bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesh fixation with fibrin glue versus tacker in laparoscopic totally extraperitoneal inguinal hernia repair
Authors: Nizam Saifullah , Saxena Neeraj , Yelamanchi Raghav , Sana Sana , Kardam Dinesh 
Published: August 2021

AbstractBackgroundThe advent of mesh was a breakthrough in the field of hernia surgery. Mechanical methods of mesh fixation are hypothesized to cause more tissue trauma than nonmechanical methods. The present study was conducted to study the outcomes of mesh fixation using fibrin glue, a nonmechanical method versus tackers in totally extraperitoneal repair (TEP) of unilateral inguinal hernia.MethodsA randomized controlled single blinded study was conducted in India from June 2017 to March 2019. Patients diagnosed with unilateral uncomplicated inguinal hernia with a hernial sac of size not more than 5 cm were invited to participate in the study. Sample size was 60 patients randomized into groups just before mesh fixation. In group A mesh was fixed using tackers while in group B mesh was fixed using fibrin glue. Patients were followed‐up prospectively for 3 months.ResultsThere was no statistical difference between the two groups with respect to operating time. Average hospital stay and pain scores at all follow‐ups were better for fibrin glue group. There was no difference in the incidence of postoperative urinary retention, seroma formation and hematoma formation between the two groups. Patients of fibrin glue group had early restart of daily activities at 15 days follow‐up when compared to tacker group.ConclusionFibrin glue fixation technique should be advocated over tackers for mesh fixation in TEP considering the better outcomes and cost‐effectiveness of the technique.
Clinical utiliy of a model‐based piperacillin dose in neonates with early‐onset sepsis
Authors: Wu Yue‐E , Hou Shan‐Shan , Fang Zeng‐Yu , Tang Bo‐Hao , Yao Bu‐Fan , Dong Yi‐Ning , Li Xue , Shi Hai‐Yan , Zheng Yi , Hao Guo‐Xiang , Huang Xin , Van Den Anker John , Yu Yong‐Hui , Zhao Wei 
Published: August 2021

AimsEarly‐onset sepsis (EOS) is a common disease in neonates with a high morbidity and mortality rate. Piperacillin/tazobactam has been used extensively and empirically for EOS treatment without clinically validated dosing regimens, although the population pharmacokinetics (PPK) of piperacillin in neonates has been reported. Therefore, we wanted to study the effectiveness and tolerance of a PPK model‐based dosing regimen of piperacillin/tazobactam in EOS patients.MethodsA prospective, single‐centre, phase II clinical study of piperacillin/tazobactam in neonates with EOS was conducted. The dosing regimen (90 mg·kg−1, q8h) was determined based on a previous piperacillin PPK model in young infants using NONMEM v7.4. The pharmacodynamics (PD) target (70%fT > MIC, free drug concentration above MIC during 70% of the dosing interval) attainment was calculated using NONMEM combined with an opportunistic sampling design. The clinical treatment data were collected.ResultsA total of 52 neonates were screened and 49 neonates completed their piperacillin/tazobactam treatment course and were included in this analysis. The median (range) values of postmenstrual age were 33.57 (range 26.14–41.29) weeks. Forty‐seven (96%) neonates reached their PD target. Eight (16%) neonates experienced treatment failure clinically. The mean (SD, range) duration of treatment and length of hospitalization were 100.1 (62.2, 36.2–305.8) hours and 31 (30, 5–123) days. There were no obvious adverse events and no infection‐related deaths occurred in the first month of life.ConclusionsA model‐based dosing regimen of piperacillin/tazobactam was evaluated clinically, was tolerated well and was determined to be effective for EOS treatment.
Dosing regimen optimisation for oseltamivir in immunocompromised paediatric patients with influenza: Extrapolation of efficacy
Authors: Jordie Eric Burroughs , Gibiansky Leonid , Knab Timothy , Lemenuel‐Diot Annabelle , Ravva Patanjali , Zwanziger Elke , Jolivet Sebastien , Bhardwaj Rajinder , Hernández‐Sánchez Jules , Nasmyth‐Miller Clare , Sturm Stefan 
Published: August 2021

AimsTo optimise the dosing regimen of oseltamivir for immunocompromised (IC) paediatric patients (<18 years) with influenza, we used an extrapolation approach alongside clinical data.MethodsEfficacy was extrapolated from adult IC patients to paediatric IC patients by leveraging existing efficacy, safety, pharmacokinetic (PK)/pharmacodynamic (PD), and disease‐progression models of oseltamivir and oseltamivir carboxylate (OC). Data of IC paediatric patients from two studies (NV25719 and NV20234) were included in the population PK (n = 30), PK/PD analysis (n = 22) and disease modelling approach (n = 36). Simulations were performed to identify the optimal dosing regimen.ResultsClearance of oseltamivir (CL) and OC (CLM) were similar in IC and otherwise‐healthy (OwH) patients <10 years, but decreased by 44.4% (95% CI: 26.8–62.0) and 49.1% (95% CI: 34.5–63.8), respectively, in IC patients aged 10–17 years versus OwH patients. There were no notable exposure–response relationships for any of the virologic PD analyses. Thus, no additional benefit was seen with oseltamivir carboxylate exposures higher than achieved with the conventional dose (75 mg twice daily, age‐ and weight‐adjusted for children <13 years). The disease model illustrated that doses above the conventional oseltamivir dose had limited impact on viral kinetics in IC paediatric patients and a prolonged treatment duration of 10 days was favoured to limit potential viral rebound.ConclusionAn oseltamivir dosage recommendation (conventional dose, twice daily for 10 days) was established in IC paediatric patients with influenza, based on extrapolation of efficacy from IC adults, leveraging population PK, PK/PD, and disease modelling, whilst taking resistance and safety data into account.
Trough polymyxin B plasma concentration is an independent risk factor for its nephrotoxicity
Authors: Han Lu , Xu Fang‐Min , Zhang Xiao‐Shan , Zhang Chun‐Hong , Dai Ying , Zhou Zi‐Ye , Wang Ye‐Xuan , Chen Fan , Shi Da‐Wei , Lin Guan‐Yang , Yu Xu‐Ben 
Published: August 2021

AimsData regarding clinical pharmacokinetic/toxicodynamic (PK/TD) of polymyxin B is short of direct quantitative data. This study aims to investigate the risk factors of polymyxin B associated acute kidney injury (AKI) and to assess the relationship between polymyxin B plasma levels and its nephrotoxicity.MethodsA retrospective study was performed in adult patients treated with polymyxin B. Risk factors associated with AKI and plasma trough concentrations of polymyxin B were identified via medical record review. A multivariate logistic regression model was established and the risk of polymyxin B‐associated AKI were predicted by a receiver operating characteristic curve, with maximal Youden index used to identify safety thresholds among the study population.ResultsFifty‐four adult patients were included in the study. AKI was detected in 14 patients during polymyxin B treatment (25.9%, 14 out of 54). Cmin (odds ratio [OR] 2.071; 95% confidence interval [CI] 1.235–3.472) and baseline serum creatinine (OR 1.024; 95% CI 1.005–1.043) were significant independent risk factors for developing AKI. The area under the ROC curve of the combined predictor was larger based on the above factors. When the Youden index was at maximum, the optimal cut‐off point was 6.678 of the ROC curve. When Cmin ≥ 3.13 mg/L, the probability of AKI was more than 50%.ConclusionIn this study, when the calculated combined predictor value was >6.678, there was an increased risk of AKI. Maintaining a polymyxin B Cmin level below 3.13 mg/L may be helpful in reducing the incidence of polymyxin B associated nephrotoxicity.
Advances in treatment of elderly primary central nervous system lymphoma
Authors: Martinez‐Calle Nicolas , Isbell Lisa K. , Cwynarski Kate , Schorb Elisabeth 
Published: August 2021

SummaryThe management of older individuals (≥60 years) with primary central nervous system lymphoma remains a clinical challenge. Identification of optimal therapy and delivering adequate dose intensity are two of the major issues in treating elderly patients. Premorbid performance status and comorbidities influence individualised treatment approaches and geriatric assessment tools are increasingly utilised. Optimal induction treatment remains high‐dose methotrexate‐based immunochemotherapy, delivery is feasible in the majority of patients and the goal of treatment remains achieving complete remission. Consolidation strategies are also relevant in the elderly, aiming to maximise duration of response and quality of life (QoL). Potential options include high‐dose therapy with haematopoietic stem cell consolidation, non‐myeloablative chemotherapy and whole‐brain radiotherapy. Efficacy of novel agents, such as Bruton tyrosine kinase inhibitors and lenalidomide, have been reported; these represent an alternative for elderly patients unfit for chemotherapy. Prognosis remains poor, improvement of outcomes in this age group is urgently needed.
Holocene evolution of a proglacial lake in southern Kamchatka, Russian Far East
Authors: Nazarova Larisa , Sachse Dirk , Fuchs Harald G. E. , Dirksen Veronika , Dirksen Oleg , Syrykh Liudmila , Razjigaeva Nadezhda G. , Rach Oliver , Diekmann Bernhard 
Published: August 2021

The Kamchatka Peninsula (Russian Far East) remains among the least studied regions of eastern Asia. Recent studies revealed a high degree of palaeoenvironmental variability between different parts of the peninsula. We investigated semi‐aquatic (chironomids) and terrestrial (leaf wax biomarkers) proxies from a sediment core collected from Lake Sokoch (southern Kamchatka) to provide reconstruction of the mean July air temperature and variations in limnic conditions. The lake formed after 10.0 cal. ka BP as a result of postglacial warming and was fed by glacial meltwaters from neighbouring glaciers. Our data show a later beginning of the Holocene thermal maximum (HTM) relative to more northern sites in Kamchatka, Siberia and Chukotka and support climate model experiments that suggest that the HTM was delayed in southern and central Kamchatka by about 2000 years compared with Alaska and NE Siberia. Warm conditions prevailed between 10.0 and 6.4 cal. ka BP with a short spell of cool and dry climate around 8.2 cal. ka BP that might be related to the 8.2 ka cooling event. The HTM took place between 6.5 and 3.4 cal. ka BP with the warmest phase from 6.0 to 5.0 cal. ka BP. An onset of Neoglacial cooling at 3.4 cal. ka BP is consistent with the strengthening of both the Siberian High and the Aleutian Low. Warming between 1.2 and 0.9 cal. ka BP can be attributed to the Mediaeval Climate Anomaly. The LIA cooling is related to another strengthening of the Siberian High and the Aleutian Low. The modern warming, though weakly traced in our record, is consistent with the recent meteorological observations. The presented palaeoenvironment record confirms the earlier findings of spatial differences within Kamchatka in timing and magnitude of the major Holocene climate fluctuations and contributes towards understanding the expression of Holocene climate change in Kamchatka.
DOC‐2/DAB2 interactive protein destabilizes c‐Myc to impair the growth and self‐renewal of colon tumor‐repopulating cells
Authors: Li Haiou , Zhou Yunjiao , Wang Meng , Wang Haizhou , Zhang Yangyang , Peng Ruyi , Zhang Ruike , Zhang Meng , Zhang Mengna , Qiu Peishan , Liu Lan , Zhao Qiu , Liu Jing 
Published: August 2021

AbstractColorectal carcinoma (CRC) remains a huge challenge in clinical treatment due to tumor metastasis and recurrence. Stem cell‐like colon tumor‐repopulating cells (TRCs) are a subpopulation of cancer cells with highly tumorigenic and chemotherapy resistant properties. The core transcription factor c‐Myc is essential for maintaining cancer stem‐like cell phenotypes, yet its roles and regulatory mechanisms remain unclear in colon TRCs. We report that elevated c‐Myc protein supported formation and growth of TRC spheroids. The tumor suppressor DOC‐2/DAB2 interactive protein (DAB2IP) suppressed c‐Myc expression to inhibit TRC expansion and self‐renewal. Particularly, DAB2IP disrupted c‐Myc stability through glycogen synthase kinase 3β/protein phosphatase 2A‐B56α‐mediated phosphorylation and dephosphorylation cascade on c‐Myc protein, leading to its eventual degradation through the ubiquitin‐proteasome pathway. The expression of DAB2IP was negatively correlated with c‐Myc in CRC specimens. Overall, our results improved mechanistic insight into how DAB2IP suppressed TRC growth and self‐renewal.
The EZH2 inhibitor tazemetostat upregulates the expression of CCL17/TARC in B‐cell lymphoma and enhances T‐cell recruitment
Authors: Yuan Hepei , Nishikori Momoko , Otsuka Yasuyuki , Arima Hiroshi , Kitawaki Toshio , Takaori‐Kondo Akifumi 
Published: August 2021

AbstractAn inhibitor of the histone methyltransferase enhancer of zeste homologue 2 (EZH2), tazemetostat, has been developed for the treatment of B‐cell lymphoma, but its mechanisms of action are not fully elucidated. We screened for genes targeted by tazemetostat in eleven B‐cell lymphoma cell lines and found that tazemetostat significantly increased the expression of chemokine (C‐C motif) ligand 17 (CCL17)/thymus‐ and activation‐regulated chemokine (TARC) in all, which codes for a chemokine that is a hallmark of Hodgkin/Reed‐Sternberg (H/RS) cells in Hodgkin lymphoma. Notably, gene set enrichment analysis demonstrated a positive correlation between the genes upregulated by tazemetostat in five follicular lymphoma (FL) cell lines and those reported to be overexpressed in H/RS cells. The CCL17 promoter region was enriched in repressive histone modification H3K27me3, and tazemetostat induced H3K27 demethylation and activated gene transcription. CCL17 protein secretion was also induced by EZH2 inhibition, which was further enhanced by concurrent CpG stimulation. In vitro transwell migration assay demonstrated that CCL17 produced by tazemetostat‐treated B cells enhanced the recruitment of T cells, which had the potential to exert antilymphoma response. Analysis of publicly available human lymphoma databases showed that CCL17 gene expression was inversely correlated with the EZH2 activation signature and significantly paralleled the CD4+ and CD8+ T‐cell–rich signature in FL and germinal center B‐cell–like diffuse large B‐cell lymphoma. Our findings indicate that tazemetostat can potentially activate antilymphoma response by upregulating CCL17 expression in B‐cell lymphoma cells and promote T‐cell recruitment, which provides a rationale for its combination with immunotherapy.
Trajectories of perinatal depressive symptoms in the context of the COVID‐19 pandemic
Authors: Gustafsson Hanna C. , Young Anna S. , Doyle Olivia , Nagel Bonnie J. , Mackiewicz Seghete Kristen , Nigg Joel T. , Sullivan Elinor L. , Graham Alice M. 
Published: August 2021

AbstractThis study sought to advance understanding of the potential long‐term consequences of the COVID‐19 pandemic for child development by characterizing trajectories of maternal perinatal depression, a common and significant risk factor for adverse child outcomes. Data came from 393 women (86% White, 8% Latina; mean age = 33.51 years) recruited during pregnancy (n = 247; mean gestational age = 22.94 weeks) or during the first year postpartum (n = 146; mean child age = 4.50 months; 55% female). Rates of depression appear elevated, relative to published reports and to a pre‐pandemic comparison group (N = 155). This study also provides evidence for subgroups of individuals who differ in their depressive symptom trajectories over the perinatal period. Subgroup membership was related to differences in maternal social support, but not to child birth outcomes.
Early life stress and behavior problems in early childhood: Investigating the contributions of child temperament and executive functions to resilience
Authors: de Maat Donna A. , Schuurmans Isabel K. , Jongerling Joran , Metcalf Stephen A. , Lucassen Nicole , Franken Ingmar H. A. , Prinzie Peter , Jansen Pauline W. 
Published: August 2021

AbstractThis preregistered study examined whether child temperament and executive functions moderated the longitudinal association between early life stress (ELS) and behavior problems. In a Dutch population‐based cohort (n = 2803), parents reported on multiple stressors (age 0–6 years), child temperament (age 5), and executive functions (age 4), and teachers rated child internalizing and externalizing problems (age 7). Results showed that greater ELS was related to higher levels of internalizing and externalizing problems, with betas reflecting small effects. Lower surgency buffered the positive association of ELS with externalizing problems, while better shifting capacities weakened the positive association between ELS and internalizing problems. Other child characteristics did not act as moderators. Findings underscore the importance of examining multiple protective factors simultaneously.
The cross‐talk between RAGE and DIAPH1 in neurological complications of diabetes: A review
Authors: Zglejc‐Waszak Kamila , Mukherjee Konark , Juranek Judyta Karolina 
Published: August 2021

AbstractNeuropathy, or dysfunction of peripheral nerve, is one of the most common neurological manifestation in patients with diabetes mellitus (DM). DM is typically associated with a hyperglycaemic milieu, which promotes non‐enzymatic glycation of proteins. Proteins with advanced glycation are known to engage a cell‐surface receptor called the receptor for advanced glycation end products (RAGE). Thus, it is reasonable to assume that RAGE and its associated molecule‐mediated cellular signalling may contribute to DM‐induced symmetrical axonal (length‐dependent) neuropathy. Of particular interest is diaphanous related formin 1 (DIAPH1), a cytoskeletal organizing molecule, which interacts with the cytosolic domain of RAGE and whose dysfunction may precipitate axonopathy/neuropathy. Indeed, it has been demonstrated that both RAGE and DIAPH1 are expressed in the motor and sensory fibres of nerve harvested from DM animal models. Although the detailed molecular role of RAGE and DIAPH1 in diabetic neurological complications remains unclear, here we will discuss available evidence of their involvement in peripheral diabetic neuropathy. Specifically, we will discuss how a hyperglycaemic environment is not only likely to elevate advanced glycation end products (ligands of RAGE) and induce a pro‐inflammatory environment but also alter signalling via RAGE and DIAPH1. Further, hyperglycaemia may regulate epigenetic mechanisms that interacts with RAGE signalling. We suggest the cumulative effect of hyperglycaemia on RAGE–DIAPH1‐mediated signalling may be disruptive to axonal cytoskeletal organization and transport and is therefore likely to play a key role in pathogenesis of diabetic symmetrical axonal neuropathy.
Primary cilia in retinal pigment epithelium development and diseases
Authors: Sun Chunjiao , Zhou Jun , Meng Xiaoqian 
Published: August 2021

AbstractRetinal pigment epithelium (RPE) is a highly polarized epithelial monolayer lying between the photoreceptor layer and the Bruch membrane. It is essential for vision through participating in many critical activities, including phagocytosis of photoreceptor outer segments, recycling the visual cycle‐related compounds, forming a barrier to control the transport of nutrients, ions, and water, and the removal of waste. Primary cilia are conservatively present in almost all the vertebrate cells and acts as a sensory organelle to control tissue development and homeostasis maintenance. Numerous studies reveal that abnormalities in RPE lead to various retinal diseases, such as age‐related macular degeneration and diabetic macular oedema, but the mechanism of primary cilia in these physiological and pathological activities remains to be elucidated. Herein, we summarize the functions of primary cilia in the RPE development and the mutations of ciliary genes identified in RPE‐related diseases. By highlighting the significance of primary cilia in regulating the physiological and pathological processes of RPE, we aim to provide novel insights for the treatment of RPE‐related retinal diseases.
Commonalities and evolutionary divergences of mandible shape ontogenies in rodents
Authors: Dubied Morgane , Montuire Sophie , Navarro Nicolas 
Published: August 2021

AbstractIn mammals, significant changes take place during postnatal growth, linked to changes in diet (from sucking to gnawing). During this period, mandible development is highly interconnected with muscle growth and the epigenetic interactions between muscle and bone control the spatialization of bone formation and remodelling in response to biomechanical strain. This mechanism contributes to postnatal developmental plasticity and may have influenced the course of evolutionary divergences between species and clades. We sought to model postnatal changes at a macroevolutionary scale by analysing ontogenetic trajectories of mandible shape across 16 species belonging mainly to two suborders of Rodents, Myomorpha and Hystricomorpha, which differ in muscle attachments, tooth growth and life‐history traits. Myomorpha species present a much stronger magnitude of changes over a shorter growth period. Among Hystricomorpha, part of the observed adult shape is set up prenatally, and most postnatal trajectories are genus‐specific, which agrees with nonlinear developmental trajectories over longer gestational periods. Beside divergence at large scale, we find some collinearities between evolutionary and developmental trajectories. A common developmental trend was also observed, leading to enlargement of the masseter fossa during postnatal growth. The tooth growth, especially hypselodonty, seems to be a major driver of divergences of postnatal trajectories. These muscle‐ and tooth‐related effects on postnatal trajectories suggest opportunities for developmental plasticity in the evolution of the mandible shape, opportunities that may have differed across Rodent clades.
Innovative approach for tear trough deformity correction using higher G prime fillers for safe, efficacious, and long‐lasting results: A prospective interventional study
Authors: Vadera Sapna , Shome Debraj , Kumar Vaibhav , Doshi Komal , Kapoor Rinky 
Published: August 2021

AbstractBackgroundOne of the most challenging areas for facial rejuvenation is the lower eyelid. Apart from the protruding orbital fat causing lower lid bags, a discrete entity called the “tear trough deformity” is distinguishable in this area.AimThe objective of this study is to compare and evaluate the standard technique of tear trough deformity correction with the lateral injection technique using a high G prime filler to establish a guideline for the safe and effective correction of tear trough deformity.MethodsA prospective, double‐blind, study was carried out from Dec 2017 to 2019 including 30 participants in the age range of 35–60 years. The participants were divided into two groups of 15 patients each. In group A patients, conventional technique with a low G Prime filler was used, whereas in group B, lateral injection technique with a high G Prime filler was used.ResultsMarked improvement was seen in appearance and skin quality on both the sides in all the patients. As compared to our technique (lateral injections) where a mean of 0.5 ml of filler was used to lift the cheek and reduce the tear trough, the standard technique (Mauricio de Maio's 3‐point tear trough reshape technique) required a mean of 1.2 ml of filler for the same. Post‐procedure complications including bruising and Tyndall effect were much higher (statistically significant) using the standard medial technique for the correction tear trough.ConclusionAesthetically satisfying results for the tear trough correction are possible, without actually injecting the tear trough directly, based on the knowledge of the underlying anatomy.