bluuebunny/crossref_metadata_2025_split huggingface dataset:
An institutional audit of the use of novel drugs in pediatric oncology
Authors: Lee Justin , Gillam Lynn , Kouw Sarah , McCarthy Maria C. , Hansford Jordan R. 
Published: May 2021

AbstractBackgroundSignificant challenges persist in treating children with rare, relapsed, or refractory malignancies. Novel molecularly targeted drugs promise improved outcomes for these children with reduced toxicity. However, there is often limited evidence to substantiate their clinical efficacy and guide their use. This raises issues for clinical decision‐making, ethical concerns surrounding equity of access to these often‐expensive agents, and the management of families' expectations for cure. This audit evaluated the off‐label use of novel drugs and associated clinical outcomes in order to guide the development of future clinical and ethical guidelines.AimTo evaluate the patterns in the off‐label use of novel drugs for treating childhood cancer and the associated clinical outcomes to guide prospective studies and inform ethical and clinical governance protocols for the use of these agents.MethodsA retrospective audit was performed for all patients who received novel drugs off‐label as treatment for their malignancy at an Australian pediatric oncology center between 2010 and 2019.ResultsOne hundred patients with 32 unique diagnoses received 133 novel drugs across 124 regimens. Eighty‐four patients received these drugs at the second line of treatment or greater. Novel drug median cost was $15 521 AUD (Range: $6.53 AUD to $258 339 AUD) and was primarily funded by the hospital (N = 60/133, 45.1%) or compassionate access from pharmaceutical companies (N = 52/133, 39.1%). Decision‐making related to novel drugs was inconsistently documented. Ninety‐one of 124 treatment regimens commenced between 2010 and 2019 resulted in objective responses (73.4%), but only 35 were still ongoing upon review in June 2020 (38.5%). Median response duration was 12.6 months (Range: 0‐93.2 months).ConclusionsWhile novel drugs were largely unable to definitively cure patients, most achieved objective responses. Prospective trials and more rigorous documentation are needed to fully inform the future use of these agents given the heterogeneity of their applications.
Investigating function of long noncoding RNA of HOTAIRM1 in progression of SKOV3 ovarian cancer cells
Authors: Ye Licui , Meng Xia , Xiang Rui , Li Wen , Wang Jingyi 
Published: May 2021

AbstractOvarian cancer is one of the most heterogeneous malignancies in the field of gynecologic oncology. Deregulation of long noncoding RNAs (lncRNAs) is implicated in carcinogenesis. Therefore, the present study was conducted to investigate the possible role of lncRNA of HOXA transcript antisense intergenic RNA myeloid‐specific 1(HOTAIRM1) in progression of SKOV3 cells in ovarian cancer and also its underlying molecular mechanisms. HOTAIRM1 expression level will be measured by real‐time polymerase chain reaction (PCR) in SKOV3 cells. For determining the effect of HOTAIRM1 silencing on progression of SKOV3 cells, siHOTAIRM1 will be designed and transfected into cells using a liposomal approach. MTT and trypan blue assays will be used to determine the effect of HOTAIRM1 silencing on cell proliferation. Apoptosis of the cells will be detected by flow cytometry. Furthermore, expressions of apoptosis‐related genes and Wnt pathway‐related proteins and genes will be analyzed by Western blot and real‐time PCR. HOTAIRM1 was overexpressed in SKOV3 cells. Silencing of HOTAIRM1 alleviated cell proliferation, and increased cell apoptosis of SKOV3 cells. Moreover, siHOTAIRM1 significantly increased expression of pro‐apoptotic agents, such as Bad and Bax, while it decreased expressions of Bid and Bcl‐2 (anti‐apoptotic agents). Also, silencing of HOTAIRM1 resulted in a suppressed expression of Wnt pathway‐related proteins and also expression of its downstream target gene, matrix metalloproteinase 9(MMP9). Our findings provided new insights into function of lncRNA of HOTAIRM1 in progression of ovarian cancer by modulating Wnt pathway and its downstream target gene, MMP9.
Understanding the unexplained: The magnitude and correlates of individual differences in residual variance
Authors: Mitchell David J. , Beckmann Christa , Biro Peter A. 
Published: May 2021

AbstractBehavioral and physiological ecologists have long been interested in explaining the causes and consequences of trait variation, with a focus on individual differences in mean values. However, the majority of phenotypic variation typically occurs within individuals, rather than among individuals (as indicated by average repeatability being less than 0.5). Recent studies have further shown that individuals can also differ in the magnitude of variation that is unexplained by individual variation or environmental factors (i.e., residual variation). The significance of residual variation, or why individuals differ, is largely unexplained, but is important from evolutionary, methodological, and statistical perspectives. Here, we broadly reviewed literature on individual variation in behavior and physiology, and located 39 datasets with sufficient repeated measures to evaluate individual differences in residual variance. We then analyzed these datasets using methods that permit direct comparisons of parameters across studies. This revealed substantial and widespread individual differences in residual variance. The magnitude of individual variation appeared larger in behavioral traits than in physiological traits, and heterogeneity was greater in more controlled situations. We discuss potential ecological and evolutionary implications of individual differences in residual variance and suggest productive future research directions.
Courtship with two spoons—Anatomy and presumed function of the bizarre antennae of Cardiocondyla zoserka ant males
Authors: Heinze Jürgen , Marschall Jella , Lautenschläger Birgit , Seifert Bernhard , Gratiashvili Nana , Strohm Erhard 
Published: May 2021

AbstractMating in ants often occurs on the wing during nuptial flights or on the ground when scattered female sexuals attract males by pheromones. In both scenarios, there is little opportunity for males to engage in prolonged aggressive competition or elaborate courtship displays. Male morphology is therefore adapted to locating female sexuals and mating, and it lacks specific weapons or other traits associated with courtship. In contrast, sexuals of the ant genus Cardiocondyla typically mate in their natal nests. As a consequence, in many species winged males have been replaced by wingless fighter or territorial males, which kill or expel rival males with their strong mandibles and show complex mating behavior. However, no wingless males are known from Cardiocondyla zoserka from West Africa, and instead, winged males have evolved a bizarre secondary sexual trait: uniquely shaped antennae with spoon‐like tips that show heavily sculptured ventral surfaces with numerous invaginations. We here report on the courtship behavior of C. zoserka males and describe antennal glands with class 3 gland cells, which presumably secrete a close range sex pheromone. Antennal glands have not yet been found in males of other ant species, including a close relative of C. zoserka, suggesting that in ants with intranidal mating sexual selection can rapidly lead to highly divergent adaptations and the evolution of novel structures.
Revisiting the drivers of acoustic similarities in tropical anuran assemblages
Authors: Sugai Larissa Sayuri Moreira , Llusia Diego , Siqueira Tadeu , Silva Thiago S. F. 
Published: May 2021

AbstractAcoustic signaling is key in mediating mate choice, which directly impacts individual fitness. Because background noise and habitat structure can impair signal transmission, the acoustic space of mixed‐species assemblages has long been hypothesized to reflect selective pressures against signal interference and degradation. However, other potential drivers that received far less attention can drive similar outputs on the acoustic space. Phylogenetic niche conservatism and allometric constraints may also modulate species acoustic features, and the acoustic space of communities could be a side‐effect of ecological assembly processes involving other traits (e.g., environmental filtering). Additionally, the acoustic space can also reflect the sorting of species relying on public information through extended communication networks. Using an integrative approach, we revisit the potential drivers of the acoustic space by addressing the distribution of acoustic traits, body size, and phylogenetic relatedness in tropical anuran assemblages across gradients of environmental heterogeneity in the Pantanal wetlands. We found the overall acoustic space to be aggregated compared with null expectations, even when accounting for confounding effects of body size. Across assemblages, acoustic and phylogenetic differences were positively related, while acoustic and body size similarities were negatively related, although to a minor extent. We suggest that acoustic partitioning, acoustic adaptation, and allometric constraints play a minor role in shaping the acoustic output of tropical anuran assemblages and that phylogenetic niche conservatism and public information use would influence between‐assemblage variation. Our findings highlight an overlooked multivariate nature of the acoustic dimension and underscore the importance of including the ecological context of communities to understand drivers of the acoustic space.
Long‐term clinical and haemodynamic results after transcatheter annuloplasty for secondary mitral regurgitation
Authors: Lavall Daniel , Bruns Julius , Stegmann Tina , Hagendorff Andreas , Stöbe Stephan , Laufs Ulrich 
Published: May 2021

AbstractAimsThe study sought to investigate the long‐term outcome after transcatheter mitral valve annuloplasty for secondary mitral regurgitation (MR).Methods and resultsConsecutive patients with symptomatic secondary MR undergoing transcatheter mitral valve annuloplasty with the Carillon device at Leipzig University Hospital between 2012 and 2018 were studied prospectively. Left ventricular (LV) function and MR severity were quantified by standardized echocardiography. 33 patients were included. Mean age was 75 ± 10 years, and 20 patients were women. A Society of Thoracic Surgeons score of 8.1 ± 7.2% indicated high‐risk status. In 24 patients, MR resulted from LV remodelling and dysfunction, eight suffered from left atrial dilatation, and one patient had MR due to combined primary and secondary aetiology. LV ejection fraction at baseline was (median) 38% [inter‐quartile range (IQR) 30–49%]. During the mean follow‐up time of 45 ± 20 months, 17 patients died, two patients withdraw consent, and four patients were lost. Of the remaining patients, four were hospitalized for decompensated heart failure. Two of these patients underwent additional transcatheter edge‐to‐edge mitral valve repair. At follow‐up, New York Heart Association (NYHA) functional class improved from 95% in Class III/IV at baseline to 70% in Class I/II with no patients in NYHA Class IV (P < 0.0001). Mitral regurgitant volume was reduced from 27 mL (IQR 25–42 mL) to 8 mL (IQR 3–17 mL) (P = 0.018) and regurgitant fraction from 42% (IQR 34–54%) to 11% (IQR 8–24%) (P = 0.014). LV end‐diastolic volume index [92 mL/m2 (IQR 74–107 mL/m2) vs. 67 mL/m2 (IQR 46–101 mL/m2), P = 0.065] and end‐systolic volume index [50 mL/m2 (IQR 44–69 mL/m2) vs. 32 mL/m2 (IQR 20–53 mL/m2), P = 0.037] decreased. Total stroke volume remained unchanged [38 mL/m2 (IQR 33–43 mL/m2) vs. 33 mL/m2 (IQR 26–44 mL/m2), P = 0.695], while LV ejection fraction increased [43% (IQR 35–49%) vs. 54% (IQR 46–57%), P = 0.014]. Forward stroke volume, heart rate, and forward cardiac output were not significantly altered.ConclusionsAmong high‐risk patients undergoing transcatheter mitral valve annuloplasty for symptomatic secondary MR, mortality was ~50% at 4 years. In the surviving patients, reduced MR severity was associated with reduced NYHA functional class, reverse LV remodelling, and improved LV function.
Sipuleucel‐T associated inflammatory cardiomyopathy: a case report and observations from a large pharmacovigilance database
Authors: Moey Melissa Y.Y. , Jiwani Rahim A. , Takeda Kotaro , Prenshaw Karyn , Kreeger R. Wayne , Inzerillo John , Liles Darla K. , Marcu C. Bogdan , Lebrun‐Vignes Bénédicte , Morris D. Lynn , Ardhanari Sivakumar , Salem Joe‐Elie 
Published: May 2021

AbstractAimsThe major cardiovascular (CV) adverse effects observed with sipuleucel‐T from large multi‐institutional clinical trials included thromboembolic events, myocardial infarction, and congestive heart failure in up to 0.3% of patients with CV risk factors. The incidence, outcomes, and mechanisms in real‐world clinical settings of these CV adverse effects to date have not been fully elucidated. Our study identified a patient with sipuleucel‐T‐induced inflammatory cardiomyopathy, which led to the identification of CV adverse effects associated with sipuleucel‐T from a large pharmacovigilance database and elucidation of its potential mechanisms.Methods and resultsUsing the MedDRA term ‘cardiac disorders’ (System Organ Class level), CV adverse events associated with sipuleucel‐T versus all other drugs were reviewed from VigiBase, a large pharmacovigilance database. Disproportionality analysis was calculated by the information component (IC), a Bayesian disproportionality indicator. A positive IC025 (IC 95% lower end credibility interval) value (>0) is the traditional threshold used in statistical signal detection at the Uppsala Monitoring Centre. From VigiBase, the total number of CV adverse drug reaction reported with sipuleucel‐T was 306 out of a total of 22 980 104 adverse drug reactions in VigiBase on 10/25/2020. MedDRA preferred terms levels were grouped into major CV adverse drug reaction categories where we observed significant reports of myocardial ischaemia, supraventricular tachycardia (particularly atrial fibrillation/atrial flutter), congestive heart failure, and valvular disorders. Myocardial ischemia included acute myocardial infarction (IC025 2.3) with n = 4/26 (15%) of these individual case safety reports considered fatal. Among patients with ‘cardiac failure congestive’ (IC025 1.5), 11 of these 43 cases (26%) were fatal with 42 (98%) of these cases considered to be solely due to sipuleucel‐T.ConclusionsPatients with CV risk factors who are receiving sipuleucel‐T may be at higher risk for congestive heart failure, myocardial ischemia, and supraventricular tachycardia. Electrocardiograms during weekly sipuleucel‐T infusions and left ventricular function monitoring with echocardiogram should be considered in these patients. Our findings are suggestive of another rare presentation of T‐cell‐mediated CV toxicity with cancer immunotherapy.
Clamped member fatigue characteristics of bolted connections subject toout‐of‐planeloading
Authors: Zambino Lee W. , Ural Ani 
Published: May 2021

AbstractIn the presence of significant cyclic loading, the design of safe and efficient structural connections requires accurate determination of the clamped member stresses, amongst other considerations. Connections with pretensioned bolts and loading applied parallel to the bolt axis constitute a challenging analysis task that is underrepresented in the literature. To address this, parametric finite element analysis was performed on a representative bolted connection subject to out‐of‐plane loading and comprised of an aluminum member and a pretensioned steel bolt – a typical configuration in the aerospace industry. Of particular interest were the flexural stresses and their contribution to fatigue damage along the member faying surface. The analysis results demonstrated that both the location and magnitude of the stress extrema varied greatly with the geometric and loading parameters considered. To quantify regions most susceptible to fatigue damage, an equivalent stress formulation in conjunction with a critical plane approach was implemented. Contour plots were generated illustrating these regions and regression analysis was performed relating the parametric geometry and load quantities to the maximum equivalent and principal stresses. Regions of greatest fatigue susceptibility were shown to vary both radially and tangentially about the fastener. The data presented are intended to improve both the efficiency and safety of bolted connections.
Association between serum 25‐hydroxyvitamin D concentrations and obesity in one‐year‐old Chinese infants
Authors: Guo Bingbing , Zhang Yue , Lu Jianan , Guo Shuang , Jiang Yingtong , Pei Jingjing , Wang Ran , Zhang Chen , Teng Haoyue , Chen Qiuyu , Jiang Xinye , Yin Jieyun 
Published: May 2021

AbstractRecent studies suggested that vitamin D is linked with obesity, but evidence in infants is scarce. Therefore, we aimed to make an exploration in infants. A total of 414 infants at one year old who visited Maternity and Child Health Care Hospital of Wuxi in China were recruited. Finger‐stick blood sampling was conducted in all the subjects, and serum 25‐hydroxyvitamin D [25(OH)D] concentrations were measured. Maternal characteristics during pregnancy and infantile information were collected by questionnaires or extracting from medical records. Multivariable linear models were performed to assess the relationship between 25(OH)D and body mass index (BMI), while multivariable logistic regression models were used to examine the association between 25(OH)D and obesity. Among the 414 infants, 69 (16.67%) and 81 (19.57%) infants were defined as obesity and vitamin D deficiency [25(OH)D < 50 nmol/L], respectively. The mean (SD) of 25(OH)D concentration was 68.05 (19.05) in infants without obesity, which was significantly higher than that of obese infants [60.36(18.49), p = .002]. Inverse linear relationships were observed between 25(OH)D level and BMI (β = −0.017, p = .004) as well as BMI Z‐score (β = −0.010, p = .004). Furthermore, vitamin D deficiency was associated with an increased risk of obesity of infants (adjusted odds ratio = 2.74, 95% confidence interval = 1.20–6.25, with 25(OH)D ≥ 75 nmol/L as a reference). The results showed that serum 25(OH)D concentrations were significantly lower in infants with obesity, suggesting vitamin D deficiency may be an independent risk factor for obesity among one‐year‐old Chinese infants.
Multianalytical investigation of wasters from the Tower 8/Porta di Nola refuse middens in Pompeii: Sr–Nd isotopic, chemical, petrographic, and mineralogical analyses
Authors: Guarino Vincenza , De Bonis Alberto , Peña J. Theodore , Verde Maria , Morra Vincenzo 
Published: May 2021

AbstractA total of nine representative pottery fragments belonging to ferruginous, carbonate, and thin‐walled wares were recovered in refuse middens outside the fortification wall of Pompeii and subjected to a program of multianalytical operations (thermal ionization mass spectrometry, X‐ray fluorescence, X‐ray powder diffraction analysis, scanning electron microscopy–energy‐dispersive spectrometry techniques, optical microscopy). The fragments bear manufacturing defects, indicating their local production in workshops located somewhere at Pompeii. These three groups display a similar volcanic coarse component that exhibits distinct chemical compositions. The volcanic component consists of alkali feldspar, clinopyroxene, plagioclase, minor garnet, and rock fragments (with primarily plagioclase and leucite), pointing to an origin from the Somma‐Vesuvius. The fingerprint of the Sr–Nd isotopes of carbonate ware suggests an affinity with high‐CaO clays from Rufoli, a subdivision of Salerno. Sr–Nd isotopes also suggest that clays from the Sorrentine Peninsula were used: A clay mixture of different argillified pyroclastic materials was employed for the low‐CaO ferruginous ware, whereas the low‐CaO thin‐walled ware was manufactured with a marine varicolored clay. The distribution of materials likely occurred by sea via the port at Salernum and Surrentum. The combination of different types of complementary data obtained through this program of analysis illustrates the importance of combining both quantitative petrographic and chemical characterization in the evaluation of archaeological pottery.
Occult parotid involvement in early‐stage squamous cell carcinoma of the external auditory canal
Authors: Chang Jae Won , Lee Seulgi , Lee Jeon Mi , Moon In Seok , Cho Young‐Sang , Cho Yang‐Sun , Choi Jin Woong 
Published: May 2021

AbstractBackgroundThe importance of elective parotidectomy in early‐stage squamous cell carcinoma (SCC) of the external auditory canal (EAC) is not well established.MethodsA retrospective study of 43 patients with early‐stage SCC of the EAC who underwent parotidectomy in conjunction with lateral temporal bone resection at three centers.ResultsOverall occult parotid involvement (OPI) rate in early‐stage SCC of the EAC was 13.9% (6/43). When considering both the anteroposterior position and the bony‐cartilaginous position, patients with SCC in both the anterior wall and cartilaginous portion exhibited significantly higher OPI than other locations (37.5% vs. 0%, p = 0.001), with an increase in the OPI predictive value.ConclusionSCC located in either the anterior wall of the EAC or the cartilaginous portion of the EAC or both simultaneously showed a high prevalence of OPI, and elective parotidectomy should be considered in those patients.
Nonmetastatic castration‐resistant prostate cancer treated with salvage focal brachytherapy after external beam radiotherapy
Authors: Yoshida Soichiro , Matsuoka Yoh , Toda Kazuma , Uehara Sho , Tanaka Hajime , Yokoyama Minato , Saito Kazutaka , Yoshimura Ryoichi , Fujii Yasuhisa 
Published: May 2021

IntroductionThe efficacy of salvage local therapy after external beam radiotherapy has recently gained attention. However, a challenge with these therapies is the risk of significant genitourinary and gastrointestinal toxicity. Focal brachytherapy may be a treatment option because of its potential to reduce side effects.Case presentationA patient with castration‐resistant prostate cancer was found to be free of metastases on whole‐body magnetic resonance imaging following external beam radiotherapy, and prostate biopsy revealed a localized recurrence in the ventral prostate. The patient underwent salvage focal brachytherapy and had a prostate‐specific antigen progression‐free survival of 23 months. No adverse effects were observed following salvage brachytherapy.ConclusionOur case suggests that salvage focal brachytherapy may be an effective local treatment option for nonmetastatic castration‐resistant prostate cancer that has relapsed after external beam radiotherapy, wherein the lesion is confined to a small area within the prostate.
Retrograde ureteroscopic lithotripsy in cross‐fused renal ectopia
Authors: Somiya Shinya , Takahashi Toshifumi , Ito Katsuhiro , Higashi Yoshihito , Yamada Hitoshi , Kanno Toru 
Published: May 2021

IntroductionCross‐fused renal ectopia is a rare congenital malformation, and few cases of urolithiasis have been treated by retrograde ureteroscopic lithotripsy. We report a case of urolithiasis in right‐to‐left and superior‐type cross‐fused renal ectopia, successfully treated by the retrograde approach.Case presentationA 69‐year‐old woman with two 14‐mm renal stones in cross‐fused renal ectopia underwent retrograde ureteroscopic lithotripsy. Although we did not recognize the anomaly preoperatively, we could diagnose urolithiasis in the ectopic kidney intraoperatively. The patient had no complication, and follow‐up computed tomography after 3 months showed only a 5‐mm renal stone.ConclusionAlthough urolithiasis in patients with cross‐fused renal ectopia is a challenging condition for the urologist, the retrograde approach is a safe and effective treatment method. It is necessary to carefully examine the urinary tract especially in a patient with a history of unidentified solitary kidney.