bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between poor sleep quality and an increased risk of dry eye disease in patients with obstructive sleep apnea syndrome
Authors: Pu Qi , Wu Zhen , Li Ao-Ling , Guo Xiao-Xiao , Hu Jing-Jie , Li Xin-Yu
Published: October 2022

Purpose

Obstructive sleep apnea (OSA) is related to an increased incidence of dry eye disease (DED). However, their exact relationship is unknown and requires further well-designed studies with advanced mechanisms detection.

Patients and methods

This case–control study included 125 OSA cases and 125 age–gender-matched controls enrolled in the hospital between 1 January and 1 October 2021. OSA diagnosis and classification were performed using a polysomnography (PSG) assay. Detailed ophthalmological examinations, including the Schirmer I test, corneal staining, and ocular surface disease index (OSDI), were used to detect DED-related parameters. A comprehensive ocular surface assay was performed to measure a series of parameters, including first non-invasive first tear film break-up time (f-NIBUT), average non-invasive first tear film break-up time (av-NIBUT), tear meniscus height (TMH), and loss of meibomian gland. In addition, the Pittsburgh Sleep Quality Index (PSQI) scale was used to assess sleep quality.

Results

Compared to the control, the OSA group showed an increased DED risk (P = 0.016) along with an increased PSQI score and a higher rate of poor quality sleep (P < 0.001 and P = 0.007, respectively). Stratification of OSA cases indicated that DED-related parameters were impaired in patients with severe OSA (P < 0.05). The analysis of DED-parameters-related factors showed significant correlations between OSA-related indexes and PSQI (P < 0.05). Moreover, the poor sleep quality group in the OSA cases showed worse DED-related parameters (P < 0.05), which was not observed in the control group.

Conclusion

OSA, especially the severe stage OSA, was related to an increased risk of DED. Also, sleep quality was correlated with the onset of both OSA and DED, where poor sleep quality revealed a relationship between OSA and the risk of DED. Overall, our findings provided evidence for advanced management of DED and OSA in future.
Inhibition of stress and spontaneous respiration: Efficacy and safety of monitored anesthesia care by target-controlled infusion remifentanil in combination with dexmedetomidine in fibreoptic bronchoscopy for patients with severe tracheal stenosis
Authors: Zhou Yi , Wu Wei , Zhu Yuanjie , Lv Xin , Liu Jianming
Published: October 2022

Objective

This study aimed to determine the effective concentration of target-controlled infusion (TCI) of remifentanil used to inhibit stress during the treatment of severe tracheal stenosis with fibreoptic bronchoscopy and to evaluate the monitored anesthesia care (MAC) by remifentanil.

Materials and methods

60 patients with severe tracheal stenosis who underwent fibreoptic bronchoscopy was performed. Dexmedetomidine was initially administered at a bolus dose (0.8 mcg/kg), followed by a 0.5 mcg/(kg⋅h) continuous infusion. Remifentanil was administered by TCI. The effective concentration (EC) of remifentanil was titrated by the improved sequential method, and 30 patients were included. The EC95 of remifentanil was set as the plasma target concentration to evaluate the safety of the MAC, and another 30 patients were included.

Results

The half effective effect-chamber concentration of remifentanil (EC50) was 2.243 ng/ml, and the EC95 was 2.710 ng/ml. Among the 30 patients who received an EC95 of remifentanil as the target concentration, one patient was remedied by injecting propofol, the score of Ramsay sedation was three. The incidence of subclinical hypoxemia (SPO2 of 90–95%) was 30%, the incidence of moderate hypoxemia (SPO2 of 75–89%, ≤60 s) was 20 and 86.7% of patients with oxygen saturation was less than 95% returned to normal by awakening. The satisfaction score of the operator was nine, the satisfaction score of the anesthesiologist was eight, the satisfaction score of the patients was 10, the rate of patient willingness to re-accept the procedure was 93.3% and the circulation was stable during the operation.

Conclusion

MAC using TCI of remifentanil with continuous pumping dexmedetomidine can effectively inhibit the stress response to fibreoptic bronchoscopy in patients with severe tracheal stenosis while maintaining spontaneous breathing. Under the anesthesia management of an experienced anesthesiologist, it provides a reference to tracheoscopic anesthesia of autonomous breathing.

Clinical trial registration

[http://www.chictr.org.cn/], identifier [ChiCTR 2100043380].
Doctors' adherence to guidelines recommendations and glycaemic control in diabetic patients in Quetta, Pakistan: Findings from an observational study
Authors: Saher Tabassum , Al-Worafi Yaser Mohammed , Iqbal Muhammad Nouman , Wahid Abdul , Iqbal Qaiser , Khan Asad , Atif Muhammad , Ahmad Nafees
Published: October 2022

Background

Poor control of diabetes mellitus (DM) is partly attributed to doctors' poor adherence to guidelines.

Objective

To evaluate doctors' adherence to pharmacotherapeutic recommendations of DM management guidelines and factors associated with guidelines adherence and glycaemic control.

Methods

This prospective observational study included 30 doctors who were treating DM patients in their private clinics in Quetta, Pakistan. On visit 1, a total of 600 prescriptions written by 30 enrolled doctors (20 patients per doctor) were noted along with patients' sociodemographic and clinical characteristics. American Diabetes Association guidelines was used as a reference. The prescriptions noted were judged for guidelines compliance. Of 600 enrolled patients, 450 patients (15 patients per doctor) were followed for one more visit and included in final analysis. Glycated hemoglobin (HbA1c) level noted one visit 2 was related with the respective prescription on visit 1. Data were analyzed by SPSS (version 23). A p-value <0.05 was considered statistically significant.

Results

Patients received a median of two antidiabetic drugs (range: 1–5). A total of 73.1% patients were on polytherapy. Metformin was the most frequently prescribed (88.4%) antidiabetic followed by gliptins (46.2%). A total of 41.6% prescriptions were judged guidelines compliant. In multivariate binary logistic regressions (MVBLR) analysis, chronic kidney disease (CKD) (OR = 0.422) and polytherapy (OR = 0.367) had statistically significant negative associations (p-value <0.05) with guidelines' compliant prescriptions. The group of doctors comprised of specialists and consultants wrote significantly (p-value = 0.004) high number of guidelines adherent prescriptions (mean rank = 20.25) than the group comprised of medical officers (mean rank = 11.34). On visit 2, only 39.5% patients were on goal glycemic levels. In MVBLR analysis, suffering from dyslipidemia (OR = 0.134) and CKD (OR = 0.111), receiving sulfonylurea (OR = 0.156) and guidelines' compliant prescription (OR = 4.195) were significantly (p-value <0 .05) associated with glycemic control.

Conclusion

Although guidelines compliant prescriptions produced better glycemic control, but doctors' adherence to guidelines and glycemic control were poor. Polytherapy and CKD emerged as risk factors for guidelines divergent prescriptions. Dyslipidemia, CKD and reception of sulfonylureas had negative association with glycemic control.
Dynamics of microbial populations and metabolites of fermenting saps throughout tapping process of ron and oil palm trees in Côte d’Ivoire
Authors: Djeni Theodore N. , Keisam Santosh , Kouame Karen H. , Assohoun-Djeni Christelle Nanouman , Ake Francine D. M. , Amoikon Laurent S. T. , Tuikhar Ngangyola , Labala Rajendra K. , Dje Marcellin K. , Jeyaram Kumaraswamy
Published: October 2022

Palm wine fermentation is a complex microbial process that evolves with tapping times. The dynamics in microbiota and metabolites throughout palm wine tapping days is still not established, which are critical for the distinctive characteristics of palm wine taste and quality, and thus the mastery of the daily quality fluctuation during tapping. We analyzed the changes in microbial community structure by amplicon sequencing of bacterial 16S rRNA gene and fungal internal transcribed spacer (ITS) region, and metabolite profile changes using mass spectrometry in palm wine collected over 25–30 days tapping of ron (Borassus aethiopum) and oil palms (Elaeis guineensis) from Côte d’Ivoire. The stage-wise collected palm wine samples showed distinct changes in microbial diversity and pH, supporting microbial community dynamics during palm wine tapping. Results highlighted the dominance ofSaccharomyces cerevisiaein early stages and the emergence of non-Saccharomycesyeasts, particularlyHanseniasporaspp. in the later stages of oil palm wine tapping, vice versa in the case of ron palm wine tapping, with a unique presence ofSaccharomycodesin the later stages (15–30 days). Fructophilic lactic acid bacteria (FLAB), mainlyFructobacillusandLeuconostoc, encountered in both types of palm wine tapping showed a decline at later stages of oil palm wine tapping. In this type of palm wine, acetic acid bacteria with generaAcetobacterandGlucanoacetobacter, by surpassingLactobacillusin the last stage become dominant, whereasLactobacillusremained dominant in ron palm wine throughout tapping days. The decline in the relative abundance of gevotroline and essential amino acids during the later stages of palm wine tapping (15–25 days) supports the difference in the health benefits of the palm wine obtained from different days of tapping, indicating that early stages of tapping is more nutritional and healthy than the later stages. The microbial dynamics may be a potential indicator of metabolite changes during palm sap fermentation, thus contributing to establish particular features of palm wines in different stages of tapping. This understanding of microbial ecology and chemical composition changes during palm wine tapping can be used as biomarkers to assess palm wine’s quality and help to design an optimum starter culture.
Understanding cognitive control in aging: A brain network perspective
Authors: Xia Haishuo , He Qinghua , Chen Antao
Published: October 2022

Cognitive control decline is a major manifestation of brain aging that severely impairs the goal-directed abilities of older adults. Magnetic resonance imaging evidence suggests that cognitive control during aging is associated with altered activation in a range of brain regions, including the frontal, parietal, and occipital lobes. However, focusing on specific regions, while ignoring the structural and functional connectivity between regions, may impede an integrated understanding of cognitive control decline in older adults. Here, we discuss the role of aging-related changes in functional segregation, integration, and antagonism among large-scale networks. We highlight that disrupted spontaneous network organization, impaired information co-processing, and enhanced endogenous interference promote cognitive control declines during aging. Additionally, in older adults, severe damage to structural network can weaken functional connectivity and subsequently trigger cognitive control decline, whereas a relatively intact structural network ensures the compensation of functional connectivity to mitigate cognitive control impairment. Thus, we propose that age-related changes in functional networks may be influenced by structural networks in cognitive control in aging (CCA). This review provided an integrative framework to understand the cognitive control decline in aging by viewing the brain as a multimodal networked system.
Sevoflurane exposure causes neuronal apoptosis and cognitive dysfunction by inducing ER stress via activation of the inositol 1, 4, 5-trisphosphate receptor
Authors: Zhang Qi , Li Yanan , Wang Xupeng , Yin Chunping , Zhou Qi , Guo Junfei , Zhao Juan , Xian Xiaohui , Hou Zhiyong , Wang Qiujun
Published: October 2022

The role of the inositol 1, 4, 5-trisphosphate receptor (IP3R) in hippocampal neuronal apoptosis and cognitive dysfunction induced by sevoflurane is currently unclear. Therefore, in this study, we investigated the role of the IP3R in endoplasmic reticulum (ER) stress and hippocampal neuronal apoptosis induced by sevoflurane in aged rats and isolated hippocampal neurons using both in vivo and in vitro experiments, including bioinformatics, functional enrichment analysis, gene set enrichment analysis, hematoxylin, and eosin staining, TUNEL assay, flow cytometry, western blot analysis and transmission electron microscopy. Furthermore, behavioral assessment was performed with the Morris water maze test. We identified 232 differentially expressed genes induced by sevoflurane exposure, including 126 upregulated genes and 106 downregulated genes. Sevoflurane exposure caused cognitive impairment and neuronal injury, and increased p-IP3R levels and ER stress. An IP3R inhibitor, 2-APB, suppressed these changes, while an IP3R agonist, FK-506, aggravated these changes. Together, these findings suggest that sevoflurane exposure causes marked cognitive dysfunction in aged rats and neuronal injury in isolated hippocampal neurons by activating the IP3R and inducing cytoplasmic calcium overload, thereby resulting in ER stress and hippocampal neuronal apoptosis.

GRAPHICAL ABSTRACT
A computational roadmap to electronic drugs
Authors: Rowald Andreas , Amft Oliver
Published: October 2022

A growing number of complex neurostimulation strategies promise symptom relief and functional recovery for several neurological, psychiatric, and even multi-organ disorders. Although pharmacological interventions are currently the mainstay of treatment, neurostimulation offers a potentially effective and safe alternative, capable of providing rapid adjustment to short-term variation and long-term decline of physiological functions. However, rapid advances made by clinical studies have often preceded the fundamental understanding of mechanisms underlying the interactions between stimulation and the nervous system. In turn, therapy design and verification are largely driven by clinical-empirical evidence. Even with titanic efforts and budgets, it is infeasible to comprehensively explore the multi-dimensional optimization space of neurostimulation through empirical research alone, especially since anatomical structures and thus outcomes vary dramatically between patients. Instead, we believe that the future of neurostimulation strongly depends on personalizable computational tools, i.e. Digital Neuro Twins (DNTs) to efficiently identify effective and safe stimulation parameters. DNTs have the potential to accelerate scientific discovery and hypothesis-driven engineering, and aid as a critical regulatory and clinical decision support tool. We outline here how DNTs will pave the way toward effective, cost-, time-, and risk-limited electronic drugs with a broad application bandwidth.
Impairments in the mechanical effectiveness of reactive balance control strategies during walking in people post-stroke
Authors: Liu Chang , McNitt-Gray Jill L. , Finley James M.
Published: October 2022

People post-stroke have an increased risk of falls compared to neurotypical individuals, partly resulting from an inability to generate appropriate reactions to restore balance. However, few studies investigated the effect of paretic deficits on the mechanics of reactive control strategies following forward losses of balance during walking. Here, we characterized the biomechanical consequences of reactive control strategies following perturbations induced by the treadmill belt accelerations. Thirty-eight post-stroke participants and thirteen age-matched and speed-matched neurotypical participants walked on a dual-belt treadmill while receiving perturbations that induced a forward loss of balance. We computed whole-body angular momentum and angular impulse using segment kinematics and reaction forces to quantify the effect of impulse generation by both the leading and trailing limbs in response to perturbations in the sagittal plane. We found that perturbations to the paretic limb led to larger increases in forward angular momentum during the perturbation step than perturbations to the non-paretic limb or to neurotypical individuals. To recover from the forward loss of balance, neurotypical individuals coordinated reaction forces generated by both legs to decrease the forward angular impulse relative to the pre-perturbation step. They first decreased the forward pitch angular impulse during the perturbation step. Then, during the first recovery step, they increased the backward angular impulse by the leading limb and decreased the forward angular impulse by the trailing limb. In contrast to neurotypical participants, people post-stroke did not reduce the forward angular impulse generated by the stance limb during the perturbed step. They also did not increase leading limb angular impulse or decrease the forward trailing limb angular impulse using their paretic limb during the first recovery step. Lastly, post-stroke individuals who scored poorer on clinical assessments of balance and had greater motor impairment made less use of the paretic limb to reduce forward momentum. Overall, these results suggest that paretic deficits limit the ability to recover from forward loss of balance. Future perturbation-based balance training targeting reactive stepping response in stroke populations may benefit from improving the ability to modulate paretic ground reaction forces to better control whole-body dynamics.
Relationship between sleep disorders and the prognosis of neurological function after stroke
Authors: Zhang Yajing , Xia Xiaoshuang , Zhang Ting , Zhang Chao , Liu Ran , Yang Yun , Liu Shuling , Li Xin , Yue Wei
Published: October 2022

Objective

This study aims to investigate the effects of sleep disorders on the prognosis of neurological function after stroke and other factors affecting the prognosis after stroke.

Method

We designed a cohort study. A total of 1,542 patients with their first stroke were hospitalized in the department of neurology of Tianjin Huanhu Hospital from 2015.6.1 to 2016.12.31. We recorded the personal histories of patients. The MMSE (mini-mental state examination), MoCA (Montreal Cognitive Assessment), HAMD (Hamilton Depression Scale), National Institutes of Health Stroke Scale (NIHSS) score, mRS (Modified Rankin Scale), BI (Barthel Index), PSQI (Pittsburgh Sleep Quality Index), ESS (Epworth Sleepiness Scale), Berlin questionnaire, and nocturnal TST (Total sleep time) were assessed before discharge, 3 months, 6 months, and 4 years (2019–2020) after stroke.

Result

Low sleep quality (OR 2.019, 95%CI 1.199–3.398, p = 0.008), nocturnal TST (<7 h) (OR 4.060, 95%CI 1.494–11.034, p = 0.006), nocturnal TST (>8 h) (OR 5.928, 95% CI 2.134–16.464, p = 0.001) were risk factors for poor neurological function recovery at 3 months after stroke. Nocturnal TST (<7 h) (OR 13.042, 95%-CI 2.576–66.027, p = 0.002) and nocturnal TST (>8 h) (OR 11.559, 95%-CI 2.108–63.390, p = 0.005) were risk factors for poor neurological function at 6 months after stroke. Nocturnal TST (<7 h) (OR 2.668, 95% CI 1.250–5.698, p = 0.011) and nocturnal TST (>8 h) (OR 2.516, 95% CI 1.080–5.861, p = 0.033) were risk factors for poor neurological function at 4 years after stroke. High risk of OSA (HR 1.582, 95%CI 1.244–2.012, p < 0.001) was a risk factor for all-cause death in patients followed up for 4 years after stroke.

Conclusion

Low sleep quality is associated with short-term poor neurological function after stroke. Unusual nocturnal TST (long or short) is associated with short-term or long-term poor neurological function after stroke. A high risk of OSA is associated with a higher risk of all-cause death after stroke.
Evaluation of changes in the cognitive function of adult cynomolgus monkeys under stress induced by audio-visual stimulation by applying modified finger maze test
Authors: Huang Ying , Wang Hong , Yang Chen , Luo Yuchong , Ding Yongyan , Jin Hongjun , Wen Shenglin
Published: October 2022

Stress in life is ubiquitous and unavoidable. Prolonged exposure to severe stress can lead to physical intolerance and impair cognitive function. Non-human primates are considered to be the best animal model for studying cognitive function, especially memory and attention. The finger maze test, with the advantages of short training time and lower cost, is recommended to evaluate learning and memory in non-human primates. In this study, we modified the finger maze test method to evaluate the cognitive function of single-housed cynomolgus monkeys. The flexibility and attention of cynomolgus monkeys were assessed by performing the complex task test and the stranger intrusion interference test, respectively, which increased the difficulty of obtaining rewards, and the ability of long-term memory was also evaluated by the memory test. Furthermore, the changes in cognitive function of the cynomolgus monkeys were tested by using the finger maze test after audio-visual stimulation, and the changes in the cortisol levels during stimulation were also analyzed. We found that, after completing the learning test, there was no significant decrease in their success rate when monkeys processed multitasks at the same time. In the stranger intrusion interference test, all subjects were distracted, but the accuracy did not decrease. The monkeys completed the memory tests in the 1st and 2nd months after the learning tests, with a high success rate. However, the success rate decreased significantly at the end of the 4th month. During audio-visual stimulation, the plasma cortisol level significantly increased in the first 2 months and was maintained at a high level thereafter. One month after audio-visual stimulation, the accuracy of the memory test was significantly reduced, and the total time of distraction was significantly prolonged. In conclusion, chronic audio-visual stimulation can increase blood cortisol levels and impair cognitive function. The modified finger maze test can evaluate many aspects of cognitive function and assess the changes in the cognitive function of adult cynomolgus monkeys under stress.
The effects of prefrontal vs. parietal cortex transcranial direct current stimulation on craving, inhibition, and measures of self-esteem
Authors: Ljubisavljevic Milos , Basha Jonida , Ismail Fatima Y.
Published: October 2022

While prefrontal cortex dysfunction has been implicated in high food cravings, other cortical regions, like the parietal cortex, are potentially also involved in regulating craving. This study explored the effects of stimulating the inferior parietal lobule (IPL) and dorsolateral prefrontal cortex (DLPFC) on food craving state and trait. Transcranial direct current stimulation (tDCS) was administered at 1.5 mA for 5 consecutive days. Participants received 20 min of IPL, DLPFC, or sham stimulation (SHAM) each day which consisted of two rounds of 10-min stimulation, divided by a 10-min mindfulness task break. In addition, we studied inhibition and subjective psychological aspects like body image and self-esteem state and trait. To decompose immediate and cumulative effects, we measured the following on days 1 and 5: inhibition through the Go/No-go task; and food craving, self-esteem, and body appreciation through a battery of questionnaires. We found that false alarm errors decreased in the participants receiving active stimulation in the DLPFC (DLPFC-group). In contrast, false alarm errors increased in participants receiving active stimulation in the IPL (IPL-group). At the same time, no change was found in the participants receiving SHAM (SHAM-group). There was a trending reduction in craving trait in all groups. Momentary craving was decreased in the DLPFC-group and increased in IPL-group, yet a statistical difference was not reached. According to time and baseline, self-esteem and body perception improved in the IPL-group. Furthermore, self-esteem trait significantly improved over time in the DLPFC-group and IPL-group. These preliminary results indicate that tDCS modulates inhibition in frontoparietal areas with opposite effects, enhancing it in DLPFC and impairing it in IPL. Moreover, craving is moderately linked to inhibition, self-esteem, and body appreciation which seem not to be affected by neuromodulation but may rely instead on broader regions as more complex constructs. Finally, the fractionated protocol can effectively influence inhibition with milder effects on other constructs.
Study of antimicrobial activity and mechanism of vapor-phase cinnamaldehyde for killing Escherichia coli based on fumigation method
Authors: Duan Xuejuan , Qin Dongying , Li Hongming , Zhang Tong , Han Yali , Huang Yu qiang , He Dong , Wu Kegang , Chai Xianghua , Chen Chun
Published: October 2022

The vapor-phase antibacterial activity of essential oils makes them suitable for applications in air disinfection and other fields. At present, vapor-phase antibacterial activity of plant-based essential oils has rarely been reported. Herein, we report a new approach to investigate the antimicrobial activity and mechanism of vapor-phase cinnamaldehyde using Escherichia coli (E. coli) and three other pathogenic bacteria (Pseudomonas aeruginosa, Salmonella, Staphylococcus aureus) as model bacteria. Plate fumigation and agar block transfer techniques were used to determine the antimicrobial activities of vapor-phase cinnamaldehyde fumigation on the four types of bacteria, and the mechanism of action was determined by electrical conductivity (EC), OD260nm measurement, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and fluorescence spectroscopy. Cinnamaldehyde had good vapor-phase antibacterial activity against the four types of bacteria. The TEM, EC, and OD260nm measurements showed that after fumigation with cinnamaldehyde, the ultrastructures of the cells were damaged, and plasmolysis, cell collapse, and leakage of intracellular substances were observed. The FTIR and fluorescence spectroscopy analyses showed that the secondary and tertiary structures of bacterial membrane proteins were altered. These findings indicate that the cell membrane is an important target for plant-based essential oils to exert their vapor-phase antimicrobial effects. The results showed that plant-based essential oils can be developed as volatile broad-spectrum disinfection products and vapor-phase antiseptics.
Comprehensive analysis of a homeobox family gene signature in clear cell renal cell carcinoma with regard to prognosis and immune significance
Authors: Zheng Di , Ning Jinzhuo , Xia Yuqi , Ruan Yuan , Cheng Fan
Published: October 2022

The homeobox (HOX) family genes have been linked to multiple types of tumors, while their effect on malignant behaviors of clear cell renal cell carcinoma (ccRCC) and clinical significance remains largely unknown. Here, we comprehensively analyzed the expression profiles and prognostic value of HOX genes in ccRCC using datasets from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. We developed a prognostic signature comprising eight HOX genes (HOXB1, HOXA7, HOXB5, HOXD8, HOXD9, HOXB9, HOXA9, and HOXA11) for overall survival prediction in ccRCC and it allowed patients to be subdivided into high- and low-risk groups. Kaplan-Meier survival analysis in all the internal and external cohorts revealed significant difference in clinical outcome of patients in different risk groups, indicating the satisfactory predictive power of the signature. Additionally, we constructed a prognostic nomogram by integrating signature-derived risk score and clinical factors such as gender, age, T and M status, which might be helpful for clinical decision-making and designing tailored management schedules. Immunological analysis revealed that the regulatory T cells (Tregs) infiltrated differently between the two subgroups in both TCGA and ICGC cohorts. ssGSEA method showed that the enrichment scores for mast cells were significantly lower in high-risk group compared with the low-risk group, which was consistent in both TCGA and ICGC cohorts. As for the related immune function, the enrichment scores of APC co-inhibition, para-inflammation, and type II IFN response were consistently lower in high-risk group in both cohorts. Of the eight HOX genes, the mRNA and protein levels of HOXD8 were downregulated in ccRCC than that in normal tissues, and decreased expression of HOXD8 was associated with increased tumor grade and stage, and lymph node metastasis. Survival analysis revealed that lower expression of HOXD8 predicted worse overall survival in ccRCC. In conclusion, our HOX gene-based signature was a favorable indicator to predict the prognosis of ccRCC cases and associated with immune cell infiltration. HOXD8 might be a tumor suppressor gene in ccRCC and a potential predictor of tumor progression.
ALK-R3HDM1 and EML4-ALK fusion as a mechanism of acquired resistance to gefitinib: A case report and literature review
Authors: Zeng Zhu , Wang Tao , He Junjun , Wang Yuehong
Published: October 2022

We report a case with a novel ALK-R3HDM1 and EML4-ALK dual fusion that might be a delicate mechanism for the acquired resistance of epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor (TKI). A patient with EGFR L858R lung adenocarcinoma developed disease progression after 72.7 months of gefitinib therapy; rebiopsy was done, and next-generation sequencing showed the disappearance of the previous EGFR mutations. In addition, two new ALK fusions emerged, indicating that the emergence of dual ALK rearrangement may be the underlying mechanism of gefitinib resistance. The patient exhibits an excellent response to second-line alectinib treatment with a significant clinical benefit and a high quality of life. Finally, we summarized previous studies in which ALK fusion is a required resistance mechanism to EGFR-TKI.
Role of radiotherapy in treatment of extramedullary relapse following total marrow and lymphoid irradiation in high-risk and/or relapsed/refractory acute leukemia
Authors: Ladbury Colton , Semwal Hemal , Hong Daniel , Yang Dongyun , Hao Claire , Han Chunhui , Liu An , Marcucci Guido , Rosenthal Joseph , Hui Susanta , Salhotra Amandeep , Ali Haris , Nakamura Ryotaro , Stein Anthony , Al Malki Monzr , Wong Jeffrey Y. C. , Dandapani Savita
Published: October 2022

Background

Total Marrow and Lymphoid Irradiation (TMLI) is a promising component of the preparative regimen for hematopoietic cell transplantation in patients with high-risk acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Extramedullary (EM) relapse after TMLI is comparable to TBI and non-TBI conditioning regimens. This study evaluates outcomes of patients treated with radiotherapy (RT) with EM relapse previously treated with TMLI.

Methods

A retrospective analysis of five prospective TMLI trials was performed. TMLI targeted bones and major lymphoid tissues using image-guided tomotherapy, with total dose ranging from 12 to 20 Gy. EM recurrences were treated at the discretion of the hematologist and radiation oncologist using RT ± chemotherapy. Descriptive statistics and survival analysis were then performed on this cohort.

Results

In total, 254 patients with refractory or relapsed AML or ALL were treated with TMLI at our institution. Twenty-one patients were identified as receiving at least one subsequent course of radiation. A total of 67 relapse sites (median=2 sites/patient, range=1-16) were treated. Eleven relapsed patients were initially treated with curative intent. Following the initial course of subsequent RT, 1-year, 3-year and 5-year estimates of OS were 47.6%, 32.7% and 16.3%, respectively. OS was significantly better in patients treated with curative intent, with median OS of 50.7 months vs 1.6 months (p<0.001). 1-year, 3-year and 5-year estimates of PFS were 23.8%, 14.3% and 14.3%, respectively. PFS was significantly better in patients treated with curative intent, with median PFS of 6.6 months vs 1.3 months (p<0.001). Following RT, 86.6% of the sites had durable local control.

Conclusions

RT is an effective modality to treat EM relapse in patients with acute leukemia who relapse after HCT achieving high levels of local control. In patients with limited relapse amenable to curative intent, radiation confers favorable long-term survival. Radiation as salvage treatment for EM relapse after HCT warrants further evaluation.
Case Report: Robot-assisted laparoscopic nephron-sparing surgery for a renal abscess mimicking a tumor
Authors: Wang Shun , Liang Xiangyi , Pan Di , Zhang Jianqing , Chen Kun , Jiang Kehua , Li Tao
Published: October 2022

The differential diagnosis of renal tumors and abscesses is crucial owing to their different treatments. Although antibacterial administration and radiological examination are excellent means for distinction, misdiagnosis is common and may lead to severe consequences, such as the need for nephrectomy. Here, we report a case involving a 52-year-old Asian woman with a renal mass for which a differential diagnosis was challenging. The mass persisted after administration of intravenous antibiotic therapy for 1 month. A computed tomography scan indicated an inflammatory lesion, whereas magnetic resonance imaging suggested a diagnosis of a tumor. Despite these indications, a right renal abscess was suspected during robot-assisted laparoscopic surgery, and nephron-sparing surgery was performed, which allowed confirmation of the final pathological result by biopsy specimen. Postoperatively, the mass gradually decreased in size after antibiotic therapy for a further month. This case, in which a renal abscess mimicked a tumor and the patient almost underwent a nephrectomy, highlights the need for caution in establishing therapeutic schedules for patients with inaccurate diagnoses. The management strategies for such patients must be reviewed and improved.
A meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer
Authors: El Helali Aya , Tao Jun , Wong Charlene H. L. , Chan Wendy Wing-Lok , Mok Ka-Chun , Wu Wing Fong , Shitara Kohei , Mohler Markus , Boku Narikazu , Pang Herbert , Lam Ka On
Published: October 2022

Background

While the efficacy of immune checkpoint inhibitors (ICIs) is increasingly recognized in advanced gastric cancer (aGC), overall survival (OS) has not been consistently improved across the different randomized controlled trials (RCTs). This meta-analysis aimed to quantify the efficacy and safety of ICI and explore potential predictive tumor tissue biomarkers in aGC.

Methods

A random-effect pairwise meta-analysis was used to evaluate the primary outcome of OS. Sensitivity analysis was performed to investigate the effects of ICIs on PD-L1 status, TMB, MSI-H, and the Asian patient population. We extracted the OS Kaplan–Meier curves from the included trials to compare the effect of PD-L1 status on response to ICIs using DigitizeIt 2.5 and Guyot’s algorithm.

Results

A pairwise meta-analysis of seven RCTs included in this study showed that ICIs were more effective than the comparator in improving OS (pooled HR: 0.84). We demonstrated that PD-1 ICIs were additive when combined with the comparator arm (pooled HR: 0.79). A sensitivity analysis showed that PD-1 ICIs were associated with better OS outcomes in the Asian patient population as monotherapy (pooled HR: 0.66) or in combination with chemotherapy (pooled HR: 0.83). We demonstrated that tumors with PD-L1 ≥1 (P = 0.02) and PD-L1 ≥10 (P = 0.006) derived OS benefit from ICI monotherapy. Equally, MSI-H (P <0.00001) and TMB-high (P <0.0001) tumors derived favorable survival benefits from ICIs.

Conclusions and relevance

The results of this meta-analysis suggest that ICIs result in improved OS outcomes in aGC. The benefits varied with different ethnicities, class of ICI, PD-L1 expression, MSI status, and TMB

Systematic Review Registration

https://www.crd.york.ac.uk/prospero, identifier (CRD42019137829).
Five-year relative survival by stage of breast and colon cancers in northern Italy
Authors: Mangone Lucia , Marinelli Francesco , Bisceglia Isabella , Braghiroli Maria Barbara , Damato Angela , Pinto Carmine
Published: October 2022

The aim of this study is to present the 5-year relative survival by stage of breast and colorectal cancer patients in a northern Italian province. For the period 2013-2015, cases were selected from the Reggio Emilia Cancer Registry. Breast cancer patients were divided into 3 age groups: <45, 45-74 (the target screening population) and 74+. Colorectal cancers patients were classified into <50, 50-69 (the target screening population), and over 69 years. Carcinomas in situ and unknown stage were both excluded from the survival analyses. The five-year relative survival was estimated using the Pohar Perme method. During the period examined, 1,450 breast cancers and 992 colorectal cancer cases were registered. Analyzing in detail the patients with breast cancer for the entire 2013-2015 period, we noted that 50.4% were in stage I, 33.6% in stage II, 10.8% in stage III and 3.8% in stage IV. The stage was unknown in only 1.3% of patients (19 cases). The stage data of patients with colorectal cancer showed 24.5% were in stage I, 26.1% in stage II, 23.4% in stage III, and 24.6% in stage IV, and 1.4% unknown. Breast cancer 5-year survival was 100%, 89.7%, 71.4%, and 29.1% for stages I, II, III and IV, respectively and for colon cancer 96.7%, 83.4%, 70.8% and 16.2%, respectively.The presence of cancer screening, associated with effective treatments, account for the high survival rate of early-stage breast and colon cancers.
Consequences of somatic mutations of GIRK1 detected in primary malign tumors on expression and function of G-protein activated, inwardly rectifying, K+ channels
Authors: Pelzmann Brigitte , Hatab Ahmed , Scheruebel Susanne , Langthaler Sonja , Rienmueller Theresa , Sokolowski Armin , Gorischek Astrid , Platzer Dieter , Zorn-Pauly Klaus , Jahn Stephan W. , Bauernhofer Thomas , Schreibmayer Wolfgang
Published: October 2022

A search in the GDC Data Portal revealed 304 documented somatic mutations of the KCNJ3 gene in primary tumors (out of 10.202 cases). Most affected tumor types were carcinomas from uterus, skin and lung, while breast cancer exerted the lowest number of somatic mutations. We focused our research on 15 missense mutations within the region between TM1 and TM2, comprising the pore helix and ion selectivity signature. Expression was measured by confocal laser scan microscopy of eGFP tagged GIRK1 subunits, expressed with and without GIRK4 in oocytes of Xenopus laevis. GIRK ion currents were activated via coexpressed m2Rs and measured by the Two Electrode Voltage Clamp technique. Magnitude of the total GIRK current, as well as the fraction of current inducible by the agonist, were measured. Ion selectivity was gauged by assessment of the PNa+/PK+ ratio, calculated by the GIRK current reversal potential in extracellular media at different Na+ and K+ concentrations. None of the tested mutations was able to form functional GIRK1 homooligomeric ion channels. One of the mutations, G145A, which locates directly to the ion selectivity signature, exerted an increased PNa+/PK+ ratio. Generally, the missense mutations studied can be categorized into three groups: (i) normal/reduced expression accompanied by reduced/absent function (S132Y, F136L, E139K, G145A, R149Q, R149P, G178D, S185Y, Q186R), (ii) normal/increased expression as well as increased function (E140M, A142T, M184I) and (iii) miniscule expression but increased function relative to expression levels (I151N, G158S). We conclude, that gain of function mutations, identical or similar to categories (ii) and (iii), may potentially be involved in genesis and progression of malignancies in tissues that exert a high rate of occurrence of somatic mutations of KCNJ3.
Computational investigation of the haemodynamics shows criticalities of central venous lines used for chronic haemodialysis in children
Authors: Bruno Claudia , Sauvage Emilie , Simcock Ian , Redaelli Alberto , Schievano Silvia , Shroff Rukshana , Capelli Claudio
Published: October 2022

Background

Haemodialysis is a life-saving treatment for children with kidney failure. The majority of children have haemodialysis through central venous lines (CVLs). The use of CVLs in pediatric patients is often associated to complications which can lead to their replacement. The aim of this study is to investigate haemodynamics of pediatric CVLs to highlight the criticalities of different line designs.

Methods

Four models of CVLs for pediatric use were included in this study. The selected devices varied in terms of design and sizes (from 6.5 Fr to 14 Fr). Accurate 3D models of CVLs were reconstructed from high-resolution images including venous and arterial lumens, tips and side holes. Computational fluid dynamics (CFD) analyses were carried out to simulate pediatric working conditions of CVLs in ideal and anatomically relevant conditions.

Results

The arterial lumens of all tested CVLs showed the most critical conditions with the majority of blood flowing through the side-holes. A zone of low flow was identified at the lines’ tip. The highest shear stresses distribution (>10 Pa) was found in the 8 Fr line while the highest platelet lysis index in the 10 Fr model. The analysis on the anatomical geometry showed an increase in wall shear stress measured in the 10 F model compared to the idealised configuration. Similarly, in anatomical models an increased disturbance and velocity of the flow was found inside the vein after line placement.

Conclusion

This study provided a numerical characterization of fluid dynamics in pediatric CVLs highlighting performance criticalities (i.e. high shear stresses and areas of stagnation) associated to specific sizes (8 Fr and 10 Fr) and conditions (i.e. anatomical test).
Successful treatment with HLA-matched peripheral hematopoietic stem cell transplantation for very severe hepatitis-associated aplastic anemia complicated with multidrug-resistant bacterial and fungal infections: A case report
Authors: Li Hua , Li Xiaofan , Chen Xianling , Li Nainong
Published: October 2022

Hepatitis-associated aplastic anemia (HAAA) is a life-threatening hematologic disorder characterized by bone marrow failure. Allogeneic hematopoietic stem cell transplantation (HSCT) is the first-line treatment for HAAA. Severe infection and complications in patients with very severe aplastic anemia are the challenges to the efficacy of HSCT. We report a rare case of successful transplantation with HLA-matched peripheral hematopoietic stem cells for a 15-year-old girl suffering from HAAA with multidrug-resistant bacterial and fungal infections. Through effectively controlling infection and optimal timing of transplantation by adjusting the conditioning regimen, the allo-HSCT was successfully performed for the patient. Updated data of following-up 26 months after transplantation showed that the patient was still in complete remission with a good quality of life. This case provided a reference for treating severely infected patients with HAAA before HSCT.
A review of neonatal peripherally inserted central venous catheters in extremely or very low birthweight infants based on a 3-year clinical practice: Complication incidences and risk factors
Authors: Wu Yaohua , Yan Jing , Tang Mengyan , Hu Yanling , Wan Xingli , Li Xiaowen , Chen Qiong , Li Xia
Published: October 2022

Background

The application of peripherally inserted central venous catheters (PICCs) in neonates has proven effective in avoiding repetitive insertions and excessive use of transfusion consumables. However, the frequent occurrence of PICC-associated complications deserves special attention, especially in extremely or very low birthweight (E/VLBW) infants, which in turn affects the quality of neonatal PICC practice. Therefore, we conducted a retrospective study of a 3-year clinical practice of neonatal PICCs in E/VLBW infants to understand the incidences of various catheter-related complications and their risk factors to help form an empirical summary and evidence-based guidance for the improvement of practice.

Methods

A retrospective study was conducted based on a 3-year practice of neonatal PICCs in E/VLBW infants. Neonatal health records were collected, including demographic characteristics, PICC placement data, and treatment information.

Results

A total of 519 E/VLBW infants were included in this study. There were 77 cases of complications involving 72 infants with an overall incidence of 12.13%. The order of incidences of different complications from high to low was phlebitis (7.71%), malposition (3.66%), leakage (1.35%), pleural effusion (1.15%), central line-associated bloodstream infection (0.58%, 0.25/1,000d), and accidental removal (0.38%). Multivariate analysis revealed that the inserted vessel was an independent risk factor for PICC-associated complications (mainly phlebitis; p = 0.002). Neonatal PICCs inserted in the axillary vein were only one-tenth (p = 0.026) as likely to cause phlebitis as in the basilic vein, whereas when applied in the saphenous vein, neonatal PICCs were five times as likely to cause phlebitis (p = 0.000).

Conclusion

E/VLBW infants might be more inclined to develop PICC-associated phlebitis. Catheters inserted in the axillary or basilic vein are preferred if possible.
Clinical features, diagnosis and management of amoxicillin-induced Kounis syndrome
Authors: Wang Chunjiang , Zhou Yulu , Fang Weijin , Li Zuojun , Zhao Shaoli
Published: October 2022

Background:The available evidence suggests that amoxicillin is often associated with the occurrence of Kounis syndrome (KS). The purpose of this study is to explore the clinical characteristics of KS induced by amoxicillin.

Methods:We searched for case reports of amoxicillin-induced KS through Chinese and English databases from 1972 to May 2022.

Results:A total of 33 patients with KS were included, including 16 patients (48.5%) receiving amoxicillin treatment and 17 patients (51.5%) receiving amoxicillin-clavulanate. The median age was 58 years (range 13–82), 75.8% were from Europe and 81.8% were male. Nearly 70% of KS patients develop symptoms within 30 min after administration. Chest pain (63.6%) and allergic reaction (75.8%) were the most common clinical manifestations. Diagnostic evaluation revealed elevated troponin (72.7%), ST-segment elevation (81.2%) and coronary artery stenosis with thrombosis (53.6%). Thirty-two (97.0%) patients recovered completely after discontinuation of amoxicillin and treatments such as steroids and antihistamines.

Conclusion:KS is a rare adverse reaction of amoxicillin. Amoxicillin-induced KS should be considered when chest pain accompanied by allergic symptoms, electrocardiogram changes and or elevated levels of myocardial injury markers. Therapeutic management of KS requires simultaneous treatment of cardiac and allergic symptoms. Epinephrine should be used with caution in patients with suspected KS.
High-temperature metasurface for polarization conversion and RCS reduction
Authors: Wang Wenjie , Jiang Jinming , Liang Jiangang , Zheng Lin , Meng Yueyu , Li Yongfeng , Xu Cuilian , Wang Jiafu , Qu Shaobo
Published: October 2022

In this study, we present a high temperature-resistant linear-to-linear polarization conversion metasurface for wideband RCS reduction in the microwave regime. The linear-to-linear polarization conversion metasurface is composed of a single layer high-temperature-resistant metallic pattern array. When linearly polarized waves impinge on the metasurface, the polarization conversion rate is greater than 90% from 9 GHz to 16.8 GHz at 800°C. The polarization conversion unit arrangement forms a checkerboard configuration metasurface, which can effectively reduce RCS reflection. The wideband RCS reduction mechanism is scattering cancellation rather than absorption. The metasurfaces were designed, fabricated, and measured, which can realize linear-to-linear polarization conversion and wideband RCS reduction. The simulation results and measurement results are all in good agreement. Meanwhile, the measurement provides a solid verification for our design. The results provide an alternative method to reduce the RCS at high temperatures.