bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanomaterials-assisted gene editing and synthetic biology for optimizing the treatment of pulmonary diseases
Authors: Lei Lanjie , Pan Wenjie , Shou Xin , Shao Yunyuan , Ye Shuxuan , Zhang Junfeng , Kolliputi Narasaiah , Shi Liyun 
Published: June 2024

AbstractThe use of nanomaterials in gene editing and synthetic biology has emerged as a pivotal strategy in the pursuit of refined treatment methodologies for pulmonary disorders. This review discusses the utilization of nanomaterial-assisted gene editing tools and synthetic biology techniques to promote the development of more precise and efficient treatments for pulmonary diseases. First, we briefly outline the characterization of the respiratory system and succinctly describe the principal applications of diverse nanomaterials in lung ailment treatment. Second, we elaborate on gene-editing tools, their configurations, and assorted delivery methods, while delving into the present state of nanomaterial-facilitated gene-editing interventions for a spectrum of pulmonary diseases. Subsequently, we briefly expound on synthetic biology and its deployment in biomedicine, focusing on research advances in the diagnosis and treatment of pulmonary conditions against the backdrop of the coronavirus disease 2019 pandemic. Finally, we summarize the extant lacunae in current research and delineate prospects for advancement in this domain. This holistic approach augments the development of pioneering solutions in lung disease treatment, thereby endowing patients with more efficacious and personalized therapeutic alternatives.
Seroprevalence of SARS-CoV-2 and humoral immune responses to COVID-19 mRNA vaccines among people who use drugs - in the light of tailored mitigating strategies
Authors: Wüsthoff Linda Elise Couëssurel , Lund-Johansen Fridtjof , Henriksen Kathleen , Wildendahl Gull , Jacobsen Jon-Aksel , Gomes Leni , Anjum Hina Sarwar , Barlinn Regine , Kran Anne-Marte Bakken , Munthe Ludvig Andre , Vaage John T. 
Published: June 2024

Abstract
Background
During the initial wave of the COVID-19 pandemic, there was a surprisingly low incidence of SARS-CoV-2 among People Who Use Drugs (PWUD) in Oslo, Norway, despite their heightened vulnerability regarding risk of infection and severe courses of the disease.This study aims to investigate the seroprevalence of SARS-CoV-2 antibodies among PWUD, their antibody responses to relevant virus infections and COVID-19 mRNA vaccines, and their vaccination coverage compared to the general population.

Methods
Conducted as a prospective cohort study, data was collected from residents in six institutions for homeless PWUD and users of a low-threshold clinic for opioid agonist treatment. Ninety-seven participants were recruited for SARS-CoV-2 seroprevalence analysis. Additional two participants with known positive SARS-CoV-2 test results were recruited for further analyses. Twenty-five participants completed follow-up. Data included questionnaires, nasal swabs and blood samples. Data on vaccination coverage was obtained from the National Vaccine Register. Serologic methods included detection of antibodies to relevant virus proteins, neutralizing antibodies to SARS-CoV-2, antibodies to the full-length spike protein, and receptor-binding domain from SARS-CoV-2.

Results
Among PWUD, antibodies to SARS-CoV-2 were detected in 2 out of 97 samples before vaccines against SARS-CoV-2 were available, comparable to a 2.8% frequency in population-based screening. Levels of serum antibodies to seasonal coronaviruses and Epstein-Barr-Virus (EBV) in PWUD were similar to population-based levels. After the second vaccine dose, binding and neutralizing antibody levels to SARS-CoV-2 in PWUD were comparable to controls. Eighty-four of PWUD received at least one dose of COVID-19 mRNA vaccine, compared to 89% in the general population.

Conclusion
Results indicate that PWUD did not exhibit increased SARS-CoV-2 seroprevalence or elevated serum antibodies to seasonal coronaviruses and EBV. Moreover, vaccine responses in PWUD were comparable to controls, suggesting that vaccination is effective in conferring protection against SARS-CoV-2 also in this population.
Genetic perturbation of IL-6 receptor signaling pathway and risk of multiple respiratory diseases
Authors: Wu Dongsheng , Gong Zhipeng , Hao Xiaohu , Liu Lunxu 
Published: June 2024

AbstractDysregulation of inflammation can lead to multiple chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma. Interleukin-6 (IL6) is crucial in regulating the inflammatory cascade, but the causal link between IL6 signaling downregulation and respiratory diseases risk is unclear. This study uses Mendelian randomization to examine the effects of IL6R blockade on respiratory diseases. Analyzing data from 522,681 Europeans, 26 genetic variants were obtained to mimic IL6R inhibition. Our findings show that IL6R blockade significantly reduces the risk of COPD (OR = 0.71, 95% CI = 0.60–9.84) and asthma (OR = 0.82, 95% CI = 0.74–0.90), with protective trends for bronchitis, pulmonary embolism, and lung cancer. Results were consistent across methods, with no significant heterogeneity or pleiotropy. These insights suggest IL6R downregulation as a potential therapeutic target for respiratory diseases, meriting further clinical investigation.
IFIT1 + neutrophil is a causative factor of immunosuppressive features of poorly cohesive carcinoma (PCC)
Authors: Liu Yuan-jie , Li Jie-pin , Han Mei , Li Jing-xiao , Ye Qian-wen , Lin Si-tian , Zhou Jin-yong , Liu Shen-lin , Zou Xi 
Published: June 2024

AbstractThe importance of the immune microenvironment in poorly cohesive carcinoma (PCC) has been highlighted due to its limited response rate to conventional therapy and emerging treatment resistance. A combination of clinical cohorts, bioinformatics analyses, and functional/molecular experiments revealed that high infiltration of Interferon Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) + tumor-associated neutrophils (TANs) is a distinguishing feature of PCC patients. Upregulation of IFIT1 + TANs promote migration and invasion of gastric cancer (GC) cell lines (MKN45 and MKN74) and stimulates the growth of cell-derived xenograft models. Besides, by promoting macrophage secreted phosphoprotein 1 (SPP1) expression and facilitating cancer-associated fibroblast and endothelial cell recruitment and activation through TANs, IFIT1 promotes a mesenchymal phenotype, which is associated with a poor prognosis. Importantly, compared to non-PCC (NPCC), PCC tumors is more immunosuppressive. Mechanistically, IFIT1 can be stimulated by IFN-γ and contributes to the expression of Programmed Cell Death 1 Ligand (PDL1) in TANs. We demonstrated in mouse models that IFIT1 + PDL1 + TANs can induce acquired resistance to anti-PD-1 immunotherapy, which may be responsible for the difficulty of PCC patients to benefit from immunotherapy. This work highlights the role of IFIT1 + TANs in mediating the remodeling of the tumor immune microenvironment and immunotherapeutic resistance and introduces IFIT1 + TANs as a promising target for precision therapy of PCC.
Transcatheter mitral valve-in-valve for pregnancy with anti-phospholipid syndrome: a case report
Authors: Wang Zhenzhong , Li Yuxin , Xiao Shuo , Wang Qiuji , Zhang Zhaolong , Han Fengzhen , Huang Huanlei 
Published: June 2024

Abstract
Background
Perioperative management and cardiac surgery in pregnant women with anti-phospholipid syndrome combined with heart valve disease have been rarely reported.

Case presentation
We describe a case of transcatheter mitral valve-in-valve replacement in a pregnant woman with bioprosthetic valve failure and anti-phospholipid syndrome at 18 weeks’ gestation. The patient underwent a cesarean section delivery at 34 weeks of gestation, resulting in the birth of a healthy baby.

Conclusions
Transapical mitral valve-in-valve surgery resulted in safe maternal and infant outcomes in a pregnant woman with anti-phospholipid syndrome combined with mitral bioprosthetic valve failure. The success of this procedure underscored the importance of multidisciplinary teamwork.
Translation, cultural adaptation and validation of Patient Health Questionnaire and generalized anxiety disorder among adolescents in Nepal
Authors: Luitel Nagendra P. , Rimal Damodar , Eleftheriou Georgia , Rose-Clarke Kelly , Nayaju Suvash , Gautam Kamal , Pant Sagun Ballav , Devkota Narmada , Rana Shruti , Chaudhary Jug Maya , Gurung Bhupendra Singh , Åhs Jill Witney , Carvajal-Velez Liliana , Kohrt Brandon A. 
Published: June 2024

Abstract
Background
Depression and anxiety are significant contributors to the global burden of disease among young people. Accurate data on the prevalence of these conditions are crucial for the equitable distribution of resources for planning and implementing effective programs. This study aimed to culturally adapt and validate data collection tools for measuring depression and anxiety at the population level.

Methods
The study was conducted in Kathmandu, Nepal, a diverse city with multiple ethnicities, languages, and cultures. Ten focus group discussions with 56 participants and 25 cognitive interviews were conducted to inform adaptations of the Patient Health Questionnaire adapted for Adolescents (PHQ-A) and Generalized Anxiety Disorder (GAD-7). To validate the tools, a cross-sectional survey of 413 adolescents (aged 12–19) was conducted in three municipalities of Kathmandu district. Trained clinical psychologists administered the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-DSM 5 version) to survey participants.

Results
A number of cultural adaptations were required, such as changing statements into questions, using a visual scale (glass scale) to maintain uniformity in responses, and including a time frame at the beginning of each item. For younger adolescents aged 12 to 14 years, a PHQ-A cut-off of > = 13 had a sensitivity of 0.93, specificity of 0.80, positive predictive value (PPV) of 0.33, and negative predictive value (NPV) of 0.99. For older adolescents aged 15–19, a cut-off of > = 11 had a sensitivity of 0.89, specificity of 0.70, PPV of 0.32, and NPV of 0.97. For GAD-7, a cut-off of > = 8 had a sensitivity of 0.70 and specificity of 0.67 for younger adolescents and 0.71 for older adolescents, with a PPV of 0.39 and NPV of 0.89. The individual symptom means of both PHQ-A and GAD-7 items showed moderate ability to discriminate between adolescents with and without depression and anxiety.

Conclusion
The PHQ-A and GAD-7 demonstrate fair psychometric properties for screening depression but performed poorly for anxiety, with high rates of false positives. Even when using clinically validated cut-offs, population prevalence rates would be inflated by 2–4 fold with these tools, requiring adjustment when interpreting epidemiological findings.
The experıance of tertıary center for adult granulosa cell tumor: whıch factors predıct survival?
Authors: Şahin Mustafa , Arslanca Tufan , Uçar Yeşim Özkaya , Güner Gülşah Tiryaki , Selçuk İlker , Yalçın Hakan Raşit 
Published: June 2024

Abstract
Background
This retrospective study aims to evaluate the clinical course and long-term outcomes of patients diagnosed with adult granulosa cell tumors (AGCT).

Methods
The study analyzed a cohort of 112 AGCT patients with a median follow-up of 87 months. Data regarding disease-free survival (DFS), overall survival (OS), recurrence rates, and prognostic factors were collected and analyzed. Surgical interventions, including lymphadenectomy and cytoreductive surgery, were assessed for their impact on outcomes.

Results
The study revealed favorable long-term outcomes, with a 5-year DFS of 85% and a 10-year DFS of 83%. Additionally, a 5-year OS of 100% and a 10-year OS of 96% were observed. Recurrence occurred in 13.4% of cases, with advanced stage and positive peritoneal cytology identified as independent poor prognostic factors for DFS. Lymph node involvement was rare, and routine lymphadenectomy did not improve outcomes. Conservative surgery showed comparable DFS rates to definitive surgery in early-stage disease. However, cytoreductive surgery was crucial for advanced and recurrent tumors, with complete tumor resection enhancing survival outcomes.

Conclusion
The study underscores the importance of vigilant follow-up and individualized treatment strategies for AGCT patients. Despite the retrospective nature of the analysis, the substantial patient cohort and meticulous surgical interventions contribute valuable insights into AGCT management. Prospective multicenter studies are warranted to further elucidate prognostic factors and optimize treatment approaches for this rare malignancy.
Potential risk factors for reduced quality of life and increased health care utilization in ARDS survivors: results from the multicenter cohort study DACAPO
Authors: Szymczak Hermann , Brandstetter Susanne , Blecha Sebastian , Dodoo-Schittko Frank , Rohr Magdalena , Bein Thomas , Apfelbacher Christian 
Published: June 2024

Abstract
Aim
To analyze the association of individual pre-ICU risk factors (obesity, physical and mental comorbidity, smoking status) on the long-term recovery process in survivors of the acute respiratory distress syndrome (ARDS; outcomes: health related quality of life, health care utilization; measured at 12, 24, and 36 months after ICU discharge).

Findings
Results show a possible causal link between pre-ICU risk factors and subsequent recovery of survivors of ARDS, especially with regard to mental health related quality of life.

Purpose
Identifying relevant pre-existing risk factors, such as mental health problems, will enable the identification of at-risk patients, thus aiding in the improvement of long-term healthcare for survivors of critical illness.
Trial participants’ self-reported understanding of randomisation phrases in participation information leaflets can be high, but acceptability of some descriptions is low, especially those linked to gambling and luck
Authors: Shiely Frances , Murphy Ellen , Gilles Katie , Hood Kerry , O’Sullivan Lydia , Harman Nicola , Isaacs Talia , Treweek Shaun 
Published: June 2024

Abstract
Background
Evidence indicates that trial participants often struggle to understand participant information leaflets (PILs) for clinical trials, including the concept of randomisation. We analysed the language used to describe randomisation in PILs and determine the most understandable and acceptable description through public and participant feedback.

Methods
We collected 280 PILs/informed consent forms and one video animation from clinical research facilities/clinical trial units in Ireland and the UK. We extracted text on how randomisation was described, plus trial characteristics. We conducted content analysis to group the randomisation phrases inductively. We then excluded phrases that appeared more than once or were very similar to others. The final list of randomisation phrases was then presented to an online panel of participants and the public. Panel members were asked to rate each phrase on a 5-point Likert scale in terms of their understanding of the phrase, confidence in their understanding and acceptability of the phrase.

Results
Two hundred and eighty PILs and the transcribed text from one video animation represented 229 ongoing or concluded trials. The pragmatic content analysis generated five inductive categories: (1) explanation of why randomisation is required in trials; (2) synonyms for randomisation; (3) comparative randomisation phrases; (4) elaborative phrases for randomisation (5) and phrases that describe the process of randomisation. We had 48 unique phrases, which were shared with 73 participants and members of the public. Phrases that were well understood were not necessarily acceptable. Participants understood, but disliked, comparative phrases that referenced gambling, e.g. toss of a coin, like a lottery, roll of a die. They also disliked phrases that attributed decision-making to computers or automated systems. Participants liked plain language descriptions of what randomisation is and those that did not use comparative phrases.

Conclusions
Potential trial participants are clear on their likes and dislikes when it comes to describing randomisation in PILs. We make five recommendations for practice.
Transcutaneous auricular vagus nerve stimulation to acutely reduce emotional vulnerability and improve emotional regulation in borderline personality disorder (tVNS-BPD): study protocol for a randomized, single-blind, sham-controlled trial
Authors: Guerriero Giuseppe , Liljedahl Sophie I. , Carlsen Hanne K. , López Muñoz Marta , Daros Alexander R. , Ruocco Anthony C. , Steingrimsson Steinn 
Published: June 2024

Abstract
Background
Borderline personality disorder (BPD) is considered a disorder of emotion regulation resulting from the expression of a biologically determined emotional vulnerability (that is, heightened sensitivity to emotion, increased emotional intensity/reactivity, and a slow return to emotional baseline) combined with exposure to invalidating environments. Vagal tone has been associated with activity in cortical regions involved in emotion regulation and a lower resting state of vagal tone has been observed in BPD patients relative to healthy controls. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has been shown to reduce temper outbursts in adults with Prader-Willi Syndrome, to enhance recognition of emotions in healthy students, and to improve depressive and anxiety symptoms. Furthermore, a single session of taVNS has been shown to acutely alter the recognition of facial expressions of negative valence in adolescents with MDD and increase emotion recognition in controls. However, the effect of taVNS on emotional vulnerability and regulation in individuals diagnosed with BPD has not been investigated. Our aims are to determine if taVNS is effective in acutely reducing emotional vulnerability and improve emotional regulation in BPD patients.

Methods
Forty-two patients will be randomized to a single session of taVNS or sham-taVNS while going through an affect induction procedure. It will consist of the presentation of one neutral and three negative affect-evoking 4-min-long videos in sequence, each of which is followed by a 4-min post-induction period during which participants will rate the quality and intensity of their current self-reported emotions (post-induction ratings) and the perceived effectiveness in managing their emotions during the video presentation. The rating of the current self-reported emotions will be repeated after every post-induction period (recovery ratings). Mixed models with individuals as random effect will be used to investigate the ratings at each stage of the study, taking into account the repeated measures of the same individuals at baseline, pre-induction, post-induction, and recovery.

Discussion
The study has potential to yield new insights into the role of vagal tone in emotion dysregulation in BPD and offer preliminary data on the effectiveness of taVNS as a possible non-invasive brain stimulation to treat a core symptom of BPD.

Trial registration
ClinicalTrials.gov NCT05892900. Retrospectively registered on Jun 07, 2023.
The effect of an online acceptance and commitment intervention on the meaning-making process in cancer patients following hematopoietic cell transplantation: study protocol for a randomized controlled trial enhanced with single-case experimental design
Authors: Kroemeke Aleksandra , Dudek Joanna , Kijowska Marta , Owen Ray , Sobczyk-Kruszelnicka Małgorzata 
Published: June 2024

Abstract
Background
Hematopoietic cell transplantation (HCT) is a highly invasive and life-threatening treatment for hematological neoplasms and some types of cancer that can challenge the patient’s meaning structures. Restoring meaning (i.e., building more flexible and significant explanations of the disease and treatment burden) can be aided by strengthening psychological flexibility by means of an Acceptance and Commitment Therapy (ACT) intervention. Thus, this trial aims to examine the effect of the ACT intervention on the meaning-making process and the underlying mechanisms of change in patients following HCT compared to a minimally enhanced usual care (mEUC) control group. The trial will be enhanced with a single-case experimental design (SCED), where ACT interventions will be compared between individuals with various pre-intervention intervals.

Methods
In total, 192 patients who qualify for the first autologous or allogeneic HCT will be recruited for a two-armed parallel randomized controlled trial comparing an online self-help 14-day ACT training to education sessions (recommendations following HCT). In both conditions, participants will receive once a day a short survey and intervention proposal (about 5–10 min a day) in the outpatient period. Double-blinded assessment will be conducted at baseline, during the intervention, immediately, 1 month, and 3 months after the intervention. In addition, 6–9 participants will be invited to SCED and randomly assigned to pre-intervention measurement length (1–3 weeks) before completing ACT intervention, followed by 7-day observations at the 2nd and 3rd post-intervention measure. The primary outcome is meaning-related distress. Secondary outcomes include psychological flexibility, meaning-making coping, meanings made, and well-being as well as global and situational meaning.

Discussion
This trial represents the first study that integrates the ACT and meaning-making frameworks to reduce meaning-related distress, stimulate the meaning-making process, and enhance the well-being of HCT recipients. Testing of an intervention to address existential concerns unique to patients undergoing HCT will be reinforced by a statistically rigorous idiographic approach to see what works for whom and when. Since access to interventions in the HCT population is limited, the web-based ACT self-help program could potentially fill this gap.

Trial registration
ClinicalTrials.gov ID: NCT06266182. Registered on February 20, 2024.
Increased triacylglycerol production in Rhodococcus opacus by overexpressing transcriptional regulators
Authors: Anthony Winston E. , Geng Weitao , Diao Jinjin , Carr Rhiannon R. , Wang Bin , Ning Jie , Moon Tae Seok , Dantas Gautam , Zhang Fuzhong 
Published: June 2024

AbstractLignocellulosic biomass is currently underutilized, but it offers promise as a resource for the generation of commercial end-products, such as biofuels, detergents, and other oleochemicals. Rhodococcus opacus PD630 is an oleaginous, Gram-positive bacterium with an exceptional ability to utilize recalcitrant aromatic lignin breakdown products to produce lipid molecules such as triacylglycerols (TAGs), which are an important biofuel precursor. Lipid carbon storage molecules accumulate only under growth-limiting low nitrogen conditions, representing a significant challenge toward using bacterial biorefineries for fuel precursor production. In this work, we screened overexpression of 27 native transcriptional regulators for their abilities to improve lipid accumulation under nitrogen-rich conditions, resulting in three strains that accumulate increased lipids, unconstrained by nitrogen availability when grown in phenol or glucose. Transcriptomic analyses revealed that the best strain (#13) enhanced FA production via activation of the β-ketoadipate pathway. Gene deletion experiments confirm that lipid accumulation in nitrogen-replete conditions requires reprogramming of phenylalanine metabolism. By generating mutants decoupling carbon storage from low nitrogen environments, we move closer toward optimizing R. opacus for efficient bioproduction on lignocellulosic biomass.