bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical APJ receptor residues in extracellular domains that influence effector selectivity
Authors: Ashokan Anisha , Harisankar Harikumar Sheela , Kameswaran Mythili , Aradhyam Gopala Krishna
Published: June 2021

Human APJ receptor/apelin receptor (APJR), activated by apelin peptide isoforms, regulates a wide range of physiological processes. The role of extracellular loop (ECL) domain residues of APJR in ligand binding and receptor activation has not been established yet. Based on multiple sequence alignment of APJ receptor from various organisms, we identified conserved residues in the extracellular domains. Alanine substitutions of specific residues were characterized to evaluate their ligand binding efficiency and Gq‐, Gi‐, and β‐arrestin‐mediated signaling. Mutation‐dependent variation in ligand binding and signaling was observed. W197A in ECL2 and L276L277W279‐AAA in ECL3 were deficient in Gi and β‐arrestin signaling pathways with relatively preserved Gq‐mediated signaling. T169T170‐AA, Y182A, and T190A mutants in ECL2 showed impaired β‐arrestin‐dependent cell signaling while maintaining G protein‐mediated signaling. Structural comparison with angiotensin II type I receptor revealed the importance of ECL2 and ECL3 residues in APJR ligand binding and signaling. Our results unequivocally confirm the specific role of these ECL residues in ligand binding and in orchestrating receptor conformations that are involved in preferential/biased signaling functions.
Squamous cell carcinoma arising within hidradenitis suppurativa: a literature review
Authors: Sachdeva Muskaan , Mufti Asfandyar , Zaaroura Hiba , Abduelmula Abrahim , Lansang Rafael Paolo , Bagit Ahmed , Alhusayen Raed
Published: June 2021

Squamous cell carcinoma (SCC) can present as a rare complication of longstanding hidradenitis suppurativa (HS) lesions. Limited data exist on characteristics and outcomes of SCC development within HS lesions. The purpose of this review is to conduct a literature review of previously reported cases of SCC development in pre‐existing HS lesions. EMBASE and MEDLINE searches were conducted in OVID on June 25, 2020, to yield 59 studies. Of the 95 patients (mean age: 52.9 years) who developed a total of 122 SCCs within HS lesions, the majority were males (77.9%, n = 74/95). The most common sites of SCC were the gluteal region (47.5%, n = 58/122), the perianal region (18.9%, n = 23/122), and the genitals (13.9%, n = 17/122). The mean duration between HS onset and SCC development was 25.5 years. Of the patients that had outcomes reported, 54.0% (n = 34/63) experienced SCC metastasis, 43.1% (n = 28/65) experienced SCC recurrences, and 58.7% (n = 44/75) experienced a mortality outcome. The most common documented reasons for death included metastasis (34.1%, n = 15/44) and sepsis (13.6%, n = 6/44). Patients with longstanding HS lesions can develop SCCs with a high rate of metastasis and mortality. Thus, chronic HS lesions, especially in the gluteal, perianal, genital, and perineal regions, should be monitored regularly for timely SCC diagnosis and management.
Development and implementation of a novel decision support tool on physical restraint use in critically ill adult patients
Authors: Chen Xiangping , Zhuang Yiyu , Lao Yuewen , Qiao Lijie , Chen Yueliang , Guo Feng
Published: June 2021

Aim

To investigate whether a novel decision support tool would effectively minimize physical restraint use in critically ill adult patients.

Design

A nonequivalent quasi‐experimental design combined with a descriptive qualitative approach was used.

Methods

A Restraint Decision Tree was developed based on a qualitative study that explored the barriers to employ the Restraint Decision Wheel. During the quasi‐experimental study, patients admitted to the unit between October 2017 and March 2018 were enrolled as the control group receiving the Restraint Decision Wheel (n = 528), whereas patients between April 2018 and September 2018 were enrolled as the intervention group receiving the Restraint Decision Tree (n = 564). The physical restraint rate, accidental catheter removal rate and nurses' satisfaction were compared.

Results

The Restraint Decision Tree significantly decreased physical restraint use. No significant difference in the rate of accidental catheter removal was found. Nurses reported increased satisfaction with the restraint decision‐making.

Conclusions

The Restraint Decision Tree could minimize physical restraint use. Physicians' involvement in the restraint decision‐making and nurses' competence in delirium assessment may be essential for successful implementation of the Restraint Decision Tree.
Botulinum toxin injections for Japanese patients with urinary incontinence caused by neurogenic detrusor overactivity: Clinical evaluation of onabotulinumtoxinA in a randomized, placebo‐controlled, double‐blind trial with an open‐label extension
Authors: Honda Masashi , Yokoyama Osamu , Takahashi Ryosuke , Matsuda Tatsuma , Nakayama Takashi , Mogi Takao
Published: June 2021

Objective

To assess the efficacy and safety of botulinum toxin treatment (onabotulinumtoxinA 200 units) for Japanese patients with neurogenic detrusor overactivity caused by spinal cord injury or multiple sclerosis.

Methods

Patients with urinary incontinence refractory to pharmacological treatment were enrolled and randomized in a phase III trial. A single dose of onabotulinumtoxinA (n = 11) or placebo (n = 10) was given in the double‐blind phase, and repeat injections of onabotulinumtoxinA were given in the subsequent open‐label phase. Outcomes included urinary incontinence episodes, urodynamics, patient‐reported outcomes and adverse events.

Results

The onabotulinumtoxinA group showed a numerically greater reduction in the number of urinary incontinence episodes per day than the placebo group, with the difference between the groups at week 6 of −3.02 (95% confidence interval −5.85 to −0.19). The onabotulinumtoxinA group also showed greater improvements in urodynamic assessments. Adverse events related to onabotulinumtoxinA injections were hematuria, urinary retention, urinary bladder hemorrhage, autonomic dysreflexia and epididymitis. Most events were deemed mild or moderate.

Conclusions

Intradetrusor injections of onabotulinumtoxinA are efficacious and tolerable for Japanese patients with neurogenic detrusor overactivity‐related symptoms that are difficult to manage with anticholinergics and/or β3‐adrenergic receptor agonists.
Maximum lethal temperature for flowering and seed set in maize with contrasting male and female flower sensitivities
Authors: Wang Yuanyuan , Liu Xiaoli , Hou Xinfang , Sheng Dechang , Dong Xin , Gao Yingbo , Wang Pu , Huang Shoubing
Published: June 2021

With a warming climate, heat events occur more frequently especially during flowering of many crops which increasingly threatens food security. The maximum temperature thresholds (TTmax) for different flowering processes and kernel formation, however, are not explicit in maize (Zea mays L.). For this, a temperature‐controlled experiment was conducted including two maize hybrids ZD958 and XY335 that were widely grown in China and six temperature levels (maximum/minimum temperature; 30/20, 32/22, 34/24, 36/26, 38/28 and 40/30℃ for 14 consecutive days bracketing the silking stage). Both tasseling and pollen shedding time were advanced with elevated temperature, but silking time was advanced from 30/20 to 36/26℃ and then delayed with further temperature increase, thus extending anthesis–silking interval (ASI). Silking rate was significantly reduced to 63% at 40/30℃ for ZD958 but maintained at 88%–95% for XY335 compared to that at 30/20℃. Pollen shed weight and pollen viability decreased with elevated temperature with larger reductions in XY335 than in ZD958. Hence, ZD958 and XY335 are female and male flower sensitive hybrids, respectively. Silking rate, pollen shed number and ASI were the most important constraints to kernel formation under HT stress. TTmax for seed set of both hybrids were estimated to be ~38℃, and different flowering processes have respective TTmax. These detailed information are important to uncover heat impacts on maize and increase simulation accuracy when modelling heat effects on maize yield. Besides, more attentions need to be directed at female flower sensitivity when breeding and/or selecting heat‐tolerant maize hybrids.
Platform is not destiny: Embodied learning effects comparing 2D desktop to 3D virtual reality STEM experiences
Authors: Johnson‐Glenberg Mina C. , Bartolomea Hannah , Kalina Elena
Published: June 2021

Experiences in immersive 3D virtual reality (VR) are more presence‐inducing, and so it may be tempting to claim that content will be learned better in VR. This randomized control trial study on natural selection challenges that assumption. This study answers the question of whether learning STEM in an immersive 3D VR environment is always superior to learning via a 2D monitor (PC). This is a 2 × 2 × 3 design. The first factor is platform immersivity (low = 2D PC, or high = 3D VR), the second factor is level of embodiment (lower = watching playback video, or higher = using mouse/controller to agentically manipulate content), and the third factor is test time (pretest, posttest, and follow‐up). There was a significant main effect for embodiment, the high embodied and agentic groups learned the most. There was not a main effect for platform, because the participants in the low embodied VR group performed significantly worse than the three other groups. Although, the one high embodied, VR group learned and retained the most knowledge. A path‐analysis revealed that the effect of platform was significantly mediated by presence, agency, and engagement. The smaller learning gain in the low embodied VR condition suggests that participants come to the immersive VR experience with expectations about agency and control of the virtual content, and when those expectations were not met, the disconnect was deleterious for learning. More agentic and interactive control of manipulable virtual content is encouraged. Design is critical, and platform is not destiny.
The stabilization of yes‐associated protein by TGFβ‐activated kinase 1 regulates the self‐renewal and oncogenesis of gastric cancer stem cells
Authors: Wang Gang , Sun Qikai , Zhu Hai , Bi Yihui , Zhu Haixing , Xu Aman
Published: June 2021

Gastric cancer (GC) is the most frequent digestive system malignant tumour and the second most common cause of cancer death globally. Cancer stem cell (CSC) is a small percentage of cancer cells in solid tumours that have differentiation, self‐renewal and tumorigenic capabilities. They have an active participation in the initiation, development, metastasis, recurrence and resistance of tumours to chemotherapy and radiotherapy. Gastric cancer stem cells (GCSCs) have been shown to be correlated with GC initiation and metastasis. In this study, we found that TAK1 expression level in GC tissues was significantly increased compared to the adjacent non‐cancerous tissues by RT‐qPCR, Western blot and immunohistochemistry. TAK1 has been identified as a critical molecule that promoted a variety of malignant GC phenotypes both in vivo and in vitro and promoted the self‐renewal of GCSCs. Mechanistically, TAK1 was up‐regulated by IL‐6 and prevented the degradation of yes‐associated protein (YAP) in the cytoplasm by binding to YAP. Thus, TAK1 promoted the SOX2 and SOX9 transcription and the self‐renewal and oncogenesis of GCSCs. Our findings provide insights into the mechanism of self‐renewal and tumorigenesis of TAK1 in GCSCs and have broad implications for clinical therapies.
ActiPso: definition of activity types for psoriatic disease: A novel marker for an advanced disease classification
Authors: Mrowietz U. , Dieckmann T. , Gerdes S. , Szymczak S. , von Spreckelsen R. , Körber A.
Published: June 2021

Background

Assessment of psoriasis is exclusively done measuring severity using somatic scores such as the psoriasis area and severity index or patient‐reported outcomes such as the dermatology life quality index. There is no established tool to measure a patient's individual psoriasis activity over time.

Objectives

Development of a new tool to classify psoriasis activity types.

Methods

Open patient interviews were performed and adapted in several steps and by using different groups of patients. Wording of the tool's axis and description how to use it was optimized with the input of patients. The final ActiPso tool was used in a prospective study in psoriasis patients.

Results

Four activity types could be identified describing psoriasis intensity (e.g. severity, itch, pain) over one typical year and an event/trigger type describing flares. In the study in 586 psoriasis patients of the 536 patients eligible for analysis 40.9% self‐classified as type 1 (‘stable’), 22.6% as type 2 (‘unstable’), 30.6% as type 3 (‘winter type’) and 6.0% as type 4 (‘summer type’), respectively. Flares of psoriasis as identified by the event/trigger type were reported in 36.1% of patients with activity type 1, 67.8% with type 2, 73.8% of type 3 and 59.4% of type 4, respectively.

Conclusions

Interviewed patients were able to describe their course of psoriatic disease and to name potential triggering factors. By doing so, activity types of psoriasis were defined for the first time and the importance of events/triggers for flares described and integrated into ActiPso types as a basis for advanced patient‐centric management. A limitation of ActiPso is that in regions with no seasonal variations types 3 and 4 may not apply.
Experiences of mothers caring for a child with an intellectual disability during the COVID‐19 pandemic in the Netherlands
Authors: Embregts P. , Heerkens L. , Frielink N. , Giesbers S. , Vromans L. , Jahoda A.
Published: June 2021

Background

During the first COVID‐19 lockdown period, various restrictions led to diminished access to both educational and professional support systems for children with an intellectual disability and their families. The aim of this study was to explore the experiences and needs of parents caring for a child with an intellectual disability during the first lockdown period in the Netherlands.

Method

Five mothers caring for a child with an intellectual disability participated in this qualitative study. The participants were interviewed using a semi‐structured interview guide. The interviews lasted between 26 and 48 min. The interview recordings were transcribed verbatim, and the transcripts were analysed thematically.

Results

Three overarching themes emerged: (1) We need to stay healthy, which centres on the mother's urge to protect their child's well‐being; (2) We make it work, which provides insight into how the mothers were handling the drastic changes in their family; and (3) My child's and family's place in the world, which focuses on the mothers' experienced position in the world around them.

Conclusions

The current study provides valuable insights into the experiences and needs of mothers caring for a child with an intellectual disability during the COVID‐19 pandemic.
Efficacy and safety of non‐pharmacological interventions for labour pain management: A systematic review and Bayesian network meta‐analysis
Authors: Hu Yinchu , Lu Hong , Huang Jing , Zang Yu
Published: June 2021

Aims and objectives

To compare and rank the efficacy and safety of non‐pharmacological interventions in the management of labour pain.

Background

Recently, various non‐pharmacological interventions have been applied to manage labour pain and have shown positive effects. However, evidence identifying which type of non‐pharmacological intervention is more efficient and safer is limited.

Design

Systematic review and Bayesian network meta‐analysis based on PRISMA‐NMA.

Methods

Seven databases were searched from database inception–March 2020. Two reviewers independently performed study selection, quality appraisal and data extraction. Conventional meta‐analysis was conducted using either fixed‐effects model or random‐effects model according to statistical heterogeneity. The Bayesian network meta‐analysis was conducted using the consistency model.

Results

43 studies involving nine non‐pharmacological interventions were included. The Bayesian network meta‐analysis showed that acupressure (SMD = −2.00, 95% CrI −3.09 to −0.94), aromatherapy (SMD = −2.01, 95% CrI −3.70 to −0.35) and massage therapy (SMD = −1.26, 95% CrI −2.26 to −0.30) had significant positive effects on alleviating labour pain, with aromatherapy being the most effective. The results also revealed that yoga (SMD = −130.85, 95% CrI −212.01 to −59.32) and acupressure (SMD = −10.14, 95% CrI −20.24 to −0.41) were the most effective interventions for shortening the first stage and the second stage of labour, respectively. There were no significant differences between non‐pharmacological interventions and usual care or placebo control on the use of pharmacological methods and neonatal 5‐min Apgar score.

Conclusions

The evidence in this network meta‐analysis illustrates that non‐pharmacological interventions are effective and safe for labour pain management in low‐risk pregnant women. In the future, well‐designed studies are needed to validate the conclusion of this network meta‐analysis.

Relevance to clinical practice

The results support the use of non‐pharmacological interventions, especially aromatherapy and acupressure, to relieve labour pain in low‐risk pregnant women. Non‐pharmacological interventions for labour pain management are recommended to apply according to maternal women's preference and values.
Genistein reverses the effect of 17β‐estradiol on exacerbating experimental occlusal interference‐induced chronic masseter hyperalgesia in ovariectomised rats
Authors: Liu Yun , Zhang Xiao‐Yu , Fan Ying‐Ying , Xu Xiao‐Xiang , Xie Qiu‐Fei
Published: June 2021

Background

Oro‐facial pain is more prevalent in women than in men, and oestrogen may underlie this sex difference. Genistein reversed the potentiation of 17β‐estradiol (E2) on glutamate‐induced acute masseter nociceptive behaviour, but its role in dental experimental occlusal interference (EOI)‐induced chronic masseter hyperalgesia remains unclear.

Objective

This study aimed to investigate sex differences, and to explore the role and underlying mechanisms of genistein in E2‐potentiated EOI‐induced chronic masseter hyperalgesia in rats.

Methods

Female and male rats were prepared to compare the sex differences of masseter hyperalgesia induced by EOI using a 0.4‐mm‐thick metal crown. Female rats were ovariectomised (OVX) and treated with E2 and genistein, followed by EOI. The head withdrawal threshold (HWT) was examined to assess masseter sensitivity. The protein expression of transient receptor potential vanilloid‐1 (TRPV1) in the trigeminal ganglion (TG) was detected using western blotting. Immunofluorescence staining was used to reveal the colocalisation of oestrogen receptors (ERs) with TRPV1 and the percentage of TRPV1‐positive neurons in the TG.

Results

To some extent, female rats displayed enhanced sensitivity to EOI‐induced chronic masseter hyperalgesia compared with males. Female rats showed the lowest HWT in the pro‐oestrus phase. Pre‐treatment with genistein antagonised E2 potentiation in EOI‐induced masseter hyperalgesia and blocked the effect of E2 by downregulating TRPV1 protein expression and the percentage of TRPV1‐positive neurons in the TG.

Conclusion

Female rats showed greater masseter hyperalgesia than males under EOI. Genistein antagonised the facilitation of EOI‐induced chronic masseter hyperalgesia by E2 probably through inhibiting TRPV1 in the TG.
Central apnea and periodic breathing in children with underlying conditions
Authors: Ghirardo Sergio , Amaddeo Alessandro , Griffon Lucie , Khirani Sonia , Fauroux Brigitte
Published: June 2021

Central sleep apneas and periodic breathing are poorly described in childhood. The aim of the study was to describe the prevalence and characteristics of central sleep apnea and periodic breathing in children with associated medical conditions, and the therapeutic management. We retrospectively reviewed all poly(somno)graphies with a central apnea index ≥ 5 events per hr in children aged > 1 month performed in a paediatric sleep laboratory over a 6‐year period. Clinical data and follow‐up poly(somno)graphies were gathered. Ninety‐five out of 2,981 patients (3%) presented central sleep apnea: 40% were < 1 year, 41% aged 1–6 years, and 19% aged ≥ 6 years. Chiari malformation was the most common diagnosis (13%). Mean central apnea index was 20 ± 30 events per hr (range 5–177). Fifty‐eight (61%) children had an exclusive central pattern with < 5 obstructive events per hr. Periodic breathing was present in 79 (83%) patients, with a mean percentage of time with periodic breathing of 9 ± 16%. Among periodic breathing episodes, 40% appeared after a sigh, 8% after an obstructive event, 6% after breathing instability and 2% after bradypnea. The highest clinical apnea index and percentage of time with periodic breathing were observed in children with encephalopathy and/or epilepsy (68 ± 63 events per hr and 30 ± 34%). Clinical apnea index did not differ according to age, while periodic breathing duration was longer in children > 1 year old. Watchful waiting was performed in 22 (23%) patients with spontaneous improvement in 20. Other treatments (upper airway or neurosurgery, nocturnal oxygen therapy, continuous positive airway pressure, non‐invasive ventilation) were effective in selected patients. Central sleep apnea is rare in children and comprises heterogeneous conditions. Sleep studies are essential for the diagnosis, characterization and management of central sleep apnea.
The impact of Baby Friendly Initiative accreditation: An overview of systematic reviews
Authors: Fair Frankie J. , Morrison Alison , Soltani Hora
Published: June 2021

Despite its reported benefits, breastfeeding rates are low globally, and support systems such as the Baby Friendly Initiative (BFI) have been established to support healthy infant feeding practices and infant bonding. Increasingly reviews are being undertaken to assess the overall impact of BFI accreditation. A systematic synthesis of current reviews has therefore been carried out to examine the state of literature on the effects of BFI accreditation. A systematic search of CINAHL, MEDLINE, Maternal and Infant Health, Scopus, the Cochrane Library and PROSPERO was undertaken. Study selection, data extraction and critical appraisal of included reviews using the AMSTAR‐2 tool were undertaken by two authors, with disagreements resolved through discussion with the third author. Due to heterogeneity, a narrative synthesis of findings was applied. Fourteen reviews met the inclusion criteria. Overall confidence in the results of the review was rated as high for three reviews, low for two reviews and critically low for nine reviews. Most evidence suggests some increase in breastfeeding initiation, exclusivity and duration of breastfeeding, and one main trial suggests decreased gastrointestinal infection and allergic dermatitis in infants. However, overall certainty in the evidence was rated as very low across all outcomes due to concerns over risk of bias within and heterogeneity between the original studies. More contemporary, good‐quality randomised controlled trials or well‐controlled prospective comparative cohorts are required to better evaluate the impact of full BFI accreditation, with particular attention paid to the context of the research and to long‐term maternal and infant health outcomes.
SWEET genes and TAL effectors for disease resistance in plants: Present status and future prospects
Authors: Gupta Pushpendra K. , Balyan Harindra S. , Gautam Tinku
Published: June 2021

SWEET genes encode sugar transporter proteins and often function as susceptibility (S) genes. Consequently, the recessive alleles of these SWEET genes provide resistance. This review summarizes the available literature on the molecular basis of the role of SWEET genes (as S genes) in the host and corresponding transcription activator‐like effectors (TALEs) secreted by the pathogen. The review has four major sections, which follow a brief introduction: The first part gives some details about the occurrence and evolution of SWEET genes in approximately 30 plant species; the second part gives some details about systems where (a) SWEET genes with and without TALEs and (b) TALEs without SWEET genes cause different diseases; the third part summarizes the available information about TALEs along with interfering/truncated TALEs secreted by the pathogens; this section also summarizes the available information on effector‐binding elements (EBEs) available in the promoters of either the SWEET genes or the Executor R genes; the code that is used for binding of TALEs to EBEs is also described in this section; the fourth part gives some details about the available approaches that are being used or can be used in the future for exploiting SWEET genes for developing disease‐resistant cultivars. The review concludes with a section giving conclusions and future possibilities of using SWEET genes for developing disease‐resistant cultivars using different approaches, including conventional breeding and genome editing.
Nonlinear plant–plant interactions modulate impact of extreme drought and recovery on a Mediterranean ecosystem
Authors: Haberstroh Simon , Caldeira Maria C. , Lobo‐do‐Vale Raquel , Martins Joana I. , Moemken Julia , Pinto Joaquim G. , Werner Christiane
Published: June 2021

Interaction effects of different stressors, such as extreme drought and plant invasion, can have detrimental effects on ecosystem functioning and recovery after drought. With ongoing climate change and increasing plant invasion, there is an urgent need to predict the short‐ and long‐term interaction impacts of these stressors on ecosystems.

We established a combined precipitation exclusion and shrub invasion (Cistus ladanifer) experiment in a Mediterranean cork oak (Quercus suber) ecosystem with four treatments: (1)Q. subercontrol; (2)Q. suberwith rain exclusion; (3)Q. suberinvaded by shrubs; and (4)Q. suberwith rain exclusion and shrub invasion. As key parameter, we continuously measured ecosystem water fluxes.

In an average precipitation year, the interaction effects of both stressors were neutral. However, the combination of imposed drought and shrub invasion led to amplifying interaction effects during an extreme drought by strongly reducing tree transpiration. Contrarily, the imposed drought reduced the competitiveness of the shrubs in the following recovery period, which buffered the negative effects of shrub invasion onQ. suber.

Our results demonstrate the highly dynamic and nonlinear effects of interacting stressors on ecosystems and urges for further investigations on biotic interactions in a context of climate change pressures.
AnAgrobacterium‐mediated stable transformation technique for the hornwort modelAnthoceros agrestis
Authors: Frangedakis Eftychios , Waller Manuel , Nishiyama Tomoaki , Tsukaya Hirokazu , Xu Xia , Yue Yuling , Tjahjadi Michelle , Gunadi Andika , Van Eck Joyce , Li Fay‐Wei , Szövényi Péter , Sakakibara Keiko
Published: June 2021

Despite their key phylogenetic position and their unique biology, hornworts have been widely overlooked. Until recently there was no hornwort model species amenable to systematic experimental investigation.Anthoceros agrestishas been proposed as the model species to study hornwort biology.

We have developed anAgrobacterium‐mediated method for the stable transformation ofA. agrestis, a hornwort model species for which a genetic manipulation technique was not yet available.

High transformation efficiency was achieved by using thallus tissue grown under low light conditions. We generated a total of 274 transgenicA. agrestislines expressing the β‐glucuronidase (GUS), cyan, green, and yellow fluorescent proteins under control of the CaMV 35S promoter and several endogenous promoters. Nuclear and plasma membrane localization with multiple color fluorescent proteins was also confirmed.

The transformation technique described here should pave the way for detailed molecular and genetic studies of hornwort biology, providing much needed insight into the molecular mechanisms underlying symbiosis, carbon‐concentrating mechanism, RNA editing and land plant evolution in general.
Variant analyses of candidate genes in orofacial clefts in multi‐ethnic populations
Authors: Li Mary , Olotu Joy , Buxo‐Martinez Carmen J. , Mossey Peter A. , Anand Deepti , Busch Tamara , Alade Azeez , Gowans Lord J. J. , Eshete Mekonen , Adeyemo Wasiu L. , Naicker Thirona , Awotoye Waheed O. , Gupta Sagar , Adeleke Chinyere , Bravo Valeria , Huang Siyong , Adamson Olatunbosun O. , Toraño Ada M. , Bello Carolina A. , Soto Mairim , Soto Marilyn , Ledesma Ricardo , Marquez Myrellis , Cordero Jose F. , Lopez‐Del Valle Lydia M. , Salcedo Maria I. , Debs Natalio , Petrin Aline , Malloy Hannah , Elhadi Khalid , James Olutayo , Ogunlewe Mobolanle O. , Abate Fekir , Hailu Abiye , Mohammed Ibrahim , Gravem Paul , Deribew Milliard , Gesses Mulualem , Hassan Mohaned , Pape John , Obiri‐Yeboah Solomon , Arthur Fareed K. N. , Oti Alexander A. , Donkor Peter , Marazita Mary L. , Lachke Salil A. , Adeyemo Adebowale A. , Murray Jeffrey C. , Butali Azeez
Published: June 2021

Objectives

Cleft lip with/without cleft palate and cleft palate only is congenital birth defects where the upper lip and/or palate fail to fuse properly during embryonic facial development. Affecting ~1.2/1000 live births worldwide, these orofacial clefts impose significant social and financial burdens on affected individuals and their families. Orofacial clefts have a complex etiology resulting from genetic variants combined with environmental covariates. Recent genome‐wide association studies and whole‐exome sequencing for orofacial clefts identified significant genetic associations and variants in several genes. Of these, we investigated the role of common/rare variants inSHH,RORA,MRPL53,ACVR1, andGDF11.

Materials and Methods

We sequenced these five genes in 1255 multi‐ethnic cleft lip with/without palate and cleft palate only samples in order to find variants that may provide potential explanations for the missing heritability of orofacial clefts. Rare and novel variants were further analyzed using in silico predictive tools.

Results

Ninteen total variants of interest were found, with variant types including stop‐gain, missense, synonymous, intronic, and splice‐site variants. Of these, 3 novel missense variants were found, one inSHH, one inRORA, and one inGDF11.

Conclusion

This study provides evidence that variants inSHH,RORA,MRPL53,ACVR1, andGDF11may contribute to risk of orofacial clefts in various populations.
Clinical Observations of Kümmell Disease Treatment Through Percutaneous Fixation Combined with Vertebroplasty
Authors: Gan Dong‐Hao , Fang Meng‐Ze , Xue Hai‐Peng , Tan Guo‐Qing , Li Nian‐Hu , Li Zhi‐Chao , Xu Zhan‐Wang
Published: June 2021

Objective

To explore the safety and efficacy of percutaneous pedicle screw fixation combined with vertebroplasty for the treatment of stage III Kümmell disease.

Methods

The clinical data and follow‐up results of 22 patients with Kümmell disease who were admitted to our department from 2014 to 2018 were analyzed. There were 14 females and eight males, and the Age range was 58–81 years. All patients were followed up for 24 months. The treatment method was percutaneous pedicle screw fixation combined with vertebroplasty. The patient general information such as age, gender, bedrest time and location of fracture vertebrae were recorded. The clinical symptoms and imaging data of visual analogue scale (VAS), bone cement leakage, Oswestry Disability Index (ODI), Cobb angle, anterior, middle and posterior height of the diseased vertebral body, and complications were recorded before operation and during follow‐up.

Results

For patients enrolled, no bone cement leakage was observed during the operation; no patients developed infections after operation. The operation was safe and resulted in a short bedrest time. The VAS score and ODI index at 3 and 24 months postoperative (2.86 ± 0.83, 31.68% ± 6.21%; 3.0 ± 0.82, 32.78% ± 6.05%) were significantly lower than that recoded preoperatively (7.59 ± 0.59, 71.5% ± 8.84%) (P < 0.05). Additionally, there was no significant difference between the records at 3 and 24 months after operation (P > 0.05). Imaging data showed that the bone cement and screws were in good position and did not move during postoperative and follow‐up. The anterior, middle and posterior height of the diseased vertebral body measured 2 days after surgery (23.46 ± 4.72, 23.12 ± 3.05, 25.81 ± 2.22) and at last follow‐up (20.83 ± 4.48, 21.78 ± 2.74, 24.74 ± 1.93) were higher than that recorded preoperatively (13.08 ± 4.49, 12.93 ± 3.53, 19.32 ± 2.73) (P < 0.05), and the Cobb angle measured 2 days and 24 months after operation (9.57 ± 4.63, 10.68 ± 3.97) were lower than that recorded preoperatively (28.24 ± 8.95) (P < 0.05), and no significant difference was found between the values recorded at 2 days and 24 months after operation (P > 0.05). Follow‐up for 24 months, there was no re‐fracture of the diseased vertebrae and internal fixation loosening, but two cases of adjacent vertebral refracture complications occurred, and the effect was good after PVP treatment.

Conclusion

Short‐segment percutaneous pedicle screw fixation combined with vertebroplasty in the treatment of stage III Kümmel disease can effectively restore the height of the diseased vertebrae, kyphosis correction, reduce trauma, prevent the diseased vertebral body from collapsing again, and effectively improves clinical symptoms.
Titanium Alloy Gamma Nail versus Biodegradable Magnesium Alloy Bionic Gamma Nail for Treating Intertrochanteric Fractures: A Finite Element Analysis
Authors: Li Ming , Zhao Kuo , Ding Kai , Cui Yun‐wei , Cheng Xiao‐dong , Yang Wei‐jie , Hou Zhi‐yong , Zhang Ying‐ze , Chen Wei , Hu Pan , Zhu Yan‐bin
Published: June 2021

Objective

To using finite element analysis to investigate the effects of the traditional titanium alloy Gamma nail and a biodegradable magnesium alloy bionic Gamma nail for treating intertrochanteric fractures.

Methods

Computed tomography images of an adult male volunteer of appropriate age and in good physical condition were used to establish a three‐dimensional model of the proximal femur. Then, a model of a type 31A1 intertrochanteric fracture of the proximal femur was established, and the traditional titanium alloy Gamma nails and biodegradable magnesium alloy bionic Gamma nails were used for fixation, respectively. The von Mises stress, the maximum principal stress, and the minimum principal stress were calculated to evaluate the effect of bone ingrowth on stress distribution of the proximal femur after fixation.

Results

In the intact model, the maximum stress was 5.8 MPa, the minimum stress was −11.7 MPa, and the von Mises stress was 11.4 MPa. The maximum principal stress distribution of the cancellous bone in the intact model appears in a position consistent with the growth direction of the principal and secondary tensile zones. After traditional Gamma nail healing, the maximum stress was 32 MPa, the minimum stress was −23.5 MPa, and the von Mises stress was 31.3 MPa. The stress concentration was quite obvious compared with the intact model. It was assumed that the nail would biodegrade completely within 12 months postoperatively. The maximum stress was 18.7 MPa, the minimum stress was −12.6 MPa, and the von Mises stress was 14.0 MPa. For the minimum principal stress, the region of minimum stress value less than −10 MPa was significantly improved compared with the traditional titanium alloy Gamma nail models. Meanwhile, the stress distribution of the bionic Gamma nail model in the proximal femur was closer to that of the intact bone, which significantly reduced the stress concentration of the implant.

Conclusion

The biodegradable magnesium alloy bionic Gamma nail implant can improve the stress distribution of fractured bone close to that of intact bone while reducing the risk of postoperative complications associated with traditional internal fixation techniques, and it has promising clinical value in the future.
Examining the association of medical complications and posttraumatic stress symptoms in pediatric solid organ transplant patients and their caregivers
Authors: Masood Saba S. , Triplett Kelli N. , Killian Michael , Mayersohn Gillian S. , Desai Dev M.
Published: June 2021

Background

Post‐traumatic stress symptoms (PTSS) have been reported by pediatric solid organ transplant (SOT) patients and their caregivers well after transplantation. This study examined the relationship between PTSS, medication adherence, and medical complications in SOT patients and their caregivers. A secondary aim examined the association between patient and caregiver‐reported PTSS.

Methods

Pediatric SOT patients (N = 69) and caregivers (N = 73) reported on PTSS by completing the Child PTSD Symptom Scale (patients 8–17 years) or the Impact of Events Scale—Revised (patients 18 years and older and caregivers). Patient medication adherence was assessed using the Medication Level Variability Index (MLVI). Patients were dichotomized as experiencing a post‐transplant medical complication (ie, transplant‐related hospital admission prior to the year completing measures of PTSS) or no complications.

Results

Medication adherence was not significantly associated with patient or caregiver PTSS. A moderate effect size was found for elevated young adult and caregiver PTSS and the presence of a medical complication. Generally, the association between self‐reported patient and caregiver PTSS was low.

Conclusions

The presence of elevated PTSS in young adult patients may be partially explained by the presence of proximal medical complications and more so by comorbid psychiatric diagnoses in child and adolescent patients (based on exploratory analyses). Caregivers of patients with medical complications within the past year reported higher levels of PTSS. Overall, transplantation and its associated impact on PTSS may be unique experience for patients versus caregivers. Qualitative research may further elucidate these experiences and inform future clinical interventions.
Large for size in pediatrics liver transplant using left lateral segment grafts: A single center experience
Authors: Zakaria Hazem Mohamed , Alobthani Salah , Elsarawy Ahmed , Saleh Yahia , Zidan Ahmed , Alabbad Saleh , Elsheikh Yasser , Algoufi Talal , Shagrani Mohammad , Troisi Roberto Ivan , Broering Dieter
Published: June 2021

Background

There are still controversies in using the large left lateral segment in pediatrics LT, with the possibility of the problem of LFS grafts, and the use of monosegmental or reduced liver grafts in small infants. This study aimed to evaluate our experience with LFSG in pediatrics LT.

Methods

A cohort retrospective analysis was conducted including pediatric recipients who underwent LT between January 2011 and October 2019. We compared recipients with GRWR ≥ 4% (LFS) vs GRWR < 4% as an average for size grafts.

Results

There were 331 pediatric LT, 74 patients with GRWR ≥ 4%, and 257 patients with GRWR < 4%. In the group of LFS grafts, temporary abdominal closure by silicon patch was done in 39 patients (52.7%), 2 patients (2.7%) had postoperative HAT, 3 patients (4.1%) early PVT, 1 patient (1.3%) bile leak, and 3 patients (4.1%) had wound infection, with no significant difference in these complications between the 2 groups. In patients with LFS‐ grafts, the 1‐, 3‐, 5‐, and 7‐year patients survival rates were 94.6%, 91.7%, 91.7%, and 91.7%, respectively, while the survival rates in patients of the other group were 96.1%, 92.6%, 91.9%, and 91.9%, respectively, with no significant difference (p = .85).

Conclusion

Using LFS graft by left lateral segment in pediatric LT with potential delayed abdominal closure is a safe and feasible option with good outcomes and unnecessary need for graft reduction if performed by an experienced multidisciplinary team.
Development strategies for middle‐income countries in a digital world—Insights from modern trade economics
Authors: Mayer Jörg
Published: June 2021

The digitalisation of economic activities, combined with a secular slowdown in the growth of global output and trade, reduces the potential of traditional export‐oriented manufacturing as a development strategy. This paper takes a trade economics perspective to outline a possible response to the changed nature of industrialisation. The outlined response currently applies mainly to middle‐income countries but deserves attention also in longer‐term development strategies of low‐income countries. The paper argues that digital technologies affect trade costs through various mechanisms, which apply differently to manufactures and services and determine decisions of multi‐product firms on what to produce for what market. Emphasising big data analysis of customer preferences as an input to manufacturing, the paper finds that (i) industrialisation and service‐oriented development strategies are complements, rather than substitutes; (ii) access to data on customer preferences is an asset for developing countries; and (iii) data governance, which harnesses the increasing dependence of manufacturing on data, and innovation policies, which give greater importance to indigenous innovation, crucially augment the potential of industrialisation as a development strategy in a digital era.
Fibrosis: Sirtuins at the checkpoints of myofibroblast differentiation and profibrotic activity
Authors: Zullo Alberto , Mancini Francesco Paolo , Schleip Robert , Wearing Scott , Klingler Werner
Published: June 2021

Fibrotic diseases are still a serious concern for public health, due to their high prevalence, complex etiology and lack of successful treatments. Fibrosis consists of excessive accumulation of extracellular matrix components. As a result, the structure and function of tissues are impaired, thus potentially leading to organ failure and death in several chronic diseases. Myofibroblasts represent the principal cellular mediators of fibrosis, due to their extracellular matrix producing activity, and originate from different types of precursor cells, such as mesenchymal cells, epithelial cells and fibroblasts. Profibrotic activation of myofibroblasts can be triggered by a variety of mechanisms, including the transforming growth factor‐β signalling pathway, which is a major factor driving fibrosis. Interestingly, preclinical and clinical studies showed that fibrotic degeneration can stop and even reverse by using specific antifibrotic treatments. Increasing scientific evidence is being accumulated about the role of sirtuins in modulating the molecular pathways responsible for the onset and development of fibrotic diseases. Sirtuins are NAD+‐dependent protein deacetylases that play a crucial role in several molecular pathways within the cells, many of which at the crossroad between health and disease. In this context, we will report the current knowledge supporting the role of sirtuins in the balance between healthy and diseased myofibroblast activity. In particular, we will address the signalling pathways and the molecular targets that trigger the differentiation and profibrotic activation of myofibroblasts and can be modulated by sirtuins.
Large Eddy Simulations on Fan Shaped Film Cooling Hole With Upstream Boundary Layer Turbulence Effect Generated by Trip Strip
Authors: Kang Young Seok , Jun Sangook , Rhee Dong-Ho
Published: June 2021

Large eddy simulations (LESs) on the well-known 7-7-7 fan shaped cooling hole were carried out. Like using a trip strip to create turbulent boundary layer in practical experiments, trip strips with different configurations were placed upstream of the cooling hole to investigate incoming turbulent boundary layer effect on the film cooling flow behavior. Without the trip, horseshoe vortex generated by laminar boundary layer induced laterally discharging cooling flow in the lateral direction. Meanwhile, the induced cooling flow formed high film cooling effectiveness region around the film cooling hole. When the incoming boundary flow was turbulent, laterally discharged cooling flow was influenced by the turbulent boundary layer to dissipate to the main flow and resultant high effectiveness region disappeared. Depending on the trip configuration, quantitative characteristics of boundary layer such as turbulent intensity, momentum thickness, and shape factor were strongly affected. Some trip configurations resulted in fully developed turbulent boundary layer just before leading edge of the film cooling hole. In such cases, distribution of the film cooling effectiveness showed a reasonable agreement with available experimental data where the quantitative properties of the turbulent boundary layer were similar. However, when the trip was located too close to the film cooling hole, the separated and reattached flow did not develop into the stabilized turbulent boundary layer. Then strong turbulence intensity in the main flow boundary layer stimulated break down of the cooling flow vortex structure and early dissipation to the main flow. It resulted in restricted film cooling flow coverage.
Particulate Emission Reduction by Fuel Injection Timing Optimization in a Gasoline Direct Injection Engine
Authors: Sharma Nikhil , Agarwal Avinash Kumar
Published: June 2021

Optimized fuel injection timings in internal combustion engines exhibit superior performance, combustion characteristics, and lower emissions. Particularly, particulate emissions from a gasoline direct injection (GDI) engines are highly dependent on fuel injection timings. GDI engines have emerged as a popular choice of power plants for automobiles among customers worldwide. They are preferred over multiple-port fuel injection (MPFI) engines in the transport sector because of their superior fuel economy and performance characteristics. The main objective of this study is to optimize a GDI engine for the lowest particulate emission at different fuel injection timings. GDI engine was investigated for particulate matter (PM) mass/particulate number (PN) emissions at five fuel injection timings (230, 250, 270, 290, and 310 deg bTDC), covering the entire envelope. Once the optimum fuel injection timing was determined, an engine exhaust particle sizer was used to measure the particle size-number distribution. Particulate samples from the engine were also collected on a filter paper for morphological investigations of particulates collected under optimized fuel injection timings. These experiments confirmed the importance and need to optimize the fuel injection timings at every engine operating point to reduce the PM/PN emissions from a GDI engine, which remains one of the biggest unresolved challenges to this technology.
A preliminary study on two-dimensional grid-free compressive beamforming for arbitrary planar array geometries
Authors: Chu Zhigang , Liu Yanli , Yang Yang , Yang Yongxin
Published: June 2021

The two-dimensional (2D) grid-free compressive beamforming based on atomic norm minimization is a promising solution for estimating the source direction-of-arrival and quantifying the source strength. However, the existing method is limited to measuring with rectangular grid arrays. To overcome this limitation, a 2D grid-free compressive beamforming strategy for arbitrary planar array geometries is proposed, where the microphone pressure is transformed into a representation of 2D Fourier series expansion. The term truncation method of Fourier series polynomials is established. The effectiveness and feasibility of the proposed method in the acoustic source identification are preliminarily verified by an experimental case, and topics worthy of further study are discussed based on the numerical simulations.