bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted RNA sequencing in the routine clinical detection of fusion genes in salivary gland tumors
Authors: Bubola Justin , MacMillan Christina M. , Demicco Elizabeth G. , Chami Rose A. , Chung Catherine T.‐S. , Leong Iona , Marrano Paula , Onkal Zeynep , Swanson David , Veremis Brandon M. , Weinreb Ilan , Zhang Lei , Antonescu Cristina R. , Dickson Brendan C.
Published: June 2021

Salivary gland tumors represent a diverse group of neoplasms that occasionally pose a diagnostic challenge for pathologists, particularly with limited sampling. Gene fusions, which may reflect genetic drivers, are increasingly recognized in a subset of these neoplasms, and can be leveraged for diagnostic purposes. We performed a retrospective analysis on a cohort of 80 benign and malignant salivary gland tumors, enriched for subtypes known to harbor recurrent fusion events, to validate the diagnostic use of a targeted RNA sequencing assay to detect fusion transcripts. Testing identified fusion genes in 71% (24/34) of pleomorphic adenoma and carcinoma‐ex‐pleomorphic adenoma, with 56% of cases showing rearrangement of PLAG1 and 15% HMGA2. In addition to confirming known partners for these genes, novel PLAG1 fusion partners were identified, including DSTN, NTF3, and MEG3; CNOT2 was identified as a novel fusion partner for HMGA2. In adenoid cystic carcinoma, 95% of cases (19/20) were positive for a fusion event. MYB was rearranged in 60% (12/20), MYBL1 in 30% (6/20), and NFIB in 5% (1/20); two tumors exhibited novel fusion products, including NFIB‐TBPL1 and MYBL1‐VCPIP1. Fusion genes were identified in 64% (9/14) of cases of mucoepidermoid carcinoma; MAML2 was confirmed to partner with either CRTC1 (43%) or CRTC3 (21%). One salivary duct carcinoma was found to harbor a novel RAPGEF6‐ACSL6 fusion gene. Finally, as anticipated, gene fusions were not detected in any of the five acinic cell carcinomas included in the cohort. In summary, targeted RNA sequencing represents a diagnostically useful ancillary technique for identifying a variety of existing, and novel, fusion transcripts in the classification of salivary gland neoplasms.
Filtration Performance Degradation of In‐Use Masks by Vapors from Alcohol‐Based Hand Sanitizers and the Mitigation Solutions
Authors: He Weidong , Guo Yinghe , Liu Jingxian , Yue Yang , Wang Jing
Published: June 2021

In the current COVID‐19 pandemic, wearing masks and hand disinfection are widely adopted hygiene practices. Alcohol‐based sanitizers are commonly used for hand disinfection, however, the alcohol vapors can dissipate the charges on electrostatic filters. In the present study, the effects of alcohol vapors from alcohol‐based sanitizers during hand disinfection on the in‐use masks are studied. The results show that the negative effects are not significant for nonelectrostatic cotton masks or N95 respirators with multiple charged layers, but noticeable for surgical masks. After five rounds of hand disinfection, the filtration efficiencies of the filtering materials of the surgical masks decrease by more than 8% for 400 and 500 nm particles and by 3.7 ± 1.8% for 1 µm particles, the effective filtration efficiency of the surgical masks worn by the volunteers (with leakage considered) decreases by about 5% for ambient aerosol. In another process to imitate intensive disinfection procedures by healthcare workers, a 30 min surface cleaning process using alcohol‐based sanitizer is performed, and the effective efficiency of the N95 respirators worn by the volunteers decreases by nearly 9%. The simple practice of avoiding vapor during hand disinfection could mitigate the effects of alcohol vapor, which is demonstrated on two brands of surgical masks.
Fabrication of Novel Functional Cell‐Plastic Using Polyvinyl Alcohol: Effects of Cross‐Linking Structure and Mixing Ratio of Components on the Mechanical and Thermal Properties
Authors: Iritani Kohei , Nakanishi Akihito , Ota Ayami , Yamashita Takashi
Published: June 2021

The current system of disposal of plastic materials fabricated from petroleum‐based resources causes serious environmental pollution. To solve the problem, a bioplastic called “cell‐plastic” is developed, in which unicellular green algal cells serve as a fundamental resource. This approach converts CO2 in the atmosphere directly into plastic products by exploiting the photosynthetic‐driven proliferation of algal cells. Herein, cell‐plastic films are fabricated using biodegradable and water‐soluble polyvinyl alcohol (PVA) as a matrix, in which the effects of a cell‐to‐matrix mixing ratio and the chemical structure of the matrix on the mechanical and thermal properties are investigated. As a method of the chemical structural change, a cross‐linking structure is introduced to the matrix by connecting hydroxy groups of PVA using aldehyde. The tensile tests reveal that the PVA‐cell‐plastic film maintains the mechanical properties of PVA film. Moreover, a cross‐linked cell‐plastic film exhibits high water absorption, making it suitable as a functional cell‐plastic material.
Identification of public health priorities, barriers, and solutions for Kuwait using the modified Delphi method for stakeholder consensus
Authors: Gasana Janvier , Vainio Harri , Longenecker Joseph , Loney Tom , Ádám Balázs , Al‐Zoughool Mustafa
Published: June 2021

The rapid modernization and economic developments in Kuwait, have been accompanied by substantial lifestyle changes such as unhealthy diet and physical inactivity. These modifiable behaviours have contributed to increased rates of non‐communicable diseases including diabetes and cardiovascular diseases. Delphi Consensus Method was implemented in the current study to draw stakeholders from all sectors together to develop a consensus on the major public health priorities, barriers and solutions. The process involves administration of a series of questions to selected stakeholders through an iterative process that ends when a consensus has been reached among participants. Results of the iteration process identified obesity, diabetes, cardiovascular diseases along with lack of enforcement of laws and regulation as priority health issues. Results also identified lack of national vision for the development of a public health system, lack of multidisciplinary research investigating sources of disease and methods of prevention and improving efficiency with existing resources in implementation and efficiency as the main barriers identified were. Solutions suggested included investing in healthcare prevention, strengthening communication between all involved sectors through intersectoral collaboration, awareness at the primary healthcare setting and use of electronic health records. The results offer an important opportunity for stakeholders in Kuwait to tackle these priority health issues employing the suggested approaches and solution.
On the enormous enhancement in water evaporation rates obtained by employing a different polar ambient
Authors: Karn Ashish , Ambs Jonathan , Deo Shashank S. , Vyas Ayush , Dwivedi Ayush , Kumar Abhay
Published: June 2021

Enhancing evaporation rates are of great practical interest in many technological applications, such as water desalination or drying in industry. Evaporation mass flux is a function of ambient temperature, relative humidity, and velocity of the air passing over it. Since the conventional methods of increasing evaporation, namely increasing temperature, surface area, and so on, may not be always practically feasible or economical, novel methods of evaporation enhancement are necessary. The current study proposes that the introduction of a polar gas ambient above an evaporating liquid can drastically enhance its evaporation rate when the dipole moments of the evaporating liquid and the ambient gas are comparable. Thus, we explore the possibility of evaporation enhancement of water by introducing a polar Tetrafluoroethane gas ambient. The weight loss of water due to evaporation as well as the ambient temperature and air circulation conditions were measured. For each case, a companion experiment was carried out simultaneously under the same ambient conditions but without the presence of polar gas ambient. Each experiment lasted for 4 h. The evaporation rate has been found to be crucially dependent upon the polar gas ambient, the temperature as well as circulation conditions. Depending upon the temperature and circulation conditions, an enhancement of 59%–373% in evaporation rate has been recorded by the introduction of tetrafluoroethane gas ambient over the water surface. Some insights into the underlying mechanisms have been suggested in light of the physics of the evaporation process. Finally, some comparisons in the measured enhancement in evaporation rates under different experimental conditions are observed to concur with the suggested physical mechanism.
Assessing urban rainfall‐runoff response to stormwater management extent
Authors: Miller Andrew J. , Welty Claire , Duncan Jonathan M. , Baeck Mary Lynn , Smith James A.
Published: June 2021

We report an empirical analysis of the hydrologic response of three small, highly impervious urban watersheds to pulse rainfall events, to assess how traditional stormwater management (SWM) alters urban hydrographs. The watersheds vary in SWM coverage from 3% to 61% and in impervious cover from 45% to 67%. By selecting a set of storm events that involved a single rainfall pulse with >96% of total precipitation delivered in 60 min, we reduced the effect of differences between storms on hydrograph response to isolate characteristic responses attributable to watershed properties. Watershed‐average radar rainfall data were used to generate local storm hyetographs for each event in each watershed, thus compensating for the extreme spatial and temporal heterogeneity of short‐duration, intense rainfall events. By normalizing discharge values to the discharge peak and centring each hydrograph on the time of peak we were able to visualize the envelope of hydrographs for each group and to generate representative composite hydrographs for comparison across the three watersheds. Despite dramatic differences in the fraction of watershed area draining to SWM features across these three headwater tributaries, we did not find strong evidence that SWM causes significant attenuation of the hydrograph peak. Hydrograph response for the three watersheds is remarkably uniform despite contrasts in SWM, impervious cover and spatial patterns of land cover type. The primary difference in hydrograph response is observed on the recession limb of the hydrograph, and that change appears to be associated with higher storm‐total runoff in the watersheds with more area draining to SWM. Our findings contribute more evidence to the work of previous authors suggesting that SWM is less effective at attenuating urban hydrographs than is commonly assumed. Our findings also are consistent with previous work concluding that percent impervious cover may have greater influence on runoff volume than percent SWM coverage.
X‐ray luminescence computed tomography using a hybrid proton propagation model and Lasso‐LSQR algorithm
Authors: Guo Hongbo , Zhao Hengna , Yu Jingjing , He Xiaowei , He Xuelei , Song Xiaolei
Published: June 2021

X‐ray luminescence computed tomography (XLCT) uses external X‐rays for luminescence excitation, which is becoming a promising molecular imaging technique with superb penetration depth and spatial resolution. To achieve the tomographic mapping of luminescence distribution, accurate optical propagation model and suitable reconstruction method are two keys for XLCT, but not satisfied. To overcome the limitation of the single proton propagation model (e.g., DE, SP3), we adopted a hybrid diffusion equation with third order simplified spherical harmonics (DE‐SP3) model for XLCT. To enable fast iteration and accurate sparse reconstruction, we also integrated in the inversion optimization, with a novel Least Square QR‐factorization based on the Lasso (Lasso‐LSQR) algorithm. We first simulated the light propagation in various kinds of organs under DE model and SP3 model, respectively. By comparison with the Monte Carlo, these tissues can be categorized into two types, namely DE‐fitted tissues that include muscle and lung, and SP3‐fitted tissues including heart, kidney, liver, and stomach. According to the above classification results, we built a hybrid DE‐SP3 model to more accurately describing light transport. Numerical simulations and in vivo experiments illustrated that hybrid DE‐SP3 model achieves superior reconstruction performance in terms of location accuracy, and spatial resolution than DE, and less computational cost than SP3. The hybrid DE‐SP3 model materializes a balance between accuracy and efficiency for XLCT.
The in vivo dissolution of tricalcium silicate bone cement
Authors: Lin Qing , Zhang Xiaojuan , Liang Dong , Li Junlin , Wang Wei , Wang Zhao , Wong Ching‐Ping
Published: June 2021

This study aimed to investigate the in vivo dissolution of tricalcium silicate (Ca3SiO5, C3S) bone cement in the rabbit femoral defect. Results indicated that C3S paste directly integrated with the bone tissue without the protection of the bone‐like apatite. Calcium silicate hydrate gel (C–S–H gel) and Ca(OH)2 were the main components of C3S paste. The dissolution model of C3S paste was a mass loss rather than a decrease in volume. The initial dissolution of C3S paste (0 ~ 6 weeks) was greatly attributed to the release of Ca(OH)2, and the later dissolution (>6 weeks) was attributed to the decalcification of C‐S‐H gel. Although the mass of C3S paste could decrease by more than 19 wt % after 6 weeks of implantation, the created pores (<1 μm) were not large enough for the bone tissue to migrate into C3S paste. The loss of Ca ions also resulted in the transformation of SiO4 tetrahedrons from Q1 and Q2 to Q0, Q3, and Q4 in C‐S‐H gel. Because only isolated SiO4 tetrahedrons (Q0) and Ca ions could be absorbed by the bone tissue, C3S paste gradually transformed into a silica‐rich gel. The fundamental reason for no decrease in volume of C3S paste was that the SiO4 tetrahedron network still maintained the frame structure of C3S paste during the implantation.
Biomarker profile predicts clinical efficacy of extracorporeal photopheresis in steroid‐resistant acute and chronic graft‐vs‐host disease after allogenic hematopoietic stem cell transplant
Authors: Amat Paula , López‐Corral Lucía , Goterris Rosa , Pérez Ariadna , López Olga , Heras Inmaculada , Arbona Cristina , Viguria María Cruz , Hernández‐Boluda Juan Carlos , Martínez‐Ruiz Francisco , Martínez Andreu , Solano Carlos
Published: June 2021

We conducted a multicenter interventional study to assess the efficacy of Therakos ECP to treat steroid‐resistant graft‐vs‐host disease (SRes‐GVHD) after allogeneic HSCT and to identify biomarkers of GVHD response. A total of 62 patients were treated for acute SRes‐GVHD (n = 37) or chronic SRes‐GVHD (n = 25). Median time to best response was 35 days (range, 28‐85) and 90 days (range, 27‐240) in acute and chronic SRes‐GVHD, respectively. Overall, 27 patients (72.9%) with SRes‐aGVHD responded to treatment (40.5% CR and 32.4% PR). The response rate was significantly higher in grade I‐II than in grade III‐IV aGVHD (100% vs 50.0%, respectively, P‐value = .001). In chronic SRes‐GVHD, 22 patients (88%) achieved a clinical response (24.0% CR and 64% PR). Response was higher in moderate than in severe SRes‐cGVHD (100% vs 75%, P = .096). In both acute and chronic SRes‐GVHD patients, the percentage of peripheral blood CD3+CD4+ was higher and CD3+CD8+ lower in responding than nonresponding patients. Acute SRes‐GVHD responding patients presented a higher number of Treg cells (CD4+CD25+CD127low/−) at day 0 (P = .028) than nonresponding patients, differences that were maintained over the observation period. Phenotypic analysis of T‐cell maturation showed a trend toward reduction in TCD8 naive cells, along with an increased percentage of TCD8 Mem Efect T cells after starting ECP in responding patients. None of the studied serum cytokines displayed statistically significant changes in either acute or chronic SRes‐GVHD. ECP is an effective treatment for patients with SRes‐GVHD. Biomarkers could help guide decision‐making on ECP treatment initiation and duration.
The efficacy and cost‐effectiveness of a family‐based economic empowerment intervention (Suubi + Adherence) on suppression of HIV viral loads among adolescents living with HIV: results from a Cluster Randomized Controlled Trial in southern Uganda
Authors: Tozan Yesim , Capasso Ariadna , Sun Sicong , Neilands Torsten B , Damulira Christopher , Namuwonge Flavia , Nakigozi Gertrude , Mwebembezi Abel , Mukasa Barbara , Sensoy Bahar Ozge , Nabunya Proscovia , Mellins Claude A , McKay Mary M , Ssewamala Fred M
Published: June 2021

Introduction

Evidence from low‐resource settings indicates that economic insecurity is a major barrier to HIV treatment adherence. Economic empowerment (EE) interventions have the potential to improve adherence outcomes among adolescents living with HIV (ALWHIV) by mitigating the effects of poverty. This study aims to assess the efficacy and cost‐effectiveness of a savings‐led family‐based EE intervention, Suubi + Adherence, aimed at improving antiretroviral therapy (ART) adherence outcomes ALWHIV in Uganda.

Methods

Adolescents (mean age 12 years at enrolment; 56% female) receiving ART for HIV at 39 health centres were randomized to Suubi + Adherence intervention (n = 358) or bolstered standard of care (BSOC; n = 344). A difference‐in‐differences analysis was employed to assess the change in the proportion of virally suppressed adolescents (HIV RNA viral load <40 copies/mL) over 24 months. The cost‐effectiveness analysis examined how much the intervention cost to virally suppress one additional adolescent relative to BSOC from the healthcare provider perspective.

Results

At 24 months, the intervention was associated with an 8.85‐percentage point [95% confidence interval (CI) 0.80 to 16.90 percentage points] increase in the proportion of virally suppressed adolescents between the study arms (p = 0.032). Per‐participant costs were US$177 and US$263 for the BSOC and intervention groups respectively. The incremental cost of virally suppressing one additional adolescent was estimated at US$970 [95% CI, US$508 to 10,725] over two years.

Conclusions

Our results support the integration of family‐based EE interventions into adherence‐support strategies as part of routine HIV care in low‐resource settings to address the underlying economic drivers of poor ART adherence among ALWHIV. Moreover, per‐participant costs to achieve viral suppression do not seem prohibitive compared to other community‐based adherence interventions targeted at ALWHIV in low‐resource settings. Further research on combination interventions at the nexus of economic security and HIV treatment and care is needed to inform the development of feasible and scalable HIV policies and programmes.
Maternal weight and birth outcomes among women on antiretroviral treatment from conception in a birth surveillance study in Botswana
Authors: Zash Rebecca , Caniglia Ellen C , Diseko Modiegi , Mayondi Gloria , Mabuta Judith , Luckett Rebecca , Hofmeyr G Justus , Morroni Chelsea , Ramogola‐Masire Doreen , Williams Paige L , Zera Chloe , Wylie Blair J , Makhema Joseph , Lockman Shahin , Shapiro Roger L
Published: June 2021

Introduction

Antiretrovirals such as dolutegravir (DTG) and tenofovir alafenamide (TAF) have been associated with excessive weight gain. The objective of this study was to understand the potential impact of ART‐associated weight gain on pregnancy outcomes among women living with HIV.

Methods

Using data from the Tsepamo birth outcomes surveillance study in Botswana, we evaluated the relationship between maternal weight (and weight gain) and severe birth outcomes (very preterm delivery <32 weeks, very small for gestational age (SGA) <3rd percentile, perinatal death), macrosomia (birthweight > 4000 g) and maternal hypertension. We estimated the relative risk of each outcome by baseline weight (first weight in pregnancy <24 weeks) and second trimester average weekly weight gain (kg/week from 12 ± 2 to 24 ± 2 weeks) using log binomial regression and evaluated effect modification by ART regimen (DTG vs. Efavirenz (EFV)).

Results

Of 22,828 women on ART at conception with singleton deliveries between August 2014 and April 2020, 16,300 (71.4%) had a weight measured <24 weeks’ gestation (baseline weight) and 4437 (19.2%) had weight measured both at 12 (±2) weeks and 24 (±2) weeks, allowing second trimester weight gain calculation. Compared to women with baseline weight 60 to 70 kg, low baseline weight (<50 kg) was associated with increased risk of very preterm delivery (aRR 1.30, 95% CI 1.03, 1.65) and very SGA (aRR1.96, 95% CI 1.69, 2.28). High baseline weight (>90 kg) was associated with increased risk of macrosomia (aRR 3.24, 95% CI 2.36, 4.44) and maternal hypertension (aRR 1.79, 95% CI 1.62, 1.97). Baseline weight was not associated with stillbirth or early neonatal death. For all outcomes, second trimester weight gain showed weaker associations than did baseline weight. Duration of pre‐pregnancy ART (years) was associated with higher baseline weight for DTG but not for EFV, and the risk of maternal hypertension by baseline weight category was higher for DTG than EFV for all strata.

Conclusions

ART regimens associated with weight gain may reduce the number of women at risk for certain severe adverse pregnancy outcomes associated with low weight but increase the number at risk of macrosomia and maternal hypertension. Further research could determine whether weight‐based ART treatment strategies improve maternal and child health.
From the top to the bottom: The global environment and microfinance institution (MFI) performance in the West African Economic and Monetary Union countries
Authors: Gbandi Tchapo , Couchoro Mawuli K. , Agossou Mawulolo J.
Published: June 2021

This paper highlights the effects of macroeconomic and macroinstitutional environments on the performance of microfinance institutions (MFIs) in the West African Economic and Monetary Union (WAEMU) countries. The quality of this relationship can help MFIs to succeed, as well as adequate policies. This analysis is conducted using panel data spanning the period 2004–2014. We find that economic performance goes hand in hand with MFIs' sustainability in WAEMU countries. By contrast, improved macroinstitutional conditions result in a decrease in MFIs financial performance. Last but not least, MFIs reach out significantly more to the poorest when countries' institutions are improving.
3‐Hydroxyisobutyrate dehydrogenase (HIBADH) deficiency—A novel disorder of valine metabolism
Authors: Meyer Melanie , Hollenbeck Jana C. , Reunert Janine , Seelhöfer Anja , Rust Stephan , Fobker Manfred , Biskup Saskia , Och Ulrike , Linden Mechthild , Sass Jörn Oliver , Marquardt Thorsten
Published: June 2021

3‐Hydroxyisobutyric acid (3HiB) is an intermediate in the degradation of the branched‐chain amino acid valine. Disorders in valine degradation can lead to 3HiB accumulation and its excretion in the urine. This article describes the first two patients with a new metabolic disorder, 3‐hydroxyisobutyrate dehydrogenase (HIBADH) deficiency, its phenotype and its treatment with a low‐valine diet. The detected mutation in the HIBADH gene leads to nonsense‐mediated mRNA decay of the mutant allele and to a complete loss‐of‐function of the enzyme. Under strict adherence to a low‐valine diet a rapid decrease of 3HiB excretion in the urine was observed. Due to limited patient numbers and intrafamilial differences in phenotype with one affected and one unaffected individual, the clinical phenotype of HIBADH deficiency needs further evaluation.
Epiblast and trophoblast morphogenesis in the pre‐gastrulation blastocyst of the pig. A light‐ and electron‐microscopical study
Authors: Harmoush Braah , Tsikolia Nikoloz , Viebahn Christoph
Published: June 2021

The epiblast of the amniote embryo is of paramount importance during early development as it gives rise to all tissues of the embryo proper. In mammals, it emerges through segregation of the hypoblast from the inner cell mass and subsequently undergoes transformation into an epithelial sheet to create the embryonic disc. In rodents and man, the epiblast cell layer is covered by the polar trophoblast which forms the placenta. In mammalian model organisms (rabbit, pig, several non‐human primates), however, the placenta is formed by mural trophoblast whereas the polar trophoblast disintegrates prior to gastrulation and thus exposes the epiblast to the microenvironment of the uterine cavity. Both, polar trophoblast disintegration and epiblast epithelialization, thus pose special cell‐biological requirements but these are still rather ill‐understood when compared to those of gastrulation morphogenesis. This study therefore applied high‐resolution light and transmission electron microscopy and three‐dimensional (3D) reconstruction to 8‐ to 10‐days‐old pig embryos and defines the following steps of epiblast transformation: (1) rosette formation in the center of the ball‐shaped epiblast, (2) extracellular cavity formation in the rosette center, (3) epiblast segregation into two subpopulations ‐ addressed here as dorsal and ventral epiblast ‐ separated by a “pro‐amniotic” cavity. Ventral epiblast cells form between them a special type of desmosomes with a characteristic dense felt of microfilaments and are destined to generate the definitive epiblast. The dorsal epiblast remains a mass of non‐polarized cells and closely associates with the disintegrating polar trophoblast, which shows morphological features of both apoptosis and autophagocytosis. Morphogenesis of the definitive epiblast in the pig may thus exclude a large portion of bona fide epiblast cells from contributing to the embryo proper and establishes contact de novo with the mural trophoblast at the junction between the two newly defined epiblast cell populations.
Evaluation of statistical downscaling methods for climate change projections over Spain: Present conditions with perfect predictors
Authors: Hernanz Alfonso , García‐Valero Juan Andrés , Domínguez Marta , Ramos‐Calzado Petra , Pastor‐Saavedra María A. , Rodríguez‐Camino Ernesto
Published: June 2021

The Spanish Meteorological Agency (AEMET) is responsible for the elaboration of downscaled climate projections over Spain to feed the Second National Plan of Adaptation to Climate Change (PNACC‐2). The main objective of this article is to establish a comparison among five statistical downscaling methods developed at AEMET: (1) Analog, (2) Regression, (3) Artificial Neural Networks, (4) Support Vector Machines and (5) Kernel Ridge Regression. This comparison has been carried out under present conditions and with perfect predictors, based on the framework established by the VALUE network, in particular, on its perfect predictor experiment. In this experiment, we evaluate the marginal aspects of the distributions of daily maximum/minimum temperatures and daily accumulated precipitation analysed by seasons, on a high resolution observational grid (0.05°) over mainland Spain and the Balearic Islands. This is the first of a set of three experiments aimed to allow us to decide which methods, and under what configuration, is more appropriate for the generation of downscaled climate projections over our region. For maximum/minimum temperatures, all methods display a similar behaviour. They capture very satisfactorily the mean values although slight biases are detected on the extremes. In general, results for maximum temperature appear to be more accurate than for minimum temperature, and the nonlinear methods display certain added value. For precipitation, remarkable differences are found among all methods. Most of the methods are capable of reproducing the total precipitation amount quite satisfactorily, whereas other aspects such as intense precipitations and the precipitation occurrence are captured with more accuracy by the Analog method.
The impact of using different probability representations in application of equidistant quantile matching for bias adjustment of daily precipitation over the Daqing River Basin, North China
Authors: Lv Mingcong , Gao Xueping , Liu Yinzhu , Ju Wenhui , Sun Bowen , Li Wenjun , Zhou Xushen
Published: June 2021

This study focuses on how the representation of daily precipitation probability distributions may affect the application of equidistant quantile matching (EDCDFm). Five representations, that is, two parametric distributions and three nonparametric approaches, are selected. The parametric distributions include Gamma and Weibull while the nonparametric approaches include empirical cumulative distribution function (ECDF) and kernel density estimation method (KDE) as well as an improved KDE named diffusion‐based kernel density estimation (DKDE). All five methods were applied to correct the daily precipitation of 11 stations over the Daqing River Basin, North China in 1981–2015. The results demonstrated that DKDE is closer to ECDF than the other three methods in the goodness‐of‐fit evaluation. Furthermore, nonparametric methods present advantages over parametric methods; especially, DKDE and ECDF are skilful equally and both of them display impressive comprehensive performance than other methods by multi‐index. These findings suggest that representing the precipitation probability distributions accurately is beneficial for the bias correction and selecting one or more suitable indexes is of great significance to the verification of EDCDFm. This study can provide guidance for future water resources management of the Daqing River Basin.
Quantitative study on the biomechanical mechanism of sacroiliac joint subluxation: A finite element study
Authors: Zhang Shaoqun , Chen Yili , Ren Ruxia , Jiang Shunwan , Cao Yafei , Li Yikai
Published: June 2021

The biomechanical mechanism of sacroiliac joint pain caused by sacroiliac joint subluxation is still unclear. And the purpose of this study is to elucidate the mechanism. In the present study, a finite element model of female lumbar spine–pelvis–femur was established. To simulate the sacroiliac joint subluxation quantitatively, the left ilium was shifted ±1, ±2, and ±3 mm along each axis, respectively. The stress and strain of articular surfaces and ligaments between the sacroiliac joint subluxation model and the normal model were compared. When the left ilium shifted along the positive direction of the X/Y/Z axis, the stress on most articular surfaces of the sacroiliac joint increased, of which the stress on the iliac surface of the right sacroiliac joint increased most obviously. The stress and strain of the ligaments increased most obviously when the left ilium shifted along the Y‐axis, of which the left sacrospinous ligament increased the most, followed by the right sacrospinous ligament and right long posterior sacroiliac ligament. While the left long posterior sacroiliac ligament decreased the most, followed by the left short posterior sacroiliac ligament. The present study suggests that when the sacroiliac joint subluxation happens, even a slight shift, different biomechanical changes of different ligaments around the sacroiliac joint will happen. This may lead to an abnormal proprioceptive sensation of the ligaments, resulting in stress imbalance of the sacroiliac joint, and finally resulting in sacroiliac joint pain.
Stability of buffered benzylpenicillin and flucloxacillin for a paediatric outpatient parenteral antibiotic therapy service
Authors: Smith Evonne Katherine , McWhinney Brett C.
Published: June 2021

Introduction

Benzylpenicillin and flucloxacillin are commonly used in outpatient parenteral antibiotic therapy (OPAT). Published evidence supporting the stability of buffered infusions, in a variety of devices and concentrations, using an Australian commercially available buffer, to suit a paediatric setting is desirable. The aim of this study was to determine if multiple concentrations of buffered benzylpenicillin and flucloxacillin, prepared in suitable infusion devices, exposed to a variety of temperatures, maintained stability.

Methods

Benzylpenicillin (15 and 60 mg/mL) and flucloxacillin (5 and 60 mg/mL) infusions in LV Elastomeric Infusor devices and sodium chloride 0.9% Viaflex bags were prepared as buffered and unbuffered solutions. Buffering was achieved by reconstituting antibiotic vials with sodium citrate 4%. Infusions were stored at 2–8°C for 6 days then 37°C for 24 h. Samples were taken on day 0, 1, 3, 6 and 7. The concentration, pH, colour and appearance were assessed at each time point.

Results

The concentration of all day 7 buffered benzylpenicillin samples was maintained between 97.70–100.36% and flucloxacillin 98.7–100.66% of the initial concentration. Unbuffered solutions did not retain antibiotic potency over the same study period. There was minimal pH change in buffered benzylpenicillin samples from 6.66 to 5.5 and flucloxacillin 6.58 to 6.19. There was no visual change in colour or appearance.

Conclusion

Buffered benzylpenicillin 15 and 60 mg/mL and flucloxacillin 5 and 60 mg/mL in LV Elastomeric Infusors and sodium chloride 0.9% Viaflex bags, appear chemically stable for 6 days refrigerated, and for a subsequent 24 h at 37°C.
Deletion of Rap‐Phr systems in Bacillus subtilis influences in vitro biofilm formation and plant root colonization
Authors: Nordgaard Mathilde , Mortensen Rasmus Møller Rosenbek , Kirk Nikolaj Kaae , Gallegos‐Monterrosa Ramses , Kovács Ákos T.
Published: June 2021

Natural isolates of the soil‐dwelling bacterium Bacillus subtilis form robust biofilms under laboratory conditions and colonize plant roots. B. subtilis biofilm gene expression displays phenotypic heterogeneity that is influenced by a family of Rap‐Phr regulatory systems. Most Rap‐Phr systems in B. subtilis have been studied independently, in different genetic backgrounds and under distinct conditions, hampering true comparison of the Rap‐Phr systems’ impact on bacterial cell differentiation. Here, we investigated each of the 12 Rap‐Phr systems of B.subtilis NCIB 3610 for their effect on biofilm formation. By studying single ∆rap‐phr mutants, we show that despite redundancy between the cell–cell communication systems, deletion of each of the 12 Rap‐Phr systems influences matrix gene expression. These Rap‐Phr systems therefore enable fine‐tuning of the timing and level of matrix production in response to specific conditions. Furthermore, some of the ∆rap‐phr mutants demonstrated altered biofilm formation in vitro and colonization of Arabidopsis thaliana roots, but not necessarily similarly in both processes, indicating that the pathways regulating matrix gene expression and other factors important for biofilm formation may be differently regulated under these distinct conditions.
Removal of Free-Living Ciliates from Stock Cultures of Two Calanoid Copepods with Sodium Hypochlorite
Authors: Daw Adam L. , Sarkisian Brie L. , Blaylock Reginald B. , Saillant Eric A. L.
Published: June 2021

Eggs of Acartia tonsa and Parvocalanus crassirostris were contaminated with ciliates (Euplotes sp.) and exposed to five concentrations of sodium hypochlorite (25, 55, 105, 205, and 405 mg/L) for durations of 15 s, 5 min, 15 min, or 30 min to assess the efficacy of household bleach for removing the ciliates. Eggs from each exposure treatment were incubated for 40 h (A. tonsa) or 12 h (P. crassirostris) to assess hatch. The presence of living ciliates was evaluated after incubation, and the egg hatch rate (%) for the copepods was estimated for each treatment and in controls. Exposure to 105 mg/L total chlorine for 15 s killed all of the ciliates and reduced the copepod hatch rate by less than 26% with respect to controls in both species. Exposure to 55 mg/L for 15 min or 25 mg/L for 30 min also killed the ciliates and achieved a mean copepod hatch rate of 38.5% and 58.1% of the control-group hatch rate, respectively, in A. tonsa. Treatments for 5 min or longer reduced the hatch rate for P. crassirostris eggs by at least 76% at all of the concentrations that we tested.
Discrete variable topology optimization for simplified convective heat transfer via sequential approximate integer programming with trust‐region
Authors: Yan Xin Yu , Liang Yuan , Cheng Geng Dong
Published: June 2021

This article presents a discrete variable topology optimization method to solve the simplified convective heat transfer (SCHT) design optimization modeled by Newton's law of cooling. The discrete variable topology optimization is based on the proposed sequential approximate integer programming with trust‐region. Due to the discrete variables, identifying the convective boundary, and implementing this design‐dependent convective boundary condition can be precisely undertaken. As a result, the consistent precise temperature field compared with the commercial software is captured. Besides, the interpolation scheme of the convective coefficient is unnecessary to analyze this SCHT problem. Furthermore, an analytical sensitivity formulation that can simultaneously incorporate the conductive and convective effect is also deduced. Finally, several 2D and 3D valid thermal designs are presented to illustrate the effectiveness of the method. Based on the optimized designs, we find that favorable configurations for a simplified convective problem may be hollowed structure or the dense needle‐like structure. Further, the checkerboard pattern should be interpreted as a convection oscillatory feature but not the discretization error because it cannot be eliminated by using higher‐order elements.
Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer: Clinical Overview and Management of Potential Toxicities
Authors: Spring Laura M. , Nakajima Erika , Hutchinson Jennifer , Viscosi Elene , Blouin Gayle , Weekes Colin , Rugo Hope , Moy Beverly , Bardia Aditya
Published: June 2021

Patients with metastatic triple-negative breast cancer have a poor prognosis. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate that contains the irinotecan active metabolite, SN-38, linked to a humanized monoclonal antibody targeting trophoblast cell surface antigen 2, which is overexpressed in many solid tumors. In a basket design phase I/II study, sacituzumab govitecan demonstrated promising single-agent therapeutic activity in multiple cancer cohorts, leading to accelerated approval by the U.S. Food and Drug Administration of sacituzumab govitecan-hziy (TRODELVY) for the treatment of patients with metastatic triple-negative breast cancer who had received at least two prior therapies in the metastatic setting. Recently, results of the phase III trial, ASCENT, were confirmatory. There is limited available information on the adverse event management with sacituzumab govitecan needed to maximize the dose and duration of effective therapy while maintaining patient quality of life. This review summarizes the clinical development and the practical management of patients receiving sacituzumab govitecan. Sacituzumab govitecan has a well-defined and manageable toxicity profile, and rapid recognition and appropriate early and proactive management will allow clinicians to optimize sacituzumab govitecan treatment for patients.

Implications for Practice

Sacituzumab govitecan (TRODELVY) is a novel antibody-drug conjugate composed of the active metabolite of irinotecan (SN-38) conjugated to a monoclonal antibody targeting trophoblast cell surface antigen 2, an epithelial cell surface antigen overexpressed in many cancers. Because of the rapid approval of sacituzumab govitecan, there is limited available information on adverse event (AE) management with this agent. As such, this article reviews the clinical development of the drug, the AE profile, and provides recommendations regarding AE management to help optimize therapy with sacituzumab govitecan.
Locally Recurrent Secretory Carcinoma of the Breast with NTRK3 Gene Fusion
Authors: Mortensen Lindsey , Ordulu Zehra , Dagogo-Jack Ibiayi , Bossuyt Veerle , Winters Loren , Taghian Alphonse , Smith Barbara L. , Ellisen Leif W. , Kiedrowski Lesli A. , Lennerz Jochen K. , Bardia Aditya , Spring Laura M.
Published: June 2021

Enhanced understanding of the molecular events underlying oncogenesis has led to the development of “tumor-agnostic” treatment strategies, which aim to target a tumor's genomic profile regardless of its anatomic site of origin. A classic example is the translocation resulting in an ETV6-NTRK3 gene fusion, a characteristic driver of a histologically diverse array of cancers. The chimeric ETV6-NTRK3 fusion protein elicits constitutive activation of the tropomyosin receptor kinase (TRK) C protein, leading to increased cell survival, growth, and proliferation. Two TRK inhibitors, larotrectinib and entrectinib, are currently approved for use in the metastatic setting for the treatment of advanced solid tumors harboring NTRK fusions. Here we report a rare case of recurrent secretory carcinoma of the breast (SCB) with NTRK3 gene fusion. Whereas most cases of SCB represent slow-growing tumors with favorable outcomes, the case detailed here is the first to the authors' knowledge of recurrence within 1 year of surgery. We review the molecular findings and potential clinical significance.

Key Points
Informed Consent 2021: The “Terms and Conditions” of the Research World
Authors: Saylor Philip J.
Published: June 2021

Most clinicians who participate in clinical research are viscerally aware that the current informed consent process is failing patients. Improving our informed consent process is important to the quality of clinical care and to the integrity of clinical trials.
Limited Impact of HER2 Expression on Survival Outcomes in Patients with Intrahepatic Cholangiocarcinoma After Surgical Resection
Authors: Hori Yutaro , Yoh Tomoaki , Seo Satoru , Minamiguchi Sachiko , Haga Hironori , Taura Kojiro
Published: June 2021

This letter to the editor remarks on the topic of HER2 expression as a potential target of adjuvant therapy for biliary tract cancer, focusing on patients with intrahepatic cholangiocarcinoma.
In Reply
Authors: Salani Francesca , Catanese Silvia , Fornaro Lorenzo , Vasile Enrico , Ugolini Clara , Cacciato Insilla Andrea , Campani Daniela , Fontanini Gabriella , Masi Gianluca , Vivaldi Caterina
Published: June 2021

This letter to the editor responds to comments by Hori et al. on the recently published study on intrahepatic cholangiocarcinoma and HER2 positivity rate.
Open intrauterine repair of spina bifida aperta: Historical aspects, current availability, and clinical outcomes from the Latin American Spina Bifida Consortium
Authors: Sepulveda Waldo , Cruz‐Martinez Rogelio , Etchegaray Adolfo , Sanin‐Blair Jose , Ventura Walter , Corral Edgardo , Marquez Rolando
Published: June 2021

Objective

To determine the historical aspects, current availability, and clinical outcomes of open intrauterine repair of spina bifida aperta (IRSBA) in Spanish‐speaking Latin American countries.

Methods

Cases were collected from centers with at least 2 years of experience and a minimum of 10 open IRSBA interventions by December 2020. Clinical variables were compared to the results of the Management of Myelomeningocele Study (MOMS) trial.

Results

Clinical experience with 314 cases from seven centers was reviewed. Most cases (n = 189, 60.2%) were performed between 24 and 25.9 weeks' gestation. Delivery at less than 30 weeks' gestation occurred in 36 cases (11.5%) and the overall perinatal mortality rate was 5.4% (17 of 314). The rate of maternal complications was low, including the need for blood transfusion (n = 3, 0.9%) and dehiscence or a thin uterine scar (n = 4, 1.3%). No cases of maternal death were recorded. Fifteen neonates required additional surgical repair of the spinal defect (4.8%) and 63 of 167 infants (37.7%) required a cerebrospinal fluid diversion procedure. Only two of the seven centers reported preliminary experience with fetoscopic IRSBA.

Conclusions

Clinical experience and outcomes were within the expected results reported by the MOMS trial. There is still very limited experience with fetoscopic IRSBA in this part of the world.
Twin chorionicity and zygosity both vary with maternal age
Authors: Yeaton‐Massey Amanda , Sparks Teresa N. , Norton Mary E. , Jelliffe‐Pawlowski Laura , Currier Robert J.
Published: June 2021

Objective

To determine the ratio of dichorionic (DC) to monochorionic (MC) twins by maternal age.

Methods

We reviewed all twin pregnancies undergoing first trimester screening (FTS) with nuchal translucency from April 2009 to December 2012 with sonographic determination of chorionicity. Cases were linked to newborn screening (NBS) results and zygosity estimated based on rates of fetal sex discordance. The ratio of DC to MC placentation by maternal age was calculated.

Results

We identified 11,351 twin pregnancies with FTS and documented chorionicity. Among these, 7861 (64.2%) had linked data on FTS and NBS to allow estimation of zygosity based on neonatal sex. Of these, 1464 (18.6%) were MC and 6406 (81.4%) DC. The MC twin rate remained constant while the DC twin rate increased with maternal age until 40 years. At <20 years, 55% of twin pregnancies were monozygotic (MZ), as compared to 29% at > 40 years. Of MZ twins, 38% were DC at < 20years, while 53% were DC at >40 years

Conclusions

Our data suggest a relationship of both zygosity and chorionicity with maternal age. DZ twinning increased with maternal age, while among MZ twins, the proportion that were DC also increased with maternal age.
Is ventriculomegaly and hindbrain herniation seen before and after prenatal neural tube defect repair associated with a worse functional level than anatomical level at birth?
Authors: Corroenne Romain , Zarutskie Alexander , Guimaraes Carolina , Yepez Mayel , Torres Paola , Shetty Anil , Lee Wesley , Espinoza Jimmy , Shamshirsaz Alireza A. , Nassr Ahmed A. , Belfort Michael , Whitehead William , Sanz Cortes Magdalena
Published: June 2021

Objective

To determine if the evaluation of the fetal ventricular system and hindbrain herniation (HBH) is associated with motor outcome at birth in prenatally repaired open neural tube defect (NTD).

Methods

Retrospective cohort study of 47 patients with NTD who underwent prenatal repair (17 fetoscopic; 30 open‐hysterotomy). At referral and 6 weeks postoperatively, the degree of HBH, ventricular atrial widths and ventricular volume were evaluated by MRI. Head circumference and ventricular atrial widths were measured on ultrasound at referral and during the last ultrasound before delivery. Anatomic level of the lesion (LL) was determined based on the upper bony spinal defect detected by ultrasound. We considered the functional level as worse than anatomical level at birth when the motor level was equal or worse than the anatomical LL.

Results

26% (12/47) of the cases showed worse functional level than anatomical level at birth. Having a HBH below C1 at the time of referral was associated with a worse functional level than anatomical level at birth (OR = 9.7, CI95 [2.2–42.8], p < 0.01). None of the other brain parameters showed a significant association with motor outcomes at birth.

Conclusions

HBH below C1 before surgery was associated with a worse functional level than anatomical level at birth.