bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of hemi-uterus pregnancy outcomes in uterine malformations: a retrospective observational study
Authors: Qian Liang , Ding Jiashan , Shi Lan , Yu Qing , Zhu Jiawei , Huang Anfeng
Published: December 2023

Background

The association between uterine malformations and adverse pregnancy outcomes is well recognized. However, studies on adverse pregnancy outcomes based on one kind of anatomical commonality between different uterine anomalies have not been reported. This study aimed to investigate pregnancy outcomes in pregnancies with uterine malformations when the pregnancy is confined to a hemi-uterus.

Methods

A retrospective observational study of 336 women who gave birth at our hospital from 2015 to 2021 was performed. Women (n = 112) with a unicornuate, complete bicornuate, or didelphic uterus were set as the study group, and women (n = 224) with a normal uterus were set as the reference group. Maternal and neonatal outcomes were evaluated and compared between the two groups using Student’s t-test, one-way ANOVA, Chi-squared test, Yates correction for continuity, or Fisher’s exact test. Modified Poisson regression analyses were used to estimate the relationships between the hemi-uterus pregnancy and preterm birth, preterm premature rupture of membranes, and cesarean section rates by adjusting for potential confounders. A P value < 0.05 was considered significant.

Results

Women in the study group had a higher history of spontaneous abortion (24.1% vs. 10.7%, P = 0.002) and intrauterine fetal death (5.4% vs. 0.4, P = 0.006). Compared with the reference group, the study group had significantly higher rates of assisted reproductive technology (9.4% vs. 2.2%, P = 0.001) and cord-around-the neck (54.5% vs. 29.9%, P = 0.000). Modified Poisson regression analyses showed that the study group was at higher risk for preterm birth (aRR, 6.8; 95% CI 2.7–16.7), preterm premature rupture of membranes (aRR, 14.1; 95% CI 3.2–62.5), malpresentation (aRR, 13.2; 95% CI 6.3–27.7), and cesarean section (aRR, 4.4; 95% CI 3.3–5.7).

Conclusion

Women with a unicornuate, didelphic, or complete bicornuate uterus are at higher risk for some adverse pregnancy outcomes than those with a normal uterus.
Identification of a Novel CD8+ T cell exhaustion-related gene signature for predicting survival in hepatocellular carcinoma
Authors: Liu Kejun , Liu Junhao , Zhang Xusheng , Liu Di , Yao Weijie , Bu Yang , Chen Bendong
Published: December 2023

Background

Hepatocellular carcinoma (HCC) is a major health concern, necessitating a deeper understanding of its prognosis and underlying mechanisms. This study aimed to investigate the mechanism and prognostic value of CD8+ T Cell exhaustion (CD8+ TEX)-related genes in HCC and construct a survival prognosis prediction model for patients with HCC.

Methods

CD8+ TEX-related genes associated with HCC prognosis were analysed and identified, and a prognostic prediction model was constructed using the ‘least absolute shrinkage and selection operator’ Cox regression model. Immunohistochemistry was used to verify the expression of the model genes in HCC tissues. A nomogram was constructed based on risk scores and clinical features, and its predictive efficacy was verified. The expression of STAM, ANXA5, and MAD2L2 in HCC cell lines was detected by western blotting; subsequently, these genes were knocked down in HCC cell lines by small interfering RNA, and their effects on the proliferation and migration of HCC cell lines were detected by colony formation assay, cck8, wound healing, and transwell assays.

Results

Six genes related to CD8+ TEX were included in the risk-prediction model. The prognosis of patients with HCC in the low-risk group was significantly better than that of those in the high-risk group. Cox regression analysis revealed that the risk score was an independent risk factor for the prognosis of patients with HCC. The differentially expressed genes in patients with high-risk HCC were mainly enriched in the nucleotide-binding oligomerization domain-containing protein-like receptor, hypoxia-inducible factor-1, and tumour programmed cell death protein (PD)-1/PD-L1 immune checkpoint pathways. The CD8+ TEX-related genes STAM, ANXA5, and MAD2L2 were knocked down in HCC cell lines to significantly inhibit cell proliferation and migration. The prediction results of the nomogram based on the risk score showed a good fit and application value.

Conclusion

The prediction model based on CD8+ TEX-related genes can predict the prognosis of HCC and provide a theoretical basis for the early identification of patients with poor HCC prognosis.
Low-level laser therapy combined with scleral graft transplantation in the treatment of contracted socket: a clinical study
Authors: Huang Qin , Fang Yangbin , Lai Yao , Liao Hongfei
Published: December 2023

Objective

To analyse the efficacy of the therapeutic use of low-level laser therapy (LLLT) on the tissue repair process of allogeneic scleral grafts in patients with contracted sockets by analysing the speed of graft vascularisation and fornice depth of contraction percentage.

Methods

A retrospective chart review was performed from April 2015 to April 2021 including 39patients with socket contraction. Allogeneic scleral grafts were used to repair the sockets in all patients. They were randomly enrolled into two groups. The laser group included 18 patients treated with LLLT after the surgery, whereas the control group included 21 patients without LLLT after the surgery who healed naturally. The LLLT equipment used in the research had a wavelength of 650 nm, 10 mW power, and 3.8 J/cm2 dosimetry, and the procedure was performed once daily for 5 min over 7 days, beginning 1 week postoperatively. All patients were followed up over 6 months to examine the changes in the size of the area of the non-vascularised graft and upper and inferior fornice depth.

Results

The laser group presented a significantly increased speed of conjunctival vascularisation compared with the control group (P = 0.003). The fornice depth of contraction percentage was more apparent in the control group than that in the laser group (P = 0.000).

Conclusion

LLLT accelerates conjunctival vascularisation, stimulates conjunctival incision healing within a short period, shortens the tissue repair process, reduces the local inflammatory response, and causes no significant shrinkage of the conjunctival sac.
Management strategies of dental anxiety and uncooperative behaviors in children with Autism spectrum disorder
Authors: Tang Shi-Jun , Wei Hong-Lin , Li Cai-Yu , Huang Ming-Na
Published: December 2023

Background

Children with Autism spectrum disorder (ASD) was frequently experienced dental anxiety and uncooperative behaviors during dental treatment. Oral health care was necessary because of the poor oral hygiene and prevalent dental diseases in this population.

Aim

In this systematic review, we evaluated the effectiveness and feasibility for pediatric dentist to manage the dental anxiety in children with ASD.

Design

PubMed, Embase, and Cochrane Library were systematically performed on the literature search. The date of eligible publications was from inception to January 2023. After that, the quality of eligible studies was assessed by the Newcastle Ottawa Scale (NOS). Review findings were summarized using the PRISMA Statement for reporting.

Results

A total of six studies were systematically evaluated according to the inclusion and exclusion criteria. Five studies were conducted to evaluate ASD Children's anxiety and uncooperative performance in the progressive oral examination, oral disease prophylaxis and fluoride application. The other one study evaluated the success rate of treatment in decayed permanent tooth treatment. In the included studies, four studies indicated that it was extremely necessary to reduce dental anxiety of ASD children to increase the cooperation in sensory-adapted dental environment (SADE).

Conclusion

It is not always effective and feasible for pediatric dentist to manage the dental anxiety in children with autism during routine oral examination. Meanwhile, it is necessary for ASD children to conduct preoperative psychological assessment, to investigate parents’ expectations and cooperation, and to determine whether to start corresponding dental treatment.
Distribution incidence, mortality of tuberculosis and human development index in Iran: estimates from the global burden of disease study 2019
Authors: Fallahzadeh Hossien , Khazaei Zaher , Najafi Moslem Lari , Pordanjani Sajjad Rahimi , Goodarzi Elham
Published: December 2023

Background

Tuberculosis is one of the most serious challenges facing the global healthcare system. This study aims to investigate the incidence and mortality of tuberculosis in Iran from 2010 to 2019 as well as its relationship with the human development index (HDI).

Methods

The present study is an ecological study aiming at investigating the incidence and mortality of tuberculosis in Iran during the years 2010 to 2019. The related data were extracted from the Global Burden of Disease (GBD) website. The spatial pattern attributed to tuberculosis in the provinces of Iran was analyzed using ArcGIS software. In this study, the two-variable correlation method was used to analyze the data extracted to study the correlation between Tuberculosis and HDI.

Result

Based on the results recorded in GBD, the incidence of tuberculosis in 2010, that is, 14.61 (12.72, 16.74), declined compared to 2019, namely 12.29 (10.71, 14.09). The age-standardized mortality rate which was 1.63 (1.52, 1.73) in 2010, has decreased compared to 2019: 1.17 (1.07, 1.32). The incidence and mortality rates of tuberculosis in Iran in all age groups have decreased in 2019 compared to 2010. The highest incidence and mortality among tuberculosis patients were recorded in Sistan and Baluchistan and Golestan provinces. The results indicated that there was a negative and significant correlation between the mortality rate of tuberculosis and the human development index in 2010 (r = -0.509, P-value = 0.003) and 2019 (r = -0.36, P-value = 0.001); however, this correlation between incidence and human development index was not significant (p > 0.05).

Conclusion

Since mortality is mostly observed in areas with low HDI, health system policymakers must pay more attention to these areas in order to improve care and perform screenings to diagnose and treat patients thus reducing the mortality rate of tuberculosis and preventing an increase in its incidence in Iran.
Study on the correlation between lifestyle and negative conversion time in patients diagnosed with coronavirus disease (COVID-19): a retrospective cohort study
Authors: Li Nan , Liu Chenbing , Qiu Lihong , Shen Chao , Zhang Feng , Lu Zhangfan , Zhou Menghao , Sheng Di , Liu Zhong
Published: December 2023

Background

As of early December 2022, China eased the coronavirus disease (COVID-19) restriction, affecting over 80% of the country’s population and posing a severe threat to public health. Previous studies mostly focused factors on the severity/mortality rate of hospitalized COVID-19 patients, but limited studies explored factors associated with virus-negative conversion, particularly lifestyles. Therefore, the aim of our study was to analyze the correlation between lifestyle factors and the negative conversion time in COVID-19 patients.

Methods

We recruited individuals aged 18 years or older who had a clear time record for both the diagnosis and negative conversion of COVID-19 and completed the electronic questionnaire with no missing data. Dietary data collected from the questionnaire was analyzed using exploratory factor analysis to establish dietary patterns. Age segmentation was performed using restricted cubic spline (RCS) plots. The association between lifestyle factors and the time to negative conversion in different age groups, was assessed using Kaplan-Meier plots and Cox regression analysis.

Result

Out of 514 participants, all achieved viral negative conversion within a median time of 11 days. Based on nutrient intake, we identified four dietary patterns. The relationship between age and negative conversion rate, as depicted by RCS plots, exhibited an inverted “U” shape. We categorized age into three segments: <35 years, 35–45 years, and ≥ 45 years. For individuals under 35, our study indicated that a higher protein intake was linked to a faster recovery among COVID-19 patients, while medical staff or those receiving prescription treatments exhibited a slower recovery rate (P < 0.05). The 35 ~ 45 age group showed that adequate sleep and physical exercise were associated with a shorter time to negative conversion, whereas southern regions and a higher intake of carbohydrates were related with a longer conversion time (P < 0.05). Among individuals aged ≥ 45 years, the negative conversion time was primarily associated with physical exercise and being a medical staff member(P < 0.05).

Conclusion

Our research suggests that adequate sleep, physical exercise and a higher protein intake can help alleviate COVID-19 symptoms, while a higher level of carbohydrates intake may hinder recovery from COVID-19.
Measuring adolescent health literacy in Taiwan: validation of the health literacy assessment scale for adolescents
Authors: Chou An-Kuo , Liao Chun-Hua , Chen Duan-Rung
Published: December 2023

Background

This study aimed to validate the Chinese version of the Health Literacy Assessment Scale for Adolescents (HAS-A) and conduct a comparative analysis of adolescent health literacy between Taiwan and other countries.

Methods

The Chinese version of the HAS-A was completed by 2,312 adolescents in the fifth and sixth grades of a primary school. Psychometric properties were examined using consistent internal reliability and confirmatory factor analysis. These assessments were compared with the results from different regions to explore health literacy inequality.

Results

Construct validity was good, and internal consistency was acceptable. The scale, particularly regarding communication health literacy, was associated with parents’ socioeconomic status, and family income had a more significant impact on children’s health literacy than community income. Health literacy disparities appear in different countries, with Taiwan exhibiting the lowest level of communication health literacy.

Conclusion

The results indicate that the HAS-A is a valuable tool for assessing the health literacy of 10–11-year-old adolescents and can uncover health literacy inequality among different regions.
Laparoscopic lateral duodenojejunostomy for pediatric superior mesenteric artery compression syndrome: a cohort retrospective study
Authors: Tang Jingfeng , Zhang Mengxin , Zhou Ying , Cao Guoqing , Li Shuai , Zhang Xi , Tang Shaotao
Published: December 2023

Purpose

There are only a few case reports of laparoscopic lateral duodenojejunostomy (LLDJ) in children with Wilkie’s syndrome, also known as superior mesenteric artery compression syndrome (SMAS). We aimed to describe our laparoscopic technique and evaluate its outcomes for SMAS in children.

Methods

From January 2013 to May 2021, SMAS children who received LLDJ were included. The procedure was carried out utilizing the four-trocar technique. The elevation of the transverse colon allows good exposure of the dilated and bulging second and third sections of the duodenum. Using a linear stapler, we established a lateral anastomosis connecting the proximal jejunum with the third part of the duodenum. Following that, a running suture was used to intracorporeally close the common enterotomy. Clinical data on patients was collected for analysis. The demographics, diagnostic findings, and postoperative outcomes were analyzed retrospectively.

Results

We retrospectively analyzed 9 SMAS patients (6 females and 3 males) who underwent LLDJ, aged between 7 and 17 years old. The mean operative time was 118.4 ± 16.5 min and the mean estimated blood loss was 5.6 ± 1.4 ml. There were no conversion, intraoperative complications or immediate postoperative complications. The mean postoperative hospital stay was 6.8 ± 1.9 days and the mean follow-up time was 5.4 ± 3.0 years. During follow-up, seven patients (77.8%) experienced complete recovery of symptoms prior to surgery. One patient (11.1%) still had mild vomiting, which resolved with medication. Another patient (11.1%) developed psychological-induced nausea, which significantly improved after treatment with education, training and diet management.

Conclusions

LLDJ represents a feasible and safe treatment option for SMAS in well-selected children. Further evaluation with more cases and case-control studies is required for the real benefits.
The lived experiences of nurse preceptors in training new nurses in Qatar: qualitative study
Authors: Varghese Bejoy , AL-Balawi Rida Moh’d Odeh A.M. , Joseph Chithra Maria , Al-Akkam Adnan Anwar Ahmad , Alomari Albara Mohammad Ali , Swallmeh Esmat
Published: December 2023

Background

The role of preceptors is vital in the successful integration of new graduate nurses in hospital settings. This study aimed to explore the experiences of nurse preceptors in training newly joined nurses in Qatar.

Methods

Qualitative study was conducted between May 2022 and May 2023. Online semi-structured interviews were conducted through MS Teams with 13 nurse preceptors who had completed preceptorship training and trained at least one newly joined nurse. Participants were recruited until data saturation was obtained and data were analyzed using qualitative thematic analysis.

Results

The results of the study revealed several main themes: teaching strategies and progressive skill development in preceptorship, challenges faced by the preceptor and preceptor better supported in training new nurses. The preceptors utilized different techniques to support new nurses including demonstration, discussion, use of technology, application of real-life clinical scenarios, simulations, and a gradual decrease in supervision to promote independence. However, a significant challenge was also reported including preceptors experienced high levels of exhaustion from the dual responsibilities of training new staff while also performing their regular care duties.

Conclusions

The study underscores the fundamental role preceptors play in the training and development of newly joined nurses. While the challenges are considerable, particularly related to managing workload, the sense of achievement following the successful completion of training a new nurse suggests a strong commitment to this role. Despite the challenges, preceptors demonstrated innovative strategies to ensure the successful development of their preceptees, highlighting the importance of preceptorship in nursing education and practice.
Models of good practice to enhance infectious disease care cascades among people who inject drugs: a qualitative study of interventions implemented in European settings
Authors: Horváth Ilonka , Mårdh Otilia , Schwarz Tanja
Published: December 2023

Background

People who inject drugs (PWID) in Europe are at an increased risk of HIV/AIDS, chronic viral hepatitis B (HBV) and C (HCV), and tuberculosis (TB). We aimed to complement the evidence base on interventions optimising their care cascade with evidence from models of good practice (MoGPs) implemented in the EU/EEA and countries from the Eastern European region.

Methods

A model of good practice (MoGP) was defined as (a package of) interventions with proven effectiveness in certain settings that are likely to be replicable and sustainable in other settings or countries. Fifteen MoGPs, identified by the European Centre for Disease Prevention and Control (ECDC) and the European Monitoring Centre on Drugs and Drug Addiction (EMCDDA) following a call launched in 2020, have been analysed. For the 15 MoGPs, a qualitative content analysis was conducted of (i) intervention characteristics and (ii) enabling factors. Information was extracted and summarised for community-based testing, linkage to care and adherence to treatment.

Results

MoGPs emerged from projects implemented in Belarus, Norway, Portugal, the Republic of Moldova, Spain, and the UK alongside the multi-country HepCare project (Ireland, Romania, Spain, the UK) targeting either HCV (6/15) or HIV/AIDS (4/15), alone or combined with HBV, and/or TB (5/15). All MoGPs used packages of interventions, with decentralisation of services (15/15), cooperation among service providers (14/15), integrated services (10/15), peer interventions (12/15), and case management (4/15) reported across all stages of the care cascade. The synthesis of enablers shows that when replicating interventions in other settings, consideration should be given to national (legal) frameworks, characteristics of and proximity between healthcare and service providers, and establishing relations of trust with PWID.

Conclusion

To improve the cascade of care for PWID in European settings, care structures and pathways should be simplified, based on cooperation and multidisciplinary. MoGPs can provide implementation-based evidence on interventions alongside evidence from peer-reviewed literature to optimise the care cascade among PWID.
Human monoclonal antibodies inhibit invasion of transgenic Plasmodium knowlesi expressing Plasmodium vivax Duffy binding protein
Authors: Watson Quentin D. , Carias Lenore L. , Malachin Alyssa , Redinger Karli R. , Bosch Jürgen , Bardelli Martino , Baldor Lea , Feufack-Donfack Lionel Brice , Popovici Jean , Moon Robert W. , Draper Simon J. , Zimmerman Peter A. , King Christopher L.
Published: December 2023

Background

Plasmodium vivax has been more resistant to various control measures than Plasmodium falciparum malaria because of its greater transmissibility and ability to produce latent parasite forms. Therefore, developing P. vivax vaccines and therapeutic monoclonal antibodies (humAbs) remains a high priority. The Duffy antigen receptor for chemokines (DARC) expressed on erythrocytes is central to P. vivax invasion of reticulocytes. P. vivax expresses a Duffy binding protein (PvDBP) on merozoites, a DARC ligand, and the DARC: PvDBP interaction is critical for P. vivax blood stage malaria. Therefore, PvDBP is a leading vaccine candidate for P. vivax and a target for therapeutic human monoclonal antibodies (humAbs).

Methods

Here, the functional activity of humAbs derived from naturally exposed and vaccinated individuals are compared for the first time using easily cultured Plasmodium knowlesi (P. knowlesi) that had been genetically modified to replace its endogenous PkDBP orthologue with PvDBP to create a transgenic parasite, PkPvDBPOR. This transgenic parasite requires DARC to invade human erythrocytes but is not reticulocyte restricted. This model was used to evaluate the invasion inhibition potential of 12 humAbs (9 naturally acquired; 3 vaccine-induced) targeting PvDBP individually and in combinations using growth inhibition assays (GIAs).

Results

The PvDBP-specific humAbs demonstrated 70–100% inhibition of PkPvDBPOR invasion with the IC50 values ranging from 51 to 338 µg/mL for the 9 naturally acquired (NA) humAbs and 33 to 99 µg/ml for the 3 vaccine-induced (VI) humAbs. To evaluate antagonistic, additive, or synergistic effects, six pairwise combinations were performed using select humAbs. Of these combinations tested, one NA/NA (099100/094083) combination demonstrated relatively strong additive inhibition between 10 and 100 µg/mL; all combinations of NA and VI humAbs showed additive inhibition at concentrations below 25 µg/mL and antagonism at higher concentrations. None of the humAb combinations showed synergy. Invasion inhibition efficacy by some mAbs shown with PkPvDBPOR was closely replicated using P. vivax clinical isolates.

Conclusion

The PkPvDBPOR transgenic model is a robust surrogate of P. vivax to assess invasion and growth inhibition of human monoclonal Abs recognizing PvDBP individually and in combination. There was no synergistic interaction for growth inhibition with the humAbs tested here that target different epitopes or subdomains of PvDBP, suggesting little benefit in clinical trials using combinations of these humAbs.
Reducing intervention- and research-induced inequalities to tackle the digital divide in health promotion
Authors: König Laura M. , Krukowski Rebecca A. , Kuntsche Emmanuel , Busse Heide , Gumbert Laura , Gemesi Kathrin , Neter Efrat , Mohamed Nor Firdous , Ross Kathryn M. , John-Akinola Yetunde O. , Cooper Rosie , Allmeta Anila , Silva Anabelle Macedo , Forbes Cynthia C. , Western Max J.
Published: December 2023

Social inequalities are an important contributor to the global burden of disease within and between countries. Using digital technology in health promotion and healthcare is seen by some as a potential lever to reduce these inequalities; however, research suggests that digital technology risks re-enacting or evening widening disparities. Most research on this digital health divide focuses on a small number of social inequality indicators and stems from Western, educated, industrialized, rich, and democratic (WEIRD) countries. There is a need for systematic, international, and interdisciplinary contextualized research on the impact of social inequality indicators in digital health as well as the underlying mechanisms of this digital divide across the globe to reduce health disparities. In June 2023, eighteen multi-disciplinary researchers representing thirteen countries from six continents came together to discuss current issues in the field of digital health promotion and healthcare contributing to the digital divide. Ways that current practices in research contribute to the digital health divide were explored, including intervention development, testing, and implementation. Based on the dialogue, we provide suggestions for overcoming barriers and improving practices across disciplines, countries, and sectors. The research community must actively advocate for system-level changes regarding policy and research to reduce the digital divide and so improve digital health for all.
Immunoproteasome function maintains oncogenic gene expression in KMT2A-complex driven leukemia
Authors: Tubío-Santamaría Nuria , Jayavelu Ashok Kumar , Schnoeder Tina M. , Eifert Theresa , Hsu Chen-Jen , Perner Florian , Zhang Qirui , Wenge Daniela V. , Hansen Fynn M. , Kirkpatrick Joanna M. , Jyotsana Nidhi , Lane Steven W. , von Eyss Björn , Deshpande Aniruddha J. , Kühn Michael W. M. , Schwaller Juerg , Cammann Clemens , Seifert Ulrike , Ebstein Frédéric , Krüger Elke , Hochhaus Andreas , Heuser Michael , Ori Alessandro , Mann Matthias , Armstrong Scott A. , Heidel Florian H.
Published: December 2023

Pharmacologic targeting of chromatin-associated protein complexes has shown significant responses in KMT2A-rearranged (KMT2A-r) acute myeloid leukemia (AML) but resistance frequently develops to single agents. This points to a need for therapeutic combinations that target multiple mechanisms. To enhance our understanding of functional dependencies in KMT2A-r AML, we have used a proteomic approach to identify the catalytic immunoproteasome subunit PSMB8 as a specific vulnerability. Genetic and pharmacologic inactivation of PSMB8 results in impaired proliferation of murine and human leukemic cells while normal hematopoietic cells remain unaffected. Disruption of immunoproteasome function drives an increase in transcription factor BASP1 which in turn represses KMT2A-fusion protein target genes. Pharmacologic targeting of PSMB8 improves efficacy of Menin-inhibitors, synergistically reduces leukemia in human xenografts and shows preserved activity against Menin-inhibitor resistance mutations. This identifies and validates a cell-intrinsic mechanism whereby selective disruption of proteostasis results in altered transcription factor abundance and repression of oncogene-specific transcriptional networks. These data demonstrate that the immunoproteasome is a relevant therapeutic target in AML and that targeting the immunoproteasome in combination with Menin-inhibition could be a novel approach for treatment of KMT2A-r AML.
Nano-modulators with the function of disrupting mitochondrial Ca2+ homeostasis and photothermal conversion for synergistic breast cancer therapy
Authors: Wang Chenglong , Li Tao , Wang Zhen , Li Yao , Liu Yan , Xu Maochang , Zhang Zongquan , Deng Yiping , Cai Liang , Zhang Chunxiang , Li Chunhong
Published: December 2023

Breast cancer treatment has been a global puzzle, and apoptosis strategies based on mitochondrial Ca2+ overload have attracted extensive attention. However, various limitations of current Ca2+ nanogenerators make it difficult to maintain effective Ca2+ overload concentrations. Here, we constructed a multimodal Ca2+ nano-modulator that, for the first time, combined photothermal therapy (PTT) and mitochondrial Ca2+ overload strategies to inhibit tumor development. By crosslinking sodium alginate (SA) on the surface of calcium carbonate (CaCO3) nanoparticles encapsulating with Cur and ICG, we prepared a synergistic Ca2+ nano-regulator SA/Cur@CaCO3-ICG (SCCI). In vitro studies have shown that SCCI further enhanced photostability while preserving the optical properties of ICG. After uptake by tumor cells, SCCI can reduce mitochondrial membrane potential and down-regulate ATP production by producing large amounts of Ca2+ at low pH. Near-infrared light radiation (NIR) laser irradiation made the tumor cells heat up sharply, which not only accelerated the decomposition of CaCO3, but also produced large amounts of reactive oxygen species (ROS) followed by cell apoptosis. In vivo studies have revealed that the Ca2+ nano-regulators had excellent targeting, biocompatibility, and anti-tumor effects, which can significantly inhibit the proliferation of tumor cells and play a direct killing effect. These findings indicated that therapeutic strategies based on ionic interference and PTT had great therapeutic potential, providing new insights into antitumor therapy.

Graphical Abstract
New insights into the stemness of adoptively transferred T cells by γc family cytokines
Authors: Luo Mengshi , Gong Wenjian , Zhang Yuewen , Li Huayi , Ma Ding , Wu Kongming , Gao Qinglei , Fang Yong
Published: December 2023

T cell-based adoptive cell therapy (ACT) has exhibited excellent antitumoral efficacy exemplified by the clinical breakthrough of chimeric antigen receptor therapy (CAR-T) in hematologic malignancies. It relies on the pool of functional T cells to retain the developmental potential to serially kill targeted cells. However, failure in the continuous supply and persistence of functional T cells has been recognized as a critical barrier to sustainable responses. Conferring stemness on infused T cells, yielding stem cell-like memory T cells (TSCM) characterized by constant self-renewal and multilineage differentiation similar to pluripotent stem cells, is indeed necessary and promising for enhancing T cell function and sustaining antitumor immunity. Therefore, it is crucial to identify TSCM cell induction regulators and acquire more TSCM cells as resource cells during production and after infusion to improve antitumoral efficacy. Recently, four common cytokine receptor γ chain (γc) family cytokines, encompassing interleukin-2 (IL-2), IL-7, IL-15, and IL-21, have been widely used in the development of long-lived adoptively transferred TSCM in vitro. However, challenges, including their non-specific toxicities and off-target effects, have led to substantial efforts for the development of engineered versions to unleash their full potential in the induction and maintenance of T cell stemness in ACT. In this review, we summarize the roles of the four γc family cytokines in the orchestration of adoptively transferred T cell stemness, introduce their engineered versions that modulate TSCM cell formation and demonstrate the potential of their various combinations.
ND630 controls ACACA and lipid reprogramming in prostate cancer by regulating the expression of circKIF18B_003
Authors: Wu Yu-Peng , Zheng Wen-Cai , Huang Qi , Huang Xu-Yun , Lin Fei , Ke Zhi-Bin , You Qi , Zheng Qing-Shui , Wei Yong , Xue Xue-Yi , Xu Ning
Published: December 2023

Background

ND630 is believed to be a new therapy pharmacologic molecule in targeting the expression of ACACA and regulating the lipid metabolism. However, the function of ND630 in prostate cancer remains unknown. KIF18B, as an oncogene, plays a vital role in prostate cancer progression. circKIF18B_003 was derived from oncogene KIF18B and was markedly overexpressed in prostate cancer tissues. We speculated that oncoprotein KIF18B-derived circRNA circKIF18B_003 might have roles in prostate cancer promotion. The aim of this study was to validate whether ND630 could control ACACA and lipid reprogramming in prostate cancer by regulating the expression of circKIF18B_003.

Methods

RT-qPCR was used to analyze the expression of circKIF18B_003 in prostate cancer cell lines and prostate cancer samples. circKIF18B_003 expression was modulated in prostate cancer cells using circKIF18B_003 interference or overexpression plasmid. We examined the function and effects of circKIF18B_003 in prostate cancer cells using CCK-8, colony formation, wound healing, and Transwell invasion assays and xenograft models. Fluorescence in situ hybridization (FISH) was performed to evaluate the localization of circKIF18B_003. RNA immunoprecipitation (RIP), RNA pull down, and luciferase reporter assay were performed to explore the potential mechanism of circKIF18B_003.

Results

The function of ND630 was determined in this study. circKIF18B_003 was overexpressed in prostate cancer tissues, and overexpression of circKIF18B_003 was associated with poor survival outcome of prostate cancer patients. The proliferation, migration, and invasion of prostate cancer cells were enhanced after up-regulation of circKIF18B_003. circKIF18B_003 is mainly located in the cytoplasm of prostate cancer cells, and the RIP and RNA pull down assays confirmed that circKIF18B_003 could act as a sponge for miR-370-3p. Further study demonstrated that up-regulation of circKIF18B_003 increased the expression of ACACA by sponging miR-370-3p. The malignant ability of prostate cancer cells enhanced by overexpression of circKIF18B_003 was reversed by the down-regulation of ACACA. We found that overexpression of circKIF18B_003 was associated with lipid metabolism, and a combination of ND-630 and docetaxel markedly attenuated tumor growth.

Conclusion

ND630 could control ACACA and lipid reprogramming in prostate cancer by regulating the expression of circKIF18B_003. ND630 and circKIF18B_003 may represent a novel target for prostate cancer.
Bioinformatics analysis of immune characteristics in tumors with alternative carcinogenesis pathways induced by human papillomaviruses
Authors: Smahel Michal , Nunvar Jaroslav
Published: December 2023

Background

Human papillomaviruses (HPVs) induce a subset of head and neck squamous cell carcinomas (HNSCC) and anogenital cancers, particularly cervical cancer (CC). The major viral proteins that contribute to tumorigenesis are the E6 and E7 oncoproteins, whose expression is usually enhanced after the integration of viral DNA into the host genome. Recently, an alternative tumorigenesis pathway has been suggested in approximately half of HNSCC and CC cases associated with HPV infection. This pathway is characterized by extrachromosomal HPV persistence and increased expression of the viral E2, E4, and E5 genes. The E6, E7, E5, and E2 proteins have been shown to modify the expression of numerous cellular immune-related genes. The antitumor immune response is a critical factor in the prognosis of HPV-driven cancers, and its characterization may contribute to the prediction and personalization of the increasingly used cancer immunotherapy.

Methods

We analyzed the immune characteristics of HPV-dependent tumors and their association with carcinogenesis types. Transcriptomic HNSCC and CC datasets from The Cancer Genome Atlas were used for this analysis.

Results

Clustering with immune-related genes resulted in two clusters of HPV16-positive squamous cell carcinomas in both tumor types: cluster 1 had higher activation of immune responses, including stimulation of the antigen processing and presentation pathway, which was associated with higher immune cell infiltration and better overall survival, and cluster 2 was characterized by keratinization. In CC, the distribution of tumor samples into clusters 1 and 2 did not depend on the level of E2/E5 expression, but in HNSCC, most E2/E5-high tumors were localized in cluster 1 and E2/E5-low tumors in cluster 2. Further analysis did not reveal any association between the E2/E5 levels and the expression of immune-related genes.

Conclusions

Our results suggest that while the detection of immune responses associated with preserved expression of genes encoding components of antigen processing and presentation machinery in HPV-driven tumors may be markers of better prognosis and an important factor in therapy selection, the type of carcinogenesis does not seem to play a decisive role in the induction of antitumor immunity.
A metabolomics study in aqueous humor discloses altered arginine metabolism in Parkinson’s disease
Authors: Serrano-Marín Joan , Marin Silvia , Bernal-Casas David , Lillo Alejandro , González-Subías Marc , Navarro Gemma , Cascante Marta , Sánchez-Navés Juan , Franco Rafael
Published: December 2023

Background

The lack of accessible and informative biomarkers results in a delayed diagnosis of Parkinson’s disease (PD), whose symptoms appear when a significant number of dopaminergic neurons have already disappeared. The retina, a historically overlooked part of the central nervous system (CNS), has gained recent attention. It has been discovered that the composition of cerebrospinal fluid influences the aqueous humor composition through microfluidic circulation. In addition, alterations found in the brain of patients with PD have a correlate in the retina. This new paradigm highlights the potential of the aqueous humor as a sample for identifying differentially concentrated metabolites that could, eventually, become biomarkers if also found altered in blood or CSF of patients. In this research we aim at analyzing the composition of the aqueous humor from healthy controls and PD patients.

Methods

A targeted metabolomics approach with concentration determination by mass spectrometry was used. Statistical methods including principal component analysis and linear discriminants were used to select differentially concentrated metabolites that allow distinguishing patients from controls.

Results

In this first metabolomics study in the aqueous humor of PD patients, elevated levels of 16 compounds were found; molecules differentially concentrated grouped into biogenic amines, amino acids, and acylcarnitines. A biogenic amine, putrescine, alone could be a metabolite capable of differentiating between PD and control samples. The altered levels of the metabolites were correlated, suggesting that the elevations stem from a common mechanism involving arginine metabolism.

Conclusions

A combination of three metabolites, putrescine, tyrosine, and carnitine was able to correctly classify healthy participants from PD patients. Altered metabolite levels suggest altered arginine metabolism. The pattern of metabolomic disturbances was not due to the levodopa-based dopamine replacement medication because one of the patients was not yet taking levodopa but a dopamine receptor agonist.
The optimisation of public health emergency governance: a simulation study based on COVID-19 pandemic control policy
Authors: Yang Keng , Qi Hanying
Published: December 2023

Background

The outbreak of the COVID-19 pandemic sparked numerous studies on policy options for managing public health emergencies, especially regarding how to choose the intensity of prevention and control to maintain a balance between economic development and disease prevention.

Methods

We constructed a cost-benefit model of COVID-19 pandemic prevention and control policies based on an epidemic transmission model. On this basis, numerical simulations were performed for different economies to analyse the dynamic evolution of prevention and control policies. These economies include areas with high control costs, as seen in high-income economies, and areas with relatively low control costs, exhibited in upper-middle-income economies.

Results

The simulation results indicate that, at the outset of the COVID-19 pandemic, both high-and low-cost economies tended to enforce intensive interventions. However, as the virus evolved, particularly in circumstances with relatively rates of reproduction, short incubation periods, short spans of infection and low mortality rates, high-cost economies became inclined to ease restrictions, while low-cost economies took the opposite approach. However, the consideration of additional costs incurred by the non-infected population means that a low-cost economy is likely to lift restrictions as well.

Conclusions

This study concludes that variations in prevention and control policies among nations with varying income levels stem from variances in virus transmission characteristics, economic development, and control costs. This study can help researchers and policymakers better understand the differences in policy choice among various economies as well as the changing trends of dynamic policy choices, thus providing a certain reference value for the policy direction of global public health emergencies.
Retrospective analysis of the 18F-FDG PET/CT cutoff value for metabolic parameters was performed as a prediction model to evaluate risk factors for endometrial cancer
Authors: Yang Ye , Pan Yu-Qin , Wang Min , Gu Song , Bao Wei
Published: December 2023

Purpose

The study retrospectively analyzed the accuracy and predictive ability of preoperative integrated whole-body 18F-FDG PET/CT for the assessment of high-risk factors in patients with endometrial carcinoma (EC).

Materials and methods

A total of 205 patients with endometrial cancer who underwent preoperative PET/CT at Shanghai General Hospital from January 2018 to December 2021 were retrospectively evaluated and last follow-up was June 2023. Our study evaluated the ability and optimal cutoff values of three metabolic and volumetric parameters—standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG)—to predict deep myometrial invasion (DMI), endocervical stroma invasion (ESI) and lymph node metastases (LNM) in endometrial cancer. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET/CT were used to assess the diagnostic performance for the prediction.

Results

Our study demonstrated a significant relationship between SUVmax (11.29, 17.38, 9.47), SUVmean (5.20, 6.12, 4.49), MTV (38.15, 36.28, 33.79 ml), and TLG (199.30, 225.10, 156.40 g) on PET/CT and histologically confirmed DMI, ESI and LNM in endometrial carcinoma (EC), with sensitivity, specificity, accuracy, PPV, and NPV of 100%/100%/100%, 96.53%/98.89%/87.14%, 97.56%/99.02%/91.22%, 92.42%/92.85%/78.31%, and 100%/100%/100%, respectively. Our study showed a risk model based on optimal cutoff values for MTV and TLG of 19.6 ml/126.3 g, 20.54 ml/84.80 g and 24 ml/49.83 g to preoperatively predict DMI, ESI, and LNM, respectively, in endometrial carcinoma. The 4-year OS (HR) for Stage IA, IB, II, III and IV according to 2009 FIGO was 98.00% (0.22), 95.20% (0.04), 83.90% (0.18), 90.50% (0.09) and 60% (0.51). Accordingly, estimated 4-year DFS (HR) for the stage IA-III was 98% (0.02), 95.20% (0.05), 76.90% (0.27) and 76.30% (0.35), all the patients in stage IV occurred recurrence and progression.

Conclusion

The present study showed patients with MTV > = 19.6 ml of MI and PET- positive LN with MTV cutoff > = 24 ml tended to predict poor OS and PFS in endometrial carcinoma. The cutoff of MTV and TLG in PET/CT assessment could be an independent prognostic factors to predict aggressive forms of EC.

Graphic Abstract
The potentially dangerous zone of the dorsomedial cutaneous nerve in minimally invasive surgery for hallux valgus: a cadaveric study
Authors: Teng Zhaolin , Geng Xiang , Song Jiafeng , Chen Li , Zhang Chao , Huang Jiazhang , Wang Xu , Ma Xin
Published: December 2023

Background

This study aims to describe the distribution of the dorsomedial cutaneous nerve (DMCN) in the middle and proximal parts of the metatarsal from a lateral view. The purpose is to provide guidance to surgeons in protecting the nerve during the 3rd and 4th generation minimally invasive surgery (MIS) for hallux valgus (HV).

Methods

A total of 20 cadaveric feet were dissected to expose the course of the DMCN and sentinel vein. Measurements of the distances between the nerve/vein and the upper border of the metatarsal, as well as the height of the metatarsal, were taken from a lateral view. The distribution area was then described in proportion.

Results

At the base of the metatarsal, the DMCN was distributed in the upper 25.7% of the area. When it reached the middle of the metatarsal, the DMCN was distributed in the upper 13.2–47.2% of the area. As for the sentinel vein, it was distributed in the upper 23.5–71.9% and upper 4.1–52.7%, respectively, at these two positions.

Conclusions

The area, which is above the line connecting the upper 1/4 point at the base of the first metatarsal and the 1/2 point at the middle of the first metatarsal, is a dangerous zone for the DMCN. Avoiding the zone is recommended during MIS for HV.
Remimazolam besylate versus propofol for deep sedation in critically ill patients: a randomized pilot study
Authors: Tang Yun , Gao Xuehui , Xu Jiqian , Ren Lehao , Qi Hong , Li Ruiting , Shu Huaqing , Zou Xiaojing , Yuan Shiying , Yang Xiaobo , Shang You
Published: December 2023

Objective

To compare the efficacy and safety of remimazolam besylate and propofol for deep sedation in critically ill patients.

Methods

In this single-center, prospective, randomized, controlled pilot study, patients in the intensive care unit (ICU) requiring deep sedation were randomized to receive remimazolam besylate or propofol intravenously. Deep sedation was defined as a Richmond Agitation and Sedation Scale (RASS) score of − 4 or − 5. Sedation depth was monitored using RASS and Narcotrend Index (NI). The primary outcome was the percentage of time within the target sedation range without rescue sedation. The secondary outcomes included ventilator-free hours within 7 days, successful extubation, length of ICU stay, and 28-day mortality. Adverse events during the interventional period were also recorded.

Results

Thirty patients were assigned to each group. The median (IQR) RASS score was − 5.0 (− 5.0, − 4.0), and the median (IQR) NI value was 29.0 (21.0, 37.0) during the intervention period. Target RASS was reached a median of 100% of the sedation time in the two groups. No significant differences were observed in ventilator-free hours within 7 days, successful extubation, length of ICU stay, or 28-day mortality among groups. Hypotension occurred in 16 (53.3%) patients of remimazolam group and 18 (60.0%) patients of propofol group (p > 0.05). No patient experienced bradycardia.

Conclusions

Remimazolam besylate appears to be an effective and safe agent for short-term deep sedation in critically ill patients. Our findings warrant large sample-sized randomized clinical trials.