bluuebunny/crossref_metadata_2025_split huggingface dataset:
NLRC5 overexpression in ovarian tumors remodels the tumor microenvironment and increases T-cell reactivity toward autologous tumor-associated antigens
Authors: Rodriguez Galaxia M. , Yakubovich Edward , Murshed Humaira , Maranda Vincent , Galpin Kristianne J.C. , Cudmore Alison , Hanna Andrew M. R. , Macdonald Elizabeth , Ramesh Shashankan , Garson Kenneth , Vanderhyden Barbara C. 
Published: January 2024

IntroductionEpithelial ovarian cancer (OC) stands as one of the deadliest gynecologic malignancies, urgently necessitating novel therapeutic strategies. Approximately 60% of ovarian tumors exhibit reduced expression of major histocompatibility complex class I (MHC I), intensifying immune evasion mechanisms and rendering immunotherapies ineffective. NOD-like receptor CARD domain containing 5 (NLRC5) transcriptionally regulates MHC I genes and many antigen presentation machinery components. We therefore explored the therapeutic potential of NLRC5 in OC.MethodsWe generated OC cells overexpressing NLRC5 to rescue MHC I expression and antigen presentation and then assessed their capability to respond to PD-L1 blockade and an infected cell vaccine.ResultsAnalysis of microarray datasets revealed a correlation between elevated NLRC5 expression and extended survival in OC patients; however, NLRC5 was scarcely detected in the OC tumor microenvironment. OC cells overexpressing NLRC5 exhibited slower tumor growth and resulted in higher recruitment of leukocytes in the TME with lower CD4/CD8 T-cell ratios and increased activation of T cells. Immune cells from peripheral blood, spleen, and ascites from these mice displayed heightened activation and interferon-gamma production when exposed to autologous tumor-associated antigens. Finally, as a proof of concept, NLRC5 overexpression within an infected cell vaccine platform enhanced responses and prolonged survival in comparison with control groups when challenged with parental tumors.DiscussionThese findings provide a compelling rationale for utilizing NLRC5 overexpression in “cold” tumor models to enhance tumor susceptibility to T-cell recognition and elimination by boosting the presentation of endogenous tumor antigens. This approach holds promise for improving antitumoral immune responses in OC.
Apatinib combined with camrelizumab in the treatment of recurrent/metastatic nasopharyngeal carcinoma: a prospective multicenter phase II study
Authors: Mo Yunyan , Pan Yufei , Zhang Bin , Zhang Jian , Su Yixin , Liu Zhengchun , Luo Meiqing , Qin Guanjie , Kong Xiangyun , Zhang Rongjun , Pan Yu , Liang Yi , Wang Defeng , Wei Yuejia , Chen Hengwei , Jiang Wei 
Published: January 2024

BackgroundPreclinical studies demonstrated that immune checkpoint inhibitors combined with antiangiogenic drugs have a synergistic anti-tumor effect. This present phase II trial aimed to evaluate the efficacy and safety of apatinib combined with camrelizumab in patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC).MethodsPatients with RM-NPC were administered with apatinib at 250 mg orally once every day and with camrelizumab at 200 mg via intravenous infusion every 2 weeks until the disease progressed or toxicity became unacceptable. The objective response rate (ORR) was the primary endpoint, assessed using RECIST version 1.1. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety were the key secondary endpoints. This study was registered with ClinicalTrials.gov, NCT04350190.ResultsThis study enrolled 26 patients with RM-NPC between January 14, 2021 and September 15, 2021. At data cutoff (March 31, 2023), the median duration of follow-up was 16 months (ranging from 1 to 26 months). The ORR was 38.5% (10/26), the disease control rate (DCR) was 61.5% (16/26), and the median PFS was 6 months (IQR 3.0-20.0). The median OS was 14 months (IQR 6.0-21.25). Treatment-related grade 3 or 4 adverse events occurred in seven (26.9%) patients, and comprised anemia (7.7%), stomatitis (3.8%), headache (3.8%), pneumonia (7.7%), and myocarditis (3.8%). There were no serious treatment-related adverse events or treatment-related deaths.ConclusionIn patients with RM-NPC, apatinib plus camrelizumab showed promising antitumor activity and manageable toxicities.
A qualitative study of pain and related symptoms experienced by people with Ehlers-Danlos syndromes
Authors: Schubart Jane R. , Mills Susan E. , Francomano Clair A. , Stuckey-Peyrot Heather 
Published: January 2024

IntroductionIndividuals with Ehlers-Danlos syndromes (EDS) often have complex and multi-faceted symptoms across the lifespan. Pain and the related symptoms of fatigue and sleep disorders are common. The objective of this qualitative study was to understand how participants manage their pain and related symptoms.MethodsThe design was a qualitative thematic content analysis. Twenty-eight interviews were conducted to collect data from individuals who were participants in a prior quantitative longitudinal study. A semi-structured interview guide was designed to focus on and understand the trajectory of pain, sleep, fatigue, and general function. The interview continued with questions about coping mechanisms and obstacles to maintaining a sense of well-being.ResultsSymptoms reported by participants were widespread and often interwoven. Pain was universal and often resulted in fatigue and disordered sleep which impacted physical function. Most participants reported that their symptoms worsened over time. Participants reported a wide range of effective interventions and most reported developing self-care strategies to adapt to their disabilities/limitations. Solutions included complementary interventions discovered when conventional medicine was unsuccessful. Very few relied on a “system” of health care and instead developed their own strategies to adapt to their disabilities/limitations.DiscussionEDS symptoms are often debilitating, and their progression is unknown. For most participants, symptoms worsened over the time. Even though participants in our study, by experience, were self-reliant, the importance of knowledgeable medical providers to help guide self-care should be emphasized.
Convergence of plasmid-mediated Colistin and Tigecycline resistance in Klebsiella pneumoniae
Authors: Zhao Yujie , Qian Changrui , Ye Jianzhong , Li Qingcao , Zhao Rongqing , Qin Ling , Mao Qifeng 
Published: January 2024

ObjectiveThe co-occurrence of colistin and tigecycline resistance genes in Klebsiella pneumoniae poses a serious public health problem. This study aimed to characterize a K. pneumoniae strain, K82, co-harboring a colistin resistance gene (CoRG) and tigecycline resistance gene (TRG), and, importantly, investigate the genetic characteristics of the plasmid with CoRG or TRG in GenBank.MethodsK. pneumoniae strain K82 was subjected to antimicrobial susceptibility testing, conjugation assay, and whole-genome sequencing (WGS). In addition, comparative genomic analysis of CoRG or TRG-harboring plasmids from K82 and GenBank was conducted. K. pneumoniae strain K82 was resistant to all the tested antimicrobials including colistin and tigecycline, except for carbapenems.ResultsWGS and bioinformatic analysis showed that K82 belonged to the ST656 sequence type and carried multiple drug resistance genes, including mcr-1 and tmexCD1-toprJ1, which located on IncFIA/IncHI2/IncHI2A/IncN/IncR-type plasmid pK82-mcr-1 and IncFIB/IncFII-type plasmid pK82-tmexCD-toprJ, respectively. The pK82-mcr-1 plasmid was capable of conjugation. Analysis of the CoRG/TRG-harboring plasmid showed that mcr-8 and tmexCD1-toprJ1 were the most common CoRG and TRG of Klebsiella spp., respectively. These TRG/CoRG-harboring plasmids could be divided into two categories based on mash distance. Moreover, we found an IncFIB/IncHI1B-type plasmid, pSYCC1_tmex_287k, co-harboring mcr-1 and tmexCD1-toprJ1. To the best of our knowledge, this is the first report on the co-occurrence of mcr-1 and tmexCD1-toprJ1 on a single plasmid.ConclusionOur research expands the known diversity of CoRG and TRG-harboring plasmids in K. pneumoniae. Effective surveillance should be implemented to assess the prevalence of co-harboring CoRG and TRG in a single K. pneumoniae isolate or even a single plasmid.
Relationship between baseline bicarbonate and 30-day mortality in patients with non-traumatic subarachnoid hemorrhage
Authors: Du Wenyuan , Yang Jingmian , Lou Yanfang , You Jiahua , Wang Qiang 
Published: January 2024

ObjectiveThis study aimed to explore the relationship between baseline bicarbonate levels and 30-day mortality in individuals with non-traumatic subarachnoid hemorrhage (SAH).MethodsPatients with non-traumatic SAH were chosen from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The relationship between baseline bicarbonate and 30-day mortality was examined using Cox regression models. Restricted cubic splines were used to test the hypothesis that there was an association between bicarbonate and mortality. With the use of Kaplan–Meier survival curve analysis, we looked deeper into the validity of these correlations. To find subgroups with differences, interaction tests were utilized.ResultsThis retrospective cohort study consisted of 521 participants in total. Bicarbonate had a negative association with death at 30 days (HR = 0.93, 95%CI: 0.88–0.98, p = 0.004). Next, we divided bicarbonate into quartile groups. In comparison to the reference group Q1 (20 mEq/L), groups Q3 (23–25 mEq/L) and Q4 (26 mEq/L) had adjusted HR values of 0.47 (95%CI: 0.27–0.82, p = 0.007) and 0.56 (95%CI: 0.31–0.99, p = 0.047). No definite conclusions can be derived from this study, since there is no obvious curve link between baseline bicarbonate and 30-day mortality. Patients’ 30-day mortality increased statistically significantly (p &lt; 0.001, K–M analysis) in patients with low bicarbonate levels. The relationship between bicarbonate and 30-day mortality remained consistent in the stratified analysis, with no observed interactions.ConclusionFinally, 30-day mortality was negatively associated with baseline bicarbonate levels. Patients with non-traumatic SAH are more at risk of mortality if their bicarbonate levels are low.
The application and sustainable development of coral in traditional medicine and its chemical composition, pharmacology, toxicology, and clinical research
Authors: Han Mengtian , Wang Zhongyuan , Li Yiye , Song Yinglian , Wang Zhang 
Published: January 2024

This review discusses the variety, chemical composition, pharmacological effects, toxicology, and clinical research of corals used in traditional medicine in the past two decades. At present, several types of medicinal coral resources are identified, which are used in 56 formulas such as traditional Chinese medicine, Tibetan medicine, Mongolian medicine, and Uyghur medicine. A total of 34 families and 99 genera of corals are involved in medical research, with the Alcyoniidae family and Sarcophyton genus being the main research objects. Based on the structural types of compounds and the families and genera of corals, this review summarizes the compounds primarily reported during the period, including terpenoids, steroids, nitrogen-containing compounds, and other terpenoids dominated by sesquiterpene and diterpenes. The biological activities of coral include cytotoxicity (antitumor and anticancer), anti-inflammatory, analgesic, antibacterial, antiviral, immunosuppressive, antioxidant, and neurological properties, and a detailed summary of the mechanisms underlying these activities or related targets is provided. Coral toxicity mostly occurs in the marine ornamental soft coral Zoanthidae family, with palytoxin as the main toxic compound. In addition, nonpeptide neurotoxins are extracted from aquatic corals. The compatibility of coral-related preparations did not show significant acute toxicity, but if used for a long time, it will still cause toxicity to the liver, kidneys, lungs, and other internal organs in a dose-dependent manner. In clinical applications, individual application of coral is often used as a substitute for orthopedic materials to treat diseases such as bone defects and bone hyperplasia. Second, coral is primarily available in the form of compound preparations, such as Ershiwuwei Shanhu pills and Shanhu Qishiwei pills, which are widely used in the treatment of neurological diseases such as migraine, primary headache, epilepsy, cerebral infarction, hypertension, and other cardiovascular and cerebrovascular diseases. It is undeniable that the effectiveness of coral research has exacerbated the endangered status of corals. Therefore, there should be no distinction between the advantages and disadvantages of listed endangered species, and it is imperative to completely prohibit their use and provide equal protection to help them recover to their normal numbers. This article can provide some reference for research on coral chemical composition, biological activity, chemical ecology, and the discovery of marine drug lead compounds. At the same time, it calls for people to protect endangered corals from the perspectives of prohibition, substitution, and synthesis.
Nanomedicine drug delivery in South Africa: a retrospective study on research, funding and collaboration
Authors: Salie Faatiema , Saidi Trust 
Published: January 2024

After nearly two decades of substantial investment in the field of nanomedicine within South Africa, this study undertakes an investigation into the specific diseases that have been targeted for research and development, as well as the key actors and collaborative networks involved in this burgeoning field. To accomplish this, the study adopts a mixed-method approach, combining bibliometric and scientometric techniques alongside a comprehensive review of existing literature. The study’s findings illuminate that the diseases selected for emphasis in nanomedicine research closely align with the prevalent health challenges faced by South Africa. Notably, these ailments encompass cancer, bacterial infections, and tuberculosis, all of which significantly contribute to the country’s disease burden. Furthermore, the investigation highlights that research-intensive South African universities play a pivotal role as the primary actors in advancing nanomedicine initiatives. Over time, collaborative endeavors among these key actors have seen a noteworthy upswing. These collaborations have fostered robust connections between South African institutions and counterparts in Asian nations and the Middle East. It is worth emphasizing that nanomedicine is a resource-intensive field, necessitating substantial capital investment. Collaborative initiatives have, in turn, granted access to critical infrastructure and materials that would have otherwise been beyond the reach of some participating entities. Remarkably, these collaborative partnerships have not only facilitated scientific progress but have also cultivated social capital and trust among involved stakeholders. These valuable intangible assets hold great potential as South Africa advances towards more exploitative phases of technology development within the domain of nanomedicine. Moreover, South Africa is strategically positioning itself to cultivate a critical mass of expertise in nanomedicine, recognising the significance of skilled human resources in harnessing the full potential of this technology in the future.Systematic Review Registration:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173875/
Identification of candidate regulators of the response to early heat stress in climate-adapted wheat landraces via transcriptomic and co-expression network analyses
Authors: Barratt Liam J. , Franco Ortega Sara , Harper Andrea L. 
Published: January 2024

IntroductionClimate change is likely to lead to not only increased global temperatures but also a more variable climate where unseasonal periods of heat stress are more prevalent. This has been evidenced by the observation of spring-time temperatures approaching 40°C in some of the main spring-wheat producing countries, such as the USA, in recent years. With an optimum growth temperature of around 20°C, wheat is particularly prone to damage by heat stress. A warming climate with increasingly common fluctuations in temperature therefore threatens wheat crops and subsequently the lives and livelihoods of billions of people who depend on the crop for food. To futureproof wheat against a variable climate, a better understanding of the response to early heat stress is required.MethodsHere, we utilised DESeq2 to identify 7,827 genes which were differentially expressed in wheat landraces after early heat stress exposure. Candidate hub genes, which may regulate the transcriptional response to early heat stress, were identified via weighted gene co-expression network analysis (WGCNA), and validated by qRT-PCR.ResultsTwo of the most promising candidate hub genes (TraesCS3B02G409300 and TraesCS1B02G384900) may downregulate the expression of genes involved in the drought, salinity, and cold responses—genes which are unlikely to be required under heat stress—as well as photosynthesis genes and stress hormone signalling repressors, respectively. We also suggest a role for a poorly characterised sHSP hub gene (TraesCS4D02G212300), as an activator of the heat stress response, potentially inducing the expression of a vast suite of heat shock proteins and transcription factors known to play key roles in the heat stress response.DiscussionThe present work represents an exploratory examination of the heat-induced transcriptional change in wheat landrace seedlings and identifies several candidate hub genes which may act as regulators of this response and, thus, may be targets for breeders in the production of thermotolerant wheat varieties.
Evaluation of the multimodal DELTA therapy for adolescents with substance use disorders: an exploratory pilot trial
Authors: Basedow Lukas A. , Kuitunen-Paul Soeren , Wiedmann Melina F. , Roessner Veit , Golub Yulia 
Published: January 2024

BackgroundIn order to address the lack of manualized treatment programs for adolescents with substance use disorders (SUDs), we developed a manualized group intervention (DELTA). DELTA focusses on substance use reduction and abstinence as well as alleviation of SUD symptoms via additional modules for co-occurring disorders. The goal of this exploratory trial was to assess if DELTA can be conducted in adolescent SUD patients and if participation is related to reductions in substance use, SUD-related problems, and further psychopathologies.MethodWe recruited adolescents at a psychiatric outpatient unit, which were then allocated to either DELTA intervention group (N = 85) or to a waiting-list control group (WL, N = 61) based on parental decision to start a therapy or not. Self-report measures were used as primary outcomes (substance use via interview, use-related problems via DUDIT—Drug Use Disorder Identification Test) and secondary outcomes (psychopathologies via YSR—Youth Self Report). T-tests and Pearson correlations were used to analyze between-group differences across time.ResultsOn average, participants attended M = 7.7 (SD = 5.1) of the 16 sessions. Substance use and use-related problems regarding all substances but nicotine was decreased after the intervention, with small to medium not significant effects in favor of DELTA. Self-reported psychopathologies were also reduced at follow-up, with non-significant advantages for DELTA.ConclusionDELTA showed small effects on SUD-related and depression-related variables. However, the interpretation is limited by the small sample size. Nonetheless, the DELTA intervention is viable in SUD outpatient treatment and will be further evaluated.Clinical trial registration: The study was registered at clinicaltrials.gov under NCT03444974. Registered February, 26th 2018 (https://clinicaltrials.gov/ct2/show/NCT03444974).
A pilot time-in-bed restriction intervention behaviorally enhances slow-wave activity in older adults
Authors: Wilckens Kristine A. , Habte Rima F. , Dong Yue , Stepan Michelle E. , Dessa Kibra M. , Whitehead Alexis B. , Peng Christine W. , Fletcher Mary E. , Buysse Daniel J. 
Published: January 2024

IntroductionIdentifying intervention methods that target sleep characteristics involved in memory processing is a priority for the field of cognitive aging. Older adults with greater sleep efficiency and non-rapid eye movement slow-wave activity (SWA) (0.5–4 Hz electroencephalographic activity) tend to exhibit better memory and cognitive abilities. Paradoxically, long total sleep times are consistently associated with poorer cognition in older adults. Thus, maximizing sleep efficiency and SWA may be a priority relative to increasing mere total sleep time. As clinical behavioral sleep treatments do not consistently enhance SWA, and propensity for SWA increases with time spent awake, we examined with a proof-of concept pilot intervention whether a greater dose of time-in-bed (TiB) restriction (75% of habitual TiB) would increase both sleep efficiency and SWA in older adults with difficulties staying asleep without impairing memory performance.MethodsParticipants were adults ages 55–80 with diary-reported sleep efficiency &lt; 90% and wake after sleep onset (WASO) &gt;20 min. Sleep diary, actigraphy, polysomnography (PSG), and paired associate memory acquisition and retention were assessed before and after a week-long TiB restriction intervention (n = 30). TiB was restricted to 75% of diary-reported habitual TiB. A comparison group of n = 5 participants repeated assessments while following their usual sleep schedule to obtain preliminary estimates of effect sizes associated with repeated testing.ResultsSubjective and objective sleep measures robustly improved in the TiB restriction group for sleep quality, sleep depth, sleep efficiency and WASO, at the expense of TiB and time spent in N1 and N2 sleep. As hypothesized, SWA increased robustly with TiB restriction across the 0.5–4 Hz range, as well as subjective sleep depth, subjective and objective WASO. Despite increases in sleepiness ratings, no impairments were found in memory acquisition or retention.ConclusionA TiB restriction dose equivalent to 75% of habitual TiB robustly increased sleep continuity and SWA in older adults with sleep maintenance difficulties, without impairing memory performance. These findings may inform long-term behavioral SWA enhancement interventions aimed at improving memory performance and risk for cognitive impairments.