bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mode of transport, genetic susceptibility, and incidence of coronary heart disease
Authors: Jiesisibieke Zhu Liduzi , Panter Jenna , Wang Mengyao , Au Yeung Shiu Lun , Luo Shan , Jang Haeyoon , Wan Eric Yuk Fai , Brage Soren , Kim Youngwon 
Published: July 2023

Abstract
Background
Car use has been associated with higher risk of coronary heart disease (CHD). However, whether the associations of transport modes with CHD vary by genetic susceptibility to CHD are unknown. This study aims to investigate the associations of genetic susceptibility and modes of transport with incidence of CHD.

Methods
We included 339,588 white British participants from UK Biobank with no history of CHD or stroke at baseline or within two years of follow-up (52.3% in work). Genetic susceptibility to CHD was quantified through weighted polygenic risk scores derived from 300 single-nucleotide polymorphisms related to CHD risk. Categories of transport mode included exclusive car use and alternatives to the car (e.g., walking, cycling and public transport), separately for non-commuting (e.g., getting about [n=339,588] excluding commuting for work), commuting (in the sub-set in work [n=177,370] who responded to the commuting question), and overall transport (transport mode for both commuting and non-commuting [n=177,370]). We used Cox regression with age as the underlying timescale to estimate hazard ratios (HR) of CHD (n=13,730; median 13.8-year follow-up) and tested the interaction between genetic susceptibility and travel modes with adjustment for confounders.

Results
Compared to those using alternatives to the car, hazards of CHD were higher for exclusive use of cars for overall transport (HR: 1.16, 95% confidence interval (CI): 1.08-1.25), non-commuting (HR: 1.08, 95% CI: 1.04-1.12) and commuting (HR: 1.16, 95% CI: 1.09-1.23), after adjusting for confounders plus genetic susceptibility. HRs of CHD were 1.45 (95% CI: 1.38-1.52) and 2.04 (95% CI: 1.95-2.12) for the second and third tertile of genetic susceptibility to CHD, respectively, compared to the first. There was, in general, no strong evidence of interactions between genetic susceptibility and categories of overall, non-commuting and commuting transport. Estimated 10-year absolute risk of CHD was lower for the alternatives to the car across strata of genetic susceptibility, compared with exclusive use of cars for overall, non-commuting and commuting transport.

Conclusion
Exclusive use of cars was associated with a relatively higher risk of CHD across all strata of genetic susceptibility. Using alternatives to the car should be encouraged for prevention of CHD for the general population including individuals at high genetic risk.
Initial analysis of the synergy of programmed cell death-1 (PD-1) inhibitor and concurrent chemoradiotherapy treatment for recurrent/metastatic head and neck squamous cell carcinoma patients
Authors: Li Lu , Chen Lu , Yan Lu , Guo Yueqian , Li Fang , Fan Ming , Lan Mei , Lai Xin , Zhou Jie , Huang Yecai , Xu Peng , Lang Jinyi , Feng Mei 
Published: July 2023

Abstract
Background
Programmed cell death-1 (PD-1) inhibitor was proven to be useful for the recurrent/metastatic head and neck squamous carcinoma (R/M HNSCC) patients. Though both PD-1 inhibitor alone and combination with chemotherapy showed some benefit for PFS and OS, the survival outcome was still not satisfactory. Some studies showed the possible benefit for PD-1 inhibitors combination with radiation for head and neck squamous carcinoma, however there was few studies concerned about synergy of concurrent PD-1 inhibitor combination with chemoradiotherapy for R/M HNSCC. So, we aimed to explore the potential effect and toxicity of the concurrent PD-1 inhibitor and chemoradiotherapy for R/M HNSCC.

Methods
We consecutively enrolled the R/M HNSCC patients treated with concurrent PD-1 inhibitor and chemoradiotherapy from August 2018 to April 2022 in Sichuan Cancer hospital. All the patients received the combination of PD-1 inhibitor and chemotherapy, and followed with synergy of concurrent PD-1 inhibitor and chemoradiotherapy, then maintenance PD-1 inhibitor. ORR and DCR was calculated by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST-1.1), and Common terminology criteria for adverse events (CTCAE-4.0) was used to evaluate the toxicity.The Kaplan–Meier method was used to analyze OS and PFS.

Results
40 R/M HNSCC patients were enrolled in our stuty. The median follow up time was 14 months. 22 patients had recurrent disease only, 16 patients had metastatic disease only, and 2 patients had both recurrence and metastasis disease. For the recurrent lesions, 23 patients received a median radiation dose of 64 Gy (range 50–70 Gy). 18 patients received a median dose of 45 Gy (range 30–66 Gy) for metastatic lesions. The median courses of PD-1 inhibitors and chemotherapy were 8 and 5 respectively. After the treatment, the ORR and DCR were 70.0% and 100%. The median OS was 19 months (range 6.3–31.7 months), with 1 and 2-years OS rates of 72.8% and 33.3%. The median PFS was 9 months (range 3.1–14.9 months), with 6 and 12 months PFS rates of 75.5% and 41.4% respectively. The PFS had no statistical significance in PD-L1 negative and positive group (7 vs 12 months, p = 0.059). The most common grade 3 or 4 adverse events(AE) were leucopenia (25.0%), neutropenia (17.5%), anemia (10.0%), thrombocytopenia (5.0%), hyponatremia (2.5%), and pneumonia(2.5%). No grade 5 AE was observed.

Conclusions
The synergy of concurrent PD-1 inhibitor treatment with chemoradiotherapy shows promise as a treatment strategy and an acceptable toxicity for the R/M HNSCC patients.
Overexpression of human alpha-Synuclein leads to dysregulated microbiome/metabolites with ageing in a rat model of Parkinson disease
Authors: Singh Yogesh , Trautwein Christoph , Romani Joan , Salker Madhuri S. , Neckel Peter H. , Fraccaroli Isabel , Abeditashi Mahkameh , Woerner Nils , Admard Jakob , Dhariwal Achal , Dueholm Morten K. D. , Schäfer Karl-Herbert , Lang Florian , Otzen Daniel E. , Lashuel Hilal A. , Riess Olaf , Casadei Nicolas 
Published: July 2023

Abstract
Background
Braak’s hypothesis states that sporadic Parkinson’s disease (PD) follows a specific progression of pathology from the peripheral to the central nervous system, and this progression can be monitored by detecting the accumulation of alpha-Synuclein (α-Syn) protein. Consequently, there is growing interest in understanding how the gut (commensal) microbiome can regulate α-Syn accumulation, as this could potentially lead to PD.

Methods
We used 16S rRNA and shotgun sequencing to characterise microbial diversity. 1H-NMR was employed to understand the metabolite production and intestinal inflammation estimated using ELISA and RNA-sequencing from feces and the intestinal epithelial layer respectively. The Na+ channel current and gut permeability were measured using an Ussing chamber. Immunohistochemistry and immunofluorescence imaging were applied to detect the α-Syn protein. LC-MS/MS was used for characterization of proteins from metabolite treated neuronal cells. Finally, Metascape and Ingenuity Pathway Analysis (IPA) bioinformatics tools were used for identification of dysregulated pathways.

Results
We studied a transgenic (TG) rat model overexpressing the human SNCA gene and found that a progressive gut microbial composition alteration characterized by the reduction of Firmicutes to Bacteroidetes ratio could be detected in the young TG rats. Interestingly, this ratio then increased with ageing. The dynamics of Lactobacillus and Alistipes were monitored and reduced Lactobacillus and increased Alistipes abundance was discerned in ageing TG rats. Additionally, the SNCA gene overexpression resulted in gut α-Syn protein expression and increased with advanced age. Further, older TG animals had increased intestinal inflammation, decreased Na+ current and a robust alteration in metabolite production characterized by the increase of succinate levels in feces and serum. Manipulation of the gut bacteria by short-term antibiotic cocktail treatment revealed a complete loss of short-chain fatty acids and a reduction in succinate levels. Although antibiotic cocktail treatment did not change α-Syn expression in the enteric nervous system of the colon, however, reduced α-Syn expression was detected in the olfactory bulbs (forebrain) of the TG rats.

Conclusion
Our data emphasize that the gut microbiome dysbiosis synchronous with ageing leads to a specific alteration of gut metabolites and can be modulated by antibiotics which may affect PD pathology.
Unexplained bacterial meat spoilage during the moose hunting in northern Norway – a review of cases 2008–2021
Authors: Josefsen Terje Domaas , Mørk Torill , Ims Anders Aarthun 
Published: July 2023

Abstract
Background
Sudden and unexpected spoilage of moose (Alces alces) carcasses has incidentally been reported in northern Norway. Hunters describe a strong foul odour and greenish discolouration of moose carcasses, hence the nickname “green moose”. Finnmark Estate has registered all reported cases of “green moose” in Finnmark county in the period 2008–2021. In 2013, a questionnaire was introduced to gather more detailed information. Bacteriological and histological examinations were performed on submitted samples of spoiled moose meat. The aim of the present report is to summarize the data gathered about the “green moose” cases, and to discuss possible causes.

Results
Ninety-three valid cases of “green moose” meat spoilage were registered in Finnmark county, giving this form of meat spoilage a prevalence of 0.85% of hunted moose. The carcass weights of spoiled carcasses were within normal weights for moose carcasses in Finnmark. Adult bulls were significantly more, and calves were less frequently affected by meat spoilage. No distinct geographical pattern or “hotspots” could be identified, but multiple cases in the same hunting area same year were reported. The meat spoilage was detected within 5 h after shooting in five cases, and 53% of cases were detected within 2 days after shooting. The meat spoilage was primarily found in deep muscle groups. Bacteriological analyses of 13 samples of spoiled meat were not conclusive. A mixture of aerobic bacteria was detected in 12 samples, and swarming clostridia in 10 samples. Histological examination of seven samples showed abundance of bacteria in fasciae and connective tissue surrounding blood vessels. Injury shootings were not more frequent in “green moose” cases than in moose hunting in general. Other possibly predisposing events to meat spoilage were evisceration later than 60 min after shooting, delayed skinning and contamination by ruminal content. Whether these events occurred more often in “green moose” than normal moose was difficult to determine, due to lack of reference data.

Conclusions
Based on the bacteriological results and the characteristics of the meat spoilage we suggest that clostridia are a main factor involved. How and why clostridia are spread to the muscles and causing the often rapid meat spoilage, is unexplained.
Independent prescribing in the UK: insights from the Department of Health Allied Health Professions Medicines Project team
Authors: Bristow Ivan , Bowen Catherine , Wilson Nicky , Borthwick Alan 
Published: July 2023

AbstractBackgroundThe UK medicines legislation was amended ten years ago (2013) to allow podiatrists and physiotherapists independent prescribing rights, the first of the allied health professions to do so. Non‐medical prescribing formed one part of a broader policy agenda promoting role flexibility in response to the challenge of an ageing population and the need to maintain effective health provision in the face of a contracting workforce.AimThe aim of this study was to outline the experiences of the Department of Health AHP medicines project board team in working towards independent prescribing for podiatry and physiotherapy, with a particular focus on the challenges encountered.MethodsIn depth, open‐ended interviews were conducted with eight of the core members of the project team, drawn from those individuals who served throughout the duration of the project (2010–2013). Included were the former Department of Health Chief and Deputy Chief Allied Health Professions Officers; the Department of Health Engagement and Communications Officer; representatives of the Health and Care Professions Council; the Medicines and Healthcare products Regulatory Agency; the Council of Deans of Health; the Royal College of Podiatry and the Chartered Society of Physiotherapy (The team also included the representative of the Allied Health Professions Federation. However, as that representative is also a researcher in this study, he has recused himself from any role as a participant.). Data were transcribed and subject to a thematic analysis.ResultsA complex picture of the project emerged revealing a range of obstacles and challenges, including inter‐professional role boundary tensions and negative prior assumptions about the two professions. Success hinged upon the adoption of a dual strategy involving submission of a robust case of need focused on patient benefit coupled with the careful management of professional expectations. Underpinning theory from the sociology of the professions offers a supportive explanatory framework for understanding the relationships between the various stakeholders involved.ConclusionsUltimately, success depended upon aligning the project aims with healthcare policy through a clear focus on patient benefit. Balancing competing professional and policy demands through a continual emphasis on improved patient care laid the foundations for future projects by other allied health professions.
Potential effects of assisted reproductive technology on telomere length and telomerase activity in human oocytes and early embryos
Authors: Tire Betul , Ozturk Saffet 
Published: July 2023

AbstractTelomeres are repetitive DNA sequences at eukaryotic chromosome ends and function in maintaining genome integrity and stability. These unique structures undergo shortening due to various factors including biological aging, consecutive DNA replication, oxidative stress, and genotoxic agents. Shortened telomeres can be lengthened by the enzyme telomerase and alternative lengthening of telomeres in germ cells, early embryos, stem cells, and activated lymphocytes. If telomeres reach to critical length, it may lead to genomic instability, chromosome segregation defects, aneuploidy, and apoptosis. These phenotypes also occur in the oocytes and early embryos, produced using assisted reproductive technologies (ARTs). Thus, a number of studies have examined the potential effects of ART applications such as ovarian stimulation, culture conditions, and cryopreservation procedures on telomeres. Herein, we comprehensively reviewed impacts of these applications on telomere length and telomerase activity in ART-derived oocytes and embryos. Further, we discussed use of these parameters in ART centers as a biomarker in determining oocyte and embryo quality.
Long noncoding RNA PSMA3-AS1 functions as a competing endogenous RNA to promote gastric cancer progression by regulating the miR-329-3p/ALDOA axis
Authors: Kan Liang , Yang Meiqi , Zhang Huijing 
Published: July 2023

AbstractLncRNA PSMA3-AS1 functions as an oncogene in several cancers, including ovarian cancer, lung cancer, and colorectal cancer. However, its role in gastric cancer (GC) progression remains unclear. In this study, the levels of PSMA3-AS1, miR-329-3p, and aldolase A (ALDOA) in 20 paired human GC tissues and adjacent nontumorous tissues were measured by real-time PCR. GC cells were transfected with recombinant plasmid carrying full-length PSMA3-AS1 or shRNA targeting PSMA3-AS1. The stable transfectants were selected by G418. Then, the effects of PSMA3-AS1 knockdown or overexpression on GC progression in vitro and in vivo were evaluated. The results showed that PSMA3-AS1 was highly expressed in human GC tissues. Stable knockdown of PSMA3-AS1 significantly restrained proliferation/migration/invasion, enhanced cell apoptosis, and induced oxidative stress in vitro. Tumor growth and matrix metalloproteinase expression in tumor tissues were markedly inhibited, while oxidative stress was enhanced in nude mice after stable PSMA3-AS1 knockdown. Additionally, PSMA3-AS1 negatively regulated miR-329-3p while positively regulated ALDOA expression. MiR-329-3p directly targeted ALDOA-3′UTR. Interestingly, miR-329-3p knockdown or ALDOA overexpression partially attenuated the tumor-suppressive effects of PSMA3-AS1 knockdown. Conversely, PSMA3-AS1 overexpression exhibited the opposite effects. PSMA3-AS1 promoted GC progression by regulating the miR-329-3p/ALDOA axis. PSMA3-AS1 might serve as a promising and effective target for GC treatment.
Seasonal variations of intensity of avian malaria infection in the Thousand Island Lake System, China
Authors: Han Yuxiao , Hellgren Olof , Wu Qiang , Liu Juan , Jin Tinghao , Bensch Staffan , Ding Ping 
Published: July 2023

Abstract
Background
Migratory birds play an important part in the spread of parasites, with more or less impact on resident birds. Previous studies focus on the prevalence of parasites, but changes in infection intensity over time have rarely been studied. As infection intensity can be quantified by qPCR, we measured infection intensity during different seasons, which is important for our understanding of parasite transmission mechanisms.

Methods
Wild birds were captured at the Thousand Island Lake with mist nets and tested for avian hemosporidiosis infections using nested PCR. Parasites were identified using the MalAvi database. Then, we used qPCR to quantify the infection intensity. We analyzed the monthly trends of intensity for all species and for different migratory status, parasite genera and sexes.

Results
Of 1101 individuals, 407 were infected (37.0%) of which 95 were newly identified and mainly from the genus Leucocytozoon. The total intensity trend shows peaks at the start of summer, during the breeding season of hosts and during the over-winter season. Different parasite genera show different monthly trends. Plasmodium causes high prevalence and infection intensity of winter visitors. Female hosts show significant seasonal trends of infection intensity.

Conclusions
The seasonal changes of infection intensity is consistent with the prevalence. Peaks occur early and during the breeding season and then there is a downward trend. Spring relapses and avian immunity are possible reasons that could explain this phenomenon. In our study, winter visitors have a higher prevalence and infection intensity, but they rarely share parasites with resident birds. This shows that they were infected with Plasmodium during their departure or migration and rarely transmit the disease to resident birds. The different infection patterns of different parasite species may be due to vectors or other ecological properties.

Graphical abstract
Comorbidity in incident osteoarthritis cases and matched controls using electronic health record data
Authors: Kamps Anne , Runhaar Jos , de Ridder Maria A. J. , de Wilde Marcel , van der Lei Johan , Zhang Weiya , Prieto-Alhambra Daniel , Englund Martin , de Schepper Evelien I. T. , Bierma-Zeinstra Sita M. A. 
Published: July 2023

Abstract
Background
Comorbidities are common in patients with osteoarthritis (OA). This study aimed to determine the association of a wide range of previously diagnosed comorbidities in adults with newly diagnosed OA compared with matched controls without OA.

Methods
A case–control study was conducted. The data were derived from an electronic health record database that contains the medical records of patients from general practices throughout the Netherlands. Incident OA cases were defined as patients with one or more diagnostic codes recorded in their medical records that correspond to knee, hip, or other/peripheral OA. Additionally, the first OA code had to be recorded between January 1, 2006, and December 31, 2019. The date of cases’ first OA diagnosis was defined as the index date. Cases were matched (by age, sex, and general practice) to up to 4 controls without a recorded OA diagnosis. Odds ratios were derived for each 58 comorbidities separately by dividing the comorbidity prevalence of cases by that of their matched controls at the index date.

Results
80,099 incident OA patients were identified of whom 79,937 (99.8%) were successfully matched with 318,206 controls. OA cases had higher odds for 42 of the 58 studied comorbidities compared with matched controls. Musculoskeletal diseases and obesity showed large associations with incident OA.

Conclusions
Most of the comorbidities under study had higher odds in patients with incident OA at the index date. While previously known associations were confirmed in this study, some associations were not described earlier.
Adipose-derived stem cell exosomes regulate Nrf2/Keap1 in diabetic nephropathy by targeting FAM129B
Authors: Ren Peiyao , Qian Fengmei , Fu Lanjun , He Wenfang , He Qiang , Jin Juan , Zheng Danna 
Published: July 2023

Abstract
Background
Exosomes from adipose-derived stem cells (ADSCs-Exos) have exhibited a therapeutic role in diabetic nephropathy (DN). Further studies are needed to investigate how ADSCs-Exos regulate oxidative stress and inflammation in high glucose-induced podocyte injury.

Methods
An enzyme-linked immunosorbent assay (ELISA) was used to detect cellular inflammation. Reactive oxygen species (ROS) levels were assessed using flow cytometry in podocytes with different treatments. A malondialdehyde (MDA) kit was used to evaluate the lipid peroxidation levels in podocytes and kidney tissues of mice. Western blotting and co-immunoprecipitation were performed to detect protein expression and protein-protein interactions.

Results
ADSCs-Exos reversed oxidative stress and inflammation in podocytes and kidney tissues of DN mice induced by high glucose levels in vitro and in vivo. Interference with heme oxygenase-1 expression could reverse the improvement effect of ADSCs-Exos on oxidative stress induced by high glucose levels. Furthermore, high glucose inhibited nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression and promoted Kelch-like ECH-associated protein 1 (Keap1) protein expression in podocytes, as well as their binding ability. As a potential target for Nrf2/Keap1 pathway regulation, FAM129B expression in podocytes is regulated by high glucose and ADSCs-Exos. Moreover, FAM129B siRNA blocked the inhibitory effect of ADSCs-Exos on intracellular ROS and MDA upregulation induced by high glucose in podocytes.

Conclusion
ADSCs-Exos regulate the Nrf2/Keap1 pathway to alleviate inflammation and oxidative stress in DN by targeting FAM129B, which may provide a potential therapeutic strategy for DN.