bluuebunny/crossref_metadata_2025 huggingface dataset:
The Safety, Toleration, and Pharmacokinetics of Two Intravenous Voriconazole Formulations in Healthy Chinese Volunteers After Increasing Dose Administrations
Authors: Chen Gang , Wang Zejuan , Liu Xiaona , Zhang Yanan , Li Min , Du Aihua , Zhen Haiqing , Wang Xiaolin , Zhang Dan , Zhang Mengke , Zang Siqi , Zhang Lina , Zhu Huiting , Wang Jin
Published: June 2022

Sulfobutyl ether‐beta‐cyclodextrin sodium salt contained in the marketed intravenous voriconazole injection as a solubilizer may cause harmful accumulations. This study aimed to evaluate the safety, tolerability, and pharmacokinetics (PKs) of two intravenous voriconazole formulations containing excipients from different manufacturers using increasing dose administrations in healthy Chinese volunteers. A randomized, double‐blind, placebo‐controlled trial was conducted in three cohorts with 42 healthy Chinese volunteers. Each cohort of 14 volunteers was allocated in proportion (8:4:2) to test the formulation, reference voriconazole, or placebo successively by single‐dose then multiple‐dose administrations of 3, 4, and 6 mg/kg. Forty‐one volunteers completed all drug administrations. The pharmacokinetics of test formulations are characterized by high interindividual variability (coefficient of variance of Cmax up to 68.0%, AUC0‐τ up to 70.2%, and nonlinear PKs with a regression coefficient of Cmax = 1.31 and AUC0‐τ = 1.75 in a single dose). In the steady state, RAuc of the test drug versus reference drug of the 3, 4, and 6 mg/kg dose group were 5.2 and 5.3, 5.6 and 6.3, and 5.8 and 5.5, respectively, and Rcmax were 2.5 and 2.7, 2.6 and 3.1, and 2.8 and 2.6, respectively. Eighty‐three adverse events with 37 transient visual disturbances were mild. PKs with high interindividual variability, nonlinear characteristics, and significant dose‐dependent accumulation were comparable between the two formulations. Overall, the safety of the test formulation was acceptable.
Pharmacokinetics of Oral Nirmatrelvir/Ritonavir, a Protease Inhibitor for Treatment of COVID‐19, in Subjects With Renal Impairment
Authors: Toussi Sima S. , Neutel Joel Michael , Navarro Jesus , Preston Richard Alfred , Shi Haihong , Kavetska Olga , LaBadie Robert R. , Binks Michael , Chan Phylinda L.S. , Demers Neil , Corrigan Brian , Damle Bharat
Published: June 2022

Nirmatrelvir coadministered with ritonavir is highly efficacious in reducing the risk of coronavirus disease 2019 (COVID‐19) adverse outcomes among patients at increased risk of progression to severe disease, including patients with chronic kidney disease. Because nirmatrelvir is eliminated by the kidneys when given with ritonavir, this phase I study evaluated the effects of renal impairment on pharmacokinetics, safety, and tolerability of nirmatrelvir/ritonavir. Participants with normal renal function (n = 10) or mild, moderate, or severe renal impairment (n = 8 each) were administered a single 100‐mg nirmatrelvir dose with 100 mg ritonavir given 12 hours before, together with and 12 and 24 hours after the nirmatrelvir dose. Systemic nirmatrelvir exposure increased with increasing renal impairment, with mild, moderate, and severe renal impairment groups having respective adjusted geometric mean ratio areas under the plasma concentration‐time profile from time 0 extrapolated to infinite time of 124%, 187%, and 304% vs. the normal renal function group. Corresponding ratios for maximum plasma concentration were 130%, 138%, and 148%. Apparent clearance was positively correlated with estimated glomerular filtration rate, and geometric mean renal clearance values were particularly lower for the moderate (47% decrease) and severe (80% decrease) renal impairment groups vs. the normal renal function group. Nirmatrelvir/ritonavir exhibited an acceptable safety profile; treatment‐related adverse events were mild in severity, and there were no significant findings regarding laboratory measurements, vital signs, or electrocardiogram assessments. These findings led to a dose reduction recommendation for nirmatrelvir/ritonavir in patients with moderate renal impairment (150/100 mg nirmatrelvir/ritonavir instead of 300/100 mg twice daily for 5 days). NCT04909853.
Durum wheat Teosinte Branched1 null mutations increase tillering
Authors: Volkman McKenna M. , Martin John M. , Hogg Andrew C. , Wright Lucas , Hale Caleb , Carr Patrick M. , Giroux Michael J.
Published: June 2022

Wheat (Triticum spp.) yield is increased by either producing and testing variants of yield‐limiting genes or crossing to create new allelic combinations. Tiller number and seeds per tiller influence wheat yield, and both are impacted by the Teosinte Branched1 (TB1) gene. We screened 16 hard red spring wheat (Triticum aestivum L.) cultivars, 15 hard red winter wheat cultivars and lines, and 10 durum wheat [Triticum turgidum L. subsp. durum (Desf.) van Slageren] cultivars and lines commonly grown in Montana and found several previously reported TB1 missense alleles along with one new silent and a missense TB1‐A1 allele among the 16 hard red spring wheat cultivars but no TB1 null alleles. Among the 10 durum cultivars, five carried a TB1‐B1‐S184G missense allele and all winter wheat cultivars carried wild‐type TB1 alleles. To determine the impact of TB1 null alleles, this study examined durum wheat genotypes varying for TB1 null alleles created by ethyl methanesulfonate (EMS) mutagenesis. The goal was to determine the impact of TB1 null alleles on tillering, agronomic, and seed traits. The impact of TB1 null alleles was studied alone and together in field trials. The TB1 single‐ and double‐null mutants produced up to 15% more tillers and 18% with positive trends toward increased plant biomass. The results of this research demonstrate that the integration of EMS‐derived TB1 null alleles may prove useful in increasing small‐grain tillering to optimize plant biomass and yield under different growing conditions.
Short‐term outcomes of patients undergoing endoscopic submucosal dissection for colorectal lesions
Authors: Nakajima Yuki , Nemoto Daiki , Nemoto Tetsutaro , Takahata Yosuke , Aizawa Masato , Utano Kenichi , Isohata Noriyuki , Endo Shungo , Lefor Alan Kawarai , Togashi Kazutomo
Published: June 2022

Objectives

Endoscopic submucosal dissection (ESD) of colorectal lesions was invented in Japan, but postoperative management including hospital stay has not been reconsidered due to the Japanese insurance system. To explore appropriate postoperative management after colorectal ESD, we reviewed short‐term outcomes after ESD in non‐selected consecutive patients.

Methods

Patients who underwent colorectal ESD from April 2013 to September 2020 in one institution were reviewed. The primary outcome measure was the occurrence of adverse events stratified by the Clavien‐Dindo classification with five grades. A logistic regression model with the Firth procedure was applied to investigate predictors of severe (grade III or greater) adverse events.

Results

A total of 330 patients (female 40%, male 60%; median 72 years; IQR 65–80 years) with colorectal lesions (median 30 mm, IQR 23–40 mm; colon 77%, rectum 23%; serrated lesion 4%, adenoma 47%, mucosal cancer 30%, invasive cancer 18%) was evaluated. The en bloc resection rate was 97%. The median dissection time was 58 min (IQR: 38–86). Intraprocedural perforation occurred in 3%, all successfully treated by endoscopic clipping. No delayed perforations occurred. Postprocedural bleeding occurred in 3% on days 1–10 (median day 2); all were controlled endoscopically. Severe adverse events included only delayed bleeding. In analyzing severe adverse events in a multivariate logistic regression model with the Firth procedure, antithrombotic agent use (p = 0.016) and rectal lesions (p = 0.0010) were both significant predictors.

Conclusions

No serious adverse events occurred in this series. Four days of hospitalization may be too long for the majority of patients after ESD.
The Marinoan cap carbonate of Svalbard: Syngenetic marine dolomite with 17O‐anomalous carbonate‐associated sulphate
Authors: Fairchild Ian J. , Bao Huiming , Windmill Richard J. , Boomer Ian
Published: June 2022

Two cap carbonates overlying Cryogenian panglacial deposits are found in North‐East Svalbard of which the younger (635 Ma) forms the base of the Ediacaran Period. It is represented by a transgressive succession in which laminated dolostone, typically around 20 m thick (Member D1), is succeeded transitionally by a similar thickness of impure carbonates (Member D2). In Spitsbergen, there is evidence of microbially influenced sediment stabilisation and carbonate precipitation in the lower part of D1, whilst the upper part of D1 and D2 show centimetre‐decimetre‐scale graded units with undulatory lamination interpreted as evidence of storm activity. Carbonate originated as possible freshwater whitings, as well as microbial precipitates. Exhumed and eroded hardgrounds display replacive 10–30 μm dolomite crystals with cathodoluminescence characteristics consistent with early diagenetic manganese and iron reduction. Regionally, carbon isotope values consistently decrease by around 2‰ from around −3‰ over 30 m of section which is both a temporal and a bathymetric signal, but not a global one. An exponential decline in carbonate production predicted by box models is fitted by a semi‐quantitative sedimentation model. A mass‐anomalous 17O depletion in carbonate‐associated sulphate in dolomite, inherited from precursor calcite, decreases from −0.6 to −0.3‰ in the basal 15 m of section and then approaches background values. The post‐glacial anomalous 17O depletion in carbonate‐associated sulphate and barite elsewhere has been interpreted in terms of ultra‐high pCO2 at the onset of deglaciation. Such anomalies, with larger amplitude, have been reported in Svalbard from underlying lacustrine and tufaceous limestones representing a hyperarid glacial environment. The anomalous sulphate could be produced contemporarily, or the internally drained landscape may have continued to release 17O‐anomalous sulphate as it was transgressed during cap carbonate deposition. The late Cryogenian to earliest Ediacaran record in Svalbard provides the most complete record of the basal 17O‐depletion event in the world.
Retinoic acid signaling regulates late stages of semicircular canal morphogenesis and otolith maintenance in the zebrafish inner ear
Authors: Mackowetzky Kacey , Dicipulo Renée , Fox Sabrina C. , Philibert Danielle A. , Todesco Hayley , Doshi Jainil D. , Kawakami Koichi , Tierney Keith , Waskiewicz Andrew J.
Published: June 2022

Background

The vitamin A derivative all‐trans retinoic acid (RA) regulates early stages of inner ear development. As the early disruption of the RA pathway results in profound mispatterning of the developing inner ear, this confounds analyses of specific roles in later stages. Therefore, we used the temporal‐specific exposure of all‐trans RA or diethylaminobenzaldehyde to evaluate RA functions in late otic development.

Results

Perturbing late RA signaling causes behavioral defects analogous to those expected in larvae suffering from vestibular dysfunction. These larvae also demonstrate malformations of the semi‐circular canals, as visualized through (a) use of the transgenic strain nkhspdmc12a, a fluorescent reporter expressed in otic epithelium; and (b) injection of the fluorescent lipophilic dye DiI. We also noted the altered expression of genes encoding ECM proteins or modifying enzymes. Other malformations of the inner ear observed in our work include the loss or reduced size of the utricular and saccular otoliths, suggesting a role for RA in otolith maintenance.

Conclusion

Our work has identified a previously undescribed late phase of RA activity in otic development, demonstrating that vestibular defects observed in human patients in relation to perturbed RA signaling are not solely due to its early disruption in otic development.
A machine learning method for estimating the probability of presence using presence‐background data
Authors: Wang Yan , Samarasekara Chathuri L. , Stone Lewi
Published: June 2022

Estimating the prevalence or the absolute probability of the presence of a species from presence‐background data has become a controversial topic in species distribution modelling. In this paper, we propose a new method by combining both statistics and machine learning algorithms that helps overcome some of the known existing problems. We have also revisited the popular but highly controversial Lele and Keim (LK) method by evaluating its performance and assessing the RSPF condition it relies on. Simulations show that the LK method with the RSPF assumptions would render fragile estimation/prediction of the desired probabilities. Rather, we propose the local knowledge condition, which relaxes the predetermined population prevalence condition that has so often been used in much of the existing literature. Simulations demonstrate the performance of the new method utilizing the local knowledge assumption to successfully estimate the probability of presence. The local knowledge extends the local certainty or the prototypical presence location assumption, and has significant implications for demonstrating the necessary condition for identifying absolute (rather than relative) probability of presence from presence background without absence data in species distribution modelling.
Estimating survival and adoption rates of dependent juveniles
Authors: Street Phillip A. , Riecke Thomas V. , Williams Perry J. , Behnke Tessa L. , Sedinger James S.
Published: June 2022

Population growth and fitness are typically most sensitive to adult survival in long‐lived species, but variation in recruitment often explains most of the variation in fitness, as past selection has canalized adult survival. Estimating juvenile survival until age of independence has proven challenging, because marking individuals in this age class may directly affect survival. For Greater Sage‐grouse, uniquely marking juveniles in the first days of life likely results in adverse effects to survival, detection of juveniles is not perfect, and females adopt juveniles from other parents. These challenges are encountered by researchers studying avian and mammalian species with similar life histories, yet methods do not exist that explicitly estimate all these components of the recruitment process. We propose a novel data collection method and demographic model to simultaneously estimate rates of detection, survival, and adoption of juvenile individuals. Using multiple cameras to film the beginning of juvenile activity on specific days, we obtained counts of juveniles associated with marked females. Increases of juveniles to broods provided information that enabled us to estimate rates of adoption that can be applied at the population level. Losses from broods informed apparent survival. These losses could be attributed to death, or they could be chicks that were adopted by other females. We found evidence that apparent survival of juveniles was influenced by localized weather patterns when chicks were young. Similarly, we found that young chicks were more susceptible to the adverse effect of attending females being flushed by an observer. Both of these patterns diminished quickly as chicks aged. We provide the first‐ever estimates of interval‐specific adoption rates. Our results suggest that researchers should be cautious when designing studies to estimate juvenile survival. More importantly, they provide insight into adoption, a behavior that has been known to exist for decades.
Growth and development of an invasive forest insect under current and future projected temperature regimes
Authors: Walter Jonathan A. , Thompson Lily M. , Powers Sean D. , Parry Dylan , Agosta Salvatore J. , Grayson Kristine L.
Published: June 2022

Temperature and its impact on fitness are fundamental for understanding range shifts and population dynamics under climate change. Geographic climate heterogeneity, behavioral and physiological plasticity, and thermal adaptation to local climates make predicting the responses of species to climate change complex. Using larvae from seven geographically distinct wild populations in the eastern United States of the non‐native forest pest Lymantria dispar dispar (L.), we conducted a simulated reciprocal transplant experiment in environmental chambers using six custom temperature regimes representing contemporary conditions near the southern and northern extremes of the US invasion front and projections under two climate change scenarios for the year 2050. Larval growth and development rates increased with climate warming compared with current thermal regimes and tended to be greater for individuals originally sourced from southern rather than northern populations. Although increases in growth and development rates with warming varied somewhat by region of the source population, there was not strong evidence of local adaptation, southern populations tended to outperform those from northern populations in all thermal regimes. Our study demonstrates the utility of simulating thermal regimes under climate change in environmental chambers and emphasizes how the impacts from future increases in temperature can vary based on geographic differences in climate‐related performance among populations.
Land‐use change shifts and magnifies seasonal variations of the decomposer system in lowland tropical landscapes
Authors: Krashevska Valentyna , Stiegler Christian , June Tania , Widyastuti Rahayu , Knohl Alexander , Scheu Stefan , Potapov Anton
Published: June 2022

Deforestation and agricultural expansion in the tropics affect local and regional climatic conditions, leading to synergistic negative impacts on land ecosystems. Climatic changes manifest in increased inter‐ and intraseasonal variations and frequency of extreme climatic events (i.e., droughts and floods), which have evident consequences for aboveground biodiversity. However, until today, there have been no studies on how land use affects seasonal variations below ground in tropical ecosystems, which may be more buffered against climatic variation. Here, we analyzed seasonal variations in soil parameters, basal respiration, microbial communities, and abundances of soil invertebrates along with microclimatic conditions in rainforest and monocultures of oil palm and rubber in Sumatra, Indonesia. About 75% (20 out of 26) of the measured litter and soil, microbial, and animal parameters varied with season, with seasonal changes in 50% of the parameters depending on land use. Land use affected seasonal variations in microbial indicators associated with carbon availability and cycling rate. The magnitude of seasonal variations in microbial parameters in the soil of monocultures was almost 40% higher than in the soil of rainforest. Measured parameters were associated with short‐term climatic conditions (3‐day period air humidity) in plantations, but not in rainforest, confirming a reduced soil buffering ability in plantations. Overall, our findings suggest that land use temporally shifts and increases the magnitude of seasonal variations of the belowground ecosystem compartment, with microbial communities responding most strongly. The increased seasonal variations in soil biota in plantations likely translate into more pronounced fluctuations in essential ecosystem functions such as nutrient cycling and carbon sequestration, and these ramifications ultimately may compromise the stability of tropical ecosystems in the long term. As the observed seasonal dynamics is likely to increase with both local and global climate change, these shifts need closer attention for the long‐term sustainable management of plantation systems in the tropics.
Forecasting the combined effects of future climate and land use change on the suitable habitat of Davidia involucrata Baill
Authors: Tang Junfeng , Zhao Xuzhe
Published: June 2022

Accurately predicting the future distribution of species is crucial for understanding how species will response to global environmental change and for evaluating the effectiveness of current protected areas (PAs). Here, we assessed the effect of climate and land use change on the projected suitable habitats of Davidia involucrata Baill under different future scenarios using the following two types of models: (a) only climate covariates (climate SDMs) and (b) climate and land use covariates (full SDMs). We found that full SDMs perform significantly better than climate SDMs in terms of both AUC (p < .001) and TSS (p < .001) and also projected more suitable habitat than climate SDMs both in the whole study area and in its current suitable range, although D. involucrate is predicted to loss at least 26.96% of its suitable area under all future scenarios. Similarly, we found that these range contractions projected by climate SDMs would negate the effectiveness of current PAs to a greater extent relative to full SDMs. These results suggest that although D. involucrate is extremely vulnerability to future climate change, conservation intervention to manage habitat may be an effective option to offset some of the negative effects of a changing climate on D. involucrate and can improve the effectiveness of current PAs. Overall, this study highlights the necessity of integrating climate and land use change to project the future distribution of species.
Creating practices and strategies towards persistence for undeclared, Black males at Predominately White Institutions (PWIs)
Authors: McElderry Jonathan A.
Published: June 2022

The majority of research on Black males highlights the problems or barriers faced by this demographic due to the low retention and completion rates. A factor that is often not discussed when students enter college is their decision around initially declaring a major and its future impact on their persistence and college completion. This chapter explores practices and strategies for senior administrators in higher education to assist undeclared, Black male students at Predominately White Institutions (PWIs) toward persistence and ultimately college completion. The recommendations for practice in this chapter offer tangible tools to create a positive campus experience for Black male collegians, as well as educate and hold members of the campus community accountable.
Circulating TREM2 as a noninvasive diagnostic biomarker for NASH in patients with elevated liver stiffness
Authors: Indira Chandran Vineesh , Wernberg Charlotte Wilhelmina , Lauridsen Mette Munk , Skytthe Maria Kløjgaard , Bendixen Sofie Marchsteiner , Larsen Frederik Tibert , Hansen Camilla Dalby , Grønkjær Lea Ladegaard , Siersbæk Majken Storm , Caterino Tina Di , Detlefsen Sönke , Møller Holger Jon , Grøntved Lars , Ravnskjaer Kim , Moestrup Søren Kragh , Thiele Maja Sofie , Krag Aleksander , Graversen Jonas Heilskov
Published: June 2022

Background and Aims:

Reliable noninvasive biomarkers are an unmet clinical need for the diagnosis of NASH. This study investigates the diagnostic accuracy of the circulating triggering receptor expressed on myeloid cells 2 (plasma TREM2) as a biomarker for NASH in patients with NAFLD and elevated liver stiffness.

Approach and Results:

We collected cross‐sectional, clinical data including liver biopsies from a derivation (n = 48) and a validation cohort (n = 170) of patients with elevated liver stiffness measurement (LSM ≥ 8.0 kPa). Patients with NAFLD activity scores (NAS) ≥4 were defined as having NASH. Plasma TREM2 levels were significantly elevated in patients with NASH of the derivation cohort, with an area under the receiver operating characteristics curve (AUROC) of 0.92 (95% confidence interval [CI], 0.84–0.99). In the validation cohort, plasma TREM2 level increased approximately two‐fold in patients with NASH, and a strong diagnostic accuracy was confirmed (AUROC, 0.83; 95% CI, 0.77–0.89; p < 0.0001). Plasma TREM2 levels were associated with the individual histologic features of NAS: steatosis, lobular inflammation, and ballooning (p < 0.0001), but only weakly with fibrosis stages. Dual cutoffs for rule‐in and rule‐out were explored: a plasma TREM2 level of ≤38 ng/ml was found to be an optimal NASH rule‐out cutoff (sensitivity 90%; specificity 52%), whereas a plasma TREM2 level of ≥65 ng/ml was an optimal NASH rule‐in cutoff (specificity 89%; sensitivity 54%).

Conclusions:

Plasma TREM2 is a plausible individual biomarker that can rule‐in or rule‐out the presence of NASH with high accuracy and thus has the potential to reduce the need for liver biopsies and to identify patients who are eligible for clinical trials in NASH.
3D PED BURN app: A precise and easy‐to‐use pediatric 3D burn surface area calculation tool
Authors: Meevassana Jiraroch , Sumonsriwarankun Piyamit , Suwajo Poonpissamai , Nilprapha Kasama , Promniyom Pasu , Iamphongsai Seree , Pungrasmi Pornthep , Jindarak Sirachai , Kangkorn Tanasit , Angspatt Apichai
Published: June 2022

Background and aims

Calculating the precise total burn surface area is crucial when treating burn patients, particularly children. The Lund and Browder chart and Rule of Nines, 2‐dimensional diagrams that are widely used, are subject to high interrater variance, and they can severely overestimate the burn area. Previously, the adult 3‐dimensional burn area calculation mobile application was developed. Aiming to improve accuracy, a 3‐dimensional pediatric burn surface area calculation mobile application (“3D PED BURN”) was developed to overcome the limitations of the conventional methods.

Method

Fifteen 3‐dimensional pediatric burn surface area models based on detailed anthropometric measurements collected from 85 patients were developed and categorized into four age groups: <1 year; 1–4 years; 5–9 years, and 10–15 years. According to their weight and height, the models in each group were fractionated into large, medium, and small body sizes.

Result

A precise and easy‐to‐use application was developed based on these data. This application is a promising and more accurate calculation tool for burn surface area in pediatric patients. Its low inter‐rater variance makes it reliable for use by various healthcare personnel.

Conclusion

The 3D PED BURN app is a pediatric 3D burn surface area calculation tool that is both accurate and simple to use.
Safety and efficacy of coronavirus disease‐19 vaccines in chronic kidney disease patients under maintenance hemodialysis: A systematic review
Authors: Mehta Neha , Shah Sangam , Paudel Kiran , Chamlagain Rajan , Chhetri Santosh
Published: June 2022

Background and aims

Patients on maintenance dialysis are a high‐risk, immune‐compromised population with 15%–25% coronavirus disease (COVID‐19) mortality rate that has been underrepresented in COVID‐19 vaccination clinical trials. The aim of study was to review of those studies to determine the safety and efficacy of the COVID‐19 vaccination in chronic kidney disease (CKD) patients receiving maintenance hemodialysis systematically.

Methods

The effectiveness was assessed by looking at the humoral and cellular responses. The humoral response is defined as de novo IgG‐ or IgA‐anti‐SpikeS1 antibody positivity. The establishment of de novo T‐cell immunity after immunization was used to measure cellular response. Adverse results were also reported of the included studies to analyze the safety of COVID‐19 vaccines. Eight previous works were included in our study.

Results

Two doses of COVID‐19 vaccines were shown to be effective with seroconversion rate of humoral response ranging from 81% to 97% among eight studies. The T‐cell response was shown 67% and 100% in two studies. COVID‐19 vaccines did not have notable adverse events and hence can be considered safe.

Conclusion

Although a single dosage has not shown to improve humoral immune response in most hemodialysis trials, a double dose has been reported to improve seroconversion rate and humoral immune response. Further research are required to observe if hemodialysis patients generate effective T‐cell responses.
Microsurgical varicocelectomy for intratesticular varicocele with a history of orchiopexy for undescended testis
Authors: Takeshima Teppei , Usui Kimitsugu , Kuroda Shinnosuke , Kawahara Takashi , Komeya Mitsuru , Teranishi Jun‐ichi , Uemura Hiroji , Yumura Yasushi
Published: June 2022

Introduction

We report a case series of six patients with a chief complaint of infertility who underwent microsurgical varicocelectomy for intratesticular varicocele (ITV) after undergoing orchiopexy for undescended testis in their childhood.

Case presentation

The patients' median age was 34 years. The median age at which orchiopexy was performed was 4.5 years. All the cases of ITV were accompanied by extratesticular varicocele (ETV). All the patients underwent a microsurgical subinguinal varicocelectomy. At 3 months after operation, the ITV and ETV had disappeared in all the cases. Sperm density and motility increased in five and four patients, respectively.

Conclusion

ITV occurs at a relatively high frequency after orchiopexy for undescended testis. Disorder of the valvular function of the testicular vein in peeling the testicular vessels was thought to be a primary cause and is often found on the left side. Doppler ultrasonography of the testis is considered important for diagnosis.
Theoretical studies on excited‐state properties and luminescence mechanism of a Carbene–Metal–Amide Au(I) complex with thermally activated delayed fluorescence
Authors: Sun Xin‐Wei , Peng Ling‐Ya , Gao Yuan‐Jun , Ye Jin‐Ting , Cui Ganglong
Published: June 2022

Two‐coordinate Carbene−Metal−Amide (CMA) complexes with thermally activated delayed fluorescence (TADF) have attracted much attention owing to their excellent luminescence properties and potential applications in organic light‐emitting devices. However, the luminescence mechanism remains unclear. Herein, we took one CMA Au(I) complex as an example and investigate its relevant photophysics using both density functional theory (DFT) and time‐dependent DFT methods with a polarizable continuum model. The calculated absorption and emission spectra agree with the experimental data and the S1 and T1 states show mixed ligand to ligand charge transfer (CT) and ligand to metal CT characters. Small spatial overlap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) minimizes the energy difference between the S1 and T1 states (ΔEST). Properly large spin‐orbit coupling promotes the reverse intersystem crossing (rISC) process. At 300 K, the rISC process is much more efficient than the T1 phosphorescent emission, which leads to the TADF emission.
CB‐103: A novel CSL‐NICD inhibitor for the treatment of NOTCH‐driven T‐cell acute lymphoblastic leukemia: A case report of complete clinical response in a patient with relapsed and refractory T‐ALL
Authors: Medinger Michael , Junker Till , Heim Dominik , Tzankov Alexandar , Jermann Philip M. , Bobadilla Maria , Vigolo Michele , Lehal Rajwinder , Vogl Florian D. , Bauer Michael , Passweg Jakob
Published: June 2022

Relapsed T cell acute lymphoblastic leukaemia (T‐ALL) has a very poor prognosis. A 24‐year‐old patient with relapsed high‐risk T‐ALL (PTEN gene deletion; NOTCH1 mutation), was treated with the NOTCH inhibitor CB‐103. Within 1 week of starting CB‐103, the bone marrow was free of T‐ALL blast infiltration (MRD+) and successfully underwent allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Sequential samples of ctDNA to monitor the disease after allo‐HSCT showed a decrease of circulating Notch1 and PTEN alterations. This is the first T‐ALL patient treated with CB‐103. The observed clinical response encourages further exploration of CB‐103 in ALL.
COVID‐19 pandemic in Southern Brazil: Hospitalizations, intensive care unit admissions, lethality rates, and length of stay between March 2020 and April 2022
Authors: Wolf Jonas Michel , Petek Helena , Maccari Juçara G. , Nasi Luiz Antonio
Published: June 2022

Coronavirus disease 2019 (COVID‐19) pandemic spread rapidly with more than 515 million cases and 6.2 million deaths. Epidemiological factors are important for understanding the state of the pandemic. This study aims to evaluate the hospitalizations, intensive care unit (ICU) admissions, and lethality from March 2020 to April 2022. Data were collected from a hospital in Porto Alegre city, southern Brazil. The Mann–Whitney, analysis of variance, and Kruskal–Wallis tests were used to compare quantitative variables. Categorical variables were compared by Pearson's χ2 test. p values <0.05 for all tests were considered significant. Were observed 3784 hospitalizations. Males were 51.4% and the age was 60.4± 20.3. Intensive care unit (ICU) patients were 31.2%, the median length of stay (LOS) was 9.0 and lethality was 13.3%. ICU lethality was 34.5% versus 4.6% in other inpatients (p < 0.01). The LOS of ICU patients was 22.0 versus 7.0 in other inpatients (p < 0.01). The first peak (July–Novemebr 2020) showed ICU occupancy of 79.1%. The second peak (December 2020–June 2021) with 91.6% occupancy. The third peak January–March 2022 with 81.0% occupancy (p < 0.01). Lethality rates were 10.3% in 2020, 14.9% in 2021 and 15.4% in 2022 (p < 0.01). In conclusion, the ICU occupancy rate was higher in 2021 and the lethality rates of ICU patients were high during pandemic years (10.3% in 2020, 14.9% in 2021, and 15.2% in 2022). The lethality of these patients ranged from 25.0% in March to 21.8% in December 2020, from 20.9% in January 22.2% in Decemebr 2021, and 35.7% in January 2022 to 21.4% in April 2022. These data demonstrate that COVID‐19 is a critical illness, even in a private hospital setting.
The Sociomateriality of the Creative Process: Script Roles in Film Production
Authors: Anjo José Edemir da Silva , Tureta César
Published: June 2022

The article aims to identify and analyze the roles played by the script in the creative process of independent short film production. The theoretical framework is based on distributed creativity and sociomateriality. These approaches are complementary and helped us discuss how the script can shape the creativity of the subjects involved in the film production. We have followed the daily teamwork during the film production through participant observation, interviews, documents, photographs, and video. We identified three roles played by the script: (1) protagonist: centralizes creative ideas around its framing; (2) feature player: responsible for mediating creative actions, and (3) antagonist: hinders creative actions. Each of these roles directly influences the different stages of the creative process, which takes place through creativity distributed between people and artifacts. We conclude that artifacts have temporary roles in the creative process, and more than enhancing or limiting this process, they are an integral part of creativity. Therefore, humans and artifacts are entangled in the creative process and should not be analyzed separately.
Managing corporate social responsibility through social learning
Authors: Castillo Maria
Published: June 2022

Corporate Social Responsibility (CSR) in the Mexican financial sector is constructed through a social learning process in which four CSR dimensions: influencers; motivations; issues; and outcomes interact, influence each other, and adjust within the boundaries of the Mexican institutional context. By looking at the case of the Mexican financial sector, this paper aims to study how firms engage in the process of managing their corporate social responsibility strategies to generate sustained competitive advantage. It posits that many organizations already consider the different dimensions, but they do so in a siloed way, and that CSR management can be more efficient by engaging in a structured double learning loop that allows firms to adapt their strategy and help them create long‐term value for the firm and its stakeholders. Successfully engaging in social learning can also enhance the firm's legitimacy, but doing so requires strong coordination between different teams and leadership and the capacity to set shared objectives. This research contributes to CSR literature by proposing a model for understanding CSR as a social learning process, and by providing empirical evidence for the understanding of CSR from an emerging country context.
Liouville integrability and explicit solutions for a Frobenius‐coupled integrable lattice hierarchy
Authors: Yang Qianqian , Li Chuanzhong
Published: June 2022

We define a Frobenius‐coupled integrable lattice hierarchy including its Lax pair. Then the bi‐Hamiltonian structures of this hierarchy are constructed, which show that this hierarchy possesses Liouville integrability. We also obtained N‐fold Darboux transformation of the Frobenius‐coupled integrable lattice hierarchy. Finally, the explicit solutions after onefold Darboux transformation of this hierarchy are investigated when we choose appropriate seed solutions.
Fracture R‐CNN: An anchor‐efficient anti‐interference framework for skull fracture detection in CT images
Authors: Lin Xian , Yan Zengqiang , Kuang Zhuo , Zhang Hang , Deng Xianbo , Yu Li
Published: June 2022

Background

Skull fracture, as a common traumatic brain injury, can lead to multiple complications including bleeding, leaking of cerebrospinal fluid, infection, and seizures. Automatic skull fracture detection (SFD) is of great importance, especially in emergency medicine.

Purpose

Existing algorithms for SFD, developed based on hand‐crafted features, suffer from low detection accuracy due to poor generalizability to unseen samples. Deploying deep detectors designed for natural images like Faster Region‐based Convolutional Neural Network (R‐CNN) for SFD can be helpful but are of high redundancy and with nonnegligible false detections due to the cranial suture and skull base interference. Therefore, we, for the first time, propose an anchor‐efficient anti‐interference deep learning framework named Fracture R‐CNN for accurate SFD with low computational cost.

Methods

The proposed Fracture R‐CNN is developed by incorporating the prior knowledge utilized in clinical diagnosis into the original Faster R‐CNN. Specifically, based on the distributions of skull fractures, we first propose an adaptive anchoring region proposal network (AA‐RPN) to generate proposals for diverse‐scale fractures with low computational complexity. Then, based on the prior knowledge that cranial sutures exist in the junctions of bones and usually contain sclerotic margins, we design an anti‐interference head (A‐Head) network to eliminate the cranial suture interference for better SFD detection. In addition, to further enhance the anti‐interference ability of the proposed A‐Head, a difficulty‐balanced weighted loss function is proposed to emphasize more on distinguishing the interference areas from the skull base and the cranial sutures during training.

Results

Experimental results demonstrate that the proposed Fracture R‐CNN outperforms the current state‐of‐the‐art (SOTA) deep detectors for SFD with a higher recall and fewer false detections. Compared to Faster R‐CNN, the proposed Fracture R‐CNN improves the average precision (AP) by 11.74% and the free‐response receiver operating characteristic (FROC) score by 11.08%. Through validating on various backbones, we further demonstrate the architecture independence of Fracture R‐CNN, making it extendable to other detection applications.

Conclusions

As the customized deep learning–based framework for SFD, Fracture R‐CNN can effectively overcome the unique challenges in SFD with less computational cost, leading to a better detection performance compared to the SOTA deep detectors. Moreover, we believe the prior knowledge explored for Fracture R‐CNN would shed new light on future deep learning approaches for SFD.
Quantitative cerebrovascular reactivityMRIin mice using acetazolamide challenge
Authors: Wei Zhiliang , Li Yuguo , Hou Xirui , Han Zheng , Xu Jiadi , McMahon Michael T. , Duan Wenzhen , Liu Guanshu , Lu Hanzhang
Published: June 2022

Purpose

To develop a quantitative MRI method to estimate cerebrovascular reactivity (CVR) in mice.

Methods

We described an MRI procedure to measure cerebral vasodilatory response to acetazolamide (ACZ), a vasoactive agent previously used in human clinical imaging. Vascular response was determined by cerebral blood flow (CBF) measured with phase‐contrast or pseudo‐continuous arterial spin labeling MRI. Vasodilatory input intensity was determined by plasma ACZ level using high‐performance liquid chromatography. We verified the source of the CVR MRI signal by comparing ACZ injection to phosphate‐buffered saline injection and noninjection experiments. Dose dependence and feasibility of regional CVR measurement were also investigated.

Results

Cerebral blood flow revealed an exponential increase following intravenous ACZ injection, with a time constant of 1.62 min. In contrast, phosphate‐buffered saline or noninjection exhibited a slow linear CBF increase, consistent with a gradual accumulation of anesthetic agent, isoflurane, used in this study. When comparing different ACZ doses, injections of 30, 60, 120, and 180 mg/kg yielded a linear increase in plasma ACZ concentration (p < 0.0001). On the other hand, CBF changes under these doses were not different from each other (p = 0.50). The pseudo‐continuous arterial spin labeling MRI with multiple postlabeling delays revealed similar vascular responses at different postlabeling delay values. There was a regional difference in CVR (p = 0.005), with isocortex (0.81 ± 0.17%/[μg/ml]) showing higher CVR than deep‐brain regions. Mice receiving multiple ACZ injections lived for a minimum of 6 months after the study without noticeable aberrant behavior or appearance.

Conclusions

We demonstrated the proof‐of‐principle of a new quantitative CVR mapping technique in mice.
Deep‐learning synthesized pseudo‐CT for MR high‐resolution pediatric cranial bone imaging (MR‐HiPCB)
Authors: Eshraghi Boroojeni Parna , Chen Yasheng , Commean Paul K. , Eldeniz Cihat , Skolnick Gary B. , Merrill Corinne , Patel Kamlesh B. , An Hongyu
Published: June 2022

Purpose

CT is routinely used to detect cranial abnormalities in pediatric patients with head trauma or craniosynostosis. This study aimed to develop a deep learning method to synthesize pseudo‐CT (pCT) images for MR high‐resolution pediatric cranial bone imaging to eliminating ionizing radiation from CT.

Methods

3D golden‐angle stack‐of‐stars MRI were obtained from 44 pediatric participants. Two patch‐based residual UNets were trained using paired MR and CT patches randomly selected from the whole head (NetWH) or in the vicinity of bone, fractures/sutures, or air (NetBA) to synthesize pCT. A third residual UNet was trained to generate a binary brain mask using only MRI. The pCT images from NetWH (pCTNetWH) in the brain area and NetBA (pCTNetBA) in the nonbrain area were combined to generate pCTCom. A manual processing method using inverted MR images was also employed for comparison.

Results

pCTCom (68.01 ± 14.83 HU) had significantly smaller mean absolute errors (MAEs) than pCTNetWH (82.58 ± 16.98 HU, P < 0.0001) and pCTNetBA (91.32 ± 17.2 HU, P < 0.0001) in the whole head. Within cranial bone, the MAE of pCTCom (227.92 ± 46.88 HU) was significantly lower than pCTNetWH (287.85 ± 59.46 HU, P < 0.0001) but similar to pCTNetBA (230.20 ± 46.17 HU). Dice similarity coefficient of the segmented bone was significantly higher in pCTCom (0.90 ± 0.02) than in pCTNetWH (0.86 ± 0.04, P < 0.0001), pCTNetBA (0.88 ± 0.03, P < 0.0001), and inverted MR (0.71 ± 0.09, P < 0.0001). Dice similarity coefficient from pCTCom demonstrated significantly reduced age dependence than inverted MRI. Furthermore, pCTCom provided excellent suture and fracture visibility comparable to CT.

Conclusion

MR high‐resolution pediatric cranial bone imaging may facilitate the clinical translation of a radiation‐free MR cranial bone imaging method for pediatric patients.
Evaluation of the bioimpedance technique in newborns with a focus on electrode positioning: A prospective, randomized, crossover study
Authors: Toledo Luana F. M. , Medeiros Thatyana R. , Vieira Alan A. , Coca Velarde Luis Guillermo
Published: June 2022

Background

Bioelectrical impedance analysis (BIA) is a good alternative for assessing total body water in newborns. However, the lack of standardization of the method for its use in the neonatal population raises doubts about its reliability and external validation.

Objective

To compare resistance (R) and reactance (Xc) values measured by BIA with electrodes placed in the anatomical position and with electrodes placed at 5‐cm intervals.

Method

Prospective, randomized, crossover study, in which R and Xc values were measured using monofrequency BIA. The choice of the first position of the electrodes to be analyzed in each NB was performed by a simple randomization, and subsequent measurements were performed in rapid succession. The calculated sample size was 203 evaluations. The paired t test was used to compare the means of R and Xc, and the Bland‐Altman plot and linear regression were used to analyze how much the measured values were influenced by the electrode position.

Results

Significant differences were found in the R (855.25 ± 147.79 vs 618.95 ± 93.28 Ω) and Xc (50.94 ± 17.34 vs 39.76 ± 18.35 Ω) values measured with electrodes in the anatomical position and at 5‐cm intervals, respectively. The electrodes in the anatomical position produced R and Xc values 37.7% and 16.6%, respectively, higher on average when compared with 5‐cm intervals.

Conclusions

The distance between the electrodes influences the measurement of R and Xc by BIA. These results highlight the importance of defining a standard for the placement of electrodes in newborns for the use of these measures in neonatal clinical practice.
Care burden, coping styles and involvement in care in mothers of autistic children in pandemic of COVID‐19
Authors: Mohammad Fateme , Sani Niloofar , Oshvandi Khodayar , Masoumi Seyedeh Zahra , Khazaei Salman , Bashirian Saeid , Jenabi Ensiyeh , Barati Majid , Rezaei Mohammad , Borzou Seyed Reza
Published: June 2022

Aim

The aim of the present study was to investigate the burden of care, coping styles and involvement in the care of mothers of autistic children in the pandemic of COVID‐19 in Iranian society.

Design

A cross‐sectional study.

Methods

A total of 134 mothers completed questionnaires online. Data were analysed by descriptive statistics (frequency, percentage, mean and standard deviation) and independent t‐test, ANOVA and multiple linear regressions. The significance level was considered p < .05.

Result

Findings of the study found that burden of care has a strong and direct correlation with involvement in care (p < .001, r = .78) and strongly and indirectly correlated with coping styles (p < .001, r = −.82). Variables of coping styles, involvement in care, mothers' occupation and number of children, age and functional level of autism can predict 81.27% of the variance in care burden in these mothers.