bluuebunny/crossref_metadata_2025 huggingface dataset:
miR‐29a‐3p promotes migration and invasion in ameloblastoma via Wnt/β‐catenin signaling by targeting catenin beta interacting protein 1
Authors: Liu Sai , Liu Dongjuan , Liu Jinwen , Liu Jiayi , Zhong Ming
Published: October 2021

Background

Ameloblastoma (AB) is a common epithelial odontogenic tumor. The Wnt/β‐catenin pathway has been found to be related to AB invasion.

Methods

The alteration expression of microRNAs (miRNAs) and messenger RNAs (mRNAs) was performed by miRNA and mRNA microarray analysis and validated by quantitative real‐time polymerase chain reaction (RT‐PCR). The effects of miR‐29a‐3p on migration and invasion in AB cells were evaluated by a transwell assay. Bioinformatic prediction was conducted using the miRSystem and validated by quantitative RT‐PCR, western blot, and a luciferase reporter assay.

Results

miR‐29a‐3p was overexpressed in AB tissues, which promoted the migration and invasion of AB cells in vitro. Catenin beta interacting protein 1 (CTNNBIP1), a negative regulator of the Wnt/β‐catenin pathway, was predicted to be a target of miR‐29a‐3p. miR‐29a‐3p inhibited the expression of CTNNBIP1 and promoted the expression of the downstream molecules of the Wnt/β‐catenin pathway.

Conclusions

miR‐29a‐3p promoted migration and invasion in AB via Wnt/β‐catenin signaling by targeting CTNNBIP1.
Identifying distinct risks of treatment failure in nasopharyngeal carcinoma: Study based on the dynamic changes in peripheral blood lymphocytes, monocytes, N classification, and plasma Epstein‐Barr virus DNA
Authors: Liu Li‐Ting , Liang Yu‐Jing , Guo Shan‐Shan , Xie Yao , Jia Guo‐Dong , Wen Dong‐Xiang , Tang Lin‐Quan , Chen Qiu‐Yan , Mai Hai‐Qiang
Published: October 2021

Background

To evaluate the prognostic value of the dynamic change in absolute lymphocyte counts (ALCs) and absolute monocyte counts (AMCs) and identify patients with N stage and plasma Epstein‐Barr virus (EBV) DNA levels in nasopharyngeal carcinoma (NPC) who are at risk of treatment failure.

Methods

A total of 1124 eligible patients with Stage II–IVb NPC treated with concurrent chemoradiotherapy (CCRT) were enrolled. Percentage changes in the ALC (ΔALC%) and AMC (ΔAMC%) were calculated.

Results

Patients with high ΔALC% were correlated with poorer 5‐year overall survival (OS), progression‐free survival (PFS), and distant metastasis‐free survival (DMFS) rates than those with low ΔALC%. Likewise, high ΔAMC% was significantly associated with worse outcome than low ΔAMC% (OS, p = 0.001; PFS, p = 0.001; DMFS, p = 0.034). Multivariate analyses revealed that ΔALC% (p = 0.046), ΔAMC% (p = 0.019), and EBV DNA level (p < 0.001) were independent prognostic factors for OS. With respect to PFS, ΔALC% (p = 0.036), ΔAMC% (p = 0.011), N classification (p = 0.016), and EBV DNA level (p < 0.001) were also independent prognosticators. Based on the aforementioned independent risk factors (ΔALC% ≥ 83.33%, ΔAMC% ≥ 40.00%, Stage N2–3, EBV DNA ≥ 4000 copies/ml), patients were divided into three different risk groups (low‐risk group [with <1 risk factor], intermediate risk group [with 1–3 risk factors], and high‐risk group [with 4 risk factors]) that correlated with disparate risks of death (p < 0.001), disease progression (p < 0.001), and distant metastasis (p < 0.001).

Conclusions

High ΔALC% and ΔAMC% were correlated with poor prognosis in patients with NPC. Risk stratification based on ΔALC%, ΔAMC%, N classification, and plasma EBV DNA levels could provide potential utility for risk‐adapted therapeutic strategies for NPC.
Parity is associated with better prognosis in ovarian germ cell tumors, but not in other ovarian cancer subtypes
Authors: Sköld Camilla , Koliadi Anthoula , Enblad Gunilla , Stålberg Karin , Glimelius Ingrid
Published: October 2021

Ovarian cancer is influenced by reproductive factors, with a reduced risk of epithelial ovarian cancer in parous women. Nonepithelial ovarian cancer frequently affects young women and often precedes or occurs during the childbearing years. However, the impact of reproductive factors on ovarian cancer survival remains unclear: in epithelial ovarian cancer, data are conflicting, and subtype‐specific associations have not been examined, and in nonepithelial ovarian cancer, it has not been studied. Using Swedish registers, we evaluated associations between women's reproductive history and cancer‐specific mortality by subtype of epithelial and nonepithelial ovarian cancer in 3791 women born 1953 and later, diagnosed from 1990 to 2018. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated using Cox‐proportional hazard models. Parity was associated with a 78% decreased risk of cause‐specific mortality in 243 women with germ cell tumors (GCTs) (parous vs nulliparous, adjusted for age at diagnosis: HR: 0.22 [95% CI 0.07‐0.62]), with a decreased risk with increasing number of births (per birth: HR: 0.60 [95% CI 0.38‐0.95]). We found no evidence of associations between parity and cause‐specific mortality among the 334 patients with sex‐cord stromal tumors, nor among the 3214 patients with epithelial ovarian cancer; neither overall, nor by subtype. In conclusion, in our large, population‐based study, parity was associated with a clearly better prognosis in GCTs but not in the other ovarian cancer subtypes. Future research on how hormone exposure impacts GCT development may lead to a better understanding of mechanisms affecting survival.
Ethmoïdal metastasis as a first presentation of breast cancer
Authors: Kolsi Naourez , Jellali Sondes , Zouari Ines , Hathri Rim , Bouattay Rachida , Koubaa Jamel
Published: October 2021

A 43‐year‐old woman presented to the ENT department with bilateral nasal obstruction, epistaxis and bilateral exophthalmos. A diagnosis of sinonasal cancer was suggested at first; however, an ethmoïdal biopsy revealed ethmoïdal metastasis resulting from breast adenocarcinoma.
Alternative suture tightening technique for achieving adequate suture tension during B‐Lynch compression suture
Authors: Ramly Fathi , Mohd Kasim Norhana
Published: October 2021

An alternate pull‐on‐compress and pull‐on‐release suture tightening technique can be considered when a surgeon encounters difficulty when performing B‐Lynch compression suture.
Information‐centric networking driven psychology recognition and health conduction of undergraduates
Authors: Zhang Weifeng
Published: October 2021

It is considerably significant to recognize the psychology of undergraduates especially during the period of COVID‐19 outbreak. This letter proposes an Information‐Centric Networking (ICN) driven psychology recognition and health conduction method based on the active data collection mode, that is, all undergraduates submit their psychology data to manger without protest by the special sensor tool. Meanwhile, the involved undergraduates and the management center construct a large network model. In order to support the mobility of undergraduates, this letter exploits ICN paradigm to help the management and transmission of psychology data. In addition, this management center deploys Deep Belief Network (DBN) to analyze the submitted psychology data. Finally, this letter makes a practical simulation on campus, and the experimental results show that the proposed psychology control method not only has good recognition effect but also contributes to health conduction. To be specific, the proposed method can improve about 2.6% psychology recognition accuracy and decrease about 46.5% psychology recognition time.
Pharmacist interventions in an outpatient pain clinic at a Veterans Affairs Medical Center
Authors: Voll Priscell , Brooks Abigail , Vartan Christine M. , DiScala Sandra
Published: October 2021

Purpose

Clinical pharmacist practitioners (CPPs) ensure safe and evidence‐based pharmacotherapy practices. However, there is little information to date characterizing the impact of pain CPP interventions on patient outcomes within a CPP‐managed outpatient chronic and postoperative pain clinic. The primary objective of this study was to classify and quantify the number of pain CPP interventions in the outpatient pain clinic at the West Palm Beach Veteran Affairs Medical Center (WPB VAMC). The secondary objective assessed general patient outcomes associated with pain pharmacotherapy management by a CPP.

A retrospective chart review of pain CPP encounters was utilized to identify interventions over a 12‐month period. A total of 805 pain management encounters with a total of 1993 interventions were recorded by pain CPPs during that time. Descriptive statistics and sample size calculations were used to summarize and evaluate results. Overall, 55% of interventions were pharmacological, 45% were nonpharmacological interventions, and 5% were referrals to other specialty providers. For the secondary objective (n = 107), patients in the pain clinic on opioid therapy experienced an average oral morphine equivalent daily dose (MEDD) reduction of 21 mg without any identified suicide or overdose events and achieved on average 45% of their SMART goals by their last visit. In patients with baseline pain, enjoyment of life, and general activity (PEG) scores (n = 69), there were 43% of patients with improved PEG scores at their last visit in which 14% (10/69) experienced a clinically meaningful improvement in PEG scores.

Conclusion

Pain CPPs demonstrated a reduction in overall MEDDs safely while following the biopsychosocial approach to pain management by incorporating and referring for nonpharmacological interventions as well as completing opioid risk mitigation. Additional studies are needed to better characterize pain CPP impact on patient outcomes.
Vitamin D Actions: The Lung Is a Major Target for Vitamin D, FGF23, and Klotho
Authors: Gayan‐Ramirez Ghislaine , Janssens Wim
Published: October 2021

Vitamin D is well known for its role as a calcium regulator and in maintenance of phosphate homeostasis in musculoskeletal health, and fibroblast growth factor 23 (FGF23) and its coreceptor α‐klotho are known for their roles as regulators of serum phosphate levels. However, apart from these classical actions, recent data point out a relevant role of vitamin D and FGF23/klotho in lung health. The expression of the vitamin D receptor by different cell types in the lung and the fact that those cells respond to vitamin D or can locally produce vitamin D indicate that the lung represents a target for vitamin D actions. Similarly, the presence of the four FGF receptor isoforms in the lung and the ability of FGF23 to stimulate pulmonary cells support the concept that the lung is a target for FGF23 actions, whereas the contribution of klotho is still undetermined. This review will give an overview on how vitamin D or FGF23/klotho may act on the lung and interfere positively or negatively with lung health. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Long noncoding RNA Gas5 induces cell apoptosis and inhibits tumor growth via activating the CHOP‐dependent endoplasmic reticulum stress pathway in human hepatoblastoma HepG2 cells
Authors: Zhang Wei‐Yi , Zhan Hao‐Lian , Li Ming‐Kai , Wu Guan‐Di , Liu Zhe , Wu Ling‐Fei
Published: October 2021

In recent years, long noncoding RNAs (lncRNAs) have been demonstrated to be important tumor‐associated regulatory factors. LncRNA growth arrest‐specific transcript 5 (Gas5) acts as an anti‐oncogene in most cancers. Whether Gas5 acts as an oncogene or anti‐oncogene in hepatocellular carcinoma (HCC) remains unclear. In the present study, the expression and role of Gas5 in HCC were investigated in vitro and in vivo. Lower expression levels of Gas5 were determined in HCC tissues and cells by quantitative reverse transcription‐polymerase chain reaction. Overexpressed Gas 5 lentiviral vectors were constructed to analyze their influence on cell viability, migration, invasion, and apoptosis. Fluorescence in situ hybridization was used to identify the subcellular localization of Gas5. Protein complexes that bound to Gas5 were isolated from HepG2 cells through pull‐down experiments and analyzed by mass spectrometry. A series of novel Gas5‐interacting proteins were identified and bioinformatics analysis was carried out. These included ribosomal proteins, proteins involved in protein folding, sorting, and transportation in the ER, some nucleases and protein enzymes involved in gene transcription, translation, and other proteins with various functions.78 kDa glucose‐regulated protein (GRP78) was identified as a direct target of Gas5 by Rip‐qPCR and Western blot analysis assay. Gas5 inhibited HepG2 cell growth and induced cell apoptosis via upregulating CHOP to activate the ER stress signaling pathway. Further studies indicated that the knockdown of CHOP by shRNA partially reversed Gas5‐mediated apoptosis in HepG2 cells. Magnetic resonance imaging showed that the ectopic expression of Gas5 inhibited the growth of HCC in nude mice. These findings suggest that Gas5 functions as a tumor suppressor and induces apoptosis through activation of ER stress by targeting the CHOP signal pathway in HCC.
Biomarkers related to fatty acid oxidative capacity are predictive for continued weight loss in cachectic cancer patients
Authors: Catanese Silvia , Beuchel Carl Friedrich , Sawall Teresa , Lordick Florian , Brauer Rommy , Scholz Markus , Ceglarek Uta , Hacker Ulrich T.
Published: October 2021

Background

Cachexia is characterized by a negative protein and energy balance leading to loss of adipose tissue and muscle mass. Cancer cachexia negatively impacts treatment tolerability and prognosis. Supportive interventions should be initiated as early as possible. Biomarkers for early prediction of continuing weight loss during the course of disease are currently lacking.

Methods

In this pilot, observational, cross‐sectional, case–control study, cachectic cancer patients undergoing systemic first‐line cancer treatment were matched 2:1 with healthy controls according to age, gender and body mass index. Alterations in amino acid and energy metabolism, as indicated by acylcarnitine levels, were analysed using mass spectrometry in plasma samples (PS) and dried blood specimen (DBS). Welch's two‐sample t‐test was used for comparative analysis of metabolites between cancer patients and healthy matched controls and to identify the metabolomic profiles related to weight loss across different time points. A linear regression model was applied to correlate weight loss and single metabolites as predictor variables. Finally, metabolite pathway enrichment analyses were performed.

Results

Eighteen cases (14 male and 4 female) and 36 paired controls were enrolled. There was a good correlation between baseline PS and DBS of healthy controls for the levels of most amino acids but not for acylcarnitine. Amino acid levels related to cancer metabolism were significantly altered in cancer patients compared with controls in both DBS and PS for arginine, citrulline, histidine and ornithine and in DBS only for asparagine, glutamine, methylhistidine, methionine, ornithine, serine, threonine and leucine/isoleucine. Metabolite enrichment analysis in PS of cancer patients revealed histidine metabolism activation (P = 0.0025). Baseline acylcarnitine analysis in DBS was indicative for alterations of the mitochondrial carnitine shuttle, related to β‐oxidation: The ratio palmitoylcarnitine/acylcarnitine (Q2) and the ratio palmitoylcarnitine + octadecenoylcarnitine/acylcarnitine (Q3) were predictive for early weight loss (P < 0.0001) and weight loss during follow‐up. Activation of tryptophan metabolism (P = 0.035) in DBS and PS and activation of serine/glycine metabolism (P = 0.017) in PS were also related to early weight loss and across successive time points.

Conclusions

We found alterations in amino acid levels most likely attributable to cancer metabolism itself in cancer patients compared with controls. Baseline DBS represent a valuable analyte to study energy metabolism related to cancer cachexia. Acylcarnitine patterns (Q2, Q3) predicted further weight loss in cachectic cancer patients undergoing systemic therapy, and pathway analyses indicated involvement of the serine/glycine and the tryptophan pathway in this condition. Validation in larger cohorts is warranted.
Traceability of products and guide for batch definition in integrated continuous biomanufacturing
Authors: Lali Narges , Jungbauer Alois , Satzer Peter
Published: October 2021

BACKGROUND

A major improvement in biomanufacturing will arise with the transition from batch processing to continuous processing. Two important challenges to address in this change are batch definition and the ability to trace raw material through the process.

RESULTS

We used an established simulation of a process train to compare the conventional batch definition based on a fixed time to a new batch definition method based on the greatest common divisor (GCD) of the time period of the unit operations. We successfully demonstrated that, by using the new concept based on GCD, we will have a constant periodic concentration of product. With this basis, we can define batches in a continuous process, which will lead to higher control over the process, and we will be able to trace the material through the process.

CONCLUSION

We achieved better control over the process using the batch definition based on the GCD method. In comparison to collecting the outlet products over arbitrary hours or days, collecting the product based on a section using the GCD method meets the criteria for knowing the residence‐time distribution of the process, as advised by regulatory authorities. This method can be used in a continuous process or a hybrid process in which there are only a few continuous unit operations along with batch process operations. © 2021 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).
Commentary on the special issue on disproportionate exposure to trauma: Disrupting single stories, broadening the aperture, and embracing the trauma socioexposome in research with minoritized individuals
Authors: Powell Wizdom
Published: October 2021

The theory‐driven studies in this special issue of the Journal of Traumatic Stress illustrate the opportunities and inherent methodological complexities that arise in traumatic stress studies when scholars consider the unique social–ecological contexts and exposure histories of minoritized individuals. Moreover, the included articles challenge the field's paradigmatic preoccupation with maladaptive individual trauma responses and invite researchers to shift their attention to the role played by a range of environmental adversities. This commentary is organized around three key recommendations regarding what is needed to enhance future research and treatment among trauma‐exposed minoritized populations: (a) disrupt single scientific stories about trauma risk, detection, protection, and resilience; (b) embrace the complexity of the trauma socioexposome; and (c) expand capacity to assess, research, and mitigate syndemic risk. The present commentary describes how these key points are highlighted and underscored in the articles in this special issue, arriving at the conclusion that, more than ever, scholars and clinicians need lenses and methods that can help in assessing and treating the whole person and community from a biopsychosocial perspective when racism contibutes to a complex trauma socioexposome rather than perpetuating scientific and clinical models based only on single stories of isolated individuals confronted by discrete traumatic events.
Efficient and Broadband LiGaP2O7:Cr3+ Phosphors for Smart Near‐Infrared Light‐Emitting Diodes
Authors: Yuan Chenxu , Li Ruiyang , Liu Yongfu , Zhang Liangliang , Zhang Jiahua , Leniec Grzegorz , Sun Peng , Liu Zehua , Luo Zhaohua , Dong Rui , Jiang Jun
Published: October 2021

Broadband near‐infrared (NIR) phosphor‐converted (pc) LED is promising next‐generation tiny light source for smart and broadband NIR spectroscopy technology. However, NIR phosphors suffer from challenges in terms of low quantum efficiency and bandwidth. By selecting a host that has a big bandgap and weakening coupling effect among Cr3+, a novel LiGaP2O7:Cr3+ (LGAP:Cr3+) NIR phosphor that has a high external quantum efficiency (28.3%) is discovered. Under ≈450 nm excitation, LGAP:Cr3+ shows broad NIR emission from 700 to 1100 nm with a bandwidth of ≈170 nm. Importantly, the fabricated pcLED demonstrates bright broadband NIR light and an excellent performance in night vision. The results promise the use of the LGAP:Cr3+ phosphor for high‐performance broadband NIR LED that employs only one tiny blue LED chip.
Expansions of Presburger arithmetic with the exchange property
Authors: Mariaule Nathanaël
Published: October 2021

Let G be a model of Presburger arithmetic. Let be an expansion of the language of Presburger . In this paper, we prove that the ‐theory of G is ‐minimal iff it has the exchange property and is definably complete (i.e., any bounded definable set has a maximum). If the ‐theory of G has the exchange property but is not definably complete, there is a proper definable convex subgroup H. Assuming that the induced theories on H and are definable complete and o‐minimal respectively, we prove that any definable set of G is ‐definable.
Upcycling Plastic Waste into High Value‐Added Carbonaceous Materials
Authors: Choi Jiho , Yang Inchan , Kim Sung‐Soo , Cho Se Youn , Lee Sungho
Published: October 2021

Even though plastic improved the human standard of living, handling the plastic waste represents an enormous challenge. It takes more than 100 years to decompose discarded or buried waste plastics. Microplastics are one of the causes of significantly pervasive environmental pollutants. The incineration of plastic waste generates toxic gases, underscoring the need for new approaches, in contrast to conventional strategies that are required for recycling plastic waste. Therefore, several studies have attempted to upcycle plastic waste into high value‐added products. Converting plastic waste into carbonaceous materials is an excellent upcycling technique due to their diverse practical applications. This review summarizes various studies dealing with the upcycling of plastic waste into carbonaceous products. Further, this review discusses the applications of carbonaceous products synthesized from plastic waste including carbon fibers, absorbents for water purification, and electrodes for energy storage. Based on the findings, future directions for effective upcycling of plastic waste into carbonaceous materials are suggested.
Analysis of PLXNA1, NRP1, and NRP2 variants in a cohort of patients with isolated hypogonadotropic hypogonadism
Authors: Men Meichao , Chen Dan‐Na , Li Jia‐Da , Wang Xinying , Zeng Wang , Jiang Fang , Zheng Ruizhi , Dai Wenting
Published: October 2021

Background

Isolated hypogonadotropic hypogonadism (IHH) is a clinical syndrome described by failure of gonadal function secondary to defects on the synthesis, secretion, or action of the gonadotropin‐releasing hormone (GnRH). The secreted glycoprotein SEMA3A binds its receptors NRP1 or NRP2 and PLXNA to participate in axonal projection, dendritic branching, synaptic formation, and neuronal migration. Deficiency in SEMA3A, NRP1, NRP2, and PLXNA1 have been related to abnormal GnRH neuron development in mice and IHH in humans.

Methods

The aim of this study was to examine the genotypic and phenotypic spectra of the NRP1, NRP2, and PLXNA1 genes in a large cohort of IHH probands from China. We screened NRP1, NRP2, and PLXNA1 variants in Chinese IHH patients by whole exome sequencing and pedigree analysis.

Results

We identified 10 heterozygous missense variants in PLXNA1, five heterozygous missense variants in NRP1, and two heterozygous missense variants in NRP2. NRP1 variants were found only in IHH patients with defective olfaction (i.e., Kallmann syndrome, KS). In addition, 85% (17/20) of patients harbored variants in other IHH‐associated genes.

Conclusion

Our study greatly enriched the genotypic and phenotypic spectra of PLXNA1, NRP1, and NRP2 in IHH. It may be conducive to the genetic counseling, diagnosis, and treatment of IHH with mutations in the PLXNA1, NRP1, and NRP2 genes. Furthermore, our results indicated that NRP1 were strongly linked to hearing loss.
Fetal akinesia deformation sequence and massive perivillous fibrin deposition resulting in fetal death in six fetuses from one consanguineous couple, including literature review
Authors: Tjon Jill K. , Lakeman Phillis , van Leeuwen Elisabeth , Waisfisz Quinten , Weiss Marjan M. , Tan‐Sindhunata Gita M. B. , Nikkels Peter G. J. , van der Voorn Patrick J. P. , Salomons Gajja S. , Burchell George L. , Linskens Ingeborg H. , van der Knoop Bloeme J. , de Vries Johanna I. P.
Published: October 2021

Background

Massive perivillous fibrin deposition (MPFD) is associated with adverse pregnancy outcomes and is mainly caused by maternal factors with limited involvement of fetal or genetic causes. We present one consanguineous couple with six fetuses developing Fetal Akinesia Deformation Sequence (FADS) and MPFD, with a possible underlying genetic cause. This prompted a literature review on prevalence of FADS and MPFD.

Methods

Fetal ultrasound examination, motor assessment, genetic testing, postmortem examination, and placenta histology are presented (2009–2019). Literature was reviewed for the association between congenital anomalies and MPFD.

Results

All six fetuses developed normally during the first trimester. Thereafter, growth restriction, persistent flexed position, abnormal motility, and contractures in 4/6, consistent with FADS occurred. All placentas showed histologically confirmed MPFD. Genetic analyses in the five available cases showed homozygosity for two variants of unknown significance in two genes, VARS1 (OMIM*192150) and ABCF1 (OMIM*603429). Both parents are heterozygous for these variants. From 63/1999 manuscripts, 403 fetal outcomes were mobilized. In 14/403 fetuses, congenital abnormalities in association with MPFD were seen of which two fetuses with contractures/FADS facial anomalies.

Conclusion

The low prevalence of fetal contractures/FADS facial anomalies in association with MPFD in the literature review supports the possible fetal or genetic contribution causing FADS and MPFD in our family. This study with literature review supports the finding that fetal, fetoplacental, and/or genetic components may play a role in causing a part of MPFDs.
Overcoming severe calcified lower extremity artery in lower limb salvage operation by using the Fogarty catheter and vein graft
Authors: Kim Dong Yeon , Kim Yesol , Moon Suk‐Ho
Published: October 2021

Background

With severe vascular calcifications, vascular clamp application and utilizing the vessel for free flap recipient vessel becomes impossible. These obstacles can be overcome with the Fogarty catheter and vein graft.

Patients and methods

When unclampable artery was encountered intraoperatively, a vein graft was used to make a clampable recipient site for six diabetic foot patients (ages from 42 to 80). The end of the Fogarty catheter was inserted into the proximal end of the vein graft and the transected calcified vessel in sequence, and the balloon of the catheter was used as an intraluminal tourniquet. The remaining end of the vein graft was connected to the distal vessel with a vascular clamp.

Results

Five short vein graft revascularization for segmental arterial occlusion, one long vein graft for recipient artery elongation was done (lengths from 2 to 13.8 cm). Three delayed, and two immediate anterolateral thigh flaps (sizes from 15 to 150 cm2) were performed, and one patient received vein graft revascularization surgery only. Postoperative vascular sonography of all six patients showed well‐maintained patency. Minor flap marginal disruption occurred at two patients but healed with conservative care. Postoperative follow‐up was done for 1–18 months (average 7.17). Limb salvage was achieved for five patients and all five free flaps survived. However, for one patient, arterial restenosis at popliteal artery a month later lead to major amputation.

Conclusion

Using a Fogarty catheter and a vein graft may obtain perfect hemostasis during micro‐anastomosis and achieve successful microvascular reconstruction in patients with severely calcified vessels.
Assessment of fully automatic segmentation of pulmonary artery and aorta on noncontrast CT with optimal surface graph cuts
Authors: Sedghi Gamechi Zahra , Arias‐Lorza Andres M. , Saghir Zaigham , Bos Daniel , de Bruijne Marleen
Published: October 2021

Purpose

Accurate segmentation of the pulmonary arteries and aorta is important due to the association of the diameter and the shape of these vessels with several cardiovascular diseases and with the risk of exacerbations and death in patients with chronic obstructive pulmonary disease. We propose a fully automatic method based on an optimal surface graph‐cut algorithm to quantify the full 3D shape and the diameters of the pulmonary arteries and aorta in noncontrast computed tomography (CT) scans.

Methods

The proposed algorithm first extracts seed points in the right and left pulmonary arteries, the pulmonary trunk, and the ascending and descending aorta by using multi‐atlas registration. Subsequently, the centerlines of the pulmonary arteries and aorta are extracted by a minimum cost path tracking between the extracted seed points, with a cost based on a combination of lumen intensity similarity and multiscale medialness in three planes. The centerlines are refined by applying the path tracking algorithm to curved multiplanar reformatted scans and are then smoothed and dilated nonuniformly according to the extracted local vessel radius from the medialness filter. The resulting coarse estimates of the vessels are used as initialization for a graph‐cut segmentation. Once the vessels are segmented, the diameters of the pulmonary artery (PA) and the ascending aorta (AA) and the ratio are automatically calculated both in a single axial slice and in a 10 mm volume around the automatically extracted PA bifurcation level. The method is evaluated on noncontrast CT scans from the Danish Lung Cancer Screening Trial (DLCST). Segmentation accuracy is determined by comparing with manual annotations on 25 CT scans. Intraclass correlation (ICC) between manual and automatic diameters, both measured in axial slices at the PA bifurcation level, is computed on an additional 200 CT scans. Repeatability of the automated 3D volumetric diameter and ratio calculations (perpendicular to the vessel axis) are evaluated on 118 scan–rescan pairs with an average in‐between time of 3 months.

Results

We obtained a Dice segmentation overlap of 0.94 ± 0.02 for pulmonary arteries and 0.96 ± 0.01 for the aorta, with a mean surface distance of 0.62 ± 0.33 mm and 0.43 ± 0.07 mm, respectively. ICC between manual and automatic in‐slice diameter measures was 0.92 for PA, 0.97 for AA, and 0.90 for the ratio, and for automatic diameters in 3D volumes around the PA bifurcation level between scan and rescan was 0.89, 0.95, and 0.86, respectively.

Conclusion

The proposed automatic segmentation method can reliably extract diameters of the large arteries in non‐ECG‐gated noncontrast CT scans such as are acquired in lung cancer screening.
Reduction of motion effects in myocardial arterial spin labeling
Authors: Aramendía‐Vidaurreta Verónica , Gordaliza Pedro M. , Vidorreta Marta , Echeverría‐Chasco Rebeca , Bastarrika Gorka , Muñoz‐Barrutia Arrate , Fernández‐Seara María A.
Published: October 2021

Purpose

To evaluate the accuracy and reproducibility of myocardial blood flow measurements obtained under different breathing strategies and motion correction techniques with arterial spin labeling.

Methods

A prospective cardiac arterial spin labeling study was performed in 12 volunteers at 3 Tesla. Perfusion images were acquired twice under breath‐hold, synchronized‐breathing, and free‐breathing. Motion detection based on the temporal intensity variation of a myocardial voxel, as well as image registration based on pairwise and groupwise approaches, were applied and evaluated in synthetic and in vivo data. A region of interest was drawn over the mean perfusion‐weighted image for quantification. Original breath‐hold datasets, analyzed with individual regions of interest for each perfusion‐weighted image, were considered as reference values.

Results

Perfusion measurements in the reference breath‐hold datasets were in line with those reported in literature. In original datasets, prior to motion correction, myocardial blood flow quantification was significantly overestimated due to contamination of the myocardial perfusion with the high intensity signal of blood pool. These effects were minimized with motion detection or registration. Synthetic data showed that accuracy of the perfusion measurements was higher with the use of registration, in particular after the pairwise approach, which probed to be more robust to motion.

Conclusion

Satisfactory results were obtained for the free‐breathing strategy after pairwise registration, with higher accuracy and robustness (in synthetic datasets) and higher intrasession reproducibility together with lower myocardial blood flow variability across subjects (in in vivo datasets). Breath‐hold and synchronized‐breathing after motion correction provided similar results, but these breathing strategies can be difficult to perform by patients.
Longitudinal relaxation in fat‐water mixtures and its dependence on fat content at 3 T
Authors: Fortier Véronique , Levesque Ives R.
Published: October 2021

Longitudinal (T1) relaxation of triglyceride molecules and water is of interest for fat‐water separation and fat quantification. A better understanding of T1 relaxation could benefit modeling for applications in fat quantification and relaxation mapping. This work investigated T1 relaxation of spectral resonances of triglyceride molecules and water in liquid fat‐water mixtures and its dependence on the fat fraction. Dairy cream and a safflower oil emulsion were used. These were diluted with distilled water to produce a variety of fat mass fractions (4.4% to 35% in dairy cream and 6.3% to 52.3% in safflower oil emulsion). T1 was measured at room temperature at 3 T using an inversion recovery STimulated Echo Acquisition Mode (STEAM) MR spectroscopy method with a series of inversion times. T1 variations as a function of fat fraction were investigated for various resonances. A two‐component model was developed to describe the relaxation in a fat‐water mixture as a function of the fat fraction. The T1 of water and of all fat resonances studied in this work decreased as the fat fraction increased. The relative variation in T1 was different for each fat resonance. The T1 of the methylene resonance showed the least variation as a function of the fat fraction. The proposed two‐component model closely fits the observed T1 variations. In conclusion, this work clarifies how the T1 of major and minor fat resonances and of the water resonance varies as a function of the fat fraction in fat‐water mixtures. Knowledge of these variations could serve modeling, analysis of MRI measurements in fat‐water mixtures, and phantom preparation.
Revisiting US–China strategic competition in Central Asia and its impact on Pakistan
Authors: Gul Azeem , Munir Muhammad , Hussain Munawar , Hussain Mujahid
Published: October 2021

Since the dissolution of the former Soviet Union, the US, and China are aspiring to enhance their strategic influence in Central Asia which has recently been intensified due to China's Belt and Road Initiative (BRI). Further, China has also increased its influence in Central Asia through regional organizations such as Shanghai Cooperation Organization (SCO). Against this backdrop, Pakistan emerged as an important pivot of China's BRI where the China–Pakistan Economic Corridor (CPEC) is the flagship project. This study begins with a theoretical debate of Heartland theory of Halford John Mackinder and the later version of Heartland theory into Rimland theory by Nicolas Spykman, which explains the geopolitical significance of Central Asia for Major Powers. Within this theoretical context, the study discusses China and the US grand strategies in Central Asia in the form of China's BRI, SCO and the US counter‐strategies such as from phase 1.0, policy to 2.0, policy, and the recent initiative of C5 + 1. The study finds out that US–China strategic competition will have implications for various states having relations with both of these two major powers. In case of Pakistan, the strategic competition between China and the US will affect various dimensions of Pakistan's security at the broader level such as political, military, and economic security. First, at the political level, it is affecting Pakistan's relations with Russia, China, Iran, and Gulf States. Second, at military level, Pakistan's strategic value has been enhanced as a frontline state against terrorism. Finally, at the economic level, CPEC provides opportunities for Pakistan's economy and regional connectivity.
The effects of written catharsis on anger relief
Authors: Zhan Jun , Yu Shuhan , Cai Ruyi , Xu Hongfei , Yang Yue , Ren Jun , Luo Jing
Published: October 2021

Previous studies have found that “general catharsis”, such as hitting sandbags, does not reduce but increases an individual's anger feeling and aggressive behavior. Although the “goal catharsis” that is directed at attacking targets can temporarily relieve anger, there is a risk of increasing the tendency of aggressive personality if it is used for a long time. These findings raise serious doubts and challenges to the traditional view that “anger must be released” held by the classic catharsis theory that many people still trust. The present study compared the effects of “general catharsis” and “goal catharsis” on anger‐related responses among Chinese people, and the Chinese written form of catharsis was used in this study. The results showed that after participants were provoked, the aggressive behavior of participants who wrote down their dissatisfaction (general catharsis condition) was significantly higher than that of participants who wrote to attack someone who irritated them (goal catharsis condition) as well as that of participants who completed a simple recall task (control condition), and there was no significant difference in the aggressive behavior level between the latter two cases. These results suggest that the catharsis effect is no better than a simple recall task similar to attention distraction, that is, aggressive catharsis is not an effective way for anger relief.
Biochemical investigation of an N‐acetyltransferase from Helicobacter pullorum
Authors: Griffiths William A. , Spencer Keelan D. , Thoden James B. , Holden Hazel M.
Published: October 2021

N‐acetylated sugars are often found, for example, on the lipopolysaccharides of Gram‐negative bacteria, on the S‐layers of Gram‐positive bacteria, and on the capsular polysaccharides. Key enzymes involved in their biosynthesis are the sugar N‐acetyltransferases. Here, we describe a structural and functional analysis of one such enzyme from Helicobacter pullorum, an emerging pathogen that may be associated with gastroenteritis and gallbladder and liver diseases. For this analysis, the gene BA919‐RS02330 putatively encoding an N‐acetyltransferase was cloned, and the corresponding protein was expressed and purified. A kinetic analysis demonstrated that the enzyme utilizes dTDP‐3‐amino‐3,6‐dideoxy‐d‐glucose as a substrate as well as dTDP‐3‐amino‐3,6‐dideoxy‐d‐galactose, albeit at a reduced rate. In addition to this kinetic analysis, a similar enzyme from Helicobacter bilis was cloned and expressed, and its kinetic parameters were determined. Seven X‐ray crystallographic structures of various complexes of the H. pullorum wild‐type enzyme (or the C80T variant) were determined to resolutions of 1.7 Å or higher. The overall molecular architecture of the H. pullorum N‐acetyltransferase places it into the Class II left‐handed‐β‐helix superfamily (LβH). Taken together, the data presented herein suggest that 3‐acetamido‐3,6‐dideoxy‐d‐glucose (or the galactose derivative) is found on either the H. pullorum O‐antigen or in another of its complex glycoconjugates. A BLAST search suggests that more than 50 non‐pylori Helicobacter spp. have genes encoding N‐acetyltransferases. Given that there is little information concerning the complex glycans in non‐pylori Helicobacter spp. and considering their zoonotic potential, our results provide new biochemical insight into these pathogens
Modularity‐based parallel protein design algorithm with an implementation using shared memory programming
Authors: Pal Abantika , Mulumudy Rohith , Mitra Pralay
Published: October 2021

Given a target protein structure, the prime objective of protein design is to find amino acid sequences that will fold/acquire to the given three‐dimensional structure. The protein design problem belongs to the non‐deterministic polynomial‐time‐hard class as sequence search space increases exponentially with protein length. To ensure better search space exploration and faster convergence, we propose a protein modularity–based parallel protein design algorithm. The modular architecture of the protein structure is exploited by considering an intermediate structural organization between secondary structure and domain defined as protein unit (PU). Here, we have incorporated a divide‐and‐conquer approach where a protein is split into PUs and each PU region is explored in a parallel fashion. It has been further analyzed that our shared memory implementation of modularity‐based parallel sequence search leads to better search space exploration compared to the case of traditional full protein design. Sequence‐based analysis on design sequences depicts an average of 39.7% sequence similarity on the benchmark data set. Structure‐based comparison of the modeled structures of the design protein with the target structure exhibited an average root‐mean‐square deviation of 1.17 Å and an average template modeling score of 0.89. The selected modeled structures of the design protein sequences are validated using 100 ns molecular dynamics simulations where 80% of the proteins have shown better or similar stability to the respective target proteins. Our study informs that our modularity‐based protein design algorithm can be extended to protein interaction design as well.
Exposure–response analysis of adverse events associated with molibresib and its active metabolites in patients with solid tumors
Authors: Krishnatry Anu Shilpa , Hanze Eva , Bergsma Tim , Dhar Arindam , Prohn Marita , Ferron‐Brady Geraldine
Published: October 2021

Molibresib (GSK525762) is an investigational orally bioavailable small‐molecule bromodomain and extraterminal (BET) protein inhibitor for the treatment of advanced solid tumors. In the first‐time‐in‐human BET115521 study of molibresib in patients with solid tumors, thrombocytopenia was the most frequent treatment‐related adverse event (AE), QT prolongation was an AE of special interest based on preclinical signals, and gastrointestinal (GI) AEs (nausea, vomiting, diarrhea, and dysgeusia) were often observed. The aims of this analysis were the following: (i) develop a population pharmacokinetic (PK)/pharmacodynamic (PD) model capable of predicting platelet time courses in individual patients after administration of molibresib and identify covariates of clinical interest; (ii) evaluate the effects of molibresib (and/or its two active metabolites [GSK3529246]) exposure on cardiac repolarization by applying a systematic modeling approach using high‐quality, intensive, PK time‐matched 12‐lead electrocardiogram measurements; (iii) evaluate the exposure–response (ER) relationship between molibresib and/or GSK3529246 exposures and the occurrence of Grade 2 or higher GI AEs. Overall, the PK/PD model (including a maximal drug effect model and molibresib concentration) adequately described platelet counts following molibresib treatment and was used to simulate the impact of molibresib dosing on thrombocytopenia at different doses and regimens. ER analyses showed no clinically meaningful QT interval prolongation with molibresib at up to 100 mg q.d., and no strong correlation between molibresib exposure and the occurrence of Grade 2 or higher GI AEs. The models described here can aid dosing/schedule and drug combination strategies and may support a thorough QT study waiver request for molibresib.
Preclinical implementation of a steerable, Da Vinci Xi® compatible CO2‐laser fibre carrier for transoral robotic surgery (TORS): A cadaveric feasibility study
Authors: Meulemans Jeroen , Vandebroek Tom , Ourak Mouloud , Vander Poorten Emmanuel , Vander Poorten Vincent
Published: October 2021

Introduction

Monopolar electrocautery is the most common dissection and coagulation tool during transoral robotic surgery (TORS) but causes significant collateral tissue damage as opposed to CO2 laser. We aimed at combining both modalities in one robotic instrument arm.

Methods

We developed a steerable CO2‐laser fibre carrier serving as an add‐on to the existing Endowrist® monopolar spatula of the Da Vinci Xi. Feasibility and safety were assessed in a preclinical setting.

Results

One radical tonsillectomy with monopolar cautery and three with the instrument prototype were performed in two cadavers by two surgeons. No serious prototype‐related intra‐operative difficulties were observed. Safe and efficient switching between energy sources proved possible in all simulated intra‐operative bleeding events. Prototype use allowed for the identification of the majority of key anatomical structures and was scored favourably on NASA‐TLX questionnaires.

Discussion

The reported prototype successfully combines the advantages of CO2‐laser with the advantages of TORS
Successive Chebyshev pseudospectral convex optimization method for nonlinear optimal control problems
Authors: Li Yang , Chen Wanchun , Yang Liang
Published: October 2021

This article aims at proposing a successive Chebyshev pseudospectral convex optimization method for solving general nonlinear optimal control problems (OCPs). First, Chebyshev pseudospectral discrete scheme is used to discretize a general nonlinear OCP. At the same time, a convex subproblem is formulated by using the first‐order Taylor expansion to convexify the discretized nonlinear dynamic constraints. Second, a trust‐region penalty term is added to the performance index of the subproblem, and a successive convex optimization algorithm is proposed to solve the subproblem iteratively. Noted that the trust‐region penalty parameters can be adjusted according to the linearization error in iterative process, which improves convergence rate. Third, the Karush–Kuhn–Tucker conditions of the subproblem are derived, and furthermore, a proof is given to show that the algorithm will iteratively converge to the subproblem. Additionally, the global convergence of the algorithm is analyzed and proved, which is based on three key lemmas. Finally, the orbit transfer problem of spacecraft is used to test the performance of the proposed method. The simulation results demonstrate the optimal control is bang‐bang form, which is consistent with the result of theoretical proof. Also, the algorithm is of efficiency, fast convergence rate, and high accuracy. Therefore, the proposed method provides a new approach for solving nonlinear OCPs online and has great potential in engineering practice.