bluuebunny/crossref_metadata_2025 huggingface dataset:
Busulfan‐containing conditioning regimens in allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia: A Taiwan observational study
Authors: Wang Yu‐Hung , Tien Feng‐Ming , Tsai Cheng‐Hong , Huang Huai‐Hsuan , Liu Jia‐Hau , Liao Xiu‐Wen , Tang Jih‐Luh , Yao Ming , Ko Bor‐Sheng
Published: July 2021

Background

Allogeneic stem cell transplantation (allo‐HSCT) is the ultimate cure for acute lymphoblastic leukemia (ALL).

Aim

This study was performed to compare the outcomes of ALL patients receiving busulfan (Bu) with cyclophosphamide (Cy)‐based or total body irradiation (TBI)‐based regimen in a Chinese population.

Methods

We enrolled 224 adult patients with ALL who received allo‐HSCT at National Taiwan University Hospital between 1997 and 2016.

Results

The median age at transplantation was 33 years. Before allo‐HSCT, 75.9% of patients attained first or late complete remission. A total of 141 patients (62.9%) received Bu/Cy‐based conditioning, either myeloablative (MA) or reduced‐intensity stem cell transplantation (RIST), and 83 patients received a TBI‐based regimen (MA‐TBI). Patients receiving the MA‐Bu regimen had longer relapse‐free survival (RFS) than those receiving the MA‐TBI regimen (median, 24.1 vs. 6.7 months, p = .044). There was no difference in overall survival (OS, MA‐Bu vs. MA‐TBI vs. RIST‐Bu: 39.4 vs. 28.2 vs. 13.1 months, p = .276), treatment‐related mortality (TRM), or incidences of grade 3–4 acute graft‐versus‐host disease (GvHD). Among patients receiving identical GvHD prophylactic regimens, there was no difference between MA‐Bu and MA‐TBI groups regarding the incidence of grade 3–4 acute GvHD, grade 2–4, and all‐grade chronic GvHD. In subgroup analysis, patients receiving oral busulfan had comparable RFS and OS to the intravenous busulfan group (p = .436 and p = .236, respectively), but a higher TRM (25% vs. 9.8%, p = .016). In the multivariable analysis, disease status before allo‐HSCT was the only risk factor impacting RFS and OS.

Conclusion

In summary, patients receiving Bu/Cy‐based or TBI‐based regimens as conditioning had similar results in terms of OS, TRM, and acute GvHD, whereas the use of myeloablative Bu/Cy resulted in a better RFS. A Bu‐based regimen could be an alternative conditioning choice for patients who are ineligible to receive TBI. Prospective and randomized controlled trials are warranted to validate the long‐term outcomes.
The influence of social media on stakeholder engagement and the corporate social responsibility of small businesses
Authors: Khanal Ananda , Akhtaruzzaman Muhammad , Kularatne Indrapriya
Published: July 2021

In recent decades, the concepts of corporate social responsibility (CSR) and social media have gained immense importance among businesses and their stakeholders. These concepts have gained popularity and acceptance among both large and small businesses of most industries. However, the existing CSR literature showed that most studies concentrated on large businesses, leaving the domain of small businesses under‐explored. The literature review revealed that only a few researchers had investigated the influence of social media on stakeholder engagement and the CSR of small businesses. This research aimed to explore the impacts of social media on the CSR of small businesses and used a concurrent mixed‐method research design, employing survey questionnaires from 82 participants and semi‐structured interviews with eight participants. The study conducted among the owners and managers of small businesses in a local government district in New Zealand discovered that many of them considered social media beneficial to engage with stakeholders and understand CSR trends. It also found that social media encouraged businesses to understand their vision, values and implement policies that are environmentally friendly and beneficial to the employees.
Asexual reproduction and vegetative growth of Bionectria ochroleuca in response to temperature and photoperiod
Authors: Zheng Yi , Xie Yichun , Xie Yan , Yu Shixiao
Published: July 2021

Growth and reproduction are two essential life‐history traits for fungi. Understanding life‐history strategies provides insight into the environmental adaption of species. Here, we investigated the colonial morphology, vegetative growth, and asexual reproduction of the ascomycete fungus Bionectria ochroleuca in response to a variety of environmental conditions. We demonstrated that the increased temperature from 15 to 25°C induced mycelial growth and conidiation in B. ochroleuca. We also found that the optimal temperatures for mycelial growth and conidial formation in this fungus species were 25 and 30°C, respectively. However, as the temperature increased from 25 to 30°C, mycelial growth was suppressed, but the total number of conidia was significantly increased. The shift in light–dark cycles dramatically changed the morphological features of the colonies and affected both vegetative growth and asexual reproduction. Under incubation environments of alternating light and dark (16:8 and 8:16 light:dark cycles), conidiophores and conidia in the colonies formed dense‐sparse rings and displayed synchronous wave structures. When the light duration was prolonged in the sequence of 0, 8, 16, and 24 hr per day, mycelial growth was suppressed, but conidiation was promoted. Together, our results indicate that temperature and light period may trigger a trade‐off between vegetative growth and asexual reproduction in B. ochroleuca.
Vericiguat in patients with atrial fibrillation and heart failure with reduced ejection fraction: insights from the VICTORIA trial
Authors: Ponikowski Piotr , Alemayehu Wendimagegn , Oto Ali , Bahit M. Cecilia , Noori Ebrahim , Patel Mahesh J. , Butler Javed , Ezekowitz Justin A. , Hernandez Adrian F. , Lam Carolyn S.P. , O'Connor Christopher M. , Pieske Burkert , Roessig Lothar , Voors Adriaan A. , Westerhout Cynthia , Armstrong Paul W. ,   for the VICTORIA Study Group
Published: July 2021

Aims

We evaluated the relation between baseline and new‐onset atrial fibrillation (AF) and outcomes, and assessed whether vericiguat modified the likelihood of new‐onset AF in patients with worsening heart failure (HF) with reduced ejection fraction in VICTORIA.

Methods and results

Of 5050 patients randomized, 5010 with recorded AF status at baseline were analysed. Patients were classified into three groups: no known AF (n = 2661, 53%), history of AF alone (n = 992, 20%), and AF on randomization electrocardiogram (n = 1357, 27%). Compared with those with no AF, those with history of AF alone had a higher risk of cardiovascular death [adjusted hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.01–1.47] without excess myocardial infarction or stroke; neither type of AF was associated with a higher risk of the primary composite outcome (time to cardiovascular death or first HF hospitalization), HF hospitalizations, or all cause‐death. The beneficial effect of vericiguat on the primary composite outcome and its components was evident irrespective of AF status at baseline. Over a median follow‐up of 10.8 months, new‐onset AF occurred in 6.1% of those with no AF and 18.3% with history of AF alone (P < 0.0001). These events were not influenced by vericiguat treatment (adjusted HR 0.93, 95% CI 0.75–1.16; P = 0.51), but were associated with an increase in the hazard of both primary and secondary outcomes.

Conclusions

Atrial fibrillation was present in nearly half of this high‐risk population with worsening HF. A history of AF alone at baseline portends an increased risk of cardiovascular death. Neither type of AF affected the beneficial effect of vericiguat. Development of AF post‐randomization was associated with an increase in both cardiovascular death and HF hospitalization which was not influenced by vericiguat.
Optimal operation of a smart railway station based on a multi‐energy hub structure considering environmental perspective and regenerative braking utilization
Authors: Akbari Saeed , Fazel Seyed Saeed , Jadid Shahram
Published: July 2021

This paper presents a stochastic bi‐objective model to reduce the operation cost and the carbon emission of a smart railway station along with dependent commercial buildings, according to a multi‐energy hub system's structure. The proposed energy hub system (EHS) includes a power, heating, and cooling subenergy hub. The recovered energy obtained from the regenerative braking (RB) during train deceleration is utilized to supply the load of EHS. To calculate the recovered energy, the motion of trains is simulated in MATLAB software. Furthermore, a demand response program (DRP) is integrated into the model to improve the flexibility of the EHS. Also, the uncertainty related to the photovoltaic generation and the power obtained from RB is considered. GAMS software is used to solve the bi‐objective model with the ɛ‐constraint approach. Then, to select the best possible solution, a fuzzy technique is engaged. Seven case studies are considered investigating the effect of exerting the DRP, utilizing the recovered energy, and employing the energy storage on operation cost and carbon emission. The simulation results demonstrate a significant improvement in operating cost and the carbon emission for the proposed EHS.
Rain on snow induced urban floods in cold maritime climate: Risk, indicators and trends
Authors: Andradóttir Hrund Ólöf , Arnardóttir Anna Rut , Zaqout Tarek
Published: July 2021

Urban floods pose a societal and economical risk. This study evaluated the risk and hydro‐meteorological conditions that cause pluvial flooding in coastal cities in a cold climate. Twenty years of insurance claims data and up to 97 years of meteorological data were analysed for Reykjavík, Iceland (64.15°N; <100 m above sea level). One third of the city's wastewater collection system is combined, and pipe grades vary from 0.5% to 10%. Results highlight semi‐intensive rain (<7 mm/h; ≤3 year return period) in conjunction with snow and frozen ground as the main cause for urban flood risk in a climate which undergoes frequent snow and frost cycles (avg. 13 and 19 per season, respectively). Floods in winter were more common, more severe and affected a greater number of neighbourhoods than during summer. High runoff volumes together with debris remobilized with high winds challenged the capacity of wastewater systems regardless of their age or type (combined vs. separate). The two key determinants for the number of insurance claims were antecedent frost depth and total precipitation volume per event. Two pluvial regimes were particularly problematic: long duration (13–25 h), late peaking rain on snow (RoS), where snowmelt enhanced the runoff intensity, elongated and connected independent rainfall into a singular, more voluminous (20–76 mm) event; shorter duration (7–9 h), more intensive precipitation that evolved from snow to rain. Closely timed RoS and cooling were believed to trigger frost formation. A positive trend was detected in the average seasonal snow depth and volume of rain and snowmelt during RoS events. More emphasis, therefore, needs to be placed on designing and operating urban drainage infrastructure with regard to RoS co‐acting with frozen ground. Furthermore, more detailed, routine monitoring of snow and soil conditions is important to predict RoS flood events.
Ammonia and nitrous oxide emission factors for excreta deposited by livestock and land‐applied manure
Authors: van der Weerden Tony J. , Noble Alasdair , de Klein Cecile A. M. , Hutchings Nicholas , Thorman Rachel E. , Alfaro Marta A. , Amon Barbara , Beltran Ignacio , Grace Peter , Hassouna Mélynda , Krol Dominika J. , Leytem April B. , Salazar Francisco , Velthof Gerard L.
Published: July 2021

Manure application to land and deposition of urine and dung by grazing animals are major sources of ammonia (NH3) and nitrous oxide (N2O) emissions. Using data on NH3 and N2O emissions following land‐applied manures and excreta deposited during grazing, emission factors (EFs) disaggregated by climate zone were developed, and the effects of mitigation strategies were evaluated. The NH3 data represent emissions from cattle and swine manures in temperate wet climates, and the N2O data include cattle, sheep, and swine manure emissions in temperate wet/dry and tropical wet/dry climates. The NH3 EFs for broadcast cattle solid manure and slurry were 0.03 and 0.24 kg NH3–N kg–1 total N (TN), respectively, whereas the NH3 EF of broadcast swine slurry was 0.29. Emissions from both cattle and swine slurry were reduced between 46 and 62% with low‐emissions application methods. Land application of cattle and swine manure in wet climates had EFs of 0.005 and 0.011 kg N2O–N kg–1 TN, respectively, whereas in dry climates the EF for cattle manure was 0.0031. The N2O EFs for cattle urine and dung in wet climates were 0.0095 and 0.002 kg N2O–N kg–1 TN, respectively, which were three times greater than for dry climates. The N2O EFs for sheep urine and dung in wet climates were 0.0043 and 0.0005, respectively. The use of nitrification inhibitors reduced emissions in swine manure, cattle urine/dung, and sheep urine by 45–63%. These enhanced EFs can improve national inventories; however, more data from poorly represented regions (e.g., Asia, Africa, South America) are needed.
Clinical characteristics of older Japanese patients with acute appendicitis: A post hoc analysis
Authors: Sasaki Yosuke , Komatsu Fumiya , Kashima Naoyasu , Maeda Tadashi , Honda Yoshiko , Shimada Nagato , Funahashi Kimihiko , Urita Yoshihisa
Published: July 2021

Background

Acute appendicitis (AA) in older patients can look different from AA in younger patients. Although it is crucial that primary care physicians can recognize AA in patients of any age, few Japanese studies have examined the characteristics of older AA patients. To address this, we evaluated the clinical characteristics of older Japanese patients with AA.

Methods

We performed a post hoc analysis of the data from a previous Japanese single‐center study. We analyzed the clinical information of both younger (age: 16–64 years) and older patients (age: ≥65 years).

Results

A cohort of 236 patients consisting of 219 (92.8%) younger patients and 17 (7.2%) older patients was evaluated. The median ages of the younger and older patients were 34 (interquartile range [IR], 24–45) and 78 years (IR, 74–81), respectively. The prevalence of complicated appendicitis (CA) (older: 41.2% vs. younger: 14.2%), comorbidities (70.6% vs. 13.2%), and thrombocytopenia (17.7% vs. 4.1%), along with serum C‐reactive protein (CRP) level (6.7 mg/dl vs. 1.0 mg/dl), was significantly higher in older patients. Significantly fewer older patients had epigastric pain (17.7% vs. 53.0%). Logistic regression evaluating the characteristics of older AA patients showed that CRP >5 mg/dl had a high odds ratio (OR) (5.01; 95% CI, 1.73–14.54), while epigastric pain had a low OR (0.24; 95% CI, 0.06–0.90).

Conclusion

Our study reveals a higher prevalence of CA and comorbidities in older patients, and suggests that a lack of epigastric pain, thrombocytopenia, and higher serum CRP level are characteristics of older AA patients.
Characterization of AlGaN/GaN based HEMT for low noise and high frequency application
Authors: Dubey Shashank Kumar , Mishra Meena , Islam Aminul
Published: July 2021

This article presents a detailed study on AlGaN/GaN based HEMT for DC (such as ID − VDS, ID − VGS and gm), RF (such as cut off frequency, fT and maximum oscillation frequency, fMAX) and noise parameters (such as minimum noise figure (NFmin), noise resistance (Rn) and optimum reflection coefficient (Гopt)). AlGaN/GaN based HEMT having gate length 250 nm and 500 nm have been simulated and verified on the Silvaco TCAD tool.
Correlational analysis of chemokine and inflammatory cytokine expression in the intervertebral disc and blood in patients with lumbar disc disease
Authors: Hiyama Akihiko , Suyama Kaori , Sakai Daisuke , Tanaka Masahiro , Watanabe Masahiko
Published: July 2021

The involvement of intervertebral disc (IVD) tissues, whole blood (WB) cytokines, and chemokines in pain in patients with lumbar degenerative disc disease (LDD) is unknown. We investigated the relationships between inflammatory cytokines and chemokines in human IVD tissues and WB samples and their association with pain. Expression levels of chemokines and cytokine gene expression were measured in samples from 20 patients with LDD and compared between IVD tissues and WB samples. The associations between WB chemokine and cytokine gene expression levels and pain intensity (numeric rating scale) were also analyzed. The mRNA of C‐C chemokine ligand 20 (CCL20), C‐C chemokine receptor 6 (CCR6), interleukin‐6 (IL‐6), IL‐1β, IL‐17, and tumor necrosis factor‐α (TNF‐α) was expressed in degenerated IVD tissues. Pearson's product–moment correlation analysis produced positive correlations between CCR6 and IL‐6 expression levels in IVD tissues (r = 0.845, p < 0.001) and WB samples (r = 0.963, p < 0.001). WB IL‐6 and CCR6 mRNA expression levels correlated significantly with present pain, maximum pain, and average pain. By contrast, low back pain (LBP) did not correlate with serum chemokine/cytokine expression. This is the first study to report correlations between chemokine and inflammatory cytokine gene expression levels in IVD tissues and WB samples in patients with LDD in relation to pain intensity. WB CCR6 and IL‐6 gene expression levels correlated significantly with present pain, maximum pain, and average pain, but not with LBP. These data provide a new understanding of the role of chemokines and inflammatory cytokines in patients with LDD and may lead to new treatment strategies for pain.
Antenatal corticosteroids affecting enteral feeding and growth of preterm infants: A retrospective cohort study
Authors: Luo Ping , Liu Xudong , Ma Liya , Chen You , Zhang Kun , Zhou Ping , Jiang Yan‐Nan , Jiang Ping‐Ping
Published: July 2021

Background

Treatment of antenatal corticosteroids (ACSs) to women at risk of preterm labor can decrease neonatal mortality and morbidity. However, effect of ACS exposure on enteral feeding and body growth of preterm infants remains elusive.

Methods

This retrospective study collected information of eligible singleton infants born between 22+0 and 36+6 weeks’ gestation from 2017 to 2019. Logistic regression and multivariate linear regression were adopted to examine the associations of the ACS exposure with various outcomes of enteral feeding and growth considering potential confounders. Stratified analysis was performed based on gestational age (GA) (<34 vs ≥34 weeks).

Results

Of the 1694 preterm infants included, 1222 (72.1%) were exposed to ACSs. Infants with ACS exposure had a higher incidence of feeding intolerance (odds ratio 1.51; 95% CI, 1.05 to 2.20; P = .03), slower advancement of enteral feeding (β coefficient −0.86; 95% CI, −1.48 to −0.25; P = .01), and lower delta body‐weight z‐scores (β coefficient−0.13; 95% CI, −0.18 to −0.08; P < .001). Unlike in infants with GA <34 weeks, ACS exposure was associated with slower advancement of enteral feeding, longer time to regain birth weight, and lower delta body‐weight z‐scores in the ones with GA ≥34 weeks.

Conclusion

ACS exposure is associated with poorer enteral feeding process and body growth in our study population, which is more prominent in late preterm infants. A multicenter prospective study and mechanistic studies using animal models are required.
Methods for population adjustment with limited access to individual patient data: A review and simulation study
Authors: Remiro‐Azócar Antonio , Heath Anna , Baio Gianluca
Published: July 2021

Population‐adjusted indirect comparisons estimate treatment effects when access to individual patient data is limited and there are cross‐trial differences in effect modifiers. Popular methods include matching‐adjusted indirect comparison (MAIC) and simulated treatment comparison (STC). There is limited formal evaluation of these methods and whether they can be used to accurately compare treatments. Thus, we undertake a comprehensive simulation study to compare standard unadjusted indirect comparisons, MAIC and STC across 162 scenarios. This simulation study assumes that the trials are investigating survival outcomes and measure continuous covariates, with the log hazard ratio as the measure of effect. MAIC yields unbiased treatment effect estimates under no failures of assumptions. The typical usage of STC produces bias because it targets a conditional treatment effect where the target estimand should be a marginal treatment effect. The incompatibility of estimates in the indirect comparison leads to bias as the measure of effect is non‐collapsible. Standard indirect comparisons are systematically biased, particularly under stronger covariate imbalance and interaction effects. Standard errors and coverage rates are often valid in MAIC but the robust sandwich variance estimator underestimates variability where effective sample sizes are small. Interval estimates for the standard indirect comparison are too narrow and STC suffers from bias‐induced undercoverage. MAIC provides the most accurate estimates and, with lower degrees of covariate overlap, its bias reduction outweighs the loss in precision under no failures of assumptions. An important future objective is the development of an alternative formulation to STC that targets a marginal treatment effect.
Establishing multilayered coating on Mo–12Si–8.5 B alloy by Si pack cementation and its oxidation behavior at 900°C–1300°C
Authors: Wang Juan , Li Bin , Li Rui , Chen Xuan , Zhang Guojun
Published: July 2021

A multilayered oxidation protection coating consisting of MoSi2 outer layer, Mo5Si3 internal layer, and Mo5SiB2/MoB inner layer was developed on the surface of Mo–12Si–8.5B 1.0 wt% ZrB2 alloy via Si pack cementation. The multilayered coating significantly enhanced the oxidation resistance of the alloy at 900°C, 1100°C, and 1300°C in the air by exhibiting negligible oxidation recession. MoSi2 outer layer provided admirable oxidation protection for the alloy at high temperatures by forming a thin and protective SiO2‐rich glass scale on its surface. This was supplemented by the Mo5Si3 internal layer and Mo5SiB2/MoB inner layer that reduced the thermal expansion mismatch between the MoSi2 outer layer and substrate, and therefore no obvious cracks were found in the MoSi2 outer layer. More importantly, the Mo5SiB2/MoB layer as an in situ barriers of Si interdiffusion ensured the stable existence of MoSi2 and Mo5Si3 layers without obvious thickness change during oxidation at 900°C and 1100°C. Mechanical property test indicated that the formation of the coating layers could not affect the fracture toughness of the alloy.
Solriamfetol for Excessive Daytime Sleepiness in Parkinson's Disease: Phase 2 Proof‐of‐Concept Trial
Authors: Videnovic Aleksandar , Amara Amy W. , Comella Cynthia , Schweitzer Paula K. , Emsellem Helene , Liu Kris , Sterkel Amanda L. , Gottwald Mildred D. , Steinerman Joshua R. , Jochelson Philip , Zomorodi Katie , Hauser Robert A.
Published: July 2021

Background

Solriamfetol is approved (US and EU) for excessive daytime sleepiness (EDS) in narcolepsy and obstructive sleep apnea.

Objectives

Evaluate solriamfetol safety/efficacy for EDS in Parkinson's disease (PD).

Methods

Phase 2, double‐blind, 4‐week, crossover trial: adults with PD and EDS were randomized to sequence A (placebo, solriamfetol 75, 150, 300 mg/d), B (solriamfetol 75, 150, 300 mg/d, placebo), or C (placebo). Outcomes (safety/tolerability [primary]; Epworth Sleepiness Scale [ESS]; Maintenance of Wakefulness Test [MWT]) were assessed weekly. P values are nominal.

Results

Common adverse events (n = 66): nausea (10.7%), dizziness (7.1%), dry mouth (7.1%), headache (7.1%), anxiety (5.4%), constipation (5.4%), dyspepsia (5.4%). ESS decreased both placebo (−4.78) and solriamfetol (−4.82 to −5.72; P > 0.05). MWT improved dose‐dependently with solriamfetol, increasing by 5.05 minutes with 300 mg relative to placebo (P = 0.0098).

Conclusions

Safety/tolerability was consistent with solriamfetol's known profile. There were no significant improvements on ESS; MWT results suggest possible benefit with solriamfetol in PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Expert recommendations and clinical considerations in the use of onasemnogene abeparvovec gene therapy for spinal muscular atrophy
Authors: Kichula Elizabeth A. , Proud Crystal M. , Farrar Michelle A. , Kwon Jennifer M. , Saito Kayoko , Desguerre Isabelle , McMillan Hugh J.
Published: July 2021

Spinal muscular atrophy (SMA) is an autosomal recessive, neurodegenerative disease caused by biallelic mutations in the survival motor neuron 1 (SMN1) gene. SMA is characterized by motor neuron degeneration, resulting in progressive muscle atrophy and weakness. Before the emergence of disease‐modifying therapies, children with the most severe form of SMA would never achieve the ability to sit independently. Only 8% survived beyond 20 months of age without permanent ventilator support. One such therapy, onasemnogene abeparvovec, an adeno‐associated virus–based gene replacement therapy, delivers functional humanSMNthrough a one‐time intravenous infusion. In addition to substantially improving survival, onasemnogene abeparvovec was found to increase motor milestone attainment and reduce the need for respiratory or nutritional support in many patients. This expert opinion provides recommendations and practical considerations on the patient‐centered decisions to use onasemnogene abeparvovec. Recommendations include the need for patient‐centered multidisciplinary care and patient selection to identify those with underlying medical conditions or active infections to reduce risks. We also describe the importance of retesting patients with elevated anti–adeno‐associated virus serotype 9 antibodies. Recommendations for prednisolone tapering and monitoring for potential adverse events, including hepatotoxicity and thrombotic microangiopathy, are described. The need for caregiver education on managing day‐to‐day care at time of treatment and patient‐ and family‐centered discussions on realistic expectations are also recommended. We detail the importance of following standard‐of‐care guidance and long‐term monitoring of all children with SMA who have received one or more disease‐modifying therapy using registries. We also highlight the need for presymptomatic or early symptomatic treatment of this disorder.
Maize genetics through the lens of many disciplines: The career of George Beadle
Authors: Hrabik Grant , Milam Noah , Lambley Madison , Durham Brooks Tessa
Published: July 2021

Core Ideas

George Beadle was a first‐generation college who eventually won the Nobel Prize.

Beadle had a central interest in the function of genes and the origin of maize.

Driven by big questions, Beadle collaborated across biological disciplines to answer them.

Beadle used three different organisms in his research to see several sides of the same problem.

Beadle showed incredible tenacity in circling back decades later to confirm maize origins.
Characterization and Management of Adverse Reactions in Patients with Advanced Endometrial Carcinoma Treated with Lenvatinib Plus Pembrolizumab
Authors: Makker Vicky , Taylor Matthew H. , Oaknin Ana , Casado Herraez Antonio , Orlowski Robert , Dutta Lea , Ren Min , Zale Melissa , O'Malley David M.
Published: July 2021

Background

The combination of lenvatinib plus pembrolizumab has shown efficacy in treatment of advanced endometrial carcinoma (that is not microsatellite instability–high or mismatch repair deficient) following prior systemic therapy in any setting in the open-label, single-arm, phase Ib/II Study 111/KEYNOTE-146. With the exception of hypothyroidism, the safety profile of the combination was comparable to that of each monotherapy. Given the medical complexity and fragility of patients with endometrial carcinoma, further characterization of adverse reactions (ARs) associated with treatment will help health care professionals to optimize treatment with lenvatinib plus pembrolizumab combination therapy.

Patients and Methods

In Study 111/KEYNOTE-146, patients received lenvatinib at a starting dose of 20 mg orally once daily and pembrolizumab 200 mg intravenously every 3 weeks. Selected ARs (hypertension, fatigue, nausea/vomiting, diarrhea, decreased appetite/weight loss, hypothyroidism, palmar-plantar erythrodysesthesia syndrome, musculoskeletal pain, stomatitis, and proteinuria) were chosen for detailed post hoc analyses.

Results

Median times to first onset of the selected ARs in this analysis all occurred within the first 10 weeks of treatment. Of the selected ARs, grade ≥3 severity of fatigue, hypertension, and nausea occurred in ≥5% of patients. Overall incidence of hypothyroidism was 51%, primarily of grade 2 severity (46%). Most of the ARs assessed were managed with a combination of study drug dose modifications and concomitant medications.

Conclusion

No new safety signals were identified and the toxicity profile in this study was manageable with supportive medications, dose interruptions, and/or lenvatinib dose reductions. This analysis provides AR management guidance for patients with endometrial cancer receiving lenvatinib plus pembrolizumab combination therapy.

Implications for Practice

Lenvatinib plus pembrolizumab has shown efficacy in the treatment of patients with advanced endometrial carcinoma (that is, not microsatellite instability–high or mismatch repair deficient) following at least one prior systemic therapy in any setting. Patients may experience toxicity associated with this combination, including adverse reactions of hypertension, fatigue, nausea/vomiting, diarrhea, decreased appetite/weight loss, hypothyroidism, palmar-plantar erythrodysesthesia syndrome, musculoskeletal pain, stomatitis, and proteinuria. These adverse reactions may be managed with a combination of concomitant supportive care medications and judicious lenvatinib dose modifications. This article provides context and guidance for the recognition and management of adverse reactions in patients receiving lenvatinib plus pembrolizumab.
A Cancer by Any Other Name
Authors: Khan Adeel M.
Published: July 2021

This narrative on multiple myeloma in a clinical setting reflects on how medical jargon may confuse patients and their families.
Microparticles based on alginate/chitosan/casein three‐dimensional system for oral insulin delivery
Authors: Xu Zhenyu , Chen Long , Duan Xiaoya , Li Xueming , Ren Hao
Published: July 2021

In the past, oral insulin has been developed to reduce the suffering of diabetic patients. However, the physiological barriers in gastrointestinal (GI) tract are the major challenges in oral delivery of insulin. In this study, a novel oral delivery system of insulin called NiM (NPs in MPs) has been developed to overcome the GI barriers, which based on a three‐dimensional system of biocompatible chitosan/alginate/casein. Alginate/chitosan nanoparticles (AC‐NPs) were firstly prepared by ionic pre‐gel method and complexation with polyelectrolytes. Then, they were subsequently coated with casein as a protective agent to form NiM, which could keep stability and physiological activity of insulin in gastric tract. The characterization of NiM showed stable hydrodynamic parameters, and the entrapment efficiency of insulin reached 51.1%. In vitro, only 13.5% of insulin was released in the simulated gastric fluid for the first 2 h. But about 57.4% of insulin was slowly released in the simulated intestinal fluid for 10 h. These results indicated that the coating of casein could increase stability of insulin in gastric tract and control release of insulin in intestinal tract. Furthermore, NiM provided a sustained and significant reduction of the blood glucose levels of diabetic mice. Overall, the results demonstrated that our formed NiM may be a promising oral delivery system of insulin for diabetic patients.
Synergistic effect of ZnO and TiO2 nanoparticles on the thermal stability and mechanical properties of glass fiber‐reinforced LY556 epoxy composites
Authors: Thipperudrappa Sridhar , Hiremath Anupama , Kurki Nagaraj Bharath
Published: July 2021

The article discusses the fabrication, mechanical characterization, and heat resistance of nano ZnO‐TiO2‐filled glass fiber‐reinforced LY556 epoxy composites, with focus on the synergistic effect of ZnO and TiO2 nanofillers. The fabrication of the composite laminates is achieved by the addition of the nanofillers in different wt% ranging from 1 to 5 wt%. The composites are prepared using simple hand layup technique followed by curing under vacuum. The 3D atomic force microscopy scans indicated even distribution of the nanofillers up to 2 wt% loading. Severe agglomeration of the nanofillers is evident for 3 to 5 wt% loading. The surface roughness, microhardness, flexural strength, tensile strength, and impact strength of the composites indicate a relationship with dispersion, wt% loading, and the wettability of the nanofiller with the LY556. In general, it is found that the incorporation of hard nanofillers favored the improvement of impact strength to a greater extent compared to tensile and flexural strengths. Detailed analysis of the obtained mechanical property values favors an optimum 2 wt% incorporation of the selected nanofillers to obtain improvement in various strength values of the fabricated composites. The thermal stability of the fabricated composites improved through the incorporation of ceramic nanofillers.
The Habitual Tendencies Questionnaire: A tool for psychometric individual differences research
Authors: Ramakrishnan Smriti , Robbins Trevor W. , Zmigrod Leor
Published: July 2021

Habits are automatic responses to learned stimuli or contextual cues that are insensitive to goals. Although habits may allow for automated behaviours that increase efficiency in our daily lives, an over‐reliance on habits has been suggested to contribute to disorders such as obsessive–compulsive disorder (OCD). There are currently few established measures of individual differences in habitual tendencies. To fill this gap, the present study generated and validated a novel 11‐item scale, the Habitual Tendencies Questionnaire (HTQ), to measure individual differences in habitual tendencies in the general population. In Study 1, factor analysis revealed three underlying subcomponents of the HTQ: Compulsivity, Preference for Regularity, and Aversion to Novelty, with Compulsivity showing the strongest association with subclinical OCD symptomatology. Study 2 validated the HTQ and replicated the findings of Study 1 in a larger sample, and explored relationships with other personality traits. The results emphasise the importance of measuring individual variation in habitual thinking styles, illustrating that different facets of habitual tendencies may contribute to diverse behavioural and clinical outcomes. The present investigation provides a new, reliable way of measuring habitual tendencies and has important implications for future explorations into the nature of individual differences from a dimensional perspective to psychiatry.
The Application of Sputtered Gallium Oxide as Buffer for Cu(In,Ga)Se2 Solar Cells
Authors: Witte Wolfram , Paetel Stefan , Menner Richard , Bauer Andreas , Hariskos Dimitrios
Published: July 2021

Crystalline gallium oxide is a promising wide‐bandgap semiconductor material, especially for applications in high‐frequency and high‐power devices. With an optical bandgap energy well above 4 eV, which implies no visible light absorption, it is also a candidate for one of the front‐side layers in thin‐film solar cells. X‐ray amorphous gallium oxide (a‐Ga2O3) deposited by RF magnetron sputtering is applied as an n‐type buffer layer in substrate‐type configuration solar cells based on industry‐relevant inline coevaporated Cu(In,Ga)Se2 (CIGS) absorbers, which include an i‐ZnO/ZnO:Al bilayer as the front electrode. The cells exhibit an efficiency peak at Ga2O3 deposition temperatures in the range of 140–180 °C and show mostly a gain in short‐circuit current density compared with the CdS‐buffered reference cells, as a result of the high optical bandgap of a‐Ga2O3 in the range of 4.6–4.8 eV. The CIGS solar cells with sputtered a‐Ga2O3 buffers reach efficiencies of almost 14%, lacking in open‐circuit voltage and fill factor, whereas the CdS‐buffered cells are on a 16–17% level. Light soaking of the cells leads to a slight improvement of the fill factor, but the gap in open‐circuit voltage of 80–100 mV in contrast to the CdS‐buffered reference cells remains unaffected.
Fractional paradigms in quantum chemistry
Authors: Mostafanejad Mohammad
Published: July 2021

The realization of fractional quantum chemistry is presented. Adopting the integro‐differential operators of the calculus of arbitrary‐order, we develop a general framework for the description of quantum nonlocal effects in the complex electronic environments. After a brief overview of the historical and fundamental aspects of the calculus of arbitrary‐order, various classes of fractional Schrödinger equations are discussed and pertinent controversies and open problems around their applications to model systems are detailed. We provide a unified approach toward fractional generalization of the quantum chemical models such as Hartree–Fock and Kohn–Sham density functional theory and develop fractional variants of the fundamental molecular integrals and correlation energy. Furthermore, we offer various strategies for modeling static‐ and dynamic‐order quantum nonlocal effects through constant‐ and variable‐order fractional operators, respectively. Possible directions for future developments of fractional quantum chemistry are also outlined.
RobustH∞output feedback control for type‐2Takagi‐Sugenofuzzy systems with multiple time‐delays and disturbances: A descriptor redundancy approach
Authors: Zheng Wei , Zhang Zhiming , Sun Fuchun , Wen Shuhuan , Li Xiaolei , Wang Hongbin
Published: July 2021

TheH∞stability analysis and interval type‐2 Takagi‐Sugeno (T‐S) fuzzy control is studied for a class of interval type‐2 T‐S fuzzy systems. Firstly, the interval type‐2 T‐S fuzzy model is employed to approximate the system plant. Secondly, the delay‐dependent interval type‐2 T‐S fuzzy dynamic output feedback controller is designed. Thirdly, two classes of stability conditions in terms of linear matrix inequalities (LMIs) are derived, and the closed‐loop system is asymptotically stable and prescribedH∞performance is achieved. The delay‐dependent interval type‐2 T‐S fuzzy dynamic output feedback controller is designed to relax the control design conditions. The descriptor redundancy method is employed for avoiding the crossing vectors between the system gain matrices and controller gain matrices. The delay‐dependent Lyapunov functional with descriptor redundancy matrix is introduced, and the upper and lower membership functions information is considered. Some slack matrices are introduced via the upper and lower membership functions information to solve the obtained LMIs. Finally, simulation examples are performed to show the effectiveness of the proposed methods.
Revisiting Solvent Additives for the Fabrication of Polymer:Fullerene Solar Cells: Exploring a Series of Benzaldehydes
Authors: Sprau Christian , Kattenbusch Jens , Li Yonghe , Müller Erich , Gerthsen Dagmar , Berger Rüdiger , Michels Jasper J. , Colsmann Alexander
Published: July 2021

The power conversion efficiencies of organic solar cells delicately depend on the morphology of the light‐harvesting bulk heterojunctions (BHJ). Upon deposition from solution, the formation of tailored bicontinuous networks of polymers and fullerenes is often achieved using combinations of solvents and solvent additives. Common wisdom infers that best solar cell performances are achieved when the solvent additives exhibit excellent fullerene solubility. Herein, this concept is revisited based on the investigation of a series of structurally similar, substituted benzaldehydes. It is concluded that the solvent additives do not only have to feature the commonly accepted good fullerene solubility, but must also exhibit lowest polymer solubility to suppress liquid–liquid demixing and hence achieve best solar cell performance. Thus, this study adds an important item to the list of selection criteria of solvent additives toward the production of polymer:fullerene solar cells with optimized power conversion efficiencies. The microscopic picture of the resulting domain configurations within the light‐harvesting layers is developed around comprehensive multiscale investigations of the BHJ morphology, using atomic force microscopy, scanning transmission electron microscopy, and nano‐infrared microscopy. The latter is operated in two complementary modes, one of which is more bulk sensitive, whereas the other mode is surface sensitive.
Gap Junction-Mediated Cell-Cell Interaction Between Transplanted Mesenchymal Stem Cells and Vascular Endothelium in Stroke
Authors: Kikuchi-Taura Akie , Okinaka Yuka , Saino Orie , Takeuchi Yukiko , Ogawa Yuko , Kimura Takafumi , Gul Sheraz , Claussen Carsten , Boltze Johannes , Taguchi Akihiko
Published: July 2021

We have shown previously that transplanted bone marrow mononuclear cells (BM-MNC), which are a cell fraction rich in hematopoietic stem cells, can activate cerebral endothelial cells via gap junction-mediated cell-cell interaction. In the present study, we investigated such cell-cell interaction between mesenchymal stem cells (MSC) and cerebral endothelial cells. In contrast to BM-MNC, for MSC we observed suppression of vascular endothelial growth factor uptake into endothelial cells and transfer of glucose from endothelial cells to MSC in vitro. The transfer of such a small molecule from MSC to vascular endothelium was subsequently confirmed in vivo and was followed by suppressed activation of macrophage/microglia in stroke mice. The suppressive effect was absent by blockade of gap junction at MSC. Furthermore, gap junction-mediated cell-cell interaction was observed between circulating white blood cells and MSC. Our findings indicate that gap junction-mediated cell-cell interaction is one of the major pathways for MSC-mediated suppression of inflammation in the brain following stroke and provides a novel strategy to maintain the blood-brain barrier in injured brain. Furthermore, our current results have the potential to provide a novel insight for other ongoing clinical trials that make use of MSC transplantation aiming to suppress excess inflammation, as well as other diseases such as COVID-19 (coronavirus disease 2019).
Impact of research on contagious ovine digital dermatitis on the knowledge and practices of UK sheep farmers and veterinarians
Authors: Duncan Jennifer S. , Angell Joseph W. , Grove‐White Dai , Walsh Tessa R. , Seechurn Nicola , Carter Stuart , Evans Nicolas
Published: July 2021

Background: Contagious ovine digital dermatitis (CODD) is a common foot disease of sheep which causes a severe form of lameness and can be difficult to control. Recent research has provided evidence‐based guidance on diagnosis, treatment and farm management control. The aim of this study was to determine the uptake of this guidance on the knowledge and practices of UK sheep farmers and veterinarians and identify priorities for future research.

Methods: Data were collected in 2019–2020 by electronic surveys of UK sheep veterinarians and farmers distributed through sheep industry organisations and social media.

Results: Two hundred eight‐four sheep farmers and 77 veterinarians responded to the surveys. Fifty‐two per cent of farmers and 70% of vets considered that their management of CODD had improved as a direct result of recent research evidence on the disease. The principle areas improved for both sectors were biosecurity advice and use of antibiotic treatments. Farmers and veterinarians reported that the priorities for future research should be in therapeutics, vaccine development and the understanding of disease transmission.

Conclusion: There has been strong uptake of recent evidence‐based veterinary medicine by farmers and veterinarians for the management of CODD, particularly in the areas of biosecurity and responsible antibiotic use.
A systematic review on the effect of Ginger (Zingiber officinale) on improvement of biological and fertility indices of sperm in laboratory animals, poultry and humans
Authors: Gholami‐Ahangaran Majid , Karimi‐Dehkordi Maryam , Akbari Javar Arefeh , Haj Salehi Maziar , Ostadpoor Mehrdad
Published: July 2021

There is an evidence that ginger enhance semen quality via improving different sperm parameters mainly count, viability, motility, morphology and DNA integrity. According to research results in various species, ginger seems to have strong antioxidant properties (due to the presence of active phenolic compounds) and androgenic activity. Ginger improves semen quality and increases fertility of sperm by disrupting the production of free radicals, dissolving oxidative chain reactions, reducing oxidative stress and altering the levels of gonadotropin hormones (LH, FSH) and sex hormones (such as testosterone). The antioxidant and androgenic properties of ginger give a sperm with normal morphological structure (head, middle and tail) and more integrated chromatin. The rate of DNA failure and damage to the mitochondrial genome in these cells is minimal and they have the most progressive motility, the highest viability and the best fertility. Therefore, the use of the ginger significantly improves the biological parameters of sperm (number, total motility, survival rate and normal morphology) and also increases all specialized fertility indicators of sperm. Tacking account of lacking literature and possibility of toxicity and adverse effect of ginger on vital organ, further clinical trial especially on evaluating the safety and clinical effect must be considered. Also, dose and duration of consumption by monitoring of health indicators and biochemical changes in all species such as human, animal and poultry must be applied.
Incidence and treatment of hand and wrist injuries in Dutch emergency departments
Authors: van Leerdam Roderick H. , Krijnen Pieta , Panneman Martien J. , Schipper Inger B.
Published: July 2021

Purpose

The purpose of this study was to describe the epidemiology, treatment and costs of hand and wrist injuries presenting to the Dutch ED. With increasing medical costs and crowding of emergency departments (ED), a more detailed description of emergency department attendance of hand and wrist injuries and their treatment may help to facilitate more adequate allocation of health care services.

Methods

The Dutch Injury Surveillance System obtained a total of 160,250 hand and wrist injuries. Patient characteristics, incidence rates, type of injury, treatment, and costs were described.

Results

The incidence of hand and wrist injuries in the Netherlands in 2016 was 11 per 1000 in males and 8 per 1000 in females. This is about 25% of all injuries presented at the ED. Of all hand injuries, only 3% was directly admitted to the hospital or received emergency surgery. Thirty percent did not need further treatment in the hospital.

Conclusion

The current data suggest that a substantial proportion of the hand and wrist injuries needed no subsequent specialized treatment. Although the severity of the injury could not be deduced from our data, the data suggest a ground for a more extensive role of primary health care (general) practitioners in the primary triage and treatment of hand and wrist injuries. This may reduce health care cost and help decongest the ED departments. Prospective studies are needed to confirm these preliminary conclusions.

Level of evidence

III.