bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of drug resistance mutations in HIV-infected individuals with low-level viraemia under combination antiretroviral therapy: an observational study in a tertiary hospital in Northern Taiwan, 2017–19
Authors: Kao Shu-Wei , Liu Zhuo-Hao , Wu Ting-Shu , Ku Stephane Wen-Wei , Tsai Chia-Lung , Shie Shian-Sen , Huang Po-Yen , Wu Yen-Mu , Hsiao Yu-Hsiang , Chen Nan-Yu 
Published: November 2020

AbstractBackgroundEffective ART is crucial for combating the HIV pandemic. Clinically, plasma viral load monitoring to achieve virological suppression is the guide for an optimal ART. The presence of low-level viraemia (LLV) below the definition level of virological failure is a risk factor for ART failure. However, there is no treatment consensus over LLV yet, mainly due to the limitation of standard HIV-RNA genotyping and the resultant insufficient understanding of LLV characteristics.ObjectivesTo better profile drug resistance mutations (DRMs) and the associated factors in cases experiencing LLV.MethodsA prospective observational study was conducted from 2017 to 2019. HIV-DNA was used as an alternative to HIV-RNA for HIV genotyping coupled with deep sequencing for ART-naive and ART-failure cases, as well as those with LLV.ResultsEighty-one ART-naive, 18 ART-failure and 16 LLV cases received HIV genotyping in the study. Three-quarters (12/16) of cases experiencing LLV harboured DRMs. Cases with LLV had higher prevalence of DRMs to NNRTIs than the ART-naive group (69% versus 20%, P &lt; 0.001), but lower DRM prevalence to NRTIs than the ART-failure group (25% versus 61%, P &lt; 0.001). Approximately half of the LLV cases had issues of suboptimal ART compliance/ART interruption, and 68.8% (11/16) did not display drug resistance to their ART at the time of LLV.ConclusionsHIV DRM profiles in LLV cases were significantly different to those in ART-naive and ART-failure cases. Approaches to consolidate ART compliance and early exploration of potential ART resistance may be needed for cases experiencing LLV episodes.
The Future of Analytical and Interpretative Toxicology: Where are We Going and How Do We Get There?
Authors: Wille Sarah M R , Elliott Simon 
Published: November 2020

Abstract(Forensic) toxicology has faced many challenges, both analytically and interpretatively, especially in relation to an increase in potential drugs of interest. Analytical toxicology and its application to medicine and forensic science have progressed rapidly within the past centuries. Technological innovations have enabled detection of more substances with increasing sensitivity in a variety of matrices. Our understanding of the effects (both intended and unintended) have also increased along with determination and degree of toxicity. However, it is clear there is even more to understand and consider. The analytical focus has been on typical matrices such as blood and urine but other matrices could further increase our understanding, especially in postmortem (PM) situations. Within this context, the role of PM changes and potential redistribution of drugs requires further research and identification of markers of its occurrence and extent. Whilst instrumentation has improved, in the future, nanotechnology may play a role in selective and sensitive analysis as well as bioassays. Toxicologists often only have an advisory impact on pre-analytical and pre-interpretative considerations. The collection of appropriate samples at the right time in an appropriate way as well as obtaining sufficient circumstance background is paramount in ensuring an effective analytical strategy to provide useful results that can be interpreted within context. Nevertheless, key interpretative considerations such as pharmacogenomics and drug–drug interactions as well as determination of tolerance remain and in the future, analytical confirmation of an individual’s metabolic profile may support a personalized medicine and judicial approach. This should be supported by the compilation and appropriate application of drug data pursuant to the situation. Specifically, in PM circumstances, data pertaining to where a drug was not/may have been/was contributory will be beneficial with associated pathological considerations. This article describes the challenges faced within toxicology and discusses progress to a future where they are being addressed.
Review and Commentary on the Importance of Bile Acids in the Life Cycle ofClostridioides difficilein Children and Adults
Authors: Faden Howard 
Published: November 2020

AbstractClostridioides difficile, a spore-forming anaerobe, resides in the intestine. The life cycle of C. difficile illustrates an interdependent relationship between bile acids, commensal microbiota, and C. difficile. Primary bile acids are critical for the germination of C. difficile spores in the small intestine, while secondary bile acids serve as a counterbalance to inhibit the growth of the organism in the colon. Many commensal bacteria especially Clostridium spp. are responsible for transforming primary bile acids into secondary bile acids. Antibiotics eliminate bacteria that convert primary bile acids into secondary bile acids and, thus, allow C. difficile to flourish and cause diarrhea. In children younger than 2 years of age, who normally only produce primary bile acids, colonization with toxin-producing C. difficile is exceedingly common. The reason for the absence of C. difficile diarrhea in the children remains unexplained.
Impact of lifetime attributable risk of radiation-induced secondary cancer in proton craniospinal irradiation with vertebral-body-sparing for young pediatric patients with medulloblastoma
Authors: Suzuki Shunsuke , Kato Takahiro , Murakami Masao 
Published: November 2020

Abstract
We used the method proposed by Schneider et al. Theor Biol Med Model 2011;8:27, to clarify how the radiation-induced secondary cancer incidence rate changes in patients after proton craniospinal irradiation (CSI) without and with vertebral-body-sparing (VBS). Eight patients aged 3–15 years who underwent proton CSI were enrolled in the study. For each case, two types of plan without and with VBS in the target were compared. The prescribed doses were assumed to be 23.4 Gy relative biological effectiveness (RBE) and 36 Gy (RBE). Using the dose–volume histograms of the two plans, the lifetime attributable risk (LAR) was calculated by both methods for each patient based on the dose data calculated using an XiO-M treatment planning system. Eight organs were analyzed as follows: lung, colon, stomach, small intestine, liver, bladder, thyroid and bone. When the prescribed dose used was 23.4 Gy (RBE), the average LAR differences and the average number needed to treat (NNT) between proton CSI without and with VBS were 4.04 and 24.8, respectively, whereas the average LAR difference and the average NNT were larger at 8.65 and 11.6, respectively, when the prescribed dose of 36 Gy (RBE) was used. The LAR for radiation-induced secondary cancer was significantly lower in proton CSI with VBS than without VBS in pediatric patients, especially for the colon, lung, stomach and thyroid. The results of this study could serve as reference data when considering how much of vertebral bodies should be included when performing proton CSI according to age in clinical settings.
Brucellosis, a forgotten cause of hepatitis in travellers
Authors: Ljubas Dominik , Lalovac Milos , Vince Adriana , Papic Neven 
Published: November 2020

A 43-year-old male patient developed fever after a trip to Balkans, which resolved on doxycycline treatment. However, abnormal liver function tests persisted, and 6 months later, he was diagnosed with non-viral chronic hepatitis. Clues to the diagnosis came from a thorough medical history. Blood cultures and molecular testing identified Brucella melitensis.
Heart Rate Variability as a Possible Predictive Marker for Acute Inflammatory Response in COVID-19 Patients
Authors: Hasty Frederick , García Guillermo , Dávila Héctor , Wittels S Howard , Hendricks Stephanie , Chong Stephanie 
Published: November 2020

ABSTRACT

Introduction
Increases in C-reactive protein (CRP) are used to track the inflammatory process of COVID-19 and are associated with disease state progression. Decreases in heart rate variability (HRV) correlate with worsening of disease states. This observational study tracks changes in HRV relative to changes in CRP in COVID-19 patients.

Materials and Methods
In accordance with an Institutional Review Board-approved study, 17 patients were followed using the wearable, noninvasive Tiger Tech Warfighter Monitor (WFM) that records HRV from a single limb electrocardiogram. Intermittent, daily short-segment data sets of 5 to 7 minutes over a minimum of 7 days were analyzed. Changes in HRV were compared to changes in CRP.

Results
Decreases in HRV of greater than 40% preceded a 50% increase in CRP during the ensuing 72 hours in 10 of the 12 patients who experienced a dramatic rise in CRP. The effectiveness of HRV as a leading indicator of a rise in CRP was evaluated; the sensitivity, specificity, positive predictive value, and negative predictive value for 40% decreases in HRV preceding 50% increases in CRP were 83.3%, 75%, 90.9%, and 60%, respectively.

Conclusion
Substantial decreases in HRV preceded elevations in CRP in the ensuing 72 hours with a 90.9% positive predictive value. Early detection of increasing inflammation may prove vital in mitigating the deleterious effects of an abnormal inflammatory response, particularly in COVID-19 patients. This capability could have a major impact in triage and care of moderate to severe COVID-19 patients in major medical centers as well as field hospitals. This study demonstrates the potential value of short-segment, intermittent HRV analysis in COVID-19 patients.
Einstein@Home discovery of the gamma-ray millisecond pulsar PSR J2039–5617 confirms its predicted redback nature
Authors: Clark C J , Nieder L , Voisin G , Allen B , Aulbert C , Behnke O , Breton R P , Choquet C , Corongiu A , Dhillon V S , Eggenstein H B , Fehrmann H , Guillemot L , Harding A K , Kennedy M R , Machenschalk B , Marsh T R , Mata Sánchez D , Mignani R P , Stringer J , Wadiasingh Z , Wu J 
Published: November 2020

ABSTRACT
The Fermi Large Area Telescope gamma-ray source 3FGL J2039.6–5618 contains a periodic optical and X-ray source that was predicted to be a ‘redback’ millisecond pulsar (MSP) binary system. However, the conclusive identification required the detection of pulsations from the putative MSP. To better constrain the orbital parameters for a directed search for gamma-ray pulsations, we obtained new optical light curves in 2017 and 2018, which revealed long-term variability from the companion star. The resulting orbital parameter constraints were used to perform a targeted gamma-ray pulsation search using the Einstein@Home-distributed volunteer computing system. This search discovered pulsations with a period of 2.65 ms, confirming the source as a binary MSP now known as PSR J2039–5617. Optical light-curve modelling is complicated, and likely biased, by asymmetric heating on the companion star and long-term variability, but we find an inclination i ≳ 60°, for a low pulsar mass between $1.1\, \mathrm{M}_{\odot } \lt M_{\rm psr} \lt $ 1.6 M⊙, and a companion mass of 0.15–$0.22\, \mathrm{M}_{\odot }$, confirming the redback classification. Timing the gamma-ray pulsations also revealed significant variability in the orbital period, which we find to be consistent with quadrupole moment variations in the companion star, suggestive of convective activity. We also find that the pulsed flux is modulated at the orbital period, potentially due to inverse Compton scattering between high-energy leptons in the pulsar wind and the companion star’s optical photon field.
Genomic Analysis Enlightens Agaricales Lifestyle Evolution and Increasing Peroxidase Diversity
Authors: Ruiz-Dueñas Francisco J , Barrasa José M , Sánchez-García Marisol , Camarero Susana , Miyauchi Shingo , Serrano Ana , Linde Dolores , Babiker Rashid , Drula Elodie , Ayuso-Fernández Iván , Pacheco Remedios , Padilla Guillermo , Ferreira Patricia , Barriuso Jorge , Kellner Harald , Castanera Raúl , Alfaro Manuel , Ramírez Lucía , Pisabarro Antonio G , Riley Robert , Kuo Alan , Andreopoulos William , LaButti Kurt , Pangilinan Jasmyn , Tritt Andrew , Lipzen Anna , He Guifen , Yan Mi , Ng Vivian , Grigoriev Igor V , Cullen Daniel , Martin Francis , Rosso Marie-Noëlle , Henrissat Bernard , Hibbett David , Martínez Angel T 
Published: November 2020

AbstractAs actors of global carbon cycle, Agaricomycetes (Basidiomycota) have developed complex enzymatic machineries that allow them to decompose all plant polymers, including lignin. Among them, saprotrophic Agaricales are characterized by an unparalleled diversity of habitats and lifestyles. Comparative analysis of 52 Agaricomycetes genomes (14 of them sequenced de novo) reveals that Agaricales possess a large diversity of hydrolytic and oxidative enzymes for lignocellulose decay. Based on the gene families with the predicted highest evolutionary rates—namely cellulose-binding CBM1, glycoside hydrolase GH43, lytic polysaccharide monooxygenase AA9, class-II peroxidases, glucose–methanol–choline oxidase/dehydrogenases, laccases, and unspecific peroxygenases—we reconstructed the lifestyles of the ancestors that led to the extant lignocellulose-decomposing Agaricomycetes. The changes in the enzymatic toolkit of ancestral Agaricales are correlated with the evolution of their ability to grow not only on wood but also on leaf litter and decayed wood, with grass-litter decomposers as the most recent eco-physiological group. In this context, the above families were analyzed in detail in connection with lifestyle diversity. Peroxidases appear as a central component of the enzymatic toolkit of saprotrophic Agaricomycetes, consistent with their essential role in lignin degradation and high evolutionary rates. This includes not only expansions/losses in peroxidase genes common to other basidiomycetes but also the widespread presence in Agaricales (and Russulales) of new peroxidases types not found in wood-rotting Polyporales, and other Agaricomycetes orders. Therefore, we analyzed the peroxidase evolution in Agaricomycetes by ancestral-sequence reconstruction revealing several major evolutionary pathways and mapped the appearance of the different enzyme types in a time-calibrated species tree.
G-Quadruplex loops regulate PARP-1 enzymatic activation
Authors: Edwards Andrea D , Marecki John C , Byrd Alicia K , Gao Jun , Raney Kevin D 
Published: November 2020

Abstract
G-Quadruplexes are non-B form DNA structures present at regulatory regions in the genome, such as promoters of proto-oncogenes and telomeres. The prominence in such sites suggests G-quadruplexes serve an important regulatory role in the cell. Indeed, oxidized G-quadruplexes found at regulatory sites are regarded as epigenetic elements and are associated with an interlinking of DNA repair and transcription. PARP-1 binds damaged DNA and non-B form DNA, where it covalently modifies repair enzymes or chromatin-associated proteins respectively with poly(ADP-ribose) (PAR). PAR serves as a signal in regulation of transcription, chromatin remodeling, and DNA repair. PARP-1 is known to bind G-quadruplexes with stimulation of enzymatic activity. We show that PARP-1 binds several G-quadruplex structures with nanomolar affinities, but only a subset promote PARP-1 activity. The G-quadruplex forming sequence found in the proto-oncogene c-KIT promoter stimulates enzymatic activity of PARP-1. The loop-forming characteristics of the c-KIT G-quadruplex sequence regulate PARP-1 catalytic activity, whereas eliminating these loop features reduces PARP-1 activity. Oxidized G-quadruplexes that have been suggested to form unique, looped structures stimulate PARP-1 activity. Our results support a functional interaction between PARP-1 and G-quadruplexes. PARP-1 enzymatic activation by G-quadruplexes is dependent on the loop features and the presence of oxidative damage.
Stereotactic Radiosurgery for Choroid Plexus Tumors: A Report of the International Radiosurgery Research Foundation
Authors: Faramand Andrew , Kano Hideyuki , Niranjan Ajay , Atik Ahmet F , Lee Cheng-chia , Yang Huai-che , Mohammed Nasser , Liscak Roman , Hanuska Jaromir , Tripathi Manjul , Kondziolka Douglas , Sheehan Jason , Mathieu David , Flickinger John C , Lunsford L Dade 
Published: November 2020

Abstract

BACKGROUND
Choroid plexus tumors (CPT) are rare epithelial tumors of the choroid plexus. Gross total resection (GTR) may be curative, but it is not always possible.

OBJECTIVE
To evaluate the role of Gamma Knife stereotactic radiosurgery (GKSRS) as either a primary or adjuvant management option for WHO grade I-III CPT through a multicenter project.

METHODS
A total of 32 patients (20 females) with a total of 43 treated tumors were included in the analysis. A total of 25 patients (78%) had undergone initial surgical resection. The median total tumor volume was 2.2 cc, and the median margin and maximum doses were 13 and 25.5 Gy, respectively.

RESULTS
Local tumor control was achieved in 69% of cases. Local tumor progression-free survival (PFS) rate for low-grade tumors at 1, 3, and 5 yr was 90%, 77%, 58%, respectively. The actuarial local tumor PFS rate for high-grade tumors at 1, 3, and 5 yr was 77%, 62%, and 62%, respectively. There was no significant difference in local tumor control rates between low- and high-grade CPT (P = .3). Gender, age, and degree of resection were not associated with treated tumor PFS. Distant intracranial spread developed in 6 patients at a median of 22 mo after initial SRS. Actuarial distant brain tumor PFS rate at 1, 2, 5, and 10 yr was 93%, 88%, 78%, and 65%, respectively. Three patients (9%) developed persistent symptomatic adverse radiation effects at a median of 11 mo after the procedure.

CONCLUSION
GKSRS represents a minimally invasive alternative management strategy for imaging defined or surgically recurrent low- and high-grade CPT.
Laparoscopic-Assisted Versus Mini-Open Laparotomy for Ventriculoperitoneal Shunt Placement in the Medicare Population
Authors: Khalid Syed I , Nunna Ravi S , Maasarani Samantha , Shanker Rachyl M , Behbahani Mandana , Edmondson Corbin P , Mehta Ankit I , Gupta Samir K , Chan Edie Y , Torquati Alfonso , Byrne Richard W , Adogwa Owoicho 
Published: November 2020

Abstract

BACKGROUND
Placement of the distal shunt catheter into the peritoneum during ventriculoperitoneal shunt (VPS) surgery can be done with either laparoscopic assistance or laparotomy.

OBJECTIVE
To compare outcomes in laparoscopic-assisted vs laparotomy for placement of VPS in the Medicare population.

METHODS
Patients undergoing VPS placement, between 2004 and 2014, were identified by International Classification of Disease, Ninth Revision and Current Procedural Terminology codes in the Medicare database. Demographic data including age, sex, comorbidities, and indications were collected. Six- and twelve-month complication rates were analyzed.

RESULTS
A total of 1966 (3.2%) patients underwent laparoscopic-assisted VPS and 60 030 (96.8%) patients underwent nonlaparoscopic-assisted VPS placement. Compared with traditional open VPS placement, the laparoscopic approach was associated with decreased odds of distal revision at 6- and 12-mo postoperatively (6 mo: odds ratio [OR] = 0.41, 95% confidence interval [CI]: 0.21-0.74; 12 mo: OR = 0.60, 95% CI: 0.39-0.94). At 6- and 12-mo postoperatively, multivariable regression analysis demonstrated increased odds of distal revision in patients with a body mass index (BMI) > 30 Kg/M2, history of open abdominal surgery, and history of laparoscopic abdominal surgery. Additionally, history of prior abdominal surgery and BMI > 30 Kg/M2 were significantly associated with increase odds of shunt infection at 6 and 12-mo, respectively.

CONCLUSION
In the largest retrospective analysis to date, patients with a history of abdominal surgery and obesity were found to be at increased risk of infection and distal revision after VPS placement. However, the laparoscopic approach for abdominal placement of the distal catheter was associated with reduced rates of distal revision in this population, suggesting an avenue for reducing complications in well-selected patients.
Sleep Disorders in Human Immunodeficiency Virus: A Substudy of the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Study
Authors: Kunisaki Ken M , De Francesco Davide , Sabin Caroline A , Winston Alan , Mallon Patrick W G , Anderson Jane , Bagkeris Emmanouil , Boffito Marta , Doyle Nicki , Haddow Lewis , Post Frank A , Sachikonye Memory , Vera Jaime , Khalil Wajahat , Redline Susan 
Published: November 2020

Abstract

Background
Self-reported sleep quality is poor in persons with human immunodeficiency virus (PWH), but prior studies commonly used nonspecific questionnaires, investigated only single sleep disorders, or lacked human immunodeficiency virus (HIV)-negative controls. We addressed these limitations in the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Sleep Substudy by assessing PWH and HIV-negative controls for insomnia, restless legs syndrome (RLS), and sleep apnea (SA).

Methods
Previously enrolled POPPY participants coenrolled in this substudy without regard to sleep symptoms. Participants completed validated sleep assessments including the Insomnia Severity Index questionnaire, International Restless Legs Syndrome Study Group questionnaire, and in-home, wrist-worn overnight oximetry. They also completed health-related quality of life questionnaires including 36-item Short Form (SF-36) and Patient-Reported Outcomes Measurement Information System (PROMIS) sleep questionnaires.

Results
We enrolled 357 PWH (246 &gt;50 years of age; 111 between 18 and 50 years) and 126 HIV-negative controls &gt;50 years of age. Among PWH, criteria were met by 21% for insomnia, 13% for RLS, and 6% for SA. Compared with HIV-negative controls, PWH had a higher risk of insomnia (adjusted odds ratio, 5.3; 95% confidence interval, 2.2–12.9) but not RLS or SA. Compared with PWH without insomnia, those with insomnia reported significantly worse scores on all SF-36 and PROMIS components; fewer than 30% reported previous diagnosis or treatment for insomnia.

Conclusions
Insomnia was more common in PWH, associated with worse health-related quality of life, and frequently undiagnosed. Further research should focus on the pathogenesis of insomnia in PWH and the development of effective screening and intervention strategies for this unique population.