bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Paxlovid on in-hospital outcomes and post-COVID-19 condition in adult patients infected with SARS-CoV-2 Omicron variant: A non-randomized controlled clinical trial
Authors: Xu Jianchao , Song Jinzhong , Xie Ziyu , Yang Jie , Wu Di , Liu Fengshuang , Zhao Yinuo , Zang Hongmin , Zhao Yubin
Published: December 2023

Background:

Nirmatrelvir plus ritonavir (Paxlovid) have been used in the treatment of adult patients with mild-to-moderate coronavirus disease 2019 (COVID-19). This study aimed to evaluate the impact of Paxlovid on in-hospital outcomes and post-COVID-19 condition in Chinese adult patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant.

Methods:

This non-randomized clinical controlled trial recruited patients infected with SARS-CoV-2 Omicron variant from the designated hospital for treating COVID-19 between November 5 and November 28, 2022, in Shijiazhuang, China. Participants were administered Paxlovid (300 mg of nirmatrelvir and 100 mg of ritonavir orally) or standard treatment. The primary outcome was the nucleic acid shedding time and post-COVID-19 condition.

Results:

A total of 320 patients infected with SARS-CoV-2 Omicron variant were included, with mean age of 29.10 ± 7.34 years old. Two hundred patients received Paxlovid. Compared to patients in the standard treatment group, those in Paxlovid group had a significantly shorter nucleic acid shedding time (3.26 ± 1.80 vs 7.75 ± 3.68 days, P < .001), shorter days until negative swab test (1.74 ± 1.15 vs 5.33 ± 2.91, P < .001), shorter days of first symptoms resolution (4.86 ± 1.62 vs 7.45 ± 2.63, P < .001), higher in nucleic acid test negative rate within 3 days [138 (70.77%) vs 14 (11.67%), P < .001], higher negative rate within 5 days [174 (89.23%) vs 26 (21.67%), P < .001], negative rate within 7 days [185 (94.87%) vs 78 (65.00%), P < .001], and were less likely to have post-COVID-19 condition [32 (18.60%) vs 30 (31.57%), P = .016]. There was no significant difference in duration of post-COVID-19 condition (43.00 ± 26.00 vs 49.00 ± 26.34 days, P = .354) between the 2 groups.

Conclusion:

Compared to standard treatment, Paxlovid significantly reduced nucleic acid shedding time, days until negative swab test, and days of first symptoms resolution, as well as improved nucleic acid test negative rate and post-COVID-19 condition.
An aging-related gene signature to predict the prognosis of hepatocellular carcinoma
Authors: Fang Yanfei , Yang Wenjing , Wu Lexi , Yao Lingya , Cao Xianghan , Chen Haotian
Published: December 2023

Aging increases the susceptibility of various diseases, including hepatocellular carcinoma (HCC). This study aimed to establish an aging-related prognostic model for HCC and to investigate the role of aging-related genes in HCC progression. Transcriptome and clinical information of HCC cases were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Aging-related prognostic genes were identified through univariate Cox regression analysis, protein-protein interaction analysis, and least absolute shrinkage and selection operator (LASSO) analysis. An aging-related risk signature was then constructed, including LDHA, MMP12, ATAD3A, CD8A, TPI1, CST3, and TPM1. The risk score was inversely associated with the overall survival of patients with HCC and correlated well with known prognostic factors. The area under the curve of 1-, 3-, and 5-year survival in the training dataset was 0.83, 0.83, and 0.84, respectively. Univariate and multivariate cox regression analysis verified that the aging-related risk signature independently predicted the overall survival in HCC. To increase the clinical utility of the prognostic model, a nomogram was developed by incorporating the risk score with key clinical features. Finally, single-cell transcriptomes of HCC were analyzed to elucidate the expression pattern of the prognostic genes across different tissues, pathologic stages, and cell types. Collectively, the aging-related prognostic model shed light on HCC pathogenesis and held potential for optimizing the management of HCC.
Clinical characteristics of psychotic disorders in patients with childhood trauma
Authors: Lovric Sanjin , Klaric Miro , Lovric Ivona , Camber Renata , Kresic Coric Martina , Kvesic Josip , Kajic-Selak Anita
Published: December 2023

Childhood trauma is an important predictor of psychotic disorders, with special emphasis on physical and sexual abuse. It influences the clinical picture and course of psychotic disorders. This study was conducted in the Department of Psychiatry of the University Clinical Hospital Mostar. The sample consisted of 135 participants, aged 18 to 65 years. The screening instrument to examine cognitive status was the short version of MMSE-2. Patients’ background information was collected using a sociodemographic questionnaire constructed for this study. To determine childhood trauma, the Child Abuse Experience Inventory was used to examine physical, sexual, and emotional abuse, neglect and domestic violence. The positive and negative syndrome scale scale was used to evaluate the clinical profile of psychoticism, the SSI questionnaire was used to evaluate the severity of suicidality, and the functionality of the participants was evaluated using the WHODAS 2.0. Results indicate that a significant number of participants with psychotic disorders experienced childhood trauma, an important determinant of their illness. Participants who had witnessed abuse had more severe clinical presentations (earlier onset and longer duration of illness) and more pronounced psychotic symptomatology and a lower degree of functionality. Decreased functionality is associated with witnessing abuse and physical abuse. During the civil war, a significant percentage of the participants were in childhood and adolescent development (26.7%) and exposed to frequent emotional abuse and domestic violence. As 1 traumatic event in childhood makes a person more susceptible to more traumatic experiences during life. Childhood trauma is a serious and pervasive problem that has a significant impact on the development, course, and severity of the clinical presentation of psychotic disorders. Accordingly, it is necessary to provide continuous education to mental health workers, primarily psychiatrists, regarding childhood trauma so that treatment may be approached more systematically and a plan of therapeutic interventions may be more adequately designed, which would necessarily include psychosocial support in addition to pharmacotherapy.
Macrocytic anemia induced by selenium deficiency in the course of anorexia nervosa: A case report
Authors: Nishi Ryusei , Sagiyama Kenichiro , Hamada Kazumasa , Fukumoto Takamasa , Kato Ryuichi , Yamamoto Takako , Fuku Yuuki , Amitani Haruka , Asakawa Akihiro
Published: December 2023

Rationale:

Anorexia nervosa is characterized by an extreme fear of weight gain. Clinicians often prescribe meal replacement shakes if patients are unable or unwilling to consume typical foods. However, these shakes sometimes lack essential micronutrients, such as selenium, which may lead to health risks. Moreover, selenium deficiency induces macrocytic anemia. Herein, we present a case of a patient with anorexia nervosa with macrocytic anemia due to selenium deficiency, which was alleviated by selenium supplementation.

Patient concerns:

An 18-year-old female was admitted to our hospital. The patient was diagnosed with anorexia nervosa. Ultimately, she was unable to walk independently because of fatigue and electrolyte disturbances.

Clinical findings:

On admission, the height, weight, and body mass index of the patient were 158.5 cm, 27.1 kg, and 10.8, respectively. Our treatment for anorexia nervosa showed relative effectiveness, and the patient’s body weight recovered to 29.2 kg by day 60. However, the mean corpuscular volume increased from day 20, suggesting macrocytic anemia.

Diagnoses, interventions, and outcomes:

Despite our vitamin B12 and folic acid supplementation interventions, the mean corpuscular volume continued to rise. On day 60, the patient was diagnosed with selenium deficiency, and selenium administration of 100 μg/day was initiated.

Outcomes:

The macrocytic anemia in the patient was alleviated, and treatment for anorexia nervosa was continued in our hospital.

Lessons:

To the best of our knowledge, this is the first case of macrocytic anemia induced by selenium deficiency with anorexia nervosa comorbidity, underscoring the importance of selenium supplementation in patients with anorexia nervosa, especially in those with macrocytic anemia.
Lifestyle factors and psychological factors are associated with central pain processing in service members with persistent low-back pain: A cross-sectional exploratory study
Authors: Prent Julia M. , van der Wurff Peter , Scholten-Peeters Gwendolyne G.M.
Published: December 2023

Persistent low-back pain (LBP) is highly prevalent in the military. Altered central pain processing is one of the mechanisms found to underlie persistent LBP. Our aim was to explore which factors are associated with altered pain processing in Dutch service members with persistent LBP. This knowledge may guide clinicians in what factors to address in the treatment of dysfunctional pain processing in service members with persistent LBP. Twenty-one service members with persistent LBP (mean age 34.0 years, 18 males) were included in this cross-sectional exploratory study. Participants completed questionnaires regarding lifestyle and psychological factors. Altered central pain processing was measured by temporal summation of pain to examine the function of the pain facilitatory system and by conditioned pain modulation to examine the pain inhibitory function. Univariable and multivariable linear regression analyses were performed. A higher local temporal summation of pain was associated with a longer sitting time, a higher level of physical activity and a higher level of pain catastrophizing. A higher local conditioned pain modulation was associated with a higher level of pain catastrophizing, anxiety and depression symptoms, and with a lower sleep quality. A higher remote conditioned pain modulation effect was associated with a higher level of physical activity, a higher body mass index and a shorter sitting time. This study succeeded in identifying lifestyle and psychological factors associated with altered pain processing in service members with persistent LBP. Prospective studies are needed to examine causality in these relationships.
Immunophenotypic p14 and p16 correlations with CDKN2A mutations in primary multiple and familial melanoma: An observational study
Authors: Boşoteanu Luana-Andreea , Gheorghe Emma , Aşchie Mariana , Cozaru Georgeta Camelia , Deacu Mariana , Orășanu Cristian Ionuț , Boşoteanu Mădălina
Published: December 2023

Melanoma represents an aggressive malignant tumor, encapsulating frequent loss of differentiation markers, with familial melanoma constituting a relatively commonly encountered entity, in direct relationship with cyclin-dependent kinase inhibitor 2A (CDKN2A). The present study aims to identify the association between the immunohistochemical p14–p16 profile, the molecular CDKN2A findings and clinically diagnosed familial or multiple primary melanomas (MPM). We conducted a 5-year retrospective cross-sectional study, on patients diagnosed with familial or MPM. P14 and p16 immunohistochemical staining has been applied on the selected surgical specimens simultaneously with the performance of fluorescence in situ hybridization (FISH) CDKN2A testing. 13 out of the 23 included cases displayed p14 and/or p16 immunohistochemical absence and the main positive relationships were encountered between CDKN2A homozygous deletion and p14 ± p16 negative immunoreactions. Cases with exclusive p16 absent reaction (n = 7) were more frequently associated with the presence of distant metastases (85.71%), while samples with exclusive p14 immunohistochemical loss exhibited more favorable histopathological prognostic markers. The average percentage of p16-stained nuclei in the superficial dermis and the deep dermis were equal (29.54% for each), therefore infirming its potential predictive and/or prognostic utility. The present study is the first of its type to approach the clinical, evolutionary and immunophenotypic correlations between p14–p16 immunohistochemical testing, CDKN2A molecular biology pattern, familial melanoma and spontaneous MPM in a cohort of Romanian patients. This analysis highlighted the value of singular p16 immunohistochemical absence as a predictor for aggressive biological behavior and unfavorable prognosis in familial melanoma and/or MPM, in comparison with the exclusive loss of p14, indifferent to the histopathological subtype. The present study emphasizes the utility of immunohistochemistry as a less expensive method of complementing the current testing arsenal and could represent the starting point for the elaboration of tailored diagnostic and therapeutic algorithms, based on the discovered p14–p16-CDKN2A significant correlation.
Verbal workplace violence in the health sector in Saudi Arabia: A cross-sectional study
Authors: Alsaqat Reem Tarik , Alhassan Aseel Khaled , Al Sweleh Fahad Saleh
Published: December 2023

Psychological abuse, such as verbal abuse, has received less attention than physical violence because of the manifested bodily harm caused by physical violence; however, verbal abuse has the highest percentage of violence worldwide. The consequences of verbal abuse in Saudi Arabia are similar to those in other countries. This study aims to determine the prevalence of verbal workplace violence in 12 months, the circumstances related to the event, and the consequences to both the attacker and the target person at all healthcare providers in the Kingdom of Saudi Arabia. This cross-sectional study included all healthcare providers registered with the Saudi Commission for Health Specialties who had worked for more than one year in the health sector in Saudi Arabia by May 2019. The researchers distributed questionnaires to the participants via email. Descriptive statistics were used to represent the basic properties of the data. Correlations between categorically measured variables were explored using the chi-square test for independence. Overall, 7398 healthcare workers (HCWs) voluntarily participated in the study. Overall, 49.1% encountered verbal abuse. Those who worked in the private sector and in shifts, particularly evening shifts, were significantly exposed to verbal abuse. Furthermore, pharmacists, followed by physicians, had the highest prevalence of workplace violence. Workplace verbal violence is highly prevalent, making it a major concern. Patients and their relatives are mostly the offenders of HCWs. Psychological ordeal, increased overwork, and reduced work capacity are the consequences of verbal abuse. Most victims do not report verbal violence, and this may result in an incorrect estimation of the problem. Therefore, encouragement to report verbal violence and additional research in Saudi Arabia are required.
Prediction of network pharmacology, molecular docking-based strategy, and vitro assays to determine potential pharmacological mechanism of Dioscoreae bulbiferae and Bruceae fructus against laryngocarcinoma
Authors: Wu Zhongbiao , Zhu Zhongyan , Cao Jian , Wu Weikun , Deng Chengcheng , Xie Qiang , Hu Shiping
Published: December 2023

Background:

Based on network pharmacology, molecular docking, and vitro assays, investigate the probable pharmacological mechanism of Dioscoreae bulbiferae and Bruceae fructus in the treatment of laryngocarcinoma.

Methods:

The active components and targets of Dioscoreae bulbiferae and Bruceae fructus were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database. Targets linked with laryngocarcinoma were gathered from the GeneCards, DisGeNET, and DrugBank databases. The String database was utilized to build a protein–protein interaction network of common medication and illness targets, after which the core targets were filtered out. The Metascape database served for gene ontology enrichment and Kyoto encyclopedia of genes and genomes pathway analysis of common targets. AutoDock then performed molecular docking between the essential component and the vital target. To investigate the biological effects of diosbulbin B, we assessed the viability of laryngocarcinoma cells after diosbulbin B therapy using the Mahalanobis Taguchi system technique. Following that, we looked at how diosbulbin B affected colony formation after 14 days of culture of treated cells. Flow cytometry was utilized to detect apoptosis in order to examine the influence of diosbulbin B on laryngocarcinoma cell apoptosis.

Results:

According to a study of the literature, the fundamental components of Dioscoreae bulbiferae and Bruceae fructus in the treatment of laryngocarcinoma include brusatol and diosbulbin B, which may operate on core targets such as cyclin D1, Cyclin Dependent Kinase Inhibitor 1A, and E2F Transcription Factor 1. The significant pathways discovered using Kyoto encyclopedia of genes and genomes enrichment analysis were the phosphoinositide 3-kinase-protein kinase B signaling route, the tumor necrosis factor signaling pathway, and so on. These pathways primarily influence the development and prognosis of laryngeal cancer by controlling cell growth, cell proliferation, angiogenesis, tumorigenesis, and metastasis. The molecular docking studies revealed that the affinity between the heart and crucial targets was robust. The results of vitro assays indicate that diosbulbin B suppressed Hep-2 cell activity in a concentration-dependent manner. Besides, diosbulbin B has powerful antiproliferative properties in Hep-2 cells. Flow cytometry results showed that diosbulbin B promoted laryngocarcinoma cell apoptosis in a concentration-dependent manner.

Conclusion:

The article delivered a preliminary discussion of the probable mechanism of Dioscoreae bulbiferae and Bruceae fructus in the treatment of laryngocarcinoma, which can serve as a theoretical basis and evidence for subsequent experimental investigation.
Evaluation of patients diagnosed with congenital hypothyroidism by newborn screening between 2011–2019 in Diyarbakir, Turkey
Authors: Toktaş İzzettin , Erdem Özgür , Saribaş Seyfettin , Özbek Mehmet Nuri
Published: December 2023

This study aimed to determine the incidence of congenital hypothyroidism in Turkey’s Diyarbakir Province and assess the development and growth conditions of people with congenital hypothyroidism. Patients born between 2011-2019 and diagnosed with congenital hypothyroidism within the scope of the newborn screening program were included. The medical records of these patients were retrospectively reviewed. The length and weight for age, weight for length, and body mass index standard deviation scores were calculated. We investigated the treatment status of the patients, whether their relatives had a similar disorder, and the presence of consanguinity between parents. Blood samples were collected from 380,592 newborns. As a result of further tests, 498 newborns were diagnosed with congenital hypothyroidism (incidence: 1/764). Demographic and anthropometric data of 241 patients were analyzed. The patients comprised 46.9% (n = 113) females and 53.1% (n = 128) males. It was determined that 44.4% of the individuals had transient congenital hypothyroidism and 53.6% had permanent congenital hypothyroidism. The parents of 29.8% of the individuals diagnosed with transient congenital hypothyroidism and 44.2% of the individuals diagnosed with permanent congenital hypothyroidism were consanguineous (P = .02). According to the latest anthropometric assessment, 6.8% of individuals diagnosed with congenital hypothyroidism had a weight z-score below −2 SD and 16.9% had a length z-score below −2 SD. The incidence of congenital hypothyroidism was higher in our region. The ratio of consanguinity between parents was higher in patients diagnosed with permanent congenital hypothyroidism than in those diagnosed with transient congenital hypothyroidism. According to the most recent follow-up, weight and age were found to be similar in patients with transient and permanent congenital hypothyroidism.
Does SARS-CoV-2 infection cause persistent ocular symptoms?: A cross-sectional study after the lifting of lockdown in Chongqing, China
Authors: Li Ruili , Zhang Jing , Zhang Yong , Wang Lihua , Qi Xiaoya , Chen Yao
Published: December 2023

To confirm whether ocular symptoms and complaints related to the COVID-19 infection persist after recovery. A cross-sectional study was conducted on people who came to the healthcare center for regular physical examinations when the lockdown lifted for nearly 1 month. Ophthalmologists performed comprehensive ocular examinations. The infection history of COVID-19 was identified by a self-reported reverse transcription-PCR (RT-PCR) test of a nasopharyngeal swab sample for SARS-CoV-2 or a novel coronavirus antigen test with self-reported typical infection symptoms. Demographic data was collected from their healthcare reports. Ocular history and ocular symptoms were collected through face-to-face interviewing. Of a total of 308 participants, 264 (85.7%) reported COVID-19 infection; 73 (27.65%) of infected persons complained of various ocular symptoms during or after infection; and only 15 (5.68%) persons reported ocular symptoms after recovery. Infection significantly increased the complaints of red eye and eye pain compared to the time before knockdown. There were no significant differences between infections and noninfectious infections in various ocular examinations at the time of examination. The duration between the day of infection onset and examination day was unrelated to all ocular examinations. COVID-19 infection can lead to some ocular symptoms, especially conjunctival congestion and ocular pain in the infective stage, but may not cause persistent ocular symptoms in about 1 month after recovery. The results of this study may help relieve public concerns about coronavirus infection in the eyes. However, more studies on various coronavirus infections, with large sample sizes, are warranted in multi-center and community-based populations.
Increased Incidence of TdT-negative Pre-B Acute Lymphoblastic Leukemia Associated With Poor Prognostic Features Among Mexican Children in Central Mexico
Authors: Vacek Meagan , Zárraga Vargas Laura C. , González Domínguez Elizabeth , Garcia Rodriguez Lilia , Tello Teran Omar A. , Mojica Cardoso Carlos , Ocampo Roosens Luisa V. , Acevedo Fernandez Juan J. , Li Weijie , Lee Brian , Olalla Tapia Jesús S. , Flatt Terrie
Published: December 2023

Mexican and Hispanic children in Mexico and the United States, respectively, have the highest incidence and worst outcomes of pre-B acute lymphoblastic leukemia (ALL) compared with other racial/ethnic groups. Terminal deoxynucleotidyl transferase (TdT) is an intranuclear DNA polymerase normally present on immature lymphocytes (TdT-positive) and distinguishes ALL from mature lymphoid malignancies. We performed a multisite retrospective study to determine the incidence of TdT-negative precursor B-cell acute lymphoblastic leukemia (pre-B ALL) among Mexican, Caucasian, and US-born Hispanic children to correlate TdT expression with patient characteristics and known prognostic factors. Fisher exact test was performed for categorical variables and the Wilcoxon rank-sum test was used for continuous variables. TdT-negative pre-B ALL was most frequently identified in patients with National Cancer Institute high-risk disease (P=0.014). TdT-negative expression was also most frequently associated with hypodiploid pre-B ALL (P=0.001) and KMT2A gene rearrangement (P=0.0012). Mexican children had the highest incidence of TdT-negative ALL compared with Caucasians and US Hispanics (P<0.001), with an increased incidence of poor prognostic features as well. This study demonstrates significant differences in TdT-negative expression, genomic alterations, and leukemic ploidy based on race and ethnicity.
Effectiveness of PrEPTECH: Findings From a 180-Day Randomized Controlled Trial of a Pre-Exposure Prophylaxis Telehealth Intervention
Authors: Erenrich Rebecca K. , Braun Rebecca A. , Torres-Mendoza David M. , Stevenson Olivia L. , Doan Thuan-Huong P. , Klausner Jeffrey D.
Published: December 2023

Background:

Telehealth approaches are increasingly being used to provide access to pre-exposure prophylaxis (PrEP), an effective but underused HIV prevention modality. This randomized controlled trial of PrEPTECH, a telehealth intervention for the provision of HIV PrEP, seeks to assess its effects on PrEP access.

Methods:

Young men who have sex with men and transgender women in Florida and California with an indication for PrEP were randomly assigned in a 1:1 allocation to receive access to PrEPTECH or a control condition, access to an online listing of PrEP resources in their communities. This intent-to-treat analysis used logistic and linear regression to compare self-reported PrEP initiation, use, and coverage between control and intervention arm participants at 90 days and 180 days of follow-up.

Results:

A total of 229 participants with a mean age of 23.7 years, 77.3% people of color enrolled in PrEPTECH. At 90 days, postbaseline initiation of PrEP was significantly higher among those in the PrEPTECH arm than among controls (odds ratio [OR]: 6.63, 95% confidence interval [CI]: 2.54 to 17.35), and this held true by 180 days post baseline. The count of sex acts for which participants were not protected by PrEP, PrEP adherence, and recent PrEP use at 180 days post baseline were not significantly different between the study arms.

Conclusions:

Receiving access to a telehealth platform for PrEP access increased PrEP initiation in this cohort of young, predominantly non-White sexual and gender minorities. PrEP telehealth may be a worthy avenue for providing access to PrEP for these populations, but additional strategies may be needed to promote adherence and persistence of PrEP use.
Diagnosis and Severity Assessment of COPD using a Novel Fast-Response Capnometer And Interpretable Machine Learning
Authors: Talker Leeran , Dogan Cihan , Neville Daniel , Lim Rui Hen , Broomfield Henry , Lambert Gabriel , Selim Ahmed B , Brown Thomas , Wiffen Laura , Carter Julian C , Ashdown Helen F , Hayward Gail , Vijaykumar Elango , Weiss Scott T , Chauhan Anoop , Patel Ameera X
Published: December 2023

Introduction

Spirometry is the gold standard for COPD diagnosis and severity determination, but is technique-dependent, non-specific, and requires administration by a trained healthcare professional. There is a need for a fast, reliable, and precise alternative diagnostic test. This study’s aim was to use interpretable machine learning to diagnose COPD and assess severity using 75-second carbon dioxide (CO2) breath records captured with TidalSense’s N-Tidal™capnometer.

Methods

For COPD diagnosis, machine learning algorithms were trained and evaluated on 294 COPD (including GOLD stages 1-4) and 705 non-COPD participants. A logistic regression model was also trained to distinguish GOLD 1 from GOLD 4 COPD with the output probability used as an index of severity.

Results

The best diagnostic model achieved an AUROC of 0.890, sensitivity of 0.771, specificity of 0.850 and positive predictive value of 0.834. A potential clinical use for this model is to rule in or rule out a diagnosis in patients where the model is most confident. Performance on test capnograms with probability>80% and<20% was also evaluated, yielding a PPV of 0.930 and NPV of 0.890. The severity determination model yielded an AUROC of 0.980, Sensitivity of 0.958, Specificity of 0.961 and PPV of 0.958 in distinguishing GOLD 1 from GOLD 4. Output probabilities from the severity determination model produced a correlation of 0.71 with percentage predicted FEV1.

Conclusion

The N-Tidal™device could be used alongside interpretable machine learning as an accurate, point-of-care diagnostic test for COPD, particularly in primary care, as a rapid rule-in or rule-out test. N-Tidal™also could be effective in monitoring disease progression, providing a possible alternative to spirometry for disease monitoring.

Trial registration

Please seeNCT03615365,NCT02814253,NCT04504838,NCT03356288andNCT04939558.
Macrophages as Key Mediators of Trp-1-Specific CD4+T Cell Therapy for Murine Melanoma
Authors: He Adam Q. , Zou Dawei , Chen Wenhao
Published: December 2023

There is a growing body of evidence indicating that CD4+T cells, alongside CD8+T cells, can effectively combat cancer. However, the mechanisms underlying the anti-tumor properties of CD4+T cells are complex and not yet fully understood. To investigate these mechanisms, we utilized a murine model of tyrosinase-related protein 1 (Trp1)-specific CD4+T cell adoptive transfer therapy for treating melanoma. By employing single-cell RNA sequencing (scRNA-seq), we analyzed the immune cells present in the tumors of mice that received adoptive transfer of Trp1-specific CD4+T cells. Unexpectedly, within the tumor-infiltrating immune cells, the Trp1 CD4+T cell population was relatively small, displaying characteristics indicative of exhaustion. In contrast, the most prominent cell cluster comprised macrophages, expressing high levels of the T cell inhibitory receptor ligand PD-L1 and the pro-inflammatory cytokine IL-1β, suggesting a distinct M1 phenotype. Systemic depletion of macrophages following Trp1 CD4+T cell transfer therapy compromised the antitumor effectiveness and resulted in tumor recurrence. These findings highlight the crucial role of innate macrophages as an effector cell population in Trp1-specific CD4+T cell adoptive cell transfer therapy.
Translational mapping of spatially resolved transcriptomes in human and mouse pulmonary fibrosis
Authors: Franzén Lovisa , Lindvall Martina Olsson , Hühn Michael , Ptasinski Victoria , Setyo Laura , Keith Benjamin , Collin Astrid , Oag Steven , Volckaert Thomas , Borde Annika , Lundeberg Joakim , Lindgren Julia , Belfield Graham , Jackson Sonya , Ollerstam Anna , Stamou Marianna , Ståhl Patrik L , Hornberg Jorrit J
Published: December 2023

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis and limited treatment options. Efforts to identify effective treatments are thwarted by limited understanding of IPF pathogenesis and poor translatability of available preclinical models. To address these limitations, we generated spatially resolved transcriptome maps of human IPF and bleomycin-induced mouse lung fibrosis. We uncovered distinct fibrotic niches in the IPF lung, characterized by aberrant alveolar epithelial cells in a microenvironment dominated by TGFβ signaling alongside factors such as p53 and ApoE. We also identified a clear divergence between the arrested alveolar regeneration in the IPF fibrotic niches, and the active tissue repair in the acutely fibrotic mouse lung. Our study offers in-depth insights into the IPF transcriptional landscape and proposes alveolar regeneration as a promising therapeutic strategy for IPF.
“Non-viral CRISPR/Cas9 Mutagenesis for Streamlined Generation of Mouse Lung Cancer Models.”
Authors: Lara-Saez Irene , Mencia Angeles , Recuero Enrique , Li Yinghao , García Marta , Oteo Marta , Gallego Marta I , Enguita Ana Belen , de Prado-Verdún Diana , Sigen A , Wang Wenxin , García-Escudero Ramón , Murillas Rodolfo , Santos Mirentxu
Published: December 2023

Functional analysis in mouse models is necessary to establish the involvement of a set of genetic variations in tumor development. Many lung cancer models have been developed using genetic techniques to create gain- or loss-of-function alleles in genes involved in tumorigenesis; however, because of their labor- and time-intensive nature, these models are not suitable for quick and flexible hypothesis testing. Here we introduce a lung mutagenesis platform that utilizes CRISPR/Cas9 RNPs delivered via cationic polymers. This approach allows for the simultaneous inactivation of multiple genes. We validate the effectiveness of this system by targeting a group of tumor suppressor genes, specificallyRb1,Rbl1,Pten, andTrp53, which were chosen for their potential to cause lung tumors, namely Small Cell Lung Carcinoma (SCLC). This polymer-based delivery platform enables the modeling of lung tumorigenesis independently of the genetic background, thus simplifying and expediting the process without the need for modifying the mouse germline or creating custom viral vectors.

Significance

The development of models to rapidly introduce gene mutations into lung tissue to study their impact on tumor growth is critical for advancing the functional genomics of lung cancer. While previous methods using viral vectors and genetic manipulation in mice have been time-consuming and expensive, here we describe a new technique using cationic polymers as non-viral carriers for CRISPR/Cas9 delivery to induce cancer driving mutations that streamlines this process. This approach mimics natural mutations in lung cancer and accelerates the generation of accurate tumor models. Our study demonstrates the effectiveness of this method in generating small cell lung cancer (SCLC) by modifying four tumor suppressor genes in different mouse genetic backgrounds. This innovative strategy holds promise for faster and more cost-effective cancer modeling.

Graphical Abstrac

Small Cell Lung Cancer(SCLC) tumors are rapidly generated in any mouse genetic background by using cationic polymers to simultaneously deliver Cas9 and gRNAs targeting theRb1,Rbl1,PtenandTrp53tumor-suppressor genes to the adult airway respiratory systemin vivo. Addition of the frt guide in the RC::FLTG mice provides a tdTomato gene editing reporter. This study shows the feasibility of rapidly generating lung cancer mouse models via somatic genome engineering through delivery of all CRISPR components in the form of nanoparticles.
SMC motor proteins extrude DNA asymmetrically and contain a direction switch
Authors: Barth Roman , Davidson Iain F. , van der Torre Jaco , Taschner Michael , Gruber Stephan , Peters Jan-Michael , Dekker Cees
Published: December 2023

Structural Maintenance of Chromosomes (SMC) complexes organize the genomeviaDNA loop extrusion. While some SMCs were reported to do so symmetrically, reeling DNA from both sides into the extruded DNA loop simultaneously, others perform loop extrusion asymmetrically toward one direction only. The mechanism underlying this variability remains unclear. Here, we examine the directionality of DNA loop extrusion by SMCs usingin vitrosingle-molecule experiments. We find that cohesin and SMC5/6 do not reel in DNA from both sides, as reported before, but instead extrude DNA asymmetrically, while the direction can switch over time. Asymmetric DNA loop extrusion thus is the shared mechanism across all eukaryotic SMC complexes. For cohesin, direction switches strongly correlate with the turnover of the subunit NIPBL, during which DNA strand switching may occur. STAG1 stabilizes NIPBL on cohesin, preventing NIPBL turnover and direction switches. The findings reveal that SMCs, surprisingly, contain a direction switch subunit.

Highlights

All eukaryotic SMC complexes extrude DNA asymmetrically.

Apparent ‘symmetric’ loop extrusion is the result of frequent direction switches.

n human cohesin, loop-extrusion direction changes require exchange of NIPBL.

STAG1 stabilizes NIPBL on human cohesin.
POMFinder: identifying polyoxometallate cluster structures from pair distribution function data using explainable machine learning
Authors: Anker Andy S. , Kjær Emil T. S. , Juelsholt Mikkel , Jensen Kirsten M. Ø.
Published: December 2023

Characterization of a material structure with pair distribution function (PDF) analysis typically involves refining a structure model against an experimental data set, but finding or constructing a suitable atomic model for PDF modelling can be an extremely labour-intensive task, requiring carefully browsing through large numbers of possible models. Presented here is POMFinder, a machine learning (ML) classifier that rapidly screens a database of structures, here polyoxometallate (POM) clusters, to identify candidate structures for PDF data modelling. The approach is shown to identify suitable POMs from experimental data, including in situ data collected with fast acquisition times. This automated approach has significant potential for identifying suitable models for structure refinement to extract quantitative structural parameters in materials chemistry research. POMFinder is open source and user friendly, making it accessible to those without prior ML knowledge. It is also demonstrated that POMFinder offers a promising modelling framework for combined modelling of multiple scattering techniques.
The perceived authenticity in food among sociological generations: the case of cheeses in Mexico
Authors: Fernández-Sánchez Héctor Yair , Espinoza-Ortega Angélica , Sánchez-Vega Laura Patricia , Moctezuma Pérez Sergio , Cervantes-Escoto Fernando
Published: December 2023

Purpose

The study aims to identify the perceived authenticity of cheeses by consumers of different sociological generations in Mexico.

Design/methodology/approach

An online questionnaire was applied to 1,204 consumers. A Free Word Association (FWA) tool was used to determine the perceived authenticity of cheeses creating categories and dimensions. The sample was segmented into sociological generations. A chi-square test and a correspondence analysis were used to identify differences in the perception between generations. The information was complemented with word clouds of the cheeses mentioned and consumer testimonials about cheese consumption.

Findings

A total of 29 categories and ten dimensions revealed consumers' perception of cheese authenticity, most important of which were hedonic, rurality and new consumption. Authenticity is a mix of the pleasure of consuming the product, the link to rural life and new consumer values. Perceived authenticity is different in each sociological generation according to the dimensions of raw material, identity, market, new consumption and distrust, since it is related to the experiences of each generation. The results made it possible to contextualise another vision of the reality of the cheeses in the search for a quality seal.

Practical implications

The information contributes to the typification and promotion of cheeses in the process of patrimonialisation, by creating differentiated marketing tools that allow their valorisation.

Originality/value

This work contributes to the knowledge of the perceived authenticity of cheeses in the sociological generations, due to their differentiation by age, sociocultural, ethical, political and consumer aspects. It enables the knowledge of the consumer's perspective on these products.
Integrated optimization of facility location, casualty allocation and medical staff planning for post-disaster emergency response
Authors: Oksuz Mehmet Kursat , Satoglu Sule Itir
Published: December 2023

Purpose

Disaster management and humanitarian logistics (HT) play crucial roles in large-scale events such as earthquakes, floods, hurricanes and tsunamis. Well-organized disaster response is crucial for effectively managing medical centres, staff allocation and casualty distribution during emergencies. To address this issue, this study aims to introduce a multi-objective stochastic programming model to enhance disaster preparedness and response, focusing on the critical first 72 h after earthquakes. The purpose is to optimize the allocation of resources, temporary medical centres and medical staff to save lives effectively.

Design/methodology/approach

This study uses stochastic programming-based dynamic modelling and a discrete-time Markov Chain to address uncertainty. The model considers potential road and hospital damage and distance limits and introduces an a-reliability level for untreated casualties. It divides the initial 72 h into four periods to capture earthquake dynamics.

Findings

Using a real case study in Istanbul’s Kartal district, the model’s effectiveness is demonstrated for earthquake scenarios. Key insights include optimal medical centre locations, required capacities, necessary medical staff and casualty allocation strategies, all vital for efficient disaster response within the critical first 72 h.

Originality/value

This study innovates by integrating stochastic programming and dynamic modelling to tackle post-disaster medical response. The use of a Markov Chain for uncertain health conditions and focus on the immediate aftermath of earthquakes offer practical value. By optimizing resource allocation amid uncertainties, the study contributes significantly to disaster management and HT research.
Is mandatory disclosure an effective panacea for buyer beware?
Authors: Waye Vicki Catherine , Snowden Collette , Knowler Jane , Zito Paula , Burton Jack , McIntyre Joe
Published: December 2023

Purpose

The purpose of this paper is to examine whether mandatory disclosure of information accompanying the sale of real estate achieves its aim of informed purchasers.

Design/methodology/approach

Using a case study approach focused on mandatory disclosure in South Australia data was collected from interviews and focus groups with key personnel in the property industry involved in the production of information required to fulfil vendors’ disclosure obligations.

Findings

The authors found that purchasers are ill-served by a long and complex form of mandatory disclosure with a short time frame that prevents the use of the information provided. Without good form design and increased digital affordances provided by the cadastral and conveyancing systems, mandatory disclosure is insufficient to ensure minimisation of information asymmetry between vendor and purchaser.

Originality/value

To the best of the authors’ knowledge, this is the first Australian qualitative study that examines the utility of mandatory vendor disclosure in real estate sales and the first to consider the impact of the digitalisation of cadastral and conveyancing systems upon the efficacy of mandatory disclosure regimes.
Utilization of recycled coarse aggregate and high volume of GGBS in self-compacting concrete – an experimental study
Authors: M. Manjunatha , T.S. Kavitha
Published: December 2023

Purpose

The purpose of this study is to investigate the behaviour of M40 grade of self-compacting concrete (SCC) with high volume of ground granulated blast furnace slag (GGBS) (50%) and recycled concrete aggregate (RCA) content up to 100% to assess the mechanical properties of SCC. As per guidelines of IS: 383 – 2016, the RCA can be replaced up to 20% of natural coarse aggregate up to M25 grade of concrete. This study assesses the mechanical properties of SCC beyond 20% of RCA content. Based on the experimental investigations, the compressive strength of mixes decreases as the content of RCA increases. It is found that concrete mixes with 20% RCA and shows the maximum compressive strength at 56 days.

Design/methodology/approach

The fresh properties as per EFNARC and IS: 10262–2019 guidelines, ultrasonic pulse velocity testing, mechanical properties and microstructure analysis have been conducted to evaluate the performance of SCC with RCA for practical applications.

Findings

From the experimental investigations, it is found that up to 50% of recycled coarse aggregate can be used for structural applications.

Originality/value

The environmental pollution and dumping of waste on green land can be reduced by effective utilization of recycled coarse aggregate and GGBS in the production of SCC.
Exploring participatory health research and its application to speech and language therapy research practices
Authors: Connery Amy , Salsberg Jon
Published: December 2023

Background

The role of participatory health research (PHR) is increasingly acknowledged by funding bodies, researchers and civil society globally; however, it continues to be under‐represented in the speech and language therapy (SLT) research literature. This collaborative research approach is associated with the increased application of research evidence, and the generation of positive impacts in practice, policy, health systems and society.

Aims

To increase researchers’ and other participatory partners’ understanding of PHR, and to demonstrate its applicability to research in the SLT field.

Methods & Procedures

This aim is achieved through a discussion on PHR, its principles, benefits and challenges, and the evaluation of its impact. A recently developed evaluation framework to support the implementation of best engagement practices is examined, and recommendations for how this framework can be used to plan and evaluate engagement in participatory stuttering research is presented.

Main contribution

This paper serves as an important conversation on the value of PHR to SLT research, and presents guidance to support its increased implementation in this research field.

Conclusions & Implications

Conclusions & Implications: PHR remains an under‐represented research approach in the SLT literature, despite increasing evidence demonstrating its effectiveness and value. It offers a potential solution to the research–practice gap, and challenges the ongoing research hierarchies by democrating the process of knowledge production.

WHAT THIS PAPER ADDS

What is already known on this subject

PHR is increasingly attracting the attention of funders, researchers and decision‐makers due to a growing body of evidence in support of this collaborative research approach. Despite its potential to bridge the research–practice gap, PHR remains significantly under‐represented in the SLT research literature.

What this paper adds to the existing knowledge

This paper discusses the principles, benefits, challenges and impact evaluation of PHR. A recently developed evaluation framework for supporting the implementation of best engagement practices is examined. A demonstration of how this framework can be used to plan and evaluate engagement in participatory stuttering research is presented.

What are the potential or actual clinical implications of this work?

Speech and language therapists play a key role in PHR, as co‐researchers contributing essential context‐based knowledge. It is therefore imperative that they understand the principles and practices of this approach in order to maximize their input in future participatory partnerships.
Addressing the rising trend of high‐risk pulmonary embolism mortality: Clinical and research priorities
Authors: Casey Scott D. , Stubblefield William B. , Luijten Dieuwke , Klok Frederikus A. , Westafer Lauren M. , Vinson David R. , Kabrhel Christopher
Published: December 2023

Background

Deaths from high‐risk pulmonary embolism (PE) appear to have increased in the US over the last decade. Modifiable risks contributing to this worrisome trend present opportunities for physicians, researchers, and healthcare policymakers to improve care.

Methods

We sought to contextualize contemporary, high‐risk PE epidemiology and examine clinical trials, quality improvement opportunities, and healthcare policy initiatives directed at reducing mortality.

Results

We observed significant and modifiable excess mortality due to high‐risk PE. We identified several opportunities to improve care including: (1) rapid translation of forthcoming data on reperfusion strategies into clinical practice; (2) improved risk stratification tools; (3) quality improvement initiatives to address presumptive anticoagulation practice gaps; and (3) adoption of health policy initiatives to establish pulmonary embolism response teams and address the social determinants of health.

Conclusion

Addressing knowledge and practice gaps in intermediate and high‐risk PE management must be prioritized and informed by forthcoming high‐quality data. Implementation efforts are needed to improve acute PE management and resolve treatment disparities.