bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Incidence of Pelvic Sepsis Following Hartmann’s Procedure for Rectal Cancer – A Retrospective Multicentre Study
Authors: Mariusdottir Elin , Jörgren Fredrik , Mondlane Amelia , Wikström Jens , Lydrup Marie-Louise , Buchwald Pamela
Published: September 2021

Background
Results of previous studies regarding pelvic sepsis after Hartmann’s procedure (HP) for rectal cancer have been inconsistent and few studies report the risk factors. This study aimed to investigate the incidence of pelvic sepsis after HP, identify risk factors and describe when as well as how pelvic sepsis was diagnosed and treated.
Methods
Data were collected from the Swedish Colorectal Cancer Registry on all patients undergoing HP for rectal cancer in the county of Skåne from 2007–2017. Patients diagnosed with pelvic sepsis were compared with patients without pelvic sepsis and risk factors for developing pelvic sepsis were analysed in a multivariable model.
Results
A total of 252 patients were included in the study, with 149 (59%) males, and a median age of 75 years (range 20–92). Altogether, 27 patients (11%) were diagnosed with pelvic sepsis. Risk factors for developing pelvic sepsis were neoadjuvant radiotherapy (OR 7.96, 95% CI 2.54–35.36) and BMI over 25 kg/m2 (OR 5.26, 95% CI 1.80–19.50). Median time from operation to diagnosis was 21 days (range 5-355) with 11 (40%) patients diagnosed beyond 30 days postoperatively. The majority of cases 19 (70%) were treated conservatively and none needed major surgery.
Conclusion
Pelvic sepsis occurred in 11% of patients. Neoadjuvant radiotherapy and higher BMI were significant risk factors for developing pelvic sepsis. Forty percent of patients were diagnosed later than 30 days postoperatively and most patients were successfully treated conservatively. Our findings suggest that HP is a valid treatment option for rectal cancer when anastomosis is inappropriate, even in patients receiving neoadjuvant radiotherapy.
The Impact of Combined Cranberry Supplementation and Weight Loss Diet on Inflammatory, Antioxidant and Apoptosis Biomarkers in Patients with Non-Alcoholic Fatty Liver Disease
Authors: Mohammadshahi Majid , Hormoznejad Razie , Rahim Fakher , Helli Bijan , Alavinejad Pezhman , Sharhani Asaad
Published: September 2021

Background

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver diseases. The aim of this study was to evaluate the effect of combined weight loss diet and cranberry supplementation on inflammatory, antioxidant and apoptosis biomarkers in patients with NAFLD.
Methods

In this randomized, double-blinded, controlled clinical trial, 41 NAFLD patients were supplemented with either a 288-mg cranberry tablet or a placebo tablet for 12 weeks. Both groups followed a diet of 500–1000 calories less than the estimated energy requirements. Serum levels of Total antioxidant capacity (TAC), Malondialdehyde (MDA), Cytokeratin 18-M30 (CK-18 M30), Chemokine C-C motif ligand 2 (CCL2) and Tumour necrosis factor alpha (TNF-α) were measured at both baseline and the end of the study.
Results

Significant improvements in TAC were observed in the cranberry group and between the two groups (p = 0.006 and p = 0.011 respectively), but the changes in the placebo group were not significant (p = 0.325). There were no statistically significant differences in the serum levels of MDA, CK-18 M30, CCL2 and TNF-α between the cranberry and the placebo groups (p > 0.05).
Conclusions

It seems that daily consumption of cranberry supplement would be beneficial in increasing serum levels of TAC. Further studies are needed to investigate the effects of anti-inflammatory and antioxidant properties of cranberry on NAFLD.
Trial registration
: Iranian Registry of Clinical Trial. http://www.irct.ir: IRCT20150124020765N2, January 2019.
Use of Prophylactic Iron Salts Supplementation During Gestation and Development of Gestational Diabetes Mellitus in Women From 2015 Pelotas (Brazil) Birth Cohort Study
Authors: Miranda Vanessa Iribarrem Avena , Pizzol Tatiane da Silva Dal , Silveira Marysabel Pinto Telis , Mengue Sotero Serrate , Silveira Mariângela Freitas , Lutz Bárbara H , Buffarini Romina , Bertoldi Andréa Dâmaso
Published: September 2021

Background

This study aims to evaluate the association between the use of iron salts during the first two trimesters in non-anemic women and the development of gestational diabetes mellitus (GDM).
Methods

The study used maternal data from 2015 Pelotas Birth Cohort. All non-anemic women at 24th week (N = 2463) were eligible for this study. GDM was self-reported by women. Crude and adjusted logistic regression were performed considering level of significance = 0.05.
Results

Among the women studied, 69.7% were exposed to prophylactic iron supplementation in the two first trimesters of gestation. The prevalence of GDM among those exposed was 8.7% (95%CI 7.4–10.1) and among those who were not exposed was 9.3% (CI95% 7.4–11.6). Iron supplementation was not associated with increased risk of GDM in crude (OR = 0.9; 95%CI 0,7–1,3) and adjusted analysis (OR = 1.1; 95% CI 0,8–1,6).
Conclusions

The results suggested that routine iron use in non-anemic pregnant women does not increase the risk of developing gestational diabetes. This evidence supports the existing national and international guidelines, whose recommendation is prophylactic iron supplementation for all pregnant women as soon as they initiate antenatal care in order to prevent iron deficiency anemia.
Impact of Maintenance Therapy Following Induction Immunochemotherapy for Untreated Advanced Non-Small Cell Lung Cancer Patients
Authors: Nakamura Ryota , Yamada Tadaaki , Morimoto Kenji , Nakao Akira , Goto Yasuhiro , Ogura Yuri , Takeda Takayuki , Takumi Chieko , Onoi Keisuke , Chihara Yusuke , Taniguchi Ryusuke , Yamada Takahiro , Hiranuma Osamu , Tanaka Satomi , Morimoto Yoshie , Iwasaku Masahiro , Tokuda Shinsaku , Kaneko Yoshiko , Uchino Junji , Takayama Koichi
Published: September 2021

Purpose
The primary objective of this study was to identify the potential predictors to assess impact of maintenance therapy after induction immunochemotherapy in the real-world setting of patients with advanced non-small cell lung cancer (NSCLC).
Methods
We retrospectively identified 152 patients with advanced NSCLC who received immunochemotherapy at eight hospitals in Japan between January 2019 to December 2019. Patients who received at least four cycles of induction immunochemotherapy and one cycle of maintenance therapy with immune-checkpoint inhibitors were included. We investigated the biomarkers for progression-free survival (PFS) for maintenance therapy after induction immunochemotherapy.
Results
Out of the 92 patients with advanced NSCLC included in the study, 42 received maintenance therapy with cytotoxic agents whereas 50 received maintenance therapy without cytotoxic agents. Among those who received maintenance therapy without cytotoxic agents, responders to prior immunochemotherapy had significantly longer PFS than non-responders (p = 0.004), except those with maintenance therapy with cytotoxic agents. In non-responders to prior immunochemotherapy, patients with maintenance therapy with cytotoxic agents had significantly longer PFS than those with maintenance therapy without cytotoxic agents (log-rank p = 0.007), whereas among responders to prior immunochemotherapy, there was no significant difference in PFS for different maintenance regimens (log-rank p = 0.31).
Conclusions
This retrospective study showed that response to prior immunochemotherapy was associated with clinical outcomes among patients with advanced NSCLC who received maintenance therapy.
Does Benzocaine Toothpaste Have More Pain-Relieving Effect Compared To Placebo Toothpaste In Orthodontic Patients? A Double-Blind Randomized Controlled Trial
Authors: Eslamian Ladan , Soheilifar Sepideh , Soheilifar Sanaz , Mortazavi Seyed Alireza
Published: September 2021

Background: Pain management in fixed orthodontic treatment is an important challenge. None of the present methods has been successful in pain relief. The objective of this double-blind cross-over trial was to compare the effect of benzocaine-contained toothpaste and placebo toothpaste on relieving pain caused by fixed orthodontic treatment.Methods and material:Patients undergoing fixed orthodontic treatment at Shahid Beheshti University of Medical Sciences with experience of pain in previous appointment were randomly assigned into 3 groups of 5% benzocaine-contained toothpaste, placebo toothpaste and control group. Eligibility criteria included being in leveling and alignment stage, 6-8 mm space deficiency, no acute or chronic pain or frequent consumption of analgesic drugs. Patients were instructed to use toothpastes 3 times in a day. Main outcome was pain experienced by patients according to Visual Analogue Scale at 8 different time intervals in 7 days. Randomization was done with random numbers in opaque envelopes for sequence of appointments. Blinding was applicable for patients, operator and outcome assessor. Data analysis was done with repeated measure ANOVA for assessing overall effect and Bonferroni for pairwise analysis. P value was assigned to be 0.05.Results: From 33 patients who participated in the study, 27 patients (23 females and 4 males) completed the study. Each patient was randomly allocated to all 3 groups in cross-over design. Mean pain in benzocaine group was less than the placebo and control group (28.63± 25.43, 31.31± 22.09 and 31.20 ± 24.09, respectively). Benzocaine toothpaste group experienced statistically significantly less pain than the other two groups at 2 hours (P˂ 0.015). No adverse event was observed in patients.Conclusion:Benzocaine contained toothpaste can decrease pain perceived at first hours after orthodontic appointment. Registration and protocol: This trial was registered in Iranian Registry of Clinical Trials (IRCT2015010120523N1) at 16/04/2015.
Structural Stability, Elasticity, Thermodynamics and Electronic Structures of L12-Type Ni3X (X=Al, Ti, V, Nb) Phases Under External Pressure Condition
Authors: Wu Y H , Chen J S , Ji J Y , Zhang Y Z , Wang Q Z , Xiong K
Published: September 2021

In this paper, the impacts of external pressure on structural stability, elasticity, thermodynamics and relevant electronic structures of L12-type Ni3X (X=Al, Ti, V, Nb) phases were investigated using the first-principles methods. The lattice parameters(a,b,c) and volume(V) of the Ni3X phases decrease with increasing pressure. however, the elastic constants(Cij ), bulk modulus(B), shear modulus(G), and Young's modulus (E) increase. The calculated elastic constants indicate that the mechanical stability and ductility of Ni3X phases enhance with increasing pressure. The mechanical anisotropy of Ni3X phases are enhanced by the raised pressure. Electronic analysis shows that increase pressure makes Ni-d-orbital and X(X=Al, Ti, V, Nb) -d-orbital hybridization stronger and electron transfer increases. The sequence in regard to electron aggregation strength is Ni3Ti>Ni3Nb>Ni3V>Ni3Al. It is more directly reflected in the charge density difference maps. This is consistent with the analysis results of the enthalpy of formation(ΔH) and Debye temperature (ΘD).
Electrocardiographic and Histopathological Characterizations of Diabetic Cardiomyopathy in Rats
Authors: Youssef Mahmoud E. , El-Azab Mona F. , Abdel-Dayem Marwa A. , Metwally Galal Yahya , Alanazi Ibtesam S. , Saber Sameh
Published: September 2021

Diabetes is a clinical condition that is associated with insulin deficiency and hyperglycemia. Cardiomyopathy, retinopathy, neuropathy, and nephropathy are well known complications of the elevated blood glucose. Diabetic cardiomyopathy is a clinical disorder that is associated with systolic and diastolic dysfunction along with cardiac fibrosis, inflammation, and elevated oxidative stress. In this study, diabetes was induced by intraperitoneal injection of streptozotocin (STZ) 50 mg/kg. We determined the plasma levels of cardiac troponin-T (cTnT), and creatinine kinase MB (CK-MB) by ELISA. Diabetic rats showed abnormal cardiac architecture and increased collagen production. significant elevation in ST-segment, prolonged QRS and QT-intervals, and increased ventricular rate were detected. Additionally, diabetic rats showed a prolongation in P wave duration and atrial tachyarrhythmia was observed. Plasma levels of cTnT and CK-MB were elevated. In conclusion, these electrocardiographic changes (elevated ST-segment, prolonged QT interval, and QRS complex, and increased heart rate) along with histopathological changes and increased collagen formation could be markers for the development of diabetic cardiomyopathy in rats.
Validating the Knowledge Bank Approach for Personalized Prediction of Survival in Acute Myeloid Leukemia: a Reproducibility Study
Authors: Xu Yujun , Mansmann Ulrich
Published: September 2021

Reproducibility is not only essential for the integrity of scientific research, but is also a prerequisite of model validation and refinement for future application of (predictive) algorithms. However, reproducible research is becoming increasingly challenging, particularly in high-dimensional genomic data analyses with complex statistical or algorithmic techniques. Given that there are no mandatory requirements in most biomedical and statistical journals to provide the original data, analytical source code, or other relevant materials for publication, accessibility to these supplements naturally suggests a greater credibility of published work. In this study, we performed a reproducibility assessment of the notable paper by Gerstung et al. published in Nature Genetics (2017) by rerunning the analysis using their original code and data, which are publicly accessible. Despite a perfect open science setting, it was challenging to reproduce the entire research project; reasons included coding errors, suboptimal code legibility, incomplete documentation, intensive computations, and an R computing environment that could no longer be re-established. We learn that availability of code and data does not guarantee transparency and reproducibility of a study; in contrast, the source code is still liable to error and obsolescence, essentially due to methodological complexity, lack of editorial reproducibility checking at submission, and updates of software and operating environment. Building on the experience gained, we propose practical criteria for the conduct and reporting of reproducibility studies for future researchers.
A Comparison Between the Adductor Pollicis Muscle and the Abductor Digiti Minimi Muscle Using Electromyography AF-201P in Rocuronium-Induced Neuromuscular Block: A Prospective Comparative Study
Authors: Iwasaki Hajime , Sato Hanae , Takagi Shunichi , Kitajima Osamu , Luthe Sarah Kyuragi , Suzuki Takahiro
Published: September 2021

Background
The AF-201P, a new electromyography (EMG)-based neuromuscular monitor has been developed recently. The aim of this clinical study was to compare two ulnar nerve innervated muscles: the adductor pollicis (AP) muscle and the abductor digiti minimi (ADM) muscle during the recovery from rocuronium-induced neuromuscular block by using EMG AF-201P.
Methods
Twenty patients undergoing surgery with general anesthesia were enrolled in the study. During total intravenous general anesthesia, train-of-four (TOF) and post-tetanic counts (PTC) responses following 0.9 mg/kg rocuronium administration were concurrently monitored at the AP and the ADM muscles with EMG AF-201P on the opposite arms. At the end of the surgery, sugammadex 2 mg/kg was administered when TOF counts of 2 was observed at both muscles. The primary outcome of the study was time from administration of rocuronium to first appearance of PTC response (first PTC). The secondary outcomes of the study were time from administration of rocuronium to first reappearance of TOF response (first TOF), time from first PTC to first TOF (PTC-TOF time), time to reappearance of TOF counts of 2, and time from administration of sugammadex to TOF ratio ≥ 0.9. Agreement between the two muscles was assessed using the Bland-Altman analysis. Data are expressed as mean ± standard deviation.
Results
Nineteen patients were included in the analysis. Time for appearance of the first PTC was significantly faster at the ADM muscle than the AP muscle (32.4 ± 13.1min vs 24.4 ± 11.4min, p = 0.006). Interval time between the first PTC and the first TOF was significantly longer with the ADM muscle than the AP muscle (19.4 ± 7.3min vs 12.4 ± 10.6min, p = 0.019). There were no significant differences in time to TOF counts of 2 and sugammadex-facilitated recovery between the two muscles. Bland-Altman analyses showed acceptable ranges of bias and limits of agreement of the two muscles.
Conclusions
The ADM muscle showed a good agreement with the AP muscle during rocuronium-induced neuromuscular block but faster recovery of PTC response when using EMG.
Trial registration
: UMIN-CTR (Registration No. UMIN000044904). Registered 19 July 2021 -Retrospectively registered,
A New Approach to Study the Degradation of the Organic Pollutants by A-Doped MxOy/B Photocatalysts
Authors: Arabameri Mojtaba , Bashiri Hadis
Published: September 2021

This work presents a new approach and a comprehensive mechanism to study the kinetics of the photodegradation of the organic pollutants. The vital role of various operational factors on the degradation of the organic pollutants is explained using this method. The proposed approach is based on the simple strategies and a powerful computational method. Two new variables “the effective concentration of photon” (Ieff) and “the effective concentration of the reactive-centers” (RC) are defined to better understanding the effect of operational parameters on the organic pollutants photodegradation. The optimum conditions of the photocatalytic degradation can be determined with the help of this method. This approach was used to study the kinetics of photodegradation of the organic pollutants on the A - doped MxOy/B photocatalysts. The provided mechanism has been examined with the some experimental data. The high correlations between the experimental data and the fitting results under different conditions prove this mechanism could be reliable.
Rice LEAFY COTYLEDONE1 regulates embryonic envelope development and chlorophyll biogenesis in embryo
Authors: Chen Chen , Niu Baixiao , Yang Zongju , Bai Tianqi , E Zhiguo , Xu Xinyu , Yun Qianbin , Zhang Juan , Zhang Zhenyu , Lu Xinming , Li Qianfeng , Liu Qiaoquan
Published: September 2021

The scutellum, coleoptile, coleorhiza, and epiblast (if it exists) consist of a complex embryonic envelope to protect the plumule and radicle inside a grass embryo. Controversies have been provoked for centuries regarding homologies of the grass embryonic structures. Here we found that the rice LEAFY COTYLEDONE1 (LEC1) gene, OsNF-YB7, is vital for embryo development. A leaf-like structure (LL) was developed from the scutellum of osnf-yb7 to replace the embryonic envelope that formed in wild-type. Additionally, osnf-yb7 developed chloroembryos due to overactivated chlorophyll biosynthesis. Thus, OsNF-YB7 likely plays a dual role in chlorophyll biogenesis in rice embryos: (1) OsNF-YB7 directly represses genes, such as rice GOLDED-LIKE1 (OsGLK1), involving chlorophyll biosynthesis; (2) OsNF-YB7 binds to OsGLK1 to repress the downstream genes of OsGLK1. Parallel phenotypes shown in osnf-yb7 and lec1 suggest functional conservation of the LEC1-type genes in plants. Both lec1 cotyledons and osnf-yb7 LL displayed true leaf characteristics. Our morphological and transcriptional evidence implied that LL replaces the embryonic envelope in osnf-yb7, raising the hypothesis that the grass embryonic envelope is an analog of Arabidopsis cotyledon. This study demonstrates that OsNF-YB7 acts as a negative regulator in chlorophyll biogenesis and is important for embryonic envelope formation.
Low Expression of PDHX is Associated with Poor Prognosis and Immune Infiltration in Gastric Cancer
Authors: Sun Biao , Li Bao , Long Ziyang , Zhang Cangyuan , Sun Qiannan , Ren Jun , Wang Daorong
Published: September 2021

Background: Pyruvate dehydrogenase protein X (PDHX) is a non-catalytic subunit of the pyruvate dehydrogenase (PDH) complex. It is located in the center of mitochondrial energy metabolism and is an essential component to maintain the biological activity of PDH complex. The purpose of this study was to explore its expression level in gastric cancer and its relationship with immune infiltration. Methods: Through immunohistochemical analysis of 80 pairs of gastric cancer tissue samples and open database analys such as Kaplan-Meier Plotter, TIMER2.0,GEPIA,String and DAVID database.Results: We found that the expression of PDHX in paracancerous tissues was significantly higher than that in gastric cancer tissues. Database analysis showed that the expression of PDHX was low in gastric cancer tissues, and the total survival time (OS) of relatively high expression in gastric cancer patients was higher. In N1~N3 and M stages, the P values of OS and PFS with high expression of PDHX were less than 0.05. It is suggested that the overexpression of PDHX may affect the prognosis of gastric cancer patients with lymph node and distant metastasis. Conclusions: Therefore, we concluded that the expression of PDHX is suppressed in gastric cancer and has a longer overall survival time of 5 years in patients with relatively high expression, and that the increased expression of PDHX may improve the prognosis of patients with lymph node and distant metastasis of gastric cancer.
Ankle Orthosis-induced Decrease in Repetitive Rebound Jump Height: Relationship With Restriction in Sagittal Ankle Range of Motion
Authors: Masanori Morikawa , Noriaki Maeda , Makoto Komiya , Toshiki Kobayashi , Yukio Urabe
Published: September 2021

Background: Ankle orthotics decreases the maximal vertical jump height. It is essential to maximize jump height and minimize ground contact time during athletic performance. However, the effect of ankle orthotics on athletic performance has not been reported. We aimed to investigate the effect of ankle orthotics on squat jump (SJ), countermovement jump (CMJ), and repetitive rebound jump (RJ) performance and the relationship between jump performance and restriction in sagittal ankle range of motion. Methods: Twenty healthy volunteers performed SJ, CMJ, repetitive RJ under no-orthosis and two orthotic conditions (orthosis 1 and orthosis 2). During SJ and CMJ, we measured the vertical ground reaction force and calculated the following parameters: jump height, peak vertical ground reaction force, rate of force development, net vertical impulse, and peak power. During repetitive RJ, the jump height, contact time, and RJ index were measured. A two-dimensional motion analysis was used to quantify the ankle range of motion in the sagittal plane during SJ, CMJ, and repetitive RJ. Results: Multivariate analysis of variance and the post hoc test showed a significant decrease in the vertical jump height (p = 0.003), peak power (p = 0.007), and maximum plantarflexion and dorsiflexion angles (p <0.001) during SJ using orthosis 2 compared to those using the no-orthosis condition. Additionally, orthosis 2 significantly decreased the jump height at the end of repetitive RJ (p = 0.046), during which a significant negative correlation was found between jump height and maximum dorsiflexion angle (r = 0.485, p = 0.030). Conclusions: An ankle orthosis-induced restriction of dorsiflexion is associated with a reduction in jump height during static jump and repetitive RJ performance.
Diabetic Retinopathy and Skin Tissue Advanced Glycation End Products Are Biomarkers of Vascular Events in Type 2 Diabetic Patients
Authors: Planas Alejandra , Simó-Servat Olga , Hernández Cristina , Ortiz-Zúñiga Ángel , Marsal Joan Ramón , Herance José Raul , Ferreira-González Ignacio , Simó Rafael
Published: September 2021

BACKGROUND AND AIMS: Vascular events are the main cause of mortality in patients with type 2 diabetes. However, the risk of vascular events is not homogeneous in subjects with type 2 diabetes and, therefore, an early identification of patients at high risk of developing vascular events remains a challenge to be met. The aim of this study is to evaluate whether the presence of diabetic retinopathy (DR) and accumulation of advanced glycation end products (AGEs) in subcutaneous tissue can help to identify those patients at high risk of vascular events.MATERIAL AND METHODS: It was a prospective study comprising 200 subjects with type 2 diabetes with no history of clinical cardiovascular disease and 60 non-diabetic controls, matched by age and sex (PRECISED study: ClinicalTrials.gov NCT02248311). The inclusion period began on September 2014 and finished on June 2017. We collected basal features of the subjects, classical cardiovascular risk factors (i.e. age, sex, hypertension, dyslipidemia and coronary artery calcium score [CACs]), presence and degree of DR, and the accumulation of AGEs in subcutaneous tissue using the AGE readerTM device (DiagnOptics Technologies). We followed these subjects until December 2020, collecting any coronary, cerebrovascular or peripheral arterial event.RESULTS: After a follow up of 4.35 ± 1.43 years, a total of 24 vascular events were registered. There was no significant difference regarding age and gender between individuals with type 2 diabetes and the control group. The number of vascular events was higher in type 2 diabetes group than in the control group (12.3% vs. 1.75%). When analysing the risk factors we found that apart from classic risk factors such as age, gender and CACs, subjects with type 2 diabetes and vascular events presented a higher prevalence of DR (47.8% vs. 24.4%; p = 0.018) and AGEs in subcutaneous tissue (63.15% vs 26.71% of values in the higher tertile, p = 0.001). DR and AGEs in subcutaneous tissue remain as independent variables related to the development of vascular events in the Cox proportional hazard multiple regression analysis (HR 2.58, 95%CI 1.14–5.85, p = 0.023, and HR 4.68, 95%CI 1.83–11.96, p = 0.001; respectively).CONCLUSIONS: As we expected, patients with type 2 diabetes have significantly more VE than non-diabetic subjects. Apart from the classic factors such as age, sex and CACs, we observed that the presence of DR and high levels of AGEs in subcutaneous tissue were predictors of vascular events.
Inflammatory Conditions Promote Resistance to Immune Checkpoint Inhibitors in High Microsatellite Instability Colorectal Cancer
Authors: Sui Qiaoqi , Zhang Xi , Tang Jinghua , Han Kai , Jiang Wu , Leen Liao , Kong Lingheng , Li Yuan , Hou Zhenlin , Zhou Chi , Zhang Chenzhi , Zhang Linjie , Xiao Binyi , Mei Wei-Jian , Xu Yanbo , Zheng Jian , Pan Zhi-Zhong , Ding Pei-Rong
Published: September 2021

Inflammatory conditions are common complications in colorectal cancer (CRC) and play significant roles in tumor progression and immunosuppression. However, the influence of inflammatory conditions on the tumor response to immune checkpoint inhibitors (ICIs) remains unclear. We included a high microsatellite instability (MSI-H) CRC patient whose primary tumor progressed and liver metastasis regressed after Pembrolizumab treatment. An organoid-T cell coculture model demonstrated an inhibited local immune response instead of systemic immunosuppression. Single-cell RNA sequencing suggested that neutrophils suppress the immune microenvironment, mostly through CTLA-4-associated pathways. A cohort of 73 patients with MSI-H CRC who received ICIs were enrolled, among whom inflammatory conditions were correlated with a poor tumor response. We demonstrated that inflammatory conditions in MSI-H CRCs correlate with resistance to ICIs through neutrophil-associated immunosuppression. Additional CTLA-4 blockade may improve the sensitivity to PD-1 blockade. Clinically, inflammatory conditions could predict a poor response to ICIs in MSI-H CRCs.
Intrinsic First and Higher-Order Topological Superconductivity in a Doped Topological Insulator
Authors: Scammell Harley , Ingham Julian , Geier Max , Li Tommy
Published: September 2021

We explore higher-order topological superconductivity in an artificial Dirac material with intrinsic spin-orbit coupling. A mechanism for superconductivity due to repulsive interactions – pseudospin pairing – has recently been shown to result in higher-order topology in Dirac systems past a minimum chemical potential [1]. Here we apply this theory through microscopic modelling of a superlattice potential imposed on an inversion symmetric hole-doped semiconductor heterostructure, and extend previous work to include the effects of spin-orbit coupling. We find spin-orbit coupling enhances interaction effects, providing an experimental handle to increase the efficiency of the superconducting mechanism. We find that the phase diagram, as a function of chemical potential and interaction strength, contains three superconducting states – a first-order topological p + ip state, a second-order topological spatially modulated p + iτp state, and a second-order topological extended s-wave state, sτ. We calculate the symmetry-based indicators for the p + iτp and sτ states, which prove these states possess second-order topology. Exact diagonalisation results are presented which illustrate the interplay between the boundary physics and spin orbit interaction. We argue that this class of systems offer an experimental platform to engineer and explore first and higher-order topological superconducting states.
Indonesian Genomic Landscape of Pathogenic Mutation of APC, KRAS, TP53, PIK3CA, and MLH1 in Colorectal Cancer
Authors: Marbun Vania Myralda Giamour , Lalisang Toar Jean Maurice , Erlina Linda
Published: September 2021

Background : Knowing colorectal cancer’s heterogeneity and dynamic features, recognizing its biological behaviour requires detailed identification of mutated genes involved. Colorectal cancer (CRC) requires several mutated genes to occur and those are dissimilar in each person hence essential to be discovered in specific population. Until recently, there is no known study describing genomic landscape of CRC in Indonesian population. This study aims to describe profile of pathogenic mutation of APC, TP53, PIK3CA, KRAS, and MLH1 in CRC patients treated at 3 different hospitals in Jakarta. Methods : This is a descriptive study conducted on CRC patients who underwent neoadjuvant, surgical, and adjuvant therapy at RSCM, RSKJ, and MRCCC in 2017-2018. DNA analysis was performed using next-generation sequencing and aligned against GRCh38. Pathogenic variant was identified using ACMG classification and FATHMM score. Data related to behaviour and survival were collected from medical records. Results : There were total 22 subjects in which APC, TP53, and PIKCA were mutated. KRAS mutation occurred in 64%, while MLH1 in 45%. Five types of mutation were identified, including nonsense, missense, frameshift, splice-site, and silent mutation. There are 4 groups of co-occurring mutations, which are APC, TP53, PIK3CA (triple mutation/TM) alone; TM+KRAS; TM+MLH1; and TM+KRAS+MLH1, presenting different nature and survival. Conclusion : Indonesia having various ethnicities with diverse diet and lifestyle has distinct profile of pathogenic mutation presenting mostly with locally-advanced stage with various outcome and survival rate.
The Pregnancy Experiences and Antenatal Care Services of Chinese Migrants in Switzerland: A Qualitative Study
Authors: CAI Ding cui , Villanueva Paulina , Stuijfzand Susannah , Lu Hong , Zimmermann Basile , Horsch Antje
Published: September 2021

Background: Differences in reproductive health outcomes according to the mother's origins have been reported in Switzerland, for example, women from European countries and non-European countries. The Swiss Federal Office of Public Health has therefore called for specific Swiss-wide studies on migrant populations. This study explores the pregnancy and antenatal care experiences of Chinese migrants in Switzerland, intending to clarify their maternity care needs.Methods: In-depth interviews of 14 Chinese mothers and 13 family members were conducted in Chinese or English and audio recorded. All audio-recordingswere transcribed verbatim. All Chinese transcripts were translated into English.Thematic analysis was performed with the assistance of the qualitative dataanalysis software, MAXQDA Analytics Pro 2020.Results: Five themes were extracted from the transcripts: (1) Motivations andconcerns about having children, (2) The merits of the Swiss maternity caresystem, (3) The inconvenience and barriers of accessing Swiss maternity careservices, (4) Strategies to deal with the inconveniences of the Swiss maternitycare system, and (5) The need for culturally sensitive care.Conclusions: The results of our study provide new knowledge and understandingof pregnancy experiences and antenatal care services of Chinese mothers andtheir families in Switzerland. Their unique positive experiences included: familyplanning, the continuity of maternity services, humane care with the privacyrespected, personalized sensitive care needs, preferences for female obstetriciansand obstetricians of Asian origin. Several barriers were highlighted, suchasinformation seeking difficulties, communication difficulties, and a rigidappointment system. Reducing barriers enabling access to maternity care serviceswithin the Swiss healthcare system is necessary to provide equal qualitymaternitycare for individuals, irrespective of their origins.
The New Putative Type III Effector SkP48 in Bradyrhizobium sp. DOA9 is Involved in Legume Nodulation
Authors: Piromyou Pongdet , Songwattana Pongpan , Boonchuen Pakpoom , Nguyen Hien P. , Manassila Monchai , Tantanuch Waraporn , Maikhunthod Bussayarat , Teamtisong Kamonluck , Tittabut Panlada , Boonkerd Nantakorn , Giraud Eric , Teaumroong Neung
Published: September 2021

Bradyrhizobium sp. DOA9 can nodulate a wide spectrum of legumes; however, unlike other bradyrhizobia, DOA9 carries a symbiotic plasmid harboring type III secretion system (T3SS) and several effector (T3E) genes, one of which encodes a new putative type III effector—SkP48. Here, we demonstrated the pivotal roles of SkP48 from Bradyrhizobium sp. DOA9 in inhibiting nodulation of various Vigna species and Crotalaria juncea and suppressing nodulation efficiency of Arachis hypogea. By contrast, the nodulation efficiency of a SkP48 mutant did not differ significantly with the DOA9 wild-type strain on Macroptilium atropurpureum and Stylosanthes hamata. An evolutionary analysis revealed that the SkP48 effector which contains a shikimate kinase and a SUMO protease (C48 cysteine peptidase) domain is distinct from the others effectors previously identified in others bradyrhizobia and pathogenic bacteria. Our findings suggest that the new putative T3E SkP48 is a key factor suppressing nodulation and nodule organogenesis in several legumes by activation of effector-triggered immunity through salicylic acid biosynthesis induction, which is deleterious to rhizobial infection. In addition, nodulation may be modulated by the function of defensins involved in jasmonic acid signalling in V. radiata SUT1.
Differential Diagnosis of Lipoma and Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma by Cytological Analysis
Authors: Sugiyama Kana , Washimi Kota , Sato Shinya , Hiruma Toru , Sakai Mai , Okubo Yoichiro , Miyagi Yohei , Yokose Tomoyuki
Published: September 2021

Background: Adipocytic tumors are the most common soft tissue tumors, with lipomas and atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDL) comprising the majority of cases. Preoperative differential diagnosis of lipoma or ALT/WDL can provide important information for decisions regarding treatment. We evaluated the cytological findings of 20 cases of lipoma and ALT/WDL.Methods: Fluorescence in situ hybridization (FISH) was performed on formalin-fixed paraffin-embedded specimens (FFPE) to examine mouse double minute 2 homolog (MDM2) amplification in all cases. Tissue samples were collected from the center of the surgical materials, stained with Papanicolaou, and evaluated for 12 cytological parameters by six cytotechnologists.Results: The findings regarding large atypical cells, multinucleated cells, and nuclear pleomorphism were highly concordant among the cytotechnologists and were associated with MDM2 amplification. Large atypical cells, considered a highly specific feature of ALT/WDL, were not observed in the lipoma cases. However, the sensitivity of the large atypical cell findings was not high (67%), and therefore, comprehensive evaluation of multinucleated cells and pleomorphism is crucial for predicting the diagnosis of ALT/WDL. FISH of MDM2 on Papanicolaou-stained specimens was performed in four cases. In two cases, the results were similar to those of MDM2 FISH performed on FFPE sections and were reproducible, whereas in two other cases, the signal could not be evaluated because of the strong background coloration. Conclusions: Cytology specimens may be useful for preoperative diagnosis of adipocytic tumors, particularly if the FISH conditions for Papanicolaou-stained specimens and the detection accuracy of MDM2 amplification can be improved.
Immunophenotypic Landscape and Prognosis-Related mRNA Signature in Diffuse Large B Cell Lymphoma
Authors: Jiang Yanan , Sun Huimeng , Xu Hong , Wu Wenqi , Lv Yangyang , Wang Jinhuan , Liu Su , Zhai Yixin , Tian LinYan , Wang Yafei , Zhao Zhigang
Published: September 2021

Diffuse large B cell lymphoma (DLBCL) exhibits a tightly complexity immune landscape. In this study, we intended to identify different immune phenotype and to examine the immune related mRNA signature for clinical characteristic, therapeutic responsiveness as well as risk stratification and survival prediction in DLBCL. We separated 738 DLCBL patients into two robust subtypes with distinct immune features based on 28 immune cell types. GO analysis uncovered the concordant classification of two robust significant subtypes of DLBCL. Immunity-L group, associated with poorer outcomes, was characterized by significantly lower immune cell infiltration. Immunity-H group, associated with better outcomes, was characterized by significantly higher immune cell infiltration. Further, a prognostic gene signature related immune infiltration was established by a least absolute shrinkage and selection operator (LASSO)-Cox regression model. The comprehensive results showed that the high-risk group was correlated with lower immune infiltration, more aggressive phenotypes, lower overall survival and more sensitive to lenalidomide. In contrast, a low-risk group score was associated with higher immune infiltration, less aggressive phenotypes, better overall survival and more likely to benefit from PD-1/PD-L1 inhibitors. Finally, a nomogram comprised of the immune risk score and IPI score was verified to more accurately predict the overall survival of DLBCL than traditional clinical prediction models. Altogether, our data demonstrate the heterogeneity of immune patterns within DLBCL and deepen our molecular understanding of this tumor entity.
An Analysis of the Selection Criteria for Postgraduate Physician Assistant Residency and Fellowship Programs in the United States
Authors: Kidd Vasco Deon , Vanderlinden Sarah , Spisak Jennifer M
Published: September 2021

BackgroundThis study aims to investigate the admission criteria used by PA postgraduate education programs in selecting licensed PA applicants for postgraduate training in the United States. To our knowledge, there have been no previously published reports on selection criteria and/or other factors influencing postgraduate PA admission decisions. This study both draws on and builds upon previous research conducted by Vasco Deon Kidd et. al in exploring the characteristics of PA postgraduate education programs in the United States.Method A non-experimental, descriptive research study was designed to obtain information from members of the Association of Postgraduate Physician Assistant Programs (APPAP). ResultsTwenty-three out of 73 postgraduate programs (35.1%) responded to the survey; the low response rate in our survey may have been attributed to the resurgence of COVID-19 fueled by the delta variant. Nevertheless, the study reported that applicant PAs and NPs are largely selected on the basis of several factors. The most heavily weighted factor is the interview itself; other selection criteria perceived to be extremely/very important included board certification/eligibility, letters of recommendation, advanced degree, and personal essay. Survey data suggest that publications, undergraduate transcripts, and class rankings are not considered to be of high importance in applicant selection. The total cost of training a PA resident or fellow in postgraduate programs is currently $93,000 whereas the average cost of training a categorical physician resident is estimated at $150,000 per year when considering both salary and benefits. The number of PA applicants applying to each postgraduate training program averages around 26 and total number of enrollees is 3.6 per program.ConclusionsThis is the first study to examine criteria and others factors used by postgraduate PA programs in selecting candidates for admission. Results can be used by postgraduate programs for quality improvement initiatives related to including additional or modifying current selection criteria to improve the quality of trainee selection. Further research is needed to examine correlations between applicant attributes, selection criteria, and trainee success in completing postgraduate training.
Pre-Trained Transformer-Based Language Models for Sundanese
Authors: Wongso Wilson , Lucky Henry , Suhartono Derwin
Published: September 2021

The Sundanese language has over 32 million speakers worldwide, but the language has reaped little to no benefits from the recent advances in natural language understanding. Like other low-resource languages, the only alternative is to fine-tune existing multilingual models. In this paper, we pre-trained three monolingual Transformer-based language models on Sundanese data. When evaluated on a downstream text classification task, we found that most of our monolingual models outperformed larger multilingual models despite the smaller overall pre-training data. In the subsequent analyses, our models benefited strongly from the Sundanese pre-training corpus size and do not exhibit socially biased behavior. We released our models for other researchers and practitioners to use.
Does Safety Netting for Lung Cancer Symptoms Help Patients to Reconsult Appropriately? A Qualitative Study
Authors: Black Georgia , Os Sandra van , Renzi Christina , Walter Fiona , Hamilton Willie , Whitaker Katriina L
Published: September 2021

Background

Safety netting in primary care is considered an important intervention for managing diagnostic uncertainty. This is the first study to examine how patients understand and interpret safety netting advice around low-risk potential lung cancer symptoms, and how this affects reconsultation behaviours.
Methods

Qualitative dyadic interview study in UK primary care. Pre-covid-19, five patients were interviewed face-to-face twice (shortly after a primary care consultation for potential lung cancer symptom(s) and 2–5 months later). The general practitioner (GP) they last saw was interviewed face-to-face once. During the covid-19 pandemic, an additional 15 patients were interviewed once via telephone. Audio-recorded interviews were transcribed verbatim and analysed using a mix of inductive and deductive thematic analysis.
Results

The findings from our thematic analysis suggest that patients prefer active safety, as part of thorough and logical diagnostic uncertainty management. Passive safety netting may be perceived as dismissive and cause delayed reconsultation. GP safety netting strategies are not always understood, potentially causing patient worry and dissatisfaction. Telephone consultations and the diagnostic overshadowing of COVID-19 on respiratory symptoms impacted GPs’ safety netting strategies and patients’ appetite for active follow up measures.
Conclusions

Safety netting guidelines do not yet offer solutions that have been proven to promote symptom vigilance and timely reconsultation for low-risk lung cancer symptoms. Patients prefer active safety netting coupled with thorough consultation techniques and a comprehensible diagnostic strategy, and may respond adversely to passive safety netting advice.
Methotrexate-Loaded Nanoparticles Ameliorate Autoimmune Arthritis by Regulating the Balance of Interleukin-17-Producing T Cells and Regulatory T and B Cells
Authors: Park Jin-Sil , Lee Donghyun , Yang SeungCheon , Na Hyun Sik , Cho Keun-Hyung , Choi JeongWon , Koo Heebeom , Cho Mi-La , Park Sung-Hwan
Published: September 2021

Background: Rheumatoid arthritis (RA) is a progressive systemic autoimmune disease that is characterized by infiltration of inflammatory cells into the hyperplastic synovial tissue, resulting in subsequent destruction of adjacent articular cartilage and bone. Methotrexate (MTX), the first conventional disease-modifying antirheumatic drug (DMARD), could alleviate articular damage in RA and is implicated in humoral and cellular immune responses. However, MTX has several side effects, so efficient delivery of low-dose MTX is important. Methods: To investigate the efficacy of MTX-loaded nanoparticles (MTX-NPs) against RA, free MTX or MTX-NPs were administered as subcutaneous route to mice with collagen-induced arthritis (CIA) at 3 weeks after CII immunization. The levels of inflammatory factors in tissues were determined by immunohistochemistry, confocal microscopy, real-time PCR, and flow cytometry. Results: MTX-NPs ameliorated arthritic severity and joint destruction in collagen-induced arthritis (CIA) mice compared to free MTX-treated CIA mice. The levels of inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α, and vascular endothelial growth factor, were reduced in MTX-NPs-treated mice. Numbers of phosphorylated STAT3-positive CD4+ cells and CD4+IL-17+ cells were reduced whereas the number of CD4+CD25+Foxp3+ cells increased in spleens from MTX- NPs-treated CIA mice compared to MTX-treated CIA mice. The frequency of CD19+CD25+Foxp3+ regulatory B cells increased in ex vivo splenocytes from MTX-loaded NPs-treated CIA mice compared to MTX-treated CIA mice. Conclusion: The results suggest that MTX-loaded NPs have therapeutic potential for RA.