bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent CD8+ T cell proliferation and activation in COVID-19 adult survivors with post-acute sequelae: a longitudinal, observational cohort study of persistent symptoms and T cell markers
Authors: LaVergne Stephanie M. , Dutt Taru S. , McFann Kim , Baxter Bridget A. , Webb Tracy L. , Berry Kailey , Tipton Maddy , Stromberg Sophia , Sullivan Brian M. , Dunn Julie , Henao-Tamayo Marcela , Ryan Elizabeth P.
Published: January 2024

Introduction

Post-acute sequelae of COVID-19 affects the quality of life of many COVID-19 survivors, yet the etiology of post-acute sequelae of COVID-19 remains unknown. We aimed to determine if persistent inflammation and ongoing T-cell activation during convalescence were a contributing factor to the pathogenesis of post-acute sequelae of COVID-19.

Methods

We evaluated 67 individuals diagnosed with COVID-19 by nasopharyngeal polymerase chain reaction for persistent symptoms during convalescence at separate time points occurring up to 180 days post-diagnosis. Fifty-two of these individuals were evaluated longitudinally. We obtained whole blood samples at each study visit, isolated peripheral blood mononuclear cells, and stained for multiple T cell activation markers for flow cytometry analysis. The activation states of participants’ CD4+ and CD8+ T-cells were next analyzed for each of the persistent symptoms.

Results

Overall, we found that participants with persistent symptoms had significantly higher levels of inflammation at multiple time points during convalescence when compared to those who fully recovered from COVID-19. Participants with persistent dyspnea, forgetfulness, confusion, and chest pain had significantly higher levels of proliferating effector T-cells (CD8+Ki67+), and those with chest pain, joint pain, difficulty concentrating, and forgetfulness had higher levels of regulatory T-cells (CD4+CD25+). Additionally, those with dyspnea had significantly higher levels of CD8+CD38+, CD8+ Granzyme B+, and CD8+IL10+ cells. A retrospective comparison of acute phase inflammatory markers in adults with and without post-acute sequelae of COVID-19 showed that CD8+Ki67+ cells were significantly higher at the time of acute illness (up to 14 days post-diagnosis) in those who developed persistent dyspnea.

Discussion

These findings suggest continued CD8+ T-cell activation following SARS-CoV-2 infection in adults experiencing post-acute sequelae of COVID-19 and that the increase in T regulatory cells for a subset of these patients represents the ongoing attempt by the host to reduce inflammation.
A novel CpG ODN compound adjuvant enhances immune response to spike subunit vaccines of porcine epidemic diarrhea virus
Authors: Wang Yating , Liu Shijia , Li Boshuo , Sun Xinyao , Pan Qi , Zheng Yuxin , Liu Jia , Zhao Yongqiang , Wang Jingyu , Liu Liming , Du Enqi
Published: January 2024

CpG oligodeoxynucleotides (CpG ODNs) boost the humoral and cellular immune responses to antigens through interaction with Toll-like receptor 9 (TLR9). These CpG ODNs have been extensively utilized in human vaccines. In our study, we evaluated five B-type CpG ODNs that have stimulatory effects on pigs by measuring the proliferation of porcine peripheral blood mononuclear cells (PBMCs) and assessing interferon gamma (IFN-γ) secretion. Furthermore, this study examined the immunoenhancing effects of the MF59 and CpG ODNs compound adjuvant in mouse and piglet models of porcine epidemic diarrhea virus (PEDV) subunit vaccine administration. The in vitro screening revealed that the CpG ODN named CpG5 significantly stimulated the proliferation of porcine PBMCs and elevated IFN-γ secretion levels. In the mouse vaccination model, CpG5 compound adjuvant significantly bolstered the humoral and cellular immune responses to the PEDV subunit vaccines, leading to Th1 immune responses characterized by increased IFN-γ and IgG2a levels. In piglets, the neutralizing antibody titer was significantly enhanced with CpG5 compound adjuvant, alongside a considerable increase in CD8+ T lymphocytes proportion. The combination of MF59 adjuvant and CpG5 exhibits a synergistic effect, resulting in an earlier, more intense, and long-lasting immune response in subunit vaccines for PEDV. This combination holds significant promise as a robust candidate for the development of vaccine adjuvant.
Predictors and perinatal outcomes of pre-labor rupture of membrane among pregnant women admitted to Hiwot Fana Comprehensive Specialized University Hospital, Eastern Ethiopia: a retrospective study
Authors: Wolde Meseret , Mulatu Teshale , Alemayehu Gemechu , Alemayehu Afework , Assefa Nega
Published: January 2024

Background

Pre-labor rupture of membrane (PROM) refers to a membrane rupture that occurs after the 28th week of pregnancy but before the start of labor. If not appropriately managed, it poses a significant risk to the health of the mother and fetus. However, information on the magnitude of PROM, contributing factors, and its perinatal outcomes was limited in Eastern Ethiopia. This study assessed the prevalence, predictors, and perinatal outcomes of PROM among pregnant women admitted to Hiwot Fana Comprehensive Specialized University Hospital (HFCSUH) in Eastern Ethiopia so as to guide specific preventive measures.

Methods

A hospital-based retrospective cross-sectional study was carried out from May 15 to June 14, 2022, and data were gathered by reviewing the chart records of 424 pregnant women who were admitted to maternity and labor wards in the previous two years, from January 1, 2019 to December 31, 2020. Records were chosen using a simple random sampling method. Mother’s socio-demographic traits, previous obstetric and gynecologic history, current pregnancy history, habit-related history (khat chewing), ultrasound findings, laboratory investigations, mode of delivery, maternal and perinatal outcomes were extracted from the maternal charts. Bi-variable and multivariable logistic regression analyses were performed to identify predictors of pre-labor membrane rupture. The association between the explanatory and outcome variables was expressed using an adjusted odds ratio with a 95% confidence interval.

Results

The prevalence of pre-labor membrane rupture was 16.27% with 95% CI: (13.05–20.11). Among 69 women who experienced pre-labor rupture of membrane, 50 (72.5%) of them had adverse perinatal outcomes. Of all 69 neonates 17 (24.64%) were delivered with low birth weight and 20 (29%) of them were born preterm. The overall perinatal mortality rate was 10.1% or 101 per 1,000 live births. History of abortion [AOR = 2.61; 95% CI (1.09, 6.24)], urinary tract infection [AOR = 2.59; 95% CI (1.23, 5.42)], antepartum hemorrhage [AOR = 3.35; 95% CI (1.38, 8.13)], and khat chewing (a leafy plant which contains psychoactive chemical) in the current pregnancy [AOR = 2.63; 95% CI (1.49, 4.63)] were all significantly associated with pre-labor rupture of membrane.

Conclusion

In this study, the magnitude of pre-labor membrane rupture was relatively high compared to the global rate. Prenatal risk identification and early detection of complications among mothers with a history of abortion, antepartum hemorrhage, urinary tract infection, and counseling on the effects of khat chewing during pregnancy are crucial to reduce the likelihood of pre-labor membrane rupture and its adverse perinatal outcome.
The use of nanoparticles in the treatment of infectious diseases and cancer, dental applications and tissue regeneration: a review
Authors: Sobhani-Nasab Ali , Banafshe Hamid Reza , Atapour Amir , Khaksary Mahabady Mahmood , Akbari Maryam , Daraei Abdolreza , Mansoori Yaser , Moradi Hasan-Abad Amin
Published: January 2024

The emergence of nanotechnology as a field of study can be traced back to the 1980s, at which point the means to artificially produce, control, and observe matter on a nanometer level was made viable. Recent advancements in technology have enabled us to extend our reach to the nanoscale, which has presented an unparalleled opportunity to directly target biomolecular interactions. As a result of these developments, there is a drive to arise intelligent nanostructures capable of overcoming the obstacles that have impeded the progress of conventional pharmacological methodologies. After four decades, the gradual amalgamation of bio- and nanotechnologies is initiating a revolution in the realm of disease detection, treatment, and monitoring, as well as unsolved medical predicaments. Although a significant portion of research in the field is still confined to laboratories, the initial application of nanotechnology as treatments, vaccines, pharmaceuticals, and diagnostic equipment has now obtained endorsement for commercialization and clinical practice. The current issue presents an overview of the latest progress in nanomedical strategies towards alleviating antibiotic resistance, diagnosing and treating cancer, addressing neurodegenerative disorders, and an array of applications, encompassing dentistry and tuberculosis treatment. The current investigation also scrutinizes the deployment of sophisticated smart nanostructured materials in fields of application such as regenerative medicine, as well as the management of targeted and sustained release of pharmaceuticals and therapeutic interventions. The aforementioned concept exhibits the potential for revolutionary advancements within the field of immunotherapy, as it introduces the utilization of implanted vaccine technology to consistently regulate and augment immune functions. Concurrently with the endeavor to attain the advantages of nanomedical intervention, it is essential to enhance the unceasing emphasis on nanotoxicological research and the regulation of nanomedications' safety. This initiative is crucial in achieving the advancement in medicine that currently lies within our reach.
Unraveling the impact of lanthanum on methane consuming microbial communities in rice field soils
Authors: Liu Ruyan , Wei Ziting , Dong Wanying , Wang Rui , Adams Jonathan M. , Yang Lin , Krause Sascha M. B.
Published: January 2024

The discovery of the lanthanide requiring enzymes in microbes was a significant scientific discovery that opened a whole new avenue of biotechnological research of this important group of metals. However, the ecological impact of lanthanides on microbial communities utilizing methane (CH4) remains largely unexplored. In this study, a laboratory microcosm model experiment was performed using rice field soils with different pH origins (5.76, 7.2, and 8.36) and different concentrations of La3+ in the form of lanthanum chloride (LaCl3). Results clearly showed that CH4 consumption was inhibited by the addition of La3+ but that the response depended on the soil origin and pH. 16S rRNA gene sequencing revealed the genus Methylobacter, Methylosarcina, and Methylocystis as key players in CH4 consumption under La3+ addition. We suggest that the soil microbiome involved in CH4 consumption can generally tolerate addition of high concentrations of La3+, and adjustments in community composition ensured ecosystem functionality over time. As La3+ concentrations increase, the way that the soil microbiome reacts may not only differ within the same environment but also vary when comparing different environments, underscoring the need for further research into this subject.
Trans-replicase helper activity of porcine circoviruses promotes the synergistic replication of torque teno virus
Authors: Ssemadaali Marvin , Islam Md-Tariqul , Fang Wenjuan , Aboezz Zeinab , Webb Brett , Ramamoorthy Sheela
Published: January 2024

While the primary pathogenic potential of torque teno viruses (TTVs) is yet to be defined, TTVs are often co-detected with other pathogens and are suspected of exacerbating clinical disease in coinfections. Swine TTVs (TTSuVs) enhance clinical signs of porcine circovirus type 2 (PCV2) in a gnotobiotic pig model. However, the mechanisms involved are unknown. In this study, we observed that co-culture of TTSuV1 and PCV1, and specifically supplementing TTSuV1 cultures with the PCV replicase protein in trans consistently resulted in higher levels of replication of TTSuV1 when compared to TTSuV1 cultured alone. Therefore, the hypothesis that the PCV replicase (rep) protein has trans-replicase helper activity for TTSuV1 was examined. Based on EMSA and reporter gene assays, it was determined that the PCV1 rep directly interacted with the TTSuV1 UTR. The TTSuV1 rep trans-complemented a PCV rep null mutant virus, indicating that the TTSuV1 and PCV1 replicase proteins supported the replication of both viruses. In mice, the administration of plasmids encoding the PCV1 rep and a TTSuV1 infectious clone resulted in the production of higher TTSuV1 genome copies in dually exposed mice when compared to singly exposed mice. Higher sero-conversion and lymphoid hyperplasia were also observed in the dually exposed experimental mice. Thus, this study provides evidence for trans-replicase activity of PCVs and TTVs as a novel mechanism of explaining enhanced viral replication in coinfections involving both viruses.
Development and validation of a prognostic computed tomography scoring model for functional outcomes in patients with large hemispheric infarction following decompressive craniectomy
Authors: Zhao Yutong , Tang Yuguang , Xie Zongyi
Published: January 2024

Background

There is no established prognostic scoring system developed for patients with large hemispheric infarction (LHI) following decompressive craniectomy (DC) based on imaging characteristics. The present study aimed to develop and validate a new computed tomography scoring model to assess the 6-month risk of poor functional outcomes (modified-Rankin scale [mRS] score of 4–6) in patients with LHI receiving DC.

Methods

This retrospective cohort study included patients at two tertiary stroke centers. A prediction model was developed based on a multivariable logistic regression. The final risk factors included the ASPECTS (Alberta Stroke Program Early Computed Tomography Score), longitudinal fissure cistern, Sylvian fissure cistern, and additional vascular territory involvement. 1,000 bootstrap resamples and temporal validation were implemented as validations for the scoring system.

Results

Of the 100 individuals included in the development cohort, 71 had poor functional outcomes. The scoring model presented excellent discrimination and calibration with C-index = 0.87 for the development cohort, and C-index = 0.83 for the temporal validation cohort with non-significant Hosmer-Lemeshow goodness-of-fit test. The scoring model also showed an improved AUC compared to the ASPECTS. For each point in the score model, the adjusted risk of poor functional outcomes increase by 47.8% (OR = 1.48, p < 0.001). The scores were inversely correlated with MAP (mean arterial pressure, paired t-test, p = 0.0015) and CPP (cerebral perfusion pressure, rho = −0.17, p = 0.04).

Conclusion

In patients with LHI following DC, the score system is an excellent predictor of poor functional outcomes and is associated with CPP and MAP, which might be worth considering in clinical settings after further external validation.
Case report: Targeted sequencing facilitates the diagnosis and management of rare multifocal pure ground-glass opacities with intrapulmonary metastasis
Authors: Yang Yingshun , Pei Guotian , Li Mingwei , Ma Xiaoxue , Wang Shuai , Min Xianjun , Meng Shushi , Qin Jiayue , Wang Huina , Liu Jun , Huang Yuqing
Published: January 2024

Introduction

Treatments for multiple ground-glass opacities (GGOs) for which the detection rate is increasing are still controversial. Next-generation sequencing (NGS) may provide additional key evidence for differential diagnosis or optimal therapeutic schedules.

Case presentation

We first reported a rare case in which more than 100 bilateral pulmonary GGOs (91.7% of the GGOs were pure GGOs) were diagnosed as both multiple primary lung cancer and intrapulmonary metastasis. We performed NGS with an 808-gene panel to assess both somatic and germline alterations in tissues and plasma. The patient (male) underwent three successive surgeries and received osimertinib adjuvant therapy due to signs of metastasis and multiple EGFR-mutated tumors. The patient had multiple pure GGOs, and eight tumors of four pathological subtypes were evaluated for the clonal relationship. Metastasis, including pure GGOs and atypical adenomatous hyperplasia, was found between two pairs of tumors. Circulating tumor DNA (ctDNA) monitoring of disease status may impact clinical decision-making.

Conclusions

Surgery combined with targeted therapies remains a reasonable alternative strategy for treating patients with multifocal GGOs, and NGS is valuable for facilitating diagnostic workup and adjuvant therapy with targeted drugs through tissue and disease monitoring via ctDNA.
Quantitative analysis of contrast-enhanced ultrasound in neoadjuvant treatment of locally advanced rectal cancer: a retrospective study
Authors: Bai Gouyang , Wang Congying , Sun Yi , Li Jinghua , Shi Xiangzhou , Zhang Wei , Yang Yilin , Yang Ruijing
Published: January 2024

Purpose

To explore the clinical value of contrast-enhanced ultrasound (CEUS) quantitative analysis in the evaluation and prognosis of neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC).

Methods

Eighty-three consecutive patients undergoing neoadjuvant chemoradiotherapy and total mesorectal excision for LARC were retrospectively included. According to pathological results, patients were categorized into complete or incomplete response groups. Differences in ultrasonic parameters, pathological results, and clinical data between groups were evaluated. The cutoff point for a complete response as determined by quantitative analysis of CEUS was assessed using a receiver operating characteristic curve; additionally, overall survival (OS) and progression-free survival (PFS) were analyzed.

Results

Of the 83 patients, 12 (14.5%) achieved a complete response and 71 (85.5%) did not. There were significant between-group differences in carcinoembryonic antigen (CEA) levels, differentiation degree, proportion of tumor occupying the lumen, anterior-posterior and superior-inferior diameters of the lesion, and intensity of enhancement (P<0.05). CEUS quantitative analysis showed significant between-group differences in peak intensity (PI) and area under the curve (AUC) values (P<0.05). The OS and PFS of patients with high PI, high AUC value, and poorly differentiated cancer were significantly worse than those with low PI, low AUC values, and moderately to highly differentiated cancer (P<0.05). High CEA levels (hazard ratio: 1.02, 95% confidence interval: 1.01–1.04; P=0.002) and low differentiation (2.72, 1.12–6.62; P=0.028) were independent risk factors for PFS and OS.

Conclusions

CEUS can predict the response to neoadjuvant treatment in patients with LARC. CEUS quantitative analysis is helpful for clinical prognosis.
Stromal area differences with epithelial-mesenchymal transition gene changes in conjunctival and orbital mucosa-associated lymphoid tissue lymphoma
Authors: Tagami Mizuki , Kasashima Hiroaki , Kakehashi Anna , Yoshikawa Atsuko , Nishio Mizuho , Misawa Norihiko , Sakai Atsushi , Wanibuchi Hideki , Yashiro Masakazu , Azumi Atsushi , Honda Shigeru
Published: January 2024

Purpose

To examine the molecular biological differences between conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma and orbital MALT lymphoma in ocular adnexa lymphoma.

Methods

Observational case series. A total of 129 consecutive, randomized cases of ocular adnexa MALT lymphoma diagnosed histopathologically between 2008 and 2020.Total RNA was extracted from formalin-fixed paraffin-embedded tissue from ocular adnexa MALT lymphoma, and RNA-sequencing was performed. Orbital MALT lymphoma gene expression was compared with that of conjunctival MALT lymphoma. Gene set (GS) analysis detecting for gene set cluster was performed in RNA-sequence. Related proteins were further examined by immunohistochemical staining. In addition, artificial segmentation image used to count stromal area in HE images.

Results

GS analysis showed differences in expression in 29 GS types in primary orbital MALT lymphoma (N=5,5, FDR q-value <0.25). The GS with the greatest difference in expression was the GS of epithelial-mesenchymal transition (EMT). Based on this GS change, immunohistochemical staining was added using E-cadherin as an epithelial marker and vimentin as a mesenchymal marker for EMT. There was significant staining of vimentin in orbital lymphoma (P<0.01, N=129) and of E-cadherin in conjunctival lesions (P=0.023, N=129). Vimentin staining correlated with Ann Arbor staging (1 versus >1) independent of age and sex on multivariate analysis (P=0.004). Stroma area in tumor were significant difference(P<0.01).

Conclusion

GS changes including EMT and stromal area in tumor were used to demonstrate the molecular biological differences between conjunctival MALT lymphoma and orbital MALT lymphoma in ocular adnexa lymphomas.
Prognostic value of platelet-to-lymphocyte ratio in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization and tyrosine kinase inhibitors plus immune checkpoints inhibitors
Authors: Guo Yiwan , Wu Wenlong , Sun Bo , Guo Tingting , Si Keke , Zheng Chuansheng , Li Xin
Published: January 2024

Purpose

To investigate the prognostic value of platelet-to-lymphocyte ratio (PLR) in patients with unresectable hepatocellular carcinoma (uHCC) treated with transarterial chemoembolization (TACE) and tailored tyrosine kinase inhibitors (TKIs) plus immune checkpoints inhibitors (ICIs).

Materials and methods

Ninety-eight patients from May 2018 to January 2022 in our hospital were enrolled in this study. The receiver operating characteristic (ROC) curve analysis was performed and the corresponding Youden index was used to determine the optimal PLR cut-off. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) of patients were evaluated based on the PLR cut-off. The factors affecting survival were assessed using univariate and multivariate Cox proportional hazards regression analyses.

Results

The PLR cut-off was 98.89. There were 49 patients in the low pretreatment PLR group (PLR ≤ 98.89) and 49 patients in the high PLR group (PLR > 98.89). Patients with low pretreatment PLR had significantly longer median OS (25.7 months vs 16.1 months; P < 0.001) and PFS (14.9 months vs 10.2 months; P < 0.001) than those with high pretreatment PLR. The multivariate analysis revealed that ALT, tumor size, and PLR are risk factors affecting OS. The three independent factors affecting PFS are tumor size, AFP, and PLR. The AEs were tolerable and manageable.

Conclusion

The low pretreatment PLR (PLR ≤ 98.89) was an independent protective factor for the survival outcomes of patients in this study. PLR was helpful for clinicians to predict the prognosis and identify the patients with uHCC who were most likely to benefit from TACE + TKIs + ICIs.
MAPK-activated protein kinase 2 is associated with poor prognosis of glioma patients and immune inhibition in glioma
Authors: Sun Jinmin , Wu Sicheng , Zhao Wenyu , Xue Senrui , Zhang Lei , Ren Jing
Published: January 2024

Introduction

An effective therapeutic method to noticeably improve the prognosis of glioma patients has not been developed thus far. MAPK-activated protein kinase 2 (MAPKAPK2) is a serine/threonine kinase, which is involved in tumorigenesis, tumor growth, metastasis, and the inflammatory process. The clinical significance and molecular function of MAPKAPK2 in glioma remain unclear.

Methods

MAPKAPK2 expression in human glioma tissues was detected by immunohistochemistry and analyzed from the transcriptome sequencing data in TCGA and CGGA. Prognostic nomogram was constructed to predict the survival risk of individual patients. GO and KEGG enrichment analyses were performed to analyze the function and pathways MAPKAPK2 involved. Single-cell RNA sequencing data was used to analyze the cell types in which MAPKAPK2 was enriched. Flow cytometry was used for cell cycle and apoptosis detection. The ability of cell proliferation and migration was analyzed by CCK8 and cell migration assay, respectively. Correlation analyses were performed to analyze the relationship of MAPKAPK2 with immune infiltration, immune regulators, chemokine, and chemokine receptors.

Results

MAPKAPK2 was not only aberrantly upregulated in glioma tissues but also correlated with poor clinical characteristics. Moreover, MAPKAPK2 was prevalent in isocitrate dehydrogenase (IDH) wild-type and 1p/19q non-codeletion glioma cohorts and predicted poor prognosis of glioma patients. MAPKAPK2 may be involved in cell proliferation, cell migration, DNA damage repair, and immune regulation in glioma. MAPKAPK2 was enriched in microglia/macrophages and malignant tumor cells. Further investigation into cellular function revealed that inhibiting MAPKAPK2 suppressed the proliferation and migration of glioblastoma multiforme (GBM) cells in vitro. The inhibition of MAPKAPK2 significantly induced the G1 cell cycle arrest and cell apoptosis of GBM cells. Consistent with the enriched function of MAPKAPK2 in immune regulation, MAPKAPK2 was correlated with immune cell infiltration in glioma tissues. Mechanistically, a series of immune regulators, immunomodulatory chemokine, and chemokine receptors were positively correlated with MAPKAPK2 expression.

Discussion

Our findings provide evidence of the clinical relevance of MAPKAPK2 in prognosis evaluation of glioma patients and highlight the underlying significance of MAPKAPK2 in glioma therapy.
Pembrolizumab-combination therapy for NSCLC- effectiveness and predictive factors in real-world practice
Authors: Knetki-Wróblewska Magdalena , Dziadziuszko Rafał , Jankowski Tomasz , Krawczyk Paweł , Bryl Maciej , Stencel Katarzyna , Wrona Anna , Bandura Artur , Smok-Kalwat Jolanta , Rok-Knapińska Jolanta , Szydziak-Zwierzyńska Kinga , Rogoziewicz Krzysztof , Czyżewicz Grzegorz , Wójtowicz Monika , Wojtukiewicz Marek , Kalinka Ewa , Wysocki Piotr J. , Łobacz Mateusz , Milanowski Janusz , Pawlik Hubert , Kowalski Dariusz M. , Krzakowski Maciej
Published: January 2024

Introduction

Pembrolizumab combined with chemotherapy has become the standard of care for patients with non-small-cell lung cancer (NSCLC) and the expression of programmed death ligand 1 (PD-L1) in <50% of tumour cells (TC).

Methods

We evaluated the efficacy of the treatment in real-world practice, paying attention to the predictive factors, with a special focus on low level of PD-L1 expression. This study is a multicenter retrospective analysis of patients with stage IV NSCLC.

Results

A group of 339 consecutive patients was analysed, among them 51% patients with low PD-L1 expression. In the overall population, the ORR was 40.6%, median PFS and OS were 13 months (95% CI 11.4-15) and 16.8 months (95% CI 13.3-20.3), respectively. In multivariate analysis for the entire study population, performance status – ECOG 1 vs. 0 (HR 2.2, 95%CI 1.1-4.6; p=0.02), neutrophil to lymphocyte ratio (NLR)>3 (HR 2.3, 95%CI 1.3-4.2; p=0.04), presence of liver (HR 2.0, 95%CI 1-3.7; p=0. 03) and bone metastases (HR 1.3, 95%CI 1-3; p=0.04), weight loss (HR 1.8, 95%CI 1.1-2.8; p=0.01) and sum of measurable lesions diameters >110 mm (HR 1.7, 95%CI 1-2.9, p=0.049) had a negative impact on OS.

Conclusions

In the real world, patients can clinically benefit from immunochemotherapy, regardless of the expression of PD-L1 and the histological type. Other clinicopathological factors such as performance status, extent, and location of secondary lesions have prognostic significance.
The association of race with thyroid eye disease presentation and outcomes
Authors: Wang Diane , Marous Charlotte , Celiker Pelin , Deng Wenyu , Kristoferson Eva , Elsayed Ali , Shinder Roman , Hodgson Nickisa
Published: January 2024

Introduction

Classification of thyroid eye disease (TED) is largely based on guidelines developed in Europe and North America. Few studies have investigated the presentation and treatment of TED in Black populations. The objective is to examine the manifestations of TED in secondary and tertiary care center-based populations with a significant proportion of Black patients.

Materials and methods

Retrospective chart review identifying patients with a reported race/ethnicity and a presenting clinical diagnosis of TED at Kings County Hospital and SUNY Downstate Medical Center and affiliated clinics from January 1, 2010 through July 31, 2021. Main outcome measures include age of disease onset, sex, smoking status, insurance status, postal code of residence, clinical exam features, number of follow-up visits, length of follow-up, and treatments received.

Results

Of the 80 patients analyzed, 49 were Black (61.2%) and 31 were White (38.8%). Between Black and White patients, there were differences in the mean age of presentation (48.1 [range 21-76] vs 56.8 [range 28-87] years, P=0.03), insurance status (51.0% vs 77.4% private insurance, P=0.02), and mean follow up length among those with multiple visits (21.6 [range 2-88] vs 9.7 [range 1-48] months, P=0.02). The distribution of EUGOGO scores were not significantly different between Black and White patients. On initial presentation, fewer Black patients had chemosis (OR 0.21, 95% CI, 0.08 to 0.57, P=0.002), and caruncular swelling (OR 0.19, 95% CI, 0.06 to 0.59, P=0.002) compared to White patients. During the overall disease course, fewer Black patients had subjective diplopia (OR 0.20, 95% CI, 0.07 to 0.56, P=0.002), chemosis (OR 0.24, 95% CI, 0.09 to 0.63, P=0.004), and caruncular swelling (OR 0.18, 95% CI, 0.07 to 0.51, P=0.001) compared to White patients. Black patients received oral steroids (42.9% vs 67.7%, P=0.03), intravenous steroids (18.4% vs 16.1%, P=0.8), orbital decompression surgery (16.7% vs 6.5%, P=0.19), and teprotumumab (22.9% vs 22.6%, P=0.99) at similar rates.

Discussion

Black patients presented with fewer external exam findings suggestive of active TED compared to White patients, but the rate of compressive optic neuropathy and decompression surgery were similar in the two groups. These differences may be due to disease phenotypes, which warrant further study.
pCO2 values in asphyxiated infants under therapeutic hypothermia after tailored respiratory management: a retrospective cohort study
Authors: Serrao Francesca , Tiberi Eloisa , Verdolotti Tommaso , Romeo Domenico Marco Maurizio , Corsello Mirta , Pede Elisa , Cota Francesco , Costa Simonetta , Gallini Francesca , Colosimo Cesare , Mercuri Eugenio Maria , Vento Giovanni
Published: January 2024

Background

Hypoxic-ischemic encephalopathy (HIE) represents one of the major causes of neonatal death and long-term neurological disability. Both hypoxic-ischemic insults and therapeutic hypothermia (TH) can affect respiratory function. Currently, there is no evidence regarding optimal respiratory management in these infants.

Methods

This is a retrospective cohort study examining newborns with HIE treated with TH between January 2015 and September 2020. The study population was divided into two groups based on different respiratory assistance during TH: spontaneous breathing (Group A) or mechanical ventilation (Group B). The primary outcome of the study was the mean pCO2 ± SD evaluation during TH in ventilated and non-ventilated asphyxiated infants. The secondary outcome was the correlation between ventilation strategy and short-term neurologic outcome according to Rutherford et al.'s MRI scoring system.

Results

A total of 126 newborns were enrolled, 75 in Group A and 51 in Group B. Respiratory management was individualized, and volume guarantee (VG) ventilation was the first choice for ventilated infants. Group B infants showed more severe conditions at birth. During TH, ventilated infants showed optimal mean pCO2 comparable with those breathing spontaneously (40.6 mmHg vs. 42.3 mmHg, respectively, p 0.091), with no significant difference in pCO2 standard deviation between (7.7 mmHg vs. 8.1 mmHg, respectively, p 0.522). Mean pH, pH standard deviation, mean pO2, pO2 standard deviation, and mean respiratory rate also did not differ between groups. MRI patterns of brain injury predictive of abnormal neurodevelopmental outcomes were similar in both groups. Logistic regression analysis demonstrated that only umbilical cord arterial blood pH-affected MRI lesions were associated with poor neurodevelopmental outcomes (OR 1.505; CI 95% 1.069–2.117).

Conclusions

Infants cooled after HIE should receive individualized respiratory management, not necessarily involving intubation. In those infants requiring mechanical ventilation, a volume-targeted strategy appeared to be effective in maintaining stable blood gas levels. Short-term neurological outcomes appeared comparable in ventilated and non-ventilated infants.
Skin temperature influence on transcutaneous carbon dioxide (CO2) conductivity and skin blood flow in healthy human subjects at the arm and wrist
Authors: Dervieux Emmanuel , Guerrero François , Uhring Wilfried , Giroux-Metgès Marie-Agnès , Théron Michaël
Published: January 2024

Objective: present transcutaneous carbon dioxide (CO2)—tcpCO2—monitors suffer from limitations which hamper their widespread use, and call for a new tcpCO2 measurement technique. However, the progress in this area is hindered by the lack of knowledge in transcutaneous CO2 diffusion. To address this knowledge gap, this study focuses on investigating the influence of skin temperature on two key skin properties: CO2 permeability and skin blood flow.

Methods: a monocentric prospective exploratory study including 40 healthy adults was undertaken. Each subject experienced a 90 min visit split into five 18 min sessions at different skin temperatures—Non-Heated (NH), 35, 38, 41, and 44°C. At each temperature, custom sensors measured transcutaneous CO2 conductivity and exhalation rate at the arm and wrist, while Laser Doppler Flowmetry (LDF) assessed skin blood flow at the arm.

Results: the three studied metrics sharply increased with rising skin temperature. Mean values increased from the NH situation up to 44°C from 4.03 up to 8.88 and from 2.94 up to 8.11 m·s−1 for skin conductivity, and from 80.4 up to 177.5 and from 58.7 up to 162.3 cm3·m−2·h−1 for exhalation rate at the arm and wrist, respectively. Likewise, skin blood flow increased elevenfold for the same temperature increase. Of note, all metrics already augmented significantly in the 35–38°C skin temperature range, which may be reached without active heating—i.e. only using a warm clothing.

Conclusion: these results are extremely encouraging for the development of next-generation tcpCO2 sensors. Indeed, the moderate increase (× 2) in skin conductivity from NH to 44°C tends to indicate that heating the skin is not critical from a response time point of view, i.e. little to no skin heating would only result in a doubled sensor response time in the worst case, compared to a maximal heating at 44°C. Crucially, a skin temperature within the 35–38°C range already sharply increases the skin blood flow, suggesting that tcpCO2 correlates well with the arterial paCO2 even at such low skin temperatures. These two conclusions further strengthen the viability of non-heated tcpCO2 sensors, thereby paving the way for the development of wearable transcutaneous capnometers.
Assessing the intention to accept inquiry-based teaching pedagogy among Chinese university students: an extension of technology acceptance model
Authors: Hu San-gen , Wang Wan-ying , Wang Xiao-Xia , Yin Ying-Mei
Published: January 2024

Introduction

Due to the limitations of traditional didactic teaching, inquiry-based teaching has attracted increasing attention and has become an important content of curriculum teaching reform in college education. Nevertheless, it is vital to investigate students’ subjective acceptance of inquiry-based instruction and its influencing factors before inquiry-based teaching methods are widely implemented.

Methods

In light of this, taking into account the psychological factors of students, an acceptance model of inquiry-based teaching pedagogy was established based on the extended technology acceptance model (TAM). Three additional variables, namely self-efficacy, implementation quality, and risk perception, were incorporated into the TAM. Firstly, subjective evaluation data of the influencing factors of inquiry teaching acceptance were obtained through a network questionnaire survey from university students in Guangdong, China, using snowball sampling and convenient sampling. A total of 485 valid questionnaires were retrieved, with an effective response rate of 88.2%. Then, internal consistency and reliability, convergent validity and discriminant validity of the model and its hypothesis were tested with reliability and validity tests. Finally, path analysis was used to examine key determinants of students’ acceptance of inquiry teaching and moderators.

Results

Results indicated that the constructed model can explain the acceptability of inquiry teaching for college students by 88.6%; Attitude has a positive significant impact on behavioral intention; Perceived ease of use indirectly affects behavioral intention through perceived usefulness, while perceived usefulness indirectly affects behavioral intention through attitude; self-efficacy not only directly affects behavioral intention but also indirectly affects behavioral intention through implementation quality; implementation quality indirectly affects behavioral intention through perceived usefulness and attitude; students’ risk perception of inquiry-based teaching has no negative impact on behavioral intention.

Conclusion

Overall, this study has implications for policymakers, teachers or learners in terms of the implementation and promotion of inquiry-based teaching in college classroom.
The Aha! experience is associated with a drop in the perceived difficulty of the problem
Authors: Moroshkina Nadezhda V. , Pavliuchik Elena I. , Ammalainen Artur V. , Gershkovich Valeria A. , Lvova Olga V.
Published: January 2024

The study investigated the correlation between the intensity of the Aha! experience and participants’ subjective difficulty ratings of problems before and after finding their solutions. We assumed that the Aha! experience arises from a shift in processing fluency triggered by changing from an initially incoherent problem representation to a coherent one, which ultimately leads to the retrieval of a solution with unexpected ease and speed. First, we hypothesized that higher Aha! experience ratings would indicate more sudden solutions, manifesting in a reduced correlation between the initial difficulty ratings and solution times. Second, we hypothesized that higher Aha! experience ratings would correspond to a greater shift in the subjective difficulty ratings between the initial and retrospective assessments. To test our hypotheses, we developed a novel set of rebus puzzles. A total of 160 participants solved rebuses and provided initial (within 5 s of problem presentation) and retrospective difficulty ratings (following the generation or presentation of a correct solution). They also rated their Aha! experience (after solution generation or presentation), confidence in solutions, and the likability of each rebus. Our findings revealed that the initial ratings of the problem’s subjective difficulty were positively correlated with the solution time and that this correlation decreased in the case of a stronger Aha! experience. Aha! experience ratings were positively correlated with the differences between initial and retrospective difficulty ratings, confidence, solution accuracy, and rebus likability. We interpreted our results to be in line with the processing fluency and metacognitive prediction error accounts.
DSM-5 suicidal behavior disorder: a systematic review of research on clinical utility, diagnostic boundaries, measures, pathophysiology and interventions
Authors: Oliogu Etinosa , Ruocco Anthony C.
Published: January 2024

Background

It has been a decade since Suicidal Behavior Disorder (SBD) was introduced in Section III of the DSM-5 under “Conditions for Further Study”. SBD is chiefly characterized by a self-initiated sequence of behaviors believed at the time of initiation to cause one’s own death and occurring in the last 24 months.

Aims

To systematically review empirical studies on SBD to identify primary research themes and promising future research directions.

Method

A search of empirical articles on SBD published between May 2013 and March 2023 was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Results

Screening of 73 records by two independent raters yielded 14 eligible articles. The primary research themes identified from these articles included clinical utility of SBD to predict future suicide risk, association of SBD with closely related disorders, psychometric properties of SBD measures, pathophysiology of SBD, and the effectiveness of interventions for people with SBD.

Conclusion

Understanding of SBD has slowly progressed since its introduction a decade ago and has mainly been applied in research to define study groups displaying suicidal behavior. The clinical utility of SBD for predicting future suicide risk is low and more research is needed to understand measurement of the diagnosis and its distinctiveness from related disorders and other self-harming behaviors.
Dietary behaviors of rural residents in northeastern China: implications for designing intervention information and targeting high-risk population
Authors: Bai Li , Tang Haiheng , Wang Mingliang
Published: January 2024

Background

Dietary behavior is a pivotal modifiable determinant in reducing the occurrence of obesity/overweight and chronic non-communicable diseases. Improving the dietary behavior of rural residents in China is imminent due to the poor performance of their dietary behavior. Nutrition knowledge and health literacy are considered as elements that are linked intimately to healthy dietary behaviors but lack research in the Chinese setting.

Purpose

The study is designed to explore the relationship between nutritional knowledge, health literacy and dietary behaviors and to analyze the performance under different demographic characteristics.

Methods

A face-to-face survey of 400 rural residents on their nutrition knowledge, functional health literacy and dietary intake of five food categories consisting of 32 items was conducted based on a validated questionnaire. Descriptive analysis, difference test including ANOVA, t-test and non-parametric test, and multivariate linear regression were used for data analysis.

Results

The results indicate that declarative nutrition knowledge, individuals’ information application capacity, and dietary behaviors, especially the intake of fruits, dairy and beans, and vegetable are not ideal and requires improvement. Male, elder, low-income, unmarried, and low-education populations performed significantly worse and were the high-risk group. Procedural nutrition knowledge, information access capacity, information understanding capacity, and information application capacity have remarkable effects on better dietary behavior.

Conclusion

This study provides evidence-based guidance for prioritizing information and populations for healthy dietary interventions.
The impact of geriatric syndromes on quality of life among older people living with HIV in Kampala, Uganda
Authors: Senkoro Elizabeth , Mbabazi Phoebe , Banturaki Grace , Naikoba Suzan , Castelnuovo Barbara
Published: January 2024

Objective

Older people living with HIV (OPWH) often have lower quality of life (QoL) compared to general population. Measuring their QoL is an important step in HIV care to ensure they have long healthy lives. This study aimed to evaluate the quality of life and its associated factors among people living with HIV aged 60 years and above in Uganda.

Methods

We used a cross-sectional analysis of older people living with HIV (OPWH) enrolled in a prospective cohort from December 2020 – December 2021. Quality of life was assessed using the World Health Organisation QoL OLD instrument (WHOQOL-OLD). Linear regression model was used to determine associated factors.

Results

Of the 500 participants enrolled, 51.2% were men and their median age was 64 years (IQR: 62 — 68). WHOQOL-OLD mean score (SD) was 90.1 (8.3) out of 120. Factors that increased overall QoL were (Coefficient [95% Confidence Interval]): being male 2.35 (1.21 — 3.73), having an income of ≥$1 1.30 (−0.16 — 2.76) and paradoxically having more than 2 non-communicable diseases 0.69 (−0.76 — 2.14) in the past, present and future domain of QoL. Those that decreased QoL in the overall and various domains included: an increasing number of geriatric syndromes, depression, pre-frailty, frailty, malnutrition, and low physical function.

Conclusion

Our findings suggest that financial stability contributed to good QoL while geriatric syndromes decreased QoL for OPWH. Integrating the screening and management of geriatric syndromes into HIV care has the potential to improve the overall QoL of OPWH.
Classification of and individual treatment strategies for complex tethered cord syndrome
Authors: Lin Hepu , Su Hui , Li Cuicui , Zhang Pengfei , Xiu Bo , Bai Yunjing , Xu Ruxiang
Published: January 2024

Objective

To study the classification, diagnosis, and treatment strategies of complex tethered cord syndrome (C-TCS) on the basis of the patients’ clinical symptoms, imaging findings, and therapeutic schedule.

Methods

The clinical data of 126 patients with C-TCS admitted to our department from January 2015 to December 2020 were retrospectively analyzed. Classification criteria for C-TCS were established by analyzing the causes of C-TCS. Different surgical strategies were adopted for different types of C-TCS. The Kirollos grading, visual analogue scale (VAS), critical muscle strength, and Japanese Orthopaedic Association (JOA) scores were used to evaluate the surgical outcomes and explore individualized diagnosis and treatment strategies for C-TCS.

Results

C-TCS was usually attributable to three or more types of tether-causing factors. The disease mechanisms could be categorized as pathological thickening and lipomatosis of the filum terminal (filum terminal type), arachnoid adhesion (arachnoid type), spina bifida with lipomyelomeningocele/meningocele (cele type), spinal lipoma (lipoma type), spinal deformity (bone type), and diastomyelia malformation (diastomyelia type). Patients with different subtypes showed complex and varied symptoms and required individualized treatment strategies.

Conclusion

Since C-TCS is attributable to different tether-related factors, C-TCS classification can guide individualized surgical treatment strategies to ensure complete release of the tethered cord and reduce surgical complications.
Laparoscopic ovarian tissue collection for fertility preservation in children with malignancies: a multicentric experience
Authors: Perelli Federica , Fusi Giulia , Lonati Luca , Gargano Tommaso , Maffi Michela , Avanzini Stefano , Palo Federico , Blanco Verdú Maria Dolores , Del Cañizo López Agustín , Garrido Colino Carmen , Perucca Giulia , Mattioli Girolamo , Gennari Fabrizio , Lima Mario , Guanà Riccardo
Published: January 2024

Introduction

Long survivors after childhood cancer are increasing thanks to oncological improvements. Their quality of life and fertility-sparing should be considered in the early phases of each oncological pathway. Cryopreservation of ovarian tissue removed before starting gonadotoxic therapies is the only fertility sparing procedure available for prepubertal children affected by cancer and it does not affect the timing of the start of the treatment.

Materials and methods

The present study shows the surgical and clinical outcomes following laparoscopic ovarian tissue collection (LOTC) for a total of 311 patients aged between 0 and 17 years old from four different European Centers.

Results

Only two major complications were reported according to the Clavien Dindo classification (0.6%).

Discussion

LOTC can be considered a safe procedure.