bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human papillomavirus load and genotype analysis improves the prediction of invasive cervical cancer
Authors: Hortlund Maria , van Mol Tine , Van de Pol Frederik , Bogers Johannes , Dillner Joakim 
Published: February 2021

AbstractHuman papillomavirus (HPV)‐based cervical screening is a globally recommended health policy. Different HPV types have different risk for cervical cancer. For optimal HPV screening, the sensitivity and specificity for each HPV type at different viral loads should be known in a screening setting. HPV test results in about 1 million cervical samples analyzed during 2006 to 2014 were compared for 319 women who had developed invasive cervical cancer up to 8.5 years later and for 1911 matched control women. Detection including low viral loads resulted in markedly increased sensitivity for cervical cancer only for HPV types 16 and 18. Testing for HPV types 31, 33, 45 and 52 also increased the sensitivity for prediction of cervical cancer, but for these viruses, detection of low viral load did not further increase sensitivity. HPV types 35, 39, 51, 56, 58, 59, 66 and 68 only predicted occasional additional cervical cancer cases. Testing for HPV16/18 at low viral load plus testing for HPV31, 33, 45 and 52 at >3000 copies/μL predicted 86.5% of cancers occurring within a year after testing, similar to the 89.4% that were predicted by testing for 14 HPV types. By contrast, the type and viral load‐restricted testing greatly increased specificity: 6.3% of healthy women tested positive as compared to 11.7% of healthy women testing positive for the 14 HPV types commonly screened for today. Adequate HPV screening sensitivity, with considerable increase in specificity, can be obtained by testing only for HPV16/18/31/33/45/52, with detection of low viral load required only for HPV16/18.
Hepatopancreatoduodenectomy with simultaneous resection of the portal vein and hepatic artery for locally advanced cholangiocarcinoma: Short‐ and long‐term outcomes of superextended surgery
Authors: Nagino Masato , Ebata Tomoki , Yokoyama Yukihiro , Igami Tsuyoshi , Mizuno Takashi , Yamaguchi Junpei , Onoe Shunsuke , Watanabe Nobuyuki 
Published: February 2021

AbstractBackgroundOnly a few authors have reported negative results for hepatopancreatoduodenectomy (HPD) with simultaneous resection of the portal vein and hepatic artery in a limited number of patients. The aim of the current study was to outline our experience with this superextended surgery and to discuss its clinical value.MethodsMedical records of consecutive patients who underwent resection of perihilar cholangiocarcinoma between 2007 and 2020 were retrospectively reviewed.ResultsDuring the study interval, 650 patients with perihilar cholangiocarcinoma underwent resection. The superextended surgery was performed in only nine (1.4%) patients. Left or right trisectionectomy was primarily performed. For portal vein reconstruction, external iliac vein graft was required in seven patients. For hepatic artery reconstruction, rotating left gastric artery was often used. The median operative time was 870 minutes and blood loss was 2,598 mL. Postoperatively, pancreatic fistula and liver failure occurred in all patients, followed by intraabdominal abscess (n = 8), and bacteremia (n = 4). One patient died on day 86 due to multiple organ failure. Two patients survived for more than 7 years.ConclusionsHPD with simultaneous resection of the portal vein and hepatic artery is demanding but worth performing as the last option, with careful patient selection in experienced centers.
Functional morphology and fiber types of the masseter muscles of two caviomorph rodents with contrasting lifestyles, Ctenomys talarum (Ctenomyidae) and Cavia aperea (Caviidae)
Authors: Longo María Victoria , Díaz Alcira Ofelia , Vassallo Aldo Iván , Cohen Mariana 
Published: February 2021

AbstractThe aim of this work is the analysis of histochemical and morphometric properties of the masseter muscles of Ctenomys talarum and Cavia aperea. The former belongs to a subterranean rodent clade, Ctenomyidae, which has evolved a robust masticatory apparatus adapted to chisel‐tooth digging and processing of abrasive grasses; C. aperea belongs to the family Caviidae, with relatively graceful jaws and mandibular musculatures, consistent with less mechanically challenging diets. Adult males were captured, immediately transported to the laboratory, and euthanized in a CO2 chamber. The musculus masseter superficialis and musculus masseter profundus on the left side of the animals were used to analyze the histochemical composition of the fiber types treated with myosin adenosine triphosphatase, succinate dehydrogenase and periodic acid Schiff. The mean fiber diameters, relative areas, and frequencies of each muscle fiber type were calculated. The mm. masseter superficialis and masseter profundus on the right side were used to measure the physiological cross‐sectional area (PCSA). Based on this measurement, the internal force (F) was estimated. In the m. masseter profundus of both species and in the m. masseter superficialis of C. aperea intermediate fast oxidative‐glycolytic fibers (FOGi) predominated. In the mm. masseter superficialis and masseter profundus of C. talarum the relative area of fast glycolytic (FG) fibers was greater than that of the muscles of C. aperea, whose main muscle fiber component is FOGi fibers. When corrected for body mass differences, PCSA was higher for the mm. masseter superficialis of C. talarum. This and the larger relative area of FG fibers, probably contributes to the exertion of large bite forces in C. talarum, as measured in previous studies.
Association of impedance ratio with corrected Geriatric Nutritional Risk Index in older patients with nondialysis chronic kidney disease stage 5
Authors: Han Byoung‐Geun , Han Jihye , Lee Kwang Hoon 
Published: February 2021

AbstractBackgroundThe usual calculation of body mass index (BMI) can be misleading in patients with advanced chronic kidney disease (CKD) because their altered fluid balances may not be reflected. We obtained corrected BMI (cBMI) and corrected Geriatric Nutritional Risk Index (cGNRI) values and investigated whether the impedance ratio (IR) of 200/5 kHz, measured using bioimpedance spectroscopy, was associated with cGNRI in older patients with nondialysis CKD stage 5 (CKD5‐ND).MethodsPatients over 65 years old (n = 118) were divided into groups by cGNRI tertiles. The differences between the correlations were tested using Steiger's z‐test. The IR and cBMI were used as both continuous and categorical variables in the regression analyses to determine the factors that were independently associated with the cGNRI.ResultsPatients in the third cGNRI tertile had a significantly lower mean IR than those in the other 2 tertiles (P < .001). Across the 3 cGNRI tertile groups, the IR was incrementally lower in the higher cGNRI tertiles (P for trend < .001). The Steiger's z‐test showed that the IR had a significantly stronger correlation with cGNRI than cBMI had with cGNRI. In the multivariable linear regression analyses, the IR was independently associated with the cGNRI, after adjusting for various confounders.ConclusionThe current results revealed that the IR was a more sensitive indicator of nutrition risk than BMI and was independently associated with cGNRI in older patients with CKD5‐ND. Our study suggests that the IR is an appropriate tool for nutrition risk screening.
Use of amnion‐derived cellular cytokine solution for the treatment of gingivitis: A 2‐week safety, dose‐ranging, proof‐of‐principle randomized trial
Authors: Hasturk Hatice , Steed David , Tosun Emre , Martins Melissa , Floros Constantinos , Nguyen Daniel , Stephens Danielle , Cugini Maryann , Starr Jacqueline , Van Dyke Thomas E. 
Published: February 2021

AbstractBackgroundA 6‐week Phase I clinical trial was performed to primarily evaluate the safety and secondarily determine the preliminary efficacy of a novel biological solution, ST266, comprised of a mixture of cytokines, growth factors, nucleic acids, and lipids secreted by cultured amnion‐derived multipotent progenitor cells on gingival inflammation.MethodsFifty‐four adults with gingivitis/periodontitis were randomly assigned to 1X ST266 or diluted 0.3X ST266 or saline topically applied on facial/lingual gingiva (20 µL/tooth). Safety was assessed through oral soft/hard tissue exam, adverse events, and routine laboratory tests. Efficacy was assessed by modified gingival index (MGI), bleeding on probing, plaque index, probing depth (PD), and clinical attachment level (CAL). Assessments were performed on day 0, 8, 12, and 42. ST266 and saline applied daily starting at day 0 through day 12 except weekend days. Plasma was analyzed for safety and proinflammatory cytokines, interleukin (IL)‐1β, IL‐6, tumor necrosis factor‐alpha, and interferon gamma. Gingival crevicular fluid (GCF) was analyzed for the same cytokines. Subgingival plaque was primarily analyzed by checkerboard DNA‐DNA hybridization. Comparisons with saline were modeled through a generalized estimating equations method adjusting for baseline.ResultsNo safety concern was found related to ST266. Statistically significant reduction in MGI was noted at day 42 by 1X ST266 compared with saline (P = 0.044). PD and CAL were reduced by both doses of ST266 at day 42 (P <0.01) and by 1X ST266 at day 12 (P <0.05). GCF IL‐1β and IL‐6 levels were reduced by both doses of ST266 at day 12 (P <0.05, P <0.01, respectively). IL‐6 was also significantly reduced in plasma of both ST266 groups (P <0.05). Significant reductions in red complex bacteria were detected in both ST266 doses.ConclusionsIn this “first in human oral cavity” study, topical ST266 was safe and effective in reducing gingival inflammation in 6 weeks. Longitudinal studies with large sample sizes are warranted to assess the therapeutic value of this novel host modulatory compound in the treatment of periodontal diseases.
The genetics of mitochondrial disease: dissecting mitochondrial pathology using multi‐omic pipelines
Authors: Alston Charlotte L , Stenton Sarah L , Hudson Gavin , Prokisch Holger , Taylor Robert W 
Published: February 2021

AbstractMitochondria play essential roles in numerous metabolic pathways including the synthesis of adenosine triphosphate through oxidative phosphorylation. Clinically, mitochondrial diseases occur when there is mitochondrial dysfunction – manifesting at any age and affecting any organ system; tissues with high energy requirements, such as muscle and the brain, are often affected. The clinical heterogeneity is parallel to the degree of genetic heterogeneity associated with mitochondrial dysfunction. Around 10% of human genes are predicted to have a mitochondrial function, and defects in over 300 genes are reported to cause mitochondrial disease. Some involve the mitochondrial genome (mtDNA), but the vast majority occur within the nuclear genome. Except for a few specific genetic defects, there remains no cure for mitochondrial diseases, which means that a genetic diagnosis is imperative for genetic counselling and the provision of reproductive options for at‐risk families. Next‐generation sequencing strategies, particularly exome and whole‐genome sequencing, have revolutionised mitochondrial diagnostics such that the traditional muscle biopsy has largely been replaced with a minimally‐invasive blood sample for an unbiased approach to genetic diagnosis. Where these genomic approaches have not identified a causative defect, or where there is insufficient support for pathogenicity, additional functional investigations are required. The application of supplementary ‘omics’ technologies, including transcriptomics, proteomics, and metabolomics, has the potential to greatly improve diagnostic strategies. This review aims to demonstrate that whilst a molecular diagnosis can be achieved for many cases through next‐generation sequencing of blood DNA, the use of patient tissues and an integrated, multidisciplinary multi‐omics approach is pivotal for the diagnosis of more challenging cases. Moreover, the analysis of clinically relevant tissues from affected individuals remains crucial for understanding the molecular mechanisms underlying mitochondrial pathology. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Pneumothorax with Ortner syndrome: an unusual presentation of aortic dissection
Authors: Lo Shan Min , Ramarmuty Hema Yamini , Kannan Kunji 
Published: February 2021

AbstractOrtner syndrome or cardiovocal syndrome is hoarseness of voice due to left recurrent laryngeal nerve palsy as a result of cardiovascular abnormality. It is not known that pneumothorax has any association with Ortner syndrome. A 56‐year‐old gentleman, with previous history of 20 pack‐year smoking and 1‐year history of hypertension, presented to us with cough for two weeks with intermittent haemoptysis, as well as hoarseness of voice for the past one year. Direct laryngoscopy confirmed that he had left vocal cord palsy. Clinical and radiological investigations suggested that he had left pneumothorax. Left chest tube thoracostomy was performed and computed tomography of chest revealed aortic isthmus aneurysm with dissection extending to distal left common iliac artery and residual left hydropneumothorax. The patient was then referred to the vascular team and cardiothoracic team for further management.
Target localization during respiration motion based on LSTM: A pilot study on robotic puncture system
Authors: Ma Yuxiang , Yang Zhikai , Wu Wei , Xie Hongzhi , Gu Lixu 
Published: February 2021

AbstractBackgroundIn the needle biopsy, the respiratory motion causes the displacement of thoracic–abdominal soft tissues, which brings great difficulty to accurate localization. Based on internal target motion and external marker motion, the existing methods need to establish a correlation model or a prediction model to compensate the respiratory movement, which can hardly achieve required accuracy in clinic use due to the complexity of the internal tissue motion.MethodsIn order to improve the tracking accuracy and reduce the number of models, we propose a framework for target localization based on long short‐term memory (LSTM) method. Combined with the correlation model and the prediction model by using LSTM, we adopted the principal component of time‐series features of external surrogate signals to predict the trajectory of the internal tumour target. Additionally, based on the electromagnetic tracking system and Universal Robots 3 robotic arm, we applied the proposed approach to a prototype of robotic puncture system for real‐time tumour tracking.ResultsTo verify the proposed method, experiments on both public datasets and customized motion phantom for respiratory simulation were performed. In the public dataset study, an average mean absolute error, and an average root‐mean‐square error of predictive results of 0.44 and 0.58 mm were achieved, respectively. In the motion phantom study, an average root mean square of puncturing error resulted in 0.65 mm.ConclusionThe experimental results demonstrate the proposed method improves the accuracy of target localization during respiratory movement and appeals the potentials applying to clinical application.
Biological sex differences in Alzheimer's preclinical research: A call to action
Authors: Waters Ansley ,   Society for Women's Health Research Alzheimer's Disease Network, Laitner Melissa H. 
Published: February 2021

AbstractIntroductionFor decades, researchers have largely ignored sex as a biological variable (SABV) within preclinical studies. Recent literature indicates scientists are increasingly including male and female subjects in studies, but fewer studies assess for sex differences in study outcome. This is particularly concerning within the field of Alzheimer's disease (AD), as disease burden is higher among women and evidence suggests sex differences exist in etiology and disease course.MethodsWe conducted an informal review of preclinical AD research studies.ResultsResults confirmed that only about one‐third of ≈150 recent studies included both male and female mice, and <15 of nearly 150 studies examined SABV as an outcome of interest.DiscussionPrevious research supports the idea that better integration of SABV could open new doors in treatment research. We provide examples of best practices and discuss the need for Alzheimer's researchers to account for SABV within preclinical studies.
Donanemab (LY3002813) dose‐escalation study in Alzheimer's disease
Authors: Lowe Stephen Loucian , Willis Brian A. , Hawdon Anne , Natanegara Fanni , Chua Laiyi , Foster Joanne , Shcherbinin Sergey , Ardayfio Paul , Sims John R. 
Published: February 2021

AbstractIntroductionThis study explored the safety and tolerability features of donanemab (LY3002813) in patients with mild cognitive impairment due to Alzheimer's disease (AD) or mild to moderate AD dementia.MethodsPatients with AD were enrolled into the single‐ascending dose phase and were administered a single, intravenous (IV) dose of donanemab (five dosing cohorts from 0.1 to 10 mg/kg) or placebo followed by a 12‐week follow‐up period for each dose level. After the follow‐up period, the same patients proceeded into the multiple‐ascending dose (MAD) phase (five cohorts) and were administered IV doses of donanemab (0.3 to 10 mg/kg) or placebo approximately once per month for up to four doses depending on the initial doses (only cohort 1 went from 0.1 mg/kg to a higher dose of 0.3 mg/kg during the MAD phase). This phase concluded with a 12‐week follow‐up period. The relative exposure assessment of an unblinded, single, subcutaneous 3‐mg/kg dose of donanemab in patients with AD was also performed, followed by a 12‐week follow‐up period. One cohort of healthy subjects received an unblinded, single, IV 1‐mg/kg dose of donanemab. These two cohorts did not continue to the MAD phase.ResultsDonanemab was generally well tolerated up to 10 mg/kg. After single‐dose administration from 0.1 to 3.0 mg/kg, the mean terminal elimination half‐life was ≈4 days, increasing to ≈10 days at 10 mg/kg. Only the 10‐mg/kg dose showed changes in amyloid positron emission tomography. Amyloid reduction of 40% to 50% was achieved. Approximately 90% of subjects developed anti‐drug antibodies at 3 months after a single intravenous dose.DiscussionIntravenous donanemab 10 mg/kg can reduce amyloid deposits in AD despite having a shorter than expected half‐life.
Association of the use of hearing aids with the conversion from mild cognitive impairment to dementia and progression of dementia: A longitudinal retrospective study
Authors: Bucholc Magda , McClean Paula L. , Bauermeister Sarah , Todd Stephen , Ding Xuemei , Ye Qinyong , Wang Desheng , Huang Wei , Maguire Liam P. 
Published: February 2021

AbstractIntroductionHearing aid usage has been linked to improvements in cognition, communication, and socialization, but the extent to which it can affect the incidence and progression of dementia is unknown. Such research is vital given the high prevalence of dementia and hearing impairment in older adults, and the fact that both conditions often coexist. In this study, we examined for the first time the effect of the use of hearing aids on the conversion from mild cognitive impairment (MCI) to dementia and progression of dementia.MethodsWe used a large referral‐based cohort of 2114 hearing‐impaired patients obtained from the National Alzheimer's Coordinating Center. Survival analyses using multivariable Cox proportional hazards regression model and weighted Cox regression model with censored data were performed to assess the effect of hearing aid use on the risk of conversion from MCI to dementia and risk of death in hearing‐impaired participants. Disease progression was assessed with Clinical Dementia Rating Sum of Boxes (CDR‐SB) scores. Three types of sensitivity analyses were performed to validate the robustness of the results.ResultsMCI participants that used hearing aids were at significantly lower risk of developing all‐cause dementia compared to those not using hearing aids (hazard ratio [HR] 0.73, 95% confidence interval [CI], 0.61 to 0.89; false discovery rate [FDR]P = 0.004). The mean annual rate of change (standard deviation) in CDR‐SB scores for hearing aid users with MCI was 1.3 (1.45) points and significantly lower than for individuals not wearing hearing aids with a 1.7 (1.95) point increase in CDR‐SB per year (P = 0.02). No association between hearing aid use and risk of death was observed. Our findings were robust subject to sensitivity analyses.DiscussionAmong hearing‐impaired adults, hearing aid use was independently associated with reduced dementia risk. The causality between hearing aid use and incident dementia should be further tested.
Veterinary antibiotics in swine and cattle wastewaters of China and the United States: Features and differences
Authors: Wan Yi‐ping , Liu Ze‐hua , Liu Yu 
Published: February 2021

AbstractVeterinary antibiotics (VAs) have been widely used in livestock for disease prevention, treatment, and growth promotion. This study compared top 20 VAs in Chinese and US swine and cattle wastewater with published literatures. The sulfonamides (SAs) were found to be predominant, accounting for 62% of the top 20 VAs in Chinese swine wastewater, while tetracyclines (TCs) contributed to about 68.7% of the 18 VAs in US swine wastewater. The average concentration of the 20 major VAs in Chinese swine wastewater was estimated to be 1145 μg/L against 253.6 μg/L in the United States. On the other hand, the five major VAs in Chinese cattle wastewater were identified to be oxytetracycline, nafcillin, apramycin, lincomycin, and amikacin, while monensin was found to be dominant in US cattle wastewater. The average concentration of the top 20 VAs in Chinese and US cattle wastewaters were found to be 54.6 and 46.2 μg/L, respectively. These analyses suggested that VAs were probably over‐used in Chinese swine industry, eventually causing the development and spreading of antibiotic resistant‐bacteria and genes, which should be paid with attention.Practitioner points

Major veterinary antibiotics (VAs) in swine and cattle wastewater were identified.
Top 20 VAs in swine and cattle wastewater of China and the United States were compared.
VAs concentration in Chinese swine wastewater was 4.52 times that in the United States.
VAs concentration in Chinese cattle wastewater was 1.18 times that of the United States.