bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the root filling quality with experimental carrier‐based obturators: a CLSM and FEG‐SEM analysis
Authors: Pirani Chiara , Generali Luigi , Iacono Francesco , Cavani Francesco , Prati Carlo 
Published: October 2021

AbstractThis study evaluated tubule penetration of GuttaFlow Bioseal with cold single cone or carrier‐based technique, under confocal laser scanning microscopy (CLSM). Twenty straight single‐rooted teeth were instrumented with Hyflex CM and divided in two groups (n = 10) according to the obturation method: single cold gutta‐percha cones; experimental carrier‐based obturators. GuttaFlow Bioseal, labelled with Rhodamine B dye, was used as sealer in both groups. Teeth transversally sectioned were observed under CLSM. Percentage of sealer penetration and integrity of sealer layer perimeter were measured. Surface and microstructural characteristics of obturators and gutta‐percha cones were compared by FEG‐SEM and EDX analysis. No significant differences were found between groups for each examined parameter. Significant differences (P < 0.05) were reported mainly within groups. Integrity was similar among and within groups. FEG‐SEM/EDX analysis of obturators revealed the presence of Ba and Zn. Carrier‐based obturation technique associated with GuttaFlow Bioseal does not seem to affect sealer penetration into dentinal tubules.
Mitigating stigma associated with recycled water
Authors: Ellis Sean F. , Savchenko Olesya M. , Messer Kent D. 
Published: October 2021

AbstractStigmatization of water and food products can constrain markets and prevent the implementation of scientifically safe solutions to environmental problems, such as water scarcity. Recycled water can be a cost‐effective, dependable, and safe solution to water shortages. However, consumers generally either require a large reduction in price to purchase products made with recycled water or reject such products outright. If emerging sustainable agricultural technologies, such as recycled water, are to be used to address growing water shortages worldwide, policymakers, water managers, and industry stakeholders must identify effective strategies for mitigating the stigma associated with recycled water. Using field experiments involving 1420 adult participants, we test the effectiveness of two stigma‐mitigating techniques. We also demonstrate a novel twist to the collection of representative samples in non‐hypothetical field experimental settings and then compare the results to a more traditional field experiment that recruited participants at large public gatherings. The analysis of these two different samples suggests a common finding: passing recycled water through a natural barrier, such as an aquifer, removes the stigma consumers would otherwise attach to it. We also find that the trophic level an organism occupies in the food chain influences stigmatizing behavior. The greater the steps in the food chain between an organism and the use of recycled water, the less it is stigmatized by consumers. These results have important implications for efforts to promote large‐scale potable and non‐potable water recycling projects and the use of recycled water in the agricultural industry.
‘Everyone’s nice, but …’: A qualitative exploration of trainees' experiences of postgraduate geriatric medicine training in Australia
Authors: Rhodes Caroline Sarah Marie , Lane Heather , Kumar Koshila , Etherton‐Beer Christopher 
Published: October 2021

AbstractObjectiveTo understand the experiences of trainees who undertake geriatric medicine advanced training in Australia.MethodsIn this qualitative study, data were collected through semi‐structured interviews with geriatric medicine advanced trainees. Data were analysed using a thematic analysis approach and data collection ceased when thematic saturation was achieved.ResultsThirteen trainees participated. Trainees enjoyed the training program, supported each other and felt prepared for independent practice as a geriatrician. However, they noted the variability of supervision and feedback practices, and educational opportunities afforded to them across different clinical learning environments. They felt unable to give feedback on their training. The research project and concerns about employment after training were also substantial sources of stress.ConclusionsWhile geriatric medicine advanced trainees reported positively on much of their training, areas for improvement could include improved training for supervisors, improved support for research projects and more robust mechanisms for providing feedback.
Androgens and estrogens predict sexual function after autologous hematopoietic stem cell transplant in men
Authors: Anderson Lindsey J. , Migula Dorota , Abay Rebecca , Crabtree Stephanie , Graf Solomon A. , Matsumoto Alvin M. , Chauncey Thomas R. , Garcia Jose M. 
Published: October 2021

AbstractBackgroundAutologous hematopoietic stem cell transplantation (AHSCT) is associated with sexual dysfunction and hypogonadism. Androgens are associated with sexual function in healthy men, but the role of estrogens is less well‐known, and the association of these sex steroids with sexual function during AHSCT has not been characterized.ObjectivesThe purpose of this study was to determine the predictive value of sex hormones before and acutely after AHSCT on sexual function recovery.Materials and methodsWe examined sex hormones and self‐reported sexual function before (PRE) and 1‐month post‐AHSCT (MONTH1; n = 19), and sexual function again 1‐year post‐AHSCT in men (YEAR1; n = 15).ResultsSexual function decreased from PRE to MONTH1 (p ≤ 0.05) with no differences between PRE and YEAR1. Erectile dysfunction was prevalent at PRE (68.4%) and increased at MONTH1 (100%; p ≤ 0.05) but was not different between PRE and YEAR1 (60.0%). From PRE to MONTH1, total testosterone (TT), dihydrotestosterone (DHT), follicle‐stimulating hormone, and sex‐hormone‐binding globulin (SHBG) increased (p ≤ 0.02) while estradiol (p ≤ 0.026) and estrone decreased (p ≤ 0.001). MONTH1 TT and DHT were associated with sexual function at MONTH1, while PRE SHBG, MONTH1 estradiol, and change in estrone predicted sexual function at YEAR1.DiscussionSexual dysfunction is very prevalent prior to AHSCT and is transiently and severely worsened acutely after. AHSCT induces acute decreases in total and free estrogens, with SHBG increases leading to increases in total androgens, without changes in free androgens.ConclusionAndrogens and estrogens are both adversely affected by AHSCT but may predict sexual dysfunction in this population. This supports the premise that estrogen impacts sexual function independent from androgens and that steroid hormones are associated with acute changes in sexual function in this setting. Larger, controlled trials with long‐term sex hormone assessment will need to confirm the association between early changes in estrogens and long‐term sexual function recovery.
Patterns of care and outcomes for gastric and gastro‐oesophageal junction cancer in an Australian population
Authors: Abbas M Nazim , Bright Tim , Price Timothy , Karapetis Christos , Thompson Sarah , Connell Caroline , Watson David , Barnes Mary , Bull Jeff , Singhal Nimit , Roy Amitesh 
Published: October 2021

AbstractBackgroundA single state‐wide upper gastrointestinal (GI) cancer video‐linked multidisciplinary team (MDT) meeting guides management and evidence‐based care for all newly diagnosed upper GI cancer patients in South Australia. This study determined the patterns of care and outcomes for patients diagnosed with gastric and gastro‐oesophageal junction (GOJ) cancers.MethodsPatients diagnosed with gastric cancer and GOJ (Siewert III) cancer between June 2012 and June 2016 were included. Patient demographics, cancer stage, histology, diagnostic modalities and treatment data was analysed from a prospective database. Stage‐specific survival outcomes were determined and analysed for each treatment modality.ResultsThe study included 218 patients and at diagnosis 132 (61%) patients had stage I–III and 86 (39%) patients had stage IV disease. One hundred and ninety‐five (89%) patients had gastric cancer and 23 (11%) had GOJ cancer (Siewert III). One hundred and nine (50%) patients underwent surgery, with 92% R0 resection rate. Forty‐six patients received perioperative chemotherapy and 111 (51%) patients received palliative intent treatment. Median overall survival for stage II, III and IV cancers was 57.6 (95% CI 57.6‐NR), 22.8 (95% CI 20.4–43.2), and 6.0 months (95% CI 4.8–8.4) respectively (p < 0.001). Median overall survival for patients who underwent perioperative chemotherapy and surgery was not reached as compared to 44.4 months (95% CI 28.8‐NR) for patients who underwent surgery alone.ConclusionTreatment outcomes for patients with gastric and GOJ cancer managed across South Australia met contemporary evidence‐based practice. However, as most patients continue to present with late‐stage disease, longer‐term survival remains poor.
Prediction model for hepatocellular carcinoma occurrence in patients with hepatitis C in the era of direct‐acting anti‐virals
Authors: Tahata Yuki , Sakamori Ryotaro , Yamada Ryoko , Kodama Takahiro , Hikita Hayato , Hagiwara Hideki , Imai Yasuharu , Hiramatsu Naoki , Tamura Shinji , Yamamoto Keiji , Oshita Masahide , Ohkawa Kazuyoshi , Hijioka Taizo , Fukui Hiroyuki , Ito Toshifumi , Doi Yoshinori , Yamada Yukinori , Yakushijin Takayuki , Yoshida Yuichi , Tatsumi Tomohide , Takehara Tetsuo ,   the Osaka Liver Forum
Published: October 2021

SummaryBackgroundSeveral factors associated with hepatocellular carcinoma (HCC) occurrence after sustained virological response (SVR) in patients with hepatitis C have been reported. However, few validation studies have been performed in the era of direct‐acting anti‐virals (DAAs).AimsTo develop a prediction model for HCC occurrence after DAA‐mediated SVR and validate its usefulness.MethodsWe analysed 2209 patients with SVR and without a history of HCC who initiated DAA treatment at 24 Japanese hospitals. These patients were divided into a training set (1473 patients) and a validation set (736 patients).ResultsIn the training set, multivariate Cox proportional hazards analysis showed that the baseline BMI (≥25.0 kg/m2, P = 0.024), baseline fibrosis‐4 (FIB‐4) index (≥3.25, P = 0.001), albumin level at SVR (<4.0 g/dL, P = 0.010) and alpha‐foetoprotein level at SVR (≥5.0 ng/mL, P = 0.006) were significantly associated with HCC occurrence. We constructed a prediction model for HCC occurrence with these four factors (2 points were added for the FIB‐4 index, and 1 point was added for each of the other three factors). Receiver operating characteristics curve analysis identified a score of 2 as the optimal cut‐off value for the prediction model (divided into 0‐1 and 2‐5). In the validation set, the sensitivity and negative predictive value for HCC occurrence were 87.5% and 99.7%, respectively, at 2 years and 71.4% and 98.0%, respectively, at 3 years.ConclusionA prediction model combining these four factors contributes to an efficient surveillance strategy for HCC occurrence after DAA‐mediated SVR.
Usefulness of structured‐cadaveric training for trans‐anal pelvic exenteration
Authors: Tominaga Tetsuro , Nonaka Takashi , Fukuda Akiko , Moriyama Masaaki , Oyama Shosaburo , Ishii Mitsutoshi , Takamura Keiko , Tsurumoto Toshiyuki , Sawai Terumitsu , Nagayasu Takeshi 
Published: October 2021

AbstractPurposeStructured training using cadaveric simulation is useful for trans‐anal surgery; however, no studies have examined the effectiveness of cadaveric training for advanced trans‐anal surgery including pelvic exenteration (PE).MethodsTwelve colorectal surgeons attended a total of 10 cadaveric simulation training courses between 2016 and 2021 and completed a questionnaire at the end of the program. We divided 14 consecutive patients who underwent trans‐anal PE between 2015 and 2021 into two groups: pre‐training group and post‐training group, and compared the clinico‐pathological features between the groups.ResultsThe median length of clinical experience of the surgeons was 12 years. There was high score agreement among the surgeons that the course was useful for recognition of anatomical and layer structure, training for trans‐anal total mesorectal excision and trans‐anal PE, and reducing complications specific to the trans‐anal approach. Compared with the pre‐training group, patients in the post‐training group had a higher rate of two‐team surgery (77.8% vs 0%, P = .021), and shorter time to specimen removal (273 vs 423 min, P = .045).ConclusionsStructured‐cadaveric training has potential use as a technical step‐up in advanced trans‐anal surgery that might contribute to better short‐term outcomes in the clinical setting.
Business Combinations under Common Control: Filling a Gap in IFRS Standards
Authors: Tarca Ann 
Published: October 2021

AbstractThe aim of this paper is to explain the International Accounting Standards Board's (IASB) preliminary views for accounting for business combinations under common control, an issue not currently addressed in International Financial Reporting Standards. Such combinations are widespread and the accounting for them is diverse. The IASB's preliminary views aim to reduce diversity in practice and to improve the information provided to investors so they can understand the effects of these transactions and compare companies that undertake them.Accounting for business combinations under common control is not currently addressed in International Financial Reporting Standards. The author describes some of the International Accounting Standard Board's proposals to reduce diversity and improve investors’ information in this area.
Population pharmacokinetics and target attainment analysis of linezolid in multidrug‐resistant tuberculosis patients
Authors: Tietjen Anna K. , Kroemer Niklas , Cattaneo Dario , Baldelli Sara , Wicha Sebastian G. 
Published: October 2021

AimThis study investigates the pharmacokinetic/pharmacodynamic (PK/PD) target attainment of linezolid in patients infected with multidrug‐resistant (MDR) tuberculosis (TB).MethodsA pharmacometric model was developed including 244 timed linezolid concentration samples from 39 patients employing NONMEM 7.4. The probability of target attainment (PTA, PK/PD target: unbound (f) area‐under‐the‐concentration‐time‐curve (AUC)/minimal inhibitory concentration (MIC) of 119) as well as a region‐specific cumulative fraction of response (CFR) were estimated for different dosing regimens.ResultsA one‐compartment model with linear elimination with a clearance (CL) of 7.69 L/h (interindividual variability 34.1%), a volume of distribution (Vd) of 45.2 L and an absorption constant (KA) of 0.679 h−1 (interoccasion variability 143.7%) allometric scaled by weight best described the PK of linezolid. The PTA at an MIC of 0.5 mg/L was 55% or 97% if patients receiving 300 or 600 mg twice daily, respectively. CFRs varied greatly among populations and geographic regions. A desirable global CFR of ≥90% was achieved if linezolid was administered at a dose of 600 mg twice daily but not at a dose of 300 mg twice daily.ConclusionThis study showed that a dose of 300 mg twice daily of linezolid might not be sufficient to treat MDR‐TB patients from a PK/PD perspective. Thus, it might be recommendable to start with a higher dose of 600 mg twice daily to ensure PK/PD target attainment. Hereby, therapeutic drug monitoring and MIC determination should be performed to control PK/PD target attainment as linezolid shows high variability in its PK in the TB population.
The immune landscape in BCR‐ABL negative myeloproliferative neoplasms: inflammation, infections and opportunities for immunotherapy
Authors: Strickland Marie , Quek Lynn , Psaila Bethan 
Published: October 2021

SummaryBreakpoint cluster region‐Abelson (BCR‐ABL) negative myeloproliferative neoplasms (MPNs) are chronic myeloid neoplasms initiated by the acquisition of gene mutation(s) in a haematopoietic stem cell, leading to clonal expansion and over‐production of blood cells and their progenitors. MPNs encompass a spectrum of disorders with overlapping but distinct molecular, laboratory and clinical features. This includes polycythaemia vera, essential thrombocythaemia and myelofibrosis. Dysregulation of the immune system is key to the pathology of MPNs, supporting clonal evolution, mediating symptoms and resulting in varying degrees of immunocompromise. Targeting immune dysfunction is an important treatment strategy. In the present review, we focus on the immune landscape in patients with MPNs – the role of inflammation in disease pathogenesis, susceptibility to infection and emerging strategies for therapeutic immune modulation. Further detailed work is required to delineate immune perturbation more precisely in MPNs to determine how and why vulnerability to infection differs between clinical subtypes and to better understand how inflammation results in a competitive advantage for the MPN clone. These studies may help shed light on new designs for disease‐modifying therapies.
Divergent impacts of tocilizumab and colchicine in COVID‐19‐associated coagulopathy: the role of alpha‐defensins
Authors: Abdeen Suhair , Abu‐Fanne Rami , Bdeir Khalil , Maraga Emad , Higazi Mohamed , Cines Douglas B. , Heyman Samuel N. , Higazi Abd Al‐Roof 
Published: October 2021

SummaryPatients who are severely affected by coronavirus disease 2019 (COVID‐19) may develop a delayed onset ‘cytokine storm’, which includes an increase in interleukin‐6 (IL‐6). This may be followed by a pro‐thrombotic state and increased D‐dimers. It was anticipated that tocilizumab (TCZ), an anti‐IL‐6 receptor monoclonal antibody, would mitigate inflammation and coagulation in patients with COVID‐19. However, clinical trials with TCZ have recorded an increase in D‐dimer levels. In contrast to TCZ, colchicine reduced D‐dimer levels in patients with COVID‐19. To understand how the two anti‐inflammatory agents have diverse effects on D‐dimer levels, we present data from two clinical trials that we performed. In the first trial, TCZ was administered (8 mg/kg) to patients who had a positive polymerase chain reaction test for COVID‐19. In the second trial, colchicine was given (0·5 mg twice a day). We found that TCZ significantly increased IL‐6, α‐Defensin (α‐Def), a pro‐thrombotic peptide, and D‐dimers. In contrast, treatment with colchicine reduced α‐Def and Di‐dimer levels. In vitro studies show that IL‐6 stimulated the release of α‐Def from human neutrophils but in contrast to colchicine, TCZ did not inhibit the stimulatory effect of IL‐6; raising the possibility that the increase in IL‐6 in patients with COVID‐19 treated with TCZ triggers the release of α‐Def, which promotes pro‐thrombotic events reflected in an increase in D‐dimer levels.
Pharmacological characterization of novel heteromeric GluCl subtypes from Caenorhabditis elegans and parasitic nematodes
Authors: Lamassiaude Nicolas , Courtot Elise , Corset Angélique , Charvet Claude L. , Neveu Cédric 
Published: October 2021

Background and PurposeMacrocyclic lactones are the most widely used broad‐spectrum anthelmintic drugs for the treatment of parasitic nematodes affecting both human and animal health. Macrocyclic lactones are agonists of the nematode glutamate‐gated chloride channels (GluCls). However, for many important nematode species, the GluCls subunit composition and pharmacological properties remain largely unknown. To gain new insights into GluCl diversity and mode of action of macrocyclic lactones, we identified and pharmacologically characterized receptors made of highly conserved GluCl subunits from the model nematode Caenorhabditis elegans, the human filarial nematode Brugia malayi and the horse parasite Parascaris univalens.Experimental ApproachAVR‐14, GLC‐2, GLC3 and GLC‐4 are the most conserved GluCl subunits throughout the Nematoda phylum. For each nematode species, we investigated the ability of these subunits to form either homomeric or heteromeric GluCls when expressed in Xenopus laevis oocytes and carried out detailed pharmacological characterization of the functional channels.Key ResultsA total of 14 GluCls were functionally reconstituted, and heteromers formation was inferred from pharmacological criteria. The GLC‐2 subunit plays a pivotal role in the composition of heteromeric GluCls in nematodes. We also found a novel GluCl subtype, combining GLC‐2/GLC‐3 subunits, for which a high concentration of the anthelmintics ivermectin and moxidectin reversibly potentiates glutamate‐induced response.Conclusion and ImplicationsThis study brings new insights into the diversity of GluCl subtypes in nematodes and promotes novel drug targets for the development of the next generation of anthelmintic compounds.
Treatment with senicapoc, a KCa3.1 channel blocker, alleviates hypoxaemia in a mouse model of acute respiratory distress syndrome
Authors: Petersen Asbjørn Graver , Lind Peter Carøe , Mogensen Susie , Jensen Anne‐Sophie Bonde , Granfeldt Asger , Simonsen Ulf 
Published: October 2021

Background and PurposeAcute respiratory distress syndrome (ARDS) is characterized by pulmonary oedema and severe hypoxaemia. We investigated whether genetic deficit or blockade of calcium‐activated potassium (KCa3.1) channels would counteract pulmonary oedema and hypoxaemia in ventilator‐induced lung injury, an experimental model for ARDS.Experimental ApproachKCa3.1 channel knockout (Kccn4‐/‐) mice were exposed to ventilator‐induced lung injury. Control mice exposed to ventilator‐induced lung injury were treated with the KCa3.1 channel inhibitor, senicapoc. The outcomes were oxygenation (PaO2/FiO2 ratio), lung compliance, lung wet‐to‐dry weight and protein and cytokines in bronchoalveolar lavage fluid (BALF).Key ResultsVentilator‐induced lung injury resulted in lung oedema, decreased lung compliance, a severe drop in PaO2/FiO2 ratio, increased protein, neutrophils and tumour necrosis factor‐alpha (TNF‐α) in BALF from wild‐type mice compared with Kccn4‐/‐ mice. Pretreatment with senicapoc (10–70 mg·kg−1) prevented the reduction in PaO2/FiO2 ratio, decrease in lung compliance, increased protein and TNF‐α. Senicapoc (30 mg·kg−1) reduced histopathological lung injury score and neutrophils in BALF. After injurious ventilation, administration of 30 mg·kg−1 senicapoc also improved the PaO2/FiO2 ratio and reduced lung injury score and neutrophils in the BALF compared with vehicle‐treated mice. In human lung epithelial cells, senicapoc decreased TNF‐α‐induced permeability.Conclusions and ImplicationsGenetic deficiency of KCa3.1 channels and senicapoc improved the PaO2/FiO2 ratio and decreased the cytokines after a ventilator‐induced lung injury. Moreover, senicapoc directly affects lung epithelial cells and blocks neutrophil infiltration in the injured lung. These findings indicate that blocking KCa3.1 channels is a potential treatment in ARDS‐like disease.