PD. Two bending methods are implemented in mbend. The first is an unweighted bending with small positive values in a descending order replacing negative eigenvalues (LRS14), and the second method is a weighted (precision-based) bending with a custom small positive value (ϵ) replacing smaller eigenvalues (HJ03). Weighted bending is beneficial, as it relaxes low precision elements to change and it reduces or prohibits the change in high precision elements. Therefore, a weighted version of LRS14 was developed in mbend. In cases where the precision of matrix elements is unknown, the package provides an unweighted version of HJ03. Another unweighted bending method (DB88) was tested, by which all eigenvalues are changed (eigenvalues less than ϵ replaced with 100 × ϵ), and it is originally designed for correlation matrices.

Results
Different bending procedures were conducted on a 5 × 5 covariance matrix (V), V converted to a correlation matrix (C) and an ill-conditioned 1000 × 1000 genomic relationship matrix (G). Considering weighted distance statistics between matrix elements before and after bending, weighting considerably improved the bending quality. For weighted and unweighted bending of V and C, HJ03–4 (HJ03, ϵ = 10−4) performed the best. HJ03–2 (HJ03, ϵ = 10−2) ranked better than LRS14 for V, but not for C. Though the differences were marginal, LRS14 performed the best for G. DB88–4 (DB88, ϵ = 10−4) was used for unweighted bending and it ranked the last. This method could perform considerably better with a lower ϵ.

Conclusions
R package mbend provides necessary tools for transforming symmetric non-PD matrices to PD, using different methods and parameters. There were benefits in both weighted bending and small positive values in a descending order replacing negative eigenvalues. Thus, weighted LRS14 was implemented in mbend. Different bending methods might be preferable for different matrices, depending on the matrix type (covariance vs. correlation), number and the magnitude of negative eigenvalues, and the matrix size.
Nucleotide diversity of functionally different groups of immune response genes in Old World camels based on newly annotated and reference-guided assemblies
Authors: Lado Sara , Elbers Jean P. , Rogers Mark F. , Melo-Ferreira José , Yadamsuren Adiya , Corander Jukka , Horin Petr , Burger Pamela A. 
Published: September 2020

AbstractBackgroundImmune-response (IR) genes have an important role in the defense against highly variable pathogens, and therefore, diversity in these genomic regions is essential for species’ survival and adaptation. Although current genome assemblies from Old World camelids are very useful for investigating genome-wide diversity, demography and population structure, they have inconsistencies and gaps that limit analyses at local genomic scales. Improved and more accurate genome assemblies and annotations are needed to study complex genomic regions like adaptive and innate IR genes.ResultsIn this work, we improved the genome assemblies of the three Old World camel species – domestic dromedary and Bactrian camel, and the two-humped wild camel – via different computational methods. The newly annotated dromedary genome assembly CamDro3 served as reference to scaffold the NCBI RefSeq genomes of domestic Bactrian and wild camels. These upgraded assemblies were then used to assess nucleotide diversity of IR genes within and between species, and to compare the diversity found in immune genes and the rest of the genes in the genome. We detected differences in the nucleotide diversity among the three Old World camelid species and between IR gene groups, i.e., innate versus adaptive. Among the three species, domestic Bactrian camels showed the highest mean nucleotide diversity. Among the functionally different IR gene groups, the highest mean nucleotide diversity was observed in the major histocompatibility complex.ConclusionsThe new camel genome assemblies were greatly improved in terms of contiguity and increased size with fewer scaffolds, which is of general value for the scientific community. This allowed us to perform in-depth studies on genetic diversity in immunity-related regions of the genome. Our results suggest that differences of diversity across classes of genes appear compatible with a combined role of population history and differential exposures to pathogens, and consequent different selective pressures.
Disrupted architecture and fast evolution of the mitochondrial genome of Argeia pugettensis (Isopoda): implications for speciation and fitness
Authors: An Jianmei , Zheng Wanrui , Liang Jielong , Xi Qianqian , Chen Ruru , Jia Junli , Lu Xia , Jakovlić Ivan 
Published: September 2020

Abstract
Background
Argeia pugettensis is an isopod species that parasitizes other crustaceans. Its huge native geographic range spans the Pacific from China to California, but molecular data are available only for a handful of specimens from North-American populations. We sequenced and characterised the complete mitogenome of a specimen collected in the Yellow Sea.

Results
It exhibited a barcode (cox1) similarity level of only 87–89% with North-American populations, which is unusually low for conspecifics. Its mitogenome is among the largest in isopods (≈16.5 Kbp), mostly due to a large duplicated palindromic genomic segment (2 Kbp) comprising three genes. However, it lost a segment comprising three genes, nad4L-trnP-nad6, and many genes exhibited highly divergent sequences in comparison to isopod orthologues, including numerous mutations, deletions and insertions. Phylogenetic and selection analyses corroborated that this is one of the handful of most rapidly evolving available isopod mitogenomes, and that it evolves under highly relaxed selection constraints (as opposed to positive selection). However, its nuclear 18S gene is highly conserved, which suggests that rapid evolution is limited to its mitochondrial genome. The cox1 sequence analysis indicates that elevated mitogenomic evolutionary rates are not shared by North-American conspecifics, which suggests a breakdown of cox1 barcoding in this species.

Conclusions
A highly architecturally disrupted mitogenome and decoupling of mitochondrial and nuclear rates would normally be expected to have strong negative impacts on the fitness of the organism, so the existence of this lineage is a puzzling evolutionary question. Additional studies are needed to assess the phylogenetic breadth of this disrupted mitochondrial architecture and its impact on fitness.
Insights into the resistance of a synthetically-derived wheat to Septoria tritici blotch disease: less is more
Authors: Benbow Harriet R. , Brennan Ciarán J. , Zhou Binbin , Christodoulou Thalia , Berry Simon , Uauy Cristobal , Mullins Ewen , Doohan Fiona M. 
Published: September 2020

Abstract
Background
Little is known about the initial, symptomless (latent) phase of the devastating wheat disease Septoria tritici blotch. However, speculations as to its impact on fungal success and disease severity in the field have suggested that a long latent phase is beneficial to the host and can reduce inoculum build up in the field over a growing season. The winter wheat cultivar Stigg is derived from a synthetic hexaploid wheat and contains introgressions from wild tetraploid wheat Triticum turgidum subsp. dicoccoides, which contribute to cv. Stigg’s exceptional STB resistance, hallmarked by a long latent phase. We compared the early transcriptomic response to Zymoseptoria tritici of cv. Stigg to a susceptible wheat cultivar, to elucidate the mechanisms of and differences in pathogen recognition and disease response in these two hosts.

Results
The STB-susceptible cultivar Longbow responds to Z. tritici infection with a stress response, including activation of hormone-responsive transcription factors, post translational modifications, and response to oxidative stress. The activation of key genes associated with these pathways in cv. Longbow was independently observed in a second susceptible wheat cultivar based on an independent gene expression study. By comparison, cv. Stigg is apathetic in response to STB, and appears to fail to activate a range of defence pathways that cv. Longbow employs. Stigg also displays some evidence of sub-genome bias in its response to Z. tritici infection, whereas the susceptible cv. Longbow shows even distribution of Z. tritici responsive genes across the three wheat sub-genomes.

Conclusions
We identify a suite of disease response genes that are involved in early pathogen response in susceptible wheat cultivars that may ultimately lead to susceptibility. In comparison, we hypothesise that rather than an active defence response to stave off disease progression, cv. Stigg’s defence strategy is molecular lethargy, or a lower-amplitude of pathogen recognition that may stem from cv. Stigg’s wild wheat-derived ancestry. Overall, we present insights into cv. Stigg’s exceptional resistance to STB, and present key biological processes for further characterisation in this pathosystem.
Differential rates of intravascular uptake and pain perception during lumbosacral epidural injection among adults using a 22-gauge needle versus 25-gauge needle: a randomized clinical trial
Authors: Raju Robin , Mehnert Michael , Stolzenberg David , Simon Jeremy , Conliffe Theodore , Gehret Jeffrey 
Published: September 2020

Abstract
Background
Inadvertent intravascular injection has been suggested as the most probable mechanism behind serious neurological complications during transforaminal epidural steroid injections. Authors believe a smaller gauge needle may lead to less intravascular uptake and less pain. Theoretically, there is less chance for a smaller gauge needle to encounter a blood vessel during an injection compared to a larger gauge needle. Studies have also shown smaller gauge needle to cause less pain. The aim of the study was to quantify the difference between a 22-gauge needle and 25-gauge needle during lumbosacral transforaminal epidural steroid injection in regards to intravascular uptake and pain perception.

Methods
This was a prospective single blind randomized clinical trial performed at outpatient spine practice locations of two academic institutions. One hundred sixty-two consecutive patients undergoing lumbosacral transforaminal epidural injections from February 2018 to June 2019 were recruited and randomized to each arm of the study – 84 patients were randomized to the 22-gauge needle arm and 78 patients to 25-gauge arm. Each transforaminal injection level was considered a separate incidence, hence total number of incidence was 249 (136 in 22-gauge arm and 113 in 25-gauge arm). The primary outcome measure was intravascular uptake during live fluoroscopy and/or blood aspiration. The secondary outcome measure was patient reported pain during the procedure on the numerical rating scale.

Results
Fisher exact test was used to detect differences between 2 groups in regards to intravascular uptake and paired t-tests were used to detect differences in pain scores. The incidence of intravascular uptake for a 22-gauge needle was 5.9% (95% confidence interval: 1.9 to 9.8%) and for a 25-gauge needle, 7.1% (95% confidence interval: 2.4 to 11.8%) [p = 0.701]. Average numerical rating scale scores during the initial needle entry for 22-gauge and 25-gauge needle was 3.46 (95% confidence interval: 2.94 to 3.98) and 3.13 (95% confidence interval: 2.57 to 3.69) respectively [p = 0.375].

Conclusions
The study showed no statistically significant difference in intravascular uptake or pain perception between a 22-gauge needle and 25-gauge needle during lumbosacral transforaminal epidural steroid injections.

Trial registration
ClinicalTrials.gov NCT04350307. Registered 4/17/2020. (Retrospectively registered).
Big data analysis techniques to address polypharmacy in patients – a scoping review
Authors: Wilfling D. , Hinz A. , Steinhäuser J. 
Published: September 2020

Abstract
Background
Polypharmacy is a key challenge in healthcare especially in older and multimorbid patients. The use of multiple medications increases the potential for drug interactions and for prescription of potentially inappropriate medications. eHealth solutions are increasingly recommended in healthcare, with big data analysis techniques as a major component. In the following we use the term analysis of big data as referring to the computational analysis of large data sets to find patterns, trends, and associations in large data sets collected from a wide range of sources in contrast to using classical statistics programs. It is hypothesized that big data analysis is able to reveal patterns in patient data that would not be identifiable using conventional methods of data analysis. The aim of this review was to evaluate whether there are existing big data analysis techniques that can help to identify patients consuming multiple drugs and to assist in the reduction of polypharmacy in patients.

Methods
A computerized search was conducted in February 2019 and updated in May 2020, using the PubMed, Web of Science and Cochrane Library databases. The search strategy was defined by the principles of a systematic search, using the PICO scheme. All studies evaluating big data analytics about patients consuming multiple drugs were considered. Two researchers assessed all search results independently to identify eligible studies. The data was then extracted into standardized tables.

Results
A total of 327 studies were identified through the database search. After title and abstract screening, 302 items were removed. Only three studies were identified as addressing big data analysis techniques in patients with polypharmacy. One study extracted antipsychotic polypharmacy data, the second introduced a decision support system to evaluate side-effects in patients with polypharmacy and the third evaluated a decision support system to identify polypharmacy-related problems in individuals.

Conclusions
There are few studies to date which have used big data analysis techniques for identification and management of polypharmacy. There may be a need to further explore interdisciplinary collaboration between computer scientists and healthcare professionals, to develop and evaluate big data analysis techniques that can be implemented to manage polypharmacy.
Clinical features and outcomes of seven patients with COVID-19 in a family cluster
Authors: Zhang Yiling , Zhang Cheng , Hu Ying , Yao Hongmei , Zeng Xianchun , Hu Changrong , Zhao Li , Zhang Xiangyan , Ye Xianwei 
Published: September 2020

Abstract
Background
The family cluster is one of most important modes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission throughout China, and more details are needed about how family clusters cause the spread of coronavirus disease 2019 (COVID-19).

Case presentation
We retrospectively reviewed 7 confirmed cases from one family cluster. Both clinical features and laboratory examination results were described. Patient 1 had been in close contact with someone who was later confirmed to have COVID-19 in Wuhan City before he returned back to his hometown. He had dinner with 6 other members in his family. All the persons developed COVID-19 successively except for one older woman who neither had dinner with them nor shared a sleeping room with her husband. Six patients had mild or moderate COVID-19 but one older man with underlying diseases progressed into the severe type. After general and symptomatic treatments, all the patients recovered.

Conclusions
In a family cluster, having dinner together may be an important mode for the transmission of SARS-CoV-2. In this setting, most cases are mild with a favorable prognosis, while elderly patients with underlying diseases may progress into the severe type. For someone who has close contact with a confirmed case, 14-day isolation is necessary to contain virus transmission.
Interventions Made to Preserve Cognitive Function Trial (IMPCT) study protocol: a multi-dialysis center 2x2 factorial randomized controlled trial of intradialytic cognitive and exercise training to preserve cognitive function
Authors: McAdams-DeMarco Mara A. , Chu Nadia M. , Steckel Malu , Kunwar Sneha , González Fernández Marlís , Carlson Michelle C. , Fine Derek M. , Appel Lawrence J. , Diener-West Marie , Segev Dorry L. 
Published: September 2020

Abstract
Background
Kidney disease and dialysis significantly impact cognitive function across the age spectrum. Cognitive training (CT) and/or exercise training (ET) are promising approaches to preserve cognitive function among community-dwelling older adults, but have not been tested for cognition preservation in hemodialysis patients of all ages. In this manuscript, we summarize the protocol for the Interventions Made to Preserve Cognitive Function Trial (IMPCT).

Methods
We will perform a 2 × 2 factorial randomized controlled trial (RCT) of eligible adult (≥18 years) hemodialysis initiates (n = 200) to test whether intradialytic CT (brain games on a tablet PC), ET (foot peddlers) and combined CT + ET while undergoing hemodialysis preserves executive function compared to standard of care (SC). Participants will engage in the interventions to which they are randomized for 6 months. The primary objective is to compare, among interventions, the 3-month change in executive function measured using the Trail Making Test A (TMTA) and B (TMTB); specifically, executive function is calculated as TMTB-TMTA to account for psychomotor speed. This primary outcome was selected based on findings from our pilot study. The secondary objectives are to compare the risk of secondary cognitive outcomes, ESKD-specific clinical outcomes, and patient-centered outcomes at 3-months and 6-months. All data collection and interventions are conducted in the dialysis center.

Discussion
We hypothesize that receiving intradialytic CT or ET will better preserve executive function than SC but receiving combined CT + ET, will be the most effective intervention. The current trial will be an important step in understanding how intradialytic interventions might preserve cognitive health.

Trial Registration
Clinicaltrials.Gov (Date: 8/6/18): # NCT03616535. Protocol Version: 10 (April 2020). Funding: NIDDK R01DK114074.