bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome sequencing and microRNA–mRNA regulatory network construction in the lens from a Na2SeO3-induced Sprague Dawley rat cataract model
Authors: Fang Rui , Yue Pei-Lin , Li Hai-Long , Ding Xue-Fei , Jia Yu-Xuan , Liu Zhao-Chuan , Zhou Hong-Gang , Song Xu-Dong
Published: November 2023

Background

A sight-threatening, cataract is a common degenerative disease of the ocular lens. This study aimed to explore the regulatory mechanism of age-related cataract (ARC) formation and progression.

Methods

Cataracts in Sprague Dawley rats were induced by adopting the method that injected selenite subcutaneously in the nape. We performed high-throughput RNA sequencing technology to identify the mRNA and microRNA(miRNA) expression profiles of the capsular membrane of the lens from Na2SeO3-induced and saline-injected Sprague Dawley rats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out to forecast the regulatory and functional role of mRNAs in cataracts by DAVID and Metascape. The protein–protein interaction(PPI) network of differentially expressed mRNA(DEmRNAs) was built via the STRING. Target miRNAs of hub genes were predicted by miRBD and TargetScan. Furthermore, differentially expressed miRNA(DEmiRNAs) were selected as hub genes’ targets, validated by quantitative real-time polymerase chain reaction(qRT-PCR), and a DEmiRNA-DEmRNA regulatory network was constructed via Cytoscape.

Result

In total, 329 DEmRNAs including 40 upregulated and 289 downregulated genes were identified. Forty seven DEmiRNAs including 29 upregulated and 18 downregulated miRNAs were detected. The DEmRNAs are involved in lens development, visual perception, and aging-related biological processes. A protein–protein interaction network including 274 node genes was constructed to explore the interactions of DEmRNAs. Furthermore, a DEmiRNA-DEmRNA regulatory network related to cataracts was constructed, including 8 hub DEmRNAs, and 8 key DEmiRNAs which were confirmed by qRT-PCR analysis.

Conclusion

We identified several differentially expressed genes and established a miRNA-mRNA-regulated network in a Na2SeO3-induced Sprague Dawley rat cataract model. These results may provide novel insights into the clinical treatment of cataracts, and the hub DEmRNAs and key DEmiRNAs could be potential therapeutic targets for ARC.
The multi-level outcome study of psychoanalysis for chronically depressed patients with early trauma (MODE): rationale and design of an international multicenter randomized controlled trial
Authors: Ambresin Gilles , Leuzinger-Bohleber Marianne , Fischmann Tamara , Axmacher Nikolai , Hattingen Elke , Bansal Ravi , Peterson Bradley S.
Published: November 2023

Background

Whether and how psychotherapies change brain structure and function is unknown. Its study is of great importance for contemporary psychotherapy, as it may lead to discovery of neurobiological mechanisms that predict and mediate lasting changes in psychotherapy, particularly in severely mentally ill patients, such as those with chronic depression. Previous studies have shown that psychoanalytic psychotherapies produce robust and enduring improvements in not only symptom severity but also personality organization in patients who have chronic depression and early life trauma, especially if therapy is delivered at a high weekly frequency.

Methods/design

Patients with chronic major depression and a history of early life trauma will be recruited, assessed, and treated across 3 international sites: Germany, Switzerland, and the United States. They will be randomized to one of two treatment arms: either (1) once weekly psychoanalytic psychotherapies, or (2) 3–4 times weekly psychoanalytic psychotherapies. They will have full clinical characterization as well as undergo MRI scanning at study baseline prior to randomization and again one year later. A group of matched healthy controls will undergo similar assessments and MRI scanning at the same time points to help discern whether study treatments induce brain changes toward or away from normal values. Primary study outcomes will include anatomical MRI, functional MRI, and Diffusion Tensor Imaging measures. Study hypotheses will be tested using the treatment-by-time interaction assessed in multiple general linear models with repeated measures analyses in an intent-to-treat analysis.

Discussion

MODE may allow the identification of brain-based biomarkers that may be more sensitive than traditional behavioral and clinical measures in discriminating, predicting, and mediating treatment response. These findings could help to personalize care for patients who have chronic depression patients and early life trauma, and they will provide new therapeutic targets for both psychological and biological treatments for major depressive illness.
Financing child rights in Malawi
Authors: Etter-Phoya Rachel , Manthalu Chisomo , Kalizinje Frank , Chigaru Farai , Mazimbe Bernadetta , Phiri Ajib , Chimowa Takondwa , Ligomeka Waziona , Hall Stephen , O’Hare Bernadette
Published: November 2023

Background

Nearly all countries have ratified the United Nations Convention on the Rights of the Child and, therefore, support children having access to their rights. However, only a small minority of children worldwide have access to their environmental, economic, and social rights. The most recent global effort to address these deficits came in 2015, when the United Nations General Assembly agreed to a plan for a fairer and more sustainable future by 2030 and outlined the Sustainable Development Goals (SDGs). One remediable cause is the lack of revenue in many countries, which affects all SDGs. However, illicit financial flows from low-income to high-income countries, including international tax abuse, continue unabated.

Methods

Using the most recent estimates of tax abuse perpetuated by multinational companies and tax evasion through offshore wealth, and precise econometric modelling, we illustrate the potential regarding child rights (or progress towards the SDGs) if there was an increase in revenue equivalent to tax abuse in Malawi, a low-income country particularly vulnerable to climate change. The Government Revenue and Development Estimations model provides realistic estimates of government revenue changes in developmental outcomes. Using panel data on government revenue per capita, it models the impact of increased revenue on governance and SDG progress.

Results

If cross-border tax abuse and tax evasion were curtailed, the equivalent increase in government revenue in one country, Malawi, would be associated with 12,000 and 20,000 people having access to basic water and sanitation respectively each year. Each year, an additional 5000 children would attend school, 150 additional children would survive, and 10 mothers would survive childbirth.

Conclusions

More children would access their economic and social rights if actions were taken to close the gap in global governance regarding taxation. We discuss the responsibility of duty bearers, the need for a global body to arbitrate and monitor international tax matters, and how the Government of Malawi could take further domestic action to mitigate the gaps in global governance and protect itself against illicit financial flows, including tax abuse.
Research on the mechanism of short video information interaction behavior of college students with psychological disorders based on grounded theory
Authors: Linlin Wang , Wanyu Huang , Yuting Li , Huimin Qiao , Zhi Li , Qinchen Jiang , Tingting Wang , Fan Wang , Minghao Pan , Wei Zhu
Published: November 2023

Background

The utilization of short videos by individuals often leads to the emergence of information exchange behavior. Previous studies have shown that certain students with psychological disorders exhibit addictive tendencies towards short video-related software. Therefore, it is essential to address the psychology and behavior of college students with psychological disorders while engaging with short videos. This study aims to explore the mechanism of short video information interaction behavior among college students with psychological disorders.

Methods

We conducted semi-structured interviews with 30 college students afflicted by psychological disorders in a prefecture-level city in Henan Province, China from September to December 2022. Based on the Grounded theory, we encoded 30 text materials across three levels to explore the mechanism of short video information interaction behavior among college students with psychological disorders, and subsequently build a model framework.

Results

The findings of this study suggest that college students with psychological disorders exhibit negative cognition tendencies that can lead to strongly negative emotions, excacerbated by a lack of social support. These adverse factors collectively drive the consumption of short video content in this demographic, providing a virtual environment where they can fulfill their unmet social needs. Therefore, the mechanism governing short video messages interaction among college students with psychological disorders encompasses negative cognitive tendencies, negative emotions, lack of social support, post-video-watching behaviors, and the gratification of social needs within the confines of a virtual environment.

Conclusions

This study comprehensively analyzes the motivation and complexity of college students with psychological disorders in short video interaction. Although short videos provide this group with some ways of self-expression and emotional support, they still have a negative impact on their physical and mental health. The short video interaction of college students with psychological disorders is affected by many factors, including their negative cognitive tendencies, negative emotions, lack of social support, post-video-watching behaviors, and the gratification of social needs within the confines of a virtual environment. These findings deepened our understanding to the mechanism of short video information interaction behavior among college students with psychological disorders, also provided us with guidance on facilitating the proper use of short video and maintaining the mental health. In future researches, researchers can discuss more about intervention measures to help this demographic cope with the challenges from short video interaction.
Ventilator-associated pneumonia in Polish intensive care unit dedicated to COVID-19 patients
Authors: Wałaszek Marta , Serwacki Piotr , Cholewa Zbigniew , Kosiarska Alicja , Świątek – Kwapniewska Wioletta , Kołpa Małgorza , Rafa Elżbieta , Słowik Róża , Nowak Karolina , Różańska Anna , Wójkowska-Mach Jadwiga
Published: November 2023

Background

Healthcare-Associated Infections (HAI) are most frequently associated with patients in the Intensive Care Unit (ICU). Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), led to ICU hospitalization for some patients.

Methods

The study was conducted in 2020 and 2021 at a hospital in southern Poland. The Healthcare-Associated Infections Surveillance Network (HAI-Net) of the European Centre for Disease Prevention and Control (ECDC) was used for HAI diagnosis. The aim of this case-control study was to retrospectively assess the epidemiology of HAIs in ICU patients, distinguishing between COVID-19 and non-COVID-19 cases.

Results

The study included 416 ICU patients: 125 (30%) with COVID-19 and 291 (70%) without COVID-19, p < 0.05. The mortality rate was 80 (64%) for COVID-19 patients and 45 (16%) for non-COVID-19 patients, p < 0.001. Ventilator-Associated Pneumonia (VAP) occurred in 40 cases, with an incidence rate density of 6.3/1000 patient-days (pds): 14.1/1000 pds for COVID-19 patients vs. 3.6/1000 pds for non-COVID-19 patients. Odds Ratio (OR) was 2.297, p < 0.01. Acinetobacter baumannii was the most often isolated microorganism in VAP, with 25 cases (incidence rate 8.5%): 16 (18.2%) in COVID-19 patients vs. 9 (4.4%) in non-COVID-19 patients. OR was 4.814 (1.084–4.806), p < 0.001.

Conclusions

Patients treated in the ICU for COVID-19 faced twice the risk of VAP compared to non-COVID-19 patients. The predominant microorganism in VAP cases was Acinetobacter baumannii.
A tangible prospect for the treatment of gingivitis using a potentially probiotic strain Lactobacillus plantarum MK06 isolated from traditional dairy products: a triple blind randomized clinical trial
Authors: Modiri Sima , Heidari Mohadeseh , Shahmohammadi Rojin , Jabbareh Leila , Maboudi Avideh , Moosazadeh Mahmood , Vali Hojatollah , Noghabi Kambiz Akbari
Published: November 2023

Background

Frequent bacterial plaque buildup at the gingival margin and crevice can provoke an inflammatory reaction in gingival tissues which manifests as gingivitis. Probiotics could serve as a beneficial complementary therapy for treating gingival inflammation. The main aim of this research was to investigate the effect of the Lactobacillus plantarum MK06 probiotic strain on the treatment of gingivitis.

Methods

Patients with gingivitis, who were referred to a private clinic and were systematically healthy, were included in this randomized, triple-blind, placebo-controlled trial. They were instructed to use either placebo or Lactobacillus plantarum suspensions for one minute two times a day after tooth-brushing for four weeks. Then, the clinical parameters of gingivitis, including plaque index (PI), gingival index (GI), bleeding on probing (BOP), and oral hygiene index (OHI-s), were measured in the first, second, and fourth weeks. A total of forty-two patients were randomly assigned to the experimental (n = 21) and control (n = 21) groups. The mean age of the experimental and control groups was 29.10 and 28.48, respectively.

Results

The mean scores of BOP, GI, PI, and OHI-s reduced over time in both the control and test groups. However, according to the Mann-Whitney test, the difference between the two groups was not significant at the same time intervals (P ≥ 0.05) and only GI showed a significant difference in the fourth week (GI-3, P = 0.006). Nevertheless, the experimental group experienced a higher overall reduction rate than the control group. The BOP, GI, PI, and OHI-s scores decreased by 0.081, 0.204, 0.186, and 0.172 times in the second week, respectively, resulting from the interaction of time and the intervention, which considerably diminished these indices.

Conclusion

This study shows the potential of the probiotic Lactobacillus plantarum MK06 suspension as a promoting therapeutic adjuvant in the treatment of gingivitis.
3D finite element analysis of stress distribution as a result of oblique and horizontal forces after regenerative endodontic treatment part II: comparison of material thickness
Authors: Demircan Beril , Demir Pınar
Published: November 2023

Aim

This study aimed to evaluate the stress distribution caused by secondary trauma forces after regenerative endodontic treatment (RET) using different thicknesses of coronary barrier material with three-dimensional finite element analysis(FEA).

Method

A control model was created using the tomography image of the immature maxillary central tooth with computer software.Study models were created with the modulus of elasticity and Poisson’s ratio of the materials used in RET.Enamel, dentin, cementum, periodontal ligament, cortical, and cancellous bone were modeled. Coronary barrier materials were applied in 3 mm and 5 mm thicknesses (Model 1: control model, model 2:3 mm/Calcium Enriched Mixture(CEM), model 3:3 mm/Mineral Trioxide Aggregate(MTA), model 4:3 mm/Biodentin, model 5:5 mm/CEM, model 6:5 mm/MTA, model 7:5 mm/Biodentin). For the trauma force simulation, 300 N force in the horizontal direction was applied to the buccal surface of the tooth in the first scenario. For the second scenario, maximum bite force simulation, a force of 240 N in the oblique direction was applied to the palatal surface of the tooth. FEA was performed with Algor Fempro. The resulting stresses were recorded as Von Mises, maximum, and minimum principal stresses.

Results

Lower stress values were obtained in 5 mm models compared to 3 mm models. However, the difference between them was insignificant. Lower stress values were obtained in all RET models compared to the control model. The lowest stress values in dental tissues and bone tissue were obtained in the CEM models.

Conclusion

This is the first study in which the stress caused by different thicknesses of CEM on dental tissues was evaluated with FEA. RET strengthens immature teeth biomechanically. CEM and Biodentin are more successful materials in stress distribution than MTA. Considering the cost of treatment, 3 mm material thickness is ideal for RET since there is no significant difference between the stress values resulting from the use of 5 mm and 3 mm coronary barrier material.
Attitudes towards induced abortion among gynecologists in Kurdistan region of Iraq
Authors: Khalid Gashaw , Saleh Abubakir Majeed , Shabila Nazar , Bogren Malin , Shakely Delér
Published: November 2023

Background

Unsafe abortion is a major contributor to maternal morbidity and mortality in countries where induced abortion is restricted. In Kurdistan Region of Iraq, induced abortion is strictly forbidden except for life-threatening situations, increasing the risk of seeking unsafe abortions. Attitudes among healthcare professionals who directly encounter cases and consequences of induced abortion can be studied to improve women’s access to safe abortion. This study aimed to examine attitudes towards induced abortion among gynecologists in Kurdistan Region of Iraq.

Methods

This cross-sectional facility-based study was conducted in the first quarter of 2022 in Kurdistan Region of Iraq in the cities of Erbil, Sulaymaniyah, and Duhok. Convenient sampling was used to invite 330 gynecologists to participate, with 171 ultimately completing the questionnaire, giving a response rate of 53%. Questionaries using the Taylor and Whitehead abortion attitude scale were sent in person or digitally. The data was then analyzed using Chi-square and Fisher’s exact tests to determine the independence of attitudes and associations between attitudes and sociodemographic factors.

Results

Among 171 gynecologists, 25% of the gynecologists agreed that induced abortion is unacceptable under any circumstances. Most (71%) disagreed that a woman has the right to choose to have an induced abortion. Around 51% considered induced abortion murder, and 41% agreed that induced abortion goes against all morals. Around 57% disagreed with the legalization of induced abortion, while 43% agreed. Gynecologists who were unmarried (P = 0.025), under the age of 40 (P = 0.044), and with less than 10 years of clinical experience (P = 0.043) were more likely to support the legalization of induced abortion in Kurdistan Region. None of the variables was found to be independently associated with attitudes towards abortion legalization.

Conclusions

Despite some younger gynecologists having more favorable attitudes towards induced abortion, most gynecologists in Kurdistan Region had less favorable views. Most gynecologists were willing to provide post-abortion care regardless of their legal status. We recommend conducting more studies to investigate the consequences of current abortion legislation among women in need of induced abortion in Kurdistan Region of Iraq.
Usability and feasibility of E-nergEYEze: a blended vision-specific E-health based cognitive behavioral therapy and self-management intervention to reduce fatigue in adults with visual impairment
Authors: Veldman M.H.J. , van der Aa H.P.A. , Knoop H. , Bode C. , Hulshof C.T.J. , van der Ham L. , van Rens G.H.M.B. , Heymans M.W. , van Nispen R.M.A.
Published: November 2023

Background

Over 50% of adults with visual impairment experience severe fatigue. Therefore, we developed a guided E-health intervention based on cognitive behavioral therapy and self-management to reduce fatigue in this population. This pilot study evaluated the usability, feasibility, fidelity and potential effectiveness of E-nergEYEze.

Methods

E-nergEYEze was developed by a design team and customized by conducting a pilot study using an iterative development strategy. The intervention was first tested in a usability study among adults with visual impairment (n = 5). Participants were asked to think-aloud while exploring the intervention features and a semi-structured interview was performed afterwards. Subsequently, the enhanced intervention was tested in a feasibility study. Adults with visual impairment and severe fatigue (n = 10) followed the intervention partially with guidance from a social worker and one-time computer trainer support. Fatigue severity (Checklist Individual Strength), fatigue impact (Modified Fatigue Impact Scale) and cognitive behavioral therapy skills (Competencies of Cognitive Therapy Scale-Self Report) were measured at baseline and at three months follow-up and analyzed with the Wilcoxon signed-rank test. The intervention was evaluated through evaluation forms.

Results

The usability study resulted in adjustments to content and lay-out with regard to optically shortened text sentences, separate pages for information and assignments with one read-aloud audio and an additional descriptive explanation of page content. Digital challenges were overcome with mandatory computer training and e-platform modifications. The feasibility study showed a positive trend in reducing fatigue severity (Z -6.108; P < .001; SD 8.4), impact of fatigue (Z − 4.451; P < .001; SD 11.4) and cognitive behavioral therapy skills (Z -2.278; P = .023; SD 19.3). Participants gave useful feedback regarding accessibility, content and guidance, with an overall positive experience. The intervention was rated with a median score of 8 (range 7–10).

Conclusion

We developed, evaluated and optimized E-nergEYEze by applying a user-centered and iterative approach. E-nergEYEze showed a promising trend to reduce fatigue severity and impact of fatigue and to increase cognitive behavioral therapy skills. The study methods were feasible and the fidelity of the intervention protocol was suitable. Performing a randomized controlled trial is warranted to give insight into whether E-nergEYEze is cost-effective in reducing severe fatigue in adults with visual impairment.

Trial registration

International Clinical Trial Registry Platform: NL7764. Date registered: 28-05-2019.
Barriers and enablers to managing challenging behaviours after traumatic brain injury in the acute hospital setting: a qualitative study
Authors: Block Heather , Bellon Michelle , Hunter Sarah C. , George Stacey
Published: November 2023

Background

Challenging behaviours after traumatic brain injury (TBI) in the acute setting are associated with risk of harm to the patient and staff, delays in commencing rehabilitation and increased length of hospital stay. Few guidelines exist to inform practice in acute settings, and specialist services providing multi-disciplinary expertise for TBI behaviour management are predominantly based in subacute inpatient services. This study aims to investigate acute and subacute staff perspectives of barriers and enablers to effectively managing challenging behaviours after TBI in acute hospital settings.

Methods

Qualitative focus groups were conducted with 28 staff (17 from acute setting, 11 from subacute setting) across two sites who had experience working with patients with TBI. Data were analysed using inductive-deductive reflexive thematic analysis. Data were applied to the constructs of the integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to generate themes representing barriers and enablers to managing challenging behaviours after TBI in the acute hospital setting.

Results

Four barriers and three enablers were identified. Barriers include (1) Difficulties with clinical decision making; (2) Concerns for risks to staff and patients; (3) Hospital environment; (4) Intensive resources are required. Enablers were (1) Experienced staff with practical skills; (2) Incorporating person-centred care; and (3) Supportive teams.

Conclusion

These findings can inform pre-implementation planning for future improvements to TBI behaviour management in acute hospital settings. Difficulties with clinical decision making, concerns for risks of injury, the hospital environment and lack of resources are major challenges. Implementation strategies developed to address barriers will need to be trialled, with multi-disciplinary team approaches, and tailored to the acute setting.
A novel autoantibody signatures for enhanced clinical diagnosis of pancreatic ductal adenocarcinoma
Authors: Li Tiandong , Xia Junfen , Yun Huan , Sun Guiying , Shen Yajing , Wang Peng , Shi Jianxiang , Wang Keyan , Yang Hongwei , Ye Hua
Published: November 2023

Background

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease that requires precise diagnosis for effective treatment. However, the diagnostic value of carbohydrate antigen 19 − 9 (CA19-9) is limited. Therefore, this study aims to identify novel tumor-associated autoantibodies (TAAbs) for PDAC diagnosis.

Methods

A three-phase strategy comprising discovery, test, and validation was implemented. HuProt™ Human Proteome Microarray v3.1 was used to screen potential TAAbs in 49 samples. Subsequently, the levels of potential TAAbs were evaluated in 477 samples via enzyme-linked immunosorbent assay (ELISA) in PDAC, benign pancreatic diseases (BPD), and normal control (NC), followed by the construction of a diagnostic model.

Results

In the discovery phase, protein microarrays identified 167 candidate TAAbs. Based on bioinformatics analysis, fifteen tumor-associated antigens (TAAs) were selected for further validation using ELISA. Ten TAAbs exhibited differentially expressed in PDAC patients in the test phase (P < 0.05), with an area under the curve (AUC) ranging from 0.61 to 0.76. An immunodiagnostic model including three TAAbs (anti-HEXB, anti-TXLNA, anti-SLAMF6) was then developed, demonstrating AUCs of 0.81 (58.0% sensitivity, 86.0% specificity) and 0.78 (55.71% sensitivity, 87.14% specificity) for distinguishing PDAC from NC. Additionally, the model yielded AUCs of 0.80 (58.0% sensitivity, 86.25% specificity) and 0.83 (55.71% sensitivity, 100% specificity) for distinguishing PDAC from BPD in the test and validation phases, respectively. Notably, the combination of the immunodiagnostic model with CA19-9 resulted in an increased positive rate of PDAC to 92.91%.

Conclusion

The immunodiagnostic model may offer a novel serological detection method for PDAC diagnosis, providing valuable insights into the development of effective diagnostic biomarkers.
Circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio predict response and outcome to immunotherapy in advanced gastric cancer patients
Authors: Liu Jiang , Liu Degan , Hu Guangyin , Wang Jingjing , Chen Dadong , Song Chuanjun , Cai Yin , Zhai Chentong , Xu Wenjing
Published: November 2023

Background

Limited benefit population of immunotherapy makes it urgent to select effective biomarkers for screening appropriate treatment population. Herein, we have investigated the predictive values of circulating CD8+ T cells and CD8+T/CD4+T cell ratio in advanced gastric cancer patients receiving immunotherapy.

Methods

A retrospective cohort analysis of 187 advanced gastric cancer patients receiving sintilimab combined with oxaliplatin and capecitabine therapy in The Affiliated Xinghua People’s Hospital, Medical School of Yangzhou University between December 2019 and February 2023 was conducted. The corresponding clinical outcomes of the variables were analyzed by receiver operating characteristic (ROC) curve, chi-square test, Kaplan–Meier methods and Cox proportional hazards regression models.

Results

The optimal cutoff values for percentages of CD8+ T cells, naive CD8+ T cells (CD8+ Tn) and memory CD8+ T cells (CD8+ Tm) expressing programmed cell death -1(PD-1) as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were 21.0, 21.5, 64.3 and 0.669, respectively. It was found that the mean percentages of CD8+ T and CD8+ Tm expressing PD-1 as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were significantly higher in responder (R) than non-responder (NonR) advanced gastric cancer patients associated with a longer progression free survival (PFS) and overall survival (OS). We also observed this correlation in programmed cell death-ligand 1(PD-L1) combined positive score (CPS) ≥ 5 subgroups. Univariate and multivariate Cox regression analyses demonstrated that lower CD8+ T and CD8+ Tm expressing PD-1 as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were independent risk factors in advanced gastric cancer patients receiving immunotherapy plus chemotherapy.

Conclusion

The circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio revealed high predictive values for response and prolonged survival outcomes in advanced gastric cancer patients receiving immunotherapy. Memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio might be effective for screening benefit population of immunotherapy in advanced gastric cancer patients based on this preliminary evidence.
Outsmarting trogocytosis to boost CAR NK/T cell therapy
Authors: Ramezani Faezeh , Panahi Meymandi Ahmad Reza , Akbari Behnia , Tamtaji Omid Reza , Mirzaei Hamed , Brown Christine E. , Mirzaei Hamid Reza
Published: November 2023

Chimeric antigen receptor (CAR) NK and T cell therapy are promising immunotherapeutic approaches for the treatment of cancer. However, the efficacy of CAR NK/T cell therapy is often hindered by various factors, including the phenomenon of trogocytosis, which involves the bidirectional exchange of membrane fragments between cells. In this review, we explore the role of trogocytosis in CAR NK/T cell therapy and highlight potential strategies for its modulation to improve therapeutic efficacy. We provide an in-depth analysis of trogocytosis as it relates to the fate and function of NK and T cells, focusing on its effects on cell activation, cytotoxicity, and antigen presentation. We discuss how trogocytosis can mediate transient antigen loss on cancer cells, thereby negatively affecting the effector function of CAR NK/T cells. Additionally, we address the phenomenon of fratricide and trogocytosis-associated exhaustion, which can limit the persistence and effectiveness of CAR-expressing cells. Furthermore, we explore how trogocytosis can impact CAR NK/T cell functionality, including the acquisition of target molecules and the modulation of signaling pathways. To overcome the negative effects of trogocytosis on cellular immunotherapy, we propose innovative approaches to modulate trogocytosis and augment CAR NK/T cell therapy. These strategies encompass targeting trogocytosis-related molecules, engineering CAR NK/T cells to resist trogocytosis-induced exhaustion and leveraging trogocytosis to enhance the function of CAR-expressing cells. By overcoming the limitations imposed by trogocytosis, it may be possible to unleash the full potential of CAR NK/T therapy against cancer. The knowledge and strategies presented in this review will guide future research and development, leading to improved therapeutic outcomes in the field of immunotherapy.
Characteristics of vaginal microbiota in various cervical intraepithelial neoplasia: a cross-sectional study
Authors: Liu Yiran , Wang Shuzhen , Liu Jun , Su Mingrui , Diao Xiaoli , Liang Xiaolong , Zhang Jianxin , Wang Qiuxi , Zhan Yuxin
Published: November 2023

Background

Precancerous lesions of cervical cancer exhibit characteristics indicative of natural progression. To prevent overtreatment of patients whose cervical intraepithelial neoplasia (CIN) in regression and to predict the onset of invasive cervical cancer at an early stage, we've identified the vaginal microbiome as a potential key factor, which is associated with both HPV infection and the various cervical intraepithelial neoplasia. This study aims to investigate the microbiome characteristics of patients with various cervical intraepithelial neoplasia.

Methods

Utilizing high-throughput 16S ribosomal RNA (16S rRNA) sequencing technology, a description of the characteristics and community composition of Vaginal Microbiota (VMB) was conducted among 692 Chinese women infected with the High-risk Human Papillomavirus (HR-HPV).

Results

As the grade of the lesions increased, the proportions of Lactobacillus and Pseudomonas demonstrated a significant declining trend, while the proportions of Gardnerella, Dialister, and Prevotella significantly increased. The diversity of the VMB was more significant in high-grade CIN. Furthermore, KEGG pathway enrichment analysis indicates that high-grade cervical intraepithelial neoplasia can inhibit various pathways, including those of phosphotransferase system, transcription factors, Fructose and mannose metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism, which may contribute to the development of early cervical cancer symptoms.

Conclusion

Patients with CIN exhibit a distinct vaginal microbial profile characterized by a decrease in Lactobacillus and Pseudomonas, and an increase in Gardnerella, Prevotella, and Dialister. The proliferation and diminution of these two types of microbial communities are interrelated, suggesting a mutual restraint and balance among them. Disruption of this regulatory balance could potentially lead to the onset of cervical lesions and carcinogenesis.

Retrospectively registered: This study was approved by the Ethics Committee of the Beijing Chaoyang Hospital affiliated with the Capital Medical University (NO.2023-S-415).
PTPRH promotes the progression of non-small cell lung cancer via glycolysis mediated by the PI3K/AKT/mTOR signaling pathway
Authors: Wang Shu , Cheng Zhiming , Cui Yan , Xu Shuoyan , Luan Qiu , Jing Shan , Du Bulin , Li Xuena , Li Yaming
Published: November 2023

Background

The protein tyrosine phosphatase H receptor (PTPRH) is known to regulate the occurrence and development of pancreatic and colorectal cancer. However, its association with glycolysis in non-small cell lung cancer (NSCLC) is still unclear. In this study, we aimed to investigate the relationship between PTPRH expression and glucose metabolism and the underlying mechanism of action.

Methods

The expression of PTPRH in NSCLC cells was evaluated by IHC staining, qRT‒PCR and Western blotting. The effect of PTPRH on cell biological behavior was evaluated by colony assays, EdU experiments, Transwell assays, wound healing assays and flow cytometry. Changes in F-18-fluorodeoxyglucose (18F‐FDG) uptake and glucose metabolite levels after altering PTPRH expression were detected via a gamma counter and lactic acid tests. The expression of glycolysis-related proteins in NSCLC cells was detected by Western blotting after altering PTPRH expression.

Results

The results showed that PTPRH was highly expressed in clinical patient tissue samples and closely related to tumor diameter and clinical stage. In addition, PTPRH expression was associated with glycometabolism indexes on 18F-FDG positron emission tomography/computed tomography (PET/CT) imaging, the expression level of Ki67 and the expression levels of glycolysis-related proteins. PTPRH altered cell behavior, inhibited apoptosis, and promoted 18F-FDG uptake, lactate production, and the expression of glycolysis-related proteins. In addition, PTPRH modulated the glycometabolism of NSCLC cells via the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, as assessed using LY294002 and 740Y-P (an inhibitor and agonist of PI3K, respectively). The same results were validated in vivo using a xenograft tumor model in nude mice. Protein expression levels of PTPRH, glycolysis-related proteins, p-PI3K/PI3K and p-AKT/AKT were measured by IHC staining using a subcutaneous xenograft model in nude mice.

Conclusions

In summary, we report that PTPRH promotes glycolysis, proliferation, migration, and invasion via the PI3K/AKT/mTOR signaling pathway in NSCLC and ultimately promotes tumor progression, which can be regulated by LY294002 and 740Y-P. These results suggest that PTPRH is a potential therapeutic target for NSCLC.

Graphical Abstract
Effects of overground gait training assisted by a wearable exoskeleton in patients with Parkinson’s disease
Authors: Otlet Virginie , Vandamme Clémence , Warlop Thibault , Crevecoeur Frédéric , Ronsse Renaud
Published: November 2023

Background

In the recent past, wearable devices have been used for gait rehabilitation in patients with Parkinson’s disease. The objective of this paper is to analyze the outcome of a wearable hip orthosis whose assistance adapts in real time to the patient’s gait kinematics via adaptive oscillators. In particular, this study focuses on a metric characterizing natural gait variability, i.e., the level of long-range autocorrelations (LRA) in series of stride durations.

Methods

Eight patients with Parkinson’s disease (Hoehn and Yahr stages 1$$-$$-2.5) performed overground gait training three times per week for four consecutive weeks, assisted by a wearable hip orthosis. Gait was assessed based on performance metrics such as the hip range of motion, speed, stride length and duration, and the level of LRA in inter-stride time series assessed using the Adaptive Fractal Analysis. These metrics were measured before, directly after, and 1 month after training.

Results

After training, patients increased their hip range of motion, their gait speed and stride length, and decreased their stride duration. These improvements were maintained 1 month after training. Regarding long-range autocorrelations, the population’s behavior was standardized towards a metric closer to the one of healthy individuals after training, but with no retention after 1 month.

Conclusion

This study showed that an overground gait training with adaptive robotic assistance has the potential to improve key gait metrics that are typically affected by Parkinson’s disease and that lead to higher prevalence of fall.

Trial registration: ClinicalTrials.gov Identifer NCT04314973. Registered on 11 April 2020.
Case report: Takotsubo syndrome following percutaneous coronary intervention
Authors: Lu Rui , Lu Mingjun , He Shangfei , Lu Jing , Liao Yi , Cui Tongtao , Wang Min
Published: November 2023

Background

Takotsubo syndrome (TTS), which is frequently secondary to severe emotional (fear, anxiety, etc.) or physical stress, is an acute reversible heart failure syndrome characterized by temporary left ventricular regional systolic dysfunction. Nevertheless, TTS after percutaneous coronary intervention (PCI) is rare, and its clinical characteristics are easily confused with complications after PCI.

Case presentation

This article reports a case of TTS induced by psychological and physical pressure after successful PCI in our institution. The patient had symptoms comparable to complications after PCI, including V1-V5 ST segment elevation and T wave changes of electrocardiogram (ECG) and troponin elevation. Coronary angiogram, left ventricle opacification (LVO), and cardiac magnetic resonance (CMR) were performed to exclude postoperative complications. Diagnosis of TTS was eventually achieved.

Conclusion

We cannot dismiss the risk of TTS in patients who have unexplained V1-V5 ST segment elevation and T wave changes of ECG and troponin elevation following successful PCI. Meanwhile, medical personnel should provide mental, cultural, and emotional services to patients in addition to essential diagnostic and treatment technical services during the perioperative period.
An expanded clinical spectrum of hypoinsulinaemic hypoketotic hypoglycaemia
Authors: Welters Alena , Leiter Sarah M , Bachmann Nadine , Bergmann Carsten , Hoermann Henrike , Korsch Eckhard , Meissner Thomas , Payne Felicity , Williams Rachel , Hussain Khalid , Semple Robert K. , Kummer Sebastian
Published: November 2023

Background

Hypoketotic hypoglycaemia with suppressed plasma fatty acids and detectable insulin suggests congenital hyperinsulinism (CHI). Severe hypoketotic hypoglycaemia mimicking hyperinsulinism but without detectable insulin has recently been described in syndromic individuals with mosaic genetic activation of post-receptor insulin signalling. We set out to expand understanding of this entity focusing on metabolic phenotypes.

Methods

Metabolic profiling, candidate gene and exome sequencing were performed in six infants with hypoketotic, hypoinsulinaemic hypoglycaemia, with or without syndromic features. Additional signalling studies were carried out in dermal fibroblasts from two individuals.

Results

Two infants had no syndromic features. One was mistakenly diagnosed with CHI. One had mild features of megalencephaly-capillary malformation-polymicrogyria (MCAP) syndrome, one had non-specific macrosomia, and two had complex syndromes. All required intensive treatment to maintain euglycaemia, with CHI-directed therapies being ineffective. Pathogenic PIK3CA variants were found in two individuals – de novo germline c.323G>A (p.Arg108His) in one non-syndromic infant and postzygotic mosaic c.2740G>A (p.Gly914Arg) in the infant with MCAP. No causal variants were proven in the other individuals despite extensive investigation, although rare variants in mTORC components were identified in one. No increased PI3K signalling in fibroblasts of two individuals was seen.

Conclusions

We expand the spectrum of PI3K-related hypoinsulinaemic hypoketotic hypoglycaemia. We demonstrate that pathogenic germline variants activating post-insulin-receptor signalling may cause non-syndromic hypoinsulinaemic hypoketotic hypoglycaemia closely resembling CHI. This distinct biochemical footprint should be sought and differentiated from CHI in infantile hypoglycaemia. To facilitate adoption of this differential diagnosis, we propose the term “pseudohyperinsulinism”.
The effect of calorie-restriction along with thylakoid membranes of spinach on the gut-brain Axis Pathway and oxidative stress biomarkers in obese women with polycystic ovary syndrome: a Randomized, Double-blind, placebo-controlled clinical trial
Authors: Nikrad Negin , Farhangi Mahdieh Abbasalizad , Fard Tabrizi Fatemeh Pourteymour , Vaezi Maryam , Mahmoudpour Ata , Mesgari-Abbasi Mehran
Published: November 2023

Background

Women with polycystic ovary syndrome (PCOS) have higher intestinal mucosal permeability, leading to the lipopolysaccharide (LPS) leakage and endotoxemia. This, in turn, leads to oxidative stress (OS) and neuro-inflammation caused by the gut-brain axis, affecting the neurotrophic factors levels such as brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100 B) levels. In this study, it was hypothesized that the thylakoid membranes of spinach supplementation along with a hypocaloric diet may have improved the LPS levels, neurotrophic factors, and OS in PCOS patients.

Methods

In this double-blind, randomized, placebo-controlled, and clinical trial, 48 women with obesity and diagnosed with PCOS based on Rotterdam criteria were randomly assigned to thylakoid (N = 21) and placebo groups (N = 23). A personalized hypocaloric diet with 500 calories less than the total energy expenditure was prescribed to all patients. The participants were daily supplemented with either a 5 g/day thylakoid-rich spinach extract or a placebo (5 g cornstarch) for 12 weeks along with a prescribed low-calorie diet. Anthropometric measurements and biochemical parameters were assessed at baseline and after the 12-week intervention.

Results

A statistically significant decrease in the LPS levels (P < 0.001) and an increase in the BDNF levels (P < 0.001) were recorded for the participants receiving the oral thylakoid supplements and a low-calorie diet. Furthermore, significant decreases were observed in fasting blood glucose, insulin, homeostatic model of assessment for insulin resistance, free testosterone index, and follicle-stimulating hormone / luteinizing hormone ratio in both groups (P < 0.05). No significant differences were detected between the two groups regarding the changes in malondialdehyde, catalase, total antioxidant capacity, and S100B levels (P > 0.05).

Conclusions

In sum, the thylakoid membranes of spinach supplemented with a hypocaloric diet reduced the LPS levels, increased the BDNF levels, and improved the glycemic profile and sex-hormone levels; however, they had no effects on the OS markers levels after 12 weeks of intervention.
Establishment of a differential diagnosis method and an online prediction platform for AOSD and sepsis based on gradient boosting decision trees algorithm
Authors: Zhou Dongmei , Xie Jingzhi , Wang Jiarui , Zong Juan , Fang Quanquan , Luo Fei , Zhang Ting , Ma Hua , Cao Lina , Yin Hanqiu , Yin Songlou , Li Shuyan
Published: November 2023

Objective

The differential diagnosis between adult-onset Still’s disease (AOSD) and sepsis has always been a challenge. In this study, a machine learning model for differential diagnosis of AOSD and sepsis was developed and an online platform was developed to facilitate the clinical application of the model.

Methods

All data were collected from 42 AOSD patients and 50 sepsis patients admitted to Affiliated Hospital of Xuzhou Medical University from December 2018 to December 2021. In addition, 5 AOSD patients and 10 sepsis patients diagnosed in our hospital after March 2022 were collected for external validation. All models were built using the scikit-learn library (version 1.0.2) in Python (version 3.9.7), and feature selection was performed using the SHAP (Shapley Additive exPlanation) package developed in Python.

Results

The results showed that the gradient boosting decision tree(GBDT) optimization model based on arthralgia, ferritin × lymphocyte count, white blood cell count, ferritin × platelet count, and α1-acid glycoprotein/creatine kinase could well identify AOSD and sepsis. The training set interaction test (AUC: 0.9916, ACC: 0.9457, Sens: 0.9556, Spec: 0.9578) and the external validation also achieved satisfactory results (AUC: 0.9800, ACC: 0.9333, Sens: 0.8000, Spec: 1.000). We named this discrimination method AIADSS (AI-assisted discrimination of Still’s disease and Sepsis) and created an online service platform for practical operation, the website is http://cppdd.cn/STILL1/.

Conclusion

We created a method for the identification of AOSD and sepsis based on machine learning. This method can provide a reference for clinicians to formulate the next diagnosis and treatment plan.
Enzyme kinetics of deoxyuridine triphosphatase from Western corn rootworm
Authors: Riera-Ruiz Carlos , Moriyama Hideaki
Published: November 2023

Objective

The Western corn rootworm (WCR), Diabrotica virgifera virgifera, is a highly adaptable insect pest that has evolved resistance to a variety of control strategies, including insecticides. Therefore, it is interesting to examine how housekeeping proteins in WCR have been changed under WCR-controlling strategies. In this study, we focused on one of such proteins in WCR, a ubiquitous enzyme 5'-triphosphate nucleotidohydrolase (dUTPase). In the thymidine synthetic pathway, dUTPase hydrolyzes deoxyuridine triphosphate (dUTP) and supplies the substrate, deoxyuridine monophosphate, for the thymidylate synthase (TS). It decreases the cellular content of uracil, reducing uracil misincorporation into DNA. Suppressing the dUTPase activity, therefore, contributes to thymineless death. In this study, we investigated the enzymatic properties of dUTPase.

Results

The WCR dUTPase gene (DUT) was synthesized with the addition of His-tag corresponding DNA sequence and then cloned and expressed in Escherichia coli, and the protein product was purified. The product of WCR DUT hydrolyzed dUTP and was designated as dUTPase. WCR dUTPase did not hydrolyze dATP, dTTP, dCTP, or dGTP. WCR dUTPase was analyzed via size-exclusion chromatography and exhibited a molecular weight corresponding to that of trimer. The present format can be interpreted as nuclear trimer type. Possible isomers will be examined once transcriptome analyses are conducted.