bluuebunny/crossref_metadata_2025 huggingface dataset:
Weyl Point and Nontrivial Surface States in a Helical Topological Material
Authors: Li Meize , Liu Yahong , Du Lianlian , Zhou Xin , Song Kun , Ji Ruonan , Zhao Xiaopeng
Published: January 2022

Topological material has been widely studied in recent years because of excellent physical properties. In this paper, a Weyl topological material composed of the double left-handed helixes is presented. It is demonstrated that the proposed structure possesses a two-dimensional complete topological nontrivial bandgap for a fixed kz in the microwave frequency, and the robust surface states are observed. This unique function provides a promising platform for the development of photonics and electromagnetics.
Decreased Systemic and Airway Sirtuin 1 Expression in Adults With Bronchiectasis
Authors: Han Xiao-rong , Cen Lai-jian , Pan Cui-xia , Lin Zhen-hong , Li Hui-min , Zhang Ri-lan , Huang Yan , Gao Yong-hua , Guan Wei-jie
Published: January 2022

Aim: Whether accelerated aging, reflected by sirtuin 1 (SIRT1) expression, is implicated in bronchiectasis remains largely unknown. We sought to determine the patterns of SIRT1 and other aging markers in systemic circulation and airways and their expression levels associated with bronchiectasis severity and exacerbation.

Methods: We enrolled 132 patients with bronchiectasis and 50 healthy subjects in a prospective cohort study to profile aging markers in systemic circulation and recruited 36 patients with bronchiectasis and 32 disease controls (idiopathic pulmonary fibrosis or tumors) in a cross-sectional study to profile aging markers in bronchial epithelium of both large-to-medium and small airways. We profiled aging marker expression from peripheral blood mononuclear cells and enumerated the positively stained cells for detection of aging marker expression in bronchial epithelium.

Results: Compared with healthy controls, the relative telomere length (median: 0.88 vs. 0.99, p = 0.009), SIRT1 (median: 0.89 vs. 0.99, p = 0.002), and Ku80 (median: 0.87 vs. 0.96, p < 0.001) expression levels were consistently lower in the peripheral blood mononuclear cells among patients with bronchiectasis and modestly discriminated patients with bronchiectasis from healthy controls. No remarkable changes in SIRT1, telomere length, or Ku70 were identified at onset of exacerbation. Within the bronchial epithelium, the percentage of positively stained cells was lower for SIRT1 (median: 25.1 vs. 57.2%, p < 0.05) and numerically lower for p16 (median: 40.0 vs. 45.1%) and p21 (median: 28.9 vs. 35.9%) in patients with bronchiectasis than in disease controls (p > 0.05).

Conclusion: SIRT1 was downregulated in systemic circulation and bronchiectatic airways, which was independent of disease severity and lung function impairment.
Low Birthweight as a Risk Factor for Non-communicable Diseases in Adults
Authors: Bianchi Maria Eugenia , Restrepo Jaime M.
Published: January 2022

According to studies undertaken over the past 40 years, low birthweight (LBW) is not only a significant predictor of perinatal death and morbidity, but also increases the risk of chronic non-communicable diseases (NCDs) in adulthood. The purpose of this paper is to summarize the research on LBW as a risk factor for NCDs in adults. The Barker hypothesis was based on the finding that adults with an LBW or an unhealthy intrauterine environment, as well as a rapid catch-up, die due to NCDs. Over the last few decades, terminology such as thrifty genes, fetal programming, developmental origins of health and disease (DOHaD), and epigenetic factors have been coined. The most common NCDs include cardiovascular disease, diabetes mellitus type 2 (DMT2), hypertension (HT), dyslipidemia, proteinuria, and chronic kidney disease (CKD). Studies in mothers who experienced famine and those that solely reported birth weight as a risk factor for mortality support the concept. Although the etiology of NCD is unknown, Barry Brenner explained the notion of a low glomerular number (nGlom) in LBW children, followed by the progression to hyperfiltration as the physiopathologic etiology of HT and CKD in adults based on Guyton's renal physiology work. Autopsies of several ethnic groups have revealed anatomopathologic evidence in fetuses and adult kidneys. Because of the renal reserve, demonstrating renal function in proportion to renal volume in vivo is more difficult in adults. The greatest impact of these theories can be seen in pediatrics and obstetrics practice.
Flexible and Stretchable Memristive Arrays for in-Memory Computing
Authors: Liu Xusheng , Cao Jie , Qiu Jie , Zhang Xumeng , Wang Ming , Liu Qi
Published: January 2022

With the tremendous progress of Internet of Things (IoT) and artificial intelligence (AI) technologies, the demand for flexible and stretchable electronic systems is rapidly increasing. As the vital component of a system, existing computing units are usually rigid and brittle, which are incompatible with flexible and stretchable electronics. Emerging memristive devices with flexibility and stretchability as well as direct processing-in-memory ability are promising candidates to perform data computing in flexible and stretchable electronics. To execute the in-memory computing paradigm including digital and analogue computing, the array configuration of memristive devices is usually required. Herein, the recent progress on flexible and stretchable memristive arrays for in-memory computing is reviewed. The common materials used for flexible memristive arrays, including inorganic, organic and two-dimensional (2D) materials, will be highlighted, and effective strategies used for stretchable memristive arrays, including material innovation and structural design, will be discussed in detail. The current challenges and future perspectives of the in-memory computing utilizing flexible and stretchable memristive arrays are presented. These efforts aim to accelerate the development of flexible and stretchable memristive arrays for data computing in advanced intelligent systems, such as electronic skin, soft robotics, and wearable devices.
SK Current, Expressed During the Development and Regeneration of Chick Hair Cells, Contributes to the Patterning of Spontaneous Action Potentials
Authors: Levic Snezana
Published: January 2022

Chick hair cells display calcium (Ca2+)-sensitive spontaneous action potentials during development and regeneration. The role of this activity is unclear but thought to be involved in establishing proper synaptic connections and tonotopic maps, both of which are instrumental to normal hearing. Using an electrophysiological approach, this work investigated the functional expression of Ca2+-sensitive potassium [IK(Ca)] currents and their role in spontaneous electrical activity in the developing and regenerating hair cells (HCs) in the chick basilar papilla. The main IK(Ca) in developing and regenerating chick HCs is an SK current, based on its sensitivity to apamin. Analysis of the functional expression of SK current showed that most dramatic changes occurred between E8 and E16. Specifically, there is a developmental downregulation of the SK current after E16. The SK current gating was very sensitive to the availability of intracellular Ca2+ but showed very little sensitivity to T-type voltage-gated Ca2+ channels, which are one of the hallmarks of developing and regenerating hair cells. Additionally, apamin reduced the frequency of spontaneous electrical activity in HCs, suggesting that SK current participates in patterning the spontaneous electrical activity of HCs.
Endovascular Treatment of Posterior Cerebral Artery Trunk Aneurysm: The Status Quo and Dilemma
Authors: Hou Kun , Lv Xianli , Yu Jinlu
Published: January 2022

The posterior cerebral artery (PCA) is an important artery that can be divided into four segments (P1-4): segments P1-2 are proximal segments, and segments P3-4 are distal segments. Various aneurysms can occur along the PCA trunk. True saccular aneurysms are rare, and most PCA trunk aneurysms are dissecting. Sometimes, the PCA trunk can give rise to flow-related aneurysms in association with high-flow arteriovenous shunt diseases or moyamoya disease and internal carotid artery occlusion. Some PCA trunk aneurysms require treatment, especially ruptured or large/giant aneurysms. Recently, endovascular treatment (EVT) has become the mainstream treatment for PCA trunk aneurysms, and it mainly involves reconstructive or deconstructive techniques. Traditional EVT includes selective coiling with/without stent or balloon assistance and parent artery occlusion (PAO). For proximal aneurysms, the PCA should be preserved. For distal aneurysms, PAO can be performed. However, during EVT, preservation of the PCA must naturally be the prime objective. Recently, flow-diverting stents have been used and are a revolutionary treatment for unruptured dissecting aneurysms of the PCA trunk. Despite the associated complications, EVT remains an effective method for treating PCA trunk aneurysms and can result in a good prognosis.
Serum Inflammatory Factors and Oxidative Stress Factors Are Associated With Increased Risk of Frailty and Cognitive Frailty in Patients With Cerebral Small Vessel Disease
Authors: Mu Lei , Jiang Limin , Chen Juan , Xiao Mei , Wang Wei , Liu Peipei , Wu Jialing
Published: January 2022

Objective: To study the correlation between serum inflammatory factors, oxidative stress factors and frailty, and cognitive frailty in patients with cerebral small vessel disease (CSVD).

Methods: A total of 281 patients with CSVD were selected from Tianjin Huanhu Hospital and Inner Mongolia People's Hospital from March 2019 to March 2021. CSVD was diagnosed by MRI. The FRAIL scale was used to evaluate the frailty of patients. Patients with CSVD with frailty and MMSE score <27 were considered to have cognitive frailty. Patients with non-cognitive frailty were included in the control group. The Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were used to evaluate the cognitive function of patients with CSVD. The serum interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase 3 (MMP-3), superoxide dismutase (SOD), and malondialdehyde (MDA) of patients with CSVD were detected. The correlation between blood inflammatory factors and oxidative stress factors with the frailty and cognitive frailty patients of CSVD were analyzed. Univariate and multivariate logistic regression were used to analyze the correlation between cognitive frailty and CSVD.

Results: Among the patients with CSVD selected in this study, female patients and older patients had a higher proportion of frailty (p < 0.001). In the Frail group, MoCA score and MMSE score were significantly lower than in the Pre-Frail and Robust groups, Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) scores were significantly higher than the Pre-Frail and Robust groups, and the differences were statistically significant (p < 0.05). Serum CRP, IL-6, TNF-α, MMP-3, and MDA levels in the Frail group were higher, but SOD levels were lower. The levels of serum CRP, IL-6, TNF-α, MMP-3, and MDA in patients with CSVD in the Cognitive Frailty group were significantly higher than those of the Control group, while the levels of SOD were significantly lower than those of the Control group, and the differences were significant (p < 0.001). The results of univariate and multivariate logistic regression analysis showed that CRP, TNF-α, MMP-3, and MDA levels were associated with cognitive frailty in patients with CSVD (p < 0.05).

Conclusion: The increase of serum CRP, TNF-α, MMP-3, and MDA levels are significantly related to the increased risk of frailty and cognitive frailty in patients with CSVD.
Altered Structural and Functional MRI Connectivity in Type 2 Diabetes Mellitus Related Cognitive Impairment: A Review
Authors: Lei Hao , Hu Rong , Luo Guanghua , Yang Tingqian , Shen Hui , Deng Hao , Chen Chunyu , Zhao Heng , Liu Jincai
Published: January 2022

Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment in many domains. There are several pieces of evidence that changes in neuronal neuropathies and metabolism have been observed in T2DM. Structural and functional MRI shows that abnormal connections and synchronization occur in T2DM brain circuits and related networks. Neuroplasticity and energy metabolism appear to be principal effector systems, which may be related to amyloid beta (Aβ) deposition, although there is no unified explanation that includes the complex etiology of T2DM with cognitive impairment. Herein, we assume that cognitive impairment in diabetes may lead to abnormalities in neuroplasticity and energy metabolism in the brain, and those reflected to MRI structural connectivity and functional connectivity, respectively.
Impact of Asymmetric Weight Update on Neural Network Training With Tiki-Taka Algorithm
Authors: Lee Chaeun , Noh Kyungmi , Ji Wonjae , Gokmen Tayfun , Kim Seyoung
Published: January 2022

Recent progress in novel non-volatile memory-based synaptic device technologies and their feasibility for matrix-vector multiplication (MVM) has ignited active research on implementing analog neural network training accelerators with resistive crosspoint arrays. While significant performance boost as well as area- and power-efficiency is theoretically predicted, the realization of such analog accelerators is largely limited by non-ideal switching characteristics of crosspoint elements. One of the most performance-limiting non-idealities is the conductance update asymmetry which is known to distort the actual weight change values away from the calculation by error back-propagation and, therefore, significantly deteriorates the neural network training performance. To address this issue by an algorithmic remedy, Tiki-Taka algorithm was proposed and shown to be effective for neural network training with asymmetric devices. However, a systematic analysis to reveal the required asymmetry specification to guarantee the neural network performance has been unexplored. Here, we quantitatively analyze the impact of update asymmetry on the neural network training performance when trained with Tiki-Taka algorithm by exploring the space of asymmetry and hyper-parameters and measuring the classification accuracy. We discover that the update asymmetry level of the auxiliary array affects the way the optimizer takes the importance of previous gradients, whereas that of main array affects the frequency of accepting those gradients. We propose a novel calibration method to find the optimal operating point in terms of device and network parameters. By searching over the hyper-parameter space of Tiki-Taka algorithm using interpolation and Gaussian filtering, we find the optimal hyper-parameters efficiently and reveal the optimal range of asymmetry, namely the asymmetry specification. Finally, we show that the analysis and calibration method be applicable to spiking neural networks.
Acupuncture Reduces the Risk of Dysphagia in Stroke Patients: A Propensity Score-Matched Cohort Study
Authors: Qiu Xuan , Yao Xiao-Jie , Han Sheng-Nan , Wu Yun-Yun , Ou Zeng-Jian , Li Tian-Shi , Zhang Hong
Published: January 2022

Background: Post-stroke dysphagia (PSD) affects the quality of life in stroke patients, impairs their rehabilitation ability, and causes other complications following stroke. Currently, there is currently some understanding of PSD risk factors, but its protective factors remain largely unknown.

Objective: To analyze the effects of acupuncture (AP) on dysphagia in stroke patients and explore its potential as a preventive therapy.

Methods: Patients with a diagnosis of stroke from 2010 to 2019 were selected and followed until 2020, utilizing factors such as age, gender, stroke location, stroke type, and baseline comorbidity. To compare the incidence of dysphagia, equal numbers of stroke patients treated with and without AP (n = 1,809) were matched by 1:1 propensity scoring. The Cox proportional hazards model and Kaplan-Meier method were used to assess the risk of dysphagia as an outcome measure.

Results: The stroke patients treated with AP had a lower risk of dysphagia after adjusting for age, gender, stroke location, stroke type, and baseline comorbidity [adjusted hazard ratio (AHR) = 0.43, 95% confidence interval = 0.37–0.49] compared with those in the non-AP cohort. AP also decreased the risk of PSD among different gender groups. The risk ratios were AHR = 0.45 and AHR = 0.33 for males and females, respectively. AP also reduced the risk for PSD among different age groups. The risk ratios were AHR = 0.20, AHR = 0.37, AHR = 0.41, and AHR = 0.45 for the 18–39, 40–59, 60–79, and >80 years-old groups. Regarding stroke types (ischemic, hemorrhagic, and mixed type), patients treated with AP had a lower risk (AHR = 0.47, 0.28 and 0.17, respectively). With respect to stroke location, the risk of PSD in AP-treated patients was decreased regardless of location: brain stem (AHR = 0.41), diencephalon (AHR = 0.13), or multiple lesions (AHR = 0.40), the risk of PSD in AP-treated patients was decreased. For all baseline comorbidities, AP attenuated the risk of dysphagia. The cumulative incidence of dysphagia was remarkably lower in the AP group than in the non-AP group (log-rank test, P = 0.000).

Limitations: First, this was a single-center clinical retrospective study. Second, we did not classify the severity of stroke and dysphagia. Third, all data were extracted manually. Lastly, the sample size was relatively small. Thus, future studies with larger sample sizes are warranted to verify our findings.

Conclusion: Acupuncture treatment attenuates the risk of dysphagia in stroke patients. Future research should increase the sample size and elaborate further on the details of the AP protocol.
Biofortified Maize Improves Selenium Status of Women and Children in a Rural Community in Malawi: Results of the Addressing Hidden Hunger With Agronomy Randomized Controlled Trial
Authors: Joy Edward J. M. , Kalimbira Alexander A. , Sturgess Joanna , Banda Leonard , Chiutsi-Phiri Gabriella , Manase Hastings , Gondwe Jellita , Ferguson Elaine L. , Kalumikiza Zione , Bailey Elizabeth H. , Young Scott D. , Matandika Limbanazo , Mfutso-Bengo Joseph , Millar Kate , Niksic Maja , Segovia de la Revilla Lucia , Likoswe Blessings H. , Phuka John C. , Phiri Felix P. , Lark R. Murray , Gashu Dawd , Langley-Evans Simon C. , Ander E. Louise , Lowe Nicola M. , Dangour Alan D. , Nalivata Patson C. , Broadley Martin R. , Allen Elizabeth
Published: January 2022

Background: Selenium deficiency is widespread in the Malawi population. The selenium concentration in maize, the staple food crop of Malawi, can be increased by applying selenium-enriched fertilizers. It is unknown whether this strategy, called agronomic biofortification, is effective at alleviating selenium deficiency.

Objectives: The aim of the Addressing Hidden Hunger with Agronomy (AHHA) trial was to determine whether consumption of maize flour, agronomically-biofortified with selenium, affected the serum selenium concentrations of women, and children in a rural community setting.

Design: An individually-randomized, double-blind placebo-controlled trial was conducted in rural Malawi. Participants were randomly allocated in a 1:1 ratio to receive either intervention maize flour biofortified with selenium through application of selenium fertilizer, or control maize flour not biofortified with selenium. Participant households received enough flour to meet the typical consumption of all household members (330 g capita−1 day−1) for a period of 8 weeks. Baseline and endline serum selenium concentration (the primary outcome) was measured by inductively coupled plasma mass spectrometry (ICP-MS).

Results: One woman of reproductive age (WRA) and one school-aged child (SAC) from each of 180 households were recruited and households were randomized to each group. The baseline demographic and socioeconomic status of participants were well-balanced between arms. No serious adverse events were reported. In the intervention arm, mean (standard deviation) serum selenium concentration increased over the intervention period from 57.6 (17.0) μg L−1 (n = 88) to 107.9 (16.4) μg L−1 (n = 88) among WRA and from 46.4 (14.8) μg L−1 (n = 86) to 97.1 (16.0) μg L−1 (n = 88) among SAC. There was no evidence of change in serum selenium concentration in the control groups.

Conclusion: Consumption of maize flour biofortified through application of selenium-enriched fertilizer increased selenium status in this community providing strong proof of principle that agronomic biofortification could be an effective approach to address selenium deficiency in Malawi and similar settings.

Clinical Trial Registration:http://www.isrctn.com/ISRCTN85899451, identifier: ISRCTN85899451.
Knockdown of LMTK3 in the Endometrioid Adenocarcinoma Cell Line Ishikawa: Inhibition of Growth and Estrogen Receptor α
Authors: Cai Guiyang , Sun Wei , Bi Fangfang , Wang Dandan , Yang Qing
Published: January 2022

Objective

The curative effect of high-efficiency progesterone and other therapeutic drugs for endometrioid adenocarcinoma patients with preservation of reproductive capacity has not been satisfactory so far. Novel therapeutic drugs need to be explored.

Methods

We investigated the cytoplastic and nuclear expression levels of LMTK3 between endometrioid adenocarcinoma tissues and adjacent endometrial tissues by immunohistochemistry. We detected the effects of LMTK3 on cell viability of Ishikawa cells by CCK-8. We detected the effects of LMTK3 on cell cycle and apoptosis of Ishikawa cells by flow cytometry. We also detected the effects of LMTK3 knockdown on mRNA and protein levels of ERα by qRT-PCR and western blotting, respectively. We also used the cBioPortal online database to analyze the coexpression of LMTK3 and ESR1 in 1647 UCEC samples.

Results

We used TMAs to identify that LMTK3 was mainly detected in the cytoplasm of endometrioid tissues, and cytoplasmic LMTK3 expression in endometrioid tissues was higher than that in adjacent endometrial tissues (P < 0.05). LMTK3 knockdown decreased the proliferation of Ishikawa cells through decreasing cell viability (P < 0.01), increasing G1 (P < 0.001) arrest, and promoting apoptosis (P < 0.01). There was a positive correlation between the mRNA expression levels of LMTK3 and ESR1 (Spearman: P=2.011e-5, R=0.13; Pearson: P=7.18e-8, R=0.17). Knockdown of LMTK3 also reduced the mRNA (P < 0.001) and protein (P < 0.001) levels of ERα.

Conclusions

Inhibitors of LMTK3 may be a possible future treatment for ERα and LMTK3 highly expressed endometrioid adenocarcinoma following appropriate studies.
MicroRNA-155-5p Contributes to 5-Fluorouracil Resistance Through Down-Regulating TP53INP1 in Oral Squamous Cell Carcinoma
Authors: Liu Bowen , Hu Jingchao , Zhao Han , Zhao Li , Pan Shiyuan
Published: January 2022

The anticancer drug 5-fluorouracil (5-FU) resistance is a major obstacle to reducing the effectiveness of cancer treatment, and its detailed mechanism has not been fully elucidated. Here, in 5-FU-resistant human oral squamous cell carcinoma (OSCC) HSC3 cells (HSC3/5-FU), the levels of 21 miRNA candidates were detected using RT-PCR and miR-155-5p level increased strikingly in HSC3/5-FU cells compared to HSC3 cells. Compared with HSC3 cells, the CCK-8 assay showed that the HSC3/5-FU cells transfected with miR-155-5p inhibitors decreased 5-FU IC50. Ectopic expression of miR-155-5p in HSC3 and HSC4 cells increased 5-FU IC50 (CCK-8 assay), migration (wound-healing and transwell assays) and invasion (transwell assay) abilities. Seven miR-155-5p target candidates were discovered by miRNA prediction algorithms (miRDB, Targetscan, and miRWalk), and the RT-PCR results showed that in HSC3/5-FU cells TP53INP1 was of the lowest mRNA expression level compared with HSC3 cells. The RT-PCR and Western blotting assays showed that ectopic expression of miR-155-5p in HSC3 and HSC4 cells decreased TP53INP1 expression level. Furthermore, the luciferase reporter and RNA pull-down assays determined the interference effect of miR-155-5p on TP53INP1 expression. The enhancement of cell viability (CCK-8 assay), migration (wound-healing and transwell assays) and invasion (transwell assay) by miR-155-5p after 5-FU treatment was reversed by TP53INP1 overexpression. After treatment with 5-FU, HSC3-miR-155-5p tumor-bearing nude mice presented growing tumors, while HSC3-TP53INP1 group possessed shrinking tumors. In conclusion, these results lead to the proposal that miR-155-5p enhances 5-FU resistance by decreasing TP53INP1 expression in OSCC.
Competing Risk Analysis of Outcomes of Unresectable Pancreatic Cancer Patients Undergoing Definitive Radiotherapy
Authors: Chen Yi-Lun , Tsai Chiao-Ling , Cheng Jason Chia-Hsien , Wang Chun-Wei , Yang Shih-Hung , Tien Yu-Wen , Kuo Sung-Hsin
Published: January 2022

Purpose

We investigated potential factors, including clinicopathological features, treatment modalities, neutrophil-to-lymphocyte ratio (NLR), carbohydrate antigen (CA) 19-9 level, tumor responses correlating with overall survival (OS), local progression (LP), and distant metastases (DMs), in patients with locally advanced pancreatic cancer (LAPC) who received definitive radiotherapy (RT).

Methods

We retrospectively analyzed demographic characteristics; biologically effective doses (BED10, calculated with an α/β of 10) of RT; and clinical outcomes of 57 unresectable LAPC (all pancreatic adenocarcinoma) patients receiving definitive RT using modern techniques with and without systemic therapy between January 2009 and March 2019 at our institution. We used Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 to evaluate the radiographic tumor response after RT. The association between prognostic factors and OS was assessed using the Kaplan–Meier analysis and a Cox regression model, whereas baseline characteristics and treatment details were collected for competing-risk regression of the association with LP and DM using the Fine–Gray model.

Results

A median BED10 of 67.1 Gy resulted in a disease control rate of 87.7%, and the median OS was 11.8 months after a median follow-up of 32.1 months. The 1-year OS rate, cumulative incidences of LP, and DM were 49.2%, 38.5%, and 62.9%, respectively. Multivariate analyses showed that pre-RT NLR ≥3.5 (adjusted hazard ratio [HR] = 8.245, p < 0.001), CA19-9 reduction rate ≥50% (adjusted HR = 0.261, p = 0.005), RT without concurrent chemoradiotherapy (adjusted HR = 5.903, p = 0.004), and administration of chemotherapy after RT (adjusted HR = 0.207, p = 0.03) were independent prognostic factors for OS. Positive lymph nodal metastases (adjusted subdistribution HR [sHR] = 3.712, p = 0.003) and higher tumor reduction after RT (adjusted sHR = 0.922, p < 0.001) were significant prognostic factors for LP, whereas BED10 ≥ 67.1 Gy (adjusted sHR = 0.297, p = 0.002), CA19-9 reduction rate ≥50% (adjusted sHR = 0.334, p = 0.023), and RT alone (adjusted sHR = 2.633, p = 0.047) were significant prognostic factors for DM.

Conclusion

Our results indicate that pre-RT NLR and post-RT monitoring of CA19-9 and tumor size reduction can help identify whether patients belong to the good or poor prognostic group of LAPC. The incorporation of new systemic treatments during and after a higher BED10 RT dose for LAPC patients is warranted.
Stimulation of Let-7 Maturation by Metformin Improved the Response to Tyrosine Kinase Inhibitor Therapy in an m6A Dependent Manner
Authors: Li Kai , Gao Shan , Ma Lei , Sun Ye , Peng Zi-Yang , Wu Jie , Du Ning , Ren Hong , Tang Shou-Ching , Sun Xin
Published: January 2022

The molecular mechanism of the tyrosine kinase inhibitor (TKI) resistant lung adenocarcinoma is currently unclear, and the role of methylated adenosine at the N6 position in the resistance of cancer stem cells (CSCs) therapy is unknown. This study identified a novel and effective strategy to enhance TKIs therapy response. We first confirmed the sensitization of Metformin enforcing on Osimertinib treatment and revealed the mature miRNAs signatures of the Osimertinib resistant H1975 and HCC827 cells. Let-7b expression was stimulated when adding Metformin and then increasing the therapy sensitivity by decreasing the stem cell groups expanding. Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3a/b) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. We revealed that the maturation processing signaling stimulated the methylation regulation of the miRNAs, and may determine the stemness control of the therapy resistance. Our findings may open up future drug development, targeting this pathway for lung cancer patients.
Prognostic Utility of Optical Coherence Tomography for Visual Outcome After Extended Endoscopic Endonasal Surgery for Adult Craniopharyngiomas
Authors: Qiao Ning , Li Chuzhong , Xu Jing , Ma Guofo , Kang Jie , Jin Lu , Cao Lei , Liu Chunhui , Zhang Yazhuo , Gui Songbai
Published: January 2022

Introduction

Owing to the close vicinity of the optic chiasma, visual dysfunction is known as one of the most common surgical indications and postoperative complications in adult patients with craniopharyngiomas, probably leading to poor quality of life. Historically, very few consistent predictive factors associated with the visual outcome are identified, which may not be helpful for patient counseling and preoperative decision making. Recently, optical coherence tomography (OCT) serving as a novel high-resolution imaging technique can assess the retinal morphology by measuring the circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex thickness. However, few studies have examined the prognostic utility of OCT parameters for visual outcome after surgery for craniopharyngiomas. This study aims to use the largest series to evaluate the association between OCT parameters and visual outcome after extended endoscopic endonasal surgery (EEES) for primary craniopharyngiomas in adults.

Material and Methods

From October 2018 to October 2020, one hundred and seventy eyes in 88 adult patients with newly confirmed craniopharyngiomas were retrospectively reviewed and pertinent prognostic factors were analyzed.

Results

Gross total resection was performed in 82 (93.2%) patients. The median postoperative follow-up time was 10.9 months. Multiple logistic regression analysis showed that increased temporal cpRNFL thickness was associated with higher odds of visual acuity (VA) improvement and maintenance (OR = 1.070; 95% CI, 1.005–1.140; p = 0.035), and greater inferior cpRNFL thickness was significantly associated with visual field (VF) improvement and maintenance (OR = 1.034; 95% CI, 1.001–1.068; p = 0.046). Furthermore, tight adhesion between optic nerves and craniopharyngiomas was demonstrated as an independent adverse factor for either postoperative VA or VF (p = 0.048, p = 0.030, respectively). The ROC results further verified the robustness of the prediction model either in VA (AUC = 0.843; 95% CI, 0.734–0.952; p < 0.001) or VF (AUC = 0.849; 95% CI, 0.741–0.958; p < 0.001).

Conclusion

Preoperative OCT can effectively predict visual outcome after EEES for adult craniopharyngiomas. It can also serve as a reliable alternative to evaluate preoperative visual field defects, especially for patients with lower compliance. Tight adhesion was confirmed as an independent risk factor for postoperative visual outcome. The OCT-based multivariable prediction models developed in the present study may contribute to patient counseling on visual prognosis.
BMT for Myelodysplastic Syndrome: When and Where and How
Authors: Jain Akriti G. , Elmariah Hany
Published: January 2022

Myelodysplastic syndromes (MDS) are a diverse group of hematological malignancies distinguished by a combination of dysplasia in the bone marrow, cytopenias and the risk of leukemic transformation. The hallmark of MDS is bone marrow failure which occurs due to selective growth of somatically mutated clonal hematopoietic stem cells. Multiple prognostic models have been developed to help predict survival and leukemic transformation, including the international prognostic scoring system (IPSS), revised international prognostic scoring system (IPSS-R), WHO prognostic scoring system (WPSS) and MD Anderson prognostic scoring system (MDAPSS). This risk stratification informs management as low risk (LR)-MDS treatment focuses on improving quality of life and cytopenias, while the treatment of high risk (HR)-MDS focuses on delaying disease progression and improving survival. While therapies such as erythropoiesis stimulating agents (ESAs), erythroid maturation agents (EMAs), immunomodulatory imide drugs (IMIDs), and hypomethylating agents (HMAs) may provide benefit, allogeneic blood or marrow transplant (alloBMT) is the only treatment that can offer cure for MDS. However, this therapy is marred, historically, by high rates of toxicity and transplant related mortality (TRM). Because of this, alloBMT is considered in a minority of MDS patients. With modern techniques, alloBMT has become a suitable option even for patients of advanced age or with significant comorbidities, many of whom who would not have been considered for transplant in prior years. Hence, a formal transplant evaluation to weigh the complex balance of patient and disease related factors and determine the potential benefit of transplant should be considered early in the disease course for most MDS patients. Once alloBMT is recommended, timing is a crucial consideration since delaying transplant can lead to disease progression and development of other comorbidities that may preclude transplant. Despite the success of alloBMT, relapse remains a major barrier to success and novel approaches are necessary to mitigate this risk and improve long term cure rates. This review describes various factors that should be considered when choosing patients with MDS who should pursue transplant, approaches and timing of transplant, and future directions of the field.
Automatic Production and Preliminary PET Imaging of a New Imaging Agent [18F]AlF-FAPT
Authors: Huang JiaWen , Fu LiLan , Hu KongZhen , Huang Shun , Han YanJiang , Lin Run , Xu WanBang , Tang Ganghua , Huang Yonghui
Published: January 2022

Background

Fibroblast activating protein (FAP) has become an important target for cancer diagnostic imaging and targeted radiotherapy. In particular, [18F]FAPI-42 has been successfully applied to positron emission tomography (PET) imaging of various tumors. However, it exhibits high hepatobiliary metabolism and is thus not conducive to abdominal tumor imaging. This study reports a novel 18F-labeled FAP inhibitor, [18F]AlF-FAPT, a better FAPI imaging agent than [18F]FAPI-42.

Materials and Methods

The precursor of [18F]AlF-FAPT (NOTA-FAPT) was designed and synthesized using the standard FMOC solid phase synthesis method. [18F]AlF-FAPT was subsequently synthesized and radiolabeled with 18F using the AllInOne synthesis module. Dynamic MicroPET and biodistribution studies of [18F]AlF-FAPT were then conducted in xenograft tumor mouse models to determine its suitability.

Results

The precursors NOTA-FAPT were obtained with a chemical purity of > 95%. [18F]AlF-FAPT was synthesized automatically using the cassette-based module AllInOne within 40 min. The non-decay corrected radiochemical yield was 25.0 ± 5.3% (n=3). In vivo imaging and biodistribution studies further demonstrated that compared with [18F]-FAPI-42, [18F]AlF-FAPT had a lower hepatobiliary uptake than [18F]FAPI-42, which was advantageous for imaging abdominal tumors.

Conclusion

[18F]AlF-FAPT can be synthesized automatically using a one-step method of aluminum fluoride. Collectively, [18F]AlF-FAPT is a better FAPI imaging agent than [18F]FAPI-42. This study proves the feasibility of using [18F]AlF-FAPT as a new radioactive tracer for PET imaging.
Effects of Neoadjuvant Chemotherapy in Ovarian Cancer Patients With Different Germline BRCA1/2 Mutational Status: A Retrospective Cohort Study
Authors: Fu Mengdi , Jin Chengjuan , Feng Shuai , Jia Zongyang , Nie Lekai , Zhang Yang , Peng Jin , Wang Xia , Bu Hualei , Kong Beihua
Published: January 2022

Background

Whether neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) against primary debulking surgery (PDS) has a differential effect on prognosis due to Breast Cancer Susceptibility Genes (BRCA)1/2 mutations has not been confirmed by current studies.

Methods

All patients included in this retrospective study were admitted to Qilu Hospital of Shandong University between January 2009 and June 2020, and germline BRCA1/2 mutation were tested. Patients in stage IIIB, IIIC, and IV, re-staged by International Federation of Gynecology and Obstetrics (FIGO) 2014, were selected for analysis. All patients with NAC received 1-5 cycles of platinum-containing (carboplatin, cisplatin, or nedaplatin) chemotherapy. Patients who received maintenance therapy after chemotherapy were not eligible for this study. All relevant medical records were collected.

Results

A total of 322 patients were enrolled, including 112 patients with BRCA1/2 mutations (BRCAmut), and 210 patients with BRCA1/2 wild-type (BRCAwt). In the two groups, 40 BRCAmut patients (35.7%) and 69 BRCAwt patients (32.9%) received NAC. The progression-free survival (PFS) of BRCAmut patients was significantly reduced after NAC (median: 14.9 vs. 18.5 months; p=0.023); however, there was no difference in overall survival (OS) (median: 75.1 vs. 72.8 months; p=0.798). Whether BRCAwt patients received NAC had no significant effect on PFS (median: 13.5 vs. 16.0 months; p=0.780) or OS (median: 54.0 vs. 56.4 months; p=0.323). Multivariate analyses in BRCAmut patients showed that the predictors of prolonged PFS were PDS (p=0.001), the absence of residual lesions (p=0.012), and FIGO III stage (p=0.020); Besides, PARP inhibitor was the independent predictor for prolonged OS in BRCAmut patients (p=0.000), for BRCAwt patients, the absence of residual lesions (p=0.041) and history of PARP inhibitors (p=0.000) were beneficial factors for OS prolongation.

Conclusions

For ovarian cancer patients with FIGO IIIB, IIIC, and IV, NAC-IDS did not adversely affect survival outcomes due to different BRCA1/2 germline mutational status.
Case Report: Rehabilitation for Lower Extremity Pain Due to Venous Stasis in a Patient With Multisystem Inflammatory Syndrome in Children
Authors: Kinoshita Tokio , Nishimura Yukihide , Umemoto Yasunori , Koike Yumi , Kouda Ken , Ogawa Takahiro , Suenaga Tomohiro , Tajima Fumihiro
Published: January 2022

Recently, it was reported that children recovering from coronavirus disease (COVID-19) developed multisystem inflammatory syndrome in children (MIS-C), which causes severe inflammation in multiple organs of the body. Because MIS-C is a new disease, the pathophysiology and prognosis are unknown. Owing to a lack of studies on this subject, we herein provide information on rehabilitation for children with MIS-C. A 12-year-old male patient presented with systemic inflammatory symptoms after approximately 2 months since recovery from COVID-19. He was treated with cyclosporine and steroid pulse therapy after admission to our hospital. His general condition improved significantly within approximately 1 week. Thereafter, his lower legs turned dark purple and he experienced intense pain whenever the lower limbs hung below the heart, such as in the sitting position. The patient was referred to the rehabilitation department, as he had difficulties during standing and walking. Because the symptoms improved with elevation of the lower extremities, we considered that the pain was related to venous stasis. The pain reduced when an elastic bandage was applied for the prevention of venous stasis; therefore, exercise therapy was implemented while the patient wore the elastic bandage. The patient's lower extremity symptoms improved in 10 days. He was discharged after 16 days and could independently perform activities of daily living (ADL). The mechanism underlying the patient's pain could not be determined; however, rehabilitation was effective when combined with compression therapy using an elastic bandage.
Leptin Concentration, Obesity, and Plasma Non-esterified Fatty Acid Levels in Children
Authors: Vales-Villamarín Claudia , Ortega-Senovilla Henar , Dios Olaya de , Pérez-Nadador Iris , Gavela-Pérez Teresa , Soriano-Guillén Leandro , Garcés Carmen
Published: January 2022

The association between obesity and higher non-esterified fatty acid (NEFA) levels has been established in adults. In contrast, lower NEFA levels have been described in children with obesity although the reason behind this association remains unclear. Leptin, which regulates body weight and plays a role in lipolysis, could be involved in this relationship. We evaluated the influence of leptin in the association between obesity and NEFA concentrations in children, analyzing two cohorts including 684 6- to 8-year-olds and 836 12- to 16-year-old children, respectively. After adjusting by leptin, insulin levels remained significantly higher in adolescents with obesity as compared with levels in those without obesity. However, insulin levels showed no differences between prepubertal children with and without obesity. The significantly lower NEFA concentrations observed in 6- to 8-year-old girls with obesity disappeared when comparing NEFA levels between girls with and without obesity after adjusting by leptin. We report an influence of leptin levels on the association between obesity and insulin and NEFA in young children that is not observed in adolescents. Our findings add information about factors that may contribute to explain the lower NEFA levels described in prepubertal children with obesity.
The Genetic Diversity of Enset (Ensete ventricosum) Landraces Used in Traditional Medicine Is Similar to the Diversity Found in Non-medicinal Landraces
Authors: Nuraga Gizachew Woldesenbet , Feyissa Tileye , Tesfaye Kassahun , Biswas Manosh Kumar , Schwarzacher Trude , Borrell James S. , Wilkin Paul , Demissew Sebsebe , Tadele Zerihun , Heslop-Harrison J. S. (Pat)
Published: January 2022

Enset (Ensete ventricosum) is a multipurpose crop extensively cultivated in southern and southwestern Ethiopia for human food, animal feed, and fiber. It has immense contributions to the food security and rural livelihoods of 20 million people. Several distinct enset landraces are cultivated for their uses in traditional medicine. These landraces are vulnerable to various human-related activities and environmental constraints. The genetic diversity among the landraces is not verified to plan conservation strategy. Moreover, it is currently unknown whether medicinal landraces are genetically differentiated from other landraces. Here, we characterize the genetic diversity of medicinal enset landraces to support effective conservation and utilization of their diversity. We evaluated the genetic diversity of 51 enset landraces, of which 38 have reported medicinal value. A total of 38 alleles across the 15 simple sequence repeat (SSR) loci and a moderate level of genetic diversity (He = 0.47) were detected. Analysis of molecular variation (AMOVA) revealed that only 2.4% of the total genetic variation was contributed by variation among the medicinal and non-medicinal groups of landraces, with an FST of 0.024. A neighbor-joining tree showed four separate clusters with no correlation to the use-values of the landraces. Except for two, all “medicinal” landraces with distinct vernacular names were found to be genetically different, showing that vernacular names are a good indicator of genetic distinctiveness in these specific groups of landraces. The discriminant analysis of the principal components also confirmed the absence of distinct clustering between the two groups. We found that enset landraces were clustered irrespective of their use-value, showing no evidence for genetic differentiation between the enset grown for ‘medicinal’ uses and non-medicinal landraces. This suggests that enset medicinal properties may be restricted to a more limited number of genotypes, might have resulted from the interaction of genotype with the environment or management practice, or partly misreported. The study provides baseline information that promotes further investigations in exploiting the medicinal value of these specific landraces.
To New Beginnings: Riboproteogenomics Discovery of N-Terminal Proteoforms in Arabidopsis Thaliana
Authors: Willems Patrick , Ndah Elvis , Jonckheere Veronique , Van Breusegem Frank , Van Damme Petra
Published: January 2022

Alternative translation initiation is a widespread event in biology that can shape multiple protein forms or proteoforms from a single gene. However, the respective contribution of alternative translation to protein complexity remains largely enigmatic. By complementary ribosome profiling and N-terminal proteomics (i.e., riboproteogenomics), we provide clear-cut evidence for ~90 N-terminal proteoform pairs shaped by (alternative) translation initiation in Arabidopsis thaliana. Next to several cases additionally confirmed by directed mutagenesis, identified alternative protein N-termini follow the enzymatic rules of co-translational N-terminal protein acetylation and initiator methionine removal. In contrast to other eukaryotic models, N-terminal acetylation in plants cannot generally be considered as a proxy of translation initiation because of its posttranslational occurrence on mature proteolytic neo-termini (N-termini) localized in the chloroplast stroma. Quantification of N-terminal acetylation revealed differing co- vs. posttranslational N-terminal acetylation patterns. Intriguingly, our data additionally hints to alternative translation initiation serving as a common mechanism to supply protein copies in multiple cellular compartments, as alternative translation sites are often in close proximity to cleavage sites of N-terminal transit sequences of nuclear-encoded chloroplastic and mitochondrial proteins. Overall, riboproteogenomics screening enables the identification of (differential localized) N-terminal proteoforms raised upon alternative translation.