bluuebunny/crossref_metadata_2025_split huggingface dataset:
DPYD genotyping and dihydropyrimidine dehydrogenase (DPD) phenotyping in clinical oncology. A clinically focused minireview
Authors: Paulsen Niels Herluf , Vojdeman Fie , Andersen Stig Ejdrup , Bergmann Troels K. , Ewertz Marianne , Plomgaard Peter , Hansen Morten Rix , Esbech Peter Skov , Pfeiffer Per , Qvortrup Camilla , Damkier Per 
Published: August 2022

AbstractBackgroundIn clinical oncology, systemic 5‐fluorouracil (5‐FU) and its oral pro‐drugs are used to treat a broad group of solid tumours. Patients with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency are at elevated risk of toxicity if treated with standard doses of 5‐FU. DPYD genotyping and measurements of plasma uracil concentration (DPD phenotyping) can be applied as tests for DPD deficiency. In April 2020, the European Medicines Agency recommended pre‐treatment DPD testing to reduce the risk of 5‐FU‐related toxicity.ObjectivesThe objective of this study is to present the current evidence for DPD testing in routine oncological practice.MethodsTwo systematic literature searches were performed following the PRISMA guidelines. We identified studies examining the possible benefit of DPYD genotyping or DPD phenotyping on the toxicity risk.FindingsNine and 12 studies met the criteria for using DPYD genotyping and DPD phenotyping, respectively.ConclusionsThe evidence supporting either DPYD genotyping or DPD phenotyping as pre‐treatment tests to reduce 5‐FU toxicity is poor. Further evidence is still needed to fully understand and guide clinicians to dose by DPD activity.
Split liver transplantation with extended right grafts on adult recipients: A propensity score matching analysis
Authors: Vargas Paola A. , Dalzell Christina , Robinson Todd , Cunningham Michaela , Henry Zachary , Stotts Matthew J. , Su Feng , Argo Curtis , Pelletier Shawn , Oberholzer Jose , Goldaracena Nicolas 
Published: August 2022

AbstractIntroductionSplit liver transplantation (SLT) emerged due to its potential to contribute to the organ pool and reduce organ shortage. However, SLT is technically challenging and has been associated with higher rates of postoperative complications leading to concerns about graft and patient survival. Moreover, there are few studies on matched‐pair adult recipients of SLT and whole‐liver transplant (WLT), with conflicting results.MethodsThis retrospective study analyze outcomes among adults who underwent SLT at our institution from 2010 to 2019. A 1:1 propensity score matching analysis was performed based on important donor and recipient variables. Baseline characteristics and postoperative outcomes were analyzed and compared between groups. Actuarial graft and patient survival were analyzed by KM curves.ResultsOut of 592 adults receiving a LT in our institution, 21 SLT adult recipients were identified and matched with 21 adults undergoing WLT. As expected donor age was significantly lower in SLT recipients (16 (15–22) vs. 32 (17–47), P = .012). Additional donor characteristics, including anthropometrics, and ischemic times were similar between groups. Baseline recipient characteristics and postoperative outcomes, including length of stay, vascular complications, biliary complications, and re‐transplantation were comparable between SLT and WLT recipients. Graft (95/95/95 vs. 100/94/94, P = .98) and patient (100/100/100 vs. 100/94/94, P = .30) survival at 1‐, 3‐, 5‐years, were similar between the SLT‐ and WLT group, respectively.ConclusionSplit liver transplantation has the potential to increase the availability of organs for adult recipients without compromising individual outcomes.
In‐hospital incidence of and risk factors for influenza‐associated respiratory failure
Authors: Ayuso García Blanca , Marchan Alvaro , Arrieta Ortubay Estíbaliz , Castillo Maza Cristina , Romay Lema Eva , Lalueza Antonio , Lumbreras Carlos 
Published: August 2022

AbstractBackgroundRespiratory failure (RF) is the most important complication of influenza virus infection. Its definition and incidence are heterogeneous in the literature.MethodsThis systematic review and meta‐analysis aim to determine the incidence of and risk factors for RF in patients hospitalized with influenza. Electronic databases were searched for articles on RF in patients hospitalized for influenza infection up to December 2021 regardless of their geographical location. Observational and experimental studies were considered for inclusion, excluding case series. The Newcastle‐Ottawa and Johanna Briggs scales were used for quality assessment. A random‐effects meta‐analysis was performed, followed by subgroup analyses according to, among others, presence/absence of pneumonia, RF definition, serotype and time period. PRISMA guidelines were followed for this review.ResultsThirty‐six studies were finally included in the meta‐analysis. Overall, RF incidence was 24% (range 5%–85%, 95% confidence interval [95CI] 19%–31%). Significantly higher incidences of RF were found in patients with pneumonia (42%, 95CI 28%–57%, p = .006), when RF was defined as hypoxemia (58%, 95CI 31%–81%, p < .001), and during the 2009 pandemic (25%, 95CI 16%–36%) and postpandemic period (23%, 95CI 15%–34%, p = .01). No differences were found between human influenza serotypes. Assessment of risk factors associated with the development of RF was not possible due to their inconsistent and heterogeneous reporting.ConclusionRespiratory failure is frequent in hospitalized influenza patients, especially in patients with pneumonia and since the 2009 pandemic, although its definition and reporting widely vary in the literature. This complicates its characterization and comparison between cohorts and with other respiratory viruses.
Remotely‐sensed slowing down in spatially patterned dryland ecosystems
Authors: Veldhuis Michiel P. , Martinez‐Garcia Ricardo , Deblauwe Vincent , Dakos Vasilis 
Published: August 2022

Regular vegetation patterns have been predicted to indicate a system slowing down and possibly desertification of drylands. However, these predictions have not yet been observed in dryland vegetation due to the inherent logistic difficulty to gather longer‐term in situ data. Here, we evaluate the theoretical prediction that regular vegetation patterns are associated with empirically derived temporal indicators (autocorrelation, variance, responsiveness) of critical slowing down in a dryland ecosystem in Sudan using different remote sensing products.We use recently developed methods using remote‐sensing EVI time‐series in combination with classified regular vegetation patterns along a rainfall gradient in Sudan to test the predicted slowing down. We tested our empirical findings against theoretical predictions from a stochastic version of a spatial explicit model that has been used to describe vegetation dynamics in drylands under aridity stress.Overall, three temporal indicators (responsiveness, temporal autocorrelation, variance) show slowing down as vegetation patterns change from gaps to labyrinths to spots towards more arid conditions, confirming predictions. However, this transition exhibits non‐linearities, specifically when patterns change configuration. Model simulations reveal that the transition between patterns temporarily slows down the system affecting the temporal indicators. These transient states when vegetation patterns reorganize thus affect the systems resilience indicators in a non‐linear way.Our findings suggest that spatial self‐organization of dryland vegetation is associated with critical slowing down, but this transition towards reduced resilience happens in a non‐linear way. Future work should aim to better understand transient dynamics in regular vegetation patterns in dryland ecosystems, because long transients make regular vegetation patterns of limited use for management in anticipating critical transitions.
Inter‐individual variability in dorsal stream dynamics during word production
Authors: Liégeois‐Chauvel Catherine , Dubarry Anne‐Sophie , Wang Irene , Chauvel Patrick , Gonzalez‐Martinez Jorge A. , Alario F.‐Xavier 
Published: August 2022

AbstractThe current standard model of language production involves a sensorimotor dorsal stream connecting areas in the temporo‐parietal junction with those in the inferior frontal gyrus and lateral premotor cortex. These regions have been linked to various aspects of word production such as phonological processing or articulatory programming, primarily through neuropsychological and functional imaging group studies. Most if not all the theoretical descriptions of this model imply that the same network should be identifiable across individual speakers. We tested this hypothesis by quantifying the variability of activation observed across individuals within each dorsal stream anatomical region. This estimate was based on electrical activity recorded directly from the cerebral cortex with millisecond accuracy in awake epileptic patients clinically implanted with intracerebral depth electrodes for pre‐surgical diagnosis. Each region's activity was quantified using two different metrics—intra‐cerebral evoked related potentials and high gamma activity—at the level of the group, the individual and the recording contact. The two metrics show simultaneous activation of parietal and frontal regions during a picture naming task, in line with models that posit interactive processing during word retrieval. They also reveal different levels of between‐patient variability across brain regions, except in core auditory and motor regions. The independence and non‐uniformity of cortical activity estimated through the two metrics push the current model towards sub‐second and sub‐region explorations focused on individualized language speech production. Several hypotheses are considered for this within‐region heterogeneity.
Spatial–temporal pattern of propagation in amyotrophic lateral sclerosis and effect on survival: A cohort study
Authors: Yang Tianmi , Wei Qianqian , Li Chunyu , Cao Bei , Ou Ruwei , Hou Yanbing , Zhang Lingyu , Gu Xiaojing , Liu Kuncheng , Lin Junyu , Cheng Yangfan , Jiang Zheng , Yang Jing , Kang Simin , Zhang Meng , Xiao Yi , Zhao Bi , Chen Yongping , Chen Xueping , Shang Huifang 
Published: August 2022

AbstractBackground and purposeClarification of propagation patterns in amyotrophic lateral sclerosis (ALS) is challenging, but understanding these has implications for individual prognostication and clinical trial design. However, systematic knowledge in this area is lacking. The aim of this study was to characterize the spatial and temporal features of propagation patterns in ALS, and to evaluate the association between propagation patterns and survival.MethodsA cohort of 833 patients with ALS, diagnosed between January 2018 and December 2019 and followed to August 2021, was analysed. Spatial and temporal features of propagation patterns were determined based on the involved functional regions (bulbar, cervical, thoracic/respiratory and lumbar) in time order. The final propagation pattern was identified in patients with at least three functional regions involved. Kaplan–Meier analysis and Cox regression analysis were performed.ResultsDuring a median follow‐up of 21.2 months, 19 final propagation patterns were identified in 657 patients (78.9%). In survival analysis, we found that the earlier the respiratory functional region becomes involved, the higher the risk of death (time order: 1st: hazard ratio [HR], 3.35, 95% confidence interval [CI] 1.23–9.15; 2nd: HR 2.45, 95% CI 1.55–3.87; 3rd: HR 1.94, 95% CI 1.52–2.49), adjusting for age, sex, diagnostic delay, revised ALS Functional Rating Scale score, cognitive impairment and riluzole. Shorter interval time between involved regions was an independent adverse prognostic factor.ConclusionsThe propagation patterns of ALS are varied. The order in which the respiratory region becomes involved and the interval time between involvement of functional regions are predictors for prognosis.
Metformin improves neurobehavioral impairments of streptozotocin‐treated and western diet‐fed mice: Beyond glucose‐lowering effects
Authors: Delanogare Eslen , Bullich Sebastien , Barbosa Lucas Antônio dos Santos , Barros Wellinghton de Medeiros , Braga Sara Pereira , Kraus Scheila Iria , Kasprowicz Júlia Nahir , dos Santos Gustavo Jorge , Guiard Bruno Pierre , Moreira Eduardo Luiz Gasnhar 
Published: August 2022

AbstractBrain insulin resistance has been pointed to as a possible link between diabetes and neuropsychiatric disorders; therefore, therapeutic approaches using anti‐diabetic drugs to improve insulin levels or signaling could prevent type 1 (T1D) and type 2 diabetes mellitus (T2D)‐induced brain dysfunction. The present study aimed to determine whether metformin exerts beneficial effects on metabolic and neurobehavioral outcomes in the streptozotocin (STZ)‐induced T1D model and western diet (WD)‐induced obesity model in male Swiss mice. T1D was induced by intraperitoneal injection of STZ (50 mg/kg, for five consecutive days). The animals were then treated daily with saline or metformin (200 mg/kg/day, oral gavage), and a battery of tests recapitulating different neurobehavioral anomalies related to anxiogenic/depressive‐like phenotype was conducted after 18 days. WD‐induced obesity was modeled in mice by high‐fat and high‐fructose diet (HFFD) feeding for 15 days. In the sequence, control and diet‐induced obesity mice were treated daily with saline or metformin (200 mg/kg/day), and a battery of behavioral tests was performed after 17 days. STZ injection and WD feeding induced metabolic and neurobehavioral impairments in mice. Remarkably, metformin improved the metabolic and neurobehavioral parameters in WD‐induced obesity mice. Moreover, metformin ameliorated STZ‐induced neurobehavioral deficits while it failed to improve the associated metabolic impairments. The beneficial effects of metformin in STZ‐induced neurobehavioral impairments were not mediated by improving peripheral insulin signaling. Our results suggest that conventional diabetes treatment could be repurposed to simultaneously improve neurobehavioral symptoms and diabetes.
Ki67 assessment in invasive luminal breast cancer: a comparative study between different scoring methods
Authors: Lashen Ayat , Toss Michael S , Green Andrew R , Mongan Nigel P , Rakha Emad 
Published: August 2022

BackgroundKi67 reflects the proliferation activity in breast cancer (BC). However, an optimal method for its assessment in clinical settings has yet to be robustly defined. In this study we compared several methods to score Ki67 to identify a reliable and reproducible method for routine practice.MethodsSections from luminal BC cohort (n = 1662) were immunohistochemically stained with Ki67 and were assessed for the percentage, pattern, and intensity of expression. Ki67 positivity was evaluated using three methods: (i) quantification of Ki67‐positive cells among 1000 invasive tumour cells within hotspot, (ii) average estimation of Ki67 within a defined hotspot, and (iii) average estimation of Ki67 positivity within the whole section. Time required for scoring, interobserver agreement and association with outcome were determined.ResultsThe mean percentage of Ki67 expression per 1000 cells method was 16%, while the mean value of Ki67 scores using the average estimation within hotspot and whole slide were 14% and 12%, respectively. Quantification of Ki67‐positive cells within 1000 cells had the highest degree of consistency between observers, and the highest hazard ratio predicting patient outcome when compared to using different common Ki67 cutoffs, which was independent of the other two methods. Granular pattern of Ki67 expression was associated with poorer outcome as compared to the other patterns.ConclusionAssessment of Ki67 expression using quantification positive cells among 1000 tumour cells is an optimal method to achieve high reliability and reproducibility. Comment on the predominant Ki67 expression pattern would add prognostic and predictive value in luminal BC.
Early culture conversion is a poor marker of treatment outcome among people with HIV and drug‐resistant TB
Authors: Baluku Joseph Baruch , Nabwana Martin , Mwanahamisi Suleiman Bwika , Kansiime Grace , Nuwagira Edwin , Turyahabwe Stavia , Kirenga Bruce 
Published: August 2022

AbstractObjectiveOur objective was to determine associations between early (≤2 months) culture conversion (ECC) among people with HIV and drug‐resistant tuberculosis (DRTB) in Uganda.MethodsThis was a countrywide retrospective cohort of people with bacteriologically confirmed DRTB and a positive baseline culture at 16 centres in Uganda between 2013 and 2019. Data were abstracted from treatment files and unit DRTB registers. Monthly sputum cultures were performed using the Lowenstein–Jensen solid medium.ResultsWe included 664 people with DRTB and a positive baseline culture, of whom 353 (53.4%) also had HIV. Among those living with HIV, 225 (63.7%) were male and 331 (94.3%) were on antiretroviral therapy. The median month of culture conversion was 2 (interquartile range [IQR] 1–3). ECC was observed among 226 people living with HIV (64.0%; 95% confidence interval [CI] 58.9–68.9). A DRTB treatment regimen of six or more drugs was associated with ECC among people living with HIV (adjusted odds ratio [aOR] 3.82; 95% CI 1.06–13.82; p = 0.041). Cure and overall treatment success was observed among 232 (65.7%) and 269 (76.2%) people living with HIV, respectively. However, ECC was not associated with cure (crude odds ratio [OR] 0.97; 95% CI 0.61–1.54; p = 0.901), death (OR 1.12; 95% CI 0.61–2.29; p = 0.610), or overall treatment success (OR 1.29; 95% CI 0.78–2.13; p = 0.326).ConclusionThe majority of people living with HIV and DRTB achieve ECC. However, ECC does not predict cure, death, or treatment success. Moreover, it may require six or more drugs to achieve ECC. ECC is not an excellent indicator of the effectiveness of DRTB regimens among people living with HIV.
Focal therapy of localized prostate cancer
Authors: Fujihara Atsuko , Ukimura Osamu 
Published: August 2022

AbstractIn the treatment of localized prostate cancer, controlling the cancer and maintaining quality of life are important. Focal therapy of localized prostate cancer aims to treat the lesion/part of the prostate that includes the index lesion, which determines the prognosis. We performed a non‐systematic review of novel studies on focal therapy of localized prostate cancer as primary treatment published between 2016 and 2021. For mainly intermediate‐risk patients, therapeutic technology, such as cryoablation, brachytherapy, high‐intensity focused ultrasound, photodynamic therapy, microwave‐coagulation, electroporation, and laser ablation, etc., were performed. These procedures are minimally invasive and safe, and provide good functional outcome: a 94–100% pad‐free rate against urinary incontinence and 47–86% erectile function, which is sufficient for sexual intercourse. Accurate three‐dimensional mapping of the targeted lesion could be an essential navigation technique for therapeutic success. Intermediate‐ to short‐term oncological outcomes were good, resulting in downstaging of the patient's status to no clinically significant cancer; however, transition to conventional whole‐gland treatment was necessary in about 10–30% of patients. It is important to select appropriate patients by both multiparametric magnetic resonance imaging and targeted biopsy, and to follow‐up postoperatively with methods such as active surveillance. Clinically significant prostate‐specific antigen reduction, image response using preoperative and postoperative multiparametric magnetic resonance imaging, and histological analysis should be combined for follow‐up.
Clinical and radiographic outcomes of customized allogeneic bone block versus autogenous bone block for ridge augmentation: 6 Month results of a randomized controlled clinical trial
Authors: Wang Maoxia , Li Yazhen , Su Zhenya , Mo Anchun 
Published: August 2022

AbstractAimTo evaluate the efficacy of customized allogeneic bone block (CABB) for ridge augmentation compared with autogenous bone block.Materials and MethodsPatients (N = 24) in need of ridge augmentation were randomly assigned to one of two treatment modalities: CABBs (CABB group) and autogenous bone blocks (ABB group). The primary outcome of the present study was the horizontal bone gain at 1 mm below the alveolar ridge crest (HBG1). Secondary outcomes were the bone gain at other levels, bone resorption rate, ridge width, operative time, postoperative pain score, and histological results. The data obtained from the current study were analysed using a generalized linear mixed effects model, two‐sample t‐test, or a Mann–Whitney U‐test.ResultsTwenty‐four patients completed a 6‐month follow‐up. One patient in the CABB group exhibited block exposure. The CABB group had significantly more horizontal bone gain (HBG1) and less horizontal bone resorption (HBRR1) at 1 mm below the alveolar ridge crest when compared with those in the ABB group (HBG1: CABB group [4.29 ± 1.48 mm] and ABB group [1.12 ± 3.25 mm]; HBRR0: CABB group [42.15 ± 14.03%] and ABB group [92.52 ± 55.78%], p < .05). In addition, a longer operative time was reported in the ABB group compared with the CABB group (p < .05). The histological observation indicated a new bone formation in both groups.ConclusionsThe use of CABBs resulted in more horizontal bone gain and less horizontal bone resorption at 1 mm below the alveolar ridge crest at 6 months post‐surgery compared with ABBs while reducing the operative time in the treatment of ridge augmentation.
Oral health status of adult hypophosphatasia patients: A cross‐sectional study
Authors: Weider Margareta , Schlagenhauf Ulrich , Seefried Lothar 
Published: August 2022

AbstractAimThis study evaluated the oral health status of adult patients with hypophosphatasia (HPP).Materials and MethodsParameters of oral health assessment comprised decayed/missing/filled teeth (DMFT) index, probing pocket depth and clinical attachment level (CAL) as well as documentation of tooth loss and periodontal health status according to CCD/AAP criteria. Findings were compared with national reference data (DMS V survey) reporting oral health status in age‐related controls. Within‐group comparisons were made between the HPP patients harbouring one versus two alkaline phosphatase liver/bone/kidney type (ALPL) gene variants.ResultsOf 80 HPP patients (64 female) with a mean age of 46.4 years (range 24–78) and one (n = 55) or two (n = 18) variants (n = 7 lacking testing) within the ALPL gene, those with two variants displayed substantially higher tooth loss rate (14.0 ± 9.3) than those affected by only one ALPL variant (4.1 ± 5.4), who did not differ substantially from healthy DMS V controls. While DMFT score and severe periodontal diseases (PDs) of HPP patients with one variant only increased with progressing age, the two‐variant sub‐cohort age independently exhibited increased DMFT scores and a higher rate of severe PDs.ConclusionsHPP patients affected by two variants of the ALPL gene exhibited a higher risk of periodontitis and tooth loss than the general population, while patients with one variant developed clinically relevant oral disease symptoms with progressing ageing. Clinicaltrials.gov identifier: NCT02291497.