bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-term response of primary human meniscus cells to simulated microgravity
Authors: Ma Zhiyao , Li David Xinzheyang , Lan Xiaoyi , Bubelenyi Adam , Vyhlidal Margaret , Kunze Melanie , Sommerfeldt Mark , Adesida Adetola B.
Published: June 2024

Background

Mechanical unloading of the knee articular cartilage results in cartilage matrix atrophy, signifying the osteoarthritic-inductive potential of mechanical unloading. In contrast, mechanical loading stimulates cartilage matrix production. However, little is known about the response of meniscal fibrocartilage, a major mechanical load-bearing tissue of the knee joint, and its functional matrix-forming fibrochondrocytes to mechanical unloading events.

Methods

In this study, primary meniscus fibrochondrocytes isolated from the inner avascular region of human menisci from both male and female donors were seeded into porous collagen scaffolds to generate 3D meniscus models. These models were subjected to both normal gravity and mechanical unloading via simulated microgravity (SMG) for 7 days, with samples collected at various time points during the culture.

Results

RNA sequencing unveiled significant transcriptome changes during the 7-day SMG culture, including the notable upregulation of key osteoarthritis markers such as COL10A1, MMP13, and SPP1, along with pathways related to inflammation and calcification. Crucially, sex-specific variations in transcriptional responses were observed. Meniscus models derived from female donors exhibited heightened cell proliferation activities, with the JUN protein involved in several potentially osteoarthritis-related signaling pathways. In contrast, meniscus models from male donors primarily regulated extracellular matrix components and matrix remodeling enzymes.

Conclusion

These findings advance our understanding of sex disparities in knee osteoarthritis by developing a novel in vitro model using cell-seeded meniscus constructs and simulated microgravity, revealing significant sex-specific molecular mechanisms and therapeutic targets.
The paradox of growing technical capacities with low global governance: a review of Voluntary National Reviews’ SDG health-related indicators
Authors: Martins Ana Luisa Jorge , Paes-Sousa Rômulo
Published: June 2024

Background

This study delves into the States’ accountability for health-related Sustainable Development Goal (SDG) indicators from 2016 to 2020. An analysis of Voluntary National Reviews (VNR) is employed as an instrument to scrutinize the alignment of States’ indicators with the global indicator framework, shedding light on global health governance within the context of the 2030 Agenda and States’ strategic prioritization. A curation of 60 health-related indicators from 195 VNRs, produced during the aforementioned period, is organized into thematic groups.

Results

Our results highlight a concerning discrepancy in the reporting frequency of various health-related themes. The findings reveal a paradoxical coexistence characterized by the concurrent strengthening and diminution of the global health governance articulated in the Agenda’s global health governance. This manifests in the increased utilization and consistency of health-related indicators over the study years, coupled with an emphasis on infectious diseases and child and maternal health indicators. Conversely, a discernible governance decline is evidenced by the inadequate representation of health-related indicators in VNRs, notably within the domains of universal health coverage and health system indicators. Furthermore, High-Income States exhibit diminished accountability.

Conclusions

The VNRs unveil a paradox wherein burgeoning technical capacity coexists with governance deficits, a phenomenon attributable to both statistical capabilities and political preferences. The prevalent use of proxy indicators in VNRs oversimplifies the presentation of official indicators, thereby compromising the aspirational goal of pioneering statistical innovations for measuring intricate issues in the SDGs. In light of our conceptualization of the 2030 Agenda’s global health as a regime complex governance, we advocate for comprehensive investigations into each health regime cluster. This approach aims to unravel disputes, discern patterns, and elucidate States’ preferences concerning specific thematic areas. Functioning as an accountability mechanism for the Agenda’s governance, VNRs underscore States’ adaptability and short-term learning capabilities, offering valuable insights for identifying harmful goal prioritization. The discretionary nature of indicator selection by States in the VNRs, enabled by the Agenda’s proposition of a contextual adaptation of the SDGs and a blind eye to the guideline’s request to review all SDG indicators, highlights a critical flaw in the VNR as an accountability mechanism.
The effectiveness of multidisciplinary interventions based on health belief model on musculoskeletal pain in the elderly living in nursing homes: a study protocol for a randomized controlled trial
Authors: Habibi Sogand , Tavafian Sedigheh Sadat , Maghbouli Reza , Montazeri Ali
Published: June 2024

Background

Due to the burden of musculoskeletal diseases in the elderly and the multifactorial nature of such conditions, controlling the pain caused by these disorders requires multidisciplinary approach. This approach requires the participation of the elderly in applying effective prevention measures. This study aims to design a multidisciplinary educational intervention based on health belief model (HBM) for elderly residents of nursing homes.

Methods

This is a parallel randomized clinical trial among elderly people aged 60 years and over living in a nursing home who suffer from musculoskeletal pain. Eligible participants will be divided into two groups including the intervention group who will receive a multidisciplinary intervention (vitamin D consumption, psycho-social stress management, and physiotherapy) and the control group who will receive usual care. Data collection instruments will include demographic data, the Depression, Anxiety, and Stress Scale (DASS), the visual analogue scale (VAS), and a self-designed questionnaire containing the HBM constructs. The interventions will be carried out by the educational team (general practitioner, psychologist, physiotherapist, and health education specialist). Interventions include changing the wrong beliefs of the elderly, taking 800 units of vitamin D daily, daily walking exercise by the elderly for at least 30 min and maintaining proper body posture during daily activities, muscle relaxation, relaxation techniques, regular exercise, examining their diet and eliminating stimulants (such as smoking and coffee), regular visits with friends and family, and deep breathing techniques. All questionnaires will be completed by the elderly before, after, 3, and 6 months after the intervention.

Discussion

The present study will evaluate the effect of an educational intervention based on a multifaceted pain control approach for elderly people who reside in nursing homes in order to reduce musculoskeletal pain in the elderly living in nursing homes. One of the features of this study is its focus on improving the health of elderly residents in nursing homes. Given the increase in the elderly population worldwide, the findings from the current trial might benefit elderly populations.

Trial registration

IRCT20220904055881N1. Registered on 11 February 2023.
Evolution of glial cells: a non-bilaterian perspective
Authors: Sheloukhova Larisa , Watanabe Hiroshi
Published: June 2024

Nervous systems of bilaterian animals generally consist of two cell types: neurons and glial cells. Despite accumulating data about the many important functions glial cells serve in bilaterian nervous systems, the evolutionary origin of this abundant cell type remains unclear. Current hypotheses regarding glial evolution are mostly based on data from model bilaterians. Non-bilaterian animals have been largely overlooked in glial studies and have been subjected only to morphological analysis. Here, we provide a comprehensive overview of conservation of the bilateral gliogenic genetic repertoire of non-bilaterian phyla (Cnidaria, Placozoa, Ctenophora, and Porifera). We overview molecular and functional features of bilaterian glial cell types and discuss their possible evolutionary history. We then examine which glial features are present in non-bilaterians. Of these, cnidarians show the highest degree of gliogenic program conservation and may therefore be crucial to answer questions about glial evolution.
Comprehensive meta-analysis of severe fever with thrombocytopenia syndrome virus infections in humans, vertebrate hosts and questing ticks
Authors: Xu Ao-Long , Xue Han , Li Yi , Wang Xu , Zheng Jin-Xin , Shi Fu-Yan , Cui Qing-Xia , Lu Yan , Cun De-Jiao , Li Lan-Hua
Published: June 2024

Background

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonosis caused by the SFTS virus (SFTSV). Understanding the prevalence of SFTSV RNA in humans, vertebrate hosts and ticks is crucial for SFTS control.

Methods

A systematic review and meta-analysis were conducted to determine the prevalence of SFTSV RNA in humans, vertebrate hosts and questing ticks. Nine electronic databases were searched for relevant publications, and data on SFTSV RNA prevalence were extracted. Pooled prevalence was estimated using a random effects model. Subgroup analysis and multivariable meta-regression were performed to investigate sources of heterogeneity.

Results

The pooled prevalence of SFTSV RNA in humans was 5.59% (95% confidence interval [CI] 2.78–9.15%) in those in close contact (close contacts) with infected individuals (infected cases) and 0.05% (95% CI 0.00–0.65%) in healthy individuals in endemic areas. The SFTSV infection rates in artiodactyls (5.60%; 95% CI 2.95–8.96%) and carnivores (6.34%; 95% CI 3.27–10.23%) were higher than those in rodents (0.45%; 95% CI 0.00–1.50%). Other animals, such as rabbits, hedgehogs and birds, also played significant roles in SFTSV transmission. The genus Haemaphysalis was the primary transmission vector, with members of Ixodes, Dermacentor, and Amblyomma also identified as potential vectors. The highest pooled prevalence was observed in adult ticks (1.03%; 95% CI 0.35–1.96%), followed by nymphs (0.66%; 95% CI 0.11–1.50%) and larvae (0.01%; 95% CI 0.00–0.46%). The pooled prevalence in ticks collected from endemic areas (1.86%; 95% CI 0.86–3.14%) was higher than that in ticks collected in other regions (0.41%; 95% CI 0.12–0.81%).

Conclusions

Latent SFTSV infections are present in healthy individuals residing in endemic areas, and close contacts with SFTS cases are at a significantly higher risk of infection. The type of animal is linked to infection rates in vertebrate hosts, while infection rates in ticks are associated with the developmental stage. Further research is needed to investigate the impact of various environmental factors on SFTSV prevalence in vertebrate hosts and ticks.

Graphical Abstract
Quantitative US fat fraction for noninvasive assessment of hepatic steatosis in suspected metabolic-associated fatty liver disease
Authors: Yin Haohao , Fan Yunling , Yu Jifeng , Xiong Bing , Zhou Boyang , Sun Yikang , Wang Lifan , Zhu Yuli , Xu Huixiong
Published: June 2024

Objectives

To evaluate the agreement between quantitative ultrasound system fat fraction (USFF) and proton magnetic resonance spectroscopy (1H-MRS) and the diagnostic value of USFF in assessing metabolic-associated fatty liver disease (MAFLD).

Methods

The participants with or suspected of MAFLD were prospectively recruited and underwent 1H-MRS, USFF, and controlled attenuation parameter (CAP) measurements. The correlation between USFF and 1H-MRS was assessed using Pearson correlation coefficients. The USFF diagnostic performance for different grades of steatosis was evaluated using receiver operating characteristic curve analysis (ROC) and was compared with CAP, visual hepatic steatosis grade (VHSG).

Results

A total of 113 participants (mean age 44.79 years ± 13.56 (SD); 71 males) were enrolled, of whom 98 (86.73%) had hepatic steatosis (1H-MRS ≥ 5.56%). USFF showed a good correlation (Pearson r = 0.76) with 1H-MRS and showed a linear relationship, which was superior to the correlation between CAP and 1H-MRS (Pearson r = 0.61). The USFF provided high diagnostic performance for different grades of hepatic steatosis, with ROC from 0.84 to 0.98, and the diagnostic performance was better than that of the CAP and the VHSG. The cut-off values of the USFF were different for various grades of steatosis, and the cut-off values for S1, S2, and S3 were 12.01%, 19.98%, and 22.22%, respectively.

Conclusions

There was a good correlation between USFF and 1H-MRS. Meanwhile, USFF had good diagnostic performance for hepatic steatosis and was superior to CAP and VHSG. USFF represents a superior method for noninvasive quantitative assessment of MAFLD.

Critical relevance statement

Quantitative ultrasound system fat fraction (USFF) accurately assesses liver fat content and has a good correlation with magnetic resonance spectroscopy (1H-MRS) for the assessment of metabolic-associated fatty liver disease (MAFLD), as well as for providing an accurate quantitative assessment of hepatic steatosis.

Key Points

Current diagnostic and monitoring modalities for metabolic-associated fatty liver disease have limitations.

USFF correlated well with 1H-MRS and was superior to the CAP.

USFF has good diagnostic performance for steatosis, superior to CAP and VHSG.

Graphical Abstract
UBQLN1 links proteostasis and mitochondria function to telomere maintenance in human embryonic stem cells
Authors: Zhao Shuang , Li Jie , Duan Songqi , Liu Chang , Wang Hua , Lu Jiangtao , Zhao Nannan , Sheng Xiaoyan , wu Yiwei , Li Yanjun , Sun Baofa , Liu Lin
Published: June 2024

Background

Telomeres consist of repetitive DNA sequences at the chromosome ends to protect chromosomal stability, and primarily maintained by telomerase or occasionally by alternative telomere lengthening of telomeres (ALT) through recombination-based mechanisms. Additional mechanisms that may regulate telomere maintenance remain to be explored. Simultaneous measurement of telomere length and transcriptome in the same human embryonic stem cell (hESC) revealed that mRNA expression levels of UBQLN1 exhibit linear relationship with telomere length.

Methods

In this study, we first generated UBQLN1-deficient hESCs and compared with the wild-type (WT) hESCs the telomere length and molecular change at RNA and protein level by RNA-seq and proteomics. Then we identified the potential interacting proteins with UBQLN1 using immunoprecipitation-mass spectrometry (IP-MS). Furthermore, the potential mechanisms underlying the shortened telomeres in UBQLN1-deficient hESCs were analyzed.

Results

We show that Ubiquilin1 (UBQLN1) is critical for telomere maintenance in human embryonic stem cells (hESCs) via promoting mitochondrial function. UBQLN1 deficiency leads to oxidative stress, loss of proteostasis, mitochondria dysfunction, DNA damage, and telomere attrition. Reducing oxidative damage and promoting mitochondria function by culture under hypoxia condition or supplementation with N-acetylcysteine partly attenuate the telomere attrition induced by UBQLN1 deficiency. Moreover, UBQLN1 deficiency/telomere shortening downregulates genes for neuro-ectoderm lineage differentiation.

Conclusions

Altogether, UBQLN1 functions to scavenge ubiquitinated proteins, preventing their overloading mitochondria and elevated mitophagy. UBQLN1 maintains mitochondria and telomeres by regulating proteostasis and plays critical role in neuro-ectoderm differentiation.
Osteochondral organoids: current advances, applications, and upcoming challenges
Authors: Faeed Maryam , Ghiasvand Mahsa , Fareghzadeh Bahar , Taghiyar Leila
Published: June 2024

In the realm of studying joint-related diseases, there is a continuous quest for more accurate and representative models. Recently, regenerative medicine and tissue engineering have seen a growing interest in utilizing organoids as powerful tools for studying complex biological systems in vitro. Organoids, three-dimensional structures replicating the architecture and function of organs, provide a unique platform for investigating disease mechanisms, drug responses, and tissue regeneration. The surge in organoid research is fueled by the need for physiologically relevant models to bridge the gap between traditional cell cultures and in vivo studies. Osteochondral organoids have emerged as a promising avenue in this pursuit, offering a better platform to mimic the intricate biological interactions within bone and cartilage. This review explores the significance of osteochondral organoids and the need for their development in advancing our understanding and treatment of bone and cartilage-related diseases. It summarizes osteochondral organoids’ insights and research progress, focusing on their composition, materials, cell sources, and cultivation methods, as well as the concept of organoids on chips and application scenarios. Additionally, we address the limitations and challenges these organoids face, emphasizing the necessity for further research to overcome these obstacles and facilitate orthopedic regeneration.
Development of an animal health testing tool to reduce antimicrobial use on farms: perceptions, implications, and needs of Irish dairy farmers and farm veterinarians
Authors: McGrath Karen , Regan Áine , Kennedy Emer , Russell Tomás
Published: June 2024

Background

The threat of antimicrobial resistance is triggering the need for behavioural change towards antimicrobial use on Irish farms. Newly introduced veterinary medicine regulations are mandating the restricted and more prudent use of antimicrobials in the animal health sector. The need to reduce antimicrobials has placed a greater emphasis on the importance of animal health testing, however, issues with current testing practices are affecting diagnosis and subsequent drug usage. There is potential for digital technologies to address these issues and reduce antimicrobial use on farms, however, for these tools to be successful, they would need to be developed in collaboration with future end users.

Results

Using qualitative approaches (focus groups), this study engages with dairy farmers and farm veterinary practitioners to detail current challenges with animal health diagnosis and to explore the initial development of a rapid, on-farm animal health testing tool to address these challenges. Issues with timing and testing, the role of knowledge and experience, and veterinarian availability all affect the ability of farmers and veterinarians to diagnose animal health issues on farm. These issues are having negative implications including the increased and unnecessary use of antimicrobials. An on-farm testing tool would help mitigate these effects by allowing veterinarians to achieve rapid diagnosis, facilitating the timely and targeted treatment of animal illnesses, helping to reduce overall antimicrobial use on farms. However, engagement with end users has highlighted that if a tool like this is not developed correctly, it could have unintended negative consequences such as misdiagnosis, increased antimicrobial use, challenges to farmer-veterinarian relationships, and data misuse. This study outlines initial end user needs and requirements for a testing tool but suggests that in order to successfully design and develop this tool, co-design approaches such as Design Thinking should be applied; to mitigate future negative impacts, and to ensure a testing tool like this is designed specifically to address Irish dairy farmers and farm veterinarians’ values and needs, ensuring responsible and successful uptake and use.

Conclusions

Digital tools can be effective in reducing antimicrobial use on farms, however, to be successful, these tools should be designed in a user centred way.
Proneness to false memory generation predicts pseudoscientific belief endorsement
Authors: Martínez Naroa , Barberia Itxaso , Rodríguez-Ferreiro Javier
Published: June 2024

Among cognitive factors that can influence the endorsement of pseudoscientific beliefs, our study focuses on proneness to false memory generation. In this preregistered study, we presented 170 fluent English speakers residing in the USA with a misinformation task aimed at generating false memories. In this task, they first completed an event encoding stage, in which two events were narrated through sequentially presented pictures. One day later, they read a series of sentences relating the same events but which included several inaccurate descriptions aimed at producing a misinformation effect. Finally, we measured the influence of the misinformation manipulation over false memory generation. After completing the misinformation task, participants responded to a questionnaire measuring pseudoscientific beliefs. Our results showed a positive correlation between pseudoscience endorsement and false memory rates, which indicates that the latter might be a key factor influencing susceptibility to pseudoscience. To our knowledge, this is the first study showing a link between the tendency to believe in pseudoscience and variability regarding proneness to develop false memories. Practical implications for the design of new interventions to effectively reduce pseudoscientific beliefs and their negative impact on our society are discussed.
Petrophysical parameter estimation using a rock-physics model and collaborative sparse representation
Authors: Wang Yaojun , Shen Bingxin , Yu Zilin , Li Lin , Zhang Tuo , Chen Ting
Published: June 2024

The estimation of petrophysical parameters is key in the identification of underground reservoirs. Current petrophysical parameter estimation methods are typically constrained by the choice of particular rock-physics models, necessitating the use of distinct models for various reservoirs. Furthermore, the inherent pronounced nonlinearity of these models presents significant challenges to the solution process in reservoir parameter inversion. Although linearized petrophysical inversion methods can simplify the solving process, they can introduce errors due to linearization. To address these limitations, we develop a petrophysical parameter estimation method driven by a rock-physics model and collaborative sparse representation (CSR). In this approach, the rock-physics model governs the fundamental pattern of the petrophysical parameters, with the CSR introducing perturbations to minimize model errors. Our method maximizes the use of well-log data and the rock-physics model, thereby reducing errors associated with linearized rock-physics (LRP) models and enhancing the method’s adaptability. We use the joint dictionary method to learn features and correlations among multiple parameters from the existing well-log data. This learned dictionary is then used as a CSR regularization constraint and applied to refine the LRP inversion objective function. Finally, the objective function is minimized using the block coordinate descent method to predict the petrophysical parameters. The effectiveness of this method in enhancing the adaptability and accuracy of petrophysical parameter estimation is confirmed through synthetic and field data tests.
Microbiome signature, immune landscape and global methylation in early onset colorectal cancer.
Authors: Jin Ning , Hoyd Rebecca , Yilmaz Ayse Selen , Zhang Shiqi , Liu YunZhou , Grencewicz Dennis , Jagjit Singh Malvenderjit , Zhu Jiangjiang , Liu Bei , Mo Xiaokui , Spakowicz Daniel ,   exORIEN Consortium
Published: June 2024

3580

Background: The incidence of colorectal cancer (CRC) in young adults (age at diagnosis < 50 years old) has been rapidly increasing. Approximately 20% of early-onset (EO) CRC cases are due to germline gene mutations. However, the etiology of sporadic EO CRC remains poorly understood. Research suggests that environmental factors such as Western diet may be associated with increased incidence of sporadic EO CRC. The gut microbiota decomposes and ferments dietary fibers to produce microbial metabolites, which play important roles in maintaining the intestinal epithelium integrity. A high-fat, low-fiber diet has been associated with intestinal dysbiosis, which disrupts intestinal bacterial homeostasis. An increased inflammation state characterizes dysbiosis and may promote an immunosuppressive tumor microenvironment (TME) and suppress antitumor immune surveillance. In addition, epigenetic modifications are influenced by environmental changes and therefore epigenetics may bridge the knowledge gap in understanding the development of sporadic EOCRC. Methods: We obtained RNA sequencing data from the Cancer Genome Atlas (TCGA) and the Oncology Research Information Exchange Network (ORIEN) from the Ohio State University biospecimen services to characterize intra-tumor microbiota composition, tumor-infiltrating lymphocytes (TILs) and differential pathways in EO CRC. We used Infinium HM450 methylation array in The Cancer Genome Atlas (TCGA) and performed genome-wide analyses using reduced representation bisulfite sequencing (RRBS) method to identify differentially methylated regions (DMRs) in EO CRC. Results: Gene expression analysis is consistent with Fusobacterium promoting inflammation in EO CRC. Intra-tumor microbes are positively correlated with M2 macrophages. Compared to late onset (LO) CRC, EO CRC patients have unique gene signatures of phagosome formation, S100 family signaling pathway and CREB signaling in neurons by using ingenuity pathway analysis (IPA). In addition, we found that methylation ages predicted by epigenetic clocks in EO CRC patients were 15 years older on average than their chronological ages, whereas methylation ages in late onset (LO) CRC patients were comparable with chronological ages. The enriched pathways based on DMRs associated with EO CRC have significant overlap with canonical pathways based on differentially expressed genes (DEGs), including CREB signaling in neurons and S100 family signaling pathways. Conclusions: These data suggest that pathogenic microbes may induce inflammation, which leads to accelerated aging in EO CRC.
Camrelizumab plus rivoceranib vs sorafenib as first-line therapy for unresectable hepatocellular carcinoma (uHCC): Final overall survival analysis of the phase 3 CARES-310 study.
Authors: Vogel Arndt , Chan Stephen Lam , Ren Zhenggang , Bai Yuxian , Gu Shanzhi , Lin Xiaoyan , Chen Zhendong , Jia Weidong , Jin Yongdong , Guo Yabing , Hu Xiaohua , Sultanbaev Alexander Valerievich , Pazgan-Simon Monika , Pisetska Margaryta , Nip Tsz Keung , Zhang Haisong , Du Jinghua , Cheng Ann-Lii , Kaseb Ahmed Omar , Qin Shukui ,   CARES-310 Study Group
Published: June 2024

4110

Background: The phase 3 CARES-310 trial is the first to demonstrate significant progression-free survival (PFS) and overall survival (OS) benefits with immunotherapy plus an anti-angiogenic tyrosine kinase inhibitor (TKI) over standard TKI as first-line treatment for uHCC. In the primary analysis of PFS (data cut-off [DCO], May. 10, 2021) and interim analysis of OS (DCO, Feb. 8, 2022), significant improvements were observed with camrelizumab (C; anti-PD-1 antibody) + rivoceranib (R; VEGFR2-TKI) vs. sorafenib (S). Here, we report updated data at the final analysis (FA), after an additional follow-up of ~16 mo. Methods: In this international, randomized, open-label, phase 3 trial, 543 patients with uHCC who had not previously received systemic treatment were randomized 1:1 to receive either C (200 mg, iv, q2w) + R (250 mg, po, qd) or S (400 mg, po, bid). As of Jun.14, 2023, 351 (65%) deaths occurred, and a protocol-specified FA was performed. Results: 272 patients were allocated to C+R and 271 to S. At DCO of FA, median follow-up was 22.1 mo in C+R group and 14.9 mo in S group. After end of study treatment, 36% of patients in C+R group and 42% in S group received subsequent targeted therapy; 17% and 36% received immunotherapy, respectively. Median OS was significantly prolonged with C+R vs . S (23.8 mo [95% CI 20.6-27.2] vs. 15.2 mo [95% CI 13.2-18.5]; hazard ratio (HR) 0.64 [95% CI 0.52-0.79]; 1-sided p <0.0001). OS rate with C+R vs.S was 49.0% vs. 36.2% at 24 mo, and 37.7% vs. 24.8% at 36 mo. OS benefits with C+R was generally consistent across subgroups, regardless of geographical region, race, and aetiology. Benefits in PFS, objective response rate (ORR) and duration of response (DoR) with C+R were also sustained after prolonged follow-up (Table). Safety data aligned with the interim OS analysis, with no new signals noted. Conclusions: At the protocol-specified FA, C+R continued to show clinically meaningful survival improvement compared with S, with manageable safety. The extended follow-up further confirmed the favorable benefit-to-risk profile of C+R, supporting it as a new first-line treatment option for uHCC. Clinical trial information: NCT03764293 . [Table: see text]
Safety analysis by treatment periods from EMERALD-1: A phase 3, randomized, placebo-controlled study of transarterial chemoembolization with durvalumab with/without bevacizumab in participants with embolization-eligible unresectable hepatocellular carcinoma.
Authors: Chan Stephen Lam , Sangro Bruno , Kudo Masatoshi , Erinjeri Joseph P. , Qin Shukui , Ren Zhenggang , Arai Yasuaki , Breder Valeriy Vladimirovich , Lin Shi-Ming , Peron Jean-Marie , Nguyen Tien Quang , Yan Lunan , Chiu Chang-Fang , Santos Florinda A. , Veluvolu Anil , Thungappa Satheesh Chiradoni , Morgan Claire , Parsons Kerry , Xynos Ioannis , Lencioni Riccardo
Published: June 2024

4122

Background: The global Phase 3 EMERALD-1 study (NCT03778957) primary endpoint was met: durvalumab (D) + bevacizumab (B) + transarterial chemoembolization (TACE) significantly improved progression-free survival vs placebos (pbos)+TACE (median 15.0 vs 8.2 mo; HR 0.77; 95% CI 0.61–0.98; p=0.032 [threshold 0.0435]) in participants (pts) with embolization-eligible unresectable hepatocellular carcinoma (uHCC) with a manageable safety profile. This post hoc, exploratory analysis assessed safety in the study’s 2 treatment (tx) periods (pds): D-TACE (D-T) and D-B. Methods: Pts were randomized 1:1:1 to D+TACE, D+B+TACE, or pbos+TACE. In the D-T pd, pts received 1–4 TACE (cTACE or DEB-TACE [investigator choice]) plus D (1500 mg Q4W) or pbo for D. In the D-B pd, post-last TACE, pts received D (1120 mg Q3W) plus pbo for B, D (1120 mg Q3W) plus B (15 mg/kg Q3W), or pbos for D and B. Adverse events (AEs), start/end date, maximum/change in CTCAE grade, and causality were assessed in the D-T and D-B pds in pts who received any study tx in the arm to which they were randomized, until end of follow-up. Results: The Table shows duration of exposure (DoE). In the D+TACE, D+B+TACE, and pbos+TACE arms, AEs were reported by 144 (74.6%), 139 (72.0%), and 148 (74.0%) pts in the D-T pd and 133 (68.9%), 147 (76.2%), and 132 (66.0%) pts in the D-B pd; were possibly related (pos rel) to study tx in 59 (30.6%), 56 (29.0%), and 41 (20.5%) pts in the D-T pd and 76 (39.4%), 114 (59.1%), and 69 (34.5%) pts in the D-B pd; and were provoked by TACE in 72 (37.3%), 90 (46.6%), and 85 (42.5%) pts in the D-T pd and 16 (8.3%), 18 (9.3%), and 21 (10.5%) pts in the D-B pd, respectively. Conclusions: D+B+TACE had a manageable safety profile across the D-T and D-B pds, consistent with the individual agents and underlying disease. These data further support D+B+TACE as a new potential standard of care in embolization-eligible uHCC. Clinical trial information: NCT03778957 . [Table: see text]
Severe Hypertriglyceridemia in a Patient With Metabolic Syndrome and Psoriasis on Risankizumab-Rzaa
Authors: Abdulwadood Isra , De melo Jose F , Scheel Robert C , Bois John P
Published: June 2024

We report a case of severe hypertriglyceridemia (HTG) complicated by hyperviscosity syndrome as a possible adverse reaction to risankizumab-rzaa in a 49-year-old male with a history of longstanding uncontrolled type 2 diabetes, obesity, and coronary artery disease with prior ST-elevation myocardial infarction. On admission, the patient presented with xanthomatous plaques, chest and epigastric discomfort, and headache. Subsequent blood testing revealed severely elevated triglyceride (TG) levels at 7670 mg/dL (86.59 mmol/L) [reference range: <150 mg/dL; 1.69 mmol/L] and total cholesterol at 934 mg/dL (24.14 mmol/L) [reference range: <200 mg/dL; 5.17 mmol/L]. Triglyceride levels decreased and symptoms resolved with dietary restrictions and plasmapheresis. At follow-up, his TG remained elevated but improved, and he was advised to continue lipid-lowering medications as well as cessation of risankizumab. While the patient presented with high risk factors, we posit that the subacute presentation of severe HTG is a possible result of his recent course of risankizumab-rzaa therapy for management of psoriasis. This is noteworthy as pharmaceutical surveys and clinical trials do not list severe HTG as an adverse effect. Postmarketing surveillance studies are essential to confirm this potential association and monitor drug safety. In summary, this case highlights a possible link between risankizumab and severe HTG, emphasizing the importance of ongoing pharmacovigilance to identify and manage unexpected adverse effects associated with new medications.
A Diagnosis of Turner Syndrome in the Eighth Decade of Life
Authors: Kaur Ruveena , O’Sullivan Susannah
Published: June 2024

Turner syndrome (TS) is the most common sex chromosome disorder affecting females and is usually diagnosed within the first 3 decades of life. It can present with primary amenorrhea or infertility and often has a typical phenotype, with associated medical conditions that require lifelong surveillance. We report the case of a 76-year-old female with a history of osteoporosis and vertebral fractures who presented to our specialist osteoporosis clinic following a neck of femur fracture. She revealed a history of short stature and primary amenorrhea as a young woman, with limited investigation and treatment. Her other medical history included coeliac disease, hypertension, and hearing and vision abnormalities. Given her phenotype, the patient was referred for a karyotype at age 76, which was consistent with mosaic TS (45, X in 78% of cells and 46, X, r(Y) in the remaining cells). We review reports of other cases of marked delay in TS diagnosis and discuss the consequences of a late diagnosis.
A Tune of Two Cities
Authors: Shadel Kevin
Published: June 2024

In the worst of times, the best of tunes. Or so might say singer Kim Hae-song (1910–195?), whose 1938 hit recording “Flowery Seoul” (“Kkot sŏul”) arguably offered more than a mere tongue-in-cheek retort to Fujiyama Ichirō’s (1911–1993) own 1936 “Tokyo Rhapsody” (“Tōkyō rapusodi”) by crooning in the Korean language over Koga Masao's (1904–1978) original composition. While both vocalists posture competitively with regard to the modern merits of their respective metropolises, the dark timbre of geopolitics dampens the otherwise playful interaction between these two popular songs, one by an imperial Japanese citizen, the other a colonial Korean subject. This article traces interwar popular music's regional, linguistic, and affective transposability to consider how the exceptional textual and melodic identity between Kim's and Fujiyama's respective city songs belies a more fundamental interpellation of Korean subjects into the transregional logic of Japanese Empire.
Nighttime Treatment of Ruptured Intracranial Aneurysms Are Associated With Poor Outcomes
Authors: Dumot Chloe , Gasimov Turab , Hatipoglu Majernik Gokce , Gurbuz Mehmet Sabri , Erginoglu Ufuk , Keles Abdullah , Arat Anil , Baskaya Mustafa K.
Published: June 2024

BACKGROUND AND OBJECTIVES:

Rebleeding of ruptured intracranial aneurysms (RIA) is associated with poor outcomes. Although immediate treatment of RIAs is preferred, optimal treatment timing is multifactorial and may be a complicating factor for achieving the best outcomes. The objective of this study was to compare outcomes for patients with RIAs as a function of treatment time of day. To the best of our knowledge, this is the first study that examines how treatment time of day influences treatment outcomes.

METHODS:

This retrospective single-center study included all patients who were treated, either surgically or endovascularly, for RIAs within 24 hours after admission. Exclusion criteria were blister, mycotic or giant aneurysms, or incomplete records. The modified Rankin Scale was used to evaluate treatment outcomes using multivariate analysis. Nighttime treatment was defined when greater than 50% of the procedure was performed between 10 pm and 7 am, with other times classified as daytime treatment. Off-hours treatment was defined when more than 50% of the procedure was performed between 7 pm and 7 am, with other times classified as on-hours.

RESULTS:

This study included 493 patients, with 84.2% (415) treated during the daytime, 15.8% (78) during the nighttime, 67.5% (333) during on-hours, and 32.5% (160) during off-hours. These groups did not differ according to age, sex, World Federation of Neurosurgical Societies and Fisher scales, aneurysm size, location, and surgical or endovascular treatment. Outcomes were favorable (modified Rankin Scale 0-2) for 72.0% (299) of patients treated during the daytime and 60.0% (46) of patients treated during the nighttime. Aneurysm treatment during the nighttime (OR: 0.50 [95% CI: 0.28-0.91], P = .023) but not during off-hours (OR: 0.76 [0.50-1.14], P = .18) was independently associated with unfavorable outcomes.

CONCLUSION:

Nighttime treatment was associated with poorer outcomes. Further studies are needed to evaluate outcomes if treatment is postponed to daytime hours.
Contribution of Streptococcus pseudopneumoniae and Streptococcus salivarius to vocal fold mucosal integrity and function
Authors: Lungova Vlasta , Gowda Madhu , Fernandez Jessica M. , Bartley Stephanie , Venkatraman Anumitha , Rey Federico E. , Thibeault Susan L.
Published: June 2024

Structural changes to the vocal fold (VF) epithelium, namely, loosened intercellular junctions, have been reported in VF benign lesions. The potential mechanisms responsible for the disruption of cell junctions do not address the contribution of resident microbial communities to this pathological phenomenon. In this study, we focused on determining the relationship between Streptococcus pseudopneumoniae (SP), a dominant bacterial species associated with benign lesions, and Streptococcus salivarius (SS), a commensal bacterium, with human VF epithelial cells in our three-dimensional model of the human VF mucosa. This experimental system enabled direct deposition of bacteria onto constructs at the air/liquid interface, allowing for the assessment of bacterium–host interactions at the cellular, molecular and ultrastructural levels. Our findings demonstrate that SP disrupts VF epithelial integrity and initiates inflammation via the exported products HtrA1 and pneumolysin. In contrast, SS attaches to the VF epithelium, reduces inflammation and induces Mmp2-mediated apical desquamation of infected cells to mitigate the impact of pathogens. In conclusion, this study highlights the complexity of microbial involvement in VF pathology and potential VF mucosal restoration in the presence of laryngeal commensals.
Muscle-specific lack of Gfpt1 triggers ER stress to alleviate misfolded protein accumulation
Authors: Zhang Ruchen , Farshadyeganeh Paniz , Ohkawara Bisei , Nakajima Kazuki , Takeda Jun-ichi , Ito Mikako , Zhang Shaochuan , Miyasaka Yuki , Ohno Tamio , Mori-Yoshimura Madoka , Masuda Akio , Ohno Kinji
Published: June 2024

Pathogenic variants in GFPT1, encoding a key enzyme to synthesize UDP-N-acetylglucosamine (UDP-GlcNAc), cause congenital myasthenic syndrome (CMS). We made a knock-in (KI) mouse model carrying a frameshift variant in Gfpt1 exon 9, simulating that found in a patient with CMS. As Gfpt1 exon 9 is exclusively expressed in striated muscles, Gfpt1-KI mice were deficient for Gfpt1 only in skeletal muscles. In Gfpt1-KI mice, (1) UDP-HexNAc, CMP-NeuAc and protein O-GlcNAcylation were reduced in skeletal muscles; (2) aged Gfpt1-KI mice showed poor exercise performance and abnormal neuromuscular junction structures; and (3) markers of the unfolded protein response (UPR) were elevated in skeletal muscles. Denervation-mediated enhancement of endoplasmic reticulum (ER) stress in Gfpt1-KI mice facilitated protein folding, ubiquitin-proteasome degradation and apoptosis, whereas autophagy was not induced and protein aggregates were markedly increased. Lack of autophagy was accounted for by enhanced degradation of FoxO1 by increased Xbp1-s/u proteins. Similarly, in Gfpt1-silenced C2C12 myotubes, ER stress exacerbated protein aggregates and activated apoptosis, but autophagy was attenuated. In both skeletal muscles in Gfpt1-KI mice and Gfpt1-silenced C2C12 myotubes, maladaptive UPR failed to eliminate protein aggregates and provoked apoptosis.
The Association of Mismatch Repair Status with Microscopically Positive (R1) Margins in Stage III Colorectal Cancer: A Retrospective Cohort Study
Authors: Smith Henry G. , Schlesinger Nis H. , Chiranth Deepthi , Qvortrup Camilla
Published: June 2024

Background

There is mounting evidence that microscopically positive (R1) margins in patients with colorectal cancer (CRC) may represent a surrogate for aggressive cancer biology rather than technical failure during surgery. However, whether detectable biological differences exist between CRC with R0 and R1 margins is unknown. We sought to investigate whether mismatch repair (MMR) status differs between Stage III CRC with R0 or R1 margins.

Methods

Patients treated for Stage III CRC from January 1, 2016 to December 31, 2019 were identified by using the Danish Colorectal Cancer Group database. Patients were stratified according to MMR status (proficient [pMMR] vs. deficient [dMMR]) and margin status. Outcomes of interest included the R1 rate according to MMR and overall survival.

Results

A total of 3636 patients were included, of whom 473 (13.0%) had dMMR colorectal cancers. Patients with dMMR cancers were more likely to be elderly, female, and have right-sided cancers. R1 margins were significantly more common in patients with dMMR cancers (20.5% vs. 15.2%, p < 0.001), with the greatest difference seen in the rate of R1 margins related to the primary tumour (8.9% vs. 4.7%) rather than to lymph node metastases (11.6% vs. 10.5%). This association was seen in both right- and left-sided cancers. On multivariable analyses, R1 margins, but not MMR status, were associated with poorer survival, alongside age, pN stage, perineural invasion, and extramural venous invasion.

Conclusions

In patients with Stage III CRC, dMMR status is associated with increased risks of R1 margins following potentially curative surgery, supporting the use of neoadjuvant immunotherapy in this patient group.
Clinical effects of basic nursing combined with psychological intervention on treatment compliance of patients with Influenza-A(H1N1)
Authors: Feng Yaning , Ma Chuntao , Feng Zhongxian , Bian Yajing , Zhu Yujiao , Li Kun
Published: June 2024

Objective: To investigate the effects of basic nursing combined with psychological intervention on treatment compliance, self-care ability, clinical efficacy, lung function and nursing satisfaction of patients with Influenza-A(H1N1).
Method: This was application research. Eighty patients with influenza-A (H1N1) admitted to The First Affiliated Hospital of Hebei North University from January 2020 to December 2022 were included as subjects and randomly divided into the observation group(n=40) and the control group(n=40). Patients in the control group were given routine basic nursing intervention, while those in the observation group were treated with combined psychological intervention in addition to basic nursing. The differences in treatment compliance, self-care ability, clinical efficacy, lung function and nursing satisfaction were compared between the two groups.
Results: After the intervention, the treatment compliance score and the total self-care ability score of the observation group were higher than those of the control group, with statistically significant differences(P<0.05). After treatment, the clinical efficacy of the observation group was significantly higher than that of the control group(P<0.05). Before treatment, no significant difference was observed between the two groups in terms of various indexes of lung function, which were better in the observation group than in the control group after treatment(P<0.05).
Conclusion: Basic nursing combined with psychological intervention results in a variety of benefits in the treatment of patients with Influenza-A(H1N1), such as improved treatment compliance and self-care ability, ameliorated lung function, as well as enhanced treatment outcomes and nursing satisfaction, which needs to be promoted in clinical practice.
doi: https://doi.org/10.12669/pjms.40.7.8675
How to cite this: Feng Y, Ma C, Feng Z, Bian Y, Zhu Y, Li K. Clinical effects of basic nursing combined with psychological intervention on treatment compliance of patients with Influenza-A(H1N1). Pak J Med Sci. 2024;40(7):---------. doi: https://doi.org/10.12669/pjms.40.7.8675
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Alteration of Maternal Serum Ferritin in Pregnancy and Maternal-fetal Infections: A retrospective cohort study
Authors: Liao Xing , Xiu Xiaoyan , Xu Guizhen , Wu Ling , Fang Zhuanji , Huang Huihui
Published: June 2024

Objectives: To investigate the association of altered serum ferritin during pregnancy with chorioamnionitis and neonatal sepsis.
Methods: This retrospective cohort study included 78,521 pregnant women who attended antenatal check-ups at maternal and child health centers in Fujian Province, China. Study lasted from January 2014 to January 2019. A total of 59,812 pregnant women were followed up. Patients with suspected infection before the delivery were selected and divided into the chorioamnionitis and non-chorioamnionitis groups according to placental pathology. Differences in late and early pregnancy serum ferritin between the two groups were compared. Multiple logistics regression was used to adjust for confounding factors and to analyze the association between serum ferritin changes and pregnancy outcomes. Importance of altered serum ferritin during pregnancy was assessed by receiver operating characteristic (ROC) curve and net reclassification index (NRI).
Results: Clinical records of 8506 pregnant women were included in the study. there were 1010 (11.9%) cases of confirmed chorioamnionitis and 263 (3.1%) cases of neonatal sepsis. There was a significant difference in maternal serum ferritin changes between the groups with and without chorioamnionitis. No significant difference was detected in cases with or without neonatal sepsis. Multiple logistic regressions, corrected for confounding factors yielded similar conclusions. Maternal serum ferritin difference NRI 12.18% (p = 0.00014) was similar to the ROC results in predicting the occurrence of chorioamnionitis.
Conclusion: Differential serum ferritin during pregnancy may predict chorioamnionitis but does not correlate well with neonatal sepsis.
doi: https://doi.org/10.12669/pjms.40.7.9160
How to cite this: Liao X, Xiu X, Xu G, Wu L, Fang Z, Huang H. Alteration of Maternal Serum Ferritin in Pregnancy and Maternal-fetal Infections: A retrospective cohort study. Pak J Med Sci. 2024;40(7):---------. doi: https://doi.org/10.12669/pjms.40.7.9160
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.