bluuebunny/crossref_metadata_2025 huggingface dataset:
Untangling harvest‐streamflow responses in foothills conifer forests: Nexus of teleconnections, summer‐dominated precipitation, and storage
Authors: Goodbrand Amy , Anderson Axel , Devito Kevin , Silins Uldis
Published: January 2022

This study re‐evaluated data from the historical Tri‐Creeks Experimental Watershed (1967–1988) in Alberta, Canada to address the initial question of forest harvest effects on streamflow and investigate the potential influence of teleconnections, summer‐dominated precipitation, and watershed storage on runoff generation. Tri‐Creeks has deep (up to 21 m) glacial deposits underlain by folded and faulted sedimentary bedrock with considerable potential for subsurface water storage. Timing of the conifer forest harvest experiment in two sub‐watersheds (>50% harvested) and one reference occurred near the 1976–77 Pacific Decadal Oscillation (PDO) phase change that led to less snowfall, but little difference in annual precipitation or runoff between phases after harvest. Established statistical and hydrological modelling methods that used regression techniques of observed and simulated streamflow to separately analyse sub‐watersheds did not detect change in average daily or annual runoff due to harvest. The interannual hydroclimatic variability influenced by the climate shift, attenuation of summer precipitation by the drier antecedent conditions in the warm period following harvest, and large potential for subsurface water storage contributed to shifts in runoff and uncertain detection of streamflow response. However, a hydrological modelling approach using calibrated parameters separately in the pre‐ and post‐harvest periods indicate significant change in rainfall‐generated peak runoff events and summer runoff following harvest, which was not detected in the reference watershed. Model calibration required less soil storage capacity in the treated watersheds in the post‐harvest period compared to the reference likely due to reduced transpiration that increased the likelihood of storm runoff during larger summer rainfall events. Within the context of streamflow responses to harvest in conifer dominated forest landscapes with seasonal snow cover, this study illustrates how complexity of climate variability and interaction with watershed storage and continental summer‐dominated precipitation may confound and mask the interpretation of harvest effects in paired‐watershed studies.
Cancer risk and mortality after solid organ transplantation: A population‐based 30‐year cohort study in Finland
Authors: Friman Terhi Kristiina , Jäämaa‐Holmberg Salla , Åberg Fredrik , Helanterä Ilkka , Halme Maija , Pentikäinen Markku O. , Nordin Arno , Lemström Karl B. , Jahnukainen Timo , Räty Riikka , Salmela Birgitta
Published: January 2022

Cancer is a significant cause of morbidity and mortality after solid organ transplantation (SOT) and related to lifelong immunosuppression. This retrospective registry study assessed for the first time in Finland population‐based cancer risk and cancer mortality after all SOTs (lung and childhood transplantations included) as standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs). Data from transplant registries were linked with the data of Finnish Cancer Registry and Statistics Finland. We followed 6548 consecutive first SOT recipients from 1 January 1987 to 31 December 2016 translating to 66 741 person‐years (median follow‐up time 8.9 years [interquartile range 4.0‐15.1]). In total, 2096 cancers were found in 1483 patients (23% of all patients). Majority of cancers (53%) were nonmelanoma skin cancers (NMSCs). The overall SIR was 3.6 (95% confidence interval [CI]: 3.5‐3.8) and the SIR excluding NMSCs was 2.2 (95% CI: 2.0‐2.3). SIR for all cancers was highest for heart (5.0) and lowest for liver (2.7) recipients. Most common cancer types after NMSCs were non‐Hodgkin lymphoma (NHL), SIR 9.9 (95% CI: 8.5‐11.4) and kidney cancer, SIR 7.3 (95% CI: 6.0‐8.8). Cancer‐related deaths were 17% (n = 408) of all deaths after first month post transplantation. SMR for all cancers was 2.5 (95% CI: 2.2‐2.7) and for NHL 13.6 (95% CI: 10.7‐16.8). Notably, overall SIR for cancer was lower in later period (2000‐2016), 3.0 (95% CI: 2.8‐3.2), than in earlier period (1987‐1999), 4.3 (95% CI: 4.0‐4.5), P < .001. Decrease in cancer incidence was temporally associated with major changes in immunosuppression in the 2000s.
Dairy product consumption and risk of cancer: A short report from the NutriNet‐Santé prospective cohort study
Authors: Deschasaux‐Tanguy Mélanie , Barrubés Piñol Laura , Sellem Laury , Debras Charlotte , Srour Bernard , Chazelas Eloi , Wendeu‐Foyet Gaëlle , Hercberg Serge , Galan Pilar , Kesse‐Guyot Emmanuelle , Julia Chantal , Babio Sánchez Nancy Elvira , Salas Salvadó Jordi , Touvier Mathilde
Published: January 2022

The impact of dairy product consumption for long‐term health remains unclear, in particular regarding their involvement in cancer etiology for frequent locations like breast or prostate. Besides, little is known about potentially different effects of dairy product subtypes. Our objective was therefore to evaluate the associations between dairy product consumption (total and subtypes) and cancer risk. A total of 101 279 participants from the French NutriNet‐Santé cohort study were included (78.7% women; mean [SD] age = 42.2 [14.5] years). Dairy product consumption was assessed using validated web‐based 24‐hour dietary records. Multiadjusted Cox models were computed. After a median [interquartile range] follow‐up time of 5.9 [2.7‐8.3] years, we documented 2503 incident cancer cases (783 breast, 323 prostate and 182 colorectal cancers). Total dairy product consumption was not significantly associated with cancer. However, the consumption of “fromage blanc” (a French type of quark/cottage cheese) was associated with an increased risk of cancer overall (HR for 1 serving increment [95% CI] = 1.11 [1.01‐1.21]; P‐trend = .03) and of colorectal cancer (HR = 1.39 [1.09‐1.77]; P‐trend < .01). Besides, sugary dairy dessert consumption was directly associated with colorectal cancer risk (HR for 1 serving increment = 1.58 [1.01‐2.46]; P‐trend = .046]. No association was observed between the consumption of dairy products or sugary dairy desserts and the risk of prostate and breast cancers. In our study, the consumption of dairy products was not associated with the risk of overall, colorectal, breast or prostate cancers. The consumption of “fromage blanc” and sugary dairy desserts were associated to an increased risk of colorectal cancer, but this warrants further investigations.
Identification of polypharmacological anticancerous molecules against Aurora kinase family of proteins
Authors: Gupta Deepali , Kumar Mukesh , Singh Mandeep , Salman Mohd , Das Uddipan , Kaur Punit
Published: January 2022

The Human Aurora Kinase (AURK) protein family is the key player of cell cycle events including spindle assembly, kinetochore formation, chromosomal segregation, centrosome separation, microtubule dynamics, and cytokinesis. Their aberrant expression has been extensively linked with chromosomal instability in addition to derangement of multiple tumor suppressors and oncoprotein regulated pathways. Therefore, the AURK family of kinases is a promising target for the treatment of various types of cancer. Over the past few decades, several potential inhibitors of AURK proteins have been identified and have reached various phases of clinical trials. But very few molecules have currently crossed the safety criteria due to their various toxic side effects. In the present study, we have adopted a computational polypharmacological strategy and identified four novel molecules that can target all three AURKs. These molecules were further investigated for their binding stabilities at the ATP binding pocket using molecular dynamics based simulation studies. The molecules selected adopting a multipronged computational approach can be considered as potential AURKs inhibitors for cancer therapeutics.
The effects of precursor concentration and morphology on photoluminescence behavior of Tb2O3 phosphors
Authors: Unal Fatma
Published: January 2022

Terbium oxide (Tb2O3) phosphors were prepared the using sol‐precipitation method with the use of different precursor concentrations. The X‐ray diffraction (XRD) patterns showed C‐type body‐centered cubic phase, space group Ia‐3, and the crystallite size values were found in the range of 19.45–32.34 nm depending on the solution composition and calcination temperature. As the crystallinity increased, the defects in the structure decreased, that is, the dislocation density decreased. Under the excitation at 325 nm, although all the Tb2O3 phosphors emitted a single peak around 544 nm (5D4‐7F5 transition) in PL spectra, when the peak was enlarged, the presence of additional peaks shifted to the red/blue region was also observed. The color chromaticity coordinates showed that it exhibited different tones of emission from light yellow to green depending on the precursor concentration and calcination temperature. With increasing the precursor concentration, nucleation rate increased and the particle shape changed from nearly spherical to rod‐like. They may be promising for laser devices and display applications due to their strong green emission.
Ultrastructural adaptation of the oropharyngeal cavity of the Eurasian common moorhen (Gallinula chloropus chloropus): Specific adaptive dietary implications
Authors: Bassuoni Naglaa F. , Abumandour Mohamed M. A. , Morsy Kareem , Hanafy Basma G.
Published: January 2022

The present investigation represents the first morphological description of the oropharyngeal cavity of Eurasian common moorhen. Nine oropharyngeal cavities were examined grossly and by stereomicroscope and scanning electron microscopic (SEM) observations. The tongue had a rounded apex with multiple acicular processes on its rostral and lateral borders. The dorsal lingual surface of the apex and body had a median sulcus. The papillary crest carried four caudally directed triangular conical papillae on its median part and four triangular conical papillae on each lateral part. The filiform papillary system; small papillae on apex and long papillae on the rostral part of the body while broad papillae on the caudal part of the body. The lingual root had a special appearance by presence of three areas: mucosal fossa, two lateral ridges, and rhomboidal elevated central part. The caudal border of the mound carried heart‐shaped pharyngeal papillae that possessed three papillary rows. The palate had a median palatine ridge rostrally that surrounded by two lateral palatine ridges. The choanae had two equal parts: rostral tapering and wide caudal. The rostral tapering choanal part was surrounded by two longitudinal rows of caudally directed conical papillae, one on each side. There was a single transverse row of conical papillae on each side of the caudal part of the rostral tapering choanal part. The caudal wide choanal part did not encircle by any papillae. Our conclusion exhibited unique structural and functional specifications of the oropharyngeal cavity with the tongue that evident with nutritional behavior.
Highly‐metastatic colorectal cancer cell released miR‐181a‐5p‐rich extracellular vesicles promote liver metastasis by activating hepatic stellate cells and remodelling the tumour microenvironment
Authors: Zhao Senlin , Mi Yushuai , Zheng Binbin , Wei Ping , Gu Yanzi , Zhang Zhengxiang , Xu Ye , Cai Sanjun , Li Xinxiang , Li Dawei
Published: January 2022

Liver metastasis of colorectal cancer (CRLM) is the most common cause of CRC‐related mortality, and is typically caused by interactions between CRC cells and the tumour microenvironment (TME) in the liver. However, the molecular mechanisms underlying the crosstalk between tumour‐derived extracellular vesicle (EV) miRNAs and the TME in CRLM have yet to be fully elucidated. The present study demonstrated that highly metastatic CRC cells released more miR‐181a‐5p‐rich EVs than cells which exhibit a low metastatic potential, in‐turn promoting CRLM. Additionally, we verified that FUS mediated packaging of miR‐181a‐5p into CRC EVs, which in‐turn persistently activated hepatic stellate cells (HSCs) by targeting SOCS3 and activating the IL6/STAT3 signalling pathway. Activated HSCs could secrete the chemokine CCL20 and further activate a CCL20/CCR6/ERK1/2/Elk‐1/miR‐181a‐5p positive feedback loop, resulting in reprogramming of the TME and the formation of pre‐metastatic niches in CRLM. Clinically, high levels of serum EV containing miR‐181a‐5p was positively correlated with liver metastasis in CRC patients. Taken together, highly metastatic CRC cells‐derived EVs rich in miR‐181a‐5p could activate HSCs and remodel the TME, thereby facilitating liver metastasis in CRC patients. These results provide novel insight into the mechanism underlying liver metastasis in CRC.
Changing patterns of son preference and fertility in Pakistan
Authors: Javed Rashid , Mughal Mazhar
Published: January 2022

Using data from two representative Demographic and Health Surveys, we examine the change in son preference over the past three decades and its effects on Pakistani women's fertility. We analyse a number of indicators and employ different empirical methods to come up with strong and persistent evidence for both the revealed and stated preference for sons. This disproportionate preference for boys is visible in increasing desired sex ratio and worsening sex ratio at last birth. Reliance over differential birth stopping has significantly increased over time as couples are more likely to stop childbearing once the desired number of boys is achieved.
Immune modulatory effects of progesterone on oxLDL-induced trained immunity in monocytes
Authors: Groh Laszlo A , Verel Dagmar E , van der Heijden Charlotte D C C , Matzaraki Vasiliki , Moorlag Simone J C F M , de Bree L Charlotte , Koeken Valerie A C M , Mourits Vera P , Keating Samuel T , van Puffelen Jelmer H , Joosten Leo A B , Netea Mihai G , Riksen Niels P
Published: January 2022

Atherosclerotic cardiovascular diseases (CVD) are among the leading causes of death in the world. Monocyte-derived macrophages are key players in the pathophysiology of atherosclerosis. Innate immune memory following exposure of monocytes to atherogenic compounds, such as oxidized low-density lipoproteins (oxLDL), termed trained immunity, can contribute to atherogenesis. The current study aimed to elucidate intracellular mechanisms of oxLDL-induced trained immunity. Using untargeted intracellular metabolomics in isolated human primary monocytes, we show that oxLDL-induced trained immunity results in alterations in the balance of intracellular steroid hormones in monocytes. This was reflected by a decrease in extracellular progesterone concentrations following LPS stimulation. To understand the potential effects of steroid hormones on trained immunity, monocytes were costimulated with oxLDL and the steroid hormones progesterone, hydrocortisone, dexamethasone, β-estradiol, and dihydrotestosterone. Progesterone showed a unique ability to attenuate the enhanced TNFα and IL-6 production following oxLDL-induced trained immunity. Single nucleotide polymorphisms in the nuclear glucocorticoid, progesterone, and mineralocorticoid receptor were shown to correlate with ex vivo oxLDL-induced trained immunity in 243 healthy volunteers. Pharmacologic inhibition experiments revealed that progesterone exerts the suppression of TNFα in trained immunity via the nuclear glucocorticoid and mineralocorticoid receptors. Our data show that progesterone has a unique ability to suppress oxLDL-induced trained immunity. We hypothesize that this effect might contribute to the lower incidence of CVD in premenopausal women.
Anterior acetabular coverage and femoral head–neck measurements predict postoperative anterior impingement: A simulation study
Authors: Hayashi Shinya , Hashimoto Shingo , Kuroda Yuichi , Nakano Naoki , Matsumoto Tomoyuki , Kamenaga Tomoyuki , Kuroda Ryosuke
Published: January 2022

The aim of this simulation study was to evaluate the relationship of elements of anterior acetabular coverage and femoral head–neck shape with the occurrence of postoperative anterior impingement after curved periacetabular osteotomy (PAO). Sixty‐two patients with symptomatic developmental dysplasia of the hip who had undergone curved PAO were selected. The likelihood of developing postoperative anterior impingement was explored through simulations of the range of motion by collision detection of the pelvis and femur. Postoperative anterior impingement was defined as impingement that occurred during postoperative bone flexion <105° or postoperative internal rotation <20° at 90° flexion. The three‐dimensional center‐edge (CE) angles, acetabular and femoral versions, radiographic alpha angles of the femoral head, combination angles of anterior CE and alpha angles, and combined anteversions of acetabular and femoral versions were compared between patients with postoperative anterior impingement and nonimpingement. A receiver operator characteristic (ROC) analysis was conducted to determine thresholds of the examined radiographic parameters and calculate their accuracy for predicting postoperative anterior impingement. A multivariate analysis was performed to test whether combined anteversion, anterior CE angle, and combination angle are associated with excellent modified Harris Hip Scores (mHHSs). ROC analysis demonstrated a combination angle ≥108° was predictive of the occurrence of postoperative anterior impingement after curved PAO, which can lead to impaired clinical outcomes. Conversely, a combination angle <108° was significantly associated with mHHS ≥ 90 points. To avoid postoperative anterior impingement, osteochondroplasty of the femoral head or anterior CE angle control should be performed for patients with preoperative combination angles ≥90°.
Safety and feasibility of early oral nutrition after endoscopic treatment for patients with liver cirrhosis: A historical prospective and comparative effectiveness study
Authors: Wang Renren , Huang Xiaoli , Zhou Tao , Li Yueyue , Ding Mengmeng , Xu Huawei , Gao Yanjing
Published: January 2022

Background

This study aimed to evaluate the safety and efficacy of early oral nutrition (EON) after endoscopic treatment compared with parenteral nutrition (PN) for patients with gastroesophageal variceal bleeding varices as cirrhotic complications.

Methods

This historical prospective study enrolled patients from Qilu Hospital of Shandong University in China with gastroesophageal varices as cirrhotic complications and who were undergoing endoscopic therapy. A total of 197 patients who fasted for 4 h after treatment were prospectively enrolled as the ON group, whereas those who fasted >48 h were retrospectively matched in a ratio of 1:1 as the PN group. The primary end point was variceal rebleeding, whereas the secondary end points were mortality and adverse events during the 42‐day follow‐up. Hospitalization duration and expenses, levels of inflammatory factors, defecation time, and the satisfaction of patients were evaluated.

Results

During the 42‐day follow‐up, no significant difference was observed in the rate of variceal rebleeding (P = 0.586) and morality (P = 1.000) between the ON and PN groups. However, the average days of hospitalization (P < 0.001) and expenses (P < 0.001) were significantly decreased in the ON group. Furthermore, the serum C‐reactive protein level (P = 0.002) and defecation time (P < 0.001) were lower and the satisfaction rate was higher (P < 0.001) for those in the ON group than for those in the PN group. Linear regression analysis showed that the tissue adhesive dosage was related to diet time (P = 0.038; 95% CI, 0.135–4.516).

Conclusion

EON was proven to be safe and feasible and, hence, was recommended after endoscopic treatment in patients with cirrhosis.
Malnutrition identification and management variability: An administrative database study of children with solid tumors
Authors: Runco Daniel V. , Stanek Joseph R. , Yeager Nicholas D. , Belsky Jennifer A.
Published: January 2022

Background

Malnutrition during cancer treatment increases treatment‐related morbidity and mortality. Our study better characterizes variability in malnutrition identification and treatment by examining nutrition‐related diagnoses and support for children with central nervous system (CNS) and non‐CNS solid tumors during therapy. We examined diagnosis of malnutrition, use of tube feeding or parenteral nutrition (PN), and appetite stimulants.

Methods

We retrospectively reviewed 0 to 21‐year‐old patients in the Pediatric Health Information System from 2015 to 2019. Patients were classified as having (1) billed malnutrition diagnosis, (2) malnutrition diagnosis or using PN and enteral nutrition (“functional malnutrition”), and (3) any previous criteria or prescribed appetite stimulants (“possible malnutrition”), as well as associated risk factors.

Results

Among 13,375 unique patients, CNS tumors were most common (24.4%). Overall, 26.5% of patients had malnutrition diagnoses, 45.4% met functional malnutrition criteria, and 56.0% had possible malnutrition. Patients with adrenal tumors had highest billed, functional, and possible malnutrition (36.6%, 64.1%, and 69.4%, respectively) followed by CNS tumors (29.1%, 52.4%, and 64.1%). Patients with adrenal tumors had highest rates of PN use (47.4%) and those with CNS tumors had the highest tube feeding use (26.8%). Hospital admissions with malnutrition had a longer hospital length of stay (LOS) (6 vs 3 days, P < 0.0001), more emergency department admissions (24.4% vs 21.8%, P < 0.0001), and more opioid use (58.6% vs 41.4%, P < 0.0001).

Conclusions

Variability in malnutrition diagnoses hinders clinical care and nutrition research in pediatric oncology. Improving disease‐specific recognition and treatment of malnutrition can target nutrition support, ensure appropriate reimbursement, and potentially improve outcomes for children with solid tumors.
Validation of a modified Caprini risk assessment model in lung cancer patients undergoing surgery: Results of a multicenter cross‐sectional observational study
Authors: Ke Lihui , Cui Songping , Yang Mei , Chen Jun , Xu Shun , Jiang Gening , Zhang Yi , Chen Shuo , Zheng E , Zhao Honglin , Fan Xiaoxi , Li Yuping , Zhi Xiuyi , Hu Bin , Li Hui ,   The China Embolism‐Thrombosis After Surgery of Thorax (ChEST) Study Group
Published: January 2022

Background and Objectives

Lung cancer patients slated for surgery are at high risk of venous thromboembolism (VTE). Precise risk assessment is necessary for providing proper thromboprophylaxis and reducing morbidity and mortality of VTE.

Methods

A multicenter, observational, cross‐sectional cohort study, involving patients with primary lung cancer undergoing surgery, was carried out from August 2016 to December 2019. All patients were assessed according to the Caprini risk assessment model (RAM) and a modified scoring system incorporating elevated D‐dimer and new stratification of surgical time. The endpoint was confirmed VTE or patient discharge.

Results

Out of 1205 patients, 87 (7.2%) were diagnosed with VTE. The area under the curve of modified scores for VTE was 0.759, which was larger than that of the original one (0.589) (p < 0.05). By modified Caprini scoring system, a higher score was associated with increased VTE risk (odds ratio [OR], 1.345; 95% confidence interval [CI], 1.197–1.512; p < 0.001), and there was an increased OR of 4.090 (95% CI, 2.472–6.768, p < 0.001) for VTE in high‐risk category patients.

Conclusion

Modified Caprini RAM showed an improved prediction of high‐risk patients with an elevated likelihood of postoperative VTE compared to the original one.
Portal Vein Gas in Neonates: Predicting Clinical Treatment Outcomes From Ultrasound Findings
Authors: Lim Yun‐Jung , Jung Hyun Kyung
Published: January 2022

Objectives

To identify sonographic findings that predict clinical outcomes in neonates with portal vein gas.

Methods

This retrospective study included neonates with portal vein gas detected using ultrasound (US). The US images were reviewed by a pediatric radiologist. US findings included the extent and amount of portal vein gas, mesenteric vein gas, intramural gas, bowel wall thickening or thinning, focal discontinuity of the bowel wall, ascites, free intra‐abdominal gas, pseudocyst, gas in the other solid organs, and bowel distension. The imaging findings and demographic factors between survivors and non‐survivors were statistically compared.

Results

The mortality rate was 26% (39 survivors, 14 non‐survivors) when iatrogenic and idiopathic causes were excluded. The causes of portal vein gas were determined to be necrotizing enterocolitis (n = 33), bowel distension or obstruction (n = 12), fetal hydrops (n = 4), pneumothorax (n = 3), immediate postoperative state for bowel perforation (n = 1), and umbilical vein catheterization (n = 9) based on surgical findings (n = 20) and clinical information (n = 46). Gas within the mesenteric vein and the other solid organs, gestational age, and birth weight were significantly different between survivors and those who succumbed (P < .05).

Conclusion

Gas within the mesenteric vein and other solid organs is a US finding that may predict poor outcomes in neonates with portal vein gas.
Second‐Harmonic Generation in Etchless Lithium Niobate Nanophotonic Waveguides with Bound States in the Continuum
Authors: Ye Fan , Yu Yue , Xi Xiang , Sun Xiankai
Published: January 2022

Bound states in the continuum (BICs) have been extensively studied in various systems since they are first proposed in quantum mechanics. Photonic BICs can enable optical mode confinement and provide field enhancement for nonlinear optics, but they have rarely been explored in nonlinear integrated photonic waveguides. Applying BICs in photonic integrated circuits enables low‐loss light guidance and routing in low‐refractive‐index waveguides on high‐refractive‐index substrates, which is suitable for integrated photonics with nonlinear materials. Here, second‐harmonic generation from telecom to near‐visible wavelengths is experimentally demonstrated on an etchless lithium niobate platform by using a photonic BIC for the second‐harmonic mode. The devices feature second‐harmonic conversion efficiency of 0.175% W−1 cm−2 and excellent thermal stability with a wavelength shift of only 1.7 nm from 25 to 100 °C. These results represent a new paradigm of nonlinear integrated photonics on a cost‐effective and convenient platform, which can enable a broad range of on‐chip applications such as optical parametric generation, signal processing, and quantum photonics.
Smart Shape Memory Polyurethane with Photochromism and Mechanochromism Properties
Authors: Wang Xiaofei , He Yang , Leng Jinsong
Published: January 2022

The combination of shape memory effects and multi‐functionalities in smart materials is becoming one of the hottest research directions in the field of actuators and robotics. In this study, N‐hydroxyethyl‐3,3‐dimethyl‐6‐nitroindoline spiropyran (SP) is chemically grafted into a polyurethane matrix to prepare ultraviolet light‐actuated shape memory thermoplastic polyurethane, which first integrates three unique properties including shape memory, photochromism, and mechanochromism. The FTIR, WAXD, SAXS, DSC, TGA, and shape memory tests reveal that the shape memory transformation temperature of 4.6 wt% SP‐based shape memory polyurethane is 41.2 °C, and it has the highest shape memory performance, as indicated by shape fixation and shape recovery ratios of 97.4% and 93.7%, respectively. Furthermore, “bionic fingers” with diversely selective actuation properties are fabricated, which exhibit a series of programmable multi‐segment motions to meet potential applications in the field of soft actuators.
mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized, Double‐Blind, Placebo‐Controlled Futility Trial and 1‐Year Biomarker Longitudinal Analysis
Authors: Palma Jose‐Alberto , Martinez Jose , Millar Vernetti Patricio , Ma Thong , Perez Miguel A. , Zhong Judy , Qian Yingzhi , Dutta Suman , Maina Katherine N. , Siddique Ibrar , Bitan Gal , Ades‐Aron Benjamin , Shepherd Timothy M. , Kang Un J. , Kaufmann Horacio
Published: January 2022

Background

Multiple system atrophy (MSA) is a fatal neurodegenerative disease characterized by the aggregation of α‐synuclein in glia and neurons. Sirolimus (rapamycin) is an mTOR inhibitor that promotes α‐synuclein autophagy and reduces its associated neurotoxicity in preclinical models.

Objective

To investigate the efficacy and safety of sirolimus in patients with MSA using a futility design. We also analyzed 1‐year biomarker trajectories in the trial participants.

Methods

Randomized, double‐blind, parallel group, placebo‐controlled clinical trial at the New York University of patients with probable MSA randomly assigned (3:1) to sirolimus (2–6 mg daily) for 48 weeks or placebo. Primary endpoint was change in the Unified MSA Rating Scale (UMSARS) total score from baseline to 48 weeks. (ClinicalTrials.gov NCT03589976).

Results

The trial was stopped after a pre‐planned interim analysis met futility criteria. Between August 15, 2018 and November 15, 2020, 54 participants were screened, and 47 enrolled and randomly assigned (35 sirolimus, 12 placebo). Of those randomized, 34 were included in the intention‐to‐treat analysis. There was no difference in change from baseline to week 48 between the sirolimus and placebo in UMSARS total score (mean difference, 2.66; 95% CI, −7.35–6.91; P = 0.648). There was no difference in UMSARS‐1 and UMSARS‐2 scores either. UMSARS scores changes were similar to those reported in natural history studies. Neuroimaging and blood biomarker results were similar in the sirolimus and placebo groups. Adverse events were more frequent with sirolimus. Analysis of 1‐year biomarker trajectories in all participants showed that increases in blood neurofilament light chain (NfL) and reductions in whole brain volume correlated best with UMSARS progression.

Conclusions

Sirolimus for 48 weeks was futile to slow the progression of MSA and had no effect on biomarkers compared to placebo. One‐year change in blood NfL and whole brain atrophy are promising biomarkers of disease progression for future clinical trials. © 2022 International Parkinson and Movement Disorder Society
Beam properties within the momentum acceptance of a clinical gantry beamline for proton therapy
Authors: Giovannelli Anna Chiara , Maradia Vivek , Meer David , Safai Sairos , Psoroulas Serena , Togno Michele , Bula Christian , Weber Damien Charles , Lomax Antony John , Fattori Giovanni
Published: January 2022

Purpose

Energy changes in pencil beam scanning proton therapy can be a limiting factor in delivery time, hence, limiting patient throughput and the effectiveness of motion mitigation techniques requiring fast irradiation. In this study, we investigate the feasibility of performing fast and continuous energy modulation within the momentum acceptance of a clinical beamline for proton therapy.

Methods

The alternative use of a local beam degrader at the gantry coupling point has been compared with a more common upstream regulation. Focusing on clinically relevant parameters, a complete beam properties characterization has been carried out. In particular, the acquired empirical data allowed to model and parametrize the errors in range and beam current to deliver clinical treatment plans.

Results

For both options, the local and upstream degrader, depth‐dose curves measured in water for off‐momentum beams were only marginally distorted (γ(1%, 1 mm) > 90%) and the errors in the spot position were within the clinical tolerance, even though increasing at the boundaries of the investigated scan range. The impact on the beam size was limited for the upstream degrader, while dedicated strategies could be required to tackle the beam broadening through the local degrader. Range correction models were investigated for the upstream regulation. The impaired beam transport required a dedicated strategy for fine range control and compensation of beam intensity losses. Our current parameterization based on empirical data allowed energy modulation within acceptance with range errors (median 0.05 mm) and transmission (median –14%) compatible with clinical operation and remarkably low average 27 ms dead time for small energy changes. The technique, tested for the delivery of a skull glioma treatment, resulted in high gamma pass rates at 1%, 1 mm compared to conventional deliveries in experimental measurements with about 45% reduction of the energy switching time when regulation could be performed within acceptance.

Conclusions

Fast energy modulation within beamline acceptance has potential for clinical applications and, when realized with an upstream degrader, does not require modification in the beamline hardware, therefore, being potentially applicable in any running facility. Centers with slow energy switching time can particularly profit from such a technique for reducing dead time during treatment delivery.
Global, regional, and national burden of cancers attributable to excess body weight in 204 countries and territories, 1990 to 2019
Authors: Safiri Saeid , Karamzad Nahid , Kaufman Jay S. , Nejadghaderi Seyed Aria , Bragazzi Nicola Luigi , Sullman Mark J. M. , Almasi‐Hashiani Amir , Mansournia Mohammad Ali , Collins Gary S. , Kolahi Ali‐Asghar , Jemal Ahmedin
Published: January 2022

Objective

The aim of this study was to report the level and trends of 13 cancers that are attributable to excess body weight (EBW) for 204 countries and territories from 1990 to 2019.

Methods

Using publicly available data, the burden of cancers attributable to EBW was reported from 1990 to 2019 based on the comparative risk assessment approach used in the Global Burden of Disease study 2019. [Correction added on 27 January 2022, after first online publication: ‘Using publicly available data,’ has been added before the first sentence and ‘estimated’ was corrected to ‘reported’.]

Results

In 2019, EBW caused 11.2 million disability‐adjusted life‐years (DALYs), or 4.4% of all cancer‐related DALYs. Between 1990 and 2019, the global EBW‐attributable age‐standardized cancer DALY rates (per 100,000) increased from 109.9 to 133.9, a relative increase of 21.9%. The age‐standardized DALY rates (per 100,000) of cancers attributable to EBW in 2019 were highest and lowest in Mongolia (611.8) and Bangladesh (30.2), respectively. The 60‐ to 64‐year age group had the highest number of DALYs attributable to EBW, whereas there were no large sex differences in the cancer‐related burden attributable to EBW. Furthermore, the association between the age‐standardized DALY rates and the sociodemographic index was generally positive.

Conclusions

Overall, the EBW‐attributable burden of cancers has increased in the past three decades. Public health efforts should focus on identifying appropriate preventive interventions at the population and individual levels, especially in the regions and countries with the highest burden.
Coating of 3D‐printed poly (ε‐caprolactone) scaffolds with silk protein sericin enhances the osteogenic differentiation of human mesenchymal stem cells
Authors: Iranpour Soodeh , Attari Farnoosh , Seyedjafari Ehsan , Nourmohammadi Jhamak
Published: January 2022

Poly (ε‐caprolactone) (PCL) as a biodegradable polymer is widely employed in scaffold fabrication. Nonetheless, PCL is a hydrophobic polymer and biologically inactive, which is considered a drawback for cell attachment and tissue engineering. Thus, some surface modifications are necessary to enhance its bioactivity. Here, NaOH‐treated scaffolds were immersed in (N‐morpholino) ethanesulfonic acid solution containing N‐hydroxysuccinimide and 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide followed by incubation in sericin solution. Scanning electron microscopy (SEM) results demonstrated 0/900 strand orientation and well‐defined interconnected pores. The presence of sericin on the treated scaffold was manifested as a light nanoscale roughness compared to the raw PCL scaffold. The average porosity percentage in PCL scaffold equaled 67.9%. The presence of bands at 1538 and 1650 cm−1 in Fourier‐transform infrared (FTIR) spectra of the sericin‐coated scaffold was attributed to Amide II and Amide I, indicative of sericin presence on PCL scaffold. The water contact angle in the PCL scaffold was 1050, where sericin coating combined with NaOH treatment decreased contact angle and increased the hydrophilicity. SEM images, EDX mapping, and X‐ray diffraction analysis indicated the presence of calcium and phosphate on sericin‐coated scaffolds as a sign of apatite formation. SEM images demonstrated enhanced cell adhesion on sericin‐coated scaffold compared to pure PCL, and cells could penetrate interconnected pores. Viability assay proved that sericin did not induce any cytotoxic effect. Also, alkaline phosphatase and calcium deposition assays demonstrated that sericin‐coated scaffolds effectively improved osteogenic differentiation of mesenchymal stem cells. Therefore, sericin as a biomaterial is expected to have promising potentials in orthopedic applications.
Design and characterization of high‐performance epoxy adhesive with block copolymer and alumina nanoparticles in aluminum‐aluminum bonded joints: Mechanical properties, lap shear strength, and thermal stability
Authors: Fallahi Mohsen , Moini Jazani Omid , Molla‐Abbasi Payam
Published: January 2022

In this research, phenolic resin and poly (butyl‐acrylate‐block‐styrene) copolymer were used in the formulation of epoxy adhesive to improve its thermal stability and toughness. Also, in order to improve the mechanical properties such as the modulus and tensile strength, aluminum oxide nanoparticles (NPs) were added to the epoxy based resin. Effects of different factors such as percent contents of phenolic resin, toughening agent, and aluminum oxide NPs on the microstructure, mechanical properties, and thermal stability of the epoxy‐based adhesives were investigated. Thermogravimetric analysis, Fourier transform infrared spectroscopy, and field‐emission scanning electron microscopy were used to investigate the thermal, mechanical, and morphological properties of the prepared epoxy adhesive samples. In addition, the curing kinetics of the optimal specimens was studied based on differential scanning calorimetry (DSC). The experimental results indicated that the phenolic decreased strength of dog‐bone samples, while increased the adhesion strength in metal‐to‐metal single‐lap strength. On the other hand, addition of block‐copolymers as toughening agent led to a consistent decrease in the modulus as well as increasing the tensile strength. Also, results of single‐lap strength tests showed that, in the optimal quad system, the four components exhibit synergetic effects and show a single‐lap strength that is 152% higher than that of pure epoxy. The DSC analysis indicated that the presence of alumina NPs and block‐copolymers tend to reduce the initial curing temperature while increasing the curing reaction heat.
Evaluation of mechanical, morphological, and biodegradation properties of natural fiber reinforced nano‐biocomposites
Authors: Behera Ajaya Kumar , Das Nigamananda , Manna Suvendu
Published: January 2022

Nanoclay modified bio resin‐based jute composites were prepared by thermopressing method to examine the effect of nanoclay on physical, mechanical, and biodegradation properties of jute‐soy composite. Fourier transform infrared spectroscopy of composite was carried out to study the chemical interactions between jute‐soy‐nanoclay, whereas, x‐ray diffractogram and transmission electron microscopic analysis revealed the formation of nanostructure at the composite interface. With 5 wt.% of clay contents, the tensile strength of the composite was 59.2 MPa, which is 65.4% higher than that of the clay‐free jute‐soy composite. The developed composite is thermally stable up to 280°C and increased in weight by only 41.66% after 24‐h water immersion. Inclusion of 5 wt.% nanoclay enhanced storage modulus of nanocomposite from 1170 to 4136 MPa. Evaluation of degradability of composites under compost condition in terms of weight and tensile loss indicated that clay reinforced composites are more durable than jute‐soy composite. Overall, a biodegradable composite material was developed which may be applied as nondegradable plastic alternate in packaging, railway coach, decorating materials, furniture, transport, and construction sector.
Exploring determinants of agonist efficacy at the CB1 cannabinoid receptor: Analogues of the synthetic cannabinoid receptor agonist EG‐018
Authors: Finlay David B. , Nguyen Thuy , Gamage Thomas F. , Chen Shuli , Barrus Daniel G. , Patel Purvi R. , Thomas Brian F. , Wiley Jenny L. , Zhang Yanan , Glass Michelle
Published: January 2022

Neutral antagonists of GPCRs remain relatively rare—indeed, a large majority of GPCR antagonists are actually inverse agonists. The synthetic cannabinoid receptor agonist (SCRA) EG‐018 was recently reported as a low efficacy cannabinoid receptor agonist. Here we report a comparative characterization of EG‐018 and 13 analogues along with extant putative neutral antagonists of CB1. In HEK cells stably expressing human CB1, assays for inhibition of cAMP were performed by real‐time BRET biosensor (CAMYEL), G protein cycling was quantified by [35S]GTPγS binding, and stimulation of pERK was characterized by AlphaLISA (PerkinElmer). Signaling outcomes for the EG‐018 analogues were highly variable, ranging from moderate efficacy agonism with high potency, to marginal agonism at lower potency. As predicted by differing pathway sensitivities to differences in ligand efficacy, most EG‐018‐based compounds were completely inactive in pERK alone. The lowest efficacy analogue in cAMP assays, 157, had utility in antagonism assay paradigms. Developing neutral antagonists of the CB1 receptor has been a long‐standing research goal, and such compounds would have utility both as research tools and in therapeutics. Although these results emphasize again the importance of system factors in determining signaling outcomes, some compounds characterized in this study appear among the lowest efficacy agonists described to date and therefore suggest that development of neutral antagonists is an achievable goal for CB1.
CMOS Compatible Al‐Doped ZnO Sol–Gel Thin‐Film Properties
Authors: Moussa Nizar Ben , Lajnef Mohamed , Jebari Nessrine , Mahut Frédéric , Villebasse Cédric , Lafosse Xavier , David Christophe , Chaste Julien , Chtourou Radhouane , Herth Etienne
Published: January 2022

Zinc oxide (ZnO) is a low‐cost class of n‐type inorganic semiconductors with a large exciton binding energy (≈60 meV), wide direct bandgap (3.37 eV), and the most important material for various fields of industrial and deep‐tech applications. Herein, a complementary metal–oxide–semiconductor (CMOS) temperature compatible (400 °C)‐ integrated circuit (IC) process based on the sol–gel method is described. The properties of aluminum (Al)‐doped ZnO (AZO) thin films were investigated. The Al content, Al/(Al+Zn) ratio, varies from 0 to 10% and exhibits compressive stresses from −4 to −1.8 GPa. At low dopant concentrations, the Al content acts as an electrical dopant, while at higher dopant concentrations, it acts as an impurity. The electrical resistivity, which was only 3 × 10−3 Ω cm, is inversely related to the orientation of the thin film, which was preferably along the (0 0 2) direction. The optical bandgap energy of AZO thin films was determined to be in the range of 3.34–3.87 eV. Herein, a novel method to change the Al content of doped AZO thin films to improve their properties is described, which is suitable for next‐generation flexible, microsystem, and optoelectronic devices.
Highly Transparent p‐AlGaN‐Based (326–341 nm)‐Band Ultraviolet‐A Light‐Emitting Diodes on AlN Templates: Recent Advances and Perspectives
Authors: Khan Muhammad Ajmal , Maeda Noritoshi , Jo Masafumi , Yamada Yoichi , Hirayama Hideki
Published: January 2022

The epitaxial growth of transparent p‐AlGaN‐based ultraviolet‐A (UVA), light‐emitting diodes (LEDs) may solve the problems of UVA light absorption through the GaN buffers and p‐GaN contact layers at (326–341 nm)‐band emission, respectively. Herein, first, an idea of conventional n‐AlGaN buffer layer (BL) and n‐AlGaN electron source layer (ESL) for the suppression of threading dislocation density (TDD) and enhancement of internal quantum efficiency (IQE) of UVA emitters, using low‐pressure metalorganic vapor‐phase epitaxy (LP‐MOVPE) is attempted. As a result, the total‐TDDs is reduced from ≈ 3 × 109 cm−2 to ≈ 1 × 109 cm−2 in the n‐AlGaN ESL of a 326 nm‐band UVA multiquantum‐wells (MQWs), and IQE is also improved from 30% to 52% at room temperature (RT). Second, an idea of Si‐doped n‐AlGaN Superlattices (SLs)‐based BL, using LP‐MOVPE is challenged. Subsequently, a record IQE of 56% at RT and high crystal quality in 341 nm‐band UVA MQWs are observed. Finally, using a well thickness ≈ 2 nm in SLs‐based UVA MQWs, the light power and external quantum efficiency (EQE), respectively, are remarkably enhanced from 3.5 mW and 0.5% to 7.5 mW and 1.4% on wafer in 341 nm‐Band UVA LED. The perspective for the improvements of UVA emitter's performances is also discussed.
Cathodoluminescence Study of m‐Plane α‐Ga2O3 Grown by Mist Chemical Vapor Deposition
Authors: Moriya Ryo , Kikawa Junjiro , Mouri Shinichiro , Shinohe Takashi , Xiao Shiyu , Miyake Hideto , Araki Tsutomu
Published: January 2022

The cathodoluminescence (CL) properties of m‐plane α‐Ga2O3 grown by mist chemical vapor deposition are investigated. The m‐plane α‐Ga2O3 is found to have two types of characteristic luminescence bands: blue luminescence (BL) band (centered at 2.8 eV) and UV luminescence (UVL) band (centered at 3.7 eV). To characterize these bands, the Sn concentration and temperature dependences of the CL spectra are investigated using samples with varying Sn concentrations from 1 × 1017 to 1 × 1019 cm−3. The Sn concentration‐dependent CL spectra show that the luminescence from the UVL band is dominant in the low Sn concentration region, while that from the BL band is dominant in the high Sn concentration region. The temperature‐dependent CL spectra indicate that the peak intensity of the UVL band depending on temperature is larger than that of the BL band. The activation energies in the UVL band of the undoped and lightly Sn‐doped samples are determined as 110 meV. In addition, the parameters of the Huang–Rhys factor in the UVL band are obtained as 28.6 and 18.8, respectively. These results strongly suggest that the UVL band is derived from self‐trapped excitons, which is the recombination of free electrons and self‐trapped holes.