bluuebunny/crossref_metadata_2025 huggingface dataset:
Vestibular disorders in patients after COVID-19 infection
Authors: Pazdro-Zastawny Katarzyna , Dorobisz Karolina , Misiak Paula , Kruk-Krzemień Anna , Zatoński Tomasz
Published: September 2022

Introduction

The COVID-19 clinical symptoms are primarily related to the respiratory system but may also be involved in many others, including the nervous system. Recently, vertigo or dizziness has been described as one of the clinical manifestations and possible complications of COVID-19.

Materials and methods

This clinical study was designed to describe the otorhinolaryngological evaluation and videonystagmographic (VNG) findings in patients with an antecedent of COVID-19 infection in the last 6 months. In this study, we sought to investigate the presence of persistent vestibular damage in healed COVID-19 patients and to determine the origin of vertigo by conducting a comprehensive vestibular examination. To evaluate the association precisely, an otoneurological assessement was conducted on all participants. The study group included 58 patients aged 23–75 years with vertigo, who were diagnosed with COVID-19 infection 6 months before the examination. Each participant was submitted to an evaluation consisting of anamnesis, otorhinolaryngological evaluation, and VNG.

Results

Spontaneous nystagmus with closed eyes was reported in 8 patients (13.8%). Positional nystagmus was observed in 15 patients (24.1%). Asymmetrical optokinetic nystagmus was observed in 18 patients (31%). A distorted record in the tracking pendulum test was present in 23 patients (39.7%). Square waves were observed in 34 COVID-19 patients (58.6%). Unilateral weakness (UW) was observed in 23 subjects (39.7%); among those with UW, 22 patients (95.7%) also demonstrated directional preponderance contralateral to the UW. Another 16 patients (27.6%) presented only directional advantage. The post-caloric recruitment was present in 38% patients.

Conclusion

Patients who had been diagnosed with COVID-19 seem to be more likely to suffer from vertigo/dizziness and to compensate more slowly. COVID-19 infection may cause inner ear damage and lead to vestibular dysfunction. The role of the central nervous system in the onset of equilibrium disorders should be considered. The presence of vertigo of central origin may indicate the neurotropic effect of SARS-CoV-2 following COVID-19. Imbalance may be the only symptom of COVID-19 and may also be a late complication of the disease due to post-infectious inflammation of the nervous tissue. Comprehensive studies are needed to investigate whether COVID-19 can cause long-term vestibular deficits.
Association between blood viscosity and early neurological deterioration in lacunar infarction
Authors: Lee Hyungwoo , Heo JoonNyung , Lee Il Hyung , Kim Young Dae , Nam Hyo Suk
Published: September 2022

Background

Understanding the factors related to early neurologic deterioration (END) is crucial in the management of patients with lacunar infarction. Blood viscosity is a significant factor for microvascular perfusion. We investigated the association between blood viscosity and occurrence of END in lacunar infarction.

Methods

We included consecutive patients admitted for lacunar infarction within 72 h from symptoms onset. END was defined as an increase in the National Institute of Health Stroke Scale (NIHSS) score ≥2 within 24 h of admission. Viscosity was measured within 24 h of hospitalization with a scanning capillary tube viscometer. Viscosity measured at a shear rate of 300 s−1 was defined as systolic blood viscosity (SBV), whereas that measured at a shear rate of 5 s−1 as diastolic blood viscosity (DBV).

Results

Of the 178 patients included (median age, 65.5; interquartile range [IQR], 56.0, 76.0], END occurred in 33 (18.5%). DBV was significantly higher in patients with END than those without END (13.3 mPa·s [IQR 11.8, 16.0] vs. 12.3 mPa·s [IQR11.0, 13.5]; P = 0.023). In the multivariate analysis, DBV was independently associated with the occurrence of END (odds ratio 1.17; 95% confidence interval 1.01–1.36; P = 0.043). Subgroup analysis showed no heterogeneity in the effect of viscosity on the occurrence of END.

Conclusions

Blood viscosity at a low shear rate (DBV) was associated with the occurrence of END in patients with lacunar infarction. Blood rheology may be important in pathophysiology of END in patients with lacunar infarction.
Felbamate for pediatric epilepsy—should we keep on using it as the last resort?
Authors: Rabinowicz Shira , Schreiber Tal , Heimer Gali , Bar-Yosef Omer , Nissenkorn Andreea , E Zohar-Dayan , Arkush Leo , Hamed Nasrin , Ben-Zeev Bruria , Tzadok Michal
Published: September 2022

Introduction

Concerns regarding felbamate adverse effects restrict its widespread use in children with drug-resistant epilepsy. We aimed to examine the efficacy and safety of felbamate in those children and identify the ones who may benefit most from its use.

Methods

We retrospectively reviewed the medical files of all patients who were treated with felbamate in a tertiary pediatric epilepsy clinic between 2009–2021. Drug efficacy was determined at the first 3 months of treatment and thereafter. Therapeutic response and adverse reactions were monitored throughout the course of treatment.

Results

Our study included 75 children (age 8.9 ± 3.7 years), of whom 53 were treated with felbamate for seizures, 16 for electrical status epilepticus during sleep and 6 for both. The median follow-up time was 16 months (range 1–129 months). The most common cause for epilepsy was genetic (29%). The median number of previous anti-seizure medications was six [4–8]. A therapeutic response ≥50% was documented in 37 (51%) patients, and a complete response in 9 (12%). Nineteen patients (25%) sustained adverse reactions, including three cases of elevated liver enzymes and one case of neutropenia with normal bone marrow aspiration. In all cases, treatment could be continued. All children with intractable epilepsy following herpes encephalitis showed a response to felbamate.

Conclusion

Felbamate is an efficacious and safe anti-seizure medication in the pediatric population.
From tumor mutational burden to characteristic targets analysis: Identifying the predictive biomarkers and natural product interventions in cancer management
Authors: Liu Cun , Yu Yang , Wang Ge , Liu Jingyang , Liu Ruijuan , Liu Lijuan , Yang Xiaoxu , Li Huayao , Gao Chundi , Lu Yi , Zhuang Jing
Published: September 2022

High-throughput next-generation sequencing (NGS) provides insights into genome-wide mutations and can be used to identify biomarkers for the prediction of immune and targeted responses. A deeper understanding of the molecular biological significance of genetic variation and effective interventions is required and ultimately needs to be associated with clinical benefits. We conducted a retrospective observational study of patients in two cancer cohorts who underwent NGS in a “real-world” setting. The association between differences in tumor mutational burden (TMB) and clinical presentation was evaluated. We aimed to identify several key mutation targets and describe their biological characteristics and potential clinical value. A pan-cancer dataset was downloaded as a verification set for further analysis and summary. Natural product screening for the targeted intervention of key markers was also achieved. The majority of tumor patients were younger adult males with advanced cancer. The gene identified with the highest mutation rate was TP53, followed by PIK3CA, EGFR, and LRP1B. The association of TMB (0–103.7 muts/Mb) with various clinical subgroups was determined. More frequent mutations, such as in LRP1B, as well as higher levels of ferritin and neuron-specific enolase, led to higher TMB levels. Further analysis of the key targets, LRP1B and APC, was performed, and mutations in LRP1B led to better immune benefits compared to APC. APC, one of the most frequently mutated genes in gastrointestinal tumors, was further investigated, and the potential interventions by cochinchinone B and rottlerin were clarified. In summary, based on the analysis of the characteristics of gene mutations in the “real world,” we obtained the potential association indicators of TMB, found the key signatures LRP1B and APC, and further described their biological significance and potential interventions.
Risk factors for postoperative pulmonary complications in elderly patients receiving elective colorectal surgery: A retrospective study
Authors: Dai Yuanqiang , Sun Guolin , Hu Hongli , Wang Chun , Wang Hengyue , Zha Yanping , Sheng Ying , Hou Jiong , Bian Jinjun , Bo Lulong
Published: September 2022

Study objective

Postoperative pulmonary complications (PPCs) are common and associated with adverse outcomes impairing long-term survival and quality of recovery. This single-centered retrospective study aimed to examine factors associated with PPCs in patients receiving elective colorectal surgery aged ≥60 years.

Methods

Between January 2019 and December 2019, 638 patients at the Shanghai Changhai Hospital who had received elective surgery for colorectal cancer were enrolled in this study. Patients were divided into the PPC group (n=38) and non-PPC group (n=600). Neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), red blood cell distribution width (RDW), and systemic inflammatory index (SII) were selected and caculated to indicate preoperative and postoperative inflammatory status. Receiver operating characteristic curve and bivariate correlation analyses were performed to evaluate the identified risk factors.

Main results

The overall incidence of PPCs was approximately 5.96%. Multivariate regression analysis identified age (OR = 1.094, 95%CI 1.038–1.153, P = 0.001), preoperative RDW (OR = 1.159, 95%CI 1.025–1.309, P = 0.018), and preoperative SII (OR = 1.001, 95%CI 1.000–1.003, P = 0.035) as independent risk factors for PPCs. The cut-off values of age, preoperative RDW, and preoperative SII for predicting PPCs were 69.5 (sensitivity 0.658, specificity 0.653), 13.2 (sensitivity 0.789, specificity 0.552) and 556.1 (sensitivity 0.579, specificity 0.672), respectively.

Conclusions

Age, preoperative RDW, and preoperative SII were identified as independent risk factors for PPC occurrence in elderly patients receiving elective colorectal surgery. Further studies are warranted to evaluate whether normalization of preoperative RDW and SII, as modifiable risk factors, are associated with improved surgical outcomes.
Differential glutamine metabolism in the tumor microenvironment – studies in diversity and heterogeneity: A mini-review
Authors: Claiborne Michael D. , Leone Robert
Published: September 2022

Increased glutamine metabolism is a hallmark of many cancer types. In recent years, our understanding of the distinct and diverse metabolic pathways through which glutamine can be utilized has grown more refined. Additionally, the different metabolic requirements of the diverse array of cell types within the tumor microenvironment complicate the strategy of targeting any particular glutamine pathway as cancer therapy. In this Mini-Review, we discuss recent advances in further clarifying the cellular fate of glutamine through different metabolic pathways. We further discuss potential promising strategies which exploit the different requirements of cells in the tumor microenvironment as it pertains to glutamine metabolism in an attempt to suppress cancer growth and enhance anti-tumor immune responses.
Trends of colorectal cancer incidence according to age, anatomic site, and histological subgroup in Bavaria: A registry-based study
Authors: Voigtländer Sven , Hakimhashemi Amir , Grundmann Nina , Rees Franziska , Meyer Martin , Algül Hana , Müller-Nordhorn Jacqueline
Published: September 2022

Background

Recent studies reported an increase in colorectal cancer incidence for adults below 50 years. There is a lack of studies distinguishing between histological subgroups, especially from Europe.

Methods

Using data from the Bavarian Cancer Registry, we analyzed incidence trends in colorectal cancer by age (20–29, 30–39, 40–49, and 50 years and above), anatomic site (colon without appendix, appendix, and rectum), and histological subgroup (adenocarcinoma and neuroendocrine neoplasm) from 2005 to 2019. We calculated 3-year average annual age-standardized incidence rates (ASIR) per 100,000 persons for the beginning (2005–2007) and the end (2017–2019) of the study period and estimated average annual percentage change.

Results

Data from 137,469 persons diagnosed with colorectal cancer were included. From 139,420 cases in total, 109,825 (78.8%) were adenocarcinomas (ACs), 2,800 (2.0%) were neuroendocrine neoplasms (NENs), and 26,795 (19.2%) had other histologies. This analysis showed a significant increase in the 3-year average annual ASIR of colorectal NENs in all age groups between 2005–2007 and 2017–2019 with the highest increase in the age groups 30–39 years (0.47 to 1.53 cases per 100,000 persons; +226%; p < 0.05) and 20–29 years (0.52 to 1.38 cases per 100,000 persons; +165%; p < 0.05). The increase was driven by appendiceal and rectal NENs but not by colonic NENs. The 3-year average annual ASIR of colorectal ACs did not change significantly for the age groups below 50 years. For those aged 50 years and above, the 3-year average annual ASIR of colorectal ACs decreased significantly (132.55 to 105.95 cases per 100,000 persons; −20%; p < 0.05]). The proportion of NENs increased across all age groups, especially in the younger age groups.

Conclusion

Future studies that analyze trends in early-onset colorectal cancer need to distinguish between anatomic sites as well as histological subgroups and may, thus, provide useful information regarding the organization of colorectal cancer screening, which primarily helps to detect adenomas and adenocarcinomas."
Case report: Durable response to alectinib in ALK-rearranged lung adenocarcinoma with acquired, crizotinib-resistant ALK C1156F mutation
Authors: Rao Chuangzhou , Nie Liangqin , Wu Xiaokang , Miao Xiaobo , Chen Ting , Chen Liuxi , Zhang Dongqing , Lin Quan
Published: September 2022

Treatment of ALK-rearranged non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors (TKIs) is challenged by the almost inevitable emergence of therapeutic resistance. Different profiles of resistance mechanisms have been reported for the currently available ALK TKIs. The ALK C1156Y mutation is reported in 2% of patients with acquired resistance to crizotinib. A rare substitution at the same site, C1156F, remains largely unknown. Existing evidence includes identification of C1156F and G1202R in an alectinib-resistant patient and sensitivity to crizotinib and resistance to later-generation 3ALK inhibitors in preclinical models. In this report, we present two cases in which NSCLC patients acquired the ALK C1156F mutation on crizotinib monotherapy. Both patients were men, and one had been heavily treated with chemotherapeutic regimens before identification of ALK rearrangement, whereas the other received crizotinib as first-line treatment. Genomic profiling of blood biopsies after progression on crizotinib suggested emergence of the ALK C1156F variant. Both patients subsequently received and responded favorably to alectinib, achieving respective progression-free survival of 21 and 15 months as of the latest follow-ups. To the best of our knowledge, this work is the first to provide clinical evidence of resistance to crizotinib and sensitivity to alectinib in NSCLC patients harboring acquired ALK C1156F mutation.
CD8+ T cell-associated genes MS4A1 and TNFRSF17 are prognostic markers and inhibit the progression of colon cancer
Authors: Song Ye , Zhang Zhipeng , Zhang Bo , Zhang Weihui
Published: September 2022

Background

Colon cancer (CC) is among the top three diseases with the highest morbidity and mortality rates worldwide. Its increasing incidence imposes a major global health burden. Immune checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1, can be used for the treatment of CC; however, most patients with CC are resistant to immunotherapy. Therefore, identification of biomarkers that can predict immunotherapy sensitivity is necessary for selecting patients with CC who are eligible for immunotherapy.

Methods

Differentially expressed genes associated with the high infiltration of CD8+ T cells were identified in CC and para-cancerous samples via bioinformatic analysis. Kaplan–Meier survival analysis revealed that MS4A1 and TNFRSF17 were associated with the overall survival of patients with CC. Cellular experiments were performed for verification, and the protein expression of target genes was determined via immunohistochemical staining of CC and the adjacent healthy tissues. The proliferation, migration and invasion abilities of CC cells with high expression of target genes were determined via in vitro experiments.

Results

Differential gene expression, weighted gene co-expression and survival analyses revealed that patients with CC with high expression of MS4A1 and TNFRSF17 had longer overall survival. The expression of these two genes was lower in CC tissues than in healthy colon tissues and was remarkably associated with the infiltration of various immune cells, including CD8+ T cells, in the tumour microenvironment (TME) of CC. Patients with CC with high expression of MS4A1 and TNFRSF17 were more sensitive to immunotherapy. Quantitative reverse transcription-polymerase chain reaction, western blotting and immunohistochemical staining validated the differential expression of MS4A1 and TNFRSF17. In addition, Cell Counting Kit-8, wound healing and transwell assays revealed that the proliferation, migration and invasion abilities of CC cells were weakened after overexpression of MS4A1 and TNFRSF17.

Conclusions

The core genes MS4A1 and TNFRSF17 can be used as markers to predict the sensitivity of patients with CC to immunotherapy and have potential applications in gene therapy to inhibit CC progression.
Nomograms predicting local and distant recurrence and disease-specific mortality for R0/R1 soft tissue sarcomas of the extremities
Authors: De Sanctis Rita , Zelic Renata , Santoro Armando
Published: September 2022

Background

Prognostic models for patients with soft tissue sarcoma (STS) of the extremities have been developed from large multi-institutional datasets with mixed results. We aimed to develop predictive nomograms for sarcoma-specific survival (SSS) and, for the first time, long-term local recurrence (LR) and distant recurrence (DR) in patients with STS of the extremities treated at our institution.

Patients and methods

Data from patients treated at Humanitas Cancer Center from 1997 to 2015 were analyzed. Variable selection was based on the clinical knowledge and multivariable regression splines algorithm. Perioperative treatments were always included in the model. Prognostic models were developed using Cox proportional hazards model, and model estimates were plotted in nomograms predicting SSS at 5 and 10 years and LR and DR at 2, 5, and 10 years. Model performance was estimated internally via bootstrapping, in terms of optimism-corrected discrimination (Harrell C-index) and calibration (calibration plots).

Results

Data on 517 patients were analyzed. At 5 and 10 years, SSS was 68.1% [95% confidence interval (CI), 63.8–72.1] and 55.6% (50.5–60.3), respectively. LR was 79.1% (95% CI, 75.3–82.4), 71.1% (95% CI, 66.7–75.1), and 66.0% (95% CI, 60.7–70.7) at 2, 5, and 10 years, respectively, whereas DR was 65.9% (95% CI, 61.6–69.9), 57.5% (95% CI, 53.0–61.8), and 52.1% (95% CI, 47.1–56.8) at 2, 5, and 10 years, respectively. SSS nomogram included age, gender, margins, tumor size, grading, and histotype. LR and DR nomograms incorporated mostly the same variables, except for age for DR; LR nomogram did not include gender but included anatomic site. The optimism-corrected C-indexes were 0.73 and 0.72 for SSS at 5 and 10 years, respectively; 0.65, 0.64, and 0.64 for LR at 2, 5, and 10 years, respectively; and 0.68 for DR at 2, 5, and 10 years. Predicted probabilities were close to the observed ones for all outcomes.

Conclusions

We developed and validated three nomograms for STS of the extremities predicting the probability of SSS at 5 and 10 years and LR and DR at 2, 5, and 10 years. By accounting for the perioperative treatment, these models allow prediction for future patients who had no perioperative treatment, thus being useful in the clinical decision-making process.
CD9- and CD81-positive extracellular vesicles provide a marker to monitor glioblastoma cell response to photon-based and proton-based radiotherapy
Authors: Jennrich Sara , Pelzer Martin , Tertel Tobias , Koska Benjamin , Vüllings Melanie , Thakur Basant Kumar , Jendrossek Verena , Timmermann Beate , Giebel Bernd , Rudner Justine
Published: September 2022

Glioblastoma multiforme (GBM) is the most aggressive tumor of the central nervous system with a poor prognosis. In the treatment of GBM tumors, radiotherapy plays a major role. Typically, GBM tumors cannot be cured by irradiation because of intrinsic resistance machanisms. An escalation of the irradiation dose in the GBM tumor is difficult due to the high risk of severe side effects in the brain. In the last decade, the development of new irradiation techniques, including proton-based irradiation, promised new chances in the treatment of brain tumors. In contrast to conventional radiotherapy, irradiation with protons allows a dosimetrically more confined dose deposition in the tumor while better sparing the normal tissue surrounding the tumor. A systematic comparison of both irradiation techniques on glioblastoma cells has not been performed so far. Despite the improvements in radiotherapy, it remains challenging to predict the therapeutical response of GBM tumors. Recent publications suggest extracellular vesicles (EVs) as promising markers predicting tumor response. Being part of an ancient intercellular communication system, virtually all cells release specifically composed EVs. The assembly of EVs varies between cell types and depends on environmental parameters. Here, we compared the impact of photon-based with proton-based radiotherapy on cell viability and phenotype of four different glioblastoma cell lines. Furthermore, we characterized EVs released by different glioblastoma cells and correlated released EVs with the cellular response to radiotherapy. Our results demonstrated that glioblastoma cells reacted more sensitive to irradiation with protons than photons, while radiation-induced cell death 72 h after single dose irradiation was independent of the irradiation modality. Moreover, we detected CD9 and CD81-positive EVs in the supernatant of all glioblastoma cells, although at different concentrations. The amount of released CD9 and CD81-positive EVs increased after irradiation when cells became apoptotic. Although secreted EVs of non-irradiated cells were not predictive for radiosensitivity, their increased EV release after irradiation correlated with the cytotoxic response to radiotherapy 72 h after irradiation. Thus, our data suggest a novel application of EVs in the surveillance of anti-cancer therapies.
Association between subtypes of metabolic syndrome and prognosis in patients with stage I endometrioid adenocarcinoma: A retrospective cohort study
Authors: Chen Man-qi , Lin Hai-xue , Liang Jin-xiao , Wu Miao-fang , Li Jing , Wang Li-juan
Published: September 2022

Purpose

To investigate the association between subtypes of metabolic syndrome (MetS) and prognosis of patients with stage I endometrioid adenocarcinoma.

Patients and methods

Patients with stage I endometrioid adenocarcinoma who received surgical treatment as primary therapy at the Department of Gynecology of the Sun Yat-sen Memorial Hospital between June 2015 and December 2019 were retrospectively enrolled. According to the diagnosis criteria of MetS, the patients were categorized as patients without MetS, patients with MetS but without raised fasting plasma glucose (FPG, including previously diagnosed diabetes), and patients with MetS and raised FPG. All the included patients were followed from the dates of surgery until death, June 2021, or loss to follow-up, whichever came first, and cancer recurrence (including metastasis) was studied as the main outcome. Cox regression was used to evaluate the associations between subtypes of MetS and the study outcome adjusting for potential confounding factors.

Results

Among the included 387 patients with stage I endometrioid adenocarcinoma, 193 (49.9%) were without MetS, 65 (16.8%) were with FPG not involving MetS, and 129 (33.3%) were with raised FPG involved MetS. With a median follow-up of 1,253 days, the cumulative incidence of cancer recurrence was 8.76% (95% confidence interval (CI) 2.5%–14.62%), 28.31% (95% CI 2.33%–47.38%), and 7.54% (95% CI 1.54%–13.17%), respectively. After adjusting for age, menopause, histological grade, tumor size, lymph-vascular space invasion, deep myometrial invasion, and treatments, comorbid FPG not involving MetS is a stronger risk factor of cancer recurrence than comorbid raised FPG involving MetS (hazard ratio 2.82 (95% CI 1.10–7.24) versus 1.18 (95% CI 0.45–3.13)) when compared to patients without MetS.

Conclusion

Comorbid MetS generally presents as a risk factor of poor prognosis in patients with stage I endometrioid adenocarcinoma after surgical treatment, but the magnitude of the association may vary between subtypes, in which FPG not involving MetS appears to be predominant.
Copper metabolism patterns and tumor microenvironment characterization in colon adenocarcinoma
Authors: Lin Jianwei , Luo Bixian , Yu Xinbo , Yang Zheyu , Wang Mingliang , Cai Wei
Published: September 2022

Copper participates in biological processes such as oxygen metabolism and iron uptake, and is a key factor in immune regulation. Based on the transcription data, mutation data and clinical data of colon adenocarcinoma (COAD) patients from The Cancer Genome Atlas (TCGA) database and Gene Expression Profiling Interactive Analysis (GEPIA2) database, the expression and mutation of copper metabolization-related genes in COAD patients and their correlation with tumor immune microenvironment were analyzed. Copper metabolization-related genes (CMRGs) were used to construct COAD subtypes and prognostic risk models for COAD patients. Furthermore, Kaplan-Meier (K-M) curve and receiver operating characteristic (ROC) curve were used to analyze the clinical value of COAD subtypes and genotyping models in distinguishing clinical characteristics of patients, and the immune infiltration of patients with different genotypes was analyzed. Finally, the clinical tissue samples from COAD patients were used to analyze the mRNA expression of genes in risk model between tumor and normal tissues by the method of Polymerase Chain Reaction (PCR). Of the 479 CMRGs, 68 genes were differentially expressed in normal and tumor tissues of COAD patients in TCGA and GEPIA2. Two subtypes with different clinical and immunological characteristics were identified by using 482 genes related to copper metabolism. Finally, a prognostic risk model consisting of five CMRGs was constructed, which could not only predict the prognosis of patients, but also correlated with COAD subtypes. In addition, some genes (glutathione S-transferase mu 1, cyclin D1and cytochrome P450 family 2 subfamily S member 1) in risk model was show significant difference between normal and tumor tissues. The COAD subtypes identified by CMRGs can help clinically distinguish patients with different prognosis and tumor progression, and the risk score can assist in clinical evaluation of patient prognosis, serving as a valuable biomarker for COAD immunotherapy.
Monitoring of telomere dynamics in peripheral blood leukocytes in relation to colorectal cancer patients’ outcomes
Authors: Tomasova Kristyna , Kroupa Michal , Zinkova Alzbeta , Korabecna Marie , Vymetalkova Veronika , Skrobanek Pavel , Sojka Ladislav , Levy Miroslav , Hemminki Kari , Liska Vaclav , Hosek Petr , Kumar Rajiv , Vodickova Ludmila , Vodicka Pavel
Published: September 2022

We investigated the possible associations between leukocyte telomere length, therapy outcomes, and clinicopathological features in patients with colorectal cancer. Additionally, telomerase reverse transcriptase (TERT) expression was evaluated. Telomere length was measured using singleplex qPCR in 478 consecutive leukocyte DNA samples from 198 patients. Blood was drawn at diagnosis prior to any therapy and then at 6-month intervals for 18 months. Following diagnosis, the telomeres gradually shortened during the course of the treatment regardless of the patient’s age. The most pronounced decrease was observed 12 months after the diagnosis (p < 0.0001). Based on tumor localization, the decrease in telomere length one year after the diagnosis followed different trajectories (p = 0.03). In patients treated with adjuvant therapy, telomere length correlated with the time elapsed after completion of therapy (p = 0.03). TERT expression did not correlate with the telomere length; however, it was higher in women than men (1.35-fold, 95% CI 1.11–1.65, p = 0.003) and in smokers than non-smokers (1.27-fold, 95% CI 1.01–1.61, p = 0.04). Leukocyte telomere length declines naturally during aging, but the accelerated shortening observed in our patients was age-independent. Telomere length manifestly reflected chemotherapy impact and could be linked to therapy toxicity.
Anti-cancer properties of Caulerpa racemosa by altering expression of Bcl-2, BAX, cleaved caspase 3 and apoptosis in HeLa cancer cell culture
Authors: Permatasari Happy Kurnia , Wewengkang Defny Silvia , Tertiana Nur Iedha , Muslim Farida Zharfani , Yusuf Muhammad , Baliulina Shintya Octaviana , Daud Vanessa Pradna Adyana , Setiawan Aurielle Annalicia , Nurkolis Fahrul
Published: September 2022

The main cause of cervical cancer is infection with Human Papilloma Virus (HPV). Loss of apoptotic control allows cancer cells to survive longer and allows time for mutation accumulation thereby increasing the ability to invade during tumor development. Treatment options for cervical cancer today are surgery, radiotherapy, and chemotherapy. Toxicity to normal cells, adverse side effects, and drug resistance are the main barriers to the use of chemotherapy. Among marine organisms such as bacteria, fungi, actinobacteria, and seaweed have been used for the treatment of cancer. Caulerpa has bioactive metabolites, namely alkaloids, terpenoids, flavonoids, steroids and tannins and its bioactivity has been reported against many diseases including cancer. This study aimed to evaluate the anticancer activity of C. racemosa on HeLa cervical cancer cells. The study used a true experimental post-test only control group design to determine the effect of C. racemosa extract on HeLa cancer cells. C. racemosa extract was given in doses of 50 μg/mL, 100 μg/mL, 200 μg/mL, and 0 μg/mL as controls. Quantitative measurement of apoptosis was measured using flowcytometry and the expression of Bcl-2, BAX, and cleaved-caspase 3 as pro and anti-apoptotic proteins was measured using immunofluorescence. Trypan blue exclusion test was performed to measure cell viability. C. racemosa extract significantly increased the expression of pro-apoptotic proteins BAX and cleaved caspase-3 compared to controls. Annexin V-PI analysis showed the induction of apoptosis in treated cells and decreased HeLa cell viability at 24 hours and 48 hours post-treatment (p-value <0.05). C. racemosa extract has potential as an anti-cancer with pro-apoptotic and anti-proliferative activity on HeLa cancer cells and can be explored further as a cervical cancer therapy.
Risk of developing depression from endocrine treatment: A nationwide cohort study of women administered treatment for breast cancer in South Korea
Authors: Oh Jooyoung , Lee Hye Sun , Jeon Soyoung , Kim Dooreh , Seok Jeong-Ho , Park Woo-Chan , Kim Jae-Jin , Yoon Chang Ik
Published: September 2022

Background

Although previous studies demonstrated no association between depression and tamoxifen in patients with breast cancer, there is still a limited amount of long-term follow-up data. This study aimed to evaluate the relationship between endocrine treatment and the risk of depression.

Methods

This nationwide population-based cohort study used data obtained over a 14-year period (January 2007 to December 2021) from the Korean National Health Insurance claims database. All female patients with breast cancer were included. We examined the incidence of depression in patients who underwent endocrine treatment, and those who did not undergo endocrine treatment constituted the control group.

Results

The data from 11,109 patients who underwent endocrine treatment and 6,615 control patients between 2009 and 2010 were analyzed. After performing matching for comorbidities and age, both groups comprised 6,532 patients. The median follow-up were 119.71 months. Before and after matching was performed, the endocrine treatment was not a significant risk factor for developing depression (p=0.7295 and p=0.2668, respectively), nor was it a significant factor for an increased risk for suicide attempt (p=0.6381 and p=0.8366, respectively).

Conclusions

Using a real-world population-based cohort, this study demonstrated that there is no evidence that the endocrine treatment increases the risk of depression.
Role of left atrial hypertension in pulmonary hypertension associated with bronchopulmonary dysplasia
Authors: Sullivan Rachel T. , Tandel Megha D. , Bhombal Shazia , Adamson Gregory T. , Boothroyd Derek B. , Tracy Michael , Moy Amanda , Hopper Rachel K.
Published: September 2022

Left atrial hypertension (LAH) may contribute to pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD). Primary causes of LAH in infants with BPD include left ventricular diastolic dysfunction or hemodynamically significant left to right shunt. The incidence of LAH, which is definitively diagnosed by cardiac catheterization, and its contribution to PH is unknown in patients with BPD-PH. We report the prevalence of LAH in an institutional cohort with BPD-PH with careful examination of hemodynamic contributors and impact on patient outcomes. This single-center, retrospective cohort study examined children <2 years of age with BPD-PH who underwent cardiac catheterization at Lucile Packard Children's Hospital Stanford. Patients with unrepaired simple shunt congenital heart disease (CHD) and pulmonary vein stenosis (only 1 or 2 vessel disease) were included. Patients with complex CHD were excluded. From April 2010 to December 2021, 34 patients with BPD-PH underwent cardiac catheterization. We define LAH as pulmonary capillary wedge pressure (PCWP) or left atrial pressure (LAP) of at least 10 mmHg. In this cohort, median PCWP was 8 mmHg, with LAH present in 32% (n = 11) of the total cohort. A majority (88%, n = 30) of the cohort had severe BPD. Most patients had some form of underlying CHD and/or pulmonary vein stenosis: 62% (n = 21) with an atrial septal defect or patent foramen ovale, 62% (n = 21) with patent ductus arteriosus, 12% (n = 4) with ventricular septal defect, and 12% (n = 4) with pulmonary vein stenosis. Using an unadjusted logistic regression model, baseline requirement for positive pressure ventilation at time of cardiac catheterization was associated with increased risk for LAH (odds ratio 8.44, 95% CI 1.46–48.85, p = 0.02). Small for gestational age birthweight, sildenafil use, and CHD were not associated with increased risk for LAH. LAH was associated with increased risk for the composite outcome of tracheostomy and/or death, with a hazard ratio of 6.32 (95% CI 1.72, 22.96; p = 0.005). While the etiology of BPD-PH is multifactorial, LAH is associated with PH in some cases and may play a role in clinical management and patient outcomes.
Protease-activated receptor 2 promotes clearance of Pseudomonas aeruginosa infection by inducing cAMP-Rac1 signaling in alveolar macrophages
Authors: Rayees Sheikh , Joshi Jagdish Chandra , Joshi Bhagwati , Vellingiri Vigneshwaran , Banerjee Somenath , Mehta Dolly
Published: September 2022

Efficient phagocytosis of pathogens by the innate immune system during infectious injury is vital for restoring tissue integrity. Impaired phagocytosis, such as in the case of infection withPseudomonas aeruginosa, a broad-spectrum antibiotic-resistant Gram-negative bacterium, can lead to a life threatening lung disorder, acute lung injury (ALI). Evidence indicates that loss of protease-activated receptor 2 (PAR2) impairedPseudomonas aeruginosaclearance leading to non-resolvable ALI, but the mechanism remains unclear. Here, we focused on the alveolar macrophages (AMs), the predominant population of lung-resident macrophages involved in sensing bacteria, to understand their role in PAR2-mediated phagocytosis ofPseudomonas aeruginosa. We found that upon bindingPseudomonas aeruginosa, PAR2-expressing but not PAR2-null AMs had increased cAMP levels, which activated Rac1 through protein kinase A. Activated Rac1 increased actin-rich protrusions to augment the phagocytosis ofPseudomonas aeruginosa. Administration of liposomes containing constitutively active Rac1 into PAR2-null mice lungs rescued phagocytosis and enhanced the survival of PAR2-null mice from pneumonia. These studies showed that PAR2 drives the cAMP-Rac1 signaling cascade that activatesPseudomonas aeruginosaphagocytosis in AMs, thereby preventing death from bacterial pneumonia.
Automatic tongue image quality assessment using a multi-task deep learning model
Authors: Xian Huimin , Xie Yanyan , Yang Zizhu , Zhang Linzi , Li Shangxuan , Shang Hongcai , Zhou Wu , Zhang Honglai
Published: September 2022

The quality of tongue images has a significant influence on the performance of tongue diagnosis in Chinese medicine. During the acquisition process, the quality of the tongue image is easily affected by factors such as the illumination, camera parameters, and tongue extension of the subject. To ensure that the quality of the collected images meet the diagnostic criteria of traditional Chinese Medicine practitioners, we propose a deep learning model to evaluate the quality of tongue images. First, we acquired the tongue images of the patients under different lighting conditions, exposures, and tongue extension conditions using the inspection instrument, and experienced Chinese physicians manually screened them into high-quality and unqualified tongue datasets. We then designed a multi-task deep learning network to classify and evaluate the quality of tongue images by adding tongue segmentation as an auxiliary task, as the two tasks are related and can promote each other. Finally, we adaptively designed different task weight coefficients of a multi-task network to obtain better tongue image quality assessment (IQA) performance, as the two tasks have relatively different contributions in the loss weighting scheme. Experimental results show that the proposed method is superior to the traditional deep learning tongue IQA method, and as an additional task of the network, it can output the tongue segmentation area, which provides convenience for follow-up clinical tongue diagnosis. In addition, we used network visualization to verify the effectiveness of the proposed method qualitatively.
Understanding the fundamentals of oscillometry from a strip of lung tissue
Authors: Bossé Ynuk
Published: September 2022

Metrics used in spirometry caught on in respiratory medicine not only because they provide information of clinical importance but also because of a keen understanding of what is being measured. The forced expiratory volume in 1 s (FEV1), for example, is the maximal volume of air that can be expelled during the first second of a forced expiratory maneuver starting from a lung inflated to total lung capacity (TLC). Although it represents a very gross measurement of lung function, it is now used to guide the diagnosis and management of many lung disorders. Metrics used in oscillometry are not as concrete. Resistance, for example, has several connotations and its proper meaning in the context of a lung probed by an external device is not always intuitive. I think that the popularization of oscillometry and its firm implementation in respiratory guidelines starts with a keen understanding of what exactly is being measured. This review is an attempt to clearly explain the basic metrics of oscillometry. In my opinion, the fundamentals of oscillometry can be understood using a simple example of an excised strip of lung tissue subjected to a sinusoidal strain. The key notion is to divide the sinusoidal reacting force from the tissue strip into two sinusoids, one in phase with the strain and one preceding the strain by exactly a quarter of a cycle. Similar notions can then be applied to a whole lung subjected to a sinusoidal flow imposed at the mouth by an external device to understand basic metrics of oscillometry, including resistance, elastance, impedance, inertance, reactance and resonant frequency.
Development of a dual-arm rapid grape-harvesting robot for horizontal trellis cultivation
Authors: Jiang Yingxing , Liu Jizhan , Wang Jie , Li Wuhao , Peng Yun , Shan Haiyong
Published: September 2022

It is extremely necessary to achieve the rapid harvesting of table grapes planted with a standard trellis in the grape industry. The design and experimental analysis of a dual-arm high-speed grape-harvesting robot were carried out to address the limitations of low picking efficiency and high grape breakage rate of multijoint robotic arms. Based on the characteristics of the harvesting environment, such as the small gap between grape clusters, standard trellis, and vertical suspension of clusters, the configuration of the dual-arm harvesting robot is reasonably designed and analyzed, and the overall configuration of the machine and the installation position of key components are derived. Robotic arm and camera view analysis of the workspace harvesting process was performed using MATLAB, and it can be concluded that the structural design of this robot meets the grape harvesting requirements with a standard trellis. To improve the harvesting efficiency, some key high-speed harvesting technologies were adopted, such as the harvesting sequence decision based on the “sequential mirroring method” of grape cluster depth information, “one-eye and dual-arm” high-speed visual servo, dual arm action sequence decision, and optimization of the “visual end effector” large tolerance combination in a natural environment. The indoor accuracy experiment shows that when the degree of obscuration of grape clusters by leaves increases, the vision algorithm based on the geometric contours of grape clusters can still meet the demands of harvesting tasks. The motion positioning average errors of the left and right robotic arms were (X: 2.885 mm, Y: 3.972 mm, Z: 2.715 mm) and (X: 2.471 mm, Y: 3.289 mm, Z: 3.775 mm), respectively, and the average dual-arm harvesting time in one grape cluster was 8.45 s. The field performance test verifies that the average harvesting cycle of the robot with both arms reached 9 s/bunch, and the success rate of bunch identification and harvesting success rate reached 88 and 83%, respectively, which were significantly better than those of existing harvesting robots worldwide.
Genome-wide characterization and sequence polymorphism analyses of cysteine-rich poly comb-like protein in Glycine max
Authors: Nisar Tayyaba , Tahir Muhammad Hammad Nadeem , Iqbal Shahid , Sajjad Muhammad , Nadeem Muhammad Azhar , Qanmber Ghulam , Baig Ayesha , Khan Zulqurnain , Zhao Zhengyun , Geng Zhide , Ur Rehman Shoaib
Published: September 2022

Cysteine-rich poly comb-like protein (CPP) is a member of cysteine-rich transcription factors that regulates plant growth and development. In the present work, we characterized twelve CPP transcription factors encoding genes in soybean (Glycine max). Phylogenetic analyses classified CPP genes into six clades. Sequence logos analyses between G. max and G. soja amino acid residues exhibited high conservation. The presence of growth and stress-related cis-acting elements in the upstream regions of GmCPPs highlight their role in plant development and tolerance against abiotic stress. Ka/Ks levels showed that GmCPPs experienced limited selection pressure with limited functional divergence arising from segmental or whole genome duplication events. By using the PAN-genome of soybean, a single nucleotide polymorphism was identified in GmCPP-6. To perform high throughput genotyping, a kompetitive allele-specific PCR (KASP) marker was developed. Association analyses indicated that GmCPP-6-T allele of GmCPP-6 (in exon region) was associated with higher thousand seed weight under both water regimes (well-water and water-limited). Taken together, these results provide vital information to further decipher the biological functions of CPP genes in soybean molecular breeding.
It gets better with age: Resilience, stigma, and mental health among lesbian, gay, bisexual, transgender and queer persons from Poland
Authors: Koziara Karolina , Mijas Magdalena E. , Galbarczyk Andrzej , Wycisk Jowita , Pliczko Mateusz P. , Krzych-Miłkowska Karolina , Grabski Bartosz
Published: September 2022

Lesbian, gay, bisexual, transgender, and queer populations are disproportionately affected by chronic stress associated with stigma which contributes to health adversities including depression. Negative impact of stigma on health can be alleviated by factors such as resilience. Little is known however on how exposure to stigma, protective factors and mental health change with age among gender and sexually diverse persons. Our study aimed at investigating this issue. Our sample consisted of (i) 245 sexually diverse cisgender women, (ii) 175 sexually diverse cisgender men, and (iii) 98 transgender and gender diverse persons. We collected data through a web-based survey. Linear regression models were performed to investigate the interactions of age and each group of participants for resilience, stigma exposure, and mental health indicators (depression and self-esteem). We hypothesized that resilience and mental health indicators will be positively associated with age in all distinguished groups despite the continued exposure to minority stress. The analysis yielded no significant relationships between stigma exposure and age among study participants. However, we observed significant interaction effects of distinguished groups of participants and age in case of self-esteem, depression, and resilience. Self-esteem and resilience were related positively, and depression was negatively associated with age in all study groups. Additionally, we observed that sexually diverse cisgender men demonstrated significantly increased resilience, reduced depression and higher self-esteem compared to other groups. Although the exposure to stigma did not decrease with age, resilience and self-esteem increased, suggesting that LGBTQ persons manage to thrive despite adversities.